1. KONGRES SLOVENSKEGA ZDRUŽENJA ZA ZDRAVLJENJE BOLEČINE Z MEDNARODNO UDELEŽBO s pridruženim SIMPOZIJEM O KLINIČNI NEVROFIZIOLOGIJI BOLEČINE s 25. predavanjem v spomin dr. Janeza Faganela Hotel Golf, Bled, 9. in 10. oktober 2009 Organizatorji: Slovensko združenje za zdravljenje bolečine, Sekcija za klinično nevrofiziologijo Slovenskega zdravniškega društva, Inštitut za klinično nevrofiziologijo Nevrološke klinike Univerzitetnega kliničnega centra Ljubljana
Število kreditnih točk Slovenske zdravniške zbornice: 12 (18 za aktivne udeležence)
Program in zbornik prispevkov Uredniki: Maja Cesar Komar, Zoran Rodi, Jelka Pirc Tehnični uredniki: Tone Žakelj, Boštjan Kastelic, Ignac Zidar Založnik: Sekcija za klinično nevrofiziologijo Slovenskega zdravniškega društva Tisk: Birografika Bori, Ljubljana
CIP - Kataložni zapis o publikaciji Narodna in univerzitetna knjižnica, Ljubljana 616-009.7(082) SLOVENSKO združenje za zdravljenje bolečine. Kongres (1 ; 2009 ; Bled) Programme and proceedings = Program in zbornik prispevkov / 1st Congress of the Slovenian Association for Pain Theraphy and Symposium on Clinical Neurophysiology of Pain with the 25th Dr. Janez Faganel Memorial Lecture with International Participation, Bled, 9-10 October 2009 ; organised by Slovenian Association for Pain Therapy [and] Section for Clinical Neurophysiology of the Slovenian Medical Association and Institute of Clinical Neurophysiology, Department of Neurology, University Medical Center Ljubljana ; editors Maja Cesar Komar, Zoran Rodi, Jelka Pirc. - Ljubljana : Section for Clinical Neurophysiology of the Slovenian Medical Association, 2009 ISBN 978-961-6526-31-9 1. Cesar-Komar, Marija 2. Simpozij o klinični nevrofiziologiji bolečine (2009 ; Bled) 3. Predavanje v spomin dr. Janeza Faganela (25 ; 2009 ; Bled) 4. Slovensko zdravniško društvo. Sekcija za klinično nevrofiziologijo 5. Klinični center (Ljubljana). Nevrološka klinika. Inštitut za klinično nevrofiziologijo 247415040
1st Congress of the Slovenian Association for Pain Therapy and
Symposium on Clinical Neurophysiology of Pain with the 25th Dr. Janez Faganel Memorial Lecture with international participation
Hotel Golf, Bled, Slovenia 9–10 October 2009 Organised by: Slovenian Association for Pain Therapy, Section for Clinical Neurophysiology of the Slovenian Medical Association, and Institute of Clinical Neurophysiology, Department of Neurology, University Medical Centre Ljubljana
CME points accredited by the Medical Chamber of Slovenia: 12 (18 for active participants)
Programme and Proceedings Editors: Maja Cesar Komar, Zoran Rodi, Jelka Pirc Technical Editors: Tone Žakelj, Boštjan Kastelic, Ignac Zidar Published by: Section for Clinical Neurophysiology of the Slovenian Medical Association Printed by: Birografika Bori, Ljubljana
CIP - Kataložni zapis o publikaciji Narodna in univerzitetna knjižnica, Ljubljana 616-009.7(082) SLOVENSKO združenje za zdravljenje bolečine. Kongres (1 ; 2009 ; Bled) Programme and proceedings = Program in zbornik prispevkov / 1st Congress of the Slovenian Association for Pain Theraphy and Symposium on Clinical Neurophysiology of Pain with the 25th Dr. Janez Faganel Memorial Lecture with International Participation, Bled, 9-10 October 2009 ; organised by Slovenian Association for Pain Therapy [and] Section for Clinical Neurophysiology of the Slovenian Medical Association and Institute of Clinical Neurophysiology, Department of Neurology, University Medical Center Ljubljana ; editors Maja Cesar Komar, Zoran Rodi, Jelka Pirc. - Ljubljana : Section for Clinical Neurophysiology of the Slovenian Medical Association, 2009 ISBN 978-961-6526-31-9 1. Cesar-Komar, Marija 2. Simpozij o klinični nevrofiziologiji bolečine (2009 ; Bled) 3. Predavanje v spomin dr. Janeza Faganela (25 ; 2009 ; Bled) 4. Slovensko zdravniško društvo. Sekcija za klinično nevrofiziologijo 5. Klinični center (Ljubljana). Nevrološka klinika. Inštitut za klinično nevrofiziologijo 247415040
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
VSEBINA / CONTENTS PREDGOVOR ................................................................................................................... FOREWORD .....................................................................................................................
2 3
OKVIRNI PROGRAM .......................................................................................................... PROGRAMME FRAMEWORK............................................................................................
4 5
PODROBNI PROGRAM ..................................................................................................... 6 DETAILED PROGRAMME ................................................................................................ 11 ČLANKI & IZVLEČKI* PAPERS & ABSTRACTS* ................................................................................................ 16 AVTORSKO KAZALO AUTHORS INDEX ............................................................................................................. 155 PREDAVANJA V SPOMIN DR. JANEZA FAGANELA IN SIMPOZIJI 1985–2009 DR. JANEZ FAGANEL MEMORIAL LECTURES AND SYMPOSIA 1985–2009 .............. 156 VABILO NA SLOVENSKI NEVROFIZIOLOŠKI SIMPOZIJ 2010 INVITATION TO THE SLOVENIAN NEUROPHYSIOLOGIC SYMPOSIUM 2010 ............ 158 ZAHVALE ACKNOWLEDGEMENTS ................................................................................................. 159 ______ Strani posameznih prispevkov so navedene v poglavju Podrobni program Na strani 6. *Pages of individual contributions are given in the Detailed Programme on page 11.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
1
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
PREDGOVOR Pred vami je Zbornik prispevkov 1. kongresa Slovenskega združenja za zdravljenje bolečine s pridruženim Simpozijem o klinični nevrofiziologiji bolečine in 25. predavanjem v spomin dr. Janeza Faganela. Slovensko združenje za zdravljenje bolečine je bilo ustanovljeno v Ljubljani leta 1996. Prizadeva si, da bi bil vsakdo z bolečino deležen izpolnitve njegove pravice, da se mu bolečina olajša ali zdravi. Združuje zdravnike različnih specialnosti. Med njegovimi glavnimi nalogami so izobraževanje, sledenje novostim, sprejemanje doktrin in smernic s področja zdravljenja bolečine, pa tudi znanstveno delo, predstavljanje na mednarodnih kongresih in strokovnih sestankih ter objavljanje v domači in tuji literaturi. Vsako leto prireja tradicionalne seminarje o zdravljenju bolečine, ki so namenjeni širokemu krogu zdravnikov in kjer sodelujejo mednarodni strokovnjaki. Letos, v trinajstem letu delovanja, je Združenje končno dozorelo za kongres, napovedan že pred tremi leti na občnem zboru. Sekcija za klinično nevrofiziologijo Slovenskega zdravniškega društva in Inštitut za klinično nevrofiziologijo ljubljanskega univerzitetnega kliničnega centra letos že petindvajsetič zapored organizirata vsakoletni simpozij s predavanjem v spomin svojega umrlega sodelavca in prijatelja dr. Janeza Faganela. Mehanizmom bolečine je bil posvečen prvi simpozij (seznam vseh je objavljen tudi v tem zborniku), tokratni, jubilejni, ki je pridružen kongresu kolegov iz Združenja za zdravljenje bolečine, pa možnostim za preučevanje bolečine z metodami in tehnikami klinične nevrofiziologije. Bolečina se zaenkrat še izmika neposrednemu objektivnemu merjenju, kako ji klinični nevrofiziologi prihajajo bliže, pa je prikazano tudi v tem zborniku. Zahvaljujeva se vsem, ki so vsebinsko, finančno in organizacijsko prispevali k izvedbi kongresa in simpozija. Marija Cesar-Komar Zoran Rodi za organizacijski in programski odbor
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
2
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
FOREWORD In front of you, there is a collection of abstracts and/or papers presented at the 1st Congress of the Slovenian Association for Pain Therapy and at the associated Symposium of Clinical Neurophysiology of Pain with the 25th Dr. Janez Faganel Memorial Lecture. The Slovenian Association for Pain Therapy was established in Ljubljana in 1996. Its endeavour is that anyone in pain would be acknowledged the right that his/her suffering is alleviated by treatment. Among its main tasks are training, following the novelties, accepting doctrines and guidelines, and organisation of annual seminars on pain therapy. Now already traditional, the latter are designed for a wide range of physicians, covering different topics by experts. In the 13th year of its activities, the Association finally reached the maturity to organise a congress that was announced at the general meeting three years ago. Organising annual symposia with lectures in the memory of their colleague and friend Dr. Janez Faganel for the last 25 years, the Section for Clinical Neurophysiology of the Slovenian Medical Association and the University Medical Centre Ljubljana Institute of Clinical Neurophysiology have reached the silver jubilee. “Mechanisms of pain” was the topics of their first symposium (a complete list can be seen also in this publication), while this year, the symposium is devoted to the possibilities of assessment of pain with neurophysiological methods and techniques. For the time being, pain still evades direct objective measuring, however, it can be approached by several clinical neurophysiological means and ways, some of which are also presented in this book. We are thankful to all who have contributed to the Congress and the Symposium, be your medical expertise, financial support, or organising skills.
Marija Cesar-Komar Zoran Rodi on behalf of the Organising and Programme Committee
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
3
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
OKVIRNI PROGRAM Petek, 9. oktober 2009 Od 7:00 dalje
Registracija
08:00–08:30
Otvoritvena slovesnost
08:30–09:00
Kongresno uvodno predavanje
09:00–09:30
25. predavanje v spomin dr. Janeza Faganela
09:30–09:45
Odmor s kavo
09:45–12:00
Vzporedno zasedanje I: Bolečina in evocirani potenciali
12:00–12:30
Predavanje zlatega sponzorja (Pfizer)
12:30–14:00
Kosilo
14:00–14:20
Farmacevtska predstavitev (PharmaSwiss)
14:20–14:30
Odmor
14:30–16:30
Vzporedno zasedanje III: Tiha kožna perioda in umaknitveni refleksi
16:30–17:00
Predavanje zlatega sponzorja (Boehringer Ingelheim)
17:00–17:15
Odmor s kavo Vzporedna delavnica II:
17:15–18:45
Vzporedna delavnica I: 17:15–17:45 Tiha kožna perioda 17:45–18:15 Umaknitveni refleksi 18:15–18:45
18:00–18:45
20:30
Evocirani dražljaji na vročinske dražljaje
Vzporedno zasedanje II: Invazivno zdravljenje bolečine
Vzporedno zasedanje IV: Organiziranje službe za zdravljenje bolečine
17:15–18:00
Ultrasonografsko vodenje regionalnih blokad (sponzor Elmed) Radiofrekvenčna analgezija (sponzor Auremiana)
Kongresna večerja
Sobota, 10. oktober 2009 07:30–14:00
Registracija
08:30–09:00
Uvodno predavanje
09:00–10:30
Zasedanje V: Zdravljenje akutne bolečine 1
10:30–11:00
Odmor s kavo
11:00–12:30
Zasedanje VI: Zdravljenje akutne bolečine 2
12:30–13:00
Predavanje zlatega sponzorja (Grűnenthal)
13:00–14:30
Kosilo in predstavitev del s plakati
14:30–15:00
Predavanje zlatega sponzorja (Medis)
15:00–17:30
Zasedanje VII: Zdravljenje kronične bolečine
17:30
Zaključek
19:00
Družabno srečanje v slovo (Blejski Grad)
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
4
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
PROGRAMME FRAMEWORK Friday, 9 October 2009 From 7:00 on
Registration
08:00–08:30
Opening address
08:30–09:00
Congress opening lecture
09:00–09:30
25th Dr. Janez Faganel memorial lecture
09:30–09:45
Coffee break
09:45–12:00
Vzporedno zasedanje I: Bolečina in evocirani potenciali Parallel Session I: Evoked potentials to nociceptive stimuli
12:00–12:30
Lecture sponsored by Golden Sponsor Pfizer
12:30–14:00
Lunch
14:00–14:20
Pharmaceutical presentation by PharmaSwiss
14:20–14:30
Break
14:30–16:30
Parallel Session III: Cutaneous silent period and withdrawal reflexes
16:30–17:00
Lecture sponsored by Golden Sponsor Boehringer Ingelheim
17:00–17:15
Coffee break Workshops, parallel set I:
17:15–18:45
20:30
17:15–17:45 17:45–18:15 18:15–18:45
Cutaneous silent period Withdrawal reflexes Evoked potentials to heat stimuli
Parallel Session II: Invasive pain treatment
Parallel Session IV: Pain service organisation
Workshops, parallel set II: 17:15–18:00 18:00–18:45
Ultrasonography-guided regional blocks (sponsored by Elmed) Radiofrequency analgesia (sponsored by Auremiana)
Congress dinner
Saturday, 10 October 2009 07:30–14:00
Registration
08:30–09:00
Keynote lecture
09:00–10:30
Session V: Acute pain treatment 1
10:30–11:00
Coffee break
11:00–12:30
Session VI: Acute pain treatment 2
12:30–13:00
Lectures sponsored by Golden Sponsor Grűnenthal
13:00–14:30
Lunch & Poster presentation
14:30–15:00
Lecture sponsored by Golden Sponsor Medis
15:00–17:30
Session VII: Chronic pain treatment
17:30
Conclusion
19:00
Farewell party (Bled Castle)
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
5
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
PODROBNI PROGRAM IN KAZALO Petek, 9. oktober 2009 Od 07:00 dalje
Registracija
08:00–08:30
Otvoritvena slovesnost (Dvorana Jupiter)
08:30–09:00
Kongresno uvodno predavanje Giustino Varrassi (Rim, Italija): Analgezija v urgentnih okoliščinah
09:00–09:30
25. predavanje v spomin dr. Janeza Faganela Giorgio Cruccu (Rim, Italija): Klinična nevrofiziologija bolečine
09:30–09:45
Odmor s kavo
09:45–12:00
Vzporedno zasedanje I: Evocirani potenciali na bolečinske dražljaje (Dvorana Concordia) Moderatorja: Luis Garcia-Larrea, Dušan Butinar
09:45–10:15
Giandomenico Iannetti (Oxford, Velika Britanija): Funkcijske pomen odzivov možganske skorje na bolečinske dražljaje
-
10:15–10:45
Praveen Anand (London, Velika Britanija): Evocirani potenciali na vročinske dražljaje
-
10:45–11:15
Luis Garcia-Larrea (Lyon, Francija) So v diagnostiki kronične bolečine evocirani potenciali uporabno orodje ali nevarna igrača?
-
11:15–12:00
Razpravljanje
09:45–12:00
Vzporedno zasedanje II: Invazivno zdravljenje bolečine (Dvorana Jupiter) Moderatorja: Marija Cesar-Komar, Zoran Zabavnik
09:45–10:10
John Loughrey (Dublin, Irska) Ultrasonografija pri regionalni blokadi obpodordne bolečine
17
10:10–10:25
Nevenka Krčevski-Škvarč (Maribor) Invazivne metode za zdravljenje kronične nemaligne bolečine
19
10:25–10:40
Milan Roman Gregorič (Ljubljana) Zdravljenje bolečine z botulinom
24
10:40–11:05
Slobodan Gligorijevic (Zurich, Švica) Perinevralne blokade po operacijah zgornjega uda
32
11:05–11:20
Silvo Lipovšek (Celje) Analgezija pri operiranih otrocih
37
11:20–11:45
Zbigniew Kirkor (Harlow, Essex, Velika Britanija) Radiofrekvenčna denervacija za zdravljenje kronične bolečine. Pogled zdravnika bolečine. Pregled dokazov
39
11:45–12:00
Razpravljanje
12:00–12:30
Predavanji v organizaciji zlatega sponzorja, družbe Pfizer (Dvorana Jupiter)
Stran 16
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
6
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
12:00–12:15
Marjan Zaletel (Ljubljana) Je fibromialgija možganska motnja?
12:15–12:30
Helena Jamnik (Ljubljana) Multidisciplinarna obravnava fibromialgije
12:30–14:00
Kosilo
14:00–14:20
Farmacevtska predstavitev družbe PharmaSwiss (Dvorana Jupiter)
14:00–14:10
Marija Cesar-Komar (Slovenj Gradec) Z opioidi povzročeno zaprtje v blažilni oskrbi in nove možnosti zdravljenja
14:10–14:20
Slavica Lahajnar-Čavlovič (Ljubljana) Prebiajoča bolečina in novo zdravljenje
14:20–14:30
Odmor
14:30–16:30
Vzporedno zasedanje III: Tiha kožna perioda in umaknitveni refleksi (Dvorana Concordia) Moderatorja: Markus Kofler, Janez Zidar
14:30–15:00
Markus Kofler (Innsbruck, Austria) Anatomija in fiziologija tihe kožne periode
40
15:00–15:30
Ivana Štětkářová (Praga, Češka) Patofiziologija tihe kožne periode
45
15:30–16:00
Ole Kæseler Andersen, Lars Arendt-Nielsen (Aalborg, Danska) Bazična in klinična nevrofiziologija humanih umaknitvenih refleksov na boleče dražljaje
48
16:00–16:30
Razpravljanje
14:30–16:30
Vzporedno zasedanje IV: Organiziranje službe za zdravljenje bolečine (Dvorana Jupiter) Moderatorja: Aleksander Manohin, Vesna Golubović
14:30–14:45
Aleksander Manohin (Ljubljana) Nekateri vidiki organizacije službe za lajšanje akutne bolečine
52
14:45–15:00
Marija Cesar-Komar (Slovenj Gradec) Organiziranost zdravljenja kronične bolečine v Sloveniji
54
15:00–15:15
Gorazd Požlep (Ljubljana) Organiziranost zdravljenja akutne bolečine v Sloveniji
15:15–15:30
Alenka Pleško-Mlakar (Postojna) Lajšanje porodne bolečine v Sloveniji
62
15:30–16:00
Rudolf Likar (Klagenfurt/Celovec, Avstrija) Center za interdisciplinarno zdravljenje bolečine, onkologijo in blažilno oskrbo
67
16:00–16:20
Vesna Golubović (Reka, Hrvaška) Organiziranost službe zdravljenja kronične bolečine na Hrvaškem
68
16:20–16:30
Razpravljanje
16:30–17:00
Predavanje v organizaciji zlatega sponzorja, družbe Boehringer Ingelheim (Dvorana Jupiter) Grubič Z (Ljubljana) Bolečina in depresija – patofiziološki vidik
17:00–17:15
Odmor s kavo
17:15–18:45
Vzporedna delavnica I (Dvorana Concordia)
-
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
7
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
17:15–17:45
Giorgio Cruccu, Markus Kofler, Ivana Štětkářová Tiha kožna perioda
17:45–18:15
Ole Kæseler Andersen Umaknitveni refleksi
18:15–18:45
Praveen Anand Evocirani potenciali na vročinske dražljaje
17:15–18:45
Vzporedna delavnica II (Dvorana Jupiter)
17:15–18:00
Ultrasonografsko vodeno regionalno blokiranje bolečine (sponzor Elmed)
18:00–18:45
Radiofrekvenčna analgezija (sponzor Auremiana)
20:30
Kongresna večerja (Grand Hotel Toplice)
Sobota, 10. oktober 2009 07:30–14:00
Registracija
08:30–09:00
Uvodno predavanje (Dvorana Jupiter) Giorgio Cruccu (Rim, Italija) Priporočilo EFNS za farmakološko zdravljenje nevropatske bolečine
09:00–10:30
Zasedanje V Zdravljenje akutne bolečine 1 Moderatorja: Vesna Novak-Jankovič, Mirt Kamenik
09:00–09:20
Katarina Šakić, Ana Markić (Zagreb, Hrvaška) Trebušna visceralna bolečina
72
09:20–09:35
Vesna Novak-Jankovič (Ljubljana) Thorakalna paravertebralna analgezija
77
09.35–09:50
Neli Vintar (Ljubljana) Katetrske tehnike za pooperacijsko analgezijo v ranI
80
09:50–10:05
Viktor Švigelj (Ljubljana) Centralna bolečina – patofiziologija in zdravljenje
86
10:05–10:20
Mirt Kamenik (Maribor) Zdravljenje bolečine po srčni operaciji
92
10:20–10:30
Razpravljanje
10:30–11:00
Odmor s kavo
11:00–12:30
11:00–11:15
11:25–11:50
Zasedanje VI Zdravljenje akutne bolečine 2 (Dvorana Jupiter) Moderatorici: Nada Kodrič, Višnja Majerić-Kogler Ksenija Mahkovic-Hergouth (Ljubljana) Načela lajšanja pooperacijske bolečine po velikih trebušnih onkoloških operacijah Višnja Majerić-Kogler, Danijela Bandić, Jana Kogler, Vilka BekavacMišak, Sanja Sakan (Zagreb, Hrvaška) Vpliv pooperacijskega zdravljenja bolečine na izid kirurškega posega
11:50–12:05
Sanja Huterer (Dunaj, Avstrija) Pregled tehnik perfirenih blokad
12:05–12:30
Razpravljanje
71
96
99 -
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
8
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
12:30–13:00
Predavanji v organizaciji zlatega sponzorja, družbe Grűnenthal (Dvorana Jupiter)
12:30–12:45
Nevenka Krčevski-Škvarč (Maribor) Rezultati postmarketinške raziskave s Transtecom v Sloveniji
12:45–13:00
Aleš Pražnikar (Ljubljana) Vloga topične terapije pri zdravljenju nevropatske bolečine
13:00–14:30
Kosilo in predstavitev prispevkov s plakati (Dvorana Libertas)
Plakat št. 1
Aleksandar Bilić (Slovenj Gradec) TAP-blok – blokada transverzalne abdominalne planote
Plakat št. 2
Plakat št. 3
Plakat št. 4
Nataša Fikfak, Jurij Karapandža, Simon Bitežnik (Nova Gorica) Diagnostika in zdravljenje fibromialgije v Splošni bolnišnici dr. Franca Derganca Nova Gorica Milica Klopčič-Spevak, Helena Jamnik (Ljubljana) Kompleksni regionalni bolečinski sindrom tip 1, zdravljen s subkutano suhoigelno terapijo Slavica Lahajnar-Čavlovič (Ljubljana) Pogostnost in zdravljenje kronične bolečine med varovanci patronažnega varstva
105 106
107
108
Plakat št. 5
Duška Meh (Ljubljana) Diagnostika somatske boleče nevropatije, motnje tankih vlaken
109
Plakat št. 6
Duška Meh (Ljubljana) Novi protokol za ugotavljanje motene somatosenzorike
110
Plakat št. 7
Duška Meh (Ljubljana), Marko Pišljar (Idrija) Kako oceniti in ovrednotit bolečino
111
Plakat št. 8
Zoran Rodi (Ljubljana), Christian Springer (Amsterdam, The Netherlands) Vpliv mišične kontrakcije in jakosti dražljaja na parametre tihe kožne periode
112
Plakat št. 9
Plakat št. 10
Plakat št. 11
Majda Šarman, Darija Armentano, Karmen Pišek-Šuta, Vlasta EkartFakin, Verdi Kerimović (Ptuj) Analgezija po totalni endoprotezi kolka z levibupivakainom preko perifernega femoralnega katetra v primerjavi s piritramidom i.v. PCA Aleksander Stepanovič (Kranj), Jelka Pirc (Nova Gorica), Slavica Lahajnar-Čavlovič, Sanja Bizilj, Darja Ambrožič (Ljubljana) Spremljanje klinične učinkovitosti zdravila Jurnista pri bolnikih s hudo kronično bolečino Mihael Zajec, Marija Cesar-Komar (Slovenj Gradec) Operacija ingvinalne kile v lokalni anesteziji – kolikšen je vpliv na pooperacijsko analgezijo
113
114
115
14:30–15:00
Predavanje v organizaciji zlatega sponzorja, družbe Medis (Dvorana Jupiter) Uwe Junker (Remscheid, Nemčija) Oksikodon, nova možnost zdravljenja bolečine
15:00–17:30
Zasedanje VII Zdravljenje kronične bolečine (Dvorana Jupiter) Moderatorja: Zmago Turk, Jelka Pirc
15:00–15:30
Uwe Junker (Remscheid, Nemčija) Nevropatska bolečina, izzvana s kemoterapijo
117
15:30–15:45
Zmago Turk, Dušan Čelan (Maribor), Kurt Ammer (Vienna, Austria) Klinične metode testiranja bolečin pri revmatskih boleznih
118
15:45–16:15
Perry Richardson (Washington, DC, ZDA) Radikularna in miofascialna bolečina: prepoznavanje in zdravljenje
119
16:15–16:30
Dušan Logar, Sonja Praprotnik (Ljubljana) Priporočila za zdravljenje bolečine kronične vnetne revmatične bolezni z zdravili
127
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
9
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
16:30–16:45
Zvezdan Pirtošek, Bernard Meglič (Ljubljana) Zdravljenje trdovratnih glavobolov in nevralgije trovejnega živca
141
16:45–17:00
Krunoslav Margić, Jelka Pirc (Nova Gorica) Compleksni sindromes z regionalno bolečino in podobna potravmatska stanja na zgornjem udu
145
17:00–11:15
Slavica Lahajnar-Čavlovič (Ljubljana) Pravilna izbira zdravila za zdravljenje bolečine glede na jakost bolečine
151
17:15–17:30
Razpravljanje
17:30
Zaključek
19:00
Srečanje v slovo (Blejski grad)
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
10
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
DETAILED PROGRAMME & CONTENTS OF THE PROCEEDINGS Friday, 9 October 2009 From 07:00 on
Registration
08:00–08:30
Opening address (Jupiter Hall)
08:30–09:00
Congress opening lecture Giustino Varrassi (Rome, Italy): Analgesia in emergency setting
Page -
th
09:00–09:30
25 Dr. Janez Faganel memorial lecture Giorgio Cruccu (Rome, Italy): Clinical neurophysiology of pain
09:30–09:45
Coffee break
09:45–12:00
Parallel Session I (Concordia Hall) Evoked potentials for pain Moderators: Luis Garcia-Larrea, Dušan Butinar
09:45–10:15
Giandomenico Iannetti (Oxford, Great Britain): Functional significance of the cortical responses to nociceptive stimuli
-
10:15–10:45
Praveen Anand (London, Great Britain): Evoked potentials to heat stimulus
-
10:45–11:15
Luis Garcia-Larrea (Lyon, France) Are evoked potentials useful tools or dangerous toys in chronic pain diagnostics
-
11:15–12:00
Discussion
09:45–12:00
Parallel Session II (Jupiter Hall) Invasive pain treatment Moderators: Marija Cesar-Komar, Zoran Zabavnik
09:45–10:10
John Loughrey (Dublin, Ireland) Ultrasonography for regional blocks in obstetric anaesthesia
17
10:10–10:25
Nevenka Krčevski-Škvarč (Maribor, Slovenia) Invasive methods for chronic non-malignant pain management
19
10:25–10:40
Milan Roman Gregorič (Ljubljana, Slovenia) Pain treatment with botulinus toxin
24
10:40–11:05
Slobodan Gligorijevic (Zurich, Switzerland) Perineural blocks after upper limb surgery
32
11:05–11:20
Silvo Lipovšek (Celje, Slovenia) Analgesia in pediatric surgery
137
11:20–11:45
Zbigniew Kirkor (Harlow, Essex, United Kingdom) Radiofrequency denervation in the treatment of chronic pain. Pain physician perspective. Review of evidence
39
11:45–12:00
Discussion
12:00–12:30
Golden Sponsor Pfizer lectures (Jupiter Hall)
12:00–12:15
Marjan Zaletel (Ljubljana, Slovenia) Fibromyalgia – a brain dysfunction?
16
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
11
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
12:15–12:30
Helena Jamnik (Ljubljana, Slovenia) Multidisciplinary management of fibromyalgia
12:30–14:00
Lunch
14:00–14:20
Pharmaceutical presentations by PharmaSwiss (Jupiter Hall)
14:00–14:10
Marija Cesar-Komar (Slovenj Gradec, Slovenia) Opioid-induced constipation in palliative care and new treatment options
14:10–14:20
Slavica Lahajnar-Čavlovič (Ljubljana, Slovenia) Break-through pain and new treatment
14:20–14:30
Break
14:30–16:30
Parallel Session III Cutaneous silent period and withdrawal reflexes (Concordia Hall) Moderators: Markus Kofler, Janez Zidar
14:30–15:00
Markus Kofler (Innsbruck, Austria) Anatomy and physiology of the cutaneous silent period
40
15:00–15:30
Ivana Štětkářová (Prague, Czech Republic) Pathophysiology of cutaneous silent period
45
15:30–16:00
Ole Kæseler Andersen, Lars Arendt-Nielsen (Aalborg, Denmark) Basic and clinical neurophysiology of human withdrawal reflexes to painful stimuli
48
16:00–16:30
Discussion
14:30–16:30
Parallel Session IV Pain service organisation (Jupiter Hall) Moderators: Aleksander Manohin, Vesna Golubović
14:30–14:45
Aleksander Manohin (Ljubljana, Slovenia) Some aspects of acute pain services organisation
52
14:45–15:00
Marija Cesar-Komar (Slovenj Gradec, Slovenia) Chronic pain service organisation in Slovenia
54
15:00–15:15
Gorazd Požlep (Ljubljana, Slovenia) Acute pain service organisation
15:15–15:30
Alenka Pleško-Mlakar (Postojna, Slovenia) Labour pain service in Slovenia
62
15:30–16:00
Rudolf Likar (Klagenfurt/Celovec, Austria) Centre for interdisciplinary pain therapy, oncology and palliative care
67
16:00–16:20
Vesna Golubović (Rijeka, Croatia) Organisation of service for the treatment of chronic pain in the Republic of Croatia
68
16:20–16:30
Discussion
16:30–17:00
Golden Sponsor Boehringer Ingelheim lecture (Jupiter Hall) Grubič Z (Ljubljana, Slovenia) Pain and depression – pathophysiological aspect
17:00–17:15
Coffee break
17:15–18:45
Workshops, Parallel set I (Concordia Hall):
17:15–17:45
Giorgio Cruccu, Markus Kofler, Ivana Štětkářová Cutaneous silent period
-
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
12
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
17:45–18:15
Ole Kæseler Andersen Withdrawal reflexes
18:15–18:45
Praveen Anand Evoked potentials to heat stimuli
17:15–18:45
Workshops, Parallel set II (Jupiter Hall):
17:15–18:00
Ultrasonography-guided regional blocks (sponsored by Elmed)
18:00–18:45
Radiofrequency analgesia (sponsored by Auremiana)
20:30
Congress dinner (Grand Hotel Toplice)
Saturday, 10 October 2009 07:30–14:00
Registration
08:30–09:00
Keynote lecture (Jupiter Hall) Giorgio Cruccu (Rome, Italy) EFNS Guidelines on pharmacological treatment of neuropathic pain
09:00–10:30
Session V Acute pain treatment 1 Moderators: Vesna Novak-Jankovič, Mirt Kamenik
09:00–09:20
Katarina Šakić, Ana Markić (Zagreb, Croatia) Abdominal visceral pain
72
09:20–09:35
Vesna Novak-Jankovič (Ljubljana, Slovenia) Thoracic paravertebral analgesia
77
09.35–09:50
Neli Vintar (Ljubljana, Slovenia) Wound catheter techniques for postoperative analgesia
80
09:50–10:05
Viktor Švigelj (Ljubljana, Slovenia) Central pain – pathophysiology and therapy
86
10:05–10:20
Mirt Kamenik (Maribor, Slovenia) Postoperative analgesia for cardiac surgery
92
10:20–10:30
Discussion
10:30–11:00
Coffee break
11:00–12:30
11:00–11:15
11:25–11:50
Session VI Acute pain treatment 2 (Jupiter Hall) Moderators: Nada Kodrič, Višnja Majerić-Kogler Ksenija Mahkovic-Hergouth (Ljubljana, Slovenia) Modes of postoperative analgesia after major abdominal oncological surgery Višnja Majerić-Kogler, Danijela Bandić, Jana Kogler,Vilka BekavacMišak, Sanja Sakan (Zagreb, Croatia) Effect of postoperative pain therapy on surgical outcome
11:50–12:05
Sanja Huterer (Vienna, Austria) Overview of peripheral block techniques
12:05–12:30
Discussion
12:30–13:00
Golden Sponsor Grűnenthal lectures (Jupiter Hall)
71
96
99 -
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
13
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
12:30–12:45
Nevenka Krčevski-Škvarč (Maribor, Slovenia) Results of Transtec postmarketing study in Slovenia
12:45–13:00
Aleš Pražnikar (Ljubljana, Slovenia) The role of topical therapy in the treatment of neuropathic pain
13:00–14:30
Lunch & Poster presentation (Libertas Hall)
Poster No 1
Aleksandar Bilić (Slovenj Gradec, Slovenia) Tap block – transversal abdominal block
Poster No 2
Poster No 3
Nataša Fikfak, Jurij Karapandža, Simon Bitežnik (Nova Gorica, Slovenia) Diagnostics and treatment of fibromyalgia in General hospital dr. Franc Derganc Nova Gorica Milica Klopčič-Spevak, Helena Jamnik (Ljubljana, Slovenia) Complex regional pain syndrome (CRPS) type I treated by subcutaneous dry needling therapy
105 106
107
Poster No 4
Slavica Lahajnar-Čavlovič (Ljubljana, Slovenia) Pravalence and treatment of chronic pain among nursing home patients
108
Poster No 5
Duška Meh (Ljubljana, Slovenia) The diagnostics of somatic painful neuropathy, small nerve fibre disorder
109
Poster No 6
Duška Meh (Ljubljana, Slovenia) A new protocol for determination of disturbed somatosensory sensation
110
Poster No 7
Duška Meh (Ljubljana, Slovenia), Marko Pišljar (Idrija, Slovenia) How to assess and evaluate pain
111
Poster No 8
Poster No 9
Poster No 10
Poster No 11
Zoran Rodi (Ljubljana, Slovenia), Christian Springer ((Amsterdam, The Netherlands) Influence of the muscle contraction and the stimulus intensity on parameters of the cutaneous silent period Majda Šarman, Darija Armentano, Karmen Pišek-Šuta, Vlasta EkartFakin, Verdi Kerimović (Ptuj, Slovenia) Postoperative analgesia following total hip endoprosthesis using a peripheral femoral catheter infusion of 0.125% levobupivacaine versus i.v. PCA piritramide Aleksander Stepanovič (Kranj, Slovenia), Jelka Pirc (Nova Gorica, Slovenia), Slavica Lahajnar-Čavlovič, Sanja Bizilj, Darja Ambrožič (Ljubljana, Slovenia) Efficacy of Jurnista for treatment of chronic severe pain in everyday practice Mihael Zajec, Marija Cesar-Komar (Slovenj Gradec) The influence of local anaesthesia for inguinal hernia surgery on postoperative analgesia
112
113
114
115
14:30–15:00
Golden Sponsor Medis lecture (Jupiter Hall) Uwe Junker (Remscheid, Germany) Oxycodone – a novel therapeutic option in pain management
15:00–17:30
Session VII Chronic pain treatment (Jupiter Hall) Moderators: Zmago Turk, Jelka Pirc
15:00–15:30
Uwe Junker (Remscheid, Germany) Chemotherapy-induced neuropathic pain
117
15:30–15:45
Zmago Turk, Dušan Čelan (Maribor, Slovenia), Kurt Ammer (Vienna, Austria) Clinical methods for pain measurement in rheumatic diseases
118
15:45–16:15
Perry Richardson (Washington, DC, USA) Radicular and myofascial pain: Recognition and management
119
16:15–16:30
Dušan Logar, Sonja Praprotnik (Ljubljana, Slovenia) Recommendation for the medicamentous treatment of chronic inflammatory rheumatic disease pain
127
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
14
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
16:30–16:45
Zvezdan Pirtošek, Bernard Meglič (Ljubljana) Resistant headaches and trigeminus neuralgia treatment
141
16:45–17:00
Krunoslav Margić, Jelka Pirc (Nova Gorica, Slovenia) Complex regional pain syndromes and similar painful posttraumatic states involving upper extremity
145
17:00–11:15
Slavica Lahajnar-Čavlovič (Ljubljana, Slovenia) Oncologic pain treatment
151
17:15–17:30
Discussion
17:30
Conclusion
19:00
Farewell party (Bled Castle)
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
15
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
25. predavanje v spomin dr. Janeza Faganela / 25th Dr. Janez Faganel Memorial Lecture
KLINIČNA NEVROFIZIOLOGIJA BOLEČINE CLINICAL NEUROPHYSIOLOGY OF PAIN Giorgio Cruccu EFNS Secretariat, Vienna, Austria, and Department of Neurological Sciences, La Sapienza University, Rome, Italy
Because pain is a complex experience, strongly influenced by cultural, social, and emotional factors, it would be most important to rely on techniques that provide its laboratory measure or at least help us in the diagnostic process. Large-size, non-nociceptive afferents have a lower electrical threshold than small-size, nociceptive afferents. Unless special techniques are adopted (experimental blocks) or special organs are stimulated (cornea, tooth pulp, glans), electrical stimuli unavoidably also excite large, non-nociceptive afferents that contaminate, hinder, or inhibit the nociceptive signals. Hence standard neurophysiological responses to electrical stimuli, such as nerve conduction studies and somatosensory evoked potentials, are useful to demonstrate, locate, and quantify damage along the peripheral or central sensory pathways. But they do not assess function of nociceptive pathways.Microneurography and intraneural microstimulation provide useful information on the physiology of nociceptors and their behaviour in various experimental pain models and have proven useful in understanding pathophysiology of positive sensory symptoms in neuropathic pain patients. Microneurography, however, is time-consuming and difficult, requiring both an expert investigator and a collaborative patient; hence it is unsuitable for the clinical setting. The electrically-elicited trigeminal reflexes (blink reflex and masseter inhibitory reflex) are diagnostically useful to differentiate classic trigeminal neuralgia from symptomatic trigeminal pains. The other reflexes have little diagnostic value. The nociceptive reflex that is most used and appears to be most reliable in assessing treatment efficacy is the RIII flexion reflex. Laser evoked potentials are the easiest and most reliable neurophysiological method of assessing function of nociceptive pathways; in clinical practice their main limit is that they are currently available in too few centres. Aδ-LEPs (which assess small-myelinated fibre pathways) are diagnostically useful in peripheral and central neuropathic pains. In contrast C-LEPs (which assess unmyelinated-fibre pathways) are technically too difficult for clinical application.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
16
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
ULTRASONOGRAFIJA PRI REGIONALNI BLOKADI OBPORODNE BOLEČINE ULTRASOUND FOR REGIONAL BLOCKS IN OBSTETRIC ANAESTHESIA John Loughrey The Rotunda Hospital, Dublin, Ireland “In the land of the blind the one-eyed man is king” (D. Erasmus 1466–1536)
The use of ultrasound in medical practice dates back to the 1950’s with one of the first descriptions of its use in clinical anaesthesia practice 30 years ago.1 While our obstetric colleagues have used ultrasound for more than 40 years, the same technology has not developed a widespread role in obstetric anaesthesia. To be successful at ultrasound-guided techniques in general, one needs to develop familiarity with the cross-sectional sono-anatomy in question and to become adept at co-ordination of the imaging probe with the needle.2 For neuraxial blockade a pre-puncture transverse image is more commonly used to identify a needle insertion point rather than ‘in-plane’ needle visualisation, although the latter technique has been described.3, 4 Ultrasound imaging for brachial plexus anaesthesia has been embraced by many regional anaesthesia enthusiasts as a tool one cannot live without in modern practice. Direct visualisation of the anatomic structures and direct visualisation of needle progress and spread of local anaesthetic solutions is now possible with newer high-resolution equipment.2, 5 These may be associated with enhanced patient safety, increased regional anaesthesia success rates and reduced anaesthesia procedure times.6 The ultrasound equipment is becoming more ‘anaesthesiafriendly’ with increased portability, durability and software enhancements to improve image quality. One of the main limitations to the adoption of ultrasound in routine obstetric anaesthesia practice, apart from cost, is lack of opportunity to develop the necessary experience in image interpretation. Furthermore, the sceptics view is that modern obstetric anaesthesia procedures have been established for more than 50 years and are ‘safe enough’ performed blindly. An experienced ‘epiduralist’ could contend that ultrasound adds little to the overall patient experience. There is indeed a relative paucity of good data charting the developing utility of ultrasound in obstetric anaesthesia practice and many of the published studies are from a small number of enthusiasts. However the National Institute for Clinical Excellence (NICE) UK has published a recommendation in 2008 stating ultrasound may be effective in achieving correct placement of epidural catheters. There are however, other clinical applications in obstetric anaesthesia practice where ultrasound may also be helpful. Placement of central venous catheters, performance of abdominal field blocks, and performance of sacroiliac or pubic symphysis blocks in pelvic girdle pain syndromes can all be guided by ultrasound equipment. Abdominal field blocks such as the Transversus Abdominis Plane (TAP) block, recently demonstrated to be efficacious for postcaesarean analgesia,7 may be performed with enhanced accuracy using ultrasound. From the technical perspective spinal ultrasound imaging is difficult, as the area if interest is protected by bone. As the ultrasound beam does not pass through bone the acoustic window is relatively narrow. Furthermore images from deep structures are poorer in resolution compared with more superficial ones. This is one of the reasons the lumbosacral region was a difficult ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
17
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
area to image with earlier equipment. Most anaesthetists will use a linear high frequency ultrasound probe for superficial vascular access and brachial plexus anaesthesia, but these probes are insufficient for neuraxial imaging. A curved array low frequency (2–5 mHz) probe provides the depth and resolution required for the purpose of imaging the ligamentum flavumepidural complex. With relatively little training, one can use ultrasound to ascertain an appropriate interspace for epidural or spinal anaesthesia. This is usually done with a longitudinal median or paramedian scan. The inaccuracy of clinical palpation to confirm an intervertebral level is well documented. A pre-puncture transverse image is used to identify a needle insertion point in the midline and can also provide an estimate of depth to the epidural space from the skin. The skin can be marked and the epidural placement performed in the standard ‘blind’ fashion. This can be especially helpful in patients where palpable landmarks are not readily identified. Placement of epidural catheters or spinal needles is an area where it remains to be seen if widespread use of ultrasound will occur. Recently published recommendations for education and training in ultrasound-guided regional anaesthesia8 provide defined core competencies and options for acquiring the required skill sets. References 1. la Grange P, Foster PA, Pretorius LK. Application of the Doppler ultrasound bloodflow detector in supraclavicular brachial plexus block. Br J Anaesth 1978; 50 (9): 965-7. 2. Gray AT. Ultrasound-guided regional anesthesia: Current state of the art. Anesthesiology 2006; 104 (2): 368-73. 3. Grau T, Leipold RW, Fatehi S, Martin E, Motsch J. Real-time ultrasonic observation of combined spinal-epidural anaesthesia. Eur J Anaesthesiol 2004; 21 (1): 25-31. 4. Carvalho JC. Ultrasound-facilitated epidurals and spinals in obstetrics. Anesthesiol Clin 2008; 26 (1): 145-58. 5. Marhofer P, Greher M, Kapral S. Ultrasound guidance in regional anaesthesia. Br J Anaesth 2005; 94 (1): 7-17. 6. Grau T, Bartusseck E, Conradi R, Martin E, Motsch J. Ultrasound imaging improves learning curves in obstetric epidural anesthesia: a preliminary study. Can J Anaesth 2003; 50 (10): 1047-50. 7. McDonnell JG, Curley G, Carney J, Benton A, Costello J, Maharaj CH, et al. The analgesic efficacy of transversus abdominis plane block after caesarean delivery: A randomized controlled trial. Anesth Analg 2008; 106 (1): 186-91. 8. Sites BD, Chan VW, Neal JM, Weller R, Grau T, Koscielniak-Neilsen ZJ, et al. The American Society of Regional Anesthesia and Pain Medicine and The European Society of Regional Anaesthesia and Pain Therapy Joint Committee recommendations for Education and Training in Ultrasound-Guided Regional Anesthesia. Reg Anesth Pain Med 2009; 34 (1): 40-6.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
18
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
INVAZIVNE METODE ZA ZDRAVLJENJE KRONIČNE NEMALIGNE BOLEČINE INVASIVE METHODS FOR CHRONIC NON-MALIGNANT PAIN MANAGEMENT Nevenka Krčevski-Škvarč Oddelek za anesteziologijo, intenzivno terapijo in terapijo bolečin, Univerzitetni klinični center Maribor Izvleček. Invazivne metode za zdravljenje kronične nemaligne bolečine so pomemben dodatek ali alternativa konservativnega zdravljenja. Uspešnost in učinkovitost teh metod je odvisna od natančne izbire bolnikov ter poznavanja zapletov in neželenih učinkov. Čim prejšnja utemeljena uporaba intervencijskih tehnik bolnikom zagotavlja lajšanje bolečine, izboljša funkcionalnost in kakovost življenja. Širša uporaba takšnega načina obravnave bolečine je omejena iz finančnih razlogov čeprav analize stroškovne učinkovitosti po določenem času kažejo pozitivne rezultate. Tehnike intervencijske obravnave bolečine se klasificirajo glede na invazivnost. Radiofrekvenčne tehnike, spinalno električno in kemično nevromodulacijo uvrščamo med bolj invazivne. V Sloveniji že vrsto let uporabljamo invazivne načine zdravljenja bolečine, sodobne intervencijske tehnike se še niso primerno razvile. Abstract. Invasive techniques in pain management are an important addition or alternative to conservative treatment. The success and efficacy depend on careful selection of patients and the knowledge of possible complications and side effects. Earlier use of interventional techniques in proper patients enables pain relief, improved functionality and improved quality of life. Wider use of such kind of pain management is limited due to the cost, although cost-effectiveness analysis indicates positive results after certain time. The interventional pain management techniques are commonly classified according to the degree of invasiveness. Radiofrequency techniques, spinal electrical and chemical neuromodulation are the more invasive. Invasive pain management have been used in Slovenia for many years, but contemporary interventional techniques have not been well implemented so far.
Uvod Različni problemi kronične nemaligne bolečine obsegajo hrbtenično bolečino, osteoartritis, ishemično, visceralno, nevropatsko bolečino in glavobole. Številni bolniki trpijo bolečino več kot pet let, prizadeti so lahko odrasli in otroci. Zato kronična bolečina ima pomemben socialni, ekonomski in zdravstveni vpliv. Zdravljenje kronične bolečine je težaven proces za bolnika in njegovega zdravnika. Zdravljenje obsega farmakološke in nefarmakološke metode. Med slednje sodi fizikalna terapija in psihoterapija. Nezadostna učinkovitost in neodzivnost na običajne metode zdravljenja kronične nemaligne bolečine sta prispevala k razvoju nove vede v bolečinski medicini – intervencijske bolečinske medicine. Intervencijska bolečinska medicina obsega blokade in minimalno invazivne posege za diagnosticiranje in zdravljenje bolečine. Tehnike intervencijske obravnave bolečine se delijo glede na stopnjo invazivnosti od terapijskih in diagnostičnih aplikacij učinkovin in fizikalne energije v tarčna mesta do nevromodulacijskih tehnik z zdravili in električno energijo. Ob pravilni diagnozi in primernih pogojih takšne tehnike lahko zagotovijo lajšanje bolečine in izboljšano kakovost življenja. Dobra izbira bolnika in razumevanje mehanizma metode zdravljenja je osnova za učinkovitost zdravljenja. Intervencijske tehnike se najpogosteje uporabljajo za bolečine spinalnega vira in nevropatsko bolečino. Izkušnje govorijo, da čim prejšnja uporaba teh načinov zdravljenja ob pravilni indikaciji zagotavlja optimalno uspešnost.1, 2. Mesto intervencijskih tehnik v zdravljenju bolečine je danes dobro opredeljeno in je del celostne multidisciplinarne obravnave bolnika3, 4 (slika 1). Ameriško združenje za obravnavo bolečine z intervencijskimi tehnikami (ASIPP: American Society of Interventional Pain Management) je letos izdalo priporočila za intervencijsko obravnavo bolečine, ki temelji na obsežni obdelavi raziskav in izkušenj. Priporočila so podana na osnovi ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
19
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
kakovosti znanstvene utemeljenosti (I, II-1, II-2, II-3, III) in so ovrednotena po veljavnosti na 1A, 1B, 1C, 2A in 2C.3 Indikacije za diagnostično blokado malih sklepov so natančno določene, zahteva se 80-odstotno olajšanje bolečine. Enako velja za provocirano diskografijo in blokado sakroiliakalnega sklepa. Terapevtske intraartikularne blokade malih sklepov se ne priporočajo. Blokada medialne veje ima priporočilo veljave 1B ali 1C. Kavdalne epiduralne injekcije steroida imajo priporočilo 1A ali 1B za obravnavo bolečine v križu in radikulitisa ter 1C za bolečine po operaciji na hrbtenici in spinalno stenozo. Enako veljavno priporočilo je za transforaminalne injekcije in spinalno adheziolizo. Za izvajanje intervencijskih posegov v sakroiliakalnem sklepu ni zadostnih podatkov. Priporočila z dobro znanstveno utemeljenostjo so podana za dekompresijo diskusa, lasersko diskektomijo in nukleoplastiko. periferni analgetiki +
rehabilitacijski programi
diagnostične in
psihosomatska obravnava
terapevtske blokade
šibki opioidi
rehabilitacijski programi
RF
psihosomatska obravnava
nevromodulacija močni opioidi
rehabilitacijski programi
skozi usta skozi kožo spinalno - intratekalno
Slika1. Algoritem za zdravljenje kronične bolečine
Radiofrekvenčne tehnike Radiofrekvenčni (RF) električni tok se uporablja za kontrolirano destrukcijo živčnih struktur s termokoagulacijo. Prvič sta ga uporabila Sweet in Wepsic (1974) za RF-obdelavo Gasserjevega ganglija pri trigeminalni nevralgiji. Za lajšanje spinalne bolečine je RF-metodo vpeljal Shealy (1975). V razvoju metode so pomembne postavke izboljšanje igel (Sluijter in Mehta, 1981) in uvajanje utripne RF-tehnike (pulsed radiofrequency – PRF). PRF je še manj nevrodestruktivna, ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
20
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
tako da se lahko uporablja tudi za periferne živce. Indikacija za RF-tehniko je zdravljenje kronične bolečine, ko konservativno zdravljenje ni uspešno. Najpogosteje indikacije so nevralgija trovejnega živca, atipična obrazna bolečina, bolečina v vratu in križu, simpatetično vzdrževana bolečina in maligna bolečina. Smatra se, da je takšno zdravljenje ob pravilni indikaciji primerno pred predpisovanjem opioidnih analgetikov.3 Po priporočilih ASIPP je RF-nevrotomija v vratnem in križnem delu ovrednotena z 1C. Nevromodulacijske tehnike Nevromodulacijske tehnike se delijo v dve glavni skupini: električno in kemično nevromodulacijo. Električne stimulacije lahko izvajamo na nivoju hrbtenjače (SCS), perifernih živcev (PNS), zatilnih živcev (ONS), živčnih korenin, globljih predelov možganov (DBS) in možganske skorje (MCS).5–9. Zdravljenje z vgrajenimi sistemi je povezano z višjimi stroški, zato so za nevromodulacijske tehnike izdelana merila in smernice, ki utemeljujejo izbiro takšnega načina zdravljenja kronične bolečine in se sproti spreminjajo na osnovi znanstveno utemeljenih dokazov.1, 10, 11 Ugotovljeno je, da s takšnim učinkovitim zdravljenjem že po drugem letu zdravljenja pride do zmanjšanja stroškov, ker bolniki potrebujejo manj medicinske obravnave in zdravil, ter se lahko vrnejo na delo.6, 12 Pomemben del procesa je dokumentacija, ki obsega natančno obravnavo bolnika od kliničnega pregleda, evidentiranja stanja bolečine, utemeljitve predvidenega posega, opisa metode, uspešnosti in zapletov ter spremljanja bolnika po posegu. Pred uporabo nevromodulacijskih tehnik treba izključiti kirurško možnost odprave bolečine in opredeliti vrsto bolečine, oziroma ali v klinični sliki prevladuje nociceptivna ali nevropatska bolečina. Splošna izbirna merila za nevromodulacijsko tehniko ob klinični oceni bolnika so: • opredeljena bolečina (po naravi in jakosti), • neučinkovitost konservativnih načinov zdravljenja v multidisciplinarnem obsegu, • izključitev možnosti kirurškega zdravljenja, • izključitev hujših psiholoških motenj, • kontraindikacij ne sme biti, • uspešno preizkusno testiranje (50–80-odstotno olajšanje bolečine). Električna stimulacija hrbtenjače Uporaba elektroterapije v obravnavi bolečine je doživela večji razmah po Melzakovi in Wallovi razlagi »teorije vrat« v letu 1965. Električna stimulacija hrbtenjače (spinal cord stimulation – SCS) je najpogostejša oblika uporabljane nevromodulacije. Tehniko je vpeljal Shealy v letu 1967. Najkoristnejša je za konvencionalno neobvladano bolečino perifernega nevrogenega vira. Učinkovitost metode pri nevropatski bolečini razlagajo kot specifično delovanje na vlakna Aβ, na transmitorsko-receptorske sisteme (snov P, serotonin, glutamat, aspartat, baklofen) in na supraspinalne sisteme.13 Kontraindikacije so nekatere koagulopatije, infekcija, zasvojenost in hude psihične spremembe. Ameriško združenje zdravnikov, ki se ukvarjajo z intervencijsko obravnavo bolečine (American Society of Inerventional Pain Physicians – ASIPP, Interventional Pain Management – IPM) priporoča SCS za dolgotrajno klinično uporabo kot priporočilo jakosti 1B ali 1C z nivojem znanstvene utemeljenosti II-1 in II-2, predvsem za indikaciji FBSS (failed back surgery) in CRPS (complex regional pain syndrome). Stroškovna učinkovitost metode se pokaže po dveh letih.1 Tehnike nevromodulacije z intratekalnim dovajanjem zdravil Intratekalno dovajanje zdravil (intrathecal drug delivery – IDD) se uporablja za lajšanje neznosne maligne bolečine že zelo dolgo. V letu 1982 so že uveljavili vgrajene sisteme za IDD učinkovin, predvsem morfina in bupivakaina. Za izvajanje takšnega načina zdravljenja za nemaligno bolečino imamo prva priporočila iz leta 1997 v ZDA (Portenoy, Savage) in 1998 v Evropi (Gybels). Danes imamo na razpolago različna zdravila in priporočila za izbiro zdravil.11 Za izbiro zdravila moramo dobro poznavati nevrofiziologijo in način delovanja zdravila, toksičnost in klinične ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
21
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
podatke o varnosti, učinkovitosti in možnosti kombiniranja različnih učinkovin. Zdravila, registrirana za intratekalno dovajanje, so morfin, baklofen in zikonotid, vendar se uporabljajo tudi številne druge učinkovine14 (razpredelnica 1). Najpogostejša indikacija za intratekalne črpalke je spinalna bolečina, specifični adhezivni arahnoiditis, postlaminektomijska bolečina, spinalna stenoza in neznosne bolečine v križu in nogah. Nivo znanstvene utemeljenosti za intratekalne infuzijske sisteme je ob pravilni izbiri bolnikov opredeljen na II-3 ali III, metoda se priporoča kot priporočilo jakosti 1C. Razpredelnica 1. Priporočilo za izbiro zdravila za intratekalno kontinuirano dovajanje
1. linija
a – morfin
2. linija
d – fentanil
3. linija
d – klonidin
4. linija
i – sufentanil
5. linija
k – ropivakain, buprenorfin, midazolam, meperidin, ketorolak
6. linija
eksperimentalna zdravila
b – hidromorfon
c – zikonotid
e – morfin /hidromorfon + zikonotid h – morfin /hidromorfon/fentanil + bupivakain + klonidin/zikonotid j – sufentanil + bupivakain + klonidin/zikonotid
f – morfin /hidromorfon + bupivakain/klonidin
Invazivne metode zdravljenja bolečine v Sloveniji Diagnostične in terapevtske periferne in centralne blokade, epiduralne injekcije steroida in dovajanje analgetičnih učinkovin v spinalni prostor z zunanjimi sistemi se uporabljajo več kot trideset let. Zametki RF-terapije so nastali v osemdesetih letih, vendar se niso razvili. Nevromodulacija z zdravili in vgrajenimi sistemi se je začela pred desetimi leti, večinoma za zdravljenje spastičnosti. Zadnjih pet let se nekoliko več uporablja metoda SCS. Razvoj intervencijske bolečinske medicine v Sloveniji je omejen iz več razlogov, predvsem ekonomskih in kadrovskih, vendar tudi v povezavi s primerno izobraženostjo in licenciranjem strokovne usmerjenosti v bolečinsko medicino. V letu 2008 smo ustanovili strokovno interdisciplinarno skupino za nevromodulacijo, ki bo skrbela za razvoj nacionalne kakovostne nevromodulacijske oskrbe. Podobna telesa imajo tudi drugje v svetu.10 Literatura 1. Van Buyten JP. Radiofrequency or neuromodulation treatment of chronic pain, when it is useful? Eur J Pain 2008; 2: 57-66. 2. Stojanovic MP. Stimulation methods for neuropathic pain control. Curr Pain Headache Reports 2001; 5: 130-7. 3. Manchikanti L, Boswell MV, Singh V, Benyamin RM, Fellows B, Abdi S, et al. Comprehensive evidence-based guidelines for interventional techniques in the management of chronic spinal pain. Pain Physician. V tisku 2009. 4. Puig M. When does chronic pain become intractable and when is pharmacological management no longer appropriate? J Pain Symptom Manage 2006; 15: S1-2. 5. Vallejo R, Kramer J, Benyamin R. Neuromodulation of cervical spinal cord in the treatment of chronic intractable neck and upper extremity pain: A case series and review of the literature. Pain Physician 2007; 10: 305-11. 6. Manca A, Kumar K, Taylor RS, Jacques L, Eldabe S, Eldabe S, et al. Quality of life, resource consumption and costs of spinal cord stimulation versus conventional medical management in neuropathic pain patients with failed back surgery syndrome (PROCESS trial). Eur J Pain 2008; 12: 1047-58. 7. Oakley JC. Spinal cord stimulation: Patient selection, technique and outcome. Neurosurgery Clin N Am 2003; 14: 365-80. 8. Slavin KV. Peripheral nerve stimulation for neuropathic pain. Neurotherapeutics 2008; 5: 100-6. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
22
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
9. Lefaucheur JP, Drouot X, Cunin P, Bruckert R, Lepetit H, Creange A, et al. Motor cortex stimulation for the treatment of refractory peripheral neuropathic pain. Brain 2009; 132: 1463-71. 10. Theuvenet PJ, Dekkers MA, Beerrse N, Klazinga NS, Spincemaille GHJJ. The development of a quality system for neuromodulation in the Netherlands. Neuromodulation 2005; 8: 28-35. 11. Deer T, Krames ES, Hassenbusch SJ, Burton A, Caraway D, Dupen S, et al. Polyanalgesic consensus conference 2007: Recommendations for the management of pain by intrathecal (intraspinal) drug delivery: Report of an interdisciplinary expert panel. Neuromodulation 2007; 10: 300-28. 12. Kumar K, Malik S, Demeria D. Treatment of chronic pain with spinal cord stimulation versus alternative therapies: Cost-effectiveness analysis. Neurosurgery 2002; 51: 106-16. 13. Meyerson BA, Linderoth B. Mode of action of spinal cord stimulation in neuropathic pain. J Pain Symptom Manage 2006; 31: S7-12. 14. Belverud S, Mogilner A, Schulder M. Intrathecal pumps. Neurotherapeutics 2008; 1: 114-22.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
23
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
ZDRAVLJENJE BOLEČINE Z BOTULINOM TREATMENT OF PAIN WITH BOTULINUM TOXIN Milan Roman Gregorič Ortopedska bolnišnica Valdoltra, Ankaran, in Inštutut Republike Slovenije za rehabilitacijo, Ljubljana Izvleček. Botulin je živčni strup, ki zavira sproščanje acetilholina na živčnomišičnem stiku in tako hromi mišice. Serološka tipa botulina A (Botox, Dysport) in B (Myobloc/NeuroBloc) uporabljamo klinično za zdravljenje številnih sindromov, predvsem tistih, ki so povezani z žariščno pretirano in nehoteno dejavnostjo mišic pri distoniji in spastičnosti otrok ter odraslih. Sproščanje mišic po botulinski terapiji zmanjšuje tudi bolečine. Klinične izkušnje in podatki raziskav kažejo, da toksin ne deluje na bolečine le prek mišic, ampak tudi na druge, farmakološko in nevrofiziološko še ne povsem pojasnjene načine. Ugotovljeno je tudi ugodno delovanje botulina na bolečine v vratu in križu, medenici, sklepih, pri miofascialnih bolečinskih sindromih, nekaterih sindromih nevropatkse bolečine, kompleksnem regionalnem bolečinskem sindromu, primarnem glavobolu in migreni. Protibolečinski učinki botulina pri teh sindromih še niso zanesljivo preverjeni po kriterijih znanstveno utemeljene medicine. Botulinska terapija je učinkovitejša, če jo izvajajo izkušeni strokovnjaki v okviru interdisciplinarne obravnave. Kljub številnim obetavnim podatkom v literaturi širša klinična uporaba toksina za zdravljenje bolečine še ni priporočena.
Abstract. Botulinum neurotoxin inhibits acetylcholine release at the neuromuscular junction resulting in muscle paresis. Serological types A (Botox, Dysport) and B (Myobloc/NeuroBloc) are clinically used in treatment of several syndromes, in particular those related to focal excessive involuntary muscle activity in dystonia and spasticity of adults and children. Muscle relaxation following botulinum treatment gives also pain relief. Clinical experiences and experimental data indicate that botulinum relieves pain not only through muscle relaxation; the analgesic effect may be exerted also by some others not yet completely recognized pharmacological and neurophysiological mechanisms. A beneficial therapeutic effect of botulinum was shown also in neck and low back pain, joint pain, myofascial pain syndromes, selected neuropathic pain syndromes, complex regional pain syndrome and primary headache including migraine. Analgesic effects of botulinum toxin in these syndromes were not completely revealed according to the criteria of the evidence based medicine. Treatment with botulinum is more effective when used by experienced personnel within an interdisciplinary management. In spite of numerous encouraging recent data in literature a widespread clinical use of botulinum would not yet be recommended.
Uvod Botulin je živčni strup, ki ga tvori anaerobna bakterija Clostridium botulinum. Botulin preprečuje sproščanje acetilholina na živčnomišičnem stiku in drugih holinergičnih sinapsah in tako povzroča reverzibilno delno denervacijo injiciranih mišic. Obstaja 7 seroloških tipov toksina (A-G). Klinično uporabljamo tip A, zadnje čase tudi tip B, medtem ko klinično uporabnost drugih tipov še raziskujejo. Na evropskem tržišču je na voljo za klinično rabo botulin tipa A z lastniškim nazivom Botox in Dysport ter tipa B z nazivom Myobloc/NeuroBlock. Pri nas uporabljamo vsa omenjena zdravila, registriran pa je le Dysport. Učinkoviti odmerki različnih oblik botulina niso enaki. Izkušnje kažejo, da je Dysport približno enako učinkovit kot Botox pri 3–5-krat večjem odmerku. Vistabel je indiciran le za kozmetično uporabo. Mišice, v katere vbrizgamo botulin, so bolj sproščene in bolj mlahave, vendar tudi manj močne. Botulin, vbrizgan v bolezensko pretirano dejavne mišice pri spastičnosti in distoniji, zmanjšuje mišični tonus, povečuje razteznost mišic, izboljša gibalne funkcije in nenormalne telesne položaje, zmanjšuje mišične krče in hkrati blaži bolečine. Fizikalna terapija je po botulinski terapiji lažja in bolj učinkovita. S kombinacijo botulinske in fizikalne terapije učinke botulina okrepimo in podaljšamo. Uspešnejša je tudi uporaba opornic in učinkovitejša je živčnomišična električna stimulacija. Botulinska terapija zato po veljavni doktrini ni samostojen terapevtski postopek, ampak je »terapevtsko okno« v okviru celostne rehabilitacije. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
24
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Učinek botulina na nenormalno mišično dejavnost traja 3 do 4 mesece po aplikaciji, redko več, najdlje 5 do 6 mesecev. Pri ponavljanju botulinske terapije lahko terapevtski učinki slabijo ali povsem prenehajo, kar je posledica tvorbe protiteles. Zato botulinske terapije praviloma ne ponavljamo v presledkih, ki so krajši od 6 mesecev. V klinični praksi uporabljamo botulin najpogosteje pri patološko pretirani mišični dejavnosti, pri žariščno povečanem mišičnem naponu in zakrčenosti mišic zaradi različnih vzrokov, predvsem pri žariščnih distonijah in spastičnosti. Zadnja leta so se indikacije botulinske terapije zelo razširile. Botulin uspešno uporabljajo tudi pri spastičnosti gladkih mišic, pri disinergiji detruzorsfinkter, analni fisuri, sialoreji, hiperhidrozi in drugih sorodnih motnjah.1 Protibolečinski učinki botulina so bili najprej ugotovljeni pri zdravljenja distonije in spastičnosti. Patološko pretirana in dolgotrajna dejavnost mišic, ki se ne morejo normalno sprostiti in spočiti, povzroča mišičnoskeletno (nociceptivno) bolečino zaradi motenj prekrvitve in drugih patogenetskih dejavnikov. Razumljivo je, da sprostitev mišic omili tudi bolečino, ki jo povzroča pretirana dejavnost teh mišic. Več kliničnih podatkov kaže, da protibolečinski učinki botulina niso zgolj posledica oslabitve pretirane žariščne mišične dejavnosti zaradi zavore sproščanja acetilholina in kemodenervacije motoričnih ploščic ekstrafuzalnih in intrafuzalnih mišičnih vlaken:2–4 • protibolečinski učinek lahko nastopa pred spremembami mišične dejavnosti; • protibolečinski učinek traja dlje od dokazljivega učinka na mišično dejavnost; • botulin omili bolečino, ki ni povezana s pretirano ali spremenjeno mišično dejavnostjo pri nekaterih sindromih nevropatske bolečine.5, 6 Mehanizmi protibolečinskega delovanja botulina so glede na klinične in eksperimentalne študije različni in so neposredni in posredni.2, 3 Neposredno protibolečinsko delovanje: • inhibicija motoričnih nevronov alfa in gama (inhibicija holinergičnega oživčenja); • inhibicija sproščanja nevropeptidov. Posredno protibolečinsko delovanje: • zmanjšanje nevrogenega vnetja; • izboljšanje prekrvitve zaradi sprememb v delovanju avtonomnega živčevja in sproščanja mišičnih spazmov; • spremenjen aferentni dotok impulzov v osrednje živčevje (spremenjen senzorični vzorec). Posledice neposrednega in posrednega delovanja botulina na živčevje in mišičje: • zmanjšanje mišičnih krčev in s tem senzitizacije ter aktivacije nociceptorjev; • zmanjšanje centralne senzitizacije; • možna nevroplastična reorganizacija v osrednjem živčevju; • preprečevanje degenerativnih sprememb mišičnih vlaken,veziva, sklepov in okostja. Povečan mišični napon povečuje potrebo po kisiku, ki presega zagotovljeno oskrbo, zaradi česar nastaja ishemija. Zaradi ishemije se sproščajo nociceptivne snovi, vzburijo se nociceptorji, različni mehanoreceptorji se spreminjajo v nociceptorje. Vse to na koncu povzroča »navito« bolečino in centralno senzitizacijo.3, 4 Lokalno povečan mišični napon povzroča spremembe drže in bolečine pri mišični distoniji in spastičnosti in je lahko vir bolečin tudi pri miofascialnem sindromu, kroničnih lumboishialgijah in cervikobrahialgijah in glavobolu tenzijskega tipa. Povezava med bolečino in spremenjeno mišično dejavnostjo pri teh sindromih pa ni vedno jasna. Bolečino lahko povzroča neposredno stalna in pretirana mišična kontrakcija, lahko pa jo povzroči tudi sekundarno draženje živčevja na različnih mestih. Botulin ne deluje le neposredno na ekstrafuzalna vlakna skeletnih mišic, ampak na holinergične živčne končiče, ki so tudi v mišičnih vretenih in drugih tkivih, denimo v tetivah.7 S tem so zavrti povratni mehanizmi, ki uravnavajo mišični tonus prek dotoka impulzov iz mišičnih vreten do motoričnih nevronov alfa. Zaviranje dejavnosti intrafuzalnih vlaken v mišičnih vretenih, ki so receptorji refleksa na nateg, zmanjšuje aferentni dotok impulzov v osrednje živčevje. Zmanjšan aferentni priliv bi lahko vplival tudi na tudi na »reorganizacijo« dejavnosti osrednjega živčevja in na zaznavanje bolečine.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
25
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Botulin vpliva tudi na delovanje avtonomnega živčevje.3 Z zaviranjem sproščanja acetilholina vpliva na delovanje parasimpatičnega živčevja. Pri poskusnih na živalih so pokazali retrogradni transport botulina po živcih do korenin in hrbtenjače ter prenos znotraj hrbtenjače.8, 9 Tako bi si lahko razložili učinke botulina, ki so oddaljeni od mesta aplikacije. Ni pa verjetno, da bi se celoten toksin širil po aksonih nespremenjen, ampak se v osrednjem živčevju verjetno retrogradno širijo produkti njegove razgradnje. Ti bi lahko delovali na osrednji senzorični nociceptivni sistem. Botulin, ki so ga vbrizgali živalim neposredno v hrbtenjačo, je deloval zaviralno predvsem na motorične nevrone.8 Ni pa izključeno, da ne delujejo metaboliti botulina zaviralno na različne živčne prenašalce. Pomemben živčni prenašalec, ki spodbuja nevrogeno vnetje, je snov P. Botulin ne zavira le sproščanja acetilholina, ampak tudi snovi P iz končičev trovejnega živca.8 Zaviranje delovanja snovi P zmanjšuje vzdražnost nociceptorjev in s tem tudi izvabljivost bolečih refleksnih spazmov. Ugotovljeno je tudi, da lahko botulin poveča vsebnost enkefalina v hrbtenjači.10 Lokalizirana bolečina pri miofascialnem sindromu je lahko posledica poškodbe mišice, ki povzroči pretiran mišični odziv s spremljajočo ishemijo ter lokalnim sproščanjem acetilholina. Pogoste spontane depolarizacije v področju prizadetih motoričnih ploščic sprožijo lokalizirano dolgotrajno krčenje mišičnih vlaken, ki povzroči pasivno raztezanje neprizadetih sosednjih mišičnih vlaken.2, 3 Tak bi bil lahko mehanizem nastajanja bolečih prožilnih točk, za katere so značilne tipne točkaste ali trakaste mišične zatrdline. Boleče točke, ki vzdržujejo bolečine po pravilu začaranega kroga, lahko pospešujejo mehanizme supraspinalne senzitizacije in »navito bolečino«. Z aplikacijo botulina v boleče točke zavremo sproščanje acetilholina in tako prekinemo začarani krog, blažimo bolečino in preprečimo razvoj kronične bolečine zaradi centralne senzitizacije. Dolgotrajne spremembe mišične dejavnosti povzročajo degenerativne spremembe mišičnih vlaken, veziva, sklepov in okostja, ki so dodaten vir bolečin. Botulin bi lahko s slabitvijo nenormalne mišične dejavnosti tudi zaviral nastajanje teh degenerativnih sprememb. Neželeni učinki botulina so redki, prehodni in večinoma niso resni. Največkrat gre za neposredne posledice učinkov botulina, ki pa so nepričakovano močni in funkcionalno moteči zaradi pretirane mlahavosti ali oslabelosti tarčnih mišic. Redkeje nastopajo splošna oslabelost, hitrejše utrujanje, glavobol in navzea. Ti zapleti so večinoma blagi in kratkotrajni. Zelo redko se učinek botulina razširi, tako da povzroči hudo splošno mišično oslabelost z disfagijo in aspiracijo. Prehodne motnje požiranja nastopajo zlasti pri aplikaciji toksina na vratnih mišicah, najpogosteje pri zdravljenju tortikolisa. Redko je potrebna prehodna mehanska ventilacija zaradi odpovedovanja respiratornih mišic. Izjemno redka so poročila o anafilaksiji in hudih zapletih s smrtnim izidom.4 Proizvajalci zdravil z botulinskim toksinom (Allergan, Solstice Neurosciences in Ipsen) so po razpravi z nacionalnimi agencijami za zdravila v Evropski uniji, tudi z Javno agencijo RS za zdravila in medicinske pripomočke (JAZMP) združeno opozorili na resne neželene učinke botulina, povezane z razširitvijo učinkov toksina z mesta aplikacije. Opozarjajo na skrajno previdnost pri dajanju botulina bolnikom z nevrološkimi boleznimi ali težavami s požiranjem, ki so posebej nagnjeni k neželenim učinkom in jih je zato treba izjemno skrbno zdraviti in spremljati. Da bi tveganje resnih reakcij zaradi širjenja učinkov toksina omejili na najmanjšo možno mero, moramo dosledno upoštevati odmerjanje, opozorila in previdnostne ukrepe: • Zdravila z botulinom lahko daje samo zdravnik z ustreznimi izkušnjami ob uporabi ustrezne opreme. • Bolnike ali negovalce in skrbnike je potrebno obvestiti o tveganju širjenja toksina in jim svetovati, da poiščejo zdravniško pomoč pri težavah s požiranjem, govorjenjem ali dihanjem. • Enote botulina med različnimi zdravili niso zamenljive. • Upoštevati je potrebno priporočene tehnike dajanja in posebna navodila glede odmerjanja. Distonija Bolečina je pogosta in v nekaterih primerih celo prevladujoča težava pri žariščni in aksialni distoniji. Posebno pogosta je pri cervikalni distoniji; bolečine opisujejo pri 60–80 % bolnikov.11 ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
26
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Pretirana nenormalna dejavnost mišic povzroča stalne biomehanske spremembe in pospešuje zgodnje okvare hrbtenice, živčnih korenin in hrbtenjače, kar so še dodatni viri bolečin. Klinične izkušnje in študije kažejo, da je zmanjšanje bolečin ena od glavnih prednosti botulinske terapije pri mišični distoniji. Analgetični učinek lahko pomembno presega stopnjo terapevtskih učinkov na nenormalno gibalno dejavnost vratnih mišic.12 Pregled objavljenih randomiziranih nadzorovanih študij uporabe botulina tipa A in B pri cervikalni distoniji (skupno 16 študij) je pokazal, da so bili učinki botulina na bolečino ugodni pri večini bolnikov.4 Bolniki so poročali o izboljšanju bolečine za 60–86 %. Tarsy in First13 sta ugotovila, da se pri 59,4 % bolnikov bolečina ni nikoli povrnila na stopnjo pred terapijo z botulinom. Ugodni učinki botulina na bolečino so opisani tudi pri mioklonični obliki tortikolisa in tremorju glave.14 Injekcija botulina v ledvene paraspinalne mišice je pomembno omilila bolečine pri bolnikih z ekstenzijsko obliko distonije hrbtnih mišic.15 Bolečine, ki jih pripisujejo dolgotrajnim mišičnim krčem, so pogoste pri bolnikih s parkinsonizmom, ki se dalj časa zdravijo z levodopo. Bolečine spremljajo medikamentno povzročeno žariščno distonijo z zgibki v obdobjih »izključevanja«. Pacchetti s sod.16 je pri 30 bolnikih s Parkinsonovo boleznijo in bolečo medikamentno povzročeno distonijo noge vbrizgal botulin v nenormalno delujoče mišice. Bolečina se je zmanjšala pri vseh bolnikih, pri 21 je celo prenehala za 3–7 mesecev. Analgetični učinek je spremljal zmanjšanje mišične distonije. Pri našem delu smo ugotovili ugodne učinke botulina tudi pri manjši skupini bolnikov z žariščno mišično distonijo po nezgodni poškodbi kosti ali sklepov in pri kompleksnem regionalnem bolečinskem sindromu (KRBS). Patološka nehotena dejavnost mišic je bila pri teh bolnikih ugotovljena klinično in elektromiografsko. Po botulinski terapiji je nehotena mišična dejavnost močno popustila, pomembno pa so se zmanjšali tudi simptomi in znaki KRBS. Spastičnost Spastičnost je lahko zelo boleča. Bolečine povzročajo nenormalna in dolgotrajna mišična dejavnost, položajne spremembe telesa in sekundarna prizadetost mehkih tkiv, sklepnih ovojnic in sklepov, ki so nenormalno obremenjeni. Spazmi spodnjih udov, spontani ali izvabljivi z lahnim dražljaji, so pogosto boleči. Posebno pogosti, moteči in boleči so pri okvarah hrbtenjače. Nenormalno pretirana mišična dejavnost, gibalne in položajne spremembe povečujejo možnosti nociceptivne bolečine, ki dodatno spodbuja refleksno pogojeno spastičnost. Neprekinjena mišična kontrakcija pri spastičnosti lahko povzroči tudi ishemijo in sproščanje vnetnih snovi, ki dražijo nociceptorje, ti pa sprožijo spazme in ojačijo bolečine. Tako nastaja začaran krog, v katerem ima bolečina ključno vlogo. Tonus mišic, v katere vbrizgamo botulin, se zmanjša in mišice se lažje ter izdatneje raztezajo. S tem se lahko pomembno izboljša funkcijsko gibanje, kadar je to zavrto zaradi spastičnosti. Pri nepopolni spastični ohromelosti moramo upoštevati, da kemodenervacija mišice dodatno oslabi, kar je lahko tudi funkcionalno moteče za gibanje in telesno držo. To velja za primere, ko spastičnost ni huda in moteča, ampak povzroča motnje gibanja predvsem mišična oslabelost in ohromelost. Pomembno je skrbno izbrati kandidate za botulinsko terapijo, ki imajo motečo žariščno spastičnost in bolečine. Evropska skupina strokovnjakov je na osnovi kliničnih izkušenj in raziskav uskladila doktrinarna izhodišča za botulinsko terapijo spastičnosti odraslih.17 V objavljenih priporočilih te skupine je med drugim zapisano, da je botulin zelo učinkovit pri zdravljenju žariščne spastičnosti, vendar je potrebna timska multidisciplinarna obravnava bolnikov. Terapijo naj izvajajo strokovnjaki, ki imajo izkušnje pri diagnosticiranju in zdravljenju spastičnosti in dobro poznajo funkcionalno anatomijo ter klinično farmakologijo. Botulinska terapija s pridruženo fizioterapijo lahko kot del celostne obravnave bolnikov s spastično ohromelostjo preprečuje ali vsaj zavira kronične zaplete in razvoj trdovratnih bolečinskih sindromov.17, 18
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
27
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Bolečine v vratu in križu Ključno vlogo pri bolečinah v vratu in križu različne etiologije ima pogosto pretirana dolgotrajna nehotena mišična kontrakcija. Bolečine, ki jih povzročajo bolezni hrbtenice in okvare živčevja, sprožijo krče mišic ob hrbtenici, na eni ali obeh straneh, ki imajo zaščitno vlogo, ker preprečujejo pretirane, potencialno škodljive gibe hrbtenice in telesa. Pri kronični bolečini pa mišični spazmi izgubijo svoj prvotni obrambni pomen in postanejo sami vir bolečin. Tako nastaja »začaran bolečinski krog«. Bolečine lahko povzročajo kemične snovi, ki nastajajo pri presnovni razgradnji v mišicah in ishemija zaradi povečane potrebe po kisiku. Zato se zdijo smiselni ukrepi, ki zmanjšujejo pretirano dejavnost mišic ob hrbtenici, ki tudi zmanjšujejo bolečine. To dosežemo s fizikalno terapijo in različnimi zdravili. V zadnjem času je v literaturi vse več podatkov o ugodnih učinkih botulina, ki ga dajemo v boleče mišice ob vratni ali ledveni hrbtenici. Botulin sprošča zakrčene mišice, morda pa ima tudi neposreden analgetični učinek. Botulin lahko omili bolečine v vratu in glavobol po nihajni poškodbi vratne hrbtenice in izboljša gibljivost vratne hrbtenice, vendar rezultati študij niso zelo prepričljivi.19, 20 Wheeler in sod.21 niso ugotovili ugodnih učinkov botulina pri bolnikih s kronično bolečino v vratu, ki niso imeli fizikalne terapije. Avtorji domnevajo, da je fizikalna terapija po aplikaciji botulina ključnega pomena za zmanjšanje težav in olajšanje bolečin. Učinki botulinske terapije pri bolečinah v križu, opisani v številnih študijah, niso povsem jasni. Pregled ugotovitev teh študij kaže, da je botulin verjetno učinkovit pri bolnikih z dobro opredeljeno bolečino, ki jo povzroča mišični spazem, potem ko so bili izključeni drugi vzroki bolečine4 in so odpovedali drugi terapevtski ukrepi.22 Na botulinsko terapijo lahko gledamo v teh primerih kot na terapevtsko okno, ki omogoča uspešnejšo konvencionalno fizikalno terapijo v času učinkovanja botulina, ki traja več mesecev. Žal pa se menja avtorjev razhajajo glede načina in optimalnega mesta aplikacije botulina. Zato tudi ni možno zanesljivo sklepati o optimalnih postopkih botulinske terapije in njenih dolgotrajnih učinkih pri bolečinah v križu. Po podatkih več različnih študij naj bi bil analgetski učinek botulina večji in dolgotrajnejši od običajnih terapevtskih postopkov fizikalne terapije in lokalne aplikacije anestetikov ter steroidov.4 V raziskavi z naključno razporejenimi bolniki z bolečinami v križu in kontrolno skupino s placebom, so ugotovili, da so se po vbrizganju botulina v ledvene paraspinalne mišice obeh strani bolečine pomembno zmanjšale (za več kot 50 %) pri večini bolnikov (67–70 %) do konca študije, trajajoče več mesecev.4, 23, 24 Vprašanje pa je, ali ni ohlapnost in oslabelost mišic ob hrbtenici, ki jo povzroča botulin, prevelika in neprimerna cena za nekajmesečno olajšanje bolečin.25 Botulin je zaenkrat le možnost zdravljenja bolečin v vratu in križu, če so izključeni znani bolezenski vzroki, ki jih lahko etiološko zdravimo. Preden pomislimo na botulin, moramo poskusiti vse druge preverjene postopke zdravljenja. Le pri tistih bolnikih, pri katerih vsi drugi postopki odpovejo, lahko izberemo botulin kot dodatno sredstvo v okviru multimodalne obravnave. Pred terapijo je potrebno skrbno poiskati ključne mišice, pri bolečinah v vratu in križu pretežno paraspinalne in prožilne točke (trigger points). Več avtorjev svari pred nekritično uporabo botulina, ki naj bi bil prihranjen za izkušene strokovnjake, in še to po možnosti v nadzorovanih študijah. Preden bi botulin prešel v širšo klinično rabo, bi morali narediti več razširjenih in poglobljenih raziskav. Podrobneje bo potrebno pojasniti merila za izbiro bolnikov, ustrezne odmerke in optimalna mesta aplikacije botulina. Glavobol Več nedavnih objav opisuje ugodne učinke botulina na primarni glavobol različnih oblik.26–29 TB so dajali v več mišic obraza in vratu, ki so bile boleče na otip ali pritisk. Podobno zmanjšanje bolečin so ugotovili pri dajanju botulina v frontalne in temporalne mišice ter v m. sternocleidomastoideus ne glede na bolečnost in žariščno občutljivost pri bolnikih, ki jim niso pomagali postopki fizikalne in medikamentne terapije.30 V primerjalni študiji so v boleče perikranialne mišice vbrizgali nekaterim bolnikom metilprednizolon, drugim botulin. Pri vseh bolnikih so ugotovili večmesečno zmanjšanje bolečin, vendar pomembno večje po terapiji z botulinom kot s steroidi.30 Troost31 je z botulinom zdravil različne oblike glavobola, ki ni bil odziven na drugo zdravljenje. Izboljšanje je ugotovil po več aplikacijah botulina pri 84 % bolnikov in je menil, da so ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
28
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
učinki lahko progresivni in kumulativni. Botulin se danes največ uporablja v kozmetiki, ker gladi gube na obrazu. Tako so slučajno odkrili, da botulin, vbrizgan v mišice obraza zaradi kozmetičnih razlogov, zmanjša tudi bolečino pri migreni.32–34 Novejše študije pri večjem številu bolnikov s kroničnim dnevnim glavobolom nakazujejo tendenco ugodnega delovanja botulina, ne odkrivajo pa prepričljivih podatkov o tako zanesljivih ugodnih učinkih, kot so opisani v prvih poročilih, ki so izzvala veliko navdušenja.1, 35 Pri pregledu objavljenih podatkov in presoji njihove vrednosti z vidika strožjih meril znanstveno utemeljene medicine avtorji ne priporočajo široke uporabe botulina za zdravljenje glavobola. Priporočajo le skrbno načrtovane klinične študije pri izbranih skupinah bolnikov.1, 4, 35 Miofascialna bolečina Za miofascialni bolečinski sindrom je značilna žariščna, akutna ali kronična bolečina z mišično okorelostjo in večjo utrudljivostjo. Mišice so napete, skrajšane z bolečimi prožilnimi točkami na otrdelih mestih. Patofiziološke spremembe, ki povzročajo ta sindrom so nejasne. Bolečino bi lahko prožila povečana dejavnost motoričnih ploščic s povečanim sproščanjem acetilholina na živčnomišičnih stikih. Ta hipoteza bi lahko razložila tudi ugoden učinek TB, ki zavira prenos na živčnomišičnem stiku in sprošča stalno pretirano mišično kontrakcijo ter lajša s tem povezano bolečino. Velika multicentrična raziskava z naključnimi nadzorovanimi preskusi pri bolnikih z zmerno ali hudo miofascialno bolečino v vratu in/ali ramenih je pokazala pomembno zmanjšanje bolečine po aplikaciji botulina pri 51 % bolnikov.4, 36, 37 V študiji z naključno izbranimi bolniki s kroničnim miofascialnim sindromom so vbrizgali botulin ali metilprednizolon z bupivakainom (0,5 %) v mišice piriformis, iliopsoas, ali scalenus anterior.38 Obe skupini bolnikov sta imeli tudi fizioterapijo. Bolečina je pomembno popustila pri obeh skupinah bolnikov, bolj pri tistih, ki so dobili botulin kot pri bolnikih, ki so prejeli steroid. Botulin je bil učinkovitejši takoj po začetku terapije in tudi 30 ter 60 dni kasneje. Razlika v učinkih pri obeh skupinah bolnikov je bila posebno izrazita 60 dni po terapiji, ko je učinek steroida že popuščal. Ugoden učinek botulina na miofascialno bolečino v primerjavi z drugimi terapevtskimi ukrepi in s placebom so pokazale tudi druge študije v več centrih, pri katerih je bil botulin vbrizgan v boleče točke vratnih paraspinalnih in obramenskih mišic.39 Nasprotno pa je sistematični pregled študij učinkov botulina pri terapiji miofascialnih prožilnih točk bolečine z upoštevanjem pravil znanstveno utemeljene medicine razkril, da izsledki študij še ne upravičujejo klinične uporabe botulina tipa A.1, 4 Drugi bolečinski sindromi Ugodni učinki botulina so opisani pri bolečinah v medenici in pri sindromu m. piriformisa.4, 40, 41 Pri bolečinah v sklepih zgornjih in spodnjih udov in v temporomandibularnem sklepu so opisani ugodni protibolečinski učinki botulina, ki omogočajo tudi večjo gibljivost in lažje izvajanje terapevtskih vaj.4 Vedno več je poročil o ugodnih protibolečinskih učinkih botulina pri nevropatski bolečini, ki jo povzročajo različne bolezni: postherpetična nevralgija, nevralgija trovejnega živca, multipla skleroza, polinevropatija, utesnitvene nevropatije, okvara vratne hrbtenjače, okvara brahialnega pleteža, nevrinomi in fantomska bolečina.4–6 Pri našem kliničnem delu smo ugotovili, da botulin lahko omili bolečino in izboljša funkcionalno gibljivost pri KRBS, kar je opisalo tudi nekaj drugih avtorjev.4 Botulin lahko za več mesecev omili bolečino pri lateralnem epikondilitisu (teniški komolec), vendar oslabi ekstenzijo prstov.42 V nasprotju s pozitivnimi rezultati več študij so ugotovitve Haytona in sod.,43 ki pri dvojno slepi randomizirani in nadzorovani študiji niso ugotovili zanesljivo ugodnih učinkov, tako da je vprašanje rabe botulina pri teniškem komolcu še odprto. Zaključki Botulin lajša bolečino, ki jo povzroča pretirana nehotena mišična dejavnost, predvsem pri distoniji in spastičnosti. Botulin lahko ugodno deluje tudi na bolečine pri mišičnih spazmih, ki spremljajo miofascialne sindrome, bolečine v križu in vratu. Po botulinski terapiji so mišice več mesecev ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
29
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
bolj sproščene, bolečine pa so manjše. Učinki toksina na bolečine in mišično dejavnost niso vselej jasno medsebojno povezani. Opisano je tudi ugodno delovanje botulina na bolečine v medenici, pri sindromu m. priformisa, pri nekaterih sindromih nevropatske bolečine. Protibolečinski učinki botulina pri teh sindromih še niso zanesljivo preverjeni po merilih znanstveno utemeljene medicine. Domnevamo, da botulin ali njegovi metaboliti ne delujejo na bolečino le z zaviranjem delovanja acetilholina, ampak tudi na druge, še ne povsem pojasnjene načine. Botulinska terapija je del interdisciplinarne obravnave bolnikov, ki jo vodijo izkušeni strokovnjaki. Indicirana je pri distoniji in spastičnosti, pri drugih bolečinskih sindromih pa le izjemoma, ko odpovejo drugi postopki zdravljenja z upoštevanjem previdnostnih ukrepov. Kljub obetavnim poročilom v literaturi širša klinična uporaba botulina pri bolečinah v vratu in križu, glavobolu in drugih bolečinskih sindromih še ni priporočena. Potrebne so nadaljnje študije, ki bodo podrobneje opredelile merila za izbiro bolnikov, postopke terapije in ugodne ter neželene učinke. Literatura 1. Naumann M, Argoff CE, Childers MK, Dykstra DD, Gronseth GS, Jabbari B, et al. Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence based review): Report of the Therapeutic and Technology Assessment Subcomittee of the American Academy of Neurology. Neurology 2008; 6/ 70 (19): 1707-14. 2. Guyer BM. Mechanism of botulinum toxin in the relief of chronic pain. Curr Rev Pain 1999; 3: 427-31. 3. Göbel H. Botulinum toxin A in pain management: Mechanisms of action and rationale for optimum use. In: Jost WH, ed. Botulinum toxin in painful diseases. Pain and headache. Basel: Karger; 2003; p14-22. 4. Jeynes LC, Gauci CA. Evidence for the use of botulinum toxin in the chronic pain setting. A review of the literature. Pain practice 2008; 8 (4): 269-76. 5. Ranoux D, Attal N, Morain F, Bouhassira D. Botulinum toxin type A induces analgesic effects in chronic neuropathic pain. Ann Neurol 2008; 64 (3): 274-83. 6. Apfel SC. Botulinum toxin for neuropathic pain? Neurology 2009; 72: 1456-57. 7. Filippi GM, Errico P, Santarelli R, Bagolini B, Manni E. Botulinum toxin effects on rat jaw muscle spindles. Acta Otolaryngol (Stockh) 1993; 113: 400-4. 8. Wiegand H, Erdmann G, Wellhöner HH. 125 I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular injection. Naunyn Schmiedebergs Arch Pharmacol 1976; 292: 161-5. 9. Hagenah R, Benecke R, Wiegand H. Effects of type A botulinum toxin on the cholinergic transmission at spinal Renshaw cells and on the inhibitory action at I a inhibitory interneurones. Naunyn Schmiedebergs Arch Pharmacol 1977; 299: 267-72. 10. Humm AM, Pabst C, Lauterburg T, Burgunder JM. Enkephalin and a FGF are differentially regulated in rat spinal motoneurons after chemodenervation with botulinum toxin. Exp Neurol 2000; 161: 361-72. 11. Chan J, Brin MF, Fahn S. Idiopathic cervical dystonia: clinical characteristics. Movement Disorders 1991; 6: 119-26. 12. Greene P, Shale H, Fahn S. Experience with high dosages of anticholinergic and other drugs in the treatment of torsion dystonia. Adv Neurol1988; 50: 547-56. 13. Tarsy D, First ER. Painful cervical dystonia: clinical faetures and response to treatment with botulinum toxin. Movement Disorders 1999; 14: 1043-5. 14. Wissel J, Masuhr F, Schelosky L. Quantitative assessment of botulinum toxin treatment in 43 patients with head tremor. Movement Disorders 1997; 12: 722-6. 15. Comella CL, Shannon KM, Jaglin J. Extensor truncal dystonia: succesful treatment with botulinum toxin injections. Movement Disorders 1998; 13: 552-5. 16. Pacchetti C, Albani G, Martignoni E. »Off« painfull dystonia in Parkinson's disease treated with botulinum toxin. Movement Disorders 1995; 10: 333-6. 17. Ward B, Aguilar M., De Beyl Z, Gedin S, Kanovsky P, Molteni F, et al. Use of botulinum toxin type A in management of adult spasticity – A European consensus statement. J Rehabil Med 2003; 35: 98-9. 18. Wissel J. Treatment of spasticity-related pain syndromes. In Jost WH ed. Botulinum toxin in painful diseases. Pain and headache. Basel: Karger 2003; p126-40. 19. Freund BJ, Schwartz M. Treatment of whiplash associated neck pain with botulinum toxin-A: A pilot study. J Rheumatol 2000; 27: 481-4. 20. Pradberg M, De Brujin SFTM, Tavy DLJ. Neck pain in whiplash syndrome treated with botulinum toxin. A double–blind placebo controlled clinical trial. J Neurol 2007; 254: 290-5. 21. Wheeler AH, Goolkasian P, Gretz SS. A randomized, double-blind, prospective pilot study of botulinum, toxin for refractory, unilateral, cevicothoracic, paraspinal, myofascial pain syndrome. Spine 1998; 23: 1662-6. 22. Foster L, Clapp L, Erickson M, Jabbari B. Botulinum toxin A in chronic low back pain. A randomized, doubleblind study. Neurology 2001; 56: 1290-3. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
30
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
23. Jost WH, Reilich P, Pongratz D. Botulinum toxin in low back pain. In Jost WH ed . Botulinum toxin in painful diseases. Pain and headache. Basel: Karger 2003; p159-69. 24. Knusel B, DeGryse R, Grant M, Loeser J, Ripp C, Stanton-Hicks M, et al. Intramuscular injection of botulinum type type A (Botox) in chronic low back pain associated with muscle spasm. Am Pain Soc 1998; 100: 110. 25. Gregorič MR. Uporaba toksina botulin v zdravljenju kronične bolečine. Use of botulinum neurotoxin for the treatment of chronic pain. Rehabilitacija 2006; 5 (1-2): 90-6. 26. Schulte-Mattler WJ, Martinez-Castrillo. Botulinum toxin therapy of migraine and tension type headache: Comparing different botulinum toxin preparations. Eur J Neurol 2006; 13 (Suppl)1): 51-4. 27. Schulte-Mattler WJ, Wieser T, Zierz S. Treatment of tension-type headache. Cephalalgia 1999; 19: 454. 28. Jost WH, Göbel H. Botulinum toxin in tension type headache. In: Jost WH, ed. Botulinum toxin in painful diseases. Pain and headache. Basel: Karger 2003; p82-101. 29. Göbel H, Jost WH. Botulinum toxin in treatment of migraine. In: Jost WH, ed. Botulinum toxin in painful diseases. Pain and headache. Basel: Karger 2003; p102-25. 30. Porta M, Loiero M, Gamba M. Treatment of tension-type headache by botulinum toxin in pericranial muscles. Cephalalgia 1999; 19: 453-4. 31. Troost B. Botulinum toxin type B (Botox) therapy for intractable headache. Headache 2002; 42: 435-6. 32. Mauskop A, Basdeo R. Botulinum toxin A is an effective prophylactic therapy of migraines. Cephalalgia 2000; 20: 422. 33. Binder W, Brin MF, Blitzer A, Schenrock L, Diamond B. Botulinum toxin type A (BTX-A) for migraine: An open label assessment. Movement Disorders 1998; 13 (Suppl 2): 241. 34. Mathew NT, Saper JR, Silberstein SD, and the BOTOX® Migraine Study Group, et al et al. A multi-center, double-blind, placebo controlled trial of two dosages of botulinum toxin type A (Botox) in the prophylactic treatment of migraine. Neurology 1999, 52 (6 Suppl 2): A256. 35. Brin M. Botulinum toxin for headache: Data and review. A publication of the Annenberg Center for Health Sciences at Eisenhower. Rancho Mirage, CA 1999; 2-4. 36. Ho KY, Tan KH. Botulinum toxin A for myofascial trigger point injection: A qualitative systematic review. Eur J Pain 2007; 11: 519-27. 37. Pereda CA, Uson Jaeger J, Carmona L. Systematic review: can botulinum toxin be recommended as treatment for pain in myofascial syndrome? Rheumatologia 2006; 2: 173-82. 38. Porta M, Maggioni G. Botulinum toxin in back pain. J Neurol 2004; 251 (Suppl.1) I/15-8. 39. Reilich P, Pongratz D. Myofascial pain syndrome. In Jost WH, ed. Botulinum toxin in painful diseases. Pain and headache. Basel: Karger 2003; p23-41. 40. Childers MK, Wilson DJ, Gnatz SM, Conway RR, Sherman AK. Botulinum toxin A use in piriformis muscle syndrome. Am J Phys Med Rehabil 2002; 81: 751-9. 41. Lang AM. Botulinum toxin type B in pirifomis syndrome. Am J Phys Med Rehabil 2004; 83: 198-202. 42. Wong SM, Hui ACF, Tong PY, Poon DWF, Yu E, Wong LKS. Treatment of lateral epicondylitis with botulinum toxin: A randomised, double-blind, placebo controlled trial. Ann Intern Med 2005; 143: 793-7. 43. Hayton MJ, Santini AJA, Hughes PJ, Frostick SP, Trail IA, Stanley JK. Botulinum toxin injection in the treatment of tennis elbow: A double blind, controlled pilot study. J Bone Joint Surg (Am) 2005; 87A: 503-7.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
31
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
PERINEVRALNE BLOKADE PO OPERACIJAH ZGORNJEGA UDA PERINEURAL BLOCKS AFTER UPPER LIMB SURGERY Slobodan Gligorijevic Department of Anaesthesiology, City Hospital Waid, University of Zürich, Switzerland
Introduction The first description of a continuous peripheral nerve block is more than 60 years old.1 Subsequently, continuous peripheral nerve blocks (CPNBs) have been described for almost every peripheral nerve or nerve plexus on upper as well as on lower extremity including axillary, interscalene, infraclavicular, paravertebral, psoas compartment, femoral, fascia iliaca as well as for proximal and distal sciatic nerve. The method involves the percutaneuous insertion of a catheter directly adjacent to the peripheral nerves. Local anesthetics, infused via catheter provide potent, site-specific analgesia with minor side effects. Unlike with epidural catheters, there is less concern regarding coagulation problems; therefore peripheral nerve catheters may be used with newer anticoagulants. Peripheral nerve blocks produce a unilateral preganglionic sympathetic block causing only minimal, if any, cardiovascular disturbances. Furthermore, perineural infusion does not require hospitalization as do epidural infusion or intravenous opioids. Combining perineural catheters with portable infusion pumps, ambulatory patients may experience the same level of analgesia previously afforded only to the inpatients. These attributes, along with higher level of patient satisfaction make CPNBs an attractive and effective solution for postoperative pain management. Upper extremity blocks Brachial plexus block can provide excellent anaesthesia and analgesia for upper extremity procedures. By preoperative placement of a perineural catheter a dense nerve block used for surgery can be smoothly transformed into efficient postoperative analgesia. For shoulder surgery, modified lateral interscalene 2, 4, 5, 7, 22 and posterior interscalene9, 10, 11 approaches are common used. Benefits of the modified anterior-lateral approach include a relatively superficial placement and a lateral direction of the puncturing needle avoiding the potential risk for serious neurological damage. Drawbacks include frequent overlying external jugular vein, difficulties in accurate catheter placement, and possible catheter dislodgement (if not tunnelled). Benefits of the posterior approach include avoiding the jugular vein, a low rate of catheter dislodgement, and a single technique that will - reportedly, but without concrete evidence – provide anaesthesia and analgesia to the entire upper extremity. Particularly suitable this approach appears in pain patients with pancoast tumor where all other approaches to the brachial plexus are almost impossible. Drawbacks include turning a superficial block into a deep block, with theoretically higher risks of epidural or intrathecal cannulation or vascular puncture. For surgery at or distal to the elbow, an infraclavicular or axillary catheter may be used.12–14 Supraclavicular catheters have been described, but perhaps because of the risk of a pneumothorax, they are rarely used.15 Benefits of the infraclavicular over the axillary approach (all theoretical as there are no published data comparing the two) include coverage of all three brachial plexus cords and a ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
32
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
catheter that is more comfortable for patients. Since the musculocutaneous and axillary nerves exit the brachial plexus distal to the level of in infraclavicular catheter tip at the brachial plexus cords, they are theoretically covered with this type of catheter. Regarding the wide opinion that catheters not treaded parallel to the nerve course are difficult to be placed, this approach seems to be an exception to the rule. Benefits of the axillary technique include a familiarity by most anesthesiologists, a superficial target, and ease of catheter placement. Theoretical drawbacks include a higher risk of catheter dislodgement, decreased patient comfort, potentially increased risk of infection and decreased analgesia potency compared with the infraclavicular placed catheters. In the last years, ultrasound-guided peripheral nerve blocks have increased in use. However, despite the potential for visualization of the catheter tip and/or spread of LA, to date there is no prospective randomized study comparing ultrasound guidance with the use of peripheral nerve stimulator for catheter placement Postoperative pain management The first randomized, controlled, double blind trial providing evidence of infusion benefits after extensive shoulder surgery was not reported until 2000.19 Subsequently, several other studies have demonstrated superior analgesia compared with intravenous opioids2, 4, 7, 12, 13 in hospitalized as well as in ambulatory patients. Dramatically lower opioid consumption in patients receiving perineural local anaesthetics resulted in fewer opioid-related side effects, including a lower incidence of nausea, vomiting, pruritus, and sedation. Whether these demonstrated benefits result in an improvement in patient’s health-related quality of life remains unexplored.16 Because of existing inherent risks with a perineural catheters, this technique is frequently limited to patients expected to have at least moderate postoperative pain of a duration of at least 48 hours and not easily managed with oral opioids.17, 18 However, infusion may be also used following mildly painful procedures in order - to decrease or totally avoid the opioid consumption and opioid-related side effects.19, 20 Despite the lack of published data perineural infusion of local anaesthetics may be particularly useful in elderly patients as a part of multimodal pain management as well as in pain management of addict patients. Choice of local anaesthetics The majority of perineural infusion publications have involved low concentrated bupivacaine (0.15%) or ropivacaine (0.125–0.2%), although levobupivacaine24 and shorter acting agents have been reported.25 One trial involving interscalene infusion found that ropivacaine 0.2% and bupivacaine 0.15% provide similar analgesia, but ropivacaine was associated with better preservation of strength in the hand and less paresthesia in the fingers.3 However, another study of interscalene infusion found ropivacaine 0.2% and levobupivacaine 0.125% equivalent following shoulder surgery, with patients receiving levobupivacaine consuming a lower volume of anaesthetic24 and a third investigation found no difference between 0.125% bupivacaine and ropivacaine provided as a bolus via an axillary catheter following less-painful surgery of the upper extremity.20 Unfortunately, the precise equipotent local anaesthetic concentrations within the peripheral nervous system remain undetermined. Currently, there is insufficient information to determine if there is an optimal local anaesthetic for ambulatory infusions. Adjuvants An alternative method of prolonging analgesia is to deliver a solution that lasts longer than the duration of the single block or reduces the amount of local anaesthetics needed. Unfortunately, while clonidine increases the duration of single-injection nerve blocks,27 the only controlled investigations of adding clonidine to a continuous ropivacaine infusion (1 or 2 µg/mL) failed to reveal any clinically-relevant benefits.28 Additionally, opioids and epinephrine have been added ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
33
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
to local anaesthetic infusions, but there are currently insufficient published data to draw any conclusions regarding these adjuvants.31 Dosing regimen There are three basic approaches to LA delivery: continuous, intermittent bolus and continuous with intermittent bolus. The optimal LA dosing regimens for interscalene26 infraclavicular, and axillary29 continuous infusion may vary with anatomic location and choice of local anaesthetic. Therefore, data from studies involving one catheter location and local anaesthetic cannot necessarily be applied to another anatomic location. In general, providing continuous infusion with patient-controlled bolus gives the practitioner and the patient the greatest flexibility and is preferred method in the most institutions. There are limited data available to base recommendations on the optimal basal rate, bolus volume, and lockout period.23, 26, 29 In all probability, confounding variables may affect the optimal regimen, including the surgical procedure, catheter location, physical therapy regimen, and specific local anesthetic infused. Most common recommended regimens use a basal rate of 5–10 ml/h, bolus volume of 3–5 ml and lockout time of 15–60 min. Additionally, the maximum safe dose for the long-acting LA remains unknown. However, multiple investigations involving patients free of renal or hepatic disease have reported blood concentrations within acceptable limits following up to five days of perineural infusion with similar dosing schedules.6, 30 Complications Several prospective studies have shown low incidence of permanent damage caused by perineural catheter itself. Performance of interscalene block followed by catheter placement was associated with a very low incidence of permanent complications.14 However, interscalene perineural infusion will frequently cause ipsilateral diaphragm paralysis but the effect on overall pulmonary function may be minimal for relatively healthy patients.32 The incidence of permanent neurological injury was found to be extremely low for continuous axillary catheters as well.34 In general, with all types of CPNBs, some minor transient neurologic disturbances may be common.3 Large prospective studies on inflammation and infection of CPNBs have shown a rare incidence for these types of complications.35, 36 However, the incidence was increased with the duration of catheter placement, and therefore a close clinical monitoring is requested. CPNBs and outcome Improved quality of analgesia is the most common outcome benefit measured in published studies in terms of any effect on surgical outcome. Analgesia provided by continuous peripheral nerve blocks, regardless of catheter location has been shown to be superior and with fewer opioid-related side effects when compared with opioid analgesia.37 However, the debate concerning the short- term use of CPNBs on functional outcome after shoulder surgery is still open and somewhat controversial.38, 39 Conclusion The use of CPNBs has grown dramatically in recent years. CPNBs have the potential to produce high quality analgesia with minimum morbidity compared to the other modalities of postoperative pain management. Outcome studies have analyzed the risks and shown the exceptional safety of CPNBs. Although already worldwide accepted as a part of the rehabilitation programs after major orthopaedic surgery, there are still open questions and many areas for further expansion. Techniques of CPNBs should be included in all teaching programs and become a part of armamentarium of every practitioner involved in the perioperative management of orthopaedic and/or trauma patient.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
34
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
References 1. Ansbro FP. A method of continuous brachial plexus block. Am J Surg 1946; 71: 716-22. 2. Borgeat A, Tewes E, Biasca N. Patient-controlled interscalene analgesia with ropivacaine after major shoulder surgery: PCIA vs PCA. Br J Anaesth 1998; 81: 603-5. 3. Borgeat A, Kalberer, Jacob H, Ruetsch YA, Gerber C. Patient-controlled interscalene analgesia with ropivacaine 0.2% versus bupivacaine 0.15% after major open shoulder surgery: The effects on hand motor function. Anesth Analg 2001; 92: 218-23. 4. Borgeat A, Schappi B, Biasca N, Gerber C. Patient-controlled analgesia after major shoulder surgery: Patientcontrolled interscalene analgesia versus patient-controlled analgesia. Anesthesiology 1997; 87: 1343-7. 5. Borgeat A, Ekatodramis G, Kalberer F, Benz C. Acute and nonacute complications associated with interscalene block and shoulder surgery. Anesthesiology 2001; 95: 875-80. 6. Ekatodramis G, Borgeat A, Huledal G, Jeppsson L, Westman L, Sjovall J. Continuous interscalene analgesia with ropivacaine 2mg/ml after major shoulder surgery. Anesthesiology 2003; 98: 143-50. 7. Ilfeld BM, Morey TE, Wright TW, Enneking FK, Chidgey LK. Enneking FK. Continuous interscalene brachial plexus block for postoperative pain control at home: a randomized, double-blinded, placebo-controlled study. Anesth Analg 2003; 96: 1089-95. 8. Klein SM, Grant SA, Greengrass RA, Nielsen KC, Speer KP, White W, et al. Interscalene brachial plexus block with a continuous catheter insertion system and a disposable infusion pump. Anesth Analg 2000; 91: 1473-8. 9. Boezaart AP, de Beer JF, du Toit C, van Rooyen K. A new technique of continuous interscalene nerve block. Can J Anaesth 1999; 46: 275-81. 10. Boezaart AP, Koorn R, Borene S, Edwards JN. Continuous brachial plexus block using the posterior approach. RAMP 2003; 28: 70. 11. Borene SC, Rosenquist RW, Koorn R, Haider N, Boezaart AP. An indication for continuous cervical paravertebral blocks (posterior approach to the interscalene space). Anesth Analg 2003; 97: 898-900. 12. Borgeat A, Ekatodramis G, Dumont C. An evaluation of the infraclavicular block via a modified approach of the RAJ technique. Anesth Analg 2001; 93: 436-41. 13. Ilfeld BM, Morey TE, Enneking FK: Continuous infraclavicular brachial plexus block for postoperative pain control at home: a randomized, double-blinded, placebo-controlled study; Anesthesiology 2002; 96: 1297-304. 14. Mezzatesta JP, Scott DA, Schweitzer SA, Selander DE. Continuous axillary brachial plexus block for postoperative pain relief. Intermittent bolus versus continuous infusion. Reg Anesth 1997; 22: 357-62. 15. Christopher C, Mayfield JB: Evaluation of a new Supraclavicular brachial plexus catheter technique for shoulder surgery anesthesia and analgesia. Anesthesiology 2000; 93: A849. 16. Wu CL, Naqubuddin M, Rowlingson AJ, Lietman SA, Jermyn RM, Fleisher LA. The effect of pain on healthrelated quality of life in the immediate postoperative period. Anesth Analg 2003; 97: 1078-85. 17. Ekatodramis G, Macaire P, Borgeat A. Prolonged Horner syndrome due to neck haematoma after continuous interscalene block. Anesthesiology 2001M95: 801-3. 18. Ribeiro FC, Georgousis H, Bertram R, Scheiber G. Plexus irritation caused by interscalene brachial plexus catheter for shoulder surgery. Anesth Analg 1996; 82: 870-2. 19. Raval N, Axelsson K, Hylander J, Allvin R, Amilon A, Lidegran G, et al. Postoperative patient-controlled local anesthetic administration at home. Anesth Analg 1998; 86: 86-9. 20. Rawal N, Alivin R. Axelsson K, Nordenson U, Johanzon E, Rawal N, et al. Patient-controlled regional analgesia (PCRA) at home: controlled comparison between bupivacaine and ropivacaine brachial plexus analgesia. Anesthesiology 2002; 96: 1290-6. 21. Salinas FV. Location, location, location: Continuous peripheral nerve blocks and stimulating catheters. RAMP 2003; 28: 79. 22. Borgeat A, Dullenkopf A, Ekatodramis G, Nagy L. Evaluation of the lateral modified approach for continuous interscalene block after shoulder surgery. Anesthesiology 2003; 99: 436-42. 23. Ilfled BM, Morey TE, Wright TW, Chidgey LK, Enneking FK. Interscalene perineural ropivacaine infusion: A comparison of two dosing regimens for postoperative analgesia. Reg Anesth Pain Med 2003; 29: 290-6. 24. Casati A, Borhi B, Fanelli G, Montone N, Rotini R, Fraschini G, et al. Interscalene brachial plexus anesthesia and analgesia for open shoulder surgery: A randomized, double-blinded comparison between levobupivacaine and ropivacaine. Anesth Analg 2003; 96: 253-9. 25. Buettner J, Klose R, Hoppe U, Wresch P. Serum levels of mepivacaine-HCl during continuous axillary brachial plexus block. Reg Anesth 1989; 14: 124-7. 26. Singelyn FJ, Seguy S, Gouverneur MJ: Interscalene brachial plexus analgesia after open shoulder surgery: continuous versus patient-controlled infusion. Anesth Analg 1999; 89: 1216-20. 27. Iskander H, Guillaume E, Dixmerias, Binje B, Rakotondriamihary S, Thiebaut R, et al. The enhancement of sensory blockade by clonidine selectively added to mepivacaine after midhumeral block. Anesth Analg 2001; 93: 771. 28. Ilfeld BM, Morey, Thannikary LJ, Wright TW, Enneking FK. Clonidine added to a continuous interscalene ropivacaine perineural infusion to improve postoperative analgesia: A randomized, double-blind, controlled study. Anesth Analg 2005; 100: 1172-8. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
35
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
29. Iskandar, Rakotondriamihary S, Dixmerias F, Binje B, Maurette P. Analgesia using continuous axillary block after surgery of severe hand injuries: Self-administrations vs continuous injection. Ann Fr Anesth Reanim 1998; 17: 1099. 30. Kaloul I, Guay J, Cote C, Halwagi A, Varin F. Ropivacaine plasma concentrations are similar during continuous lumbar plexus blockade using the anterior three-in-one and the posterior psoas compartment technique. Can J Anesth 2004; 34: 468-72. 31. Murphy DB, McCartney CJ, Chan VW. Novel analgesic adjuncts for brachial plexus block: A systematic review. Anesth Analg 2000; 90: 1122-8. 32. Borgeat A, Perschak H, Bird P, Hodler J, Gerber C. Patient-controlled interscalene analgesia with ropivacaine 0.2% versus patient-controlled intravenous analgesia after major shoulder surgery: Effects on diaphragmatic and respiratory function. Anesthesiology 2000; 92: 102-8. 33. Bergmann BD, Hebl JR, Kent J, Horlocker TT. Neurologic complications of 400 consecutive continuous axillary catheters Anesth Analg 2003; 96: 247-52. 34. Wiegel M, Gottschaldt U, Hennebach R, Hirschberg T, Reske A. Complications and adverse effects associated with continuous peripheral nerve blocks in orthopedic patients. Anesth Analg 2007; 104: 1578-82. 35. Capdevila X, Pirat P, Bringuier S, Gaertner E, Singelyn F, Bernard N, et al. Continuous peripheral nerve blocks in hospital wards after orthopedic surgery: A multicenter prospective analysis of the quality of postoperative analgesia and complications in 1,416 patients. Anesthesiology 2005; 103: 1035-45. 36. Neuburger M, Büttner J, Blumenthal S, Breitbarth J, Borgeat A. Inflammation and infection complications of 2285 perineural catheters: a prospective study. Acta Anaesthesiol Scand 2008; 51: 108-14. 37. Richmann JM, Liu SS, Courpas G, Wong R, Rowlingson AJ, McGready J, et al. Does continuous peripheral nerve block provide superior pain control to opioids? A meta-analysis. Anesth Analg 2006; 102: 248-57. 38. Ilefeld BM,Wright TW, Enneking FK, Morey TE. Joint range of motion after total shoulder arthroplasty with and without a continuous interscalene block: a retrospective, case control study. Reg Anesth Pain Med 2005; 30: 429-33. 39. Hofmann-Kiefer K, EiserT, Chappell D, Leuschner S, Conzen P, Schwender D. Does patient-controlled continuous interscalene block improve early functional rehabilitation after open shoulder surgery? Anesth Analg 2008; 106: 991-6.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
36
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
ANALGEZIJA PRI OPERIRANIH OTROCIH ANALGESIA IN PEDIATRIC SURGERY Silvo Lipovšek Otroški oddelek kirurških strok, Splošna učna bolnišnica Celje, Celje
»Pacient ima pravico do preprečevanja in lajšanja trpljenja« Tako piše v zakonu pacientovih pravicah. Pri otrocih, ki so po naravi šibkejši kot odrasli, je lajšanje pooperacijske bolečine prav tako temeljna pravica. Ampak žal, lajšanje pooperacijske bolečine je bilo dolgo let podcenjeno, in je še danes. Bolečina onesposobi vsakega človeka in bolečina pri otrocih je še bolj škodljiva kot pri odraslih. Pooperacijska bolečina pri otrocih ne povzroča samo trpljenja in slabe kakovosti življenja, ampak pusti v začetku sicer nevidne, a dolgotrajne psihološke travmatične posledice. Znanstvene raziskave so strokovno in brez dvoma dokazale, da v pooperacisjkem obdobju 75 % otrok občuti zmerne do močne bolečine. Znanje na področju nevrofiziologije, farmakodinamike in klinične farmakologije je z raziskavami izredno napredovalo, tako da je uporaba zdravil za lajšanje bolečin pri otrocih v zadnjih deset letih veliko bolj varna. Znanstveno je tudi dokazano, da so periferne, spinalne in supraspinalne aferentne poti za bolečino že razvite na zarodku, starem 26 tednov. Potrjeno je tudi, da nezadostno zdravljenje akutne pooperacijske bolečine pri novorojenčku povzroča dolgotrajno večmesečno znižanje bolečinskega praga, starejše otroke pa zadržuje dalj časa v bolnišnici in onemogoča hitro vrnitev v normalno življenje. Zato je neizogibno in potrebno, da se čimprej vsi zdravniki zavedamo in prepričamo o škodljivosti bolečine pri otrocih, novorojenčkih, nedonošencih in tudi o njenih posledicah. Nesprejemljivo je, da ostaja otroška bolečina kljub dokazom in napredku znanja na tem področju še vedno podcenjena med večino kirurgov in zdravnikov. Otrok po operaciji ne sme boleti ne glede na stare predsodke, doktrine in druga na pamet naučena pravila. Na podlagi vsega, kar sem omenil, pokazal in predstavil, in na osnovi priznane svetovne izkušnje in literature predstavljam naše delo na tem področju v Sloveniji na Otroškem oddelku kirurških strok Splošne učne bolnišnice Celje. Treba je poudariti, da smo bili od leta 2005 prvi v Sloveniji, ki smo se temeljito lotili zdravljenja pooperacijske bolečine pri otrocih z metodo infiltracije pooperacijske rane z dolgotrajnim lokalnim anestetikom. Uporabili smo levobupivakain (Chirocaine TM ) v odmerku 1–2 mg/kg telesne teže. Predstavljam vam statistiko, ugotovitve, ugodnosti, koristi in zaključke pri uporabe omenjene metode. Blokada senzoričnih živcev podaljša in okrepi učinek ostalih protibolečinskih zdravil in zmanjša ali ukine uporabo pooperacijskih analgetikov, kar pomeni ne samo izvrstno zaščito organizma (zaradi manjše uporabe zdravil), ampak tudi pomemben denarni prihranek. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
37
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Medicina in naši mali bolniki zahtevajo od nas, da se naše znanje in operacijske tehnike stalno dopolnjujejo v njihovo prid. Zato se moramo soočiti z resnico današnjega sveta, spremeniti moramo nekatere dogme, ki so bile globoko zakoreninjene v naših glavah, in sprejeti napredek, ki lajša življenje. Vsi moramo razumeti in se zavedati, da otrok zasluži, da mu kirurgi ponudimo najnovejše in preproste metode za lajšanje pooperacijske bolečine. Otroci imajo pravico, da jih ne boli po operaciji, in kirurgi imamo dolžnost, da to pravico omogočimo. Kot zaključek ocenjujemo, da je predlagana metoda poceni, učinkovita, varna in preprosta.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
38
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
RADIOFREKVENČNA DENERVACIJA ZA ZDRAVLJENJE KRONIČNE BOLEČINE. POGLED ZDRAVNIKA BOLEČINE. PREGLED DOKAZOV RADIOFREQUENCY DENERVATION IN THE TREATMENTOF CHRONIC PAIN. PAIN PHYSICIAN PERSPECTIVE. REVIEW OF EVIDENCE Zbigniew Kirkor Princess Alexandra Hospital, Harlow, Essex, United Kingdom
Radiofrequency (RF) denervation has been used in clinical practice since 1965, initially for percutaneous cordotomy. Introduction of small-diameter electrodes initiated new era in radiofrequency treatment in 1980. Radiofrequency lesioning has been used for the treatment of facet joints pain (medial branch denervation), dorsal root ganglion lesioning, sacroiliac joint pain. Pulsed RF is used for peripheral nerves lesioning. Patients for RF denervation should be carefully selected. Clinical diagnosis must be confirmed with successful medial branch block. International Association for the Study of Pain (IASP) and International Spine Interventions Society (ISIS) recommend two consecutive blocks with consistent response i.e. complete pain relief following both blocks. The RF denervation is carried out in operating theatre with the use of C-arm image intensifier. Patient might be sedated, however clear communication is necessary during the procedure. ISIS recommends unilateral denervation at a time at no more then three levels to avoid postoperative discomfort. The procedure is considered successful if it brings at least 80% pain relief which lasts at least six months. Current literature and evidence based publications will be reviewed in this presentation.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
39
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
ANATOMIJA IN FIZIOLOGIJA TIHE KOŽNE PERIODE ANATOMY AND PHYSIOLOGY OF THE CUTANEOUS SILENT PERIOD Markus Kofler Department of Neurology, Hospital Hochzirl, Zirl, Austria
Introduction Transient inhibition of volitional tonic muscle activity – either complete or incomplete – following peripheral stimulation is termed exteroceptive electromyographic (EMG) suppression. It may be caused by a variety of external stimuli, e.g. mechanical, via stretching the muscle tendon, or electrical, via stimulation of the supplying mixed or a nearby cutaneous nerve.46 The first description originates from Hoffmann,10 who studied the effect of an electrically induced muscle twitch during volitional EMG activity. Later, Caccia et al.,2 McLellan38 and Kranz et al.27 contributed substantially to the investigation of exteroceptive EMG-suppression. The cutaneous silent period (CSP) represents a spinal inhibitory reflex mainly mediated by Adelta fibers.6, 14, 29, 42, 54 Upper limb CSPs constitute the inhibitory part of a complex pre-attentional protective reflex mechanism,13, 14, 24, 32 which operates in a timely manner with excitatory withdrawal flexor reflexes which serve to retract the hand away from a noxious stimulus.6, 43 Both inhibitory and excitatory reflex components seem to share common spinal neural circuitry which is activated by high-threshold, low-diameter fibers. CSPs are considered to be robust cutaneomuscular reflexes following high-intensity afferent stimulation5 and constitute a basic strategy of the central nervous system to effectively simplify motor behavior by "turning off” and “turning on" muscle synergies.32 In recent years, CSPs have received increasing attention in health5, 12, 14, 15, 20-25, 28, 32, 42-44, 50 and disease.4, 8, 9, 16, 19, 33-35, 39, 45, 47-49, 51, 52, 56, 57 Much has been learned so far about functional anato–my and pathophysiology, less, however, about pharmacology of CSPs. Functional anatomy CSPs can be elicited in all hand muscles following stimulation to each finger.32 They differ slightly, but significantly, depending on which combination of muscle and finger is tested.14 The distinct timing and magnitude of EMG suppression in different upper limb muscles indicate a functional – task-related – organization of protective reflexes in the human upper extremity, rather than a merely metameric – anatomically based – order of activation of the neuronal circuitry.14, 24 CSPs are most pronounced in abductor pollicis brevis muscle following digit II and, somewhat less, following digit V stimulation. First dorsal interosseous and abductor digiti minimi muscles differ in CSP onset latency following digit II stimulation, and in the overall amount of suppression following digit V stimulation, despite being supplied by the same nerve and the same myotome. Excitatory long-loop reflexes seem to be suppressed by increasing stimulus intensities, yet they may interfere with CSPs, even when applying noxious stimulation, in first dorsal interosseous muscle following digit II stimulation, and in both abductor digiti minimi and first dorsal interosseous muscles following digit V stimulation.14 CSPs can be elicited by laser stimulation to the volar surface of the hand, but not to the hand dorsum, consistent with the functional importance of protecting the reaching and grasping hand from noxious input.42 Stimulus intensity exerts a significant influence on various CSP parameters (probability, onset and end latency, duration, index of suppression).14, 32, 54 When keeping stimulus intensities constant, CSP parameters do not differ significantly between right and left hands.22 Regression ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
40
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
analysis revealed powerful correlations between individual CSP parameters of dominant and non-dominant hands. Calculated upper normal limits of maximum interside differences were 17% for CSP onset latency, 14% for CSP end latency, 22% for CSP duration, and 45% for the index of suppression. CSP parameters in right-handed subjects did not differ significantly from those in left-handed subjects, but females tended to have shorter CSP onset latencies, longer CSP duration, and a smaller index of suppression, resulting in a larger overall suppression, than males.22 Interside differences should be considered when testing patients with predominantly unilateral disease symptoms. CSPs are strictly unilaterally organized, and there is no influence from or to the contralateral side.23 Noxious digit II stimulation evokes consistent CSPs in ipsilateral thenar muscles during voluntary contraction, while there is no consistent influence on EMG activity in contralateral thenar muscles at rest. Furthermore, noxious digit II stimulation neither consistently affects EMG activity in ipsilateral thenar muscles at rest nor in contralateral thenar muscles during voluntary contraction. Finally, there is no significant difference between any CSP parameter obtained during unilateral versus bilateral target muscle contraction.23 Muscle force was reported to be an important factor determining CSPs;54 however, more recently CSP onset and end latency, CSP duration, and the magnitude of EMG suppression were shown to be not influenced by volitional muscle contraction ranging from 10% to 50% of the maximum, while background EMG levels increased significantly with the amount of muscle force.21 This non-dependence on the amount of volitional target muscle activation over a range from 10% to 50% of individual maximum force levels renders CSPs particularly suitable for clinical use in patients with peripheral and spinal disorders affecting the A-delta fiber system.21 CSPs are found in forearm muscles, but are more pronounced in flexors than in extensors.32 Lacking CSPs in biceps brachii muscle in the presence of distinct CSPs in triceps brachi muscle are consistent with a functional organization of protective reflexes in the proximal human upper limb across several metameric segments. Different elbow positions exert a significant influence on CSP onset and end latency, and duration, indicating that spinal inhibitory neurons serving to rapidly suppress basic muscle synergies may compete with neural circuitry involved in postural control.24 The post-inhibitory rebound of EMG activity following the CSP has been mainly attributed to resynchronization of motoneurons.27 However, inhibition of the EMG rebound by non-noxious prepulse stimulation 100 ms preceding noxious fingertip stimulation supports the hypothesis that the excitatory EMG activity following the CSP contains not only resynchronization of motoneuronal firing, but also an excitatory reflex component. The most probable type of reflex seems to be a somatosensory startle reflex, a defense reaction which is generated in structures located in the caudal brainstem following an unexpected intense stimulus. Reduction of the discomfort associated with high-intensity electrical fingertip stimulation by a prepulse without affecting CSP parameters underlines the utility of prepulse inhibition in the context of CSP testing.28 Pharmacology To date, little is known about neurotransmitters involved in CSP generation. In fact, only transmitters are known which seem to be not involved to a substantial degree. Single case observations are consistent with absence of a significant role of gamma-amino butyric acid (GABA), a widely distributed and potent inhibitor in the central nervous system. So far, no systematic studies have been published, but an intrathecal bolus of 50 µg baclofen, a GABAB agonist, did not influence CSP duration in a patient with severe generalized dystonia, in whom the “spinal portion” of the cortical silent period induced by transcranial magnetic stimulation was shortened.26 Cholinergic attenuation of CSPs has been observed in one other patient.19 Other protective reflexes, such as the auditory startle response, involve glycine as an inhibitory neurotransmitter,1 rendering glycine another potential candidate in CSP generation. Glycine receptors are abundantly present on alpha-motoneurone synapses and are closely involved in motor control.41 In fact, a patient with GAD-positive stiff-limb syndrome presented without CSPs in his affected leg, while the unaffected leg had normal CSPs.53 This is in seeming contrast to ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
41
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
the report that masseteric silent periods are unaffected in stiff-person syndrome.36 However, the physiology and neurotransmitters involved in the generation of the masseteric silent periods, which occur bilaterally following unilateral stimulation, and cutaneous silent periods, which are unilaterally organized,23 may be different. Inghilleri et al.12 showed that CSP onset latency and duration as well as nociceptive MEP modulation are opiate-insensitive. Abnormally prolonged CSPs were partially normalized by LDopa in idiopathic Parkinson’s disease, but not in patients with atypical parkinsonism who did not respond clinically to L-Dopa.45 Notably, CSP prolongation was also noted in the lower limbs of patients with restless legs syndrome, and was normalized by dopamine agonist treatment.9 Conversely, the abnormally reduced I1 phase of the cutaneomuscular reflex in patients with idiopathic Parkinson’s disease was normalized by L-Dopa,7 and cutaneomuscular inhibition was substantially enhanced by subcutaneous apomorphine.3 These seemingly contradictory findings of an increase in EMG inhibition following low-intensity afferent stimulation and reduced inhibition following high-intensity stimulation are consistent with distinct spinal circuitry mediated by lowand high-threshold afferents.5, 14, 17, 44 These findings, however, do not allow certainty as to whether dopamine alters CSPs or whether it only influences that “portion” of the CSP that is due to concomitant activation of low-threshold afferents which inevitably occurs when applying electrical stimuli to peripheral nerves. Botulinum toxin failed to shorten prolonged CSPs in focal dystonia.5, 40 Anecdotal observations lead to the assumption that antihistaminic medication may counteract nociceptive EMG suppression, as the known CSP in one male subject was temporarily lost following ingestion of an antihistaminic drug for acute rhinitis. A second otherwise healthy male subject, who was on long-term cetirizine for allergic rhinitis, presented without clearly defined CSPs when volunteering for normal values. However, in a systematic study in 4 healthy subjects who underwent serial CSP testing after ingestion of 10 mg cetirizine, CSP onset latency, CSP end latency and CSP duration, as well as the index of suppression did not change significantly over a period of 360 minutes.20 These findings suggest that histamine also plays no major role as a neurotransmitter of CSPs. Spinal neurophysiology Studies using H-reflexes, F-waves, and motor evoked potentials suggest that motoneuron inhibition is mediated by spinal inhibitory interneurons.5, 11, 13, 17, 18, 30, 31, 35, 37, 54, 55 Only very few synapses seem to be interspersed, as habituation is virtually absent at repetition rates up to 5 Hz or following double pulse stimulation with interstimulus intervals of 100 ms.5, 27, 54 Interaction with large-myelinated afferent fibers is suggested by the effect of high-frequency transcutaneous electrical nerve stimulation (TENS) on the CSP.15 CSP duration was shortened relative to baseline recordings following 15 min of TENS. The amount of exteroceptive EMG inhibition was slightly increased due to a concomitant suppression of transcortical long-loop reflexes, which may be present within the CSP. Thus, TENS exerts an influence on both inhibitory and excitatory circuits involved in protective reflexes. These effects are likely mediated at the spinal segmental level through TENS-associated presynaptic inhibition of nociceptive A-delta fibers.15 The findings are in agreement with a known opiate-insensitive mechanism of TENS at the spinal level, and a previously reported insensitivity to fentanyl of CSPs.12 Supraspinal influence upon pathways mediating the CSP has been postulated based on studies in patients with spinal cord injury, minor stroke, amyotrophic lateral sclerosis, and compressive cervical myelopathy.8, 35, 47 The putative spinal reflex pathway has been elaborated in patients with intramedullary spinal cord lesions.19, 48 In recent years, CSPs have been increasingly applied in the assessment of peripheral neuropathies4, 16, 39, 49, 51, 56, 57 and have become a valuable and sensitive neurophysiological tool in the assessment of spinal centromedullary dysfunctions.19, 33, 34, 47, 48 References 1. Bakker MJ, van Dijk JG, van den Maagdenberg AM, Tijssen MA. Startle syndromes. Lancet Neurol 2006; 5: 513-24. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
42
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
2. Caccia MR, McComas AJ, Upton ARM, Blogg T. Cutaneous reflexes in the small muscles of the hand. J Neurol Neurosurg Psychiatry 1973; 36: 960-77. 3. Clouston PD, Lim CL, Sue C, Morris JGL, Yiannikas C. Apomorphine can increase cutaneous inhibition of motor activity in Parkinson's disease. Electroencephalogr Clin Neurophysiol 1996; 101: 8-15. 4. Corsi FM, Fausti S, Serrao M, Casali C, Parisi L, Piazza G. Electromyographic mixed nerve and cutaneous silent period in evaluating the A-delta fibers in a patient with hereditary sensory-autonomic neuropathy. Funct Neurol 2002; 17: 31-4. 5. Floeter MK. Cutaneous silent periods. Muscle Nerve 2003; 28: 391-401. 6. Floeter MK, Gerloff C, Kouri J, Hallett M. Cutaneous withdrawal reflexes of the upper extremity. Muscle Nerve 1998; 21: 591-8. 7. Fuhr P, Zeffiro T, Hallett M. Cutaneous reflexes in Parkinson's disease. Muscle Nerve 1992; 15: 733-9. 8. Gilio F, Bettolo CM, Conte A, Iacovelli E, Frasca V, Serrao M, Giacomelli E, Gabriele M, Prencipe M, Inghilleri M. Influence of the corticospinal tract on the cutaneous silent period: A study in patients with pyramidal syndrome. Neurosci Lett 2008; 433: 109-13. 9. Han JK, Oh K, Kim BJ, Koh SB, Kim JY, Park KW, Lee DH. Cutaneous silent period in patients with restless leg syndrome. Clin Neurophysiol 2007; 118: 1705-10. 10. Hoffmann P. Untersuchungen über die Eigenreflexe (Sehnenreflexe) menschlicher Muskeln. Berlin: Springer; 1922. p66. 11. Inghilleri M, Berardelli A, Cruccu G, Manfredi M, Priori A, Rothwell JC. Inhibition of hand muscle motoneurones by peripheral nerve stimulation in the relaxed human subject. Antidromic versus orthodromic input. Electroencephalogr Clin Neurophysiol 1995; 97: 63-68. 12. Inghilleri M, Conte A, Frasca V, Berardelli A, Manfredi M, Cruccu G. Is the cutaneous silent period an opiatesensitive nociceptive reflex? Muscle Nerve 2002; 25: 695-9. 13. Inghilleri M, Cruccu G, Argenta M, Polidori L, Manfredi M. Silent period in upper limb muscles after noxious cutaneous stimulation in man. Electroencephalogr Clin Neurophysiol 1997; 105: 109-15. 14. Kofler M. Functional organization of exteroceptive inhibition following nociceptive electrical fingertip stimulation in humans. Clin Neurophysiol 2003; 114: 973-80. 15. Kofler M. Influence of transcutaneous electrical nerve stimulation on cutaneous silent periods in humans. Neurosci Lett 2004; 360: 69-72. 16. Kofler M, Fröhlich K, Saltuari L. Preserved cutaneous silent periods in severe entrapment neuropathies. Muscle Nerve 2003; 28: 711-714. 17. Kofler M, Fuhr P, Leis AA, Glocker FX, Kronenberg MF, Wissel J, Štetkárová I. Modulation of upper extremity motor evoked potentials by cutaneous afferents in humans. Clin Neurophysiol 2001; 112: 1053-63. 18. Kofler M, Glocker FX, Leis AA, Seifert C, Wissel J, Kronenberg MF, Fuhr P. Modulation of upper extremity motoneurone excitability following noxious finger tip stimulation in man: a study with transcranial magnetic stimulation. Neurosci Lett 1998; 246: 97-100. 19. Kofler M, Kronenberg MF, Brenneis C, Felber A, Saltuari L. Cutaneous silent periods in intramedullary spinal cord lesions. J Neurol Sci 2003; 216: 67-79. 20. Kofler M, Kumru H, Stetkarova I, Ruegg S, Fuhr P, Leis AA. Cutaneous silent periods are not affected by the antihistaminic drug cetirizine. Clin Neurophysiol 2009; 120: 1016. 21. Kofler M, Kumru H, Štetkárová I, Schindler C, Fuhr P. Muscle force up to 50% of maximum does not affect cutaneous silent periods in thenar muscles. Clin Neurophysiol 2007; 118: 2025-30. 22. Kofler M, Poustka K. Interside comparison of cutaneous silent periods in thenar muscles of healthy male and female subjects. Clin Neurophysiol 2004; 115: 2123-7. 23. Kofler M, Poustka K. Ipsi- and contralateral exteroceptive EMG modulation in uni- and bilaterally activated thenar muscles. Clin Neurophysiol 2005; 116: 300-7. 24. Kofler M, Štetkárová I, Wissel J. Nociceptive EMG suppression in triceps brachii muscle in humans. Clin Neurophysiol 2004; 115: 1052-6. 25. Kofler M, Valls-Solé J, Fuhr P, Schindler C, Zaccaria BR, Saltuari L. Sensory modulation of voluntary and TMSinduced activation in hand muscles. Exp Brain Res 2008; 188: 399-409. 26. Kofler M, Wissel J, Müller J, Brenneis C. Influence of intrathecal baclofen on silent periods in dystonia. Muscle Nerve 2000; 23: 1145-6. 27. Kranz H, Adorjani C, Baumgartner G. The effect of nociceptive cutaneous stimuli on human motoneurons. Brain 1973; 96: 571-90. 28. Kumru H, Opisso E, Valls-Sole J, Kofler M. The effect of a prepulse stimulus on the EMG rebound following the cutaneous silent period. J Physiol 2009; 587: 587-95. 29. Leis AA, Kofler M, Ross MA. The silent period in pure sensory neuronopathy. Muscle Nerve 1992; 15: 1345-8. 30. Leis AA, Štetkárová I, Beric A, Stokic DS. Spinal motor neuron excitability during the cutaneous silent period. Muscle Nerve 1995; 18: 1464-70. 31. Leis AA, Štetkárová I, Beric A, Stokic DS. The relative sensitivity of F wave and H reflex to changes in motoneuronal excitability. Muscle Nerve 1996; 19: 1342-4. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
43
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
32. Leis AA, Stokic DS, Fuhr P, Kofler M, Kronenberg MF, Wissel J, Glocker FX, Seifert C, Štetkárová I. Nociceptive fingertip stimulation inhibits synergistic motoneuron pools in the human upper limb. Neurology 2000; 55: 1305-9. 33. Lo YL. The role of electrophysiology in the diagnosis and management of cervical spondylotic myelopathy. Ann Acad Med Singapore 2007; 36: 886-8. 34. Lo YL, Tan YE, Fook-Chong S, Boolsambatra P, Yue WM, Chan LL, Tan SB. Role of spinal inhibitory mechanisms in whiplash injuries. J Neurotrauma 2007; 24: 1055-67. 35. Logigian EL, Plotkin GM, Shefner JM. The cutaneous silent period is mediated by spinal inhibitory reflex. Muscle Nerve 1999; 22: 467-72. 36. Mamoli B, Heiss W-D, Maida E, Podreka I. Electrophysiological studies on the "Stiff-man" Syndrome. J Neurol 1977; 217: 111-21. 37. Manconi FM, Syed NA, Floeter MK. Mechanisms underlying spinal motor neuron excitability during the cutaneous silent period in humans. Muscle Nerve 1998; 21: 1256-64. 38. McLellan DL. The electromyographic silent period produced by supramaximal electrical stimulation in normal man. J Neurol Neurosurg Psychiatry 1973; 36: 334-41. 39. Osio M, Zampini L, Muscia F, Valsecchi L, Comi C, Cargnel A, Mariani C. Cutaneous silent period in human immunodeficiency virus-related peripheral neuropathy. J Peripher Nerv Syst 2004; 9: 224-31. 40. Pullman SL, Ford B, Elibol B, Uncini A, Su PC, Fahn S. Cutaneous electromyographic silent period findings in brachial dystonia. Neurology 1996; 46: 503-8. 41. Rekling JC, Funk GD, Bayliss DA, Dong XW, Feldman JL. Synaptic control of motoneuronal excitability. Physiol Rev 2000; 80: 767-52. 42. Romaniello A, Truini A, Galeotti F, De Lena C, Willer JC, Cruccu G. Cutaneous silent period in hand muscle is evoked by laser stimulation of the palm, but not the hand dorsum. Muscle Nerve 2004; 29: 870-2. 43. Rossi P, Pierelli F, Parisi L, Perrotta A, Bartolo M, Amabile G, Serrao M. Effect of painful heterotopic stimulation on the cutaneous silent period in the upper limbs. Clin Neurophysiol 2003; 114: 1-6. 44. Serrao M, Parisi L, Pierelli F, Rossi P. Cutaneous afferents mediating the cutaneous silent period in the upper limbs: evidences for a role of low-threshold sensory fibres. Clin Neurophysiol 2001; 112: 2007-14. 45. Serrao M, Parisi L, Valente G, Martini A, Fattapposta F, Pierelli F, Rossi P. L-Dopa decreases cutaneous nociceptive inhibition of motor activity in Parkinson's disease. Acta Neurol Scand 2002; 105: 196-201. 46. Shahani BT, Young RR. Studies of the normal human silent period. In: Desmedt JE, ed. New Developments in Electromyography and Clinical Neurophysiology. Vol. 3. Basel: Karger; 1973. p 589-602. 47. Štetkárová I, Kofler M. Cutaneous silent periods in the assessment of mild cervical spondylotic myelopathy. Spine 2009; 34: 34-42. 48. Štetkárová I, Kofler M, Leis AA. Cutaneous and mixed nerve silent periods in syringomyelia. Clin Neurophysiol 2001; 112: 78-85. 49. Svilpauskaite J, Truffert A, Vaiciene N, Magistris MR. Cutaneous silent period in carpal tunnel syndrome. Muscle Nerve 2006; 33: 487-93. 50. Svilpauskaite J, Truffert A, Vaiciene N, Magistris MR. Electrophysiology of small peripheral nerve fibers in man. A study using the cutaneous silent period. Medicina (Kaunas) 2006; 42: 300-13. 51. Syed NA, Sandbrink F, Luciano CA, Altarescu G, Weibel T, Schiffmann R, Floeter MK. Cutaneous silent periods in patients with Fabry disease. Muscle Nerve 2000; 23: 1179-86. 52. Tataroglu C, Uludag B, Karapinar N, Bademkiran F, Ertekin C. Cutaneous silent periods of the vastus medialis evoked by the stimulation of lateral femoral cutaneous nerve. Clin Neurophysiol 2005; 116: 1335-41. 53. Thaler, C., Kiechl, S., Kofler, M., Willeit, J., Wissel, J., and Poewe, W. Stiff leg syndrome - a focal form of stiff man syndrome? Movement Disorders 1998; 13 (Suppl 2), 308. 54. Uncini A, Kujirai T, Gluck B, Pullman S. Silent period induced by cutaneous stimulation. Electroencephalogr Clin Neurophysiol 1991; 81: 344-52. 55. Walk D, Fisher MA. Effects of cutaneous stimulation on ipsilateral and contralateral motoneuron excitability: an analysis using H reflexes and F waves. Electromyogr Clin Neurophysiol 1993; 33: 259-64. 56. Yaman M, Uluduz D, Solak O, Pay G, Kiziltan ME. The cutaneous silent period in carpal tunnel syndrome. Electromyogr Clin Neurophysiol 2007; 47: 215-20. 57. Yaman M, Uluduz D, Yuksel S, Pay G, Kiziltan ME. The cutaneous silent period in diabetes mellitus. Neurosci Lett 2007; 419: 258-62.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
44
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
PATOFIZIOLOGIJA TIHE KOŽNE PERIODE PATHOPHYSIOLOGY OF CUTANEOUS SILENT PERIOD Ivana Štětkářová Department of Neurology, Na Homolce Hospital, Prague, Czech Republic
Cutaneous reflexes are useful tests to study sensorimotor integration at spinal and supraspinal levels. One of the most robust cutaneous reflexes is designated the cutaneous silent period (CSP). It is a simple non-invasive test available for studying nociceptive fibers. The CSP is a brief pause in the voluntary EMG activity that occurs in response to a strong stimulus applied to a cutaneous nerve. Such painful stimulation evokes CSPs in several muscles simultaneously. CSP testing may be particularly useful in evaluation of certain segments of the nervous system and of certain components of sensory nerves that are not well assessed by routine electrodiagnostic methods. Conditions that affect this reflex pathway might be associated with absence or delay of the CSP. The physiological mechanisms generating the CSP remain uncertain, but most investigators agree that it is a spinal inhibitory reflex1–6 with afferent impulses entering the spinal dorsal horn and suppressing activity in motor nuclei. Afferent impulses that generate the CSP are carried primarily by the smaller, slower conducting A-delta fibers. The CSP can be obtained using standard EMG equipment. Recording surface electrodes are applied over the muscle belly. Digital or skin nerves are activated by painful stimuli that are delivered while the subject maintains a moderately strong voluntary muscle contraction. The CSP is defined as clear reduction or absence of voluntary EMG activity following the stimulus at appropriate latencies. The CSP is recordable across a wide range of muscle contraction strengths, however muscle force has recently been shown to be less critical for CSP recordings than as previously thought.7 For clinical purposes, the beginning, duration and end of the CSP can be measured in individual traces. The end of the CSP is typically more consistent than the onset latency and duration of the CSP. Clinical application CSPs have been studied in a number of pathological conditions in order to assess A-delta fiber conduction of the peripheral and central nervous system. CSP in disorders of the peripheral nervous system The CSP technique can be used to quickly determine whether afferent impulses in smaller fibers pass through peripheral nerve, cervical roots and enter the spinal cord at dorsal horns. Neuropathy and entrapment syndrome. A number of studies have examined the CSP in patients with different types of neuropathies,8-20, however, the utility of CSPs to diagnose polyneuropathy has been insufficient so far. Normal CSPs have been found in patients with large-fiber neuropathies with absent SNAP or somatosensory evoked potentials,2, 8 in Friedreich’s ataxia,11 in mild to moderate carpal tunnel syndrome.14, 18 The small afferent fibers appear to be relatively less affected and its dysfunction occurs late in the course of neuropathy. The CSP abnormallities have been found only in patients with profound abnormalities of small-fiber function. Only transection of a peripheral nerve, but not severe ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
45
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
entrapment, abolished the CSP.15 Preserved CSPs may serve to document residual nerve continuity in severe entrapment neuropathies when fast-conducting fibers were so compromised that their continuity could not be detected by standard electrodiagnostic techniques.16 On the other hand, a significant increase of the latency of the CSP was found in all 26 HIV-positive patients with polyneuropathy.17 A-delta fibers are probably very robust and resistant to compression, probably due to their less vulnerable small diameter. Preserved CSPs can prove residual continuity of the peripheral nerve or root in such clinical situations, when standard sensory responses are no longer recordable from large myelinated fibers. Radiculopathy. In a recent study Leis et al21 found that cervical radiculopathy is not associated with absence or delay of the CSP. Even in more severe root lesions, the vast majority of radiculopathies were not severe enough to alter conduction in the smaller, slower conducting A-delta fibers. Thus they concluded that CSP studies are of little use in detecting cervical radiculopathy. CSP in disorders of the central nervous system The CSP has been studied in a variety of disorders of the central nervous system. Syringomyelia. In syringomyelia, CSPs were absent or shortened on the side affected by impaired pain and thermal sensation and normal on the unaffected side.22, 23 The authors concluded that CSPs, generated at the spinal level by A-delta fibers, can be used to assess spinothalamic function in the centromedullary region already early in the course of syringomyelia, in which abnormality may relate to direct disruption of spinothalamic afferents originating from the posterior horn of the spinal cord and crossing contralaterally anterior to the central canal. Cervical myelopathy. In patients with mild cervical spondylogenic myelopathy CSPs are often significantly delayed, shortened, or absent as compared to healthy controls.24, 25 CSPs were highly associated with upper limb spinothalamic dysfunction: all patients who presented with abnormal CSPs had clinical evidence of afferent pain system abnormalities (hypalgesia, paresthesia, dysesthesia), while no patient with normal CSPs complained of abnormal pain sensation. Altered corticospinal projections in patients with pyramidal syndrome may affect CSP onset latency by modulating the balance of excitability in the underlying circuits.26 An alternative explanation of CSP alterations in cervical myelopathy may be a compromised vascular supply of the spinal cord, thereby affecting synaptic transmission within spinal cord neurons. The spinal inhibitory reflex circuitry subserving the CSP may be also modulated by supraspinal centers. The utility of CSP testing in the assessment of intramedullary cervical spinal cord lesions of various etiology has previously been documented.27 Recently the CSP abnormalities have been found in whiplash syndrome.28 Authors suggest that neurological dysfunction of whiplash may occur at several possible spinal cord localities in the CSP functional pathway. Neurodegenerative disorders. Abnormally prolonged CSPs were partially normalized by L-Dopa in idiopathic Parkinson’s disease,29 however, levodopa had no effect on CSPs or clinical symptoms in a few patients with multiple system atrophy and progressive supranuclear palsy. Prolonged CSPs have been reported in patients with unilateral hand dystonia,30 and in patients with Parkinson’s disease.31, 32 CSP is a simple electrodiagnostic method suitable for measurement of small slow conducting nerve fibers. Clinical interest of CSP is to better understand peripheral and central nervous system disorders that affect motor or sensory processing. Alteration of CSP in patients with these disorders could reflect differential effects on underlying circuits. References 1. Shefner JM, Logigian EL. Relationship between stimulus strength and the cutaneous silent period. Muscle Nerve 1993; 16: 278-82. 2. Uncini A, Kujirai T, Gluck B, Pullman S. Silent period induced by cutaneous stimulation. Electroencephalogr Clin Neurophysiol 1991; 81: 344-52. 3. Leis AA, Kofler M, Ross MA. The silent period in pure sensory neuronopathy. Muscle Nerve 1992; 15 (12): 1345-8. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
46
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
4. Leis AA. Conduction abnormalities detected by silent period testing. Electroencephalogr Clin Neurophysiol 1994; 93 (6): 444-9. 5. Floeter MK. Cutaneous silent periods. Muscle Nerve 2003; 28 (4): 391-401. 6. Svilpauskaite J, Truffert A, Vaiciene N, Magistris MR. Electrophysiology of small peripheral nerve fibers in man. A study using the cutaneous silent period. Medicina (Kaunas). 2006; 42 (4): 300-13. 7. Kofler M, Kumru H, Stetkarova I, Rüegg S, Fuhr P, Leis AA. Cutaneous silent periods are not affected by the antihistaminic drug cetirizine. Clin Neurophysiol 2009; 120 (5): 1016-9. 8. Leis AA, Kofler M, Ross MA. The silent period in pure sensory neuronopathy. Muscle Nerve 1992; 15: 1345-8. 9. Corsi FM, Fausti S, Serrao M, Casali C, Parisi L, Piazza G. Electromyographic mixed nerve and cutaneous silent period in evaluating the A-delta fibres in a patient with hereditary sensory-autonomic neuropathy. Funct Neurol 2002; 17 (1): 31-4. 10. Valls-Sole J, Graus F, Font J, Pou A, Tolosa ES. Normal proprioceptive trigeminal afferents in patients with Sjögren's syndrome and sensory neuronopathy. Ann Neurol 1990; 28 (6): 786-90. 11. Serrao M, Parisi L, Pierelli F, Rossi P. Cutaneous afferents mediating the cutaneous silent period in the upper limbs: evidences for a role of low-threshold sensory fibres. Clin Neurophysiol 2001; 112: 2007-14. 12. Syed NA, Sandbrink F, Luciano CA, Altarescu G, Weibel T, Schiffmann R, Floeter MK. Cutaneous silent periods in patients with Fabry disease. Muscle Nerve 2000; 23 (8): 1179-86. 13. Yaman M, Uludüz D, Yüksel S, Pay G, Kiziltan ME. The cutaneous silent period in diabetes mellitus. Neurosci Lett 2007; 419 (3): 258-62. 14. Aurora SK, Ahmad BK, Aurora TK. Silent period abnormalities in carpal tunnel syndrome. Muscle Nerve 1998; 21 (9): 1213-5. 15. Svilpauskaite J, Truffert A, Vaiciene N, Magistris MR. Cutaneous silent period in carpal tunnel syndrome. Muscle Nerve 2006; 33 (4): 487-93. 16. Kofler M, Fröhlich K, Saltuari L. Preserved cutaneous silent periods in severe entrapment neuropathies. Muscle Nerve 2003; 28 (6): 711-4. 17. Osio M, Zampini L, Muscia F, Valsecchi L, Comi C, Cargnel A, Mariani C. Cutaneous silent period in human immunodeficiency virus-related peripheral neuropathy. J Peripher Nerv Syst 2004; 9 (4): 224-31. 18. Truini A, Padua L, Biasiotta A, Caliandro P, Pazzaglia C, Galeotti F, Inghilleri M, Cruccu G. Differential involvement of A-delta and A-beta fibres in neuropathic pain related to carpal tunnel syndrome. Pain 2009;145 (1): 105-9. 19. Han JK, Oh K, Kim BJ, Koh SB, Kim JY, Park KW, Lee DH. Cutaneous silent period in patients with restless leg syndrome. Clin Neurophysiol 2007; 118 (8): 1705-10. 20. Tataroglu C, Uludag B, Karapinar N, Bademkiran F, Ertekin C. Cutaneous silent periods of the vastus medialis evoked by the stimulation of lateral femoral cutaneous nerve. Clin Neurophysiol 2005; 116 (6): 1335-41. 21. Leis AA, Kofler M, Stetkarova I, Stokic DS. The cutaneous silent period in cervical radiculopathy. Muscle Nerve 2009 (submitted) 22. Stetkarova I, Kofler M, Leis AA. Cutaneous and mixed nerve silent periods in syringomyelia. Clin Neurophysiol 2001; 112 (1): 78-85. 23. Kaneko K, Kawai S, Fuchigami Y, Morita H, Ofuji A. Cutaneous silent period in syringomyelia. Muscle Nerve 1997; 20 (7): 884-6. 24. Stetkarova I, Kofler M. Cutaneous silent periods in the assessment of mild cervical spondylotic myelopathy. Spine 2009; 34 (1): 34-42. 25. Lo YL, Tan YE, Dan YF, Leoh TH, Tan SB, Tan CT, Chan LL. Cutaneous silent periods in the evaluation of cord compression in cervical spondylosis. J Neurol 2007; 254 (1): 14-9. 26. Gilio F, Bettolo CM, Conte A, Iacovelli E, Frasca V, Serrao M, Giacomelli E, Gabriele M, Prencipe M, Inghilleri M. Influence of the corticospinal tract on the cutaneous silent period: a study in patients with pyramidal syndrome. Neurosci Lett 2008; 433 (2): 109-13. 27. Kofler M, Kronenberg MF, Brenneis C, Felber A, Saltuari L. Cutaneous silent periods in intramedullary spinal cord lesions. J Neurol Sci 2003; 216 (1): 67-79. 28. Lo YL, Tan YE, Fook-Chong S, Boolsambatra P, Yue WM, Chan LL, Tan SB. Role of spinal inhibitory mechanisms in whiplash injuries. J Neurotrauma 2007; 24 (6): 1055-67. 29. Serrao M, Parisi L, Valente G, Martini A, Fattapposta F, Pierelli F, Rossi P. L-Dopa decreases cutaneous nociceptive inhibition of motor activity in Parkinson's disease. Acta Neurol Scand 2002; 105 (3): 196-201. 30. Espay AJ, Morgante F, Purzner J, Gunraj CA, Lang AE, Chen R. Cortical and spinal abnormalities in psychogenic dystonia. Ann Neurol 2006; 59 (5): 825-34. 31. Pullman SL, Ford B, Elibol B, Uncini A, Su PC, Fahn S. Cutaneous electromyographic silent period findings in brachial dystonia. Neurology 1996; 46 (2): 503-8.
32. Nakashima K, Takahashi K. Silent periods in the abductor pollicis brevis muscle in patients with Parkinson's disease. Electromyogr Clin Neurophysiol 1992; 32 (4-5): 215-9.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
47
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
BAZIČNA IN KLINIČNA NEVROFIZIOLOGIJA HUMANIH UMAKNITVENIH REFLEKSOV NA BOLEČE DRAŽLJAJE BASIC AND CLINICAL NEUROPHYSIOLOGY OF HUMAN WITHDRAWAL REFLEXES TO PAINFUL STIMULI Ole Kæseler Andersen, Lars Arendt-Nielsen Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, Aalborg, Denmark
Introduction In the pain clinic, it has always been the dream to have an objective measure of patient’s pain – this is not possible and will most likely never be possible. The nociceptive withdrawal reflex is an objective measure of the spinal nociceptive activity. The reflex excitability is closely related to the perceived intensity of the sensory stimulus. This paper will focus on methods for quantitative assessment of nociceptive withdrawal reflexes and the use in clinical settings. A nociceptive withdrawal reflex is a protective reflex that serves to minimise tissue injury in relation to a peripheral nociceptive input. The reflex is generated at the spinal level but with strong modulation by segmental and descending activity. Hence, the neural connection from the primary sensory neurons to the motor neurons is a polysynaptic pathway and other afferent input, descending activity, and the excitability of the neurons in this pathway modulate the generation of the nociceptive reflex. The nociceptive withdrawal reflex may be used as an additional supplement to psychophysical methods to elucidate aspects of spinal nociceptive processing. In relation to pain research, the reflex is normally evoked by electrical stimulation of a peripheral nerve or a skin area on the foot. Heat can also be used for eliciting the nociceptive withdrawal reflex,1, 2 but high intensities are required combined with activation of a large skin area (spatial summation)3 to ensure sufficient, phasic afferent activity. Electrical stimulation is not damaging the skin and is highly reproducible. The reflex is typically acquired by surface electrodes on hamstring muscles. The excitability of the reflex can be assessed in two ways; either by the reflex threshold, or by the reflex amplitude for a given stimulus intensity. The reflex has an onset latency shorter than 100 ms indicating that A fibres are mediating the first response. Additional bursts may appear for higher stimulus intensities. Hugon (1973)4 broke the A-fibre mediated reflex response into a component mediated by tactile (group II) afferents with a latency of 4060 ms, and a component mediated by group III afferents (Aδ fibres) with a latency of 85– 120 ms. He denoted these two reflex components the RII and RIII reflex, respectively. Since then, the term RIII reflex is often used in relation to experimental pain research. In fact, close analysis of the theoretical delays in the reflex pathway indicate that latencies longer than 60 ms might reflect Aδ (group III) afferent activity.5 Kugelberg (1960)6 found that stimulation strengths sufficient to depolarise Aδ-fibres were most effective in eliciting the reflex though large fibres may contribute. The reflex has been claimed to be a very robust outcome measure with a strong correlation to pain intensity.1, 7, 8 However, a number of studies have observed poor correlation between reflex size and pain intensity ratings2,9–11 calling for caution in the design of experimental pain studies. Spinal reflex organisation It is generally accepted that the reflex is mediated via a spinal pathway but under supraspinal influence. Research into the spinal neuronal organisation has focused on the role of the reflex ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
48
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
from a sensory or a motor control perspective. From a motor control viewpoint, the sensory input initiating any reflex is part of the control of ongoing motor programmes. Hence, afferent activity has been regarded as feedback which partly left nociceptive input as an exception12 because the input may perturb the ongoing motor activities rather than serve as regulatory feedback. This reflex organisation has been termed ’Flexor Reflex Afferents’ simply to outline which afferents convey acitivty that may initiate a flexor reflex. From a sensory viewpoint, in particular nociceptive afferent activity, variation in reflex sensitivity depending on stimulation site has been tested and has revealed a modular reflex organisation. A module consists of a muscle (or group of synergists) and the associated cutaneous Reflex Receptive Field (RRF). The module is highly related to the biomechanical properties of the particular muscle13, 14 to ensure the muscle is only activated when it contributes to the optimal withdrawal. All reflex modules are regarded as independent so the net withdrawal is obtained by a combination of the activated modules. How this integration is affected by different motor tasks has not been fully investigated. The encoding of the reflex receptive field is occurring at the spinal level. This method is highly relevant in relation to pain research as it may be a way to probe the receptive field of dorsal horn neurons. Reflex receptive fields are mapped by stimulating several sites in random order, the spatial sensitivity of the reflex is determined which indirectly depict neuronal spatial encoding of the reflex, see figure 1. This non-invasive method is very interesting in relation to central sensitization as variation in neuronal receptive field size is accepted as a fundamental mechanism behind allodynia/hyperalgesia.15
50μV
30
10 Figure 1. The reflex receptive field for the tibialis anterior muscle to stimulation on the sole of the foot. The largest reflexes are seen when stimulation is applied to the arch of the foot. The colour scale represents the RMS amplitude of the EMG in the interval from 60 to 120 ms after stimulus onset.
Relation to research into pain physiology The reflex can be used to assess the response to both a single stimulus and a repeated stimulus (temporal summation, see figure 2).16 Temporal summation mimics the initial phase of wind-up, which is the response of spinal neurons to repeated nociceptive stimulation and is believed to be a key mechanism of spinal nociceptive processing under normal and pathological conditions. The reflex has been used extensively for assessment of drug actions.10, 17–20. Lower reflex thresholds and lower reflex temporal summation thresholds have been observed in chronic pain patients.21
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
49
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
12 125
Reflex size (μV)
10 0
75
50
25
0 0
0,5
1,0
1,5
2,0
2,5 Time (s)
Figure 2. A rectified and averaged reflex response from the biceps femoris muscle to five repetitive stimuli applied to the sural nerve (onset indicated by arrows). The stimulation frequency was 2 Hz. Notice the gradual build up in reflex size (temporal summation).
Normally, quantification of a reflex response involves two different parameters; one describing the temporal aspects and one quantifying the energy in the reflex response. The typical procedure involves averaging a number of sweeps (between 5-15), because of the stochastic nature of the response. Based on the averaged signal, onset latencies may be quantified using strict methods.14 The amplitude of the NWR response may be quantified using different methods e.g. ‘area under the rectified response’, Root-Mean-Square of the individual recordings in fixed intervals after the stimulus. Other methods focus on the area under the curve for the envelope of the recetified response etc. Reflex thresholds can be determined using different criteria22 where one recommendation is to base it on calculation of Z-scores from pre-stimulus EMG activity. Use of RRF for indirect assessment of neuronal receptive field relies on identification of the size of the RRF which also might be based on calculation of Z-scores to identify statistically significant reflex EMG activity.23. Expansion of RRF following injections of capsaicin has been observed in spinal cord injured24 but not in spinal intact healthy volunteers5. Normal values for the RRF characteristics across age and sex have just been published.25 Conclusion An objective measure of nociceptive activity may be obtained by assessing withdrawal reflexes in both experimental and clinical settings. In chronic pain patients, lower reflex thresholds have been observed. Assessment of reflex receptive fields seems to be a promising new method for assessment of the excitability of the nociceptive system in relation to chronic pain syndromes.
References 1. Willer JC. Comparative study of perceived pain and nociceptive flexion reflex in man. Pain 1977; 3: 69-80. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
50
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
2. Campbell IG, Carstens E, Watkins LR. Comparisons of human pain sensation and flexion withdrawal evoked by noxious radiant heat. Pain 1991; 45: 259-68. 3. Morch CD, Andersen OK, Graven-Nielsen T, Arendt-Nielsen L. Nociceptive withdrawal reflexes evoked by uniform-temperature laser heat stimulation of large skin areas in humans. J Neurosci Methods 2007; 160: 85-92. 4. Hugon M. Exteroceptive reflexes to stimulation of the sural nerve in man. In: Desmedt JE, ed. New developments in electromyography and clinical neurophysiology. Vol. 3. Basel: Karger, 1973. p713-29. 5. Andersen OK. Studies of the organization of the human nociceptive withdrawal reflex. Focus on sensory convergence and stimulation site dependency. Acta Physiol 2007; 189 (Suppl 654): 1-35. 6. Kugelberg E, Eklund K, Grimby L. An electromyographic study of the nociceptive reflexes of the lower limb. Mechanism of the plantar responses. Brain 1960; 83: 394-410. 7. Debroucker T, Willer JC, Bergeret S. The nociceptive flexion reflex in humans: a specific and objective correlate of experimental pain. In: Chapman CR, Loeser JD, eds. Issues in pain measurement. New York: Raven press, 1989. p337-64. 8. Chan CWY, Dallaire M. Subjective pain sensation is linearly correlated with the flexion reflex in man. Brain Res 1989; 479: 145-50. 9. García-Larrea L, Charles N, Sindou M, Mauguičre F. Flexion reflexes following anterolateral cordotomy in man: Dissociation between pain sensation and nociceptive reflex RIII. Pain 1993; 55: 139-49. 10. Andersen OK, Felsby S, Nikolajsen L, Bjerring P, Jensen TS, Arendt-Nielsen l. The effect of ketamine on stimulation of primary and secondary hyperalgesic areas induced by capsaicin - an double-blind, placebo-controlled, human experimental study. Pain 1996; 66: 51-62. 11. Terkelsen AJ, Andersen OK, Molgaard H, Hansen J, Jensen TS. Mental stress inhibits pain perception and heart rate variability but not a nociceptive withdrawal reflex. Acta Physiol Scand 2004; 180: 405-14. 12. Lundberg A. Multisensory control of spinal reflex pathways. In: Granit R, Pomeiano O, eds. Reflex control of posture and movement, progress in brain res. Amsterdam: Elsevier, 1979. p11-28. 13. Schouenborg J, Kalliomäki J. Functional organization of the nociceptive withdrawal reflexes. I. Activation of hindlimb muscles in the rat. Exp brain res 1990; 83: 67-78. 14. Andersen OK, Sonnenborg FA, Arendt-Nielsen L. Modular organization of human leg withdrawal reflexes elicited by electrical stimulation of the foot sole. Muscle nerve 1999; 22: 1520-30. 15. Dubner R. Neuronal plasticity and pain following peripheral tissue inflammation or nerve injury. In: Bond MR, Charlton JE, Woolf CJ, eds. Proceedings of the vith world congress on pain. Amsterdam: Elsevier, 1991. p263-76. 16. Arendt-Nielsen L, Sonnenborg FA, Andersen OK. Facilitation of the withdrawal reflex by repeated transcutaneous electrical stimulation: an experimental study on central integration in humans. Eur J Appl Physiol 2000; 81: 165-73. 17. Petersen-Felix S, Arendt-Nielsen L, Bak P, Bjerring P, Breivik H, Svensson P, Zbinden AM. Ondansetron does not inhibit the analgesic effect of alfentanil. Br J Anaesth 1994; 73: 326-30. 18. Arendt-Nielsen L, Petersen-Felix S, Fischer M, Bak P, Bjerring P, Zbinden AM. The effect of n-methyl-d-aspartate antagonist (ketamine) on single and repeated nociceptive stimuli: a placebo-controlled experimental human study. Anesth Analg 1995; 81: 63-8. 19. France CR, Al'absi M, Ring C, France JL, Harju A, Wittmers LE. Nociceptive flexion reflex and pain rating responses during endogenous opiate blockade with naltrexone in healthy young adults. Biol Psychol 2007; 75: 95-100. 20. Baars JH, Mager R, Dankert K, Hackbarth M, Von DF, Rehberg B. Effects of sevoflurane and propofol on the nociceptive withdrawal reflex and on the h reflex. Anesthesiology 2009; 111: 72-81. 21. Banic B, Petersen-Felix S, Andersen OK, Radanov BP, Villiger PM, Arendt-Nielsen L, Curatolo M. Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia. Pain 2004; 107: 7-15. 22. Rhudy JL, France CR. Defining the nociceptive flexion reflex (nfr) threshold in human participants: A comparison of different scoring criteria. Pain 2007; 128: 244-53. 23. Neziri AY, Curatolo M, Bergadano A, Petersen-Felix S, Dickenson A, Rendt-Nielsen L, Andersen OK. New method for quantification and statistical analysis of nociceptive reflex receptive fields in humans. J Neurosci Methods 2009; 178: 24-30. 24. Andersen OK, Finnerup NB, Johannesen Il, Biering-Sorensen F, Jensen TS, Arendt-Nielsen L. Expansion of nociceptive withdrawal reflex receptive fields in spinal cord injured humans following injection of intramuscular capsaicin. Abstracts for the 12th world congress on pain , no. Pf341. 2008. 25. Neziri AY, Andersen OK, Petersen-Felix S, Radanov B, Dickenson AH, Scaramozzino P, Rendt-Nielsen L, Curatolo M. The nociceptive withdrawal reflex: Normative values of thresholds and reflex receptive fields. Eur J Pain 2009. V tisku.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
51
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
NEKATERI VIDIKI ORGANIZACIJE SLUŽBE ZA LAJŠANJE AKUTNE BOLEČINE SOME ASPECTS OF THE ORGANISATION OF AN ACUTE PAIN SERVICE Aleksander Manohin Klinični oddelek za anesteziologijo in intenzivno terapijo operativnih strok Univerzitetni klinični center Ljubljana, Ljubljana
Izvleček. Avtor kot uvod v sklop o organizaciji službe za lajšanje akutne bolečine opozori na nekatere redkeje poudarjane dejavnike, ki lahko vplivajo na njeno delovanje. Abstract. As an introduction to the section dealing with the organization of an acute pain service, the author calls attention to some less frequently mentioned factors that may interfere with the functioning of such a service.
Uvod Pri organizaciji službe za lajšanje akutne bolečine je treba opozoriti na nekatere vidike, ki morda niso tako opazni, so pa zelo pomembni za pravilno in uspešno delo. Razpravljanje Čeprav je bolečina stara toliko kot človeštvo in so jo že od nekdaj poskušali lajšati na razne načine, se je organizirana oblika lajšanja bolečine razvijala počasi in je šele v novejšem času dosegla zavidljivo raven. Ko sem bil še sam študent, so nas učili, da se zdravnik v dveh primerih rad neopazno izmuzne iz bolniške sobe, ker ne ve, kaj naj bi pri bolniku naredil: ob umiranju in pri bolečinah. Med mojim pripravniškim stažem je kirurg neki bolnici, ki je tožila, da jo boli, rekel, da vse bolečine odvzame samo zemlja. Še pred nekaj leti so študenti medicine v zadnjem letniku študija pri preverjanju znanja iz anesteziologije na vprašanje, ali je prav, da bolnik po operaciji opozori na bolečino, v velikem odstotku odgovarjali, da to ni treba, saj po operaciji mora boleti, ali pa celo, da ni prav, ker je osebje tako in tako preobremenjeno. Med ljudmi je pogosto veljalo prepričanje, da tisti, ki toži o bolečinah, ni pravi pacient ('trpeči'), da je siten in da ne sme stokati za vsako malenkost. V isti bolniški sobi so na primer ležali bolniki, ki so eden pred drugim skrivali bolečino, da ne bi izpadli slabiči. Ko smo anesteziologi pred leti pričeli poudarjati pomen lajšanja bolečine, predvsem akutne, pooperacijske, pa seveda tudi kronične, se je navedena miselnost na vseh ravneh začela počasi spreminjati. Sedaj pa nastajata novi težavi, na kateri želim opozoriti. Sprememba miselnosti se lahko kaj hitro zaustavi, če bolniku, ki smo ga prepričevali in učili, da mora opozoriti na bolečino, le-te ne zmoremo olajšati, kadar opozori nanjo. V mislih imam kronično pomanjkanje anesteziologov. Kot primer naj navedem lajšanje porodne bolečine. Vsi vemo, da jo najučinkoviteje lajšamo z epiduralno analgezijo, vendar pa pogosto ni dovolj anesteziologov, ki bi jo lahko dali. Zato se tudi dogaja, da porodnicam sploh ne ponudijo te možnosti, saj bi je ne zmogli zagotoviti vsem, ki bi jo želele; dobijo jo samo tiste, ki posebej zaprosijo zanjo. Akademik Janez Milčinski je večkrat poudarjal, da zdravnik, ki ve, da se nekaj lahko zgodi, pa upa, da se to ne bo zgodilo, naklepa. Če to misel nekoliko preoblikujemo, bi lahko rekli, da anesteziolog, ki ve, da je najučinkovitejša metoda za lajšanje porodne bolečine epiduralna analgezija, pa tega ne ponudi, naklepa proti Hipokratovi prisegi. Seveda nismo sami krivi, da ni dovolj anesteziologov. Lahko pa začnemo aktivno obveščati odgovorne in javnost, da ne zmoremo zagotoviti lajšanja porodne bolečine po najsodobnejših postopkih vsem porodnicam. Začeti moramo tudi dodatno usmerjati ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
52
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
večje število že aktivnih anesteziologov, da se začno ukvarjati s porodno analgezijo. Ne smemo samo čakati, da se bo samo po sebi kaj uredilo in se hkrati bati, če si bo preveč porodnic zaželelo dobiti epiduralno analgezijo. Drug takšen primer je sedacija med gastroenterološkimi diagnostičnimi posegi. Ker ni možnosti, da bi bil pri vsakem takšnem posegu anesteziolog, smo pustili, da bolnike boli, ali pa, kar je še huje, molčali, ko so neanesteziologi poskušali lajšati bolečino, kar medtem ko so izvajali endoskopsko preiskavo. V Nemčiji na primer imajo podobno težavo: tam poznajo poseben profil, ki ga imenujejo 'propofolska sestra' samo za dajanje propofola med endoskopijo, čeprav vsi vemo, da dajanje propofola ni preprosto in da mora tisti, ki ga daje, obvladati vse stopnje sedacije, vključno s splošno anestezijo. Pri nas smo, da bi omilili bolečino med endoskopijo, zaprosili Glavni strokovni svet SZD za uvedbo pouka v obliki posebnih znanj – šolo za specialiste gastroenterologe za dajanje povsem določenih oblik sedacije pri odraslih bolnikih skupine ASA 1 in ASA 2, kadar ne potekajo ob neposrednem sodelovanju anesteziologa. Treba je torej biti aktiven in prevzeti vodilno vlogo v izboljšanju pomanjkljivega lajšanja bolečine, ne pa pustiti, da stvari tečejo same po sebi, prav tako pa ne dovoliti zniževanja že pridobljenih strokovnih standardov. Druga težava, ki se mi zdi pomembna, pa je organizacija protibolečinskih enot. Seveda je prav in nujno potrebno, da jih imamo, vendar pa ni prav, da se ob tem ne zavedamo dejstva, da je lajšanje bolečine osnovna naloga vsakega anesteziologa in da je ne smemo preprosto prenesti na protibolečinsko enoto. Ko sem bil 1985. leta v takratni Sovjetski zvezi, kjer so imeli dva profila anesteziologov – anesteziologe in reanimatologe (po naše bi temu rekli specialiste za intenzivno zdravljenje) – sem, sem v operacijski dvorani slišal, da je anesteziologinja med anesteziranjem zavpila, da je tlak padel in naj pokličejo reanimatologa, sama pa ni naredila ničesar, ampak je samo čakala na tega reanimatologa. S to primerjavo želim opozoriti, da mora vsak anesteziolog znati lajšati bolečino in ne misliti ali pričakovati, da jo lahko lajša samo protibolečinska enota, naloga protibolečinske enote pa je izdelava enotnih smernic za lajšanje bolečine, nadzor tega lajšanja in zagotavljanje podaljšane analgezije v pooperacijskem obdobju ter vključevanje v zahtevnejše primere lajšanja bolečine. Izdelane smernice morajo biti poenotene na vseh anestezioloških oddelkih, ob upoštevanju vrste operacij in stopnje bolečine pri njih. Ne sme se zgoditi tako, kot se je v preteklosti pogosto dogajalo, kadar sem študente medicine vprašal, katere smernice za oživljanje bodo uporabljali, in so mi odgovarjali, da je to odvisno od inštruktorja. Čim več protibolečinskih shem imamo, tem pogosteje se v konkretnem primeru odločimo za neustrezno shemo oziroma za shemo 'po občutku' in tem manj je možnosti za sprotno preverjanje učinka izbrane mešanice, saj je premalo bolnikov, ki bi jo dobili in je vzorec premajhen. Sklep Med anesteziologom 'na terenu' in protibolečinsko enoto morata vladati medsebojna povezanost in odlično sodelovanje. Protibolečinska enota ni in tudi ne sme postati izolirana enota anesteziološkega oddelka, ampak odločilni dejavnik za vodenje lajšanja bolečine, ki ga operacionalizirajo vsi anesteziologi. Samo na ta način bo organizacija protibolečinskih enot smiselna in bo dosegla raven, ki ga v modernem lajšanju bolečine mora imeti.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
53
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
ORGANIZIRANOST ZDRAVLJENJA KRONIČNE BOLEČINE V SLOVENIJI CHRONIC PAIN SERVICE ORGANISATION IN SLOVENIA Marija Cesar-Komar Splošna bolnišnica Slovenj Gradec, Slovenj Gradec Izvleček. Uvod. Začetki organizirane terapije kronične bolečine segajo v leto 1977, ko je v Ljubljani prim. dr. Jasna Müller, ki je na Kitajskem opravila tečaj iz akupunkture, začela aktivnosti pri Ministrstvu za zdravje republike Slovenije za priznanje akupunkture kot terapevtske metode v Sloveniji. Zaradi tega je bila opredeljena kot uradna terapevtska metoda v Zeleni knjigi medicinskih storitev. Isto leto, 1978, je pod okriljem oddelka za anesteziologijo v Kliničnem centru Ljubljana uradno začela delovati protibolečinska ambulanta (PBA). Sedaj imamo v Sloveniji 16 protibolečinskih ambulant, pri anestezioloških oddelkih splošnih bolnišnic, v Univerzitetnem kliničnem centru Ljubljana in Maribor, na Onkološkem inštitutu, na Oddelku za medicinsko rehabilitacijo UKC Maribor, na Nevrološki kliniki UKC Ljubljana in zasebni PBA Vrabl in Bem. Metoda dela. Z anketo, ki je vsebovala 10 vprašanj in sem jo razposlala vsem vodjem PBA v Sloveniji, sem želela dobiti sliko organiziranosti in zdravljenja kronične bolečine v Sloveniji. Vprašanja so bila o delovnem urniku posamezne PBA, koliko zdravnikov dela v njej , na koliko časa se menjavajo, število bolnikov, povprečno obdelanih na delovni dan, uporabljene terapevtske metode in v kolikšnem odstotnem deležu posamezna, sodelovanje z drugimi specialisti, ali je potreba po širitvi dejavnosti, kje so omejitve, želje za v prihodnje. Zadnje vprašanje je bilo, koliko storitev (faktorjev) in prvih pregledov so opravili v letu 2008. Rezultati. Od 16 poslanih anket je bilo vrnjenih in izpolnjenih le 13, kar je 81 %. Dala je zanimive rezultate, ki jih predstavljam v nadaljevanju. O nekaterih od teh podatkov smo poročali na 5. Kongresu anesteziologov Slovenije v Portorožu maja 2009. Razpravljanje. Protibolečinska dejavnost zdravljenja kronične bolečine v Sloveniji je organizirana v protibolečinskih ambulantah, ki so večinoma v okviru oddelkov za anesteziologijo splošnih bolnišnic, pri UKC Ljubljana in Maribor, Onkološkem inštitutu Ljubljana, Nevrološki kliniki UKC Ljubljana, Oddelku za medicinsko rehabilitacijo UKC Maribor. Uporabljajo različne terapevtske metode v različnih odstotnih deležih. Število zdravnikov, ki delajo v PBA v Sloveniji, je 33. Opravijo 351.933 faktorjev (2008) in obdelajo 9241 novih bolnikov na leto (2008). Zaključek. Zdravljenje kronične bolečine v Sloveniji je mlada dejavnost, stara le dobra tri desetletja .Organizirana je v protibolečinskih ambulantah. Njihovo število se veča – od prve v letu 1978, naslednje v letu 1979 in tretje v letu 1980. Dobrih 10 let po prvi ambulanti se je število začelo strmo dvigati, še hitreje v zadnjem desetletju. V večjih centrih delajo vsak dan, v ostalih bolnišnicah različno število ur in dni v tednu. Delujejo multidisciplinarno, s sodelovanjem več različnih strokovnjakov. Delo v protibolečinski ambulanti zahteva dodatno znanje in nenehno izobraževanje ter uvajanje vedno novih terapevtski metod. Pomemben del je dokumentiranje dela, objavljanje rezultatov na domačih in mednarodnih kongresih, seminarjih in simpozijih. Zahvala za dokaj dobro stanje protibolečinske dejavnosti gre zdravnikom, ki se s tem ukvarjajo in se nenehno dodatno izobražujejo. Stanje se je gotovo izboljšalo tudi zaradi delovanja Slovenskega združenja za zdravljenje bolečine (SZZB), združenja zdravnikov raznih specialnosti, ki se zavedajo problema bolečine in si prizadevajo, da bi jo pravilno in dobro zdravili. Abstract. Background. Beginning of the organised chronic pain therapy in Slovenia dates back to the year 1977, when prim. Jasna Müller, after acupuncture course in the China, began the activities for recognition of acupuncture in Slovenia. Acupuncture was included in our western medical system and indexed as a lawful procedure in our book of medical procedures. At present time we have 16 official pain therapy centres, as branches of the Anaesthesiology departments in Ljubljana University Medical Centre, Maribor University Medical Centre, Department of Medical Rehabilitation in Maribor, Institute for Oncology Ljubljana, Neurology Clinic Ljubljana, and private pain therapy offices (PBA) Vrabl and Bem. Methods. An enquiry was designed and mailed to all pain therapy leaders in Slovenia in order to get the picture of pain therapy activities in Slovenia. The enquiry consisted of ten questions with which we wanted to find out about working hours of every centre, the number of medical doctors involved, their rotations, mean number of patients per centre per day, therapeutical methods used along with the percentage for each method. Furthermore, we wanted to know about any cooperation with other specialists, whether there was a need for expanding, if they were limited in their work, what their wishes for the future would be, how many procedures and how many first examinations were done in each centre in 2008. Results. Thirteen questioners were returned out of 16 (81%) and interesting results, herewith presented, were obtained. th Preliminarily they were reported at the 5 Congress of Slovenian anaesthesiologists in Portorož, in May 2009. Discussion. Chronic pain therapy is organised in ambulances for pain therapy in all general hospitals, both University Medical Centres (UMC) – Ljubljana and Maribor –, at the Institute of Oncology, Department for Medical Rehabilitation UMC Maribor, and in two private ambulances. SZZB is an organization of medical professionals in different specialties, ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
54
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
contributing to improvement of pain therapy, better informing of professional and general public about pain and organising educational workshops, designing the studies from the field of pain, and also for better organisation of anti-pain services. We are especially proud of a study on the incidence of chronic pain in Slovenia. It was conducted after the great European study in 2005 which included 15 European countries and Israel, without Slovenia. The results of our study are quite comparable with the results in Europe. Conclusion. Relatively young pain service in Slovenia (30 years) has given good results in chronic pain treatment, development of many new pain therapy centres, centres with more working hours, introduction of new therapeutical methods, and active involvement in international seminars, symposiums and congresses. The credit for that goes to all doctors involved in pain therapy, because they needed not only knowledge from their basic specialties, but also additional education. That is the reason we are trying to achieve a better validation for the educational programme we are preparing. For sure, the progress, the distinction and recognition of this work depends also on individuals, specially active in the field, contributing additional effort, time, energy and knowledge for recognition of this medical branch.
Uvod Akutna pooperacijska bolečina in njeno zdravljenje je naravno nadaljevanje dela vsakega specialista anesteziologa v pooperacijskem obdobju. Prav zato so se tudi s terapijo kronične bolečine začeli najprej intenzivneje ukvarjati anesteziologi. Terapija kronične bolečine je še danes marsikje zanemarjeno, nepokrito ali nezadovoljivo delujoče področje. Začetki organizirane terapije kronične bolečine segajo v leto 1977, ko je v Ljubljani prim. dr. Jasna Müller, ki je na Kitajskem opravila tečaj iz akupunkture, začela aktivnosti pri Ministrstvu za zdravje republike Slovenije za priznanje akupunkture kot terapevtske metode v Sloveniji. Ta je bila nato tako tudi opredeljena v Zeleni knjigi medicinskih storitev. Na pobudo prim dr. Draga Plešivčnika, takratnega direktorja, je bil 1978 v Slovenj Gradcu, organiziran mednarodni simpozij o tradicionalni kitajski medicini in akupunkturi, s predstavniki ministrstva za zdravje obeh držav - Kitajske in Slovenije. Sprva se je uporabljala v večjem delu akupunkturna terapija, ki se ji je kmalu pridružilo urejanje medikamentne terapije, farmakološke in električne blokade (TENS, TNB ), katetri. Leto 1996 je bilo prelomno za zdravljenje kronične bolečine v Sloveniji, saj je bilo ustanovljeno Slovensko združenje za zdravljenje bolečine (SZZB) v Ljubljani, s sedežem v Splošni bolnišnici Maribor in prvo predsednico prim. mag. Nevenko Krčevski-Škvarč, dr. med. V Sloveniji je 16 protibolečinskih ambulant. V njih zdravimo kronično bolečino po posameznih bolnišnicah dokaj podobno, tako po urnikih delovanja ambulant kot po uporabi terapevtskih metod. Metode dela Anketo z 10 vprašanji sem razposlala vsem vodjem protibolečinskih ambulant v Sloveniji. Odgovori, ki so prispeli, so bili zanimivi. Od poslanih 16 anket je bilo vrnjenih 13, kar je 81 %. Nekaj odgovorov je bilo dvoumnih, da je bil potreben še osebni telefonski intervju. Z anketo smo želeli izvedeti, kolikokrat na teden dela protibolečinska ambulanta (PBA) in koliko ur; koliko različnih zdravnikov dela v njej in na koliko časa se menjavajo pri delu; koliko je približno obdelanih pacientov na delovni dan, koliko faktorjev je bilo opravljenih po posameznih PBA v letu 2008 in koliko novih bolnikov je bilo obdelanih v letu 2008 (prvih pregledov). Zanimale so nas metode zdravljenja v PBA, približno v odstotnih deležih – akupunktura, farmakološke blokade, vstavljanje katetrov (EKD, subarahnoidno), urejanje medikamentne terapije, vstavljanje in urejanje subkutanih elastomerskih črpalk in vstavljanje subarahnoidnih elektrod za centralno stimulacijo. Kakšno je sodelovanje z zdravniki družinske medicine, z drugimi specialisti in s psihiatri in psihologi, saj vemo, da je bolečina multidisciplinaren problem, ki zahteva multidisciplinarno obdelavo. Naslednje, kar nas je zanimalo, je, ali je potreba pri bolnikih določenega področja po razširitvi obsega dela PBA in kje so omejitve ter kaj si želijo v prihodnje v posameznih PBA. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
55
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Povprašali smo, koliko storitev so opravili v posamezni ambulanti v letu 2008, število faktorjev in koliko bolnikov je bilo na novo obdelanih v letu 2008 – število prvih pregledov. Rezultati Z analizo ankete smo ugotovili, da dela polni delovni čas (8 ur) 5 dni v tednu UKC Ljubljana, UKC Maribor, Onkološki inštitut Ljubljana, Splošna bolnišnica Novo mesto, Splošna bolnišnica Jesenice in Ambulanta Vrabl. V ostalih protibolečinskih ambulantah v Sloveniji je delovni čas nekoliko krajši, in sicer v vseh ostalih nekaj manj ur na teden, v Murski Soboti 32 ur, v Slovenj Gradcu 28 ur, na Ptuju, v Izoli in Celju po 16 ur, v Brežicah in UKC Maribor (Oddelek za medicinsko rehabilitacijo) 10 ur in v Splošni bolnišnici Nova Gorica 8 ur na teden. Razpredelnica 1. Začetek delovanja PBA v Sloveniji in sedanje trajanje dela (delovnih ur/teden) PBA UKC Ljubljana UKC Maribor OI Ljubljana SB Jesenice ZPBA Vrabl Novo mesto Murska Sobota SB Slovenj Gradec SB Izola SB Ptuj SB Celje SB Brežice Rehab. UKC Mb SB Nova Gorica Nevrol. Klinika Ljubljana PBA Bem
Začetek delovanja 1978 4. 5. 1982 2003 16. 6. 2004 1988 11. 4. 1979 2. 12. 2004 1. 7. 1991 1991 2004 1988 2007
Ure/teden 40 40 40 0 40 40 32 28 16 16 16 10 10 8 0 0
Razpredelnica 2. Število zdravnikov in njihovo izmenjevanje v ambulantah PBA OI Ljubljana UKC Ljubljana UKC Maribor SB Murska Sobota Rehab. UKC Mb SB Slovenj Gradec SB Izola SB Ptuj SB Nova Gorica SB Novo mesto SB Brežice SB Celje SB Jesenice ZPBA Vrabl Nevrol. klinika Ljubljana PBA Bem
Št. zdravnikov več kot 3 3 3 3 2 2 2 2 2 2 1 1 1 1 0 0
Menjave vsak mesec po potrebi vsak dan vsak drugi dan vsak teden vsak mesec vsak drugi dan vsak drugi dan vsak mesec vsak drugi dan ni menjav ni menjav ni menjav ni menjav 0 0
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
56
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Največ različnih zdravnikov dela v PBA na Onkološkem inštitutu Ljubljana – več kot trije. Po trije različni zdravniki delajo v PBA pri UKC Ljubljana, UKC Maribor in v Splošni bolnišnici Murska Sobota (zunanji sodelavci). Po dva različna zdravnika delata v PBA UKC Maribor – medicinska rehabilitacija, Splošni bolnišnici Slovenj Gradec, Splošni bolnišnici Izola, Ptuj, Nova Gorica, Novo mesto. Ti zdravniki se menjavajo v ambulanti na različne časovne intervale. Sodelovanje zdravnikov družinske medicine, psihiatrov in psihologov je povsod zadovoljivo (razpredelnica 3). Razpredelnica 3. Sodelovanje z zdravniki drugih specialnosti PBA UKC Ljubljana UKC Maribor OI Ljubljana Rehab. UKC Mb SB Slovenj Gradec SB Murska Sobota SB Izola SB Ptuj SB Nova Gorica SB Brežice SB Novo mesto SB Celje SB Jesenice ZPBA Vrabl PBA Bem Nevrol. klinika Ljubljana
zdrav. druž. med zadovoljivo zadovoljivo dobro dobro odlično zadovoljivo dobro dobro odlično dobro zadovoljivo dobro 0 zadovoljivo 0 0
Sodelovanje drugi spec. dobro odlično dobro dobro dobro dobro dobro dobro zadovoljivo dobro zadovoljivo odlično 0 dobro 0 0
psihiater/psiholog zadovoljivo dobro nezadovoljio dobro zadovoljivo dobro nezadovoljio dobro dobro nezadovoljio zadovoljivo zadovoljivo 0 zadovoljivo 0 0
Bolečinska dejavnost še vedno ni zadovoljiva. Še vedno imajo bolniki različno dolge čakalne dobe, odvisno pač od narave obolenja. Onkološki bolniki je nimajo oziroma naj je za obravnavo v PBA ne bi imeli nikjer. Vsi zdravniki so v anketi izrazili potrebo po širitvi dejavnosti oziroma urnika delovanja PBA. Vzroka za to sta predvsem pomanjkanje usposobljenih zdravnikov in prostorske omejitve. Po PBA v Sloveniji se razne metode za zdravljenje kronične bolečine uporabljajo v različnih odstotnih deležih. Največ se uporablja akupunktura, in sicer vse od 90 % v Novem mestu pa do 10 % drugod. Akupunkture ne uporabljajo v UKC Maribor in v Splošni bolnišnici Nova Gorica. Farmakološke blokade delajo v vseh PBA. V PBA Rehabilitacija UKC Maribor, v Brežicah, PBA Vrabl, na Jesenicah in v Novi Gorici (delno le hospitalno) ne vstavljajo katetrov, v vseh drugih PBA pa jih. V vseh PBA urejajo medikamentno analgetično in adjuvantno terapijo kroničnih bolečinskih bolnikov, vendar v različnih odstotnih deležih. Vstavljajo črpalke za subkutano aplikacijo analgetikov, predpisujejo, urejajo sestave analgetičnih mešanic, in to vse v različnih odstotnih deležih. Tega ne delajo v vseh PBA (ne v PBA na Jesenicah, Vrabl, v Brežicah in v Rehabilitaciji UKC Maribor). Epiduralne elektrode za centralno stimulacijo vstavljajo le v UKC Maribor, in to s sodelovanjem nevrokirurga, in eno baklofensko črpalko subarahnoidno.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
57
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Razpredelnica 4. Potreba za širitev in omejitve PBA
Potreba za širitev da
UKC Ljubljana UKC Maribor OI Ljubljana Rehab. UKC Mb SB Slovenj Gradec SB Murska Sobota SB Izola SB Ptuj SB Nova Gorica SB Brežice SB Novo mesto SB Celje SB Jesenice ZPBA Vrabl PBA Bem Nevrol. klinika Ljubljana
ne
X X X X X X X X X X X X 0 X 0 0
premalo osebja
Omejitve premalo prostoa
X
X
X X X
X
ZZZS X X
X X
X X X X X
X
X X X 0 X 0 0
0 0 0
0 0
0 0
Razpredelnica 5. Uporabljane metode [v % od vseh] PBA UKC Ljubljana UKC Maribor OI Ljubljana Rehab. UKC Mb SB Slovenj Gradec SB Murska Sobota SB Izola SB Ptuj SB Nova Gorica SB Brežice SB Novo mesto SB Celje SB Jesenice ZPBA Vrabl PBA Bem Nevrol. klinika Ljubljana
Akupunktura 50 0 10 10 70 30 10 10 0 85 90 15 0 27 0
Farmakol. blokade 15 60 50 60 10 10 20 30 30 8 5 10 0 28 0
0
0
1 10 30 0 5 1 10 20 0 0 1-2 2 0 0 0
Medikam. terapija 33 100 100 20 10 50 30 20 65 7 100 90 0 42 0
0
0
Katetri
Črpalke
Elektrode
1 10 50 0 5 5 20 20 5 0 1-2 2 0 0 0
0 1 0 0 0 0 0 0 0 0 0 0 0 0 0
0
0
Vodje PBA si v prihodnje želijo več prostora za dejavnost, boljšo in dodatno opremo, širitev dejavnosti na področje invazivnih metod in še boljše sodelovanje s specialisti drugih specialnosti, kar je razvidno iz razpredelnice 6.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
58
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Razpredelnica 6. Želje v PBA PBA UKC Ljubljana UKC Maribor OI Ljubljana Rehab. UKC Mb SB Slovenj Gradec SB Murska Sobota SB Izola SB Ptuj SB Šempeter SB Brežice SB Novo mesto SB Celje SB Jesenice ZPBA Vrabl PBA Bem Nevrol. klinika Ljubljana
Prostor
Oprema
X
X X
X X X X X X 0 X 0 0
X X X Χ X X X X 0 0 0
Invaz. post.
Več sodelovanja
X X
X X
X
X X X X 0 X 0 0
X Χ X X 0 X 0 0
Število storitev v posamezni PBA je bilo v letu 2008 različno, odvisno tudi od velikosti ustanove, pri kateri je posamezna PBA, in števila različnih zdravnikov, ki delajo v njej. Največ storitev so opravili v letu 2008 v PBA UKC Ljubljana, nato PBA Murska Sobota, UKC Maribor, v Novem mestu, v Slovenj Gradcu, Izoli, na Ptuju, v Brežicah, Celju. Iz PBA Onkološkega inštituta Ljubljana, Nove Gorice in PBA Vrabl nismo dobili teh podatkov – z razlago, da teh podatkov nimajo. Po številu prvih pregledov je na prvem mestu PBA UKC Ljubljana s 1537 prvimi pregledi, nato PBA Vrabl s 1296, Murska Sobota s 1284, nato UKC Maribor s 1184, Brežice s 987, nato OI Ljubljana s 500–550, Ptuj s 521, Novo mesto s 469, Slovenj Gradec 458, Rahabilitacija UKC Maribor, Izola s 230, Celje s 225, Nova Gorica s 150, iz preostalih dveh ambulant nimamo podatkov. Razpredelnica 7. Število opravljenih prvih pregledov in storitev PBA UKC Ljubljana ZPBA Vrabl SB Murska Sobota UKC Maribor SB Brežice OI Ljubljana SB Ptuj SB Novo mesto SB Slovenj Gradec SB Jesenice Rehab. UKC Mb SB Izola SB Celje SB Nova Gorica Nevrol. klinika Ljubljana PBA Bem
Št. prvih pregledov 1.537 1.296 1.284 1.184 987 500-550 521 469 458 0 350 230 225 150 0 0
Storitve (faktorji) 87.564,00 100 konces. 78.702,00 47.397,38 1.016 ni znano 1.074 41.681,28 27.840,00 11.000 26.880,00 939 ni znano 0 0
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
59
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Razpravljanje Organizirana terapija kronične bolečine v Sloveniji je mlada dejavnost. Od prvih začetkov pred 30 leti se je postopoma zgradila kar zadovoljiva mreža PBA. Zelo narobe je, če je delovanje PBA odvisno od enega samega zdravnika, saj nastanejo težave, ko ga dlje ni na delo in zaradi tega ambulanta sploh ne deluje (kar se dogaja v eni od slovenskih bolnišnic). Ambulante delujejo navadno v okviru anestezioloških oddelkov pri obeh Univerzitetnih kliničnih centrih, Ljubljani in Mariboru, in v splošnih bolnišnicah po Sloveniji, pri UKC Rehabilitacija Maribor, Onkološkem Inštitutu Ljubljana, Nevrološki kliniki UKC Ljubljana in zasebnih ambulantah Vrabl in Bem. Na Inštitutu republike Slovenije za medicinsko rehabilitacijo v Ljubljani (Soča) je delovala PBA, ki pa je z odhodom zdravnika v novo ustanovo prenehala delovati (vir: telefonski pogovor). V letu 2008 je bilo v slovenskih PBA opravljenih 351.933,00 faktorjev, kar je veliko število. Na novo obdelanih bolnikov je bilo 9.241. Velika zasluga za dobro stanje gre Slovenskemu Združenju za zdravljenje bolečine (SZZB), ki je bilo ustanovljeno 1996 v Ljubljani. Skrbi za strokovni razvoj protibolečinske medicine v Sloveniji, prenaša v slovenski prostor novosti, njegovi člani aktivno sodelujejo na mednarodnih, domačih in tujih kongresih, simpozijih in seminarjih ter v okviru Slovenskega zdravniškega društva pripravljajo predavanja s področja bolečine po vsej Sloveniji. SZZB je član mednarodnih strokovnih združenj – IASP (International Association for Pain therapy) in EFIC (European Federation of IASP Chapters). Veliko število storitev v PBA ostaja neplačanih ali pa so le hospitalne ali le ambulantne. Ta problem rešujemo v SZZB z Zdravniško zbornico in zavarovalnico in aktivnostmi za dopolnitev seznama evidentiranih in plačanih storitev v Zeleni knjigi. Vsako leto pripravimo novinarsko konferenco z izbrano temo s področja bolečine, da seznanimo širšo slovensko javnost o svojih prizadevanjih za izboljšanje zdravljenja bolečine. Vsako leto pripravimo tudi seminar o terapiji bolečine z različnimi izbranimi temami in mednarodno udeležbo. Zastavljen je multidisciplinarno, z vključevanjem čim več različnih medicinskih področij, saj je bolečina tema in področje, s katerim se srečujejo vsi zdravniki. Da bi spoznali, koliko je kronične bolečine v Sloveniji, smo s pomočjo farmacevtske firme v letu 2006 opravili prevalenčno raziskavo. Dobili smo rezultate, ki so podobni, a večji kot v Evropi (pri nas 23, v Evropi pa povprečno 19). Na področju dolgotrajne kronične bolečine (5 in več let) smo v Sloveniji boljši kot evropsko povprečje – v Sloveniji v 50 evropsko povprečje je 66. To kaže, da je terapija kronične bolečine v Sloveniji vendarle dokaj dobra; če ne bi bilo tako, bi se razvilo več kroničnih, dolgotrajnih bolečin, ki so težje za zdravljenje. Zaključek Protibolečinska dejavnost na področju Slovenije je dokaj na visoki ravni, če pomislimo, da segajo prvi začetki zdravljenja kronične bolečine dobra tri desetletja v preteklost, ko se je ta dejavnost začela najprej v UKC Ljubljana, naslednje leto v Splošni bolnišnici Slovenj Gradec, v splošni bolnici Maribor (UKC MB ), nato postopoma po vsej Sloveniji. Veliko je dejavnost pridobila z ustanovitvijo Slovenskega združenja za zdravljenje bolečine v letu 1997, saj se je njegovo članstvo zvečalo od ustanovnih 30 zdravnikov na 140 in so v njem zastopani številni različni specialisti, številne stroke medicine, medtem ko so bili prvotno člani le anesteziologi. Literatura in viri 1. Cesar-Komar M. Anketa o protibolečinski dejavnosti v Sloveniji. Januar 2009. 2. Brevik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: Prevalence, impact on daily life and treatment. Eur J Pain 2006; 10: 287-333.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
60
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
3. Pirc J, Cesar-Komar M, Bizilj S. Kronična bolečina v Sloveniji. Poročilo o prevalenci kronične bolečine in primerjava z evropskimi podatki. Slovensko združenje za zdravljenje bolečine-SZZB, Janssen-Cillag, 2007:137. 4. Müller J. Začetki protibolečinske dejavnosti v Sloveniji, osebni kontakti. 5. Plešivčnik D. Mednarodni simpozij o tradicionalni kitajski medicini. Slovenj Gradec, 1978, osebni kontakti. 6. Cesar-Komar M. Dejavnost zdravljenja kronične bolečine v Sloveniji. Zbornik predavanj. 5. Slovenski kongres anesteziologov, Portorož, 8.-10. maj 2009; 83-92.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
61
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
LAJŠANJE PORODNE BOLEČINE V SLOVENIJI LABOUR PAIN SERVICE IN SLOVENIA Alenka Pleško-Mlakar Bolnišnica za ženske bolezni in porodništvo Postojna, Postojna Izvleček. Porodna bolečina je ena najhujših, ki jih ženska izkusi v življenju. Ker so načini lajšanja porodne bolečine in organizacija neenotni, smo želeli preveriti trenutno stanje v vseh slovenskih bolnišnicah. Rezultate smo dobili s pomočjo ankete, ki smo jo poslali v vseh štirinajst porodnišnic. Odgovore smo dobili iz trinajst porodnišnic. Lajšanje porodne bolečine je še vedno organizirano neenotno, dostopnost za vse porodnice ni enaka. V ospredju je pomanjkanje anesteziologov in skrb za zagotavljanje varnosti porodnic in novorojencev. Abstract. Labour pain is one of the most excruciating pains a woman can experience in her life. Since the organisation of labour pain relief in Slovenia is not uniform, we wanted to check the current situation in all Slovenian maternity hospitals. We have sent questionnaires to 14 hospitals and got results from 13. Labour pain relief is still not organised equally and not accessible to all. The main problem is the lack of anaesthesiologists and ensuring safe delivery for the women in labour and the newborn.
Uvod Porodno bolečino, ki je sicer normalen spremljevalec poroda in ima vse značilnosti akutne bolečine, je težko opisati. Vendar jo, ne glede na individualno toleranco za porodno bolečino, večina porodnic smatra za najhujšo bolečino, ki so jo doživele.1 Zato smo želeli ugotoviti, kako zagotavljamo lajšanje porodne bolečine v Sloveniji in v kakšni meri smo v to vključeni anesteziologi. Metode Pripravili smo anketo z osmimi vprašanji, ki smo jo poslali desetim predstojnikom anestezioloških oddelkov slovenskih bolnišnic, ki imajo v organizacijski shemi ginekološko-porodniške oddelke, UKC Maribor, UGK Ljubljana in v dve specialni bolnišnici za ginekologijo in porodništvo. Skupaj štirinajst. Anketo je razposlala 15. januarja 2009 predsednica ZZZB, pridobljeni podatki pa prikazujejo pregled stanja pri lajšanju porodne bolečine v slovenskih bolnišnicah v letu 2008. Pričakovali smo odgovore na naslednja vprašanja: 1. Ali v vaši bolnišnici izvajate porodno analgezijo? 2. Katero vrsto uporabljate? 3. Ali je dostopnost bolnic za porodno analgezijo pri vas 24 ur na dan, vsak dan, ob praznikih in nedeljah? 4. Ali izvajajo porodno analgezijo vsi anesteziologi na vašem oddelku? 5. Koliko porodov je bilo v vaši porodnišnici v letu 2008? 6. Ali interes za porodno analgezijo v vaši ustanovi narašča v primerjavi z letom 2007? 7. Kolikšen je odstotni delež glavobolov po epiduralni porodni analgeziji (približno)? 8. Kakšno je bilo zadovoljstvo porodnic z lajšanjem porodne bolečine? Rezultati Odgovore smo dobili iz trinajstih porodnišnic in so prikazani v razpredelnici št. 1 (odgovor iz ene bolnišnice je nepopoln).
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
62
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
63
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Razpravljanje V vseh slovenskih porodnišnicah se zavedajo nujnosti izvajanja porodne analgezije. O možnostih, ki so na voljo, in o problemih, ki ob tem nastajajo, je bil govor že na več simpozijih, seminarjih in strokovnih sestankih. Naj omenim le zadnja dva: Seminar o akutni bolečini z mednarodno udeležbo (1. in 2. 6. 2007 – SZZB) in Simpozij o porodni analgeziji (26. 3. 2009 – SZAIM). Iz rezultatov te ankete pa je razvidno: 1. Anesteziologi sodelujejo pri izvajanju porodne analgezije na enajstih porodniških oddelkih, le na dveh občasno oziroma sporadično. 2. Regionalna analgezija, predvsem epiduralna, je na voljo na desetih od trinajstih oddelkov, vendar je le na šestih dosegljiva 24 ur dnevno. 3. Pri lajšanju porodne bolečine z intravenskimi opioidi sodelujejo anasteziologi pri uporabi remifentanila; pri uporabi drugih opioidov pa le izjemoma. Uporabo le-teh (petidin, tramadol) nadzorujejo porodničarji in babice. 4. 24-urna dosegljivost lajšanja porodne bolečine je možna v sedmih od trinajstih porodnišnic. 5. Pri lajšanju porodne bolečine ne sodelujejo vsi zaposleni anesteziologi, kar kaže na specifiko tega dela. 6. V večini porodnišnic (enajstih) narašča interes za porodno analgezijo. 7. Menim, da delež glavobolov po EA ni realno prikazan. 8. Porodnice so z lajšanjem porodne bolečine s pomočjo epiduralne analgezije večinoma zelo zadovoljne (ocena 5). Zadovoljstvo ocenjujejo večinoma kot dobro (ocena 3) pri uporabi remifentanila, medtem ko se podatki o zadovoljstvu pri lajšanju porodne bolečine z drugimi i.v. opioidi večinoma ne zapisujejo. 9. Pri nefarmakoloških načinih lajšanja porodne bolečine (akupunktura, TENS) sodelujejo anesteziologi le v eni porodnišnici. Podatkov, kako se spreminjajo načini porodne analgezije po posameznih letih za vse porodnišnice, ni bilo mogoče zbrati. Objavljeni so le podatki o pogostosti epiduralne analgezije v osmih slovenskih porodnišnicah za leto 2006 in so prikazani v razpredelnici št. 2.2 Razpredelnica 2. Uporabljena epiduralna porodna analgezija v letu 2006 Bolnišnica Postojna Kranj Maribor Slovenj Gradec Nova Gorica Izola Novo mesto Celje
Število porodov 1470 1293 2000 859 650 602 1099 1902
Število porodov z EA 430 54 200 151 0 70 0 70
% porodov z EA 29,2 4,2 10,0 17,7 0 9,34 0 3,8
Takrat je znašal delež epiduralne porodne analgezije v teh bolnišnicah 9,7 %, v letu 2008 pa 7,2 %. Glede na te podatke delež epiduralne porodne analgezije pada, kar je zaskrbljujoče. Za ilustracijo prikazujem gibanje posameznih načinov lajšanja porodne bolečine za 10-letno obdobje v Bolnišnici za ženske bolezni in porodništvo Postojna, ki ima v Sloveniji doslej največje število regionalnih porodnih analgezij (Razpredelnica 3).3
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
64
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Razpredelnica 3: Gibanje posameznih načinov lajšanja porodne bolečine v Bolnišnici Postojna v zadnjih 10 letih
Št. porodov
Inhalacijska analgezija N2O : O2
I.v. analgezija z opioidnimi analgetiki (meperidin, tramadol)
Kombinacija inhalacijske in intravenske analgezije
Regionalna epiduralna analgezija EA
Porod v vodi
1999
916
**
**
**
1
31
2000
1003
**
**
**
6
27
2001
1034
**
**
**
3
26
2002
1048
140
176
261
147 (14%)
20
2003
1336
128
192
288
342 (25,6 %)
19
2004
1232
85
209
294
300 (24,4 %)
15
2005
1298
73
279
220
366 (28,2 %)
12
2006
1470
47
421
175
430 (29,3 %)
13
2007
1481
23
461
83
494 (33,3 %)
11
2008
1497
27
354*
75
565 (37,7 %)
15
2009 (do 31. 8. 09)
1075
372 (34,6 %)
18
Leto
* Od tega 11 x Ultiva ** V letih 1999–2001 smo zapsovali samo anestezije, ki so bile splošne ali lokalne.
600 500
2002
400
2003 2004
300
2005
200
2006
100
2007
0
2008 inhalacijs k a analge zija
i.v. analge zija
k om binacija
re gionalna analge zija
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
65
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Zaključki 1. Lajšanje porodne bolečine ni organizirano enotno in ni enako dostopno vsem porodnicam. 2. Velik problem je v pomanjkanju anesteziologov, ki ob že dosedanjem obsegu dela in obveznostih večinoma ne morejo zagotoviti stalnega nadzora in s tem absolutne varnosti porodnice, ki ima enega od načinov porodne analgezije. 3. Vsi anesteziologi ne opravljajo porodne analgezije, kar kaže na veliko specifičnost tega dela in potrebo po nadaljnjem izobraževanju. 4. Delež epiduralne analgezije se kljub drugačnim željam porodnic ne veča. 5. Problem uporabe i.v. opioidnega analgetika remifentanila zaradi zapleta ob registraciji zdravila. Literatura 9. Premru-Sršen T. Fiziologija in lajšanje porodne bolečine. In: Cesar-Komar M, Pirc J, Kožar E, editors. Akutna bolečina. Zbornik predavanj 11. seminar o bolečini z mednarodno udeležbo; 2007 jun 1-2; Maribor. Maribor: SZZB – Slovensko združenje za zdravljenje bolečine, 2007; 43-7. 10. Cesar-Komar M. Pregled uporabljene porodne analgezije v Sloveniji - povdarek na epiduralni. In: Cesar-Komar M, Pirc J, Kožar E, editors. Akutna bolečina. Zbornik predavanj 11. seminar o bolečini z mednarodno udeležbo; 2007 jun 1-2; Maribor. Maribor: SZZB - Slovensko združenje za zdravljenje bolečine, 2007; 39-42. 11. Bolnišnična statistika Bolnišnice za ženske bolezni in porodništvo Postojna. 12. Ankete, januar 2009
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
66
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
CENTER ZA INTERDISCIPLINARNO ZDRAVLJENJE BOLEČINE, ONKOLOGIJO IN BLAŽILNO OSKRBO CENTRE FOR INTERDISCIPLINARY PAIN THERAPY, ONCOLOGY AND PALLIATIVE CARE Rudolf Likar The Center for Interdisciplinary Pain Therapy, Oncology and Palliative Care – “ZISOP”, General Hospital in Klagenfurt, Klagenfurt, Austria
The Centre for Interdisciplinary Pain Therapy, Oncology and Palliative Care – “ZISOP” – is a unique, interdepartmental competence centre for the treatment of pain patients. The Interdisciplinary Outpatient Pain Clinic, the Department of Interdisciplinary Oncology (under the organisational direction of DDr. Klocker), as well as the Palliative Care ward are all in the ZISOP. The Interdisciplinary Out-patient Pain Clinic of the General Hospital in Klagenfurt was established in 1992. Departments of Anaesthesiology, Neurology, Radiology, Neurosurgery, Orthopaedics and Clinical Psychology there work together. In 2005, the Centre for Interdisciplinary Pain Therapy, Oncology and Palliative Care was created which included a palliative care ward with 14 beds and a semi-in-patient (5 beds in day care) ward for chronic pain patients. In 2007, there were 22,323 treatments performed in the Interdisciplinary Pain Clinic of the General Hospital in Klagenfurt, compared to 21,562 in 2004. In the Interdisciplinary Day Clinic, there were 1,915 treatments performed in 2004 and in 2007, 2,037 treatments. In both areas there is a recognisable increase in the frequency of treatments. Within the ZISOP there is a plan for the implementation of the multi-modal therapy scheme for patients with diseases of the spine and/or with headaches, as well as for other chronic pain patients. 1998
2001
2004
2007
587
804
1,750
2,150
Follow-up examinations of out-patients
2,386
4,047
5,927
6,630
Counselling of in-patients
5,529
6,490
7,019
9,190
Out-patients
In cooperation with the department of neurosurgery, the following implants were done: 25–30 SCS sensors and 10–15 pain pumps. The area of responsibility of the interdisciplinary pain clinic is chronic pain therapy, palliative care for in- and out-patients, post-operative pain therapy, as well as performing regional anaesthetic procedures. The post-operative pain therapy begins in the recovery room and continues on the ward through the department of anaesthesiology and intensive care.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
67
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
ORGANIZIRANOST SLUŽBE ZDRAVLJENJA KRONIČNE BOLEČINE NA HRVAŠKEM ORGANISATION OF SERVICE FOR THE TREATMENT OF CHRONIC PAIN IN THE REPUBLIC OF CROATIA Vesna Golubović Department of Anaesthesiology, Reanimathology and Intensive Therapy, Medical Faculty Rijeka, University of Rijeka, Rijeka, Croatia
This review article outpoints historical dates important for the development of pain service in Croatia. In three decades pain management outgrew from medical practice of minor importance in Croatian Society for Pain Management which is a member of the European Federation of IASP Chapters (EFIC) and International Association for the Study of Pain (IASP). Croatian Society for Hospicium/Paliative Care was founded within the Croatian Medical Association (CMA), strongly supporting and promoting education and organisation of pain management in Croatia. From data of the Croatian Insurance Health Organisation for 2008, there are 23 registered pain services throughout Croatia. The anaesthesiologists started with the pain management at the Department of Neurosurgery in Clinical Hospital Centre Zagreb in 1978. The Clinic for Pain Management was founded in the General Hospital in Karlovac in 1979, and then in 1986 in the Clinical Hospital Centre in Rijeka, and afterwards in the General Hospital in Osijek in 1988. The Clinics outgrew in the Departments for Pain Management in Karlovac and in Osijek, while in Zagreb, the Centre for Pain Management was founded by merging anaesthesiologists from different Departments of Pain Management that were part of the Clinics for Anaesthesiology. In 1994 the Croatian Society for Anaesthesiology, Reanimation and Intensive Care (HDAIL) within the Croatian Medical Association (CMA) started the organisation of centres for the treatment of pain, but the activity ended with the change of presidency. In the same year, the Croatian Society for Hospicium/Palliative Care (HDH/PS) was founded at CMA (at that time the President was Prof. Dr. sc. Anica Jušić). Anaesthesiologists were included in the activity of this society from the very first day (Dr. Marijana Persoli-Gudelj was the vice-president of the Society). On 31st March 2000, the Croatian Society for the Treatment of Pain (HDAIL) within the Croatian Medical Association (CMA) was founded in Zagreb. The founders and actuators of the Society were the Clinic for the pain management from General Hospital Karlovac, the Croatian Society for Hospicium/Palliative care (HDH/PS) at CMA and the Department for Anaesthesiology of Medical Faculty Zagreb. The first President of the Society was Prim. Dr. Marijana Persoli-Gudelj. The Croatian Society for Pain Management became member of the European Federation of IASP Chapters (EFIC), and International Association for the Study of Pain (IASP) in 2002. Since 2002, the Croatian Society for the Pain Management (HDAIL) has been included in the global project Europe against Pain (EAP) in which the World Health Organisation (WHO), European Federation of IASP Chapters (EFIC), and the International Association for the Study of Pain (IASP) were taking part. Each year during the first week in October in many Croatian cities medical educational personal and volunteers organise lectures about pain and treatment provoking media attention (TV, radio, newspapers, etc.). Since 27th November 2003, by the decision of the Croatian Insurance Health Organisation (HZZO), clinics for the pain treatment have become specially registered (coded) sub-services within the frame of anaesthesiology. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
68
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
The data of the Croatian Insurance Health Organisation (HZZO) for 2008 are the following: Centre for Pain Management – Clinical Hospital Zagreb, Department for Pain Management and Palliative Medicine – General Hospital Karlovac, Department for Pain Management and Hyperbaric Medicine – Clinical Hospital Osijek, 24 Pain Management ambulances – as a part of departments of anaesthesiology and one clinic for pain management within neurology department. It was proclaimed in 1989 in the USA that the pain treatment is the fourth field of the anaesthesiologists practice, besides anaesthesia, intensive therapy and reanimatology. The treatment of pain (algology) is today growing into a new clinical discipline in most developing countries of the world and our association is promoting the modern approach to the treatment of pain in Croatia. Pain treatment as entirely new medical branch based on particular education. All medical personnel including doctors (especially of primary medical care) and in particular anaesthesiologists have to be additionally educated at the Faculty of Medicine, through postgraduate lectures, and sub-specialisation for treatment of pain (algology). Curriculum for subspecialisation in pain medicine in Croatia was made 4 years ago, and still it has not been approved by Ministry of Health and Social Welfer. “Pain medicine as a speciality, a sub-speciality or supraspeciality, has been realised in some countries, as Turkey, Finland and Sweden. This is a very important political topic that EFIC need to have to focus on, and helping other national societies in their efforts to establish pain medicine as a recognised sub-speciality” (Harald Brevik, President of EFIC, President's Message in EFIC Newsletter, January 16th, 2003). In our country, every year since 1997, in Karlovac, a one day symposium dedicated to the treatment of pain has been organised and has been held in co-operation with many worldknown experts in this field (V. Ventafrida, MD PhD, E. Klaschik, J. Luczak, M. Zimmerman, N. Krčevski-Škvarč, and others). The topics of the symposium included the following topics: Treatment of malignant pain – modern approach; Three step analgesic scale – WHO; analgesics-opiates/neo-opiates; Ethics, Palliative medicine; Pain in the elderly; Pain in children; Pain in women; Neuropathic pain. Since 2000, postgraduate courses of first category have been held and organised by the Department of Anaesthesiology of the University of Zagreb and Osijek Medical Faculties. Postgraduate courses of first category last for 3 days (during weekend) and include lectures, workshops and final written exam. Until nowadays, the topics were: Chronic pain – diagnosis and treatment – general part; chronic pain – diagnosis and treatment – special part; Pain in children – diagnosis and treatment; Pain treatment in cancer patients; Acute pain – diagnosis and treatment; Neuropathic pain – diagnosis and treatment. The 1st Congress of the Croatian Society for Pain Management with international participation was held in the Lakes of Plitvice from 12 – 14th October 2006. The goal of the Congress was to promote multidisciplinary approach for the treatment of acute and chronic pain and to inform and discuss with the audience on the contemporary model for the treatment of pain in Croatia. Members of the Croatian Society for Pain Management regularly participate in numerous other symposiums and congresses (oncology, physiatrics, neurology, surgery, or maxillofacial surgery, plastic and reconstructive surgery, primary care medicine etc.). Educational lectures have been held in more than 20 towns in Croatia; courses for doctors to educate patients, schools for the treatment of pain, and educative workshops all over Croatia. There have also been lectures for education of population (gerontology public lectures, symposium for 100% war invalids, symposium for paraplegic patients, education for employees in the old people homes, public lectures etc.). The members of the Croatian Society for Pain Management have issued many papers: Book of neuropathy pain; University Book "ABC of Surgery Everyday 1, 2, and 3" and "Decubitus", J. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
69
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Hančević, Chapters of Pain Treatment, and Chapter of Acute Pain and Prevention of its Chronification; Script on Chronic pain, Pain in children, Pain in the elderly; Directions for Pharmacological treatment of neuropathy pain – translation of the EFNS directions; Supplement to Liječnički vjesnik – 1st Congress of the Croatian Society for Pain Management with international participation (HDLB); Handbook: On Chronic Pain again; Woman and Pain – translations of the IASP and EFIC materials; Declaration of Chronic Pain – EFIC – Osijek/2005, Brochure for patients – EFIC, HDLB; Brochure on Chronic Pain Treatment for Patients, etc. Members of the Society took active part as invited lecturers, oral or poster presenters and participants in numerous home congresses (Croatian Society for Pain Management – HDLB); Croatian Society of Regional Anaesthesia and Analgesia (HDRAA), and in International congresses and seminars (WCP, EFIC, IASP, WCA, WIP, ESRA etc.). The EFIC – Gruenenthal scholarship (EEG scholarship) for 2008 was won by a member of the Society, Prof. Marijana Braš, from Clinical Hospital Centre in Zagreb on the topic: Connection of COMT polymorphism with chronic lumbar pain syndrome of PTSP linked with war. The Society for Pain Management advocated and supported registration of many drugs in our country (Kapanol, Durogestic (TTS fentanyl), MST Continus, Sevredol, Transtec (Buprenorfinplaster), Fentanyl M, Oxycontin, Zaldiar, Palladon). Croatian Society for Pain Management (HDLB) has been increasing in membership every year, having 163 members nowadays. Our Society for Pain Management has been working intensively on educational programmes for health care professionals, patients, and common people, and on recognition of the society in Croatia, Europe and world wide. References 1. Barada A, Fingler M, Bielen I. Smjernice za farmakološko liječenje neuropatske boli. Europ J of Neurol 2006; 13: 1153-1169. 2. I. Kongres Hrvatskog društva za liječenje boli s međunarodnim sudjelovanjem. Liječ Vjesn 2006; 128 (5):1-90. 3. Kiseljak V, Persoli-Gudelj M. O kroničnoj boli iznova. Zagreb: Priručnik Medicinske naklade, 2009. 4. Hrvatsko društvo za liječenje boli. Liječenje boli u Republici Hrvatskoj. Liječničke Novine 2009; 77: 25-7. 5. Hrvatsko društvo za liječenje boli. Liječenje boli u Republici Hrvatskoj. Liječničke Novine 2009; 79: 22. 6. Persoli-Gudelj M, Lončarić-Katušin M. Akutna bol i prevencija njene kronifikacije. In: Hančević J, et al., eds. Prevencija, detekcija i liječenje dekubitusa. Naklada Slap; poglavlje u Sveučilišnom udžbeniku Zagreb; 2009.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
70
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
PRIPOROČILO EFNS ZA FARMAKOLOŠKO ZDRAVLJENJE NEVROPATSKE BOLEČINE EFNS GUIDELINES ON PHARMACOLOGICAL TREATMENT OF NEUROPATHIC PAIN Giorgio Cruccu EFNS Secretariat, Vienna, Autsria, and Department of Neurological Sciences, La Sapienza University, Rome
In 2004 the European Federation of Neurological Societies (EFNS) launched a task force composed of experts in pain or evidence-based medicine with the duty of systematically review the literature and produce neurological guidelines on pharmacological treatment of neuropathic pain. These first guidelines were published in 2006.1 According to those guidelines, tricyclic antidepressants, gabapentin, and pregabalin were indicated as first line for postherpetic neuralgia and painful polyneuropathy, with opioids, tramadol, lamotrigine, duloxetine, and venlafaxine as second line. Carbamazepine and oxcarbazepine were recommended as first line for trigeminal neuralgia, and topical lidocaine as add-on therapy in patients with postherpetic neuralgia to relieve allodynia in small skin areas. Regarding the various central pain conditions (mostly post-stroke pain, spinal cord injury, and multiple sclerosis) the available controlled studies were too few to allow definite evidence-based recommendations. Afterwards, several new pharmacological trials on neuropathic pain have been published and new opinions have gained consensus about polytherapy2 and pharmacoresistance.3 Hence, EFNS launched a new task force in order to revise the previous guidelines. This revision is currently still ongoing. We expect it will be concluded and submitted to the EFNS review by October 2009. References 1. Attal N, Cruccu G, Haanpää M, Hansson P, Jensen TS, Nurmikko T, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol 2006; 13: 1153-69. 2. Cruccu G. Treatment of painful neuropathy. Curr Opin Neurol 2007; 20: 531-5. 3. Hansson PT, Attal N, Baron R, Cruccu G. Toward a definition of pharmacoresistant neuropathic pain. Eur J Pain 2009; 13: 439-40.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
71
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
TREBUŠNA VISCERALNA BOLEČINA ABDOMINAL VISCERAL PAIN Katarina Šakić, Ana Markić Department of Anaesthesiology, Reanimatology and Intensive Medicine, General Hospital Sveti Duh, Zagreb, Croatia
Abstract. Advances in the knowledge of neurophysiology, neuroanatomy, and pharmacology have allowed a greater understanding of the peripheral and central mechanisms of pain and newer, more sophisticated drugs and interventional techniques have advanced our levels of expertise in controlling pain. Still, the management of abdominal pain, being both common and often inconsequential, remains a major challenge for clinicians. A novel therapeutic option for patients with visceral pain have given insight into the role of dorsal columns in visceral abdominal and pelvic pain. The long-term efficacy, however, needs to be proven in further clinical trials.
Introduction Estimates on the prevalence of abdominal pain have varied from 20% to 46%.1 In fact pain is the most prevalent symptom in any gastroenterological clinic. Despite an adequate work up and multiple physician evaluations the aetiology of their pain remains unknown. Many patients with abdominal and pelvic pain have visceral pain. Characteristics of visceral pain have been described extensively in literature. Acute abdominal pain Acute and severe abdominal pain is almost always a symptom of intraabdominal disease. It may be the only indicator of the need for surgery and must be attended to with urgency. A correct early diagnosis of the acute abdomen while signs of local peritonitis are still absent (appendicitis in atypical location, recurrent acute appendicitis, spontaneous reopening of an occlusion) is facilitated by the awareness for the characteristics and symptoms of visceral pain, and therefore careful taking of the patient's history. A history lacking visceral pain on the other hand represents an important clue for the diagnosis of other conditions (gynecological, diverticulititis, etc.) with acute pelvic peritonitis. Chronic abdominal pain In contrast with acute pain in which the pathophysiology is relatively well known and has several satisfactory therapeutic options, the management of patients with chronic pain is often inadequate, resulting in frustration for both patients and physicians. This may in part be explained by the lack of understanding of the mechanisms underlying chronic pain. Chronic abdominal visceral pain (CAVP) has a significant clinical impact and represents one of the most frequent and debilitating disorders in the general population. It also leads to a significant economic burden due to workdays lost, reduced productivity, and long-term use of medications with their associated side effects. Clinical evaluation of abdominal pain Visceral pain comes from the abdominal viscera, which are innervated by autonomic nerve fibres and respond mainly to the sensations of distention and muscular contraction of the visceral muscular wall or obstruction of hollow gastrointestinal organs. They do not respond to ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
72
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
cutting, tearing, or local irritation. Unlike the somatic pain due to peritonitis, visceral pain is typically diffuse, epigastric, periumbilical, vague, dull and often accompanied by nausea, vomiting and restlessness. When caused by obstruction, visceral pain can be crampy and colicky. It is poorly localized and tends to be referred to areas corresponding to the embryonic origin of the affected structure. Foregut structures (stomach, duodenum, liver, and pancreas) cause upper abdominal pain. Midgut structures (small bowel, proximal colon, and appendix) cause periumbilical pain. Hindgut structures (distal colon and GU tract) cause lower abdominal pain. A remarkable aspect of visceral pain is the development of visceral hyperalgesia – an increased sensitivity to visceral stimulation following an injury or inflammation of an internal organ. The increased sensitivity of the viscera after inflammation has two causes: an alteration of the sensory neurons in the viscera so that they now respond more intensely to naturally occurring stimuli and an enhanced sensitivity of the sensory pathways in the brain that mediate sensations from the viscera. Both processes are known as “sensitization” either peripherally (in the viscera) or centrally (in the brain) and are thought to be responsible not only for the pain produced by the inflammatory disease but also for hyperalgesic sensations that can occur in the absence of an identifiable cause, such as pain in conditions like irritable bowel syndrome. This process of sensitization is currently the subject of a great deal of research, to identify its molecular basis and to find ways to restore normal sensitivity to the distorted system. The aim is to reduce hyperalgesic sensations caused by the regular functioning of internal organs without interfering with the normal sensitivity of the viscera or with the digestive, secretory or reproductive functions of the organ.2 Model of pain transmission in the abdomen There are two distinct classes of nociceptive sensory receptors in viscera. The first class is composed of "high-threshold"receptors that respond to mechanical stimuli within the noxious range. These have been identified within many viscera, including the heart, lungs, gastrointestinal tract, ureters, and urinary bladder. The second class is composed of receptors that have a low threshold to natural stimuli and encode the stimulus intensity in the magnitude of their discharges, the so-called "intensity-encoding" receptors. Both receptor types are mainly concerned with mechanical stimuli such as stretch and are involved in the peripheral encoding of noxious stimuli in viscera. Experimental data suggest that viscera contain nociceptive afferents that are normally considered "silent." In the presence of local inflammation or tissue injury, these afferents become sensitized and respond to previously innocuous natural stimuli. The clinical significance of this inflammation-induced sensitivity is unknown. High-threshold afferents signal acute visceral pain. Local ischemia, hypoxia, and inflammation cause pain by sensitizing highthreshold receptors and these previously "silent" or unresponsive receptors. Inflammatory mediators released locally lower their firing threshold and, by peripheral sensitization, augment and perpetuate the transmission of noxious stimuli.3, 4 Spinal and vagal afferent fibers convey sensory information from the upper gastrointestinal tract to the central nervous system. The dorsal root ganglia contain cell bodies of vagal and spinal afferents. The vagal afferents enter the brain stem and spinal afferents enter the spinal cord and make synaptic connections with second order neurons and conduct visceral information to the central nervous system. The ascending spinal pathways project to the thalamic nuclei. Pathways with visceral and somatic information converge on to spinothalamic and spinoreticular pathways. Visceral nociceptors are capable of responding to a variety of stimuli including mechanical (i.e. abdominal distension) and chemical (i.e. inflammation). Vagal afferents transmit predominantly physiological information while spinal afferents transmit noxious events predominantly.5.The role of the dorsal column pathway has been described more recently The spinothalamic tract was considered to be the major pathway for nociception. The role of the dorsal column system was considered to be predominantly transmission of physiological data. The role of the dorsal column may be greater than just transmission of visceral nociception. The dorsal column path------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
73
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
way may be the part of an “Amplification Loop” as described by Palecek. This “Amplification Loop” may lead to potentiation of the responsiveness of the spinal cord neurons and responses of different projection neurons in the spinothalmic and dorsal column neurons.6 Management of visceral abdominal pain Therapeutic advances are needed in view of the high prevalence of chronic or recurrent visceral pain. The utility of nonsteroidal anti-inflammatory drugs and opioids is limited by their severe adverse effects on gastrointestinal mucosal homeostasis and motility. Treatment of chronic abdominal pain differs based on the origin of pain. The ultimate goal of any therapy is always functional rehabilitation, i.e. going back to doing whatever one was able to do prior to the onset of pain. Interventions used in the management of chronic abdominal pain include diagnostic blocks and therapeutic interventions. Examples of diagnostic blocks used in the treatment of abdominal pain include diagnostic peripheral nerve blocks and differential epidural blockade. Examples of therapeutic interventions in the management of abdominal pain include peripheral nerve radiofrequency ablation or cryoablation, epidural steroid injections, facet nerve radiofrequency ablation. Therapeutic interventions aimed at visceral abdominal pain include celiac plexus block or splanchnic nerve blocks for upper abdominal visceral pain and superior hypogastric block for lower abdominal/pelvic pain of visceral origin. Other interventions may include spinal cord stimulation or spinal infusion pumps in selected cases. Physical therapy and medications are often prescribed in conjunction with the therapeutic procedures to assist in the rehabilitation process. Visceral pain can be managed by both pharmacological and interventional techniques. Combinations of opioids, NSAIDs, and adjuvant medications form the mainstay of therapy. When pharmacological therapies prove ineffective or are limited by side effects, regional anaesthesia techniques or neurosurgical techniques should be considered. The former techniques involve the administration of local anaesthetics, opioids, or neurolytic agents to the neural axis or visceral plexi. The goals of these interventional procedures are to provide superior analgesia and to allow for a decrease in opioid consumption. Continuous epidural or intrathecal infusion of local anaesthetics or opioids can be effective for controlling abdominal or pelvic cancer pain. Hence, neurolytic block of celiac plexus is indicated for visceral pain in the upper abdomen, especially when pancreatic in origin.6 Opioids Acute severe visceral pain requiring hospitalization arises after surgery (acute pancreatitis, acute cholecystitis, acute inflammatory bowel disease) or as an acute exacerbation of a chronic disease state (Crohn’s flare, cancer etc.). Almost all opioids (especially morphine) can be given intravenously. A loading dose is titrated to desired analgesic effect and should remain the standard of care for severe acute pain. Use of a basal infusion (adjusted every 8–24-hours), minimizes the patient's need to request a bolus dose. Buprenorphine is an opioid partial agonist producing less euphoria and respiratory depression than other agonists, and especially beneficial in children providing safe, rapid and long-acting analgesia.7 Oxycodone is superior to other opioids in the treatment of visceral pain.8, 9 Meperidine (Demerol) has a short half-life and requires frequent dosing to maintain adequate serum levels. Its use has been discouraged because repeated dosing leads to the accumulation of the metabolite normeperidine that causes neuromuscular irritation and seizures.9 Thoracic epidural catheters Thoracic epidural catheters used as patient-controlled epidural analgesia (PCEA) may provide excellent pain relief with a low continuous infusion rate and small bolus doses, compared with a ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
74
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
lumbar epidural catheter and PCEA pump. Thoracic epidural catheters also let the patient move more easily and clear secretions more effectively soon after surgery and are also convenient in intensive care treatment of severe acute pancreatitis.10–12 Neurolytic celiac plexus block (NCPB) Effective management of severe pain in acute pancreatitis as well as in some patients with pancreatic malignancy. Although opioid derivatives are still clinically in use, the direct interruption of afferent nociceptive visceral stimulation (e.g., by segmental epidural block) is claimed to be much more effective method of pain relief. Intermittent or continuous unilateral celiac plexus block offers an effective alternative treatment for pain in acute pancreatitis, especially in patients with alcohol aetiology and history of drug/opioid addiction, in whom the conventional methods fail to give proper pain relief.13 A useful alternative to coeliac plexus block in the management of patients with chronic upper abdominal pain is splanchnic nerve block. The predictable relationship of the splanchnic nerves to other structures allows for accurate needle placement and hence a low risk of iatrogenic damage. Radiofrequency ablation (RFA) uses a high frequency alternating current to heat tissues leading to thermal coagulation. It produces predictable and accurate lesions and hence is useful alternative to more conventional phenol and alcohol neurolytic method.14 Transversus abdominis plane (TAP) block is a new regional anaesthetic technique that blocks abdominal neural afferents by introducing local anaesthetic into the neuro-fascial plane between the internal oblique and the transversus abdominis muscles. Ultrasound-guided TAP block significantly reduced postoperative morphine consumption in the first 24 h. Therefore, ultrasound-guided TAP block holds considerable promise as a part of a balanced postoperative analgesic regimen for patients undergoing open appendectomy.15 Spinal cord stimulator (SCS) Spinal cord stimulation (SCS) has traditionally been applied to the treatment of neuropathic pain with good to excellent outcomes. Visceral pain syndromes can be just as debilitating and disabling as somatic and neuropathic pain, however, there seems to be a general lack of consensus on appropriate treatment strategies for these disorders. In a study by Khan YN, Raza and Khan EA,16 several case studies were presented to demonstrate the viscerotomal distribution of abdominal visceral pain pathways and the application of traditional SCS techniques for its management. Nine patients, experiencing abdominal visceral pain due to various conditions including chronic non-alcoholic pancreatitis, post-traumatic splenectomy, and generalized abdominal pain seconddary to laparotomies, were treated with SCS. Efficacy of treatment was evaluated using the Visual Analog Scale (VAS) for pain intensity and a reduction, if any, in opioid intake. There was an overall mean reduction of 4.9 points in the VAS score for pain intensity and a substantial (> 50%) decrease in narcotic use. All patients were followed for more than one year with excellent outcomes and minimal complications.16, 17 References 1. Loesser JD. General considerations of abdominal pain. In: Bonica JJ, Graney DO, eds. Bonica’s Management of Pain, 3rd ed. Philadelphia, PA: Lippincott Williams & Williams; 2001. p1235–68. 2. Cervero F, Laird JMA. Visceral pain. The Lancet 1999; 353: 2145-8. 3. Hobson AR, Aziz Q. Central nervous system processing of human visceral pain in health and disease. News Physiol Sci 2003; 18,109-14. 4. Regan JM, Peng P, Chan VW. Naurophysiology of cancer pain: from the laboratory to the clinic. Curr Rev Pain 1999; 3 (3): 214-25. 5. Paleček J. The role of dorsal columns pathway in visceral pain. Physiol Res 2004; 53 (Suppl 1): 125-30. 6. Kapural L, Rakic M. Spinal cord stimulation for chronic visceral pain secondary to chronic non-alcoholic pancreatitis: A case report. Clinical Gastroenterology and Hepatology. V tisku: 2009.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
75
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
7. Oifa S, Sydoruk T, White I, Ekstein MP, Marouani N, Chazan S, et al. Effects of intravenous patient-controlled analgesia with buprenorphine and morphine alone and in combination during the first 12 postoperative hours: A randomized, double-blind, four-arm trial in adults undergoing abdominal surgery. Clin Ther 2009; 31 (3): 527-41. 8. Koch S, Ahlburg P, Spangsberg N, Brock B, Tønnesen E, Nikolajsen L. Oxycodone vs. fentanyl in the treatment of early post-operative pain after laparoscopic cholecystectomy: A randomised double-blind study. Acta Anaesthesiol Scand 2008; 52 (6): 845-50. 9. Riley J, Eisenberg E, Mueller-Schwefe G, Drewes AM, Arendt-Nielsen L. Oxycodone: A review of its use in the management of pain. Curr Med Res Opin 2008; 24 (1): 175-92. 10. Bruns H, Rahbari NN, Loeffler T, Diener MK, Seiler CM, Glanemann M, et al. 23 European participating centres of the DISPACT trial and a review of literature. Trials 2009; 26; 10: 58. 11. Darvas K, Futó J, Okrös I, Gondos T, Csomós A, Kupcsulik P. Principles of intensive care in severe acute pancreatitis in 2008. Orv Hetil 2008; 149 (47): 2211-20. 12. Horlocker TT, Abel MD, Messick JM Jr, Schroeder DR. Small risk of serious neurologic complications related to lumbar epidural catheter placement in anesthetized patients. Anesth Analg 2003; 96 (6): 1547-52. 13. Rykowski JJ, Hilgier M. Efficacy of neurolytic celiac plexus block in varying locations of pancreatic cancer: Influence on pain relief. Anesthesiology 2000; 92 (2): 347-54. 14. Garcea G, Thomasset S, Berry DP, Tordoff S. Percutaneous splanchnic nerve radiofrequency ablation for chronic abdominal pain. ANZ J Surg 2005; 75 (8): 640-4. 15. Niraj G, Searle A, Mathews M, Misra V, Baban M, Kiani S, et al. Analgesic efficacy of ultrasound-guided transversus abdominis plane block in patients undergoing open appendectomy. Br J Anaesth 2009; 103: 601-5. 16. Khan YN, Raza SS, Khan EA. Application of spinal cord stimulation for the treatment of abdominal visceral pain syndromes: case reports. Neuromodulation 2005; 8: 16-29. 17. Kapural L, Narouze SN, Janicki TI, Mekhail N. Spinal cord stimulation is an effective treatment for the chronic intractable visceral pelvic pain, Pain Medicine 2006; 7 (5): 440-3.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
76
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
TORAKALNA PARAVERTEBRALNA ANALGEZIJA THORACIC PARAVERTEBRAL ANALGESIA Vesna Novak-Jankovič Klinični oddelek za anesteziologijo in intenzivno terapijo operativnih strok, Univerzitetni klinični center Ljubljana, Ljubljana Izvleček. Torakalni paravertebralni blok je bil v široki uporabi že v začetku 20. stoletja. V zadnjem desetletju je doživel svojo renesanso. To je oblika aferentnega bloka, kjer se lokalni anestetik vbrizga v torakalni paravertebralni prostor. Torakalna paravertebralna analgezija je indicirana za enostranske kirurške posege v prsnem košu in trebuhu. V primerjavi z ostalimi področnimi tehnikami, kot so epiduralna, interkostalna in intraplevralna anestezija, omogoča paravertebralni blok primerljivo ali celo boljšo analgezijo z manj stranskih učinkov. Torakalni paravertebralni blok si zasluži več pozornosti kot doslej. th Abstract. Thoracic paravertebral block was widely practised at the beginning of the 20 century. It has enjoyed a renaissance in the past decade. This form of afferent blockade is the technique of injecting local anaesthetic into the thoracic paravertebral space. Thoracic paravertebral analgesia is mostly indicated for unilateral surgical procedures of the thorax and abdomen. Compared to the other available regional techniques such as epidural, intercostal and interpleural, paravertebral blocks offer comparable or better analgesia with less side effects. Thoracic paravertebral blocks deserve greater consideration and investigation.
Uvod Bolečina po torakotomiji je ena najhujših pooperacijskih bolečin. Povzročajo jo vlečenje, rezanje, zlomi reber in poškodbe medrebrnih živcev. Do sedaj je bila torakalna epiduralna analgezija (TEA) zlati standard za zdravljenje akutne pooperacijske bolečine po operacijskih posegih v prsnem košu in v trebuhu. Sedaj se paravertebralni blok vse več uporablja pri teh operacijskih posegih za zdravljenje akutne pooperacijske bolečine.1 Torakalni paravertebralni blok (TPB) je metoda analgezije, pri kateri vbrizgamo lokalni anestetik v torakalni paravertebralni prostor v bližino spinalnih živcev, kar povzroči istostransko senzorično, motorično in simpatično blokado.2 TPB je prvič izvedel leta 1906 Hugo Sellhaim iz Leipziga.3 Eason in Wyatt sta leta 1979 ponovno povečala zanimanje za to vrsto bloka z uvedbo katetra.4 Karmakar, Sabanathan, Richardson in Lönnqvist so raziskovalci v zadnjem desetletju, ki so blok ponovno uvedli v klinično prakso.5, 6
Anatomija Torakalni paravertebralni prostor je prostor v obliki klina ob hrbtenici. Od zadaj je prostor omejen z zgornjim kostotransverzalnim ligamentom, lateralno z zadajšnjo medrebrno membrano, od spredaj pa s parietalno plevro. Medialno so telesa vretenc, medvretenčne ploščice in medvretenčne odprtine (foramina). Spinalni živci vstopajo v paravertebralni prostor skozi medvretenčne odprtine oviti v duralne vrečke (’cuff’). V paravertebralnem prostoru izgubijo to fascialno ovojnico in se delijo v sprednje in zadajšnje veje. Zadajšnje veje oživčujejo zadajšnje spinalne mišice in kožo v področju hrbtenjače (2). Sprednje veje od T1-T11 tvorijo medrebrne živce, T12 pa tvori podrebrni (subkostalni) živec. Vsak segmentalni spinalni živec je povezan s simpatično verigo, ki poteka na ventralni strani telesa vretenc (slika 1). Indikacije Torakalni paravertebralni blok je še posebej primeren za enostranske kirurške posege, kot so torakotomija, kirurgija dojke, kirurgija pljuč in srčna kirurgija. Omogoča odlično analgezijo pri ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
77
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
zlomih reber.7 Uporablja se pri zdravljenju postherpetične nevralgije in pri različnih kroničnih bolečinskih sindromih.
Slika 1. Prečni (transverzalni) prikaz paravertebralnega prostora Legenda k puščicam: Pleura – plevra; sympathetic chain – simpatična veriga; endothoracic fascia – endotorakalna fascia; spinal nerve – spinalni živec; superior costotransverse ligament – zgornji kostotransverzalni ligament
Kontraindikacije in zapleti Vnetje na mestu vboda, empiemi, tumorji plevre in paravertebralnega prostora so kontraindikacije za izvajanje tega bloka. Koagulopatije in antikoagulantna terapija so relativne kontraindikacije za TPB. Previdnost je potrebna pri deformacijah prsnega koša in skoliozah, da bi se izognili subarahnoidnemu oziroma epiduralnemu bloku. Plevralna punkcija (v 1,1 %) in pnevmotoraks (v 0,5 %) sta tudi možna zapleta pri izvajanju bloka.8, 9
Klinične študije Torakalni paravertebralni prostor se lahko spozna z metodo izgube upora (”loss of resistance”), z uporabo živčnega spodbujevalnika ali z metodo merjenja pritiska.10 V študiji Richardsona in sodelavcev so ugotovili, da TPB z bupivakainom bolj olajša pooperacijsko bolečino, bolj ohranja pljučne funkcije in ima manj stranskih učinkov v primerjavi s TEA.6 V študiji Casatija in sodelavcev so prikazali, da je TPB enako učinkovit v lajšanju pooperacijske bolečine kot TEA, vendar so bili bolniki v skupini, ki je dobila TPB, bolj hemodinamsko stabilni.11 V študiji, v kateri so primerjali paravertebralno analgezijo z intraplevralno analgezijo, so pokazali, da so bili bolniki v paravertebralni skupini manj zmedeni in da je bila pljučna funkcija pri njih bolj ohranjena.12 Pri endoskopskih posegih v prsnem košu je enkratno izveden paravertebralni blok predoperacijsko izboljšal pooperacijsko analgezijo.13 Pri dojenčkih je bilo lajšanje bolečine po torakotomiji z neprekinjeno paravertebralno infuzijo bupivakaina zelo uspešno in je potekalo brez zapletov.14 V preglednih člankih so pokazali, da je TPB v lajšanju pooperacijske bolečine enako učinkovita kot TEA, ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
78
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
vendar pa so zapleti in stranski učinki manj izraženi; zato je TPB priporočena metoda za lajšanje pooperacijske bolečine.1, 15
Zaključek Navdušenje za uporabo TPB-ja pri bolnikih, operiranih v prsnem košu, v zadnjem desetletju narašča.16 V primerjavi z interkostalnim blokom, intraplevralno analgezijo in TEA TPB zelo učinkovito lajša pooperacijsko bolečino z manj zapletov in stranskih učinkov. Literatura 1. Davies RG, Myles PS, Graham JM. A comparison of the analgesic efficacy and side-effects of paravertebral vs epidural blockade for thoracotomy – a systematic review and meta-analysis of randomized trials. Br J Anaesth 2006; 96 (4): 418-26. 2. Karmakar MK. Thoracic paravertebral block. Anesthesiology 2001; 95 (3): 771-80. 3. Bonica JJ. The management of pain with analgesic block. The management of pain. London: Henry Kimpton, 1953; p166-84. 4. Eason MJ, Wyatt R. Paravertebral thoracic block – a reappraisal. Anaesthesia 1979; 34: 638-42. 5. Richardson J, Lönnqvist PA. Thoracic paravertebral block. Br J Anaesth 1998; 81: 230-8. 6. Richardson J, Sabanathan S, Jones J, Shah RD, Cheema S, Mearns AJ. A prospective, randomized comparison of preoperative and continuous balanced epidural or paravertebral bupivacaine on post-thoracotomy pain, pulmonary function and stress responses. Brit J Anaesth 1999; 83 (3): 387-92. 7. Karmakar MK, Critchley LAH. Continuous thoracic paravertebral infusion of bupivacaine for pain management in patients with multiple fractured ribs. Chest 2003; 123: 423-31. 8. Richardson J, Sabanathan S. Thoracic paravertebral analgesia. A review. Acta Anaesthesiol Scand 1995; 39: 1005-15. 9. Lönnqvist PA, MacKenzie J, Soni AK, Conacher ID. Paravertebral blockade: failure rate and complications. Anaesthesia 1995; 50: 813-5. 10. Richardson J, Cheema SP et al. Thoracic paravertebral space location; a new method using pressure measurement. Anaesthesia 1996; 51: 137-9. 11. Casati A, Alessandrinin P, Nuzzi M, Tosi M, Iotti E, Ampollini L, et al. A prospective, randomized, blinded comparison between continuous thoracic paravertebral and epidural infusion of 0.2 % ropivacaine after lung resection surgery. Eur J Anaesth 2006; 23 (12): 999-1004. 12. Richardson J, Sabanathan S, Mearns AJ, Shan RD, Goulden C. A prospective, randomized comparison of intrapleural and paravertebral analgesia in thoracic surgery. Brit J Anaesth 1995; 75: 405-8. 13. Vogt A, Stieger DS, Theurillat C, Curatolo M. Single-injection thoracic paravertebral block for postoperative pain treatment after thoracoscopic surgery. Brit J Anaesth 2005; 95 (6): 816-21. 14. Karmakar MK, Booker PD, Franks R, Pozzi M. Continuous extrapleural paravertebral infusion of bupivacaine for post-thoracotomy analgesia in young infants. Brit J Anaesth 1996; 76: 811-5. 15. Joshi GP, Bonnet F, Shah R, Wilkinson RC, Camu F, Fischer B, et al. A systemic review of randomized trials evaluating regional techniques for postthoracotomy analgesia. Anesth Analg 2008; 107 (3): 1026-40. 16. Daly DJ, Myles PS. Update on the role of paravertebral blocks for thoracic surgery: are they worth it? In: Van Aken H, Barash PG, eds. Campos JH: Thoracic anesthesia. Curr opin in Anaesthesiol 2009; 22 (1): 38-43.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
79
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
KATETRSKE TEHNIKE ZA POOPERACIJSKO ANALGEZIJO V RANI WOUND CATHETER TECHNIQUES FOR POSTOPERATIVE ANALGESIA Neli Vintar Clinical Department of Anaesthesiology and Intensive Therapy, University Medical Centre Ljubljana, Ljubljana, Slovenia
Introduction Effective postoperative analgesia is important from the patient's perspective and can also improve clinical outcome.1, 2. Regional analgesic techniques are an efficient, non-opioid pharmacological approach to postoperative analgesia. Advanced analgesic techniques, such as epidural or perineural catheters, provide successful analgesia. However, many of these analgesic modalities are labor – intensive and carry specific risks related to central or peripheral nerve blocks. A promising modality that might help improve postoperative analgesia is the relatively simple technique in which the surgeon directly places a catheter to infuse local anaesthetic into wounds at the end of the procedure. Reports from the literature and our clinical results are quite promising: Wound catheter technique is technically efficient after various surgical procedures, offers substantially reduction of the needs for opioids and their related side effects, can be used for several days and can now, with the introduction of new portable pumps, be used on an ambulatory basis. Although there are multiple reports and small randomized controlled trials, there have been conflicting reports of the overall efficacy.1 Abdominal surgery Midline incision is one of the most comonly used for abdominal surgery. The effect of bupivacaine infusion in the midline wound on postoperative pain and postoperative opioid requirements was studied.3, 4 Results showed less daily opioid requirements in patients with intrawound bupivacaine infusion and earlier ambulation, but no difference in overall pain scores and length of hospitalization.3, 4 Continuous intrawound infusion was studied after cesarean delivery and abdominal hysterectomy with opioid sparing effect.5–8 Gupta studied analgesic effects of ropivacaine via a catheter placed intraperitoneally after laparoscopic holecystectomy.9 Early postoperative pain could be relieved by ropivacaine administered into the bed of the gall bladder with lower pain scores for deep pain and coughing, but opioid consumption and times to walk, drink and eat at home were similar in the ropivacine and in the placebo group. Continuous preperitoneal infusion of ropivacaine improved pain relief, reduced morphine consumption and accelerated recovery after colorectal surgery.10 After appendectomy, a reduction in postoperative pain and in rescue analgesic consumption was observed in the ropivacaine wound infusion group, but no statistically significant differences in the frequency of adverse effects could be found between the ropivacaine and placebo group.11 Wound catheter local anesthetic technique was most widely studied after inguinal hernia repair. Ropivacaine and bupivacaine wound infusion provided safe and adequate analgesia.12–15 It provided effective analgesia especially when patients were mobilizing. This has implications for earlier discharge from hospital and associated cost-savings. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
80
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Shoulder surgery Several studies concluded that postoperative wound infiltration with ropivacaine or bupivacaine provided smaller pain scores and opioid requirement in comparison with saline after arthroscopic and open shoulder surgery.16–22 Catheters were placed subacromially. After subacromial arthroscopy, also intrabursal infusion of bupivacaine and morphine provided affective analgesia.23 Lower limb surgery After cruciate ligament reconstruction, intraarticular catheter technique was studied. When only bupivacaine was used for continuous infusion, analgesia was not effective.24, 25 With a multimodal approach the intraarticular infusion of ropivacaine, morphine and ketorolac combination provided effective pain relief and lower daily opioid consumption, but the difference in the incidence of opioid-related side effects was not statistically significant.26 After primary total knee replacement Rasmussen showed lower pain scores, lower opioid consumption, increased knee flexion and reduced hospital stay with continuous intraarticular infusion of morphine and ropivacaine.27 Single shot postoperative wound infiltration of a high dose of ropivacaine, ketorolac and adrenalin and placement of intraarticular catheter for one repeated smaller dose of the same drug combination after 24 hours improved early analgesia and mobilization after total knee replacement.28, 29 The combination of wound infiltration and intraarticular catheter technique was effective also after total hip replacement.30, 31 Bianconi showed that postoperative infiltration and continuous wound infusion with ropivacaine reduced pain and opioid requirements after total hip replacement compared to systemic analgesia.32 Iliac crest Different orthopaedic procedures require autogenous bone graft from the ilium, resulting in two painful sites for the patient. The pain at the donor site usually resolves within the first postoperative weeks, but it may persist and represent a significant source of postoperative morbidity. Compared with placebo, continuous infusion of ropivacaine through an iliac crest catheter provided significantly better control of postoperative pain both at rest and during motion at the donor site, significant reduction of morphine consumption, and significantly higher patient satisfaction. The beneficial effect on pain was still present during motion 3 months after surgery.33 Singh and Gundes found similar positive results in their studies.34, 35 However, the results of Morgan and Puri showed no significant differences in pain scores neither in the amount of opioids used in the local anesthetic group compared with placebo.36, 37 Breast surgery Postoperative pain is a common problem following ambulatory breast augmentation surgery. In the study of Rawal patients received a subcutaneously placed multiple-hole catheter through the incision along the periphery of each breast.38 The results of this study provide evidence that patients receiving patient-controlled wound infusion with ropivacaine experienced better pain relief, required less rescue analgesics. Efficacy of a continuous bupivacaine infusion at postoperative surgical sites in patients with autologus breast reconstruction with a latissimus dorsi pedicled flap immediately after mastectomy was also studied.39 A two-site infusion kit with split flow to two catheters was inserted at the donor and recipient sites before skin closure. Significantly lower pain scores and lower opioid consumption was observed in the study group compared with placebo. In the study of Holmgren analgesic catheter was left in each breast postoperatively: in the two study groups catheters were placed deep in the cavity or subcutaneously along the surgical incision, in the saline group catheters were placed deep in the cavity. Postoperative intermittent infusion of bupivacaine in both study groups reduced the need for intravenous opioids and ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
81
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
improved pain relief after reduction mastectomy compared to placebo.40 There were no significant differences in pain relief between the two bupivacaine groups, which means that both sites of catheter placement provided effective analgesia.40 Cardiothoracic surgery Pain after cardiac surgery is most often related to the median sternotomy. In some studies they used two catheters: either in different wound layers, one subfascially and one subcutaneously41 or one after another to cover the whole length of the incision.42 In both studies continuous delivery of local anesthetic significantly improved pain relief and decreased the amount of opioids required. They also observed a significant decrease in the length of hospital stay, which significantly reduced costs. In the study where only one catheter was placed presternally no significant reduction in pain scores or in opioid requirements could be found.43 Wound healing There is growing evidence that local anaesthetics can inhibit local inflammatory response to injury. They reduce release of inflammatory mediators from neutrofils, reduce neutrophil adhesion to endothelium and decrease oedema formation.44 In most of the studies wound healing was specifically observed and was found normal. Continuous wound infusion of local anesthetic did not impair or delay healing compared to continuous saline infusion. Local anaesthetic toxicity No clinical signs of local anesthetic toxicity were observed in any of the studies. Local anaesthetic blood levels were measured in several studies.7, 9, 10, 22, 32. 33, 45 Plasma concentrations remained well bellow toxic levels in all the reports. Conclusion Liu et al performed a quantitative and qualitative systematic review of wound catheter analgesia and found improved analgesia, reduced opioid use, increased patient satisfaction, and perhaps reduced hospital stay.1 The most notable feature was the consistent evidence of these benefits across wide range of surgical procedures, location of wound catheters, and dosing regimens accompanied with low incidences of catheter-related complications. Additional double blind placebo-controlled studies are needed to help us understand the procedure specific optimal flow rates, local anesthetic concentrations, site of catheter placement. More well designed studies are needed to understand if potential benefits of this technique optimize outcomes, such as conversion of inpatient procedures to ambulatory procedures. Inspite of many unanswered questions, both the efficacy and technical simplicity of this technique encourage its clinical use. Practical details Catheters Several types of catheters may be used. Epidural catheters may have three or more side-holes near the tip. Multiholed (fenestrated) catheters have a section of varying length with evenly distributed holes. Catheter placement For each indication recommendations are based on expert opinions, more studies are needed to define best wound layer for catheter placement.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
82
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Preclosure bolus administration Priming the surgical site with a bolus of local anaesthetic may be beneficial. Drug and dosing regimen The application of a long-acting local anaesthetic such as bupivacaine 0.25%, levobupivacaine 0.25% or ropivacaine 0.2–0.3% is suggested. Flow rate Flow rates of 2 ml/h, 4 ml/h and 10ml/h have all been used. Flow rate may be a major determinant of efficacy, because long surgical incisions require a large volume of local anaesthetic. Duration of infusion Duration varies from 48 h to 72 h. At least 48 h is suggested, but duration should be tailored to the patient’s needs. References 1. Liu SS, Richman JM, Thirlby RC, Wu CL. Efficacy of continuous wound catheters delivering local anesthetic for postoperative analgesia: a quantitative and qualitative systematic review of randomized controlled trials. J Am Coll Surg 2006; 203 (6): 914-32. 2. Ranta PO, Ala-Kokko TI, Kukkonen JE, Ohtonen PP, Raudaskoski TH, Reponen PK, et al. Incisional and epidural analgesia after caesarean delivery: A prospective, placebo-controlled, randomised clinical study. Int J Obstet Anesth 2006; 15 (3): 189-94. 3. Padmanabhan J, Rohatgi A, Niaz A, Chojnowska E, Baig K, Woods WG. Does rectus sheath infusion of bupivacaine reduce postoperative opioid requirement? Ann R Coll Surg Engl 2007; 89 (3): 229-32. 4. Baig MK, Zmora O, Derdemezi J, Weiss EG, Nogueras JJ, Wexner SD. Use of the ON-Q pain management system is associated with decreased postoperative analgesic requirement: Double blind randomized placebo pilot study. J Am Coll Surg 2006; 202 (2): 297-305. 5. Lavand'homme PM, Roelants F, Waterloos H, De Kock MF. Postoperative analgesic effects of continuous wound infiltration with diclofenac after elective cesarean delivery. Anesthesiology 2007; 106 (6): 1220-5. 6. Zohar E, Shapiro A, Eidinov A, Fishman A, Fredman B. Postcesarean analgesia: the efficacy of bupivacaine wound instillation with and without supplemental diclofenac. J Clin Anesth 2006; 18 (6): 415-21. 7. Gupta A, Perniola A, Axelsson K, Thorn SE, Crafoord K, Rawal N. Postoperative pain after abdominal hysterectomy: A double-blind comparison between placebo and local anesthetic infused intraperitoneally. Anesth Analg 2004; 99 (4): 1173-9. 8. Gupta S, Maheshwari R, Dulara SC. Wound instillation with 0.25% bupivacaine as continuous infusion following hysterectomy. Middle East J Anesthesiol 2005; 18 (3): 595-610. 9. Gupta A, Thorn SE, Axelsson K, Larsson LG, Agren G, Holmstrom B, et al. Postoperative pain relief using intermittent injections of 0.5% ropivacaine through a catheter after laparoscopic cholecystectomy. Anesth Analg 2002; 95 (2): 450-6. 10. Beaussier M, El'Ayoubi H, Schiffer E, Rollin M, Parc Y, Mazoit JX, et al. Continuous preperitoneal infusion of ropivacaine provides effective analgesia and accelerates recovery after colorectal surgery: a randomized, double-blind, placebo-controlled study. Anesthesiology 2007; 107 (3): 461-8. 11. Ansaloni L, Agnoletti V, Bettini D, Caira A, Calli M, Catena F, et al. The analgesic efficacy of continuous elastomeric pump ropivacaine wound instillation after appendectomy. J Clin Anesth 2007; 19 (4): 256-63. 12. Vintar N, Pozlep G, Rawal N, Godec M, Rakovec S. Incisional self-administration of bupivacaine or ropivacaine provides effective analgesia after inguinal hernia repair. Can J Anaesth 2002; 49 (5): 481-6. 13. Schurr MJ, Gordon DB, Pellino TA, Scanlon TA. Continuous local anesthetic infusion for pain management after outpatient inguinal herniorrhaphy. Surgery 2004; 136 (4): 761-9. 14. Sanchez B, Waxman K, Tatevossian R, Gamberdella M, Read B. Local anesthetic infusion pumps improve postoperative pain after inguinal hernia repair: A randomized trial. Am Surg 2004; 70 (11): 1002-6. 15. LeBlanc KA, Bellanger D, Rhynes VK, Hausmann M. Evaluation of continuous infusion of 0.5% bupivacaine by elastomeric pump for postoperative pain management after open inguinal hernia repair. J Am Coll Surg 2005; 200 (2): 198-202. 16. Savoie FH, Field LD, Jenkins RN, Mallon WJ, Phelps RA, 2nd. The pain control infusion pump for postoperative pain control in shoulder surgery. Arthroscopy 2000; 16 (4): 339-42. 17. Quick DC, Guanche CA. Evaluation of an anesthetic pump for postoperative care after shoulder surgery. J Shoulder Elbow Surg 2003; 12 (6): 618-21.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
83
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
18. Klein SM, Nielsen KC, Martin A, White W, Warner DS, Steele SM, et al. Interscalene brachial plexus block with continuous intraarticular infusion of ropivacaine. Anesth Analg 2001; 93 (3): 601-5. 19. Harvey GP, Chelly JE, AlSamsam T, Coupe K. Patient-controlled ropivacaine analgesia after arthroscopic subacromial decompression. Arthroscopy 2004; 20 (5): 451-5. 20. Gottschalk A, Burmeister MA, Radtke P, Krieg M, Farokhzad F, Kreissl S, et al. Continuous wound infiltration with ropivacaine reduces pain and analgesic requirement after shoulder surgery. Anesth Analg 2003; 97 (4): 1086-91. 21. Barber FA, Herbert MA. The effectiveness of an anesthetic continuous-infusion device on postoperative pain control. Arthroscopy 2002; 18 (1): 76-81. 22. Axelsson K, Nordenson U, Johanzon E, Rawal N, Ekback G, Lidegran G, et al. Patient-controlled regional analgesia (PCRA) with ropivacaine after arthroscopic subacromial decompression. Acta Anaesthesiol Scand 2003; 47 (8): 993-1000. 23. Park JY, Lee GW, Kim Y, Yoo MJ. The efficacy of continuous intrabursal infusion with morphine and bupivacaine for postoperative analgesia after subacromial arthroscopy. Reg Anesth Pain Med 2002; 27 (2): 145-9. 24. Parker RD, Streem K, Schmitz L, Martineau PA. Efficacy of continuous intra-articular bupivacaine infusion for postoperative analgesia after anterior cruciate ligament reconstruction: a double-blinded, placebo-controlled, prospective, and randomized study. Am J Sports Med 2007; 35 (4): 531-6. 25. Alford JW, Fadale PD. Evaluation of postoperative bupivacaine infusion for pain management after anterior cruciate ligament reconstruction. Arthroscopy 2003; 19 (8): 855-61. 26. Vintar N, Rawal N, Veselko M. Intraarticular patient-controlled regional anesthesia after arthroscopically assisted anterior cruciate ligament reconstruction: ropivacaine/morphine/ketorolac versus ropivacaine/morphine. Anesth Analg 2005; 101 (2): 573-8. 27. Rasmussen S, Kramhoft MU, Sperling KP, Pedersen JH. Increased flexion and reduced hospital stay with continuous intraarticular morphine and ropivacaine after primary total knee replacement: open intervention study of efficacy and safety in 154 patients. Acta Orthop Scand 2004; 75 (5): 606-9. 28. Vendittoli PA, Makinen P, Drolet P, Lavigne M, Fallaha M, Guertin MC, et al. A multimodal analgesia protocol for total knee arthroplasty. A randomized, controlled study. J Bone Joint Surg Am 2006; 88 (2): 282-9. 29. Toftdahl K, Nikolajsen L, Haraldsted V, Madsen F, Tonnesen EK, Soballe K. Comparison of peri- and intraarticular analgesia with femoral nerve block after total knee arthroplasty: a randomized clinical trial. Acta Orthop 2007; 78 (2): 172-9. 30. Andersen LJ, Poulsen T, Krogh B, Nielsen T. Postoperative analgesia in total hip arthroplasty: a randomized double-blinded, placebo-controlled study on peroperative and postoperative ropivacaine, ketorolac, and adrenaline wound infiltration. Acta Orthop 2007; 78 (2): 187-92. 31. Andersen KV, Pfeiffer-Jensen M, Haraldsted V, Soballe K. Reduced hospital stay and narcotic consumption, and improved mobilization with local and intraarticular infiltration after hip arthroplasty: a randomized clinical trial of an intraarticular technique versus epidural infusion in 80 patients. Acta Orthop 2007; 78 (2): 180-6. 32. Bianconi M, Ferraro L, Traina GC, Zanoli G, Antonelli T, Guberti A, et al. Pharmacokinetics and efficacy of ropivacaine continuous wound instillation after joint replacement surgery. Br J Anaesth 2003; 91 (6): 830-5. 33. Blumenthal S, Dullenkopf A, Rentsch K, Borgeat A. Continuous infusion of ropivacaine for pain relief after iliac crest bone grafting for shoulder surgery. Anesthesiology 2005; 102 (2): 392-7. 34. Singh K, Samartzis D, Strom J, Manning D, Campbell-Hupp M, Wetzel FT, et al. A prospective, randomized, double-blind study evaluating the efficacy of postoperative continuous local anesthetic infusion at the iliac crest bone graft site after spinal arthrodesis. Spine 2005; 30 (22): 2477-83. 35. Gundes H, Kilickan L, Gurkan Y, Sarlak A, Toker K. Short- and long-term effects of regional application of morphine and bupivacaine on the iliac crest donor site. Acta Orthop Belg 2000; 66 (4): 341-4. 36. Puri R, Moskovich R, Gusmorino P, Shott S. Bupivacaine for postoperative pain relief at the iliac crest bone graft harvest site. Am J Orthop 2000; 29 (6): 443-6. 37. Morgan SJ, Jeray KJ, Saliman LH, Miller HJ, Williams AE, Tanner SL, et al. Continuous infusion of local anesthetic at iliac crest bone-graft sites for postoperative pain relief. A randomized, double-blind study. J Bone Joint Surg Am 2006; 88 (12): 2606-12. 38. Rawal N, Gupta A, Helsing M, Grell K, Allvin R. Pain relief following breast augmentation surgery: a comparison between incisional patient-controlled regional analgesia and traditional oral analgesia. Eur J Anaesthesiol 2006; 23 (12): 1010-7. 39. Baroody M, Tameo MN, Dabb RW. Efficacy of the pain pump catheter in immediate autologous breast reconstruction. Plast Reconstr Surg 2004; 114 (4): 895-8; discussion 9-900. 40. Holmgren RT, Tarpila E. Intermittent injection of bupivacaine into the margin or the cavity after reduction mammaplasty. Scand J Plast Reconstr Surg Hand Surg 2005; 39 (4): 218-21. 41. White PF, Rawal S, Latham P, Markowitz S, Issioui T, Chi L, et al. Use of a continuous local anesthetic infusion for pain management after median sternotomy. Anesthesiology 2003; 99 (4): 918-23. 42. Dowling R, Thielmeier K, Ghaly A, Barber D, Boice T, Dine A. Improved pain control after cardiac surgery: Results of a randomized, double-blind, clinical trial. J Thorac Cardiovasc Surg 2003; 126 (5): 1271-8. 43. Magnano D, Montalbano R, Lamarra M, Ferri F, Lorini L, Clarizia S, et al. Ineffectiveness of local wound anesthesia to reduce postoperative pain after median sternotomy. J Card Surg 2005; 20 (4): 314-8. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
84
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
44. Hahnenkamp K, Theilmeier G, Van Aken HK, Hoenemann CW. The effects of local anesthetics on perioperative coagulation, inflammation, and microcirculation. Anesth Analg 2002; 94 (6): 1441-7. 45. Fredman B, Shapiro A, Zohar E, Feldman E, Shorer S, Rawal N, et al. The analgesic efficacy of patient-controlled ropivacaine instillation after Cesarean delivery. Anesth Analg 2000; 91 (6): 1436-40.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
85
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
CENTRALNA BOLEČINA – PATOFIZIOLOGIJA IN TERAPIJA CENTRAL PAIN – PATHOPHYSIOLOGY AND THERAPY Viktor Švigelj Oddelek intenzivne nevrološke terapije, Nevrološka klinika, Univerzitetni klinični center Ljubljana, Ljubljana
Izvleček. Izhodišča. Bolečina je senzorično in čustveno doživetje, povezano z dejanskim ali potencialnim delovanjem dražljajev, ki okvarijo tkiva. Bolečina je vedno subjektivna in povezana z izkušnjami poškodb v zgodnji dobi življenja. Centralna ali nevropatska centralna bolečina je zaradi okvare v osrednjem živčevju. Lahko je posledica preboleli možganske kapi, poškodbe hrbtenjače, multiple skleroze ali pa so lahko tudi drugi vzroki zanjo. Bolečina je lahko žgoča, prebadajoča, srbeča, pikajoča in je pogosto spremljana z dizestezijami, hiperalgezijo ali alodinijo, še posebno na mraz in krtačenje. Po opisu talamičnega sindroma leta 1906 so sledili tudi opisi zunajtalamičnih vzrokov za nastanek nevropatske centralne bolečine; nedavno objavljene študije so pokazale, da lahko okvara kjer koli v spinotalamični poti, preklopih ali projekcijah lahko povzroči tako bolečino, kar dokazujejo tudi moderne nevroradiološke tehnike. Zaključki. Patogenetske študije kažejo, da je pri patofizioloških mehanizmih nevropatske centralne bolečine vpletena različna regulacija delovanja prenašalcev na receptorje, še posebno noradrenergičnih in delovanje je v določenem času. Katera koli razlaga patofiziologije NCB je pravilna ali vsaj približno pravilna je pravzaprav pomembno raziskovalno področje, ki bo morda v prihodnosti prineslo nove terapevtske opcije. Sedanje zdravljenje je lahko uspešno pri približno dveh tretjinah bolnikov, vendar pa moramo pričeti zdraviti zgodaj. V nekaterih primerih ko antidepresivna ali antiepileptična zdravila ne delujejo, je smiselno dodati še zdravila drugega reda, vendar pa je pomembno, da ne izgubljamo časa s predpisovanjem, klasičnih protibolečinskih zdravil, ki pri nevropatski centralni bolečini ne delujejo. Abstract. Background. Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Pain is always subjective. Each individual learns the application of the word through experiences related to injury in early life. Central pain or central neuropathic pain is pain due to a lesion in the central nervous system. It can be a consequence of stroke, spinal cord injury, multiple sclerosis, but also other etiologies. Pain may be burning, shooting, aching, or pricking and is often accompanied by dysesthesia, hyperalgesia or allodynia, particularly to brush or cold. Since the thalamic syndrome was described in 1906, cases with lesions in extrathalamic sites have been described; more recently it has been suggested that a lesion anywhere in the spinothalamic pathway, its relays, or projections may cause central pain, and modern radiological techniques have tended to confirm this. Conclusions. The pathogenetic hypothesis which seems best to fit the latest findings is that there is up regulation or down regulation of receptors for transmitters, possibly mainly noradrenergic, over time. Whatever may be the true pathophysiology of central pain, it has been found that some two thirds of patients can be relieved by treatment with adrenergically active antidepressants. These drugs are more effective the sooner they are prescribed after pain onset. In some cases in which antidepressants alone are not effective, relief may be gained by the addition of other oral drugs. To obtain maximal effect from adrenergically active antidepressants, it is important not to lose time by trying the effect of classic analgesics, which are virtually devoid of action in central neuropathic pain.
Uvod Mednarodno združenje za proučevanje bolečine (International Association for the Study of Pain) in njena delovna skupina1 je nazadnje novembra 2007 v Kyotu, Japonska, opredelila bolečino kot senzorično in čustveno doživetje, povezano z dejanskim ali potencialnim delovanjem dražljajev, ki okvarijo tkiva. Ista skupina1 je opredelila centralno bolečino kot bolečino, ki začne ali je povzročena z primarno lezijo ali disfunkcijo v osrednjem živčevju. Bolečina je vedno subjektivna in povezana z izkušnjami poškodb v zgodnji dobi življenja, vendar pa nezmožnost verbalnega komuniciranja ne izključuje možnosti, da oseba doživlja bolečino. Številne osebe navajajo bolečino tudi v odsotnosti poškodbe tkiva ali katerega koli patofiziološkega vzroka. Pogosto je vzrok za to psihološki, kar pa težko ločimo od bolečine kot posledica tkivne poškodbe, če upoštevamo samo subjektivno ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
86
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
navajanje. Nekateri opredeljujejo bolečino kot najbolj neprijetno čutno izkušnjo, ki povzroča hudo trpljenje, in sicer takrat, ko je le-ta dovolj intenzivna in dolgotrajna. Vsekakor pa je bolečina pomemben obrambni mehanizem, ki preprečuje poškodbe in omogoča ustrezno ravnanje, kadar imamo poškodovano tkivo. Nevropatska centralna bolečina (NCB) nastane zaradi patofizioloških sprememb v centralnem živčnem sistemu, ki jih sproži poškodba ali bolezenski proces. Pri nevropatski bolečini se namreč razvijejo patološki mehanizmi, ki povzročijo povečano vzdraženost bolečinskega sistema. Posledica je znižanje bolečinskega praga, kar povzroči bolečino ob nebolečinskem dražljaju. Ta pojav imenujemo alodinija. Poleg tega, bolečinski dražljaj povzroči pretirano zaznavanje bolečine oziroma hiperalgezijo. Sočasno se lahko pri bolnikih z nevropatsko bolečino pojavi spontana bolečina, ki je neodvisna od bolečinskega dražljaja. Značilnost NCB je tudi, da poteka kronično. Najpogosteje je NCB posledica možganske kapi (MK), najverjetneje zato, ker je MK najpogostejša nevrološka bolezen.2 Zdravljenje NCB je kljub novim spoznanjem še vedno zapleteno. V ta namen se že dolgo časa uporabljajo zdravila, ki delujejo na strukture, vpletene v nastanek NCB. Namen prispevka je prikazati patofiziologijo in terapijo centralne bolečine. Prikaz patofizioloških mehanizmov nevropatske centralne bolečine na modelu možganske kapi Možganska kap pomeni nenaden nastanek nevroloških simptomov in znakov, in sicer zaradi ishemije v možganih ali krvavitve v osrednje živčevje. Je najpogostejša akutna nevrološka bolezen, ki je na tretjem mestu (v nekaterih državah celo na drugem) kot vzrok smrtnosti in na prvem kot vzrok invalidnosti. Delež ishemične MK je 75–80 % vseh oblik MK. Vzrok zanjo je okluzija možganske žile, ki prekine preskrbo možganskih struktur s kisikom in glukozo, čemur sledi razpad metabolnega procesa. Posledica je infarkt, ki pomeni strukturno lezijo predela osrednjega živčevja in je ireverzibilno stanje.3 Ena od možnih dolgotrajnih posledic MK je tudi NCB in vse od leta 1906 dalje, ko je prvič opisan talamični sindrom,4 se raziskovalci ubadajo s problemov iskanja patofizioloških mehanizmov NCB in njenega zdravljenja. Značilnost NCB zaradi MK (ali drugih nevroloških bolezni, ki povzroče NCB) je pogosta stalna bolečina ali bolečina, ki se pojavlja v napadih. V literaturi zasledimo podatke, da se NCB po MK pojavlja pri 1,5–2,0 % vseh oblik MK,5 Andersen in sod. pa so v prospektivni raziskavi ugotavljali NCB po MK celo pri 8 % bolnikov v prvem letu po možganski kapi.6 Zaradi velike incidence možganske kapi NCB verjetno prizadene veliko število bolnikov.2 Bolečina se običajno pojavi v področju, kjer je motena senzorika, sama razporeditev pa nima stalnega vzorca, lahko se pojavlja v napadih. Bolniki jo opisujejo kot pekočo, zbadajočo, trgajočo ali utripajočo in jo lahko občutijo na površini, v globini ali v obeh predelih. Bolečino lahko povečajo telesne in čustvene obremenitve, omili pa jo sprostitev.7 Take vrste bolečina je za bolnika po MK pogosto obremenjujoča, neučinkovito zdravljenje pa lahko povzroči hudo depresijo, zaradi česar je tudi nagnjenost k samomorom v tej skupini bolnikov večja.8 Bolečina se lahko pojavi takoj (najpogosteje, če je prizadet talamus) ali pa celo nekaj let (do 10 let) po MK, običajno pa 3–6 mesecev po akutni MK.7 Najpogostejša oblika CNB po MK, ki jo opisujejo bolniki, je paradoksna žgoča bolečina, senzacija, ki jo opišejo, kot da pomakajo roko v ledeno mrzlo vodo (pri skoraj 50 % bolnikov po MK),9 kar je podobno, kot opisujejo bolniki, ki imajo NCB zaradi drugih centralnih vzrokov (npr. multipla skleroza, siringomielija, dizestezija po hordotomiji) ali pa zaradi verjetno perifernega vzroka (simpatična refleksna distrofija, postherpetična nevralgija, boleča diabetična nevropatija). Natančna patofiziologija NCB po MK ni povsem jasna. Patofiziološki mehanizem, ki bi jo lahko povzročil, je morda nepravilna aktivnost nevronov v osrednjem živčevju zaradi deaferentacije (zmanjšan dotok senzoričnih impulzov) ali pa povečane nevronske vzdraženosti (centralna senzitacija).10, 11 Porazdelitev bolečine je lahko neobičajna, še posebno kadar bolniki želijo pojasniti področje najhujše bolečine, pri tem pa ne moremo ugotoviti jasnega vzorca nastanka. Maksimalna (ali celo edina) bolečina se lahko pojavi v proksimalnih delih udov ali na trupu, kot tudi v okončinah. Včasih je področje bolečine tako majhno, še posebno če je to na obrazu, da moramo diferencialno diagnostično vzrok ločiti od nevralgije trigeminusa.12 Vestergaard in sod. opisujejo na 11 primerih samo lokalizirano bolečino v področju tenarja,13 medtem ko so Leijon in sod. ugotovili ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
87
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
NCB po MK pri 74 % bolnikov le v polovici telesa, brez prizadetosti obraza.9 Kot zaključuje Garcin je pričakovati tako distribucijo NCB pri pravem talamičnem sindromu,9 ker ima največ nevronov v ventroposteriornem talamičnem jedru receptivna polja za regijo rok in ust.14 Potrebno je poudariti, kot so tudi zaključili Vestergaard in sod., da se bolečina, ne glede na lokacijo, vedno pojavi znotraj največjega področja senzorične spremembe.13 Tudi pojavnost NCB glede na hemisfero je v nekaterih študijah opisana enaka,7, 13 medtem, ko druge opisujejo povečano pojavnost NCB, če je bila lezija v dominantni9 ali pa nedominantni polobli možganov.15 Prav tako pa relativna odsotnost težjih motoričnih izpadov ne izključuje NCB,7 kar sta opisovala tudi že Dejerine in Roussy leta 1906.4 Alodinijo (bolečina, ki je povzročena s stimulusom, ki običajno ne sproži bolečine) opisuje Bowsher v svoji seriji bolnikov po MK kar pri 2/37 in jo lahko sprožijo že muha, ki sede na obraz, ali pa prhanje ali če na bolnika padajo dežne kaplje. Alodinija se redkeje pojavlja kot pri postherpetični nevralgiji, kjer je ponavadi kardinalni simptom.16 Taktilna alodinija je najpogostejša oblika, saj jo ugotovimo pri 50 % bolnikov z alodinijo po MK in se včasih sproži tudi zunaj bolečega področja (npr. sprožijo jo mehanoreceptorji, ki imajo hitro adaptirajoči se nizek prožitveni prag), medtem ko močan stisk lahko tudi odpravi tako bolečino,17 lahko pa se tovrstna bolečina sproži tudi z gibanjem, z izometrično ali izotonoično kontrakcijo mišic.18 Nastop NCB lahko sprožijo tudi stres in okolje (npr. mraz) ali pa hrup (tudi glasba), kar opisuje tudi Bowsher v svoji seriji bolnikov7 kot tudi druge študije.9 Opisane so tudi avtonomne motnje, čeprav so te pogostejše pri bolnikih po MK, ki nimajo NCB, vendar pa so področja na koži, ki so najobčutljivejša oziroma se pojavlja NCB, tudi hladnejša.7, 20 Pri tako povzročeni kožni vazokonstrikciji so učinkoviti nizki odmerki zaviralcev kalcijevih kanalčkov.21 Iz patofiziološkega vidika je najzanimivejši vidik senzoričnega primanjkljaja. Polovico bolnikov po MK ima senzorični primanjkljaj dotika z ostrim predmetom ob tudi drugih senzoričnih primanjkljajih, le peščica samo primanjkljaj dotika z ostrim predmetom,5 vendar pa imajo skoraj vsi bolniki z NCB po MK (97 %) senzorični primanjkljaj dotika z ostrim predmetom in/ali toplote, kar je verjetno, glede na anatomijo poti v slednjem primeru, ker ni periferne prizadetosti po MK, to le posledica motnje v centralnem procesiranju informacije, ki pride po A-delta in primarnih C-aferentnih vlaknih, še posebno po slednjih.22 Primanjkljaj dotika z ostrim predmetom, toplote ali mraza, ne pa globoke bolečine, je večji v področjih hujše kot pa milejše bolečine, medtem pa ni razlike v dotiku (s von Freyevimi vlakni), vibracijah, preiskavi dveh diskriminatornih točk, ščipanju in stimulaciji z vročino.7 Tudi kvantitativno merjenje toplotnega in hladnega praga je večje v bolečih kot zraven ležečih nebolečih področjih, vendar pa je pri draženju z vročino ta razlika občutno manjša, medtem ko je primanjkljaj dotika s von Freyevimi vlakni večji v nebolečih kot bolečih področjih.23 Verjetno je vzrok za to centralno procesiranje informacij po A-delta vlaknih kot pa Abeta ali C-perifernih aferentih vlaknih (tako lahko včasih tudi uspešno blokiramo paradoksne pekoče senzacije, če blokiramo mielinizirana vlakna na periferiji).10, 24 Poleg tega pa ostaja tudi razlika med supraspinalno in spinalno okvaro, kar se tiče mehanoreceptorskega draženja, in sicer je bolečina bistveno hujša pri spinalni kot supraspinalni okvari, kar verjetno najdemo v anatomski razlagi bolečinske poti.25 Patofiziološki mehanizmi, ki privedejo do NCB, se razvijejo v centralnem živčevju po okvari, ki nastane npr. zaradi MK. V osrednjem živčevju tako nastane že omenjena centralna senzitizacija, kar pomeni povečano vzdražnost sekundarnih bolečinskih nevronov v zadnjem rogu hrbtenjače. Centralno senzitizacijo sproži prekomerna in stalna aktivnost nociceptorjev, ki spremeni sinaptične povezave v hrbtenjači. Aktivirajo se kanalčki, kot npr. N-metil-D-aspartat (NMDA)-kanalčki, ki normalno niso aktivni. Posledica je zvišana koncentracija kalcija v centralnih nevronih, kar povzroči številne spremembe na receptorjih, kot tudi na kanalčkih, zaradi česar je aktivnost teh nevronov povečana. Poleg tega pride tudi do spremembe genske ekspresije in tvorbe encimov, kot je ciklooksigenaza, kar ima dolgoročne učinke. V predelu zadnjih rogov lahko pride tudi do strukturne reorganizacije. Tanka C-vlakna, ki se končajo v prvih dveh laminah zadnjih rogov hrbtenjače, lahko degenerirajo in posledica je razrast živčnih končičev iz globljih lamin, ki jih oživčujejo debela A-delta vlakna iz mehanoreceptorjev v koži. Tako pride do nenormalnega oživčenja centralnih bolečinskih nevronov (t.i. spinalna reorganizacija).26 Tako kot pri periferni senzitizaciji se tudi pri centralni senzitizaciji aktivirajo znotrajcelične kinaze s fosforilacijo kanalčkov in receptorjev in indukcijo genov. Posledica tega je nova funkcijska značilnost ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
88
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
nevronov (plastičnost). V bistvu je centralna senzitizacija pogojena s perifernim dogajanjem in je lahko povzročena z aktivnostjo ali odvisna od transkripcijskih sprememb v signalizirajočih substancah. Glutamat, ki deluje na različnih receptorjih v hrbtenjači, kot je npr. metabotropni glutamat, alfa-amino-3-hidroksi-5-metill-izoksazol-4-propionska kislina (AMPA) ali NMDA receptorji, so najpomembnejši prenašalci, ki pridodajo pri nevronski vzdražnosti. Druga pomembna kategorija prenašalcev z vlogo regulatorja na vzdraženost nevronov dorzalnih rogov pa so nevroni, ki vsebujejo gama-aminobutaratno (GABA) ali glicinergično kislino. Ti nevroni imajo kontrolno vlogo pri razvoju aktivnosti sinhronizacije valov.26, 27 Posebno vlogo ima tudi mikoglija, ki so imunsko delujoče celice in sestavljajo manjši del celične slike v osrednjem živčevju; v normalnih pogojih so mirujoče celice, se pa aktivirajo, ko pride do okvare nevronov. Aktivirana mikroglija je povezana z aktivacijo mitogen-aktiviranih proteinskih (MAP)-kinaz. Fosforilacija p38 je lahko centralni znotrajcelični signal pri odzivu glije na nevropatsko bolečino.28 V zadnjem času so opisani tudi mehanizmi NCB, ki govore o spremembi delovanja sistema, ki modulira bolečinski prenos. Poleg sistema, ki zavira prenos bolečinskih impulzov (descendentni inhibitorni sistem), obstaja tudi sistem, ki prenos impulzov pospešuje (descendentni facilitatorni sistem). Prevelika aktivnost v bolečinskem sistemu naj bi spremenila ravnotežje med obema sistemoma v prid pospeševanju prenosa bolečinskih impulzov v zadnjih rogovih hrbtenjače. S funkcijskimi nevroradiološkimi metodami, kot sta funkcijska magnetna resonanca (fMRI) in pozitronska emisijska tomografija (PET), so tudi ugotovili, da se pri bolečini aktivirajo predeli inzule, sprednjega cinguluma, določeni prefrontalni deli in talamus na nasprotni strani in tako ugotovimo pri bolnikih z NCB po MK spremenjen vzorec možganske aktivacije.29
Zdravljenje nevropatske centralne bolečine Farmakološke metode Že Dejerine in Roussy4 in kasneje Garcin18 so ugotovili, da konvencionalna protibolečinska zdravila pri NCB ne delujejo. Tudi danes, več kot sto let po prvem opisu NCB, je še vedno malo znanega o uspešnem farmakološkem zdravljenju tovrstne bolečine. Proučevali so že veliko različnih zdravil, vendar se niti eno ni izkazalo za popolnoma učinkovito. Randomizirane primerjalne klinične študije o zdravljenju NCM so redke, v njih je bilo vključenih le majhno število bolnikov. Algoritem za zdravljenje NCB naj bi se zgledoval po algoritmu za zdravljenje periferne nevropatske bolečine. Amitriptilin je prvo peroralno zdravilo, ki se je izkazalo za učinkovito pri bolnikih z NCB.9 Zmerno učinkoviti zdravili sta še tudi lamotrigin in gabapentin.30, 31 Ta zdravila so tudi zdravila prve izbire pri zdravljenju NCB. Meksiletin (peroralna oblika lidokaina) in fenitoin sta pokazala učinkovitost le pri majhnem številu bolnikov, je pa meksiletin vseeno zdravilo druge izbire pri zdravljenju NCB.32 Karbamazepin, ki se pogosto uporablja pri zdravljenju NCB, pa ne kaže v raziskavi učinkovitosti pri bolnikih z NCB po MK.9 Uporaba intravenskih zdravil (lidokain, propofol in ketamin) je učinkovita, kar so pokazale raziskave, ki so primerjale učinkovitost s placebom, vendar je slaba stran, da je delovanje le kratkoročno, vendar pa so pogosti stranski učinki in niso tudi primerni zaradi načina dajanja.33–35 Učinkovitost selektivnih zaviralcev noradrenalinskega prevzema (SNRI) (duloksetin, venlafaksin), levetiracetama in ostalih novejših antidepresivov in nevromodulacijskih zdravil na NCB po MK bo treba še proučiti. Nefarmakološke metode Lezije dorzalne korenine na mestu vstopa (dorsal root entry zone lesion – DREZL): Ena od metod nefarmakološkega zdravljenja pri farmakološko rezistentni obliki NCB je tudi kirurška metoda DREZL, ki je uspešnejša pri okvarah hrbtenjače, pri bolnikih z NCB po MK pa še ni proučena.36 ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
89
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Stimulacija motorične skorje: Tsubokawa in sod.37 so prvi opisali uspešno zdravljenje NCB po MK, vendar pa je vprašljiva učinkovitost pri drugih oblikah NCB.38 Repetitivna transkranialna magnetna stimulacija (rTMS) je neivazivna stimulacija motorične skorje, ki je lahko učinkovita pri zdravljenju NCB po MK, in sicer je učinek lahko dolgotrajen.39 Globoka možganska stimulacija je uporabna še posebno pri paraplegikih, vendar je metoda vprašljiva, saj lahko ablacija določenih struktur povzroči celo zvečanje bolečine,36 vendar pa so bili rezultati pri zdravljenju NCB po MK razočarajoči.40 Vestibulararna kalorična stimulacija: Opisani so primeri uspešnega zdravljenja talamične NCB, vendar študij s to metodo ni.41 Transkutana električnal žvična stimulacija (TENS): občasno pomaga pri NCB, še posebno če dražimo akupunkturne točke ali z nizko frekvenco.42 Pri vseh metodah je pomembna tudi psihološka podpora in vedenjsko-kognitivno zdravljenje. Pri vsakem bolniku moramo ugotoviti, ali ima kako komorbidno stanje, kot sta depresija in nespečnost. Tudi ta problem je treba zdraviti, saj bolečino veča in vzdržuje.36 Zaključek Katera koli razlaga patofiziologije NCB je pravilna ali vsaj približno pravilna, je pravzaprav pomembno raziskovalno področje, ki bo morda v prihodnosti prineslo nove terapevtske opcije. S sedanjimi smo lahko uspešni pri približno dveh tretjinah bolnikov. Vsekakor je najpomembnejše, da na tako težavo pomislimo zgodaj in čim hitreje tudi pričnemo zdraviti, saj je lahko odstotek uspešnega zdravljenja le tako večji. Literatura 1. http://www.iasp-pain.org/AM/Template.cfm?Section=Pain_Definitions&Template=/CM/HTMLDisplay.cfm& ContentID=1728#Pain 2. Bowsher D, Nurmikko T. Central post-stroke pain. Drug treatment options. CNS Drugs 1996; 5: 160-5. 3. Švigelj V. Mednarodni register za zdravljenje akutne ishemične možganske kapi. V: Švigelj V, Žvan B, ur. Akutna možganska kap: učbenik za zdravnike in zdravstvene delavce. Ljubljana: Aventis Pharma; 2006: 137-44. 4. Dejerine J, Roussy J. Le syndrome thalamique. Rev Neurol 1906; 14: 521-32. 5. Bowsher D. Cerebrovascular Disease: Sensory consequences of stroke. Lancet 1993; 341: 156. 6. Andersen G, Vestergaard K, Ingeman-Nielsen M, Jensen TS. Incidence of central post-stroke pain. Pain 1995; 61: 187-93. 7. Bowsher D. Central pain: clinical and physiological characteristics. J Neurol Neurosurg Psychiatry 1996; 61: 62-9. 8. Gonzales GR. Suicide in central pain patients. Neurology 1994; 44 Suppl 2: A318. 9. Leijon G, Boivie J, Johansson I. Central post-stroke pain-- neurological symptoms and pain characteristics. Pain 1989; 36: 13-25. 10. Yarnitsky D, Ochoa, JL. Release of cold-induced burning pain by block of cold-specific afferent input. Brain 1990; 113: 893-902. 11. Craig AD, Bushnell MC. The thermal grill illusion: unmasking the burn of cold pain. Science 1994; 265: 252-5. 12. Garcin R, Lapresle J. Deuxieme observation personelle de syndrome sensitive de type thalamique et a topographie cheiro-orale par lesion localisee du thalamus. Rev Neurol 1960; 103: 474-81. 13. Vestergaard K, Nielsen J, Andersen G, Ingeman-Nielsen M, Arendt-Nielsen L, Jensen TS. Sensory abnormalities in consecutive, unselected patients with central post-stroke pain. Pain 1995; 61: 177-86. 14. Lenz FA, Dostrovsky JO, Tasker RR, Yamashiro K, Kwan HC, Murphy JT. Single-unit analysis of the human ventral thalamic nuclear group: somatosensory responses. J Neurophysiol 1988; 59: 299-316. 15. Kameyama M. Vascular lesions of the thalamus on the dominant and nondominant side. Appl Neurophysiol 1976; 39: 171-7. 16. Nurmikko T, Bowsher D. Somatosensory findings in postherpetic neuralgia. J Neurol Neurosurg Psychiatry 1990; 53: 135-41. 17. Nurmikko T, Wells C, Bowsher D. Pain and allodynia in postherpetic neuralgia: role of somatic and sympathetic systems. Acta Neurol Scand 1991; 84: 146-52. 18. Garcin R. La douleur dans les affections organiques du systeme nerveux central. Rev Neurol 1937; 68: 105-53. 19. Riddoch, G. The clinical features of central pain. Lancet 1938; i:1093-8;1150-6;1205-9. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
90
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
20. Boivie J, Leijon G. Clinical findings in patients with central poststroke pain. V: Casey KL, ed. Pain and central nervous system disease: the central pain syndromes. New York: Raven Press; 1991: p65-75. 21. Korpelainen JT, Sotaniemi KA, Myllyl VV. Asymmetric sweating in stroke. A prospective quantitative study of patients with hemispheral brain infarction. Neurology 1993; 43: 1211-4. 22. Schmahmann JD, Leifer D. Parietal pseudothalamic pain syndrome: clinical features and anatomic correlates. Arch Neurol 1992; 49: 1032-7. 23. Eide PK, Jorum E, Stenehjem AE. Somatosensory findings in patients with spinal cord injury and central dysaesthesia pain. J Neurol Neurosurg Psychiatry 1996; 60: 411-5. 24. Asbury AK. Pain in generalised neuropathies. V: Fields HL, ur. Pain syndromes in neurology. London: Butterworth; 1990: p131-41. 25. Bowsher, D. Central pain. Pain Rev 1995; 2: 175-86. 26. Finnerup NB, Jensen TS. Mechanism-based classification of neuropathic pain: A critical analysis. Nat Clin Prac Neurol 2006; 2: 107-15. 27. Jensen TS, Baron R. Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 2003; 102: 1-8. 28. Woolf CJ. Pain: Moving from symptom control toward machanismspecific pharamcologic treatment. Ann Int Med 2004; 140: 441-51. 29. Jensen TS. Pathophysiology of pain: from theory to clinical evidence. European Journal of Pain Supplements 2008; 2: 13-7. 30. Vestergaard K, Andersen G, Gottrup H, Kristensen BT, Jensen TS. Lamotrigine for central poststroke pain. A randomized controlled trial. Neurology 2001; 56: 184-90. 31. Attal N, Parker F, Brasseur L, Chauvin M, Bouhassira D. Effects of gabapentin on the different components of neuropathic pain syndromes: a pilot study. Eur Neurol 1998; 40: 191-200. 32. Awerbuch GI, Sandyk R. Mexiletine for thalamic pain syndrome. Int J Neurosci 1990; 55: 129-33. 33. Attal N, Gaude V, Brasseur L, Dupuy M, Guirimand F, Parker F, Bouhassira D. Intravenous lidocaine in central pain: a doubleblind, placebo-controlled, psychophysical study. Neurology 2000; 54: 564-74. 34. Backonja M, Arndt G, Gombar KA, Check B, Zimmermann M. Response of chronic neuropathic pain syndromes to ketamine: a preliminary study. Pain 1994; 56: 51-7. 35. Canavero S, Bonicalzi V, Pagni CA, Castellano G, Merante R, Gentile S. Propofol analgesia in central pain: preliminary clinical observations. J Neurol 1995; 242: 561-7. 36. Gonzales GR. Central pain: diagnosis and treatment strategies. Neurology 1995; 45 (12 Suppl 9): S11-6. 37. Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T, Koyama S. Chronic motor cortex stimulation for the treatment of central pain. Acta Neurochir Suppl (Wien) 1991; 52: 137-9. 38. Hosobuchi Y. Motor cortical stimulation for control of central deafferentation pain. Adv Neurol 1993; 63: 215-7. 39. Khedr EM, Kotb H, Kamel NF, Ahmed MA, Sadek R, Rothwell JC. Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J Neurol Neurosurg Psychiatry 2005; 76: 833-8. 40. Triggs WJ, Beric A. Dysaesthesiae induced by physiological and electrical activation of posterior column afferents after stroke. J Neurol Neurosurg Psychiatry 1994; 57: 1077-80. 41. Ramachandran VS, McGeoch PD, Williams L, Arcilla G. Rapid relief of thalamic pain syndrome induced by vestibular caloric stimulation. Neurocase 2007; 13: 185-8. 42. Leijon G, Boivie J. Central post-stroke pain–the effect of high and low frequency TENS. Pain 1989; 38: 187-91.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
91
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
ZDRAVLJENJE BOLEČINE PO SRČNI OPERACIJI POSTOPERATIVE ANALGESIA FOR CARDIAC SURGERY Mirt Kamenik Oddelek za anesteziologijo, intenzivno terapijo in terapijo bolečine, Univerzitetni klinični center Maribor, Maribor
Uvod Kljub hitremu razvoju intervencijske kardiologije ostaja kirurško zdravljenje pomemben način zdravljenja ishemične bolezni srca in bolezni zaklopk. Razvoj sodobne kardiokirurgije v zadnjih letih poteka v smeri t.i. kirurgije »fast track«, s hitrim prehodom bolnika skozi perioperacijsko obdobje. »Fast track«-kirurgija zahteva prilagajanje anesteziološke tehnike, z uporabo nižjih odmerkov opioidov, kar omogoča hitrejše zbujanje bolnika iz anestezije, zgodnjo odstranitev dihalne cevke, zgodnji odpust bolnika iz enote intenzivne terapije, zgodnjo mobilizacijo bolnika po operaciji ter zgodnji odpust bolnika iz bolnišnice. Pomemben dejavnik za doseganje teh ciljev je tudi učinkovito zdravljenje po operacijske bolečine. Vzroki za bolečino po srčni operaciji so lahko: sternotomija, vlek reber, kirurška priprava notranje arterije mamarije, draženje sapnika zaradi lege dihalne cevke in čiščenja dihalnih poti, kakor tudi površinski rezi na nogah zaradi odvzema vene saphene ali na roki zaradi odvzema radialne arterije. Izjemoma zahteva srčna operacija tudi uporabo razširjenega kirurškega reza, ki vključuje torakotomijo ali zgornjo laparatomijo.1 Bolečina po srčni operaciji ima največjo intenziteto prvi in drugi dan po operaciji in nato postopno pojema v času od tretjega do sedmega dneva po operaciji. Mlajši bolniki običajno občutijo večjo intenziteto bolečine v primerjavi s starostniki, spol pa na intenziteto bolečine nima pomembnega vpliva.2 Tudi mesto bolečine se v po operacijskem obdobju spreminja. Prvi in drugi dan po operaciji bolniki običajno opisujejo najmočnejšo bolečino za prsnico in v žlički, medtem ko je sedmi dan po operaciji bolečina najmočnejša med lopaticama in v spodnjih okončinah. Podobno kot zdravljenje po operacijske bolečine na drugih področjih kirurgije poteka tudi zdravljenju bolečine po srčni operaciji po načelih t.i. multimodalnega pristopa. Multimodalni pristop zdravljenja bolečine zajema kombinacijo opiatnih analgetikov z neopiatnimi analgetiki, kar omogoča učinkovitejše lajšanje bolečine ob minimalnih stranskih učinkih. Za lajšanje bolečine po srčnih operacijah so v literaturi opisane tudi številne tehnike področne analgezije, ki pa v večini centrov praviloma ne predstavljajo standardnega načina zdravljenja bolečine po srčni operaciji. Sistemski opiati v zdravljenju bolečine po srčni operaciji Sistemski opiati so še vedno najpogosteje uporabjena zdravila v zdravljenju bolečine po srčni operaciji. Praviloma ostajajo bolniki po srčni operaciji vsaj za krajši čas (običajno okoli 6 ur) orotrahealno intubirani in umetno predihavani v enoti intenzivne terapije ali v sobi za prebujanje bolnika iz anestezije, dokler ne izzvenijo učinki med anestezijo uporabljenih zdravil in so bolniki sposobni samostojnega dihanja. V tem zgodnjem obdobju po operaciji imamo na voljo dva pristopa za dajanje zdravil proti bolečinam. Prvi pristop je da bolniku ne vbrizgamo analgetika dokler se ne prične prebujati in lahko sporoči intenziteto svoje bolečine. Drugi pristop pa je, da nadaljujemo z vzdrževalnimi odmerki analgetikov takoj po operaciji. Pri izboru pristopa moramo pretehtati tveganje za podaljšano sedacijo in depresijo dihanja po operaciji na eni strani in tveganje za nepopolno analgezijo na drugi strani. Pri izboru pristopa je se običajno odločamo tudi glede na vrsto anestezije in zlasti odmerke opioidov, ki jih je bolnik dobil med anestezijo. Dokler bolnik ni zbujen in lahko aktivno sodeluje pri zdravljenju mu dajemo zdravila proti bolečinam po načelih t.i. NCA (nurse controlled analgesia = od medicinske sestre vodeno zdravljenje bolečine). Po odstranitvi dihalne cevke lahko uporabimo tudi t.i. »od bolnika voden pristop« (PCA = Patient ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
92
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
controlled analgesia). Nekateri podatki v literaturi kažejo, da ima PCA-pristop prednosti pred NCA-pristopom zaradi boljše analgezije in manjše pogostosti zapletov s strani dihal.3–5 Najpogosteje uporabljena opiata za zdravljenje bolečine po srčni operaciji sta morfin in piritramid. Po uvedbi remifentanila v klinično prakso so raziskave pokazale, da lahko remifentanil uspešno uporabimo tudi za zdravljenje bolečine po srčni operaciji.6, 7 Če je potek operacije nezapleten in je bolnik primeren za multidisciplinarni plan hitrega okrevanja z zgodnjo mobilizacijo in zgodnjo respiratorno fizioterapijo avtorji priporočajo hiter prehod na peroralne opiate. Prehod na peroralne opiate lahko naredimo že 24 ur po operaciji z uporabo zdravil s počasnim sproščanjem (morfin ali oksikodon) v kombinaciji s hitro delujočimi opiati za prebijajočo bolečino.1, 8 Uporaba nesteroidnih antirevmatikov za zdravljenje bolečine po srčni operaciji Podobno kot v drugih vejah kirurgije je sodobno zdravljenje bolečine tudi po srčnih operacijah usmerjeno v t.i. multimodalni pristop, ki temelji na kombinaciji opiatov z neopiatnimi analgetiki. Ta kombinacija omogoča zmanjšanje odmerka opiatnih analgetikov ob učinkoviti analgeziji in s tem zmanjšanje stranskih učinkov opiatnih analgetikov. Kot neopiatni analgetiki se po podatkih iz literature najpogosteje uporabljajo nesteroidni antirevmatiki (NSAID). Raziskave kažejo, da se lahko ob uporabi nesteroidnih antirevmatikov poraba opiatnih analgetikov zmanjša za 20 %, čeprav še vedno ni jasno ali lahko s tem pristopom zmanjšamo obolevnost in/ali umrljivost kirurških bolnikov.9 Tudi na področju kardiokirurgije so lahko z uporabo nesteroidnih antirevmatikov pomembno zmanjšamo VAS in porabo opiatnih analgetikov po srčni operaciji. V ta namen so primerna različna zdravila kot so: naproksen,10 indometacin11 ali diklofenak.12 Nasprotniki uporabe nesteroidnih antirevmatikov opozarjajo na morebitne stranske učinke teh zdravil kot so: krvavitev iz prebavil, ledvična odpoved in povečano tveganje za krvavitev zaradi učinka na funkcijo trombocitov.13 Vendar pa podatki iz literature kažejo, da je tveganje za zaplete nizko, če zdravil ne uporabimo pri bolnikih s povečanim tveganjem pred operacijo (ulkusna bolezen, ledvična ali jeterna okvara, alergija na nesteroidne antirevmatike, povečana krvavitev po operaciji). Bainbridge s sodelavci14 je v svoji metaanalizi obdelal dvajset randomiziranih raziskav, ki so preučevale učinkovitost in zaplete ob uporabi nesteroidnih antirevmtikov po srčnih operacijah. V metaanalizo je bilo vključenih 1065 bolnikov. Avtorji so ugotovili, da uporaba nesteroidnih antirevmatikov pri zdravljenju bolečine po srčnih operacijah pomembno zmanjša VAS vrednosti v prvih 24 urah po operaciji in porabo opiatov. Vendar med skupinama ni bilo razlik v umrljivosti, pogostosti srčnega infarkta ter pogostosti ledvične ali jeterne okvare po operaciji. Večina raziskav, ki so preučevale uporabo nesteroidnih antirevmatikov tudi ni potrdila povečanega tveganja za krvavitev ali povečane porabe krvi in krvnih pripravkov po operaciji.10 Posebna previdnost je potrebna pri uporabi zdravil iz skupine zaviralcev COX-2. Raziskava Nussmeierja s sodelavci15 je pokazala, da uporaba zdravil iz skupine COX-2 zaviralcev (parekoksib in valdekoksib) v zdravljenju bolečine po operaciji na venčnih arterijah pomembno poveča tveganje za zaplete s strani obtočil kot so srčni infarkt, srčni zastoj, možganska kap in pljučna embolija. Na podlagi te velike randomizirane raziskave večina avtorjev svetuje, da se zdravila iz skupine zaviralcev COX-2 ne uporabljajo v zdravljenju bolečine po premostitvi venčnih arterij.1 Uporaba tehnik področne anestezije v zdravljenju bolečine po srčnih operacijah Izmed tehnik področne anestezije sta v zdravljenju bolečine po srčni operaciji najpogosteje omenjeni tehniki torakalna epiduralna analgezija (TEA) in intratekalna analgezija, čeprav so se kot uspešne v raziskavah pokazale tudi nekatere druge tehnike kot intraplevralna analgezija16 in podkožna infuzija rane z lokalnim anestetikom.17 Torakalna epiduralna analgezija lahko po podatkih iz literature zmanjša jakost bolečine po srčni operaciji, skrajša čas do odstranitve dihalne cevke, izboljša funkcijo dihal po operaciji, ter zaradi visoke blokade simpatičnega avtonomnega živčevja izboljša pretok skozi koronarno žilje. Metaanaliza Liu-ja s sodelavci18 je pokazala, da lahko TEA po srčni operaciji pomembno zmanjša tveganje za motnje srčnega ritma (OR 0,52), zmanjša zaplete s strani dihal (OR 0,41), skrajša čas do odstranitve dihalne cevke v povprečju za 4,5 ure in zmanjša VAS vrednosti v mirovanju in med aktivnostjo. Ob tem pa je ista raziskava pokazala, da TEA ni vplivala na umrljivost bolni------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
93
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
kov po operaciji (0,7 % TEA vs. 0,3 % parenteralna analgezija) in tudi ne na pogostost srčnega infarkta (2,3 % TEA vs. 3,4 % parenteralna analgezija). Podobne rezultate je pokazal sistematski pregled Djaianija s sodelavci.19 Pomembno je omeniti, da je bila večina raziskav, ki sta jih zajeli navedeni metaanalizi opravljenih v obdobju, pred vpeljavo t.i. »fast track«-pristopa v srčni kirurgiji, zato bo potrebno v bodočnosti pravo vrednost TEA v srčni kirurgiji ponovno ovrednotiti. Najpomembnejši argument proti uporabi TEA v srčni kirurgiji je morebitno povečano tveganje za nastanek epiduralnega hematoma, kot najnevarnejšega zapleta te anesteziološke tehnike. Natančno tveganje za pojav epiduralnega hematoma pri bolnikih operiranih na srcu, ki potrebujejo med operacijo visoke odmerke heparina, ni poznano. Ho s sodelavci20 je v svoji raziskavi ocenil tveganje okoli 1/1500 za epiduralno anestezijo in 1/3500 za spinalno anestezijo. Po najnovejših podatkih iz literature pa je resnično tveganje verjetno precej manjše in je primerljivo s tveganjem pri drugih operiranih bolnikih (okoli 1/12000 primerov).21 Kljub temu večina avtorjev priporoča, da je potrebno pri uporabi TEA pri bolnikih operiranih na srcu upoštevati stroge varnostne ukrepe, ki lahko zmanjšajo tveganje za nastanek epiduralnega hematoma. Bolniki morajo imeti normalno koagulacijo pred vstavitvijo in pred odstranitvijo katetra, potrebno je načrtovati čas heparinizacije vsaj 1 uro po vstavitvi katetra in preložiti operacijo, če se pojavijo tehnične težave pri vstavitvi katetra ali če med nastavljanjem katetra opazimo kri na mestu vstavitve. Po vstavitvi katetra je potrebno bolnika nadzirati vsaj dvakrat dnevno do tri dni po odstranitvi katetra. Subarahnoidno vbrizganje morfina je preprosta tehnika, ki jo lahko izvedemo z enkratnim vbrizganjem zdravila v subarahnoidni prostor in zagotavlja zelo učinkovito analgezijo tudi do 24 ur po srčni operaciji. Nedavno objavljena metaanaliza Meylana s sodelavci22 je pokazala zmanjšano intenziteto bolečine 12 in 24 ur po srčni operaciji pri bolnikih, ki so pred operacijo prejeli morfin v subarahnoidni prostor. Zmanjšala se je tudi poraba opiatov med operacijo in v času do 48 ur po operaciji. Vendar je te ugodne učinke spremljala nekoliko povečano tveganje za depresijo diha in nekoliko povečana pojavnost srbeža po operaciji. Tudi sistematski pregled Richardsona s sodelavci23 je potrdil ugoden analgetični učinek v subarahnoidni prostor vbrizganega morfina, ob tem pa je ostala pogostost stranskih učinkov opiatov primerljiva v obeh skupinah. Ker so vsi bolniki po srčni operaciji praviloma vsaj za krajši čas umetno predihavani v enoti intenzvne terapije ali v sobi za prebujanje, morebitna depresija dihanja po operaciji bolnika ne ogroža, lahko pa vpliva na uspešnost zgodnje ekstubacije in zgodnjega odpusta bolnika iz enote intenzivne terapije. Djaiani s sodelavci19 je v svoji metaanalizi ugotovil, da je optimalni odmerek v subarahnoidni prostor vbrizganega morfina, če načrtujemo zgodnjo odstranitev dihalne cevke, med 10 in 50 μg/kg. Zaključek Čeprav so v literaturi opisane številne tehnike za zdravljenje bolečine po srčnih operacijah, je najpogosteje uporabljen pristop še vedno dajanje opiatnih analgetikov v žilo, čemur sledi čim hitrejši prehod na peroralni vnos opiatnih analgetikov. Multimodalni pristop z dodatkom neopiatnih analgetikov kot so nesteroidni antirevmatiki, paracetamol ali ketorolak omogoča uporabo manjših odmerkov opiatnih analgetikov. Tak pristop zmanjša stranske učinke opiatnih analgetikov ob učinkoviti analgeziji. Izmed tehnik podraočne analgezije sta v literaturi najpogosteje opisana torakalna epiduralna analgezija in vbrizganje morfina v subarahnoidni prostor. Obe tehniki lahko izboljšata kvaliteto analgezije in morda zmanjšata pogostost zapletov s strani dihal in pogostost ishemije srčne mišice, vendar sta povezana z morebitnim povečanim tveganjem za razvoj epiduralnega hematoma zaradi uporabe visokih odmerkov heparina med operacijo. Nove področne tehnike, kot so infuzija lokalnega anestetika s pomočjo katetra v okolico operacijske rane so obetavne vendar v literaturi še niso zadostno ovrednotene. Literatura 1. Konstantatos A, Silvers AJ, Myles PS. Analgesia best practice after cardiac surgery. Anesthesiol Clin 2008; 26 (3): 591-602. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
94
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
2. Mueller XM, Tinguely F, Tevaearai HT, Revelly JP, Chioléro R, von Segesser LK. Pain location, distribution, and intensity after cardiac surgery. Chest 2000; 118 (2): 391-6. 3. Bainbridge D, Martin JE, Cheng DC. Patient-controlled versus nurse-controlled analgesia after cardiac surgery-a meta-analysis. Can J Anaesth 2006; 53 (5): 492-9. 4. Pettersson PH, Lindskog EA, Owall A. Patient-controlled versus nurse-controlled pain treatment after coronary artery bypass surgery. Acta Anaesthesiol Scand 2000; 44 (1): 43-7. 5. Gust R, Pecher S, Gust A, Hoffmann V, Böhrer H, Martin E. Effect of patient-controlled analgesia on pulmonary complications after coronary artery bypass grafting. Crit Care Med 1999; 27 (10): 2218-23. 6. Krishnan K, Elliot SC, Berridge JC, Mallick A. Remifentanil patient-controlled analgesia following cardiac surgery. Acta Anaesthesiol Scand 2005; 49 (6): 876-9. 7. Baltali S, Turkoz A, Bozdogan N, Demirturk OS, Baltali M, Turkoz R, Arslan G. The efficacy of intravenous patient-controlled remifentanil versus morphine anesthesia after coronary artery surgery. J Cardiothorac Vasc Anesth 2009; 23 (2): 170-4. 8. Reimer-Kent J. From theory to practice: preventing pain after cardiac surgery. Am J Crit Care 2003; 12 (2): 13643. 9. Tramèr MR, Williams JE, Carroll D, Wiffen PJ, Moore RA, McQuay HJ. Comparing analgesic efficacy of nonsteroidal anti-inflammatory drugs given by different routes in acute and chronic pain: a qualitative systematic review. Acta Anaesthesiol Scand 1998; 42 (1): 71-9. 10. Kulik A, Ruel M, Bourke ME, Sawyer L, Penning J, Nathan HJ, Mesana TG, Bédard P. Postoperative naproxen after coronary artery bypass surgery: a double-blind randomized controlled trial. Eur J Cardiothorac Surg 2004; 26 (4): 694-700. 11. Rapanos T, Murphy P, Szalai JP, Burlacoff L, Lam-McCulloch J, Kay J. Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgery. Can J Anaesth 1999; 46 (8): 725-30. 12. Fayaz MK, Abel RJ, Pugh SC, Hall JE, Djaiani G, Mecklenburgh JS. Opioid-sparing effects of diclofenac and paracetamol lead to improved outcomes after cardiac surgery. J Cardiothorac Vasc Anesth 2004; 18 (6): 742-7. 13. Griffin M. Con: nonsteroidal anti-inflammatory drugs should not be routinely administered for postoperative analgesia after cardiac surgery. J Cardiothorac Vasc Anesth 2000; 14 (6): 735-8. 14. Bainbridge D, Cheng DC, Martin JE, Novick R; Evidence-Based Perioperative Clinical Outcomes Research (EPiCOR) Group. NSAID-analgesia, pain control and morbidity in cardiothoracic surgery. Can J Anaesth 2006; 53 (1): 46-59. 15. Nussmeier NA, Whelton AA, Brown MT, Langford RM, Hoeft A, Parlow JL, Boyce SW, Verburg KM. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005; 352 (11): 1081-91. 16. Ogus H, Selimoglu O, Basaran M, Ozcelebi C, Ugurlucan M, Sayin OA, Kafali E, Ogus TN. Effects of intrapleural analgesia on pulmonary function and postoperative pain in patients with chronic obstructive pulmonary disease undergoing coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2007; 21 (6): 816-9. 17. Koukis I, Argiriou M, Dimakopoulou A, Panagiotakopoulos V, Theakos N, Charitos C. Use of continuous subcutaneous anesthetic infusion in cardiac surgical patients after median sternotomy. J Cardiothorac Surg 2008; 3: 2. 18. Liu SS, Block BM, Wu CL. Effects of perioperative central neuraxial analgesia on outcome after coronary artery bypass surgery: a meta-analysis. Anesthesiology 2004; 101 (1): 153-61. 19. Djaiani G, Fedorko L, Beattie WS. Regional anesthesia in cardiac surgery: a friend or a foe? Semin Cardiothorac Vasc Anesth 2005; 9 (1): 87-104. 20. Ho AM, Chung DC, Joynt GM. Neuraxial blockade and hematoma in cardiac surgery: estimating the risk of a rare adverse event that has not (yet) occurred. Chest 2000; 117 (2): 551-5. 21. Royse CF. High thoracic epidural anaesthesia for cardiac surgery. Curr Opin Anaesthesiol 2009; 22 (1): 84-7. 22. Meylan N, Elia N, Lysakowski C, Tramèr MR. Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: meta-analysis of randomized trials. Br J Anaesth 2009; 102 (2): 156-67. 23. Richardson L, Dunning J, Hunter S. Is intrathecal morphine of benefit to patients undergoing cardiac surgery. Interact Cardiovasc Thorac Surg 2009; 8 (1): 117-22.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
95
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
NAČELA LAJŠANJA POOPERACIJSKE BOLEČINE PO VELIKIH TREBUŠNIH ONKOLOŠKIH OPERACIJAH MODES OF POSTOPERATIVE ANALGESIA AFTER MAJOR ABDOMINAL ONCOLOGICAL SURGERY Ksenija Mahkovic-Hergouth Onkološki inštitut, Ljubljana
Izvleček. V prispevku razpravljamo o načinih in prednostih lajšanja bolečine po obsežnih operacijah v trebuhu zaradi maligne bolezni, ki sprožijo sistemski vnetni odgovor na operacijo in izrazito bolečino. Najbolj razširjena sta predvsem dva načina lajšanja bolečine, in sicer torakalna epiduralna analgezija, ki temelji na lokalnih anestetikih, in intravenska analgezija, ki temelji na opioidih. Pri obeh načinih je uveljavljena možnost dodatnih odmerkov po izbiri bolnika samega: PC(E)A – patient controlled (epidural) analgesia. Torakalna epiduralna analgezija blokira tudi simpatično nitje za trebušne organe in poleg bolečine zmanjša zavoro peristaltike ter ima še druge ugodne fiziološke učinke. Kljub ugotovljenim prednostim epiduralne analgezije in njenim ugodnim učinkom na nekatere parametre okrevanja doslej še niso ugotovili pomembnih razlik med obema načinoma lajšanja bolečine glede obolevnosti in preživetja po operaciji. Abstract. We discuss the modes of postoperative analgesia after major abdominal surgery due to malignancy. Besides systemic inflammatory response there is also strong pain after such a procedure. There are two most widely used ways of postoperative analgesia: thoracic epidural analgesia based on local anaesthetics and intravenous analgesia based on opioids. Both are most efficient as patient controlled (epidural) analgesia - PC(E)A technique. Thoracic epidural analgesia has many positive physiologic effects and also reduces negative influence of sympathetic system on bowel motility by blocking sympathetic fibres. Despite some known advantages of epidural analgesia in postoperative recovery there are no significant differences between intravenous and epidural postoperative analgesia in major morbidity and mortality after abdominal surgery.
Uvod Obsežne onkološke operacije so pogosto operacije v prsni oz. trebušni votlini zaradi karcinomov ali drugih malignih tumorjev. Povezane so s pooperacijskim sistemskim vnetnim odzivom telesa na operacijski stres in z močno pooperacijsko bolečino.1,2 V prispevku bomo obravnavali lajšanje pooperacijske bolečine po obsežnih onkoloških operacijah v trebušni votlini. Sistemski vnetni odziv in pooperacijska bolečina sta praviloma bolj izražena po operacijah v trebušni votlini kot po operacijah v prsni votlini.3 Pooperacijska bolečina po operacijah v trebuhu Po operaciji v trebušni votlini nastane pooperacijska bolečina, ki je posledica somatske bolečine zaradi prizadetih dermatomov pri laparatomijski rani in visceralne bolečine, ki izhaja iz reseciranih ali poškodovanih visceralnih organov med operacijo. Jakost bolečine je gotovo deloma pogojena tudi z dedno zasnovo bolnika, med drugim z variabilnostjo gena OPRM1.4 Poleg somatskih živcev je pri bolečini po trebušni operaciji udeležen še avtonomni živčni sistem, predvsem simpatično nitje, ki prenaša bolečinske impulze iz trebušnih organov v prsne segmente hrbtenjače. Celotno bolečino (somatsko in visceralno) lahko uspešno lajšamo z ustreznimi odmerki opioidnih analgetikov ali pa s prevodno analgezijo po epiduralnem katetru, ki ima poleg lajšanja bolečine v pooperacijskem obdobju še druge ugodne učinke.5–8 1. Intravenska opioidna analgezija je dovajanje opioidnih učinkovin v žilo bodisi kontinuirano, ali pa, ob neprekinjeni bazični infuziji, še z dodatnim določenim odmerkom po potrebi (patient controlled analgesia – PCA). Po velikih abdominalnih operacijah uporabljamo bodisi morfin, piritramid ali sufentanil v odmerkih: morfin 30 - 60 mg/24 h, piritramid 30–60 mg/ 24 h, sufentanil 50–150 μg/24 h in pripadajoče rešilne odmerke. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
96
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
2. Kontinuirana epiduralna analgezija za lajšanje pooperacijske bolečine po velikih abdominalnih operacijah je v današnjem času in tudi v naši vsakdanji praksi na Onkološkem inštitutu standardni način pooperacijske analgezije z možnim dodatnim odmerkom po potrebi (patient controlled epidural analgesia - PCEA). V kontinuirani epiduralni infuziji uporabljamo bodisi 0,20–0,25-odstotni bupivacain ali pa levobupivacain v enaki koncentraciji, hitrost infuzije 3–6 ml/h. Rešilni odmerki so 3–5 ml, interval do ponovnega odmerka je 30–60 min. Samo v posameznih primerih je tej mešanici treba dodati opioidni analgetik (morfin 4 mg/100 ml lokalnega anestetika ali sufentanil 25 μg/ 100 ml lokalnega anestetika). Epiduralni kateter za abdominalne operacije je treba uvesti v torakalnem predelu hrbtenice med Th 7 in Th 12 glede na mesto operacije v trebuhu. Poleg analgetičnega učinka ima epiduralna analgezija še druge ugodne fiziološke učinke, kot so: zmanjšanje porabe kisika v srcu, ugoden vpliv na respiratorno funkcijo, zaviranje simpatične aktivnosti v splanhničnem področju, izboljšanje prekrvitve prebavil ter izboljšanje peristaltike.9 Za učinkovito analgezijo je pomemben odmerek lokalnega anestetika (LA) oz. celokupna doza LA, kar dosežemo bodisi z večjim volumnom nižje koncentracije ali večjo koncentracijo in manjšim volumnom LA.10 V nedavni študiji so primerjali učinke 3,3 ml 0,15-odstotnega levobupivacaina z 1 ml 0,5-odstotnega levobupivacaina – torej enkratni odmerek 5 mg – in med skupinama ni bilo razlik v analgeziji kot tudi ne v neželenih učinkih.11 3. Periferno delujoči analgetik. Tako opioidno intravensko kot epiduralno lajšanje bolečine dopolnjujemo z metamizolom, nesteroidnim antirevmatikom, ali paracetamolom. 4. Infuzija lokalnega anestetika v operacijsko rano. Z razvojem tehnologije katetrov za namestitev v rano, ki imajo več drobnih odprtin za enakomerno pronicanje LA vzdolž katetra, je možno uspešno lajšanje pooperacijske bolečine v trebuhu tudi z dovajanjem LA neposredno v rano. Kateter je povezan z elastomersko bučko, ki je rezervoar LA in ga hkrati potiska po katetru. Pri abdominalnih operacijah je ta način preizkušen in uspešen za nekatere ginekološke operacije, npr. histerektomije. Infuzija LA nad abdominalno fascijo je učinkovitejša kot pod fascijo.12 V več študijah in metaanalizah ugotavljajo, da ima po abdominalnih operacijah torakalna epiduralna analgezija nekatere prednosti pred intravensko, in sicer večjo učinkovitost (zlasti pri gibanju), manj zapletov s strani dihal in obtočil ter hitrejšo rehabilitacijo zlasti starejših bolnikov.13–15 V študiji primerov 70 starejših bolnikov so ugotovili, da je PCEA glede lajšanja bolečine učinkovitejša kot intravenska PCA z opioidi, v epiduralni skupini pa so bili bolniki tudi manj zmedeni in so imeli boljše delovanje črevesja.16. Kljub temu pa metaanalize analgezije po abdominalnih operacijah doslej še niso pokazale, da se preživetje po epiduralni analgeziji pomembno razlikuje od preživetja po intravenski analgeziji.17 Zaključek Uspešno analgezijo po operacijah v trebuhu je mogoče doseči tako s kontinuirano intravensko infuzijo opioidnega analgetika (morfij/ piritramid/ sufentanil) kot s kontinuirano epiduralno infuzijo LA dodatkom opioidnega analgetika ali brez njega ter tudi z infuzijo LA v rano. V vseh primerih je treba izbiro načina prilagoditi operacijskemu posegu, dati dovolj velike odmerke analgetikov, jih titrirati glede na bolnikovo bolečino in bolniku omogočiti možnost rešilnih odmerkov. Za uspešno lajšanje bolečine pa je temeljnega pomena redno monitoriranje bolečine, npr. z vizualno analogno skalo do 10 točk (VAS). Literatura 1. Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000; 85 (1): 109-17. 2. Ahlers O, Nachtigall I, Lenze J, Goldmann A, Schulte E, Hohne C, et al. Intraoperative thoracic epidural anaesthesia attenuates stress-induced immunosuppression in patients undergoing major abdominal surgery. Br J Anaesth 2008; 101 (6): 781-7. 3. Sun X, Iles M, Weissman C. Physiologic variables and fluid resuscitation in the postoperative intensive care unit patient. Critical Care medicine 1993; 21: 555-61.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
97
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
4. Hayashida M, Nagashima M, Satoh Y, Katoh R. Tagami M. Ide S, et al. Analgesic requirements after major abdominal surgery are associated with OPRM1 gene polymorphism genotype and halotype. Pharmacogenomics 2008; 9 (11): 1605-16. 5. Holte K, Kehlet H. Epidural anaesthesia and analgesia – effects on surgical stress responses and implications for postoperative nutrition. Clin Nutr 2002; 21 (3): 199-206. 6. Kehlet H. Modification of responses to surgery by neural blockade: Clinical implications. In: Cousins MJ, Bridenbaugh PS, eds. Neural blockade in clinical anaesthesia and management of pain. 3rd ed. Philadelphia (PA): Lippincott-Raven; 1998: p. 129-75. 7. Carli F, Holliday D. Modulation of protein metabolism in the surgical patient. Effect of 48-hour continuous epidural block with local anaesthetics on leucin kinetics. Reg Anesth 1996; 21 (5): 430-5. 8. Segawa H, Mori K, Kasai K, Fukata J, Nakao K. The role of the phrenic nerves in stress respose in upper abdominal surgery. Anesth Analg 1996; 82 (6): 1215-24. 9. Clemente A, Carli F. The physiological effects of thoracic epidural anesthesia and analgesia on the cardiovascular, respiratory and gastrointestinal systems. Minerva Anestesiol 2008; 74 (10): 549-63. 10. Dernedde M, Stadler M, Bardiau F, Seidel L, Boogaerts JG. Low vs. high concentration of levobupivacaine for post-operative epidural analgesia: influence of mode of delivery. Acta Anaesthesiol Scand 2006; 50 (5): 613-21. 11. Dernedde M, Stadler M, Taviaux N, Boogaerts JG. Postoperative patient-controlled thoracic epidural analgesia: importance of dose compared to volume or concentration. Anaesth Intensive Care 2008; 36 (6): 814-21. 12. Hafizoglu MC, Katircioglu K, Ozkalkanli MY, Savaci S. Bupivacaine infusion above or below the fascia for postoperative pain treatment after abdominal hysterectomy. Anesth Analg 2008; 107 (6): 2068-72. 13. Nishimori M, Ballantyne JC, Low JH. Epidural pain relief versus systemic opioid-based pain relief for abdominal aortic surgery. Cochrane Database Syst Rew 2006; 3: CD 005059. 14. Popping DM, Elia N, Marret E, Remy C, Tramer MR. Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic surgery: a meta-analysis. Arch Surg 2008; 143 (10): 990-9. 15. Saeki H, Ishimura H, Kitagawa D, Kitagawa D, Tanaka J, Maruyama R, et al. Postoperative management using intensive patient-controlled analgesia and early rehabilitation after an esophagectomy. Surg Today 2009; 39 (6): 476-80. 16. Mann C, Pouzeratte Y, Boccara G, Peccoux C, Vergne C, Brunat G, et al. Comparison of intravenous or epidural patient-controlled analgesia in the elderly after major abdominal surgery. Anesthesiology 2000; 92 (2): 433-41. 17. Werawatganon T, Charuluxanun S. Patient controlled intravenous opioid analgesia versus continuous epidural analgesia for pain after intra-abdominal surgery. Cochrane Database Syst Rev 2005; 25 (1): CD004088.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
98
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
VPLIV POOPERACIJSKEGA ZDRAVLJENJA BOLEČINE NA IZID KIRURŠKEGA POSEGA EFFECT OF POSTOPERATIVE PAIN THERAPY ON SURGICAL OUTCOME Višnja Majerić-Kogler1, Danijela Bandić1, Jana Kogler2, Vilka Bekavac-Mišak1, Sanja Sakan1 1
Department for Anaesthesiology, Reanimatology and Intensive Care, Zagreb University Hospital Centre, Zagreb Rebro, Zagreb, Croatia 2 Department for Anaesthesiology and Intensive Care «Jordanovac», University Hospital for Chest Diseases, Zagreb, Croatia Abstract. Although efficient treatment of post-surgical pain is considered to be a pre-condition for a normal course of post surgical period, epidemiological and clinical researches show that still a significant number of patients suffer strong pain after major surgery. Intense nociceptive somatic and visceral post-surgical pain has in the last ten years been considered the most important of development of endocrine and neurohumoral disorders in the immediate post-surgical period, the vital organs functions disorders, occurrence of serious postoperative complications and prolonged hospitalisation. The effects of a successful perioperative analgesia on the course and outcome of surgical patients remain disputable, particularly because there is no consensus on the optimal procedure specific pain therapy. The multimodal analgesia (defined as use of NSAIDs, COX-2 inhibitors or paracetamol in combination with i.v. opioid PCA ) results in an opioid sparing effect, but this opioid reduction does not consistently result in decreased opioid side effects. The overall negative outcome effects by i.v. opioids PCA correspond well with minor effects on postoperative dynamic pain, stress response and organ dysfunctions. At present the entire role of perioperative epidural technique on patient outcome is unclear. Beside that the advantages of epidural analgesia have to be balanced against their risk and cost. The concept of multi-modal analgesia is an area of most importance and where future research efforts should focus on the combination of several techniques, such as continuous peripheral nerve-blocks, continuous wound-infusion of local anaesthetics, NSAIDs/COX-2 inhibitors, paracetamol, a-2 agonists, ketamine, dextromethorphane, gabapentin/pregabalin, glucocorticoids etc.
Introduction Intense nociceptive somatic and visceral post-surgical pain has in the last ten years been considered the most important of development of endocrine and neurohumoral disorders in the immediate post-surgical period. That period is therefore characterized by increased catabolism, increased secretion of stress hormones, increased burdening of cardiovascular system, lung function disorder, occurrence of hypercoagulability, fybrinolysis decline, immunological suppression, paralytic ileus and post-surgical nausea and vomiting. A disorder of glucose homeostasis and lipid and protein metabolism is the consequence of the above mentioned events.1 Intensity and duration of the stated disorders depend on the intensity of surgical injury, on efficient treatment of post-surgical pain and the application of a number of measures leading to fast rehabilitation of the patients. The occurrence of central and peripheral sensitization and the development of a chronic pain syndrome are a particular problem of insufficiently efficient suppression of the dynamic and static pain in surgeries performed on thorax in the upper abdomen. The frequency of chronic post-surgical pain occurrence with significant influence on the patient¢ s life quality is high and affects up to 40% of the patients.2 There is scientific evidence proving that immunological system, connected to the nervous system by cytokines and opioid pepsins, also participates in forming painful sensation. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
99
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
During peripheral sensitization, immunological cells release pro-inflammatory cytokines TNF, IL6 and IL8, which lead to additional stimuli of the nociceptors and have the same analgesic effect.3 A number of clinical researches in recent years have confirmed better efficiency of the epidural analgesia in suppressing stress response and treating dynamic pain, but so far there is no scientific evidence on the favourable effect of the epidural analgesia on the length of treatment, reduction of the vitally threatening complications and the overall treatment results. The main cause of it lies in insufficient understanding and use of principles of multimodal balanced analgesia and adjusting the medicines and doses to patients on individual basis. Apart from the above mentioned, special emphasis lies on the fact that analgesic system must be optimally integrated in the function of complete procedures of post-surgical treatment and fast rehabilitation («fast track»), which implies applying minimum doses of the opioid analgesics.4 Types of analgesia Acetaminophen and NSAID Acetaminophen (paracetamol) is devoid of anti-inflammatory activity, but is an effective analgesia that has minimal side effects in clinical doses. This drug is the foundation of many analgesic regime and should be used routinely as part of the basic treatment of acute pain. Nonsteroidal anti-inflammatory drugs (NSAID) are also a standard treatment for postoperative pain. Drugs in this group are also very effective but suffer from the drawback of having numerous side-effect profile. These agents may have significant central actions in addition to their recognized peripheral activity.5 Acethaminophen and NSAIDs do not appear to have any effect upon the surgical stress response or upon organ dysfunction. Their main benefit appears to lie in providing moderate pain relief that will reduce opioid requirements by 20–30%.6 Despite the well demonstrated opioid-sparing effects the effects of NSAIDs, specific COX-2 inhibitors and paracetamol on postoperative outcome is debatable. Most previous studies included different types of surgery and a only simple assessment of opioid related side effects as PONV, duration of ileus, sedation etc. Recent studies with a more detailed assessment of opioid related side effects suggest benefits in some procedures as knee surgery and cholecystecomy.5–7 An improved outcome by opioid sparing combination would be in minor or moderate surgery procedures where the stress responses and organ dysfunctions are small. On the basis of evidence from 4 meta analyses and 1 systematic review it appears that multimodal analgesia (defined as use of NSAIDs, COX-2 inhibitors or paracetamol in combination with i.v. opioid PCA) results in an opioid sparing effect, but this opioid reduction does not consistently result in decreased opioid side effects. Based on current literature Rathmell et al concluded that “Despite much rhetoric about combining multiple analgesic technique to provide multimodal analgesia, only limited evidence suggests that this approach will improve pain control or perioperative outcomes.”8 Opioids Opioids are the main method of controlling acute postoperative pain. Morphine its derivates and synthetic compounds are capable of very good pain relief. Despite this, there remain significant number of patients who do not receive adequate pain relief. A reason is also poor understanding of the drugs by patients and medical staff. Clinicians may fail to asses and compensate for interpatient variability, the length of action may be overestimated and the dosage prescribed inadequate. Patient- controlled analgesia (PCA) has been compared to conventional methods in several studies.9 Most studies favour PCA, and the general belief seems to be that patients satisfaction is improved. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
100
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
The effect of PCA on postoperative outcome is debatable since morbidity and hospital stay have not been demonstrated to be improved in randomised trials.10 The overall negative outcome effects by PCA correspond well with minor effects on postoperative dynamic pain, stress response and organ dysfunctions. A meta-analysis of 15 randomized control trials (RTCs) with 787 patients found greater analgesic efficacy with PCA without increase in side effects. However, the length of hospital stay was not reduced.11 A meta-analysis of 32 RCTs and 2072 patients showed that PCA was associated with analgesia and reduced risk of pulmonary complications.12 Regional analgesic tehniques Epidural anaesthesia and analgesia As afferent neural stimuli and activation of the autonomic nervous system by pain may release the endocrine metabolic responses, it has been hypothesised that a reduction in surgical stress responses (endocrine, metabolic and inflammatory) will lead to a reduced incidence of postoperative organ dysfunction and to an improved surgical outcome. Regional continuous techniques with local anaesthetic may lead to a substantial reduction in the surgical stress response.13 The studies investigating lower extremity surgery have shown continuous lumbar epidural local anaesthetic techniques to be most effective, probably because of a more effective afferent blocade.14 A systematic overview of the available randomised controlled trials – 141 with more than 10000 patients over the 30 years – showed that the use of the epidural and spinal block resulted in a statistically and clinically significant reduction in morbidity and mortality after surgery. Furthermore, perioperative anaesthesia and analgesia decreased the risk of deep venous thrombosis, pulmonary embolism and pneumonia by 39–55%.15 The effect of postoperative epidural analgesia on the incidence of myocardial ischemia or infarction in controlled trials has shown that the use of thoracic, but not lumbar, epidural analgesia significantly decreases the incidence of postoperative myocardial infarction.16 Kehlet 1997 has also provided evidence that continuous thoracic epidural local anaesthetic techniques reduce postoperative paralytic ileus. It is important to emphasise that location of the catheter tip and choice of analgesia drug can independently influence postoperative morbidity. A review of randomized and observational studies showed that when epidural catheter tip correspond to the dermatomes of surgical incision, earlier return of gastrointestinal function.17 However, several recent large randomized controlled trials have failed to show any major advantages of perioperative epidural technique.18, 19 In the study of 915 patients identified as high risk patients undergoing major abdominal surgery, Rigg et al. concluded that the most adverse morbid outcomes are not reduced by use of combined epidural and general anaesthesia and postoperative epidural analgesia, but the improvement in analgesia, reduction in respiratory failure, and low risk of serious adverse consequences suggest that many high-risk patients undergoing major intra-abdominal surgery will receive substantial benefit from combined general and epidural anaesthesia intraoperatively with continuing postoperative epidural analgesia. Epidural opioid techniques are less effective on the stress response, and are comparable with systemic opioid techniques and the use of NSAIDs. High-dose opioid anaesthesia suppresses intra- but not postoperative stress responses.13 On the basis of evidence from 7 meta-analyses and 3 large randomized trials the investigators concluded that there is a beneficial effect of epidural anaesthesia and analgesia in terms of some measures of cardiac and pulmonary function and evidence of superior analgesic efficacy, but a reduction in duration of hospital stay was not observed. At present the entire role of perioperative epidural technique on patient outcome is unclear. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
101
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Beside that the advantages of epidural analgesia have to be balanced against their risk and cost. The regional catheter techniques The use of regional perineural anaesthetic techniques for any suitable surgery may offer many advantages. Patients can be discharged early with effective pain control, the requirement for opioids will be reduced, and the side effects associated with the use of these agents such as nausea, vomiting, sedation and pruritus will be reduced.20 There is even evidence that long-term outcome can be influenced positively by the use of regional anaesthetic technique for a short time postoperatively.21 However, there are no randomized control studies addressed effects of these techniques on major morbidity and mortality. Beside that the general applicability of perineural catheter techniques is uncertain because of the required level of technical skill and infrastructure to manage the catheters. In a recent controlled comparison of perfusion of local anaesthetic through an incisional catheter and more invasive epidural technique the same analgesic effect was demonstrated. A metaanalysis of 45 randomized controlled studies with 203 patients of continuous wound catheter technique for postoperative analgesia showed reduced pain scores (32%) and opioids consumption (25%), decreased risk of postoperative nausea and vomiting and 30% increase in patients satisfaction in 5 studies of abdominal surgery, 13 studies of cardiothoracic surgery, 6 studies of gynaecologic surgery, 12 studies of orthopaedic surgery.22 There was for limited number of patients a one day reduction of hospitalization.23 Perioperative analgesia and CPSP Poorly managed pain can slow recovery and create burdens for patients and their families. Though various risk factors have been suggested, has been associated with development of chronic postoperative pain. The most striking predictive post-operative factor for acute pain chronification is the severity of acute pain after breast surgery, thoracic surgery and hernia repair. The link between early post-operative pain and chronic pain does not necessarily imply causality but is nonetheless interesting and deserves further investigation. Kawamata et al24 subjected volunteers to a small incision in the volar forearm and then mapped the area of hyperalgesia outside of the injured area. It is one measure of enhanced responsiveness of the CNS, i.e. central sensitisation. It was noted that the area of flare or redness (possibly the result of axon reflexes) caused by incision was distinct from the area of hyperalgesia. The large area of hyperalgesia did not develop when a local anaesthetic injection was given before the incision. De Kock et al25 demonstrated that reducing the area of hyperalgesia after colectomy did not greatly reduce acute pain, but was associated with a decrease in the number of patients who developed residual pain as late as six months after colectomy. Therefore, the area of hyperalgesia – one measure of central sensitisation – could perhaps predict patients likely to develop persistent pain after surgery. Several studies suggest that effective treatment of acute pain after surgery can reduce the incidence of CPSP. It seems that the specific modality of pain relief is not as important as the degree of analgesia achieved. Prospective randomised studies are needed to determine how different pain management strategies influence the incidence of CPSP. Future strategies If persistent pain after surgery results from sensitisation, prevention may be possible if sensitisation can be blocked.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
102
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Pre-emptive analgesia If the trigger signal is prevented from gaining access to the CNS, pain would be diminished, and treatment aimed at reducing nay enhanced excitability within the CNS initiated by trigger would reduce hyperalgesia and allodynia. Thus, the concept of pre-emptive analgesia for post-operative pain was developed. Two methods are available for preventing central sensitisation: conduction blocade with local anaesthetics and suppression of the excitability of the nervous system before it receives the nociceptive input. Many trials evaluating preemptive analgesia have been conducted in patients undergoing elective surgery, but the results have been inconclusive. Multimodal analgesia Pre-emptive multimodal analgesia not only improves short-term recovery, but may theoretically prevent chronic post-surgical pain by preventing suprasensitisation of the CNS irrespective of the surgical injury. Pre-operative opiates and non-steroidal anti-inflammatory drugs (NSAIDs), preincisional regional block or epidural, together with NSAIDs, have been promoted as the ideal combination for near total analgesia following thoracotomy. Multimodal fast-track rehabilitation and outcome The concept of multi-modal analgesia is area of most importance and where future research efforts should focus on the combination of several techniques such as continuous peripheral nerve-blocks, continuous wound-infusion of local anaesthetics, NSAIDs/COX-2 inhibitors, paracetamol, a-2 agonists, ketamine, dextromethorphane, gabapentin/pregabalin, glucocorticoids etc. Each medication and technique component already has been demonstrated to provide analgesia and opioid sparing, but multiple combinations to enhance analgesia, reduce stress response and dynamic pain and prevent chronic pain are required.26–28 The concept of a multimodal postoperative rehabilitation programme in which pain relief is a key factor is a major task for the future. References 1. Kehlet H, Holte K. Effect of postoperative analgesia on surgical outcome. Br J Anaesth 2002; 87: 62-72. 2. Kehlet H. The role of the anaesthesiologist and perioperative pain management Refresher Course Lectures Euroanaesthesia Munich 2007; 153-5. 3. Kehlet H. Surgical stress and outcome-from here to where. Reg Anesth Pain Med 2006; 131: 47-52. 4. Kehlet H. Acute pain control and accelerated postoperative surgical recovery. Surg Clin N Am 1999; 79: 431-45. 5. Mc Comrack K. Non steroidal anti-inflamatory drugs and spinal nociceptive processing. Pain 1994; 59: 9-43. 6. Power I, Barratt H. Analgesic agents and postoperative period. Nonopioids. Surg Clin N Am 1999; 79: 275-95. 7. Rawal N. Analgesia for day case surgery. Br J Anaesth 2001; 87: 73-87. 8. Rahtmell JP, Wu CL, Sinatra RS, Ballantyne JC, Ginsberg B, Gordon DB, et al. Acute post-surgical pain management: A critical appraisal of current practice. Reg Anesth Pain Med 2006; 31: 1-42. 9. Macintyre PE. Pain in elderly. In: Rowbotham DJ, Macintyre PE, eds. Clinical Pain Management: Acute Pain. London: Arnold; 2006. 10. Walder B, Schafer M, Henzi I, Tramer MR. Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. A quantitative systematic review. Acta Anaesthesiol Scand 2001; 45: 795-804. 11. Ballantyne JC, Car DB, Chalmers TC, Dear KB, Angelillo IF, Mosteller F. Postoperative patient-controlled analgesia: Meta analysis of initial randomized control trial. J Clin Anesth 1993; 5: 182-93. 12. Kehlet H. Postoperative opioid sparing to improve outcome – what are the issues. Anesthesiology 2005; 102: 1083-85. 13. Kehlet H. Modification of responses to surgery by neural blocade: Clinical implications. In: Cousins MJ, Bridenbaugh, eds. Neural blocade in clinical anesthesia and management of pain. 3rd ed. Philadelphia: Lippnocott-Raven, 1998; p.129-71. 14. Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg2002; 183: 630-41. 15. Rodgers A, Walker N, Schug S, McKee A, Kehlet H, van Zundert A, et al. Reduction of postoperative mortality and morbidity with epidural and spinal anesthesia: Results from overwiev of randomised trials. BMJ 2000; 321: 1493-7. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
103
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
16. Beattie WS, Badner NH, Choi P. Epidural analgesia reduces postoperative myocardial infarction. A metaanaliysis. Anesth Analg 2001; 93: 598-612. 17. Hodgson PS, Liu SS. Thoracic epidural anaesthesia and analgesia for abdominal surgery: Effects on gastrointestinal function and perfusion. Ballier’s Clin Anaesthesiol 1999; 13: 9-22. 18. Rigg JR, Jambrozik K, Myles PS. Epidural anesthesia and analgesia and outcome of major surgery: A randomised trial. Lancet 2002; 359: 1276-82. 19. Park WY, Thompson JS, Lee KK. Effects of epidural anesthesia and analgesia on perioperative outcome: A randomized controlled Veterans Affairs cooperative study. An Surg 2001; 234: 560-9. 20. Rawal N. Postoperative analgesia and patient outcome. Refresher Course Lectures Euroanaesthesia Munich, 2007; 157-9. 21. Capedvila X, Barthelet Y, Biboulet P, Ryckwaert Y, Rubenovitch J; D'athis F. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999; 91: 8-15. 22. Ranta PO, Ala-Kokko JE, Kukkonen PP, Ohtonen PP, Raudaskoski TH, Reponen PK, et al. Incisional and epidural analgesia after caesarean delivery: A prospective, placebo-controlled, randomised clinical study. Int J Obstetric Anesthesia 2006; 15: 189-94. 1. Richman JM, Liu SS, Courpas G, Gong R, Rowlingson AJ, McGready J, et al. Does continuous peripheral nerve block provide superior pain control to opioids? A meta- analysis. Anesth Analg 2006; 102: 248-57. 2. Kawamata M, Watanabe H, Nishikawa K. Different mechanisms of development and maintenance of experimental incision-induced hyperalgesia in human skin. Anesthesiology 2002; 97: 550-9. 3. De Kock M, Lavandhomme P, Waterloos H. Balanced analgesia in perioperative period. Is there a place for ketamine? Pain 2001; 92: 373-80. 4. Ho KY, Gan TJ, Habib HS. Gabapentin in postoperative pain – a systematic review of randomized controlled trials. Pain 2006; 126: 91-101. 5. Holte K, Kehlet H. Perioperative single-dose glucocorticoid administration: Pathophysiologic effects and clinical implications. J Am Coll Surg 2002; 195: 694-712. 6. Procedure-specific postoperative pain relief (www.postoppain.org).
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
104
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
TAP-BLOK – BLOKADA TRANSVERZALNE ABDOMINALNE PLANOTE TAP BLOCK – TRANSVERSAL ABDOMINAL BLOCK Aleksandar Bilić Splošna bolnišnica Slovenj Gradec
Uvod: TAP-blok (Tranversal abdominal plain block) je blokada, ki sodi v skupino blokad abdominalnih regij. Vuporabi je od leta 2001 (Rafi A.N. Galway, Irska). Anatomski pristop je iz trianguluma Petit. V osnovi gre za blokado ileoingvinalnega in ileohipogastričnega živca. Bolniki in metode: V Splošni bolnišnici Slovenj Gradec smo metodo preizkušali na bolnikih za operacijo ingvinalne hernije. Skupino 20 bolnikov operiranih zaradi ingvinalne hernije smo analgezirali s TAP-blokom. Opustili smo primere, kjer je bila narejena nenapetostna hernioplastika, ker smo opazili, da v takšnih primerih večjih bolečin ni. Cilj nam je bila primerjava klasične postoperacijske anestezije in TAP-bloka. Predpostavka, da bo v skupini s TAP-blokom uporaba opiatnih analgetikov manjša. Za blokado smo uporabljali lokalni anestetik Chirocaine 0,25 % v odmerku 20 ml. Za ocenjevanje bolečine smo uporabili lestvico VAS, na 6 ur, 12 ur in 24 ur po operaciji. Zapisovali smo tudi čas aplikacije analgetika. V primerjalni skupini so bili bolniki, ki niso prejeli TAP-bloka in so se zdravili s klasično protibolečinsko terapijo – Analgin 2,5 g iv/12 h + Dipidolor 15 mg im/8 h. Metoda blokade. Z epiduralno iglo G18 vstopimo skozi triangulum Petit pod kotom 90 stopinj. Ko z iglo prehajamo skozi fascijo mišice obliquus externus začutimo jasen pok. Z iglo napredujemo, dokler se pok ne ponovi, ko prebijemo še fascijo mišice internus obliquus. Aspiriramo in ob negativni aspiraciji damo lokalni anestetik. Rezultati: Narejenih je bilo 20 blokad, 8 bolnikov je potrebovalo Dipidolor in Analgin. Zaradi velike verjetnosti, da je bil pri navedenih bolnikih anestetik vbrizgan na napačno mesto, predvidevamo, da bi blokada bila še učinkovitejša, če bi jo dali ob ultrasonografski pomoči. Trajanje blokade je bilo do 24 ur, kar bi bilo možno razložiti s počasno resorpcijo lokalnega anestetika v interfascijalnem prostoru. Zaenkrat se je TAP-blok pokazal kot koristen za lajšanje pooperacijske bolečine. Uporaba opiatnih analgetikov je bila bistveno manjša v skupini, ki je blok dobila, izognili smo se zapletom opiatnih analgetikov in počutje bolnikov je bilo boljše. Razpravljanje: Zapletov ni bilo. Zaradi uporabe tope epiduralne igle je majhna možnost perforacije votlega organa, še posebej ob uporabi ultrasonografskega nadzora. Če bi prebili žilo, bi ob hemoragični diatezi lahko nastal intermuskularni ali subfascijski hematom. Nezadostna analgezija se pojavi zaradi vbrizganja anestetika preplitvo, ali pregloboko – v abdominalno votlino.TAP-blok je težje izvedljiv pri debelih. Zaključek: TAP (Transversal Abdominal Plain block – blokada transverzalnega abdominalnega polja) se je pokazala kot uspešna za zdravljenje bolečine. Za še boljši uspeh priporočam uporabo ultrasonografije pri izvedbi blokade. Prednost blokade pred klasično analgezijo je, da zmanjša potrebo po opiatnih analgetikih. Literatura 1. Rafi AN.Abdominal field block: a new approach via the lumbar triangle. Anaesthesia 2001; 56 (10): 1024-6. 2. McDonnell, J.G.et al.The analgesic efficacy of Transversus abdominis plain block after abdominal surgery:A prospective randomized controlled trial. Anesth Analg 2007; 104: 193-7. 3. Netter FH. Back and spinal cord. In: Netter FH, ed. Atlas of human anatomy summit. New Jersey, USA: The CIBA-Geigy Corporation, 1989: 145-55. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
105
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
DIAGNOSTIKA IN ZDRAVLJENJE FIBROMIALGIJE V SPLOŠNI BOLNIŠNICI DR. FRANCA DERGANCA NOVA GORICA DIAGNOSTICS AND TREATMENT OF FIBROMYALGIA IN GENERAL HOSPITAL DR. FRANC DERGANC NOVA GORICA Nataša Fikfak, Jurij Karapandža, Simon Bitežnik Splošna bolnišnica dr. Franca Derganca Nova Gorica
Fibromialgija je etiopatogenetsko še nepopolnoma pojasnjen kronični bolečinski sindrom z največjo pojavnostjo pri ženah v srednjem starostnem obdobju.Značilna je razpršena bolečina v mišicah in mišično-skeletnih spojih , utrujenost in neosvežujoč spanec.Diagnoza temelji na kliničnem pregledu bolečinskih točk upoštevajoč kriterije American College of Rheumatology iz leta 1990.Zdravljenje je malo uspešno,predvsem pa multidisciplinarno, po merilih z dokazi podprte medicine z zdravili in nefarmakološko. V prispevku prikazujemo obravnavo bolnice s kroničnim bolečinskim sindromom in afektivno motnjo ( depresivna motnja ), diagnostične in terapevtske postopke in izid zdravljenja ali naravni potek bolezni. Bolnica JS, 1962, ki je bila sprva obravnavana v revmatološki ambulanti zaradi bolečin. Z osnovnimi kliničnimi, laboratorijskimi in morfološkimi preiskavami je bila izključena vnetna bolezen veziva in prezgodnja spondiloartroza. Simptomatsko zdravljenje z analgetiki, antirevmatiki in fizioterapijo ni bilo učinkovito. Zaradi izražene depresivne afektivne motnje je bila večkrat obravnavana pri psihiatru in vključena v skupinsko obravnavo z malo uspeha. Dodatna fiziatrična priporočila niso bila učinkovita. V delovno okolje se ni vključevala. Zaradi sočasne anemije in motenj menstrualnega ciklusa je bila obravnavana pri hematologu in ginekologu, ob prebavnih težavah pa pri gastroenterologu. Izključeni so bili organski vzroki obolevnosti. Po romanju v Medjugorje je nastopilo nenadno ozdravljenje. Sedaj živi zdravo normalno življenje brez zdravil. Literatura: 1. Burkham J, Harris ED. Fibromyalgia: A chronic pain syndrome. In: Harris ED, Budd RC, Firestein GS, Genovese MC, eds. Kelley's Textbook of Rheumatology, 7th ed. Elsevier: Philadelphia, 2001: p522-36. 2. Logar D. Sindrom fibromialgije. In: Kos-Golja M, Praprotnik S. Revmatološki priročnik za družinskega zdravnika, 3. izpolnjena izdaja, 2008: p126-34.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
106
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
KOMPLEKSNI REGIONALNI BOLEČINSKI SINDROM TIP 1, ZDRAVLJEN S SUBKUTANO SUHOIGELNO TERAPIJO COMPLEX REGIONAL PAIN SYNDROME (CRPS) TYPE I TREATED BY SUBCUTANEOUS DRY NEEDLING THERAPY Milica Klopčič-Spevak, Helena Jamnik Rehabilitation Institute, Ljubljana, Slovenia
Objective: To show efficiency of subcutaneous dry needling applied to the most painful tender points in CRPS patients. Design: A prospective case study with analysis of pain relief and function changes after dry needling followed by a massage. Method: Structured evaluation of outpatients before and after a 1–6 weeks treatment. Fifteen patients: 8 females, 7 males, 21–67 years of age, mean 51.5. They were at the chronic stage of CRPS lasting from 2 to 6 months. Five of them experienced hand pain and 10 of them foot pain. Interventions: The number of tender points (Tp) treated by dry needling was 2–9, mean 5.4. The number of treatments was 2 to 5, mean 2.2. After the needling, all Tps were covered by plaster and gentle massage was applied on all treated points for 20 minutes. Outcome measure: Tender point pressure algometry and Brief Pain Inventory Cleeland (BPI). Results: Mean pressure pain threshold of typical Tender Point was 1.37 kg/cm2 before and 2.97kg/cm2 at control. The change is significant P = 0.002. BPI maximal, mean and actual pain intensity was lower at the follow up, the change wasstatistically significant (P = 0.0009, 0.017, and 0.001, respectively). Significant improvement was observed in the general activity (P=0.01), mood (P 0.035), normal work limitation (P 0.001), relations with other people (P = 0.01), sleep (P = 0.008) and enjoyment of life (P 0.02). Due to 5 hand involved subjects no significant change was calculated in walking ability. Conclusion: Dry needling therapy can improve local and central sensitization involving sensory, motor and autonomic imbalance. Pain relief and improvement of function was achieved in all 15 consecutive patients suffering from CRPS.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
107
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
POGOSTNOST IN ZDRAVLJENJE KRONIČNE BOLEČINE MED VAROVANCI PATRONAŽNEGA VARSTVA PRAVALENCE AND TREATMENT OF CHRONIC PAIN AMONG NURSING HOME PATIENTS Slavica Lahajnar-Čavlovič Onkološki inštitut Ljubljana, Ljubljana Namen raziskave: ugotoviti, koliko bolnikov v patronažnem varstvu v Sloveniji ima kronično bolečino in kako je ta zdravljena. Metode: 4181 osrbovancem patronažnega varstva po vsej Sloveniji je, na njihovih domovih, v tednu bolečine (v septembru 2006), 420 patronažnih sester razdelilo kratek vprašalnik o bolečini (BPI). Za ocenjevanje primernosti izbranega analgetika, glede na jakost bolečine, smo uporabili indeks zdravljenja bolečine (PMI - pain management index). Za izračun smo upoštevali povprečno bolečino v prejšnjem tednu. Rezultati: Vprašalnik BPI je izpolnilo 1962 bolnikov s kronično bolečino t.j. 47 % anketiranih. Večina je bila starejših od 50 let, 68 % je bila starejših od 70 let in dve tretjini je bilo žensk. 85 % bolnikov je imelo ne-onkološko bolečino. 87 % (1690) bolnikov s kronično bolečino je imelo neobvladano bolečino, VAS štiri ali več in skoraj polovica (42 %) močno bolečino, VAS sedem do deset. Negativen PMI smo izračunali pri 67 % bolnikov z neobvladano bolečino, kar pomeni, da so jemali premalo močan analgetik glede na jakost bolečine (3-stopenjska lestvica zdravljenja bolečine). Bolniki z rakom so imeli manjkrat neobvladano bolečino, večkrat so jemali močne opioide in imeli manjkrat izračunan negativen PMI (31 %) glede na bolnike z ne-onkološko kronično bolečino (73 %). Zaključki: Presenetil nas je velik delež bolnikov z neobvladano in močno bolečino. Negativen PMI, izračunan pri 67 % bolnikov, je pokazatelj neprimernega izbora jakosti analgetika glede na jakost bolečine, predvsem premajhnega predpisovanja močnih opioidov, kar je eden od razlogov za slabo zdravljeno bolečino. Starostnikom se premalokrat predpisujejo močni opioidi, kar je posledica strahu pred neželenimi učinki zdravil v tej starostni skupini in miselnosti, da jih bolniki, ki nimajo raka ne potrebujejo, kljub močni bolečini. Literatura 1. Deandrea S, Montanari M, Moja L, Apolone G. Prevalence of undertreatment in cancer pain. A review of published literature. Ann. Oncol 2008; 19 (12): 1985-91. 2. Smalbrugge M, Jongenelis L, Pot AM, Beekman A, Eefsting J. Pain among nursing home patients in the Netherlands: Prevalence, course, clinical correlates, recognition and analgesic treatment – an observational cohort study. BMC Geriatrics 2007; 7: 3.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
108
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
DIAGNOSTIKA SOMATSKE BOLEČE NEVROPATIJE, MOTNJE TANKIH VLAKEN THE DIAGNOSTICS OF SOMATIC PAINFUL NEUROPATHY, SMALL NERVE FIBRE DISORDER Duška Meh Department for Physical and Rehabilitation Medicine, Faculty of Medicine, University of Ljubljana, and Institute for Rehabilitation, Ljubljana, Slovenia
Background: The disturbed nerve function in symptomatic patients could frequently not be confirmed by conventional electrophysiological tests. The accurate neurophysiological, psychophysical assessment of temperature specific and thermal pain sensations could be helpful in diagnostics and evaluation of patients complaining of neuropathic symptoms. Patients and methods: We studied 759 elderly symptomatic patients, suffering from different neuropathies and consecutively attending our out-patient clinic in the last 10 years. 435 had diabetic and 324 different others neuropathies. The pathological results of nerve conduction studies were exclusion criteria. Results: The neuropathic pain was confirmed by appropriate questionnaires and scales. The thermal specific and thermal pain perception thresholds were assessed by the psychophysical test. The TSA 2001 Thermal Sensory Analyser (Medoc Ltd., Ramat Yishai, Israel) was applied at different sites of the body. Our new protocol for psychophysical assessment of sensory alterations was used. In all symptomatic patients thermal specific and thermal pain sensitivity determination showed quantitative and/or qualitative and/or spatial and/or time / temporal abnormalities, evaluated according to normal values determined in our laboratory. Quantitative changes were found in all patients, and qualitative, spatial and temporal in more advanced disease. The sensitivity of the lower extremity was more frequently impaired as the sensitivity of the upper. Conclusions: A normal result of conventional electrophysiological tests, which rule out the function of large myelinated fibres, does not exclude the presence of peripheral neuropathy. Sensory functions, attributable to unmyelinated and small myelinated nerve fibres, should be examined by the psychophysical somatosensory examination. The new protocol for psychophysical sensory testing established different stages and types of somatic small nerve fibre sensory neuropathy.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
109
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
NOVI PROTOKOL ZA UGOTAVLJANJE MOTENE SOMATOSENZORIKE A NEW PROTOCOL FOR DETERMINATION OF DISTURBED SOMATOSENSORY SENSATION Duška Meh Department for Physical and Rehabilitation Medicine, Faculty of Medicine, University of Ljubljana, and Institute for Rehabilitation, Ljubljana, Slovenia
Objectives: Sensation, the process of accepting the environment, and perception, the process of attaining awareness or understanding of sensory information, elicit the experience, prerequisite for cognitive processing of incoming stimuli. The sensations elicited clinically or psychophysically could be identified by the recognition of the evoked signs. Due to the subjectivity of experience sensory disturbances may be described in different terms. Different categories of sensations have to be defined. Subjects and methods: Perception characteristics were assessed in 2884 persons, 303 volunteers (at 3184 sires) and in 2581 patients (at 13964 sites). Thermal sensations were elicited clinically by thermorollers or psychophysically by thermode. For the assessment of thermal specific and thermal pain sensibility the Medoc (Medoc Ltd., Ramat Yishai, Israel) and SOMEDIC (SOMEDIC AB, Stockholm, Sweden), NeuroSensory Analyzer and Thermotest, respectively, were used. Results: The thermal sensations elicit 4 groups of somatosensory recognition descriptors and signs. The somatosensory sensation is complex information, expressed by 23 clinically revealed recognition symptoms and signs. Psychophysically were determined 30 items. For the clinician use, a list of peripherally and / or centrally induced recognition symptoms and signs was created. Conclusions: Disturbed sensation could be most early, convincingly and realistically assessed by the alternations of perception. It could be functionally tested by clinical and psychophysical evaluation of natural stimuli. Somatosensory sensation changes evoke recognition alternations. Quantitative, qualitative, spatial and time / temporal changes could affect classification and staging of the diseases.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
110
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
KAKO OCENITI IN OVREDNOTIT BOLEČINO HOW TO ASSESS AND EVALUATE PAIN Duška Meh,1 Marko Pišljar2 1
Department for Physical and Rehabilitation Medicine, Faculty of Medicine, University of Ljubljana, and Institute for Rehabilitation, Ljubljana, Slovenia 2 Psychiatric Hospital Idrija, Idrija, Slovenia
Background with subjects, methods and results: The complex pattern of responses, characterizing the perception of pain in conscious brain, is subserved by the wide spectrum of physiologically specialized nervous processes, running from spinal to neocortical or higher central levels. The assessment and evaluation of pain related activity in nervous structures is possible by accurate electrophysiological and functional imaging instruments. But the pain as a complex perceptual phenomenon is more then just the electricity. Influenced by internal and external factors, the perception of pain can be divided into multiple components – including sensory-discriminative, affective-motivational, and cognitive-evaluative dimensions. It is a uniquely personal experience, not necessarily proportional to the physiological process of nociception. Reliance on patients' self report--pain intensity, unpleasantness, or interaction with thoughts and life--is essential. Additionally, pain levels as rated by patients may not agree with ratings made by a physician, another member of the medical team or family. The assessment of perceived sensations, necessary for diagnosis, for choice of treatment, and for the evaluation of treatment efficacy, is based on patient report, clinical assessment, rating scales, questionnaires and. more sophisticated psychophysical instruments and protocols. Conclusions: Pain like a subjective, multidimensional experience, built up by the coordinated activation of diverse structures and processes, is much more then just a somatic sensation, nociceptive activity in pain pathways. A careful assessment of the patient with pain should include categorization of the pain, determination of its aetiology, and consideration of its associated medical, social, emotional and psychological factors. To understand the phenomenon of pain in the broad sense we have to accept it as a conscious phenomenon.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
111
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
VPLIV MIŠIČNE KONTRAKCIJE IN JAKOSTI DRAŽLJAJA NA PARAMETRE TIHE KOŽNE PERIODE INFLUENCE OF THE MUSCLE CONTRACTION AND THE STIMULUS INTENSITY ON PARAMETERS OF THE CUTANEOUS SILENT PERIOD Zoran Rodi,1 Christian Springer2 1
Institute of Clinical Neurophysiology, Division of Neurology, University Medical Centre, Ljubljana, Slovenia 2 Vrije Universiteit Medical Centre, Amsterdam, The Netherlands
Background and Aims: A transient suppression in EMG signal during a muscle contraction in response to a painful electric digital nerve stimulus is known as the cutaneous silent period (CSP). The aim of the study was to explore the influence of muscle activation and stimulus intensity on CSP parameters. Methods: CSP was measured in 15 healthy subjects at 20%, 40% and 60% of maximal voluntary muscle activation and with an electric stimulus of 10, 15 and 20 times sensory threshold. Stimulation was applied at the index finger through ring electrodes, and disposable surface electrodes were used for detection over abductor pollicis muscle. CSP onset and endpoint latencies were determined at the first crossing of the 80% of the baseline to the left and to the right of the lowest CSP point. CSP duration was interval between the onset and the endpoint latencies. Index of suppression was the ratio of the CSP area and the 80 % baseline area. Results: The CSP onset latency was shorter, the duration longer, and the suppression index was greater with the higher stimulus intensity, and were not influenced by the rate voluntary muscle contraction. Conclusion: Our results show that the temporal CSP parameters such as onset, and duration, as well as the index of suppression vary with the intensity of the stimulation, and not with the level of the muscle activation.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
112
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
ANALGEZIJA PO TOTALNI ENDOPROTEZI KOLKA Z LEVIBUPIVAKAINOM PREKO PERIFERNEGA FEMORALNEGA KATETRA V PRIMERJAVI S PIRITRAMIDOM I.V. PCA POSTOPERATIVE ANALGESIA FOLLOWING TOTAL HIP ENDOPROSTHESIS USING A PERIPHERAL FEMORAL CATHETER INFUSION OF 0.125% LEVOBUPIVACAINE VERSUS IV PCA PIRITRAMIDE Majda Šarman, Darija Armentano, Karmen Pišek-Šuta, Vlasta Ekart-Fakin, Verdi Kerimović Oddelek za intenzivno terapijo, nego, anestezijo in terapijo bolečin, Splošna bolnišnica dr. Jožeta Potrča Ptuj, Slovenija
Izhodišče in namen študije: oceniti učinkovitost pooperacijske analgezije po totalni kolčni endoprotezi z uporabo 0,125-odstotnega levobupivakaina preko perifernega femoralnega katetra v kontinuirani infuziji preko elastomerne črpalke v primerjavi z uporabo piritramida IV s črpalko, ki jo bolnik uravnava sam (PCA). Metode: 76 pacientov je po totalni endoprotezi kolka prejemalo analgezijo v obliki kontinuirane infuzije 0,125-odstotnega levobupivakaina preko perifernega femoralnega katetra (skupina levobupivakain, n = 46) ali v obliki infuzije piritramida preko črpalke PCA, ki jo regulira bolnik sam (skupina piritramid PCA, n = 30). Poraba piritramida in dodatne analgezije v 72 urah po randomizaciji, jakost bolečine, pojavnost stranskih učinkov in zadovoljstvo bolnika ob koncu zdravljenja so bili parametri, beleženi s strani neodvisnega opazovalca. Rezultati: Povprečna poraba (± stdev) piritramida v 72 urah je znašala 72,3 mg (± 31,6 mg) v skupini piritramid PCA in 20,7 mg (± 13,5 mg) v skupini levobubivakain (P = 0,000). Kakovost lajšanja bolečine je bila ustrezna (VAS < 3,0) pri obeh skupinah, vendar so bolniki v skupini piritramid PCA po 12 urah po operaciji navajali nižje vrednosti VAS kot skupina levobupivakain, tako ob mirovanju (P = 0,025), kot ob gibanju (P = 0,005). Pojavnost stranskih učinkov, kot so bruhanje in slabost, je bila nekoliko manjša v skupini levobupivakain (17 %) kot v skupini piritramid PCA (30 %), medtem ko je 7 % bolnikov iz skupine levobupivakain opisovalo parestezije v operirani nogi. Zaključek: Rezultati prospektivne, odprte, randomizirane študije so pokazali, da smo po totalni endoprotezi kolka pri analgeziji z uporabo 0,125-odstotnega levobupivakaina preko perifernega femoralnega katetra porabili 70% manj piritramida kot pri analgeziji s piritramidom IV PCA, hkrati pa zagotovili primerljivo olajšanje bolečine in boljše zadovoljstvo bolnikov.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
113
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
SPREMLJANJE KLINIČNE UČINKOVITOSTI ZDRAVILA JURNISTA PRI BOLNIKIH S HUDO KRONIČNO BOLEČINO EFFICACY OF JURNISTA FOR TREATMENT OF CHRONIC SEVERE PAIN IN EVERYDAY PRACTICE Aleksander Stepanovič,1 Jelka Pirc,2 Slavica Lahajnar-Čavlovič,3 Sanja Bizilj,4 Darja Ambrožič4 1
Zdravstveni dom Kranj, 2Splošna bolnišnica Nova Gorica, 3Onkološki inštitut Ljubljana 4 Janssen Cilag Ljubljana
Namen raziskave: Namen raziskave je bil spremljanje klinične učinkovitosti zdravljenja z zdravilom Jurnista pri bolnikih s hudo kronično bolečino. Metode: Sodelovalo je 52 zdravnikov, ki so v obdobju od 17. 4. 2008 do 18. 3. 2009 vključili skupaj 197 bolnikov, od tega 129 žensk in 68 moških. Vključeni so bili bolniki, ki so prejemali zdravilo Jurnista glede na strokovno presojo zdravnika in ustaljeno klinično prakso. Za merjenje bolečine smo uporabili VAS lestvico. Bolniki so izpolnili vprašalnik o vplivu bolečine na kakovost življenja. Spremljali smo pojav prebijajoče bolečine in beležili neželene učinke. Ob zadnjem obisku smo ocenili zadovoljstvo z zdravljenjem s strani bolnika in zdravnika. Rezultati: Od 197 vključenih bolnikov s kronično bolečino je imelo 127 bolnikov (64 %) neonkološko bolečino in 70 bolnikov (36 %) onkološko bolečino. 71 % bolnikov z neonkološko bolečino in 48 % bolnikov z onkološko bolečino je imelo po 90 dneh zdravljenja z zdravilom Jurnista obvladano bolečino. Povprečni odmerek je bil 14,1 mg oziroma 16,3 mg. Bolnikov s prebijajočo bolečino več kot 3x dnevno je bilo ob koncu raziskave le 4 %. 45 (23 %) bolnikov je poročalo o enem ali večih neželenih učinkih, značilnih za zdravljenje z opioidnimi analgetiki. 96 % zdravnikov in 89 % bolnikov je bilo z zdravljenjem zadovoljnih oziroma zelo zadovoljnih. Zaključki: Jurnista je učinkovito zdravilo za lajšanje bolečine. Z lajšanjem bolečine izboljšamo tudi kakovost življenja bolnikov. Z zdravilom Jurnista smo zadovoljivo lajšali neonkološko bolečino. Z zdravljenjem onkološke bolečine nismo zadovoljni. Zdi se, kot da še vedno ne prilagajamo odmerka opioida bolnikovi oceni jakosti bolečine in se prehitro ustavimo pri titraciji.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
114
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
OPERACIJA INGVINALNE KILE V LOKALNI ANESTEZIJI – KOLIKŠEN JE VPLIV NA POOPERACIJSKO ANALGEZIJO THE INFLUENCE OF LOCAL ANAESTHESIA FOR INGUINAL HERNIA SURGERY ON POSTOPERATIVE ANALGESIA Mihael Zajec, Marija Cesar-Komar Splošna bolnišnica Slovenj Gradec, Slovenj Gradec
Izhodišče: Operacija dimeljske kile je ena najpogostejših operacij v splošni kirurgiji. Za njeno izvedbo lahko izbiramo med različnimi vrstami anestezije: splošna anestezija, področna anestezija, lokalna anestezija ter kombinacija sedacije in lokalne anestezije. Bolniki in metode: Izbira metode je odvisna predvsem od zdravstvenega stanja bolnika, bolnikovih želja, doktrine ustanove (kirurga in anesteziologa) in možnosti pooperacijskega nadzora. Dodatno na izbiro anestezije vplivajo še: varnost, ekonomičnost in pooperacijska analgezija. V zadnjih letih se pri operacijah dimeljskih kil uporablja predvsem lokalna anestezija, ki je zelo primerna za ambulantno (enodnevno) oskrbo skrbno izbranih bolnikov. Lokalno anestezijo za operacijo dimeljske kile izvaja kirurg. Anesteziolog sodeluje, ko se izvaja kombinacija lokalne anestezije in sedacije – monitored anaesthesia care (MAC). Rezultati: Prednosti lokalne anestezije: - preprosta metoda - varna metoda tudi za bolnike z velikim tveganjem za operacijo - ni poanestezijskih stranskih učinkov - dobra pooperativna analgezija - zgodnja mobilizacija bolnika - ekonomski prihranek. Kontraindikacije - bolnikova odklonitev - preobčutljivost na lokalne anestetike - motnje koagulacije - okužba v dimeljskem predelu. Uspešnost operiranja dimeljske kile v lokalni anesteziji je odvisna od: - dobrega izbora bolnikov – konziliarnega pregleda anesteziologa - pozitivne motiviranosti informiranega bolnika - izkušenosti kirurga in operativne ekipe - poznavanja anatomije dimeljskega predela - primerne tehnike operiranja. Ob upoštevanju maksimalnih terapevtskih odmerkov lokalnega anestetika ali s primerno kombinacijo dveh različnih lokalnih anestetikov se izognemo toksičnemu učinku zdravil. Bolečina po operaciji dimeljske kile običajno ni močna. Nanjo lahko učinkovito vplivamo že z vodenjem anestezije. Najmanj je pooperacijska bolečina izražena, če je bila operacija kile izvedena v lokalni anesteziji. Za lajšanje pooperacijske bolečine običajno zadostuje NSAID (npr. paracetamol), občasno uporabimo opioidni analgetik (npr. Tramadol) ali kombinacijo, ko je VAS 3 ali več. Bolniki, ki so bili zaradi dimeljske kile operirani v lokalni anesteziji, po operaciji nimajo poanestezijskih težav, kot so glavobol, motnje uriniranja ali večurno ležanje v postelji. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
115
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Zaključek: Poleg tega, da je operiranje dimeljske kile v lokalni anesteziji preprosto, učinkovito, varno in poceni, ima za bolnika še poseben pomen, da po operaciji hitro vstane iz postelje in da je poseg med operacijo in po njej malo občutljiv. Bolniki praviloma potrebujejo manj protibolečinskih zdravil (2 do 3-krat manj) kot po enakih operacijah z druge vrste anestezijo.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
116
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
NEVROPATSKA BOLEČINA, IZZVANA S KEMOTERAPIJO CHEMOTHERAPY-INDUCED NEUROPATHIC PAIN Uwe Junker Sana-Klinikum Remscheid, Remscheid, Germany
Chemotherapeutic agents, such as Docetaxel and Oxaliplatinum, have a wide indication range in patients, for example with breast cancer or colorectal carcinoma. Peripheral neuropathy is one of the most frequent side effects, unfortunately often forgotten during information and therapy of patients. As neuropathic pain significantly reduces life quality, its prophylaxis and therapy should be done thoroughly. There are prophylactic measures that could be undertaken by the patient himself such as cooling tongue and fingertips during infusion. Neuroprotective effects of glutamine, gluthation or n-acetyl-cystein are discussed for future therapeutic concepts, recently. Neuropathic pain occurring during the first application of chemotherapy should be treated instantly, because each further infusion is going to deteriorate the situation. Concepts combining calcium-channelblockers, such as pregabalin with modern sustained release opioids, like oxycodone, have shown good efficacy, so far.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
117
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
KLINIČNE METODE TESTIRANJA BOLEČIN PRI REVMATSKIH BOLEZNIH CLINICAL METHODS FOR PAIN MEASUREMENT IN RHEUMATIC DISEASES Zmago Turk,1 Dušan Čelan,1 Kurt Ammer2 1
Oddelek za medicinsko rehabilitacijo, Univerzitetni klinični center Maribor, Maribor Ludwig Boltzmann Forschungsstelle für Physicalische Diagnostik, Vienna, Austria
2
Veliko ljudi meni, da je bolečina zgolj subjektivna izkušnja in da se je ne da meriti. Kljub temu pa je za evalvacijo zdravljenja z metodami, ki lajšajo bolečino, potrebna vsaj semikvantitativna ocena bolečine. V prispevku so predstavljene metode, ki so bile razvite za klinično merjenje/opredelitev bolečine. Z anamnezo in opisom bolečine se da izračunati frekvenca. Verbalne ocenjevalne lestvice in vizualne analogne lestvice (VAS) omogočajo, da lahko intenzivnost bolečine izrazimo s številom. Provokacija bolečine, npr. z algometrom pritiska, prikazuje intenzivnost bolečine na validirani lestvici naprave. Vprašalniki, kot npr. McGillov, pa omogočajo večdimezionalen opis bolečine in z nizanjem odgovorov ponujajo možnost pridobitve skupne vrednosti za želeno kvantifikacijo. Posredne meritve bolečine lahko opisujemo tudi pri preiskavah, ki povzročajo bolečino pri testiranju omejene gibljivosti sklepov ali okončin (nagib kolka pri Lasèguovem testu). Za klinično prakso je potrebna najmanj redna primerjalna kvantifikacija simptomov bolečine v smislu verbalne in vizualne skale. Termini, kot npr. izboljšanje ali poslabšanje, naj se ne pojavljajo v kartoteki bolnika, ampak naj se uporabljajo zgolj v kvantitativni primerjavi stanja v obdobju A in obdobju B. Te termine ni možno kvantificirati. Celosten pristop bi pripomogel k boljši objektivnosti ocen terapevtskih obravnav.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
118
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
SINDROMA MIOFASCIALNE IN RADIKULARNE BOLEČINE: PREPOZNAVANJE IN ZDRAVLJENJE RADICULAR AND MYOFASCIAL PAIN SYNDROMES: RECOGNITION AND MANAGEMENT Perry K. Richardson Department of Neurology, George Washington University, Washington, DC, USA
Introduction Spine and limb pain are common entities and may lead to disability. Clinicians are often asked to evaluate limb pain in the context of neck or back pain, often concluding to the patient that these symptoms represent “pinched nerves.” Such diagnoses may be misleading if the differentiation of radicular (nerve root) pain from referred pain (pain referred from a distant non-neural site) is not kept in mind. Advances in understanding the pathophysiology of muscle as a pain generator suggests that myofascial pain syndrome deserves more attention and study as an imitator of radiculopathy.
Spinal anatomy Intervertebral disc herniation is a relatively common cause of injury to spinal roots, and knowledge of the peculiarities of spinal anatomy assists the clinician in localizing both the root and disc level involved. The spinal roots course laterally just beneath the pedicle before passing through the neural foramen at each level. A herniated disc between the C6 and C7 vertebral bodies may injure the C7 nerve root. In the lumbar region, the root susceptible to disc herniation is more variable. For example, the L4 root exits between L4-L5, but is situated far enough laterally that a typical paracentral disc herniation will more likely injure the descending L5 nerve root. The course of cervical spinal roots is generally horizontal, or perpendicular to the axis of the spinal cord, as opposed to the lumbar spinal roots, which descend through the spinal canal in an oblique fashion, comprising the cauda equine. Therefore, multiple lumbosacral nerve roots are in proximity, enabling more than one root to become injured from disc herniation or other mass lesions. A herniated cervical disc is likely to injure only one cervical nerve root when lateral and the spinal cord when central in location.
Chararacteristics of limb pain Radicular pain Pain resulting from injury to a nerve root can be local, but is usually felt in the distribution of the dermatome supplied by the root, primarily the distal portion of the dermatome. It is sharp or shooting, worse w/cough or sneeze, and may have associated objective neurological abnormalities. The term radiculopathy refers to pathologic nerve root disease. A number of nonmalignant processes may lead to nerve root compression or inflammation. Among the most common are disc herniation, spondylosis with attendant osteophyte formation, spinal stenosis and spondylolisthesis. These conditions may develop as a result of trauma or as degenerative processes of aging, and there is evidence for a genetic predisposition to stenosis. There are ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
119
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
also non-compressive causes of radiculopathy, e.g. diabetes, in which nerve root ischemia leads to radicular symptoms. Referred pain With tissue injury, released chemical entities trigger nerve impulses potentially perceived as pain via either unmyelinated or small myelinated peripheral nerve fibers. This information is carried via the dorsal roots into the dorsal horn of the spinal cord, where synapses occur with nociceptive neurons and other neurons that receive input also from nerve fibers transmitting non-painful stimuli. Sensory nerve fibers from muscles, facet joints, ligaments and visceral organs may also converge on these sites. As a result, pathology in these deeper structures may result in pain experienced in one or more dermatomes of a limb. This is known as referred pain.
Myofascial pain Regional musculoskeletal pain syndromes have been recognized in the European literature for over 200 years. More recently, myofascial pain has been defined as a regional pain syndrome accompanied by muscle trigger points. A descriptive paper published by Travell and Rinzler (1952) led to a large monograph (Travell, 1999), but many terms have been used through the years to describe this phenomenon, including myofibrositis, myogelosis, fibrositis, and tendomyotic and pseudoradicular syndromes. Attempts have been made to distinguish myofascial pain from fibromyalgia syndrome. Trigger points A trigger point has been defined as a localized area of tenderness that refers pain to a distant site. The constancy of the referral pattern between subjects suggests an anatomic basis for such pain similar to visceral referred pain. “Active” and “latent” trigger points are differentiated by spontaneous pain in the former. Associated signs include palpable taut bands in muscle and a local twitch response to palpation or needling. There may also be associated paresthesias, subjective weakness or restricted range of motion. This subtype of soft tissue pain, although relatively common according to some authors (Skootsky, et al, 1989), is controversial since, historically, no histopathological findings nor reliably reproducible clinical findings have been validated. Nonetheless, with careful exclusion of nerve root disease by neurological examination, electrodiagnosis and imaging studies, a proportion of patients remains with pain referred to a limb spontaneously and by palpation of tender taut bands in muscles. To make matters more complicated, trigger points and myofascial pain can coexist with underlying radiculopathy in a given patient. Mechanisms The pathogenesis of myofascial pain is not well understood. It is generally accepted that an acute injury in the form of muscle overload or acute strain may cause tissue damage with release of mediators of pain and inflammation. In a proportion of cases pain will outlast any ongoing evident tissue injury. One proposed mechanism involves continued muscle fiber contraction from disruption of sarcoplasmic reticulum with release of calcium. This sustained contraction may lead to muscle ischemia and release of more noxious substances that cause local acidosis and perpetuate the pain in a vicious cycle (Travell, et al, 1999). Excessive acetylcholine release from motor endplates may also underlie sustained muscle contraction. Other postulated peripheral mechanisms include dysfunctional muscle motor endplates (Simons, 1976). Evidence for this is based on allegedly characteristic electrical abnormalities found on needle electromyography of trigger points, but these assertions have not been critically evaluated. The “integrated hypothesis” of myofascial pain pathophysiology attempts to gather several ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
120
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
biological factors together resulting in a local failure of energy production with release of nociceptive factors. Recent data using an innovative immunocapillary electrophoretic method has shown altered pH and concentrations of a number of pro-inflammatory and nociceptive biochemicals in muscle from volunteers with active and latent trigger points in the trapezius muscle as compared to controls (Shah, 2005). The same investigators repeated the study in other volunteers, confirming the findings and adding data from a remote uninvolved muscle. Somewhat surprisingly, the gastrocnemius muscle showed reduced pH and elevated levels of nociceptive chemicals in those with trapezius trigger points. This was interpreted as consistent with central sensitization or a diffuse inflammatory state (Shah, 2008).
Clinical features Neurological examination The neurological examination is an excellent tool that allows detection of significant peripheral nerve or root dysfunction by the logical application of its principles. Attention is directed to the location and radiation of pain, reflex, motor and sensory changes. Focal muscle atrophy is a helpful lower motor neuron sign that is often overlooked. Sensory loss may not be demonstrable in root injury. In fact, marked sharply delineated sensory loss is rather diagnostic of focal peripheral nerve, as opposed to root, damage. Asymmetry or loss of deep tendon reflexes may be the most sensitive indicator of root or nerve dysfunction. Musculoskeletal examination The musculoskeletal examination should include inspection for asymmetry or postural abnormality. Active range of motion of the cervical and lumbar spine is examined, paying attention to signs of discomfort that suggest patient guarding. In these cases range of motion may be greater when palpated by the examiner. Exaggerated lumbar lordosis suggests trunk weakness, where reduced lordosis may signal spinal muscle overcontraction. Signs of significant muscle imbalance include visible muscle fullness or elevation of one shoulder or iliac crest. Palpation should be systematic and include the spine and soft tissues. Local pain on percussing the spinous processes may indicate a destructive bony process. Radicular pain produced by spine percussion suggests disc herniation. Some of the most common areas of muscle tenderness associated with limb pain include the upper trapezius, rhomboid and levator scapula, gluteal, iliocostalis and quadratus lumborum muscles. Tenderness is often noted also at the sciatic notch, trochanteric bursa and the region above the posterior superior iliac spine and overlying the sacroiliac joint. A thorough hands-on approach is important, and is the hallmark of detecting myofascial trigger points. The patient should always be asked if the pain produced by palpation is familiar, and whether pain is felt at a distant site.
Cervical root syndromes C7 root injury The most common cervical radicular syndrome involves the C7 root. Pain is often felt in the area of the scapula and down the dorsal forearm and hand. It may predominate in the dorsum of digits II to IV. Paresthesias may be felt in the same area. Weakness may be detected in triceps, pronator teres or forearm extensor muscles, and the triceps jerk is often reduced. The differential diagnosis includes carpal tunnel syndrome if tingling predominates, which classically causes nocturnal paresthesias in the fingertips. Myofascial trigger points in the scalene, teres ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
121
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
major and triceps muscles may refer pain to the same location, causing confusion in the diagnosis. In this case there would be no deep tendon reflex change. C6 root Injury of the C6 root is associated with pain and paresthesias radiating to the base of the thumb or first two digits. The biceps jerk is reduced with biceps brachii or brachioradialis weakness. Trigger points in the scalenus anterior, infraspinatus, brachialis or biceps brachii muscles may mimic this radicular syndrome. C5 radiculopathy C5 radiculopathy causes pain and paresthesias radiating to the outer upper arm. Since the C5 dermatome is proximal, it may be difficult to confidently exclude radiculopathy on clinical grounds. If present, weakness is found in the deltoid and infraspinatus. Occasionally the biceps jerk is reduced. The pain referral zone is common to many muscles where myofascial trigger points may be palpated, namely the upper trapezius, levator scapulae, scalene, supraspinatus, infraspinatus, teres major and deltoid muscles. C8 root injury Medial forearm and hand pain presents the examiner a particular challenge. This area receives radiation of pain and paresthesias from C8 root injury. The identical pattern is frequently seen in referred pain from diverse causes, including myocardial ischemia, cervical strain injuries and myofascial pain syndrome. The latissimus dorsi, serratus posterior superior, pectoralis major and triceps muscles each may have trigger points with referred pain and paresthesias into the medial forearm and medial two digits. Intrinsic hand muscle weakness is a clue to root or nerve injury. Ulnar neuropathy should also be considered and EMG studies may be needed for diagnosis.
Lumbar root syndromes Low back pain associated with leg pain may also represent either radicular or referred pain. Back pain associated with pain in the distal leg is more likely to represent radiculopathy, since myofascial pain referred to the foot usually arises from the leg muscles below the knee. Pain felt primarily in the back and proximal leg raises some diagnostic difficulties, but careful neurological and muscle examination may define the lesion. L5-S1 disc herniation Disc herniation at L5-S1 may cause S1 nerve root injury, with pain and tingling felt in the posterior leg and calf as far as the lateral foot and sole. A reduced ankle jerk ipsilaterally is an important clue. Positive straight leg raising tests are very helpful. Weakness of the gastrocnemius muscle is difficult to detect while supine: toe walking should be checked to more effectively assess the strength of this muscle. Confusion commonly arises when disc herniation detected by MRI scanning is associated with back and buttock or posterior thigh pain without neurological findings. Careful palpation for trigger points may disclose reproduction of identical symptoms with trigger points in the gluteus maximus, gluteus medius, piriformis, quadratus lumborum, longissimus thoracis or iliocostalis lumborum. L5 root injury L5 root injury may result from a paracentral L4-5 disc herniation or a lateral disc herniation and L5-S1. Pain radiates to the lateral leg and anterior or lateral shin to the ankle or dorsum of foot with tingling often felt in the great toe. Impaired heel walking or weakness of ankle or to dorsi------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
122
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
flexion may be found. Trigger points in the gluteus minimus, gluteus medius, piriformis or quadratus lumborum muscles may refer pain to the lateral thigh or rarely as far as the ankle. L4 radiculopathy Radiculopathy affecting the L4 root is characterized by pain radiating to the anterior thigh and knee, and may be mimicked by hip joint disease or by trigger points in the iliopsoas or quadriceps muscles. A reduced knee jerk allows presumptive diagnosis of root disorder.
Diagnostic studies Laboratory, imaging and electrodiagnostic studies may be helpful but may cloud the diagnosis because of incidental findings. Furthermore, many acute back and neck pain syndromes, defined as those lasting four weeks or less, have an excellent prognosis for recovery in the absence of certain red flags. The clinician should consider further studies if a potentially dangerous systemic disease such as cancer, visceral organ damage or spinal infection is suspected, with significant neurological deficit or trauma. Soft-tissue imaging For imaging soft tissues, magnetic resonance imaging (MRI) or computed tomography (CT) myelography is preferred. MRI scanning has become a popular but overused study for back pain. The likelihood of findings incidental structural abnormalities is significant. A recent study of lumbosacral MRI in asymptomatic persons showed a 52 percent incidence of bulging discs and a further 27 percent disc protrusions (Jensen, et al, 1994). Similarly, incidental findings on cervical MRI are reported in 19 percent of asymptomatic subjects (Boden, et al, 1990a). Nonetheless, MRI scanning can confirm pathology predicted by a localizing clinical examination. On recent study found a sensitivity of 53 to 60 percent of MRI scanning in detecting abnormalities with lumbar radiculopathy (Nardin, et al, 1999). Other ancillary studies, such as CT scan, CT myelography or electrodiagnostic studies may be necessary to fully evaluate the patient. CT myelography, with contrast filling the root sleeves out into the neural foramina, is superior to MRI for detecting lateral recess stenosis. A sensitivity of 75 to 84 percent has been found for detecting radiculopathy (Wilbourn, 1982), although myelography is an invasive procedure. Electrodiagnostic studies Electrodiagnostic testing with nerve conduction studies and electromyography (EMG) utilizes physiological data to detect nerve or nerve root abnormality. It therefore complements the anatomic data afforded by imaging studies in the assessment of back and limb pain when neural damage is suspected. Electrodiagnostic studies have a higher yield than imaging, with 73 to 94 percent of studies showing abnormality in subjects with clinical evidence of radiculopathy (Wilbourn, et al, 1982). In equivocal cases, both imaging and EMG may be performed to improve diagnostic yield. Advantages of EMG include localizing the level of root injury, excluding other causes of symptoms such as entrapment neuropathy or plexopathy, and assessing the severity of nerve injury for prognostic purposes and to guide therapy, especially if surgery is considered. EMG studies are normal in myofascial or other musculoskeletal pain syndromes. Needle EMG is mildly uncomfortable but has no other adverse effects. Any positive findings on ancillary tests must be put in the context of the symptoms and signs in order to assess their significance, bearing in mind that muscle and root syndromes can coexist.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
123
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Treatment Goals of treatment in neck and back pain include restoration of function and the avoidance of a chronic pain syndrome. The natural history of radicular pain syndromes depends upon the etiology of the root injury. Spinal infection or malignancy may require urgent intervention with antibiotics, surgical resection or radiation therapy. The more common disorders causing radiculopathy, namely disc herniation and bony compression from osteophyte formation or spinal stenosis, may be given a trial of conservative therapy. Generally, indications for surgery in these non-urgent cases include neural element compression with loss of function in the limb, bony instability or intractable limb pain. Myofascial pain is most often managed by physical methods directed at resolving muscle trigger points. Conservative management Although many patients with radiculopathy are referred for surgery, satisfactory outcomes may be obtained with physical therapy, analgesics and anti-inflammatory agents or muscle relaxants. Epidural steroid therapy may significantly reduce limb pain as a temporizing measure, but a recent evidence analysis of its use in sciatica concluded it does not necessarily lessen the need for surgery (Armon et al, 2007). There is no consensus on the efficacy of cervical traction, which is contraindicated in destructive spine injuries. Some authors feel cervical traction should be avoided in frank disc herniation. For low back pain with sciatica, traction is not likely to benefit the patient beyond a brief period of bed rest. A fairly large randomized trial of low back pain found no difference in efficacy for chiropractic manipulation over physical therapy (Cherkin et al, 1998). Surgical management Up until very recently, there was only one randomized controlled study to compare surgical versus nonsurgical treatment of lumbar disc herniation. In that study outcomes were similar at one year (Weber, 1983). Recent prospective, randomized studies are marred by high rates of crossover, but show that disc surgery is likely to lead to more rapid relief of radiculopathy symptoms, especially when severe (Peul et al, 2007, Weinstein et al, 2008). However, surgery is not necessarily more likely to return the patient to employment or reduce worker’s compensation (Atlas et al, 1996). Patients should be carefully selected in order to avoid unnecessary surgery and the slippery slope of the multiply-operated patient (Junge et al, 1995). Even in cases with obvious organic pathology, a biopsychosocial model of illness should be adopted, and attention paid to illness behaviors and secondary gain issues. Myofascial pain without radiculopathy In the case of myofascial pain without concurrent radiculopathy, therapy is directed at reduction of pain, restoration of function, and correction of perpetuating factors. A variety of treatment methods have been used through the years to release or unload trigger points. The most common techniques utilized currently under the rubric of myofascial pain therapy are vapocoolant spray and stretch (Jaeger and Reeves, 1986) and trigger point injections. Deep stroking massage, “myotherapy,” osteopathic strain and counterstrain, shiatsu and acupressure are other manual techniques that may be effective at resolving trigger points. Interestingly, acupuncture sites needled for neck and back pain often overlap with those treated by trigger point injections. Appropriate muscle “re-education” is employed in the form of instructing patients on ways to reduce muscle overload. These include postural awareness, muscle stretching, periods of activity interposed between sedentary periods, and specific myofascial pain interventions. When myofascial pain is unresponsive to manual methods trigger point injections or needling may be considered (Jaeger and Skootsky, 1987). Injections may also be helpful when the muscle cannot be stretched for mechanical reasons, or for rapid reduction of pain to accomplish ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
124
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
more effective stretching. In addition to subjective reports of pain reduction, there is evidence that overall muscle tension is reduced after injection, as measured by surface electromyography (Hendler et al, 1983). Although post-injection soreness can be reduced by the instillation of local anesthetic, studies have actually shown no difference in outcome between this method and dry needling (Hong, 1994). Small uncontrolled studies have shown the benefit of injecting botulinum toxin into trigger points (Cheshire et al, 1994), but other controlled studies have been negative, but there is no consensus on study methodology. The addition of injected corticosteroids offers no advantage unless an inflammatory response is suspected. This may occur at the so-called attachment trigger points, where myofascial pain and enthesopathy may coexist. Adverse effects of trigger point injections are relatively few. Microscopic myotoxic changes from local anesthetics are of no functional consequence if concentrations of 0.5 percent or less are used. Epinephrine is to be avoided. Rarely, pneumothorax has been caused by injections into intercostal muscles. Inadvertent nerve block may occur, so patients must be observed for several minutes after the procedure.
Prognosis Given the emotional experience of pain and the attendant suffering, the clinician should engender patient trust and avidly educate him on the nature of the findings. In this way, appropriate physician and patient expectations can be communicated and unnecessary tests and operations may be avoided. The role of the treatment team thus includes neutralizing the patient’s fear that pain implies bodily destruction. Although the body reacts to guard against further damage after an acute injury, the patient with ongoing myofascial pain should be taught to minimize guarding of painful areas in order to restore normal posture and function. Incorporating these principles into treatment may reduce the changes of progression to chronic pain.
Conclusion The patient complaining of pain affords the clinician many challenges. A reasonably thorough understanding of relevant anatomy, referral zones and the common radicular syndromes should allow the clinician to distinguish between myofascial and radicular pain syndromes. Imaging and ancillary testing may confirm the diagnosis, but test results must be critically analyzed as to their significance, given the frequency of irrelevant findings on such tests. New biochemical data lend support to the so-called “energy crisis” theory of trigger point patients, but further research is needed to elucidate the cause and significance of these findings.
References 23. Armon C, et al. Assessment: use of epidural steroid injections to treat radicular lumbosacral pain: report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology 2007; 68 (10): 723-9. 24. Atlas SJ, et al. The Maine Lumbar Spine Study. Part II. 1-year outcomes of surgical and non-surgical management of sciatica. Spine 1996; 21:1777-86. 25. Boden SD, et al. Abnormal magnetic resonance scans of the cervical spine in asymptomatic subjects. A prospective investigation. J Bone Joint Surg (Am.) 1990a; 72: 1178-84. 26. Boden SD, et al. Abnormal magnetic resonance scans of the lumbar spine in asymptomatic subjects. A prospective investigation. J Bone Joint Surg (Am.) 1990b; 72: 403-8. 27. Cherkin DC, et al. A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low back pain. NEJM 1998; 339: 1021-9. 28. Cheshire WP, et al. Botulinum toxin in the treatment of myofascial pain syndrome. Pain 1994; 59: 65-. 29. Hendler N, et al. Myofascial syndrome: Response to trigger-point injections. Psychosom 1983; 24: 993-9. 30. Hong CZ. Lidocaine injection versus dry needling to myofascial trigger points: the importance of the local twitch response. Am J Phys Med Rehabil 1994; 73: 256-63. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
125
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
31. Jaeger B, Reeves JL. Quantification of changes in myofascial trigger point sensitivity with the pressure algometer following passive stretch. Pain 1986; 27: 203-10. 32. Jaeger B, Skootsky SA. Double blind, controlled study of different myofascial trigger point injection techniques (Abstr.). Pain 1987; 4 (Suppl): S92. 33. Jensen MC, et al. Magnetic resonance imaging of the lumbar spine in people without back pain. NEJM 1994; 331: 69-73. 34. Junge A, et al. Predictors of bad and good outcomes of lumbar disc surgery: a prospective clinical study with recommendations for screening to avoid bad outcomes. Spine 1995; 20: 460-8. 35. Nardin RA et al. Electromyography and magnetic resonance imaging in the evaluation of radiculopathy. Musc Nerve 1999; 22: 151-5. 36. Peul WC, et al. Surgery versus prolonged conservative treatment for sciatica. NEJM 2007; 356: 2245-56. 37. Shah JP, et al. An in vivo microanalytical technique for measuring the local biochemical milieu of human skeletal muscle. J Appl Physiol 2005; 99: 1977-84. 38. Shah JP, et al. Biochemicals associated with pain and inflammation are elevated in sites near to and remote from active myofascial trigger points. Arch Phys Med Rehabil 2008; 89:16-23. 39. Simons DG. Electrogenic nature of palpable bands and “jump sign” associated with myofascial trigger points. Adv Pain Res Ther 1976; 1: 913-8. 40. Skootsky SA, et al. Prevalence of myofascial pain in general internal medicine practice. West J Med 1989; 151: 157-60. 41. Travell J, Rinzler SH. The myofascial genesis of pain. Postgrad Med 1952; 11: 425-34. 42. Travell J, et al. Myofascial Pain and Dysfunction: The Trigger Point Manual, 2nd ed. Baltimore: Williams & Wilkins, 1999. 43. Weber H. Lumbar disc herniation: a controlled, prospective study with ten years of observation. Spine 1983; 8: 131-40. 44. Weinstein JN, et al. Surgical versus nonoperative treatment for lumbar disc herniation: Four-year results for the Spine Patient Outcomes Research Trial (SPORT). Spine 2008; 33: 2789-800. 45. Wilbourn AJ. The value and limitations of electromyographic examination in the diagnosis of lumbosacral radiculopathy. In: Hardy RW, ed. Lumbar Disc Disease. New York: Raven Press, 1982.
Thanks to Dr. David Simons for helpful commentary.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
126
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
PRIPOROČILA ZA ZDRAVLJENJE BOLEČINE KRONIČNE VNETNE REVMATIČNE BOLEZNI Z ZDRAVILI RECOMMENDATION FOR THE MEDICAMENTOUS TREATMENT OF CHRONIC INFLAMMATORY RHEUMATIC DISEASE PAIN Dušan Logar, Sonja Praprotnik Klinični oddelek za revmatologijo, Univerzitetni klinični center Ljubljana, Ljubljana
Izvleček. Kronična bolečina vnetne sklepne revmatične bolezni je sprožena s sklepnim vnetjem, vendar nanjo vplivajo številni drugi dejavniki. Zdravljenje bolečine teh bolezni je najučinkovitejše ob hkratnem zdravljenju z zdravili in nefarmakoloških ukrepih. Ker je zdravljenje z zdravili dolgotrajno je pomembna ne samo njihova učinkovitost, temveč tudi varnost in prenosljivost uporabljenih zdravil. Ker sta bolečina in vnetje medsebojno povezana in soodvisna, z zdravljenjem vnetja vplivamo na bolečino in obratno. Strategija zdravljenja revmatoidnega artritisa (RA), je v čim popolnejšem obvladovanju sklepnega vnetja z pravilno uporabo zdravil, ki spreminjajo naravni potek bolezni (DMAR) ali bioloških zdravil in zdravljenje bolečine z analgetiki, glukokortikoidi vbrizganimi v sklep ali mišico in nesteroidnimi antirevmatiki (NSAR) v najnižjih učinkovitih odmerkih, krajši čas. Predstavljena so tudi priporočila za zdravljenje z opioidnimi analgetiki. Abstract. Although chronic arthritic pain is initiated by joint inflammation, it is also influenced by range of other factors which are discussed. A combination of both pharmacological and non-pharmacological approaches offers the best opportunity for therapeutic success. Pharmacological therapy is often prolonged, and safety and tolerability issues become as important as efficacy over time. The fact that pain and inflammation are inherently linked indicates that interventions that relieve the symptoms of arthritis may also moderate the severity of underlying disease and vice versa. The main strategy of pain management in rheumatoid arthritis (RA) is to control synovitis with better use of disease modifying antirheumatic drugs (DMARDs) or biologic therapy and pain control using analgesics, intraarticular or intramuscular steroid injections and nonsteroidal antirheumatic drugs (NSAIDs) in the lowest possible dose, the shortest possible time. The recommendations for pain management using opioids are discussed as well.
Uvod Kronični mišično-skeletna bolečina ki traja dalj kot tri mesece, pomembno poslabšuje psihično in fizično zdravje posameznika. Kronična bolečina tudi vpliva na njegov socialni in ekonomski položaj, socialni in ekonomski položaj njegove družine in stroške sistema zdravstvenega varstva. Revmatoidni artritis (RA), je kronična vnetna revmatična bolezen, ki jo spremlja sklepna bolečina povzročena z draženjem bolečinskih receptorje v sklepni kapsuli, ligamentih, meniskusih, periostu, subhondralni kosti in okolnih mehkih tkivih. Bolečinski receptorji imajo na svoji površini različne receptorje, ki uravnavajo njihovo občutljivost na dražljaje (receptorje gama amino maslene kisline-GABA, opioidne receptorje in receptorje bradikinina, histamina, serotonina in kapsaicina). V hrbtenjačnem mozgu in možganih posredujejo prenos bolečinskega signala vzdražni nevro transmitorji: glutamat, tahikinini (snov P, nevrokinin A in B), somatostatin, vazoaktivni intestinalni polipeptid, bombezin in peptid povezan z genom za kalcitonin. Prenos bolečinskih dražljajev oslabe v osrednjem živčevju številni zaviralni nevro transmitorji, med njimi je najpomembnejša gama amino maslena kislina (GABA). Bolečinske dražljaje uravnavajo še noradrenalin z α-2 spodbujevalnim učinkom, serotonin in endogeni opioidi. Zanimivo je spoznanje, da je pri vnetem sklepu pri RA povrhnja sinovija denervirana, kar razloži dejstvo, zakaj je vnet sklep, če je popolnoma imobiliziran, neboleč. Vnetna bolečina (nevroplastična bolečina) je posledica normalnega odgovora na dalj časa trajajočo tkivno okvaro. Ta bolečina, ki jo bolnik občuti kot topo, žgočo, lahko pulzirajočo, je kompleksen preplet čutilnih, čustvenih in kognitivnih procesov, ki vključujejo številne abnormne celične mehanizme v sklepih in osrednjem živčevju.1 Revmatično bolečino lahko delimo na akutno, ki jo povzroči akutno vnetje in kronično, ki je posledica razgradnje tkiv in mehanskih ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
127
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
sprememb hrustanca, kosti in obsklepnih mehkih tkiv. Bolečina akutno vnetega sklepa je posledica predvsem učinka pravega koktejla vnetnih mediatorje in citokinov na bolečinske receptorje, zato je zdravljenje s protivnetnimi zdravili v tem obdobju tudi najučinkovitejše. Za kronični potek vnetne revmatične bolezni pa je značilna aktivacija nevrogenih mehanizmov s čezmerno periferno in centralno vzdražnostjo.2 Kar 65 odstotkov bolnikov z RA, da je bolečina najpomembnejši simptom bolezni, ki ga je potrebno začeti zdraviti. Po 62. letu starosti se jakost bolečine pri revmatoidnem artritisu rahlo manjša, kar je verjetno odraz manjših psihofizičnih obremenitev po upokojitvi. Tudi določeni demografski dejavniki vplivajo na jakost bolečine pri RA, čeprav ta učinek ni velik. Tako je ta nekoliko močnejša pri ženskah v primerjavi z moškimi, pri kadilcih v primerjavi z nekadilci, pri neporočenih v primerjavi s poročenimi, pri manj izobraženih v primerjavi z bolj izobraženim. Zanimiva je ugotovitev, da jakost bolečine izraženo z vidno analogno lestvico (VAS 0–10) različno povečuje bolečina določenih sklepov. Tako se ta najbolj poveča z bolečino rame, kolena, gležnja in kolka. Za kvaliteto bolnikovega življenja pa je pomembna tista najmanjša sprememba jakosti bolečine, ki že povzroči spremembo bolnikovega zadovoljstva s svojim zdravjem (MCIC-minimal clinical important change), ki je 0,5 enote VAS. Za 75 odstotkov bolnikov z RA, ki so zelo zadovoljni s svojim zdravjem, je še sprejemljiva bolečina ocenjena z VAS med 0,5–2,0.3 Razumevanje patofiziologije nastanka bolečine pri revmatoidnem artritisu Akutna bolečina vnetega sklepa se prevaja po tankih mieliniziranih vlaknih živcev Aδ. Bolečino okrepe tudi vzdražena nemielizirana vlakna C, ki so običajno inaktivna (topa bolečina). Pri sklepnem vnetju so aktivirana tudi mielinizirana vlakna večjega preseka Aβ, ki sicer prevajajo mehanske dražljaje nizke intenzitete (prisk, gibanje sklepa), potem, ko se fenotipsko spremene in ob gibanju sklepa začnejo prevajati bolečinske dražljaje. V vnetem sklepu se aktivirajo tudi tako imenovani »speči« bolečinski receptorji receptorji, kar dodatno zveča število aferentnih impulzov, ki potujejo v zadnje rogove hrbtenjačnega mozga. Primarni čutilni nevroni prevajajo dražljaje preko sinaps v zadnjih rogovih hrbtenjačnega mozga na različne nevrone, vključno na povezovalne vmesne nevrone, descendentne inhibitorne nevrone in na nevrone simpatikusa. Bolečinski dražljaji se tu modulirajo predno potujejo v podaljšano hrbtenjačo, talamus, limbični sistem in skorjo možganov.2 Dejavniki, ki prispevajo k čezmerni vzdražnosti bolečinskih receptorjev v sklepu Mehanski dejavniki Značilno bolečino vnetega sklepa pri RA, ki jo bolnik občuti pri gibanju, povzroča draženje bolečinskih receptorjev z vnetnimi mediatorji v sklepni kapsuli, periostu, sinoviji, entezah, senzoričnih živcev v kostnem mozgu in čezmerna vzdražnost osrednjega živčevja. Edem tkiv in sproščanje mediatorjev vnetja, povzročijo tudi zmanjšanje mehanskega praga potrebnega za aktivacijo bolečinskih receptorjev, zaradi česar so že običajni gibi boleči. Žile v sinoviji postanejo ob vnetju močno propustne za beljakovine plazme, zaradi česar se zveča onkotski tlak v sklepu in precejanje tekočine, kar zveča intraartikularni tlak. Porast tlaka je strm zaradi zadebeljene sinovije in slabo raztezne sklepne kapsule, kar aktivira bolečinske receptorje. Okvara živcev v obolelih sklepih lahko vzdraži aferentna vlakna simpatikusa, kar vpliva na pretok krvi v sinoviji in bolečino.4 Zaradi edema kostnega mozga se zveča intraosalni tlak ob zmanjšani venski drenaži. Posledica je kopičenje razgradnih produktov, pospešena apoptoza osteoblastov in zvečana aktivnost osteoklastov, kar ob vneti sinoviji prispeva k nastanku kostnih erozij. Kostni mozeg je bogato oživčen in zvečan intraosalni tlak zveča številčnost bolečinskih dražljajev.2 Vnetni mediatorji in periferna prekomerna vzdražnost Tkivna okvara povzroči sproščanje vnetnih mediatorjev iz živcev, celic vnetnic, celic sinovije in žilnega endotelija. Za primarne čutilne nevrone je ob tkivni okvari značilen zmanjšan prag za nastanek akcijskega potenciala in povečan odgovor perifernih bolečinskih receptorjev – feno------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
128
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
men, ki ga imenujemo periferna čezmerna vzdražnost (senzitacija) s posledično hiperalgezijo. Hkrati pa periferno vnetje povzroči povečano vzdražnost membran nevronov zadnjih rogov hrbtenjačnega mozga-centralno čezmerno vzdražnost. Poznane so številne snovi, ki vzdračijo bolečinske receptorje: nevropeptidi (na primer snov P), eikozanoidi, aktivin, ki je predstavnik družine transformirajočega rastnega faktorja β (TGF β), citokini, kot je dejavnik tumorske nekroze (TNF), kemokini, histamin, serotonin sproščen iz mastocitov, bradikinin, regulatorne beljakovine kot so prokinetikini, vnetne proteaze kot sta triptaza mastocitov in tripsini, rastni faktor živcev in dušikov oksid. Vsi ti dejavniki vzdražijo živčne končiče, posledica tega pa je, da na primer mehanski dražlaji nizke jakosti (kot je na primer že običajen gib), ki sicer ne bi povzročili občutka bolečine, povzroče bolečino (alodinija). Ti dejavniki spodbujajo tudi centralno čezmerno vzdražnost. Eikozanoidi so presnovki arahidonske kisline, med katere prištevamo prostaglandine (PG), levkotriene, lipoksine, tromboksane in endokanabinoide. Prostaciklini PGE1 in E2 vzdražijo bolečinske receptorje v sklepu, njihovo delovanje je hitro in zveča število aferentnih impulzov, kot odgovor na mehanske in kemične dražljaje. Endokanabinoid anandamid je neselektivni ligand, ki se veže na CB1 in CB2 kanabinoidna s proteinom G- povezana receptorja. Visoke ravni andanamida v sklepu vzdražijo čutilne živce, nizke ravni pa delujejo analgetično. V vnetem sklepu so zvečane tudi ravni nevropeptidov, kot so snov P, z genom za kalcitonin povezan peptid (calcitonin gene-related peptide), vazoaktivni intestinalni peptid in nociceptin/orfanin FQ, ki je opioidu podoben neuropeptid. Nociceptin/orfaninFQ povzroči v visokih koncentracijah, s sprostitvijo snovi P hiperalgezijo in alodinijo.5 Vloga biokemičnih sprememb sinovijske tekočine Med biokemičnimi spremembami v vnetem sklepu pri RA je pomembna predvsem tvorba prostaglandina E2 (PGE2), ki lahko sproži vzdraženje bolečinskih receptorjev. Bolečinski receptorji so posuti z različnimi ionskimi kanali. Prenos bolečinskega dražljaja zahteva njihovo neposredno aktivacijo ali aktivacijo z vezavo z receptorji. Kronično vnetje zveča izražanje napetostno-uravnavanih (voltage-gated) natrijevih kanalov. Tudi odprtje napetostno-uravnavanih kalcijevih kanalov na primarnih aferentnih živcih zveča znotrajcelično raven kalcija in posledično sprostitev nevrotransmitorjev v okolico živca, kar spodbuja nastajanje in številčnost bolečinskih dražljajev. Poleg napetostno-uravnavanih ionskih kanalov se aktivirajo tudi mehansko-uravnavani ionski kanali, ki se konformacijsko spremenijo ob spremembi strižnih sil v celični membrani živčnega vlakna. Ko postanejo gibi vnetega,oteklega sklepa boleči, so izvedeni z večjo silo, ob tem se odpro mehansko-uravnavani ionski kanali, sledi depolarizacija in prevajanje vse številčnejših bolečinskih dražljajev.6 Biokemična značilnost RA je tudi acidifikacija sinovijske tekočine. V prenos bolečine pri revmatoidnem artritisu so vpleteni ionski kanali, ki zaznavajo acidifikacijo- sproščanje protonov iz okvarjenih celic (acid-sensing ion channels – ASIC)). Pomembna družina ionskih kanalov, so kanali TRP (transient receptor potential ion channels). Predvsem sta pomembni poddružini TRPM (melanostatin) in TRPV (vaniloid). Med tem ko osmi član družine kanalov TRPM (TRPM8) aktivirajo nizke temperature, aktivacija tega kanala pa ima protibolečinski učinek, pa termosenzitivni ionski kanal V1 (TRPV1), ki zaznava spremembe v temperaturi in zunajceličnem pH aktivira temperatura nad 43°C, občutljiv pa je tudi na protone, lipide forbole in kanabinoide, njegova aktivacija pa ravno tako sproži nastanek bolečinskih dražljajev.7 Zanimivo je, da kapsaicin sicer sprva vzdraži bolečinske receptorje, s sekundarno sprostitvijo vnetnih nevropeptidov v sklep pa postane ta nato neobčutljiv za bolečinske mehanske dražljaje.8 Vloga citokinov Osrednja, vnetje spodbujajoča citokina sta tumorski nekrozni faktor alfa (TNF-α) in interlevkin-1 beta (IL-1 β), ki spodbudita tudi tvorbo drugih citokinov (IL-6, IL-8), ki so udeleženi pri vnetju in razgradnji sklepa. Oba citokina spodbujata tvorbo metaloproteinaz v medceličju, ki imajo pri razgradnji sklepa pomembno vlogo. IL-1 β aktivira bolečinske receptorje neposredno z aktivacijo znotrajcelične kinaze, posredno pa z spodbujanjem tvorbe kininov in prostanoidov. TNF-α ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
129
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
aktivira čutilne nevrone neposredno preko receptorjev TNFR1 in TNFR2.9 Ravni TNF-α, IL-1 β in snovi P so v sinovijski sklepni tekočini bolnika z revmatoidnim artritisom zvečane. Po prepričanju Omoiuia in sodelavcev (Division of Inflammation and pain research, L.A. Pain Clinic, Los Angeles, ZDA) so tudi vsi drugi bolečinski sindromi, vključno z nevropatsko bolečino, sproženi z vnetjem, vsak pa ima svoj profil vnetnih mediatorjev.10 IL-6 sproži vnetni proces in spodbuja imunski odziv, saj okrepi tvorbo PGE2 in NO z indukcijo encimov COX-2 in inducibilne NO sintetaze.11 Sodelovanje živčevja in imunskega sistema pri nastanku bolečine Dokazali so neposredno sodelovanje celic vnetnic v nastanku nevrogenega vnetja in bolečine. Številni nevropeptidi čutilnih živcev aktivirajo mastocite in nevtrofilce, kar povzroči trenutno degranulacijo in sprostitev vnetnih mediatorjev v lokalno mikrookolje.12, 13 Mastocite aktivirajo tudi serinske proteinaze, ki povzroče encimsko razgradnjo hrustanca in drugih znotrajsklepnih tkiv. Ti encimi ne delujejo samo proteolitično, temveč usmerjajo preko specializiranih receptorjev spojenih s proteinom G tudi signalizacijo nevronov. Do sedaj so odkrili štiri receptorje, aktivirane s proteinazo (PAR), ki so udeleženi v signalizaciji bolečine. Z inhibicijo proteinazne aktivnosti lahko preprečimo razgradnjo sklepa in zmanjšamo bolečino.14 Vpliv cirkadianega ritma izločanja kortizola, melatonina, prolaktina na bolečino pri RA Biološki procesi in funkcije so časovno urejeni in izražajo dnevni, mesečni in letni ritem, na katerega pa vplivajo pri ženskah še menstrualni cikel, nosečnost in menopavza. Na ta ritem vpliva menjava svetlobe in teme, pri tem pa so vpleteni: osrednje živčevje, avtonomni živčni sistem, žleze z notranjim izločanjem, periferno endokrino tkivo in imunski sistem. Tako je znano, da so pri bolnikih z RA bolečine, sklepna okorelost in funkcijska oviranost največje zgodaj zjutraj. Izločanje kortizola je pri bolnikih z močno aktivno boleznijo, čeprav je lahko zvečano pa glede na vnetje nezadostno, predvsem v jutranjem času. Tudi cirkadiani ritem izločanja melatonina in prolaktina je spremenjen, saj se vrh izločanja melatonina, ki je ob 3h zjutraj, pri bolnikih z RA pojavi že dve uri prej. Serumska raven prolaktina pa je pri bolnikih z RA ponoči večja, kot pri zdravih. Visok nivo melatonina in prolaktina v času, ko je raven kortizola nizka (okoli 2h zjutraj), vzpostavlja provnetno okolje. Oba hormona namreč spodbujata TH1 imunski odziv in s tem celični odziv. Tudi raven provnetnih citokinov TNF-alfa in IL-6, je pri bolnikih v primerjavi z zdravimi premaknjena s 3. in 6. ure na 6. in 7. uro zjutraj in je približno desetkrat večja. Ravni teh citokinov se pri zdravih začnejo zniževati med 6.-9. uro zjutraj, pri bolnikih z RA pa šele med 10. in 11.uro, kar je posledica nezadostnega izločanja kortizola. Zvečane so tudi ravni IFN-gama, IL-2 in IL-12 v nočnem času, kar zveča aktivnost sklepnega vnetja pri bolnikih z RA zgodaj zjutraj, to spodbudi otekanje sklepov z udeležbo bradikinina, prostaglandinov in substance P in zveča bolečino z draženjem bolečinskih receptorjev.15 Endogeni protibolečinski ligandi V sklepu so na kapsaicin senzitivnih živcih, ki oživčujejo sinovijo, odkrili ligand endogenega opioidnega receptorja μ, endomorfin-1, ki zmanjšuje vnetje in bolečinske dražljaje. Vendar je protibolečinsko delovanje endomorfina-1 pri kroničnem vnetju, zaradi manjše ekspresije μopioidnih receptorjev v sklepu, zanemarljivo. Bolečinske dražljaje lahko med rotacijo sklepa zmanjšata tudi galanin in somatostatin, ki sta prav tako endogena protibolečinska mediatorja.16 Pomen čezmerne vzdražnosti osrednjega živčevja (centralne senzitacije) Čezmerna vzdražnost osrednjega živčevja povzroči zvečan odziv ascendentnih nevronov zadnjih rogov hrbtenjačnega mozga, z ojačanjem bolečinskega odziva (hiperalgezija) in širitvijo občutenja bolečine na neprizadete predele. Pomembna značilnost čezmerne vzdražnosti osrednjega živčevja, ki nastane z intenzivno in dolgotrajno bolečinsko stimulacijo, je sprememba načina ekspresije genov s posledično spremembo fenotipa nevronov, kot so nevroni Aβ. Ti zato ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
130
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
začnejo prevajati bolečinske dražljaje. Zmanjšana je tudi aktivnost descendentnih inhibitornih nevronov.17 V osnovi tega dogajanja je predvsem s fosforilacijo inducirana sprememba biofizikalnih lastnosti inotropnih glutamatnih receptorjev (N-metil-D-aspartata -NMDA in AMPA) in spodbuda prometa receptorjev AMPA v postsinaptično membrano. Indukcijo in/ali vzdrževanje čezmerne vzdražnosti osrednjega živčevja usmerjajo tudi metabotropni glutamatni receptorji pre ali postsinaptično. AMPA receptorji, ki jih aktivira glutamat okrepe sinaptični prenos signala tako na nivoju hrbtenjačnega mozga (lamina I, II), kot v hipokampusu in delih možganov udeleženih v občutenju bolečine (na mestu vstopa čutilnih nevronov v možgansko deblo in talamus in talamičnih nevronov v možgansko deblo).2 Danes je znano, da se bolečina procesira skozi mrežje struktur možganov, ki ga imenujemo matrica bolečine.18, 19 V tej matrici so ugotovili dva vzporedna sistema: središčni bolečinski sistem in lateralni bolečinski sistem z različnimi funkcijami. Središčni bolečinski sistem sestavljajo medialni talamus in perigenualna, srednja cingulatna in inzularna možganska skorja, ki so udeleženi pri procesiranju čustvenega vidika bolečine.20 Lateralni sistem je udeležen v procesiranju čutilno-ločevalnih vidikov zaznave bolečine (jakost, lokacija, trajanje) in ga sestavljajo lateralni talamus in njegove povezave s primarno in sekundarno somatosenzorično možgansko skorjo in povezave med ventromedialnim jedrom talamusa in inzularno možgansko skorjo.21 Pri bolečini RA so s pozitronsko emisijsko tomografijo možganov z 18F-fluorodeoksiglukozo ugotovili izrazito aktivacijo cingulatne skorje možganov. Izrazita aktivacija perigenualnega in srednjega cingulatnega korteksa je skladna s predelavo občutkov-emocij in spomina bolečine. Povečana aktivnost tega predela je povezana z emocionalnim odzivom na bolečino pri RA. Hkrati je povečana aktivnost tudi v amigdalah, orbitofrontalni skorji možganov in putamnu, predeli, ki so povezani z averzivnimi stanji, kaznijo in strahom. Zelo verjetno vlogo igra pri dojemanju bolečini RA strah pred bodočo poškodovanostjo sklepov in invalidnostjo. Ugotovili so tudi aktivacijo prefrontalnega dela skorje možganov in spodnjega zadnjega parietalnega dela skorje možganov, ki imata vlogo v nadzoru pozornosti. Raziskava Kulkarneja in sodelavcev je pokazala pomen središčnega bolečinskega sistema v doživljanju bolečine RA, ki igra vlogo v afektu, odporu in motivaciji. V tem sistemu so odkrili velike koncentracije opioidnih receptorjev. Morda bo v bodočnosti mogoče zdraviti bolečino RA z upoštevanjem teh spoznanj in razvojem inhibitorjev razgradnje enkefalinov, ki kot naravni opioidi zasedejo te receptorje.22 Vloga celic glie v nastanku vnetne bolečine S citokini inducirana aktivacija ciklooksigenaze-2 (COX-2) v celicah glie, astrocitih in endotelijskh celicah prispeva k ojačenju bolečinskega signala. Aktivacija celic glie (mikroglia, astrociti, DRG, satelitne celice, Schwanove celice) uravnava aktivnost nevronov, s tesno medsebojno povezavo pa te celice dodatno razširijo področje vzdraženosti možganov. Celice glie izločajo tudi številne mediatorje (NO, nevtrofine, IL-1 β, TNF-α, proste radikale), ki nekateri povzročajo sinaptogenezo, povezani pa so tudi z degeneracijo nevronov in izginjanjem inhibitornih internevronov.1
Zdravljenje bolečine pri RA K zmanjševanju bolečine pri RA lahko pripomorejo poučitev bolnika o naravi bolezni, o potrebi po spremembi življenskega sloga, kot je zmanjšanje telesne teže, gibalne vaje. Bolečino lahko zmanjšajo tudi vaje za krepitev grobe mišične moči, vaje za povečanje obsega giba, TENS, tudi ortoze in pomagala. Pri delu bolnikov, kjer kronična vnetna bolezen spremeni vedenje, pa psihološko spoznavna-vedenjska terapija. Pri težjih destruktivnih okvarah sklepov so potrebne vstavitve umetnih sklepnih endoprotez, ki povrnejo sklepno funkcijo in zmanjšajo bolečino. Temelj zdravljenja bolečine pa so seveda zdravila tako protibolečinska kot imunomodulirajoča protivnetna zdravila (slika 1).
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
131
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Zdravljenje z zdravili Paracetamol Paracetamol lahko uporabimo za zdravljenje blage do zmerne bolečinepri RA. Protibolečinsko verjetno deluje z inhibitornim učinkom na ciklooksigenazo-3 (COX-3) v osrednjem živčevju, z inhibicijo aktivnost receptorjev NMDA in stimulacijo descendentnih inhibitornih poti. Deluje tudi z inhibicijo COX-2, ki, je ključna za tvorbo prostaglandinov E. COX-2 je spodbujena v vnetem tkivu, poteh, ki vodijo v zadnje rogove hrbtenjače in višje centre osrednjega živčevja in celicah vnetnicah kot so makrofagi in endotelijskh celicah z učinkom IL-1 in drugih pro-vnetnih citokinov.3 Dokazano je, da paracetamol deluje proulcerogeno z inhibicijo tvorbe prostaglandinov pri kroničnem vnetju in s hipersekrecijo solne kisline v želodcu.24 Ugotovili so, da je relativno tveganje za nastanek razjede želodca ali dvanajstnika za paracetamol pri dnevnem odmerku večjem od 2000 mg 3,6. Ker je torej pracetamol v odmerkih večjih od 2000 mg proulcerogen, hkrati pa je protibolečinsko manj učinkovit kot NSAR ni učinkovita alternativa za zdravljenje bolečine pri bolnikih z RA in tudi drugimi vnetnimi revmatičnimi boleznimi. Paracetamol je tudi nevaren pri čezmernih uživalcih alkohola in bolnikih z jetrnimi boleznimi.25 Slika 1. Zdravljenje bolečine pri revmatoidnem artritisu
PARACETAMOL IN/ALI NSAR,* PARACETAMOL/TRAMADOL, OPIOIDNI ANALGETIKI
BOLEČINA
POUČITEV BOLNIKA, FIZIKALNA TERAPIJA, ORTOZE, POMAGALA
LEGENDA:
KOREKTIVNI OPERATIVNI POSEGI
GLUKOKORTIKOIDI,** DMAR,*** BIOLOŠKA ZDRAVILA
VNETJE
STRUKTURNE OKVARE SKLEPOV
*NSAR-nesteroidni antirevmatiki tako tradicionalni kot koksibi, ** glukokortikoidi per-os, parenteralno ali intraartikularno *** DMARD-imunomodulirajoča zdravila, ki spremene naravni potek bolezni (metotreksat, sulfasalazin, leflunomid, klorokvin/hidroksiklorokvin, ciklosporin A)
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
132
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Nesteroidni antirevmatiki (NSAR) NSAR delujejo protibolečinsko, protivnetno in protivročinsko. Že pred več kot dvajsetimi leti so odkrili, da so delovanje in neželeni učinki povezani z biosintezo prostaglandinov. Pri vnetju se iz poškodovanih fosfolipidnih celičnih membran z delovanjem encima fosfolipaze sprošča arahidonska kislina. Iz nje se s pomočjo encimov COX-1 in COX-2 sintetizirajo prostaglandini, s pomočjo 5-lipooksigenaze pa levkotrieni. Skupna lastnost prostaglandinov, ki nastajajo s pomočjo encima COX-2, je sprožitev in vzdrževanje vnetne reakcije. Prostaglandini pa ne nastajajo le na mestu vnetja, temveč imajo tudi pomembno fiziološko vlogo (nastajajo z delovanjem encima COX-1): v prebavilih ščitijo želodčno sluznico, vplivajo na gibanje debelega črevesja, v ledvicah uravnavajo krvni pretok, glomerulno filtracijo, izločanje vode in elektrolitov, na mestu okvare žilne stene endotelijski prostaciklin preprečuje nastanek krvnega strdka, tromboksan pa preprečuje krvavitev. Večina "klasičnih" nesteroidnih antirevmatikov, ki jih imamo pri nas, neselektivno zavira COX-1 in COX-2 ali imajo celo večjo afiniteto za COX-1 (npr. acetilsalicilna kislina, piroksikam, indometacin). NSAR in paracetamol zmanjšujejo bolečino še na številne druge načine: salicilati, nimesulid, paracetamol odstranjujejo kisikove radikale, NSAR zavrejo delovanje mieloperoksidaz sproščenih iz aktiviranih polimorfonuklearnih levkocitov, zavrejo nekatere metaloproteinaze odgovorne za razpad veziva vključno veziva v hrustancu in sinoviji. Nekateri NSAR zavirajo andamidno hidroksilazo in povzroče zvečano tvorbo andanamida, naravnega kanabinoida, ki deluje analgetično v višjih centrih osrednjega živčevja. Protibolečinski učinek različnih NSAR je odvisen tudi od njihove farmakokinetike in lastnosti, da se kopičijo v sinovialnem tkivu in tekočini.26 Osnovne smernice za uporabo nesteroidnih antirevmatikov so:27 • zdravila ne smemo prehitro menjavati; preden ga proglasimo za neučinkovitega, moramo počakati od 10 do 14 dni; • različnih nesteroidnih antirevmatikov med seboj ne kombiniramo; kombinacije delujejo antagonistično (tekmujejo za vezalne beljakovine), kar zmanjšuje njihov učinek in zveča možnost neželenih učinkov; • starejšim ne predpisujemo nesteroidnih antirevmatikov z dolgo razpolovno dobo (retardnih oblik preparatov), ker se s tem zveča tveganje za pojav neželenih učinkov; • otrokom in starejšim dajemo manjše odmerke; • lahko jih kombiniramo z analgetiki, če je njihov protibolečinski učinek prešibek, prav tako pa tudi z večino drugih zdravil, ki se uporabljajo v revmatologiji; Metaanaliza 15 randomiziranih placebo kontroliranih raziskav (RCT), ki je zajela 5986 zdravljenih, je pokazala, da so NSAR učinkovitejši od paracetamola za zmanjšanje bolečine pri artrozi kolena in kolka, zmerno učinkoviti so tudi za zmanjšanju bolečine pri revmatoidnem artritisu.28 Zaradi zmerno zvečanega tveganja za kardiovaskularne zaplete tako klasičnih NSAR, kot selektivnih zaviralcev COX-2 (koksibov), uporabljamo ta zdravila pri bolnikih s kardiovaskularnim tveganjem v najnižji učinkoviti dozi, kratek čas. Ta zdravila ne uporabljamo pri bolnikih z napredovalo ledvično boleznijo, težko vodljivo hipertenzijo in svežo razjedo dvanajstnika. Tveganje za pojav resnih stranskih učinkov je pri starostnikih večje.Ugotovili so, da je relativni rizik za nastanek razjede želodca ali dvanajstnika za nizke ali srednje odmerke NSAR 2,4, za visoke odmerke NSAR 4,9, za NSAR s kratkim plazemskim razpolovnim časom 3,1, za tiste z dolgim razpolovnim časom 4,4 in za za NSAR s počasnim podaljšanim sproščanjem kar 5,4.29, 30 Pri starejših od 65 let in bolnikih z anamnestičnim podatkom o razjedi zgornjih prebavil, krvavitvi ali perforaciji razjede, lahko predpišemo koksib, če bolnik ne prejema antiagregacijskih zdravil ali inhibitorjev protonske črpalke, če pa se odločimo za predpis klasičnega NSAR pa moramo starostniku hkrati predpisati inhibitor protonske črpalke. V Angliji priporočajo kot prvi NSAR uporabo nizkih odmerkov ibuprofena.31 V metanalizi osmih RCT, ki so ocenjevale tveganje za pojav perforacij razjed želodca in dvanajstnika, obstrukcij in krvavitev iz GIT, pri skupinah bolnikov zdravljenih s koksibi v primerjavi z bolniki zdravljenimi s neselektivnimi NSAR, so Rostom in sod. potrdili zmanjšanje relativnega tveganja pri jemalcih koksibov za 61 odstotkov, vendar je to predstavljalo le 0,4 % zmanjšanje absolutnega tveganja. Zmanjšanje tveganja je torej pri bolnikih, zdravljenih s koksibi, bolj statistično značilno, kot klinično pomembno.32 Tveganje za krvavitev iz GIT je pri bolnikih zdravljenih s kumarini in hkrati selektivnimi zaviralci COX-2, čeprav ti le malo inhibirajo trombocite, ali neselektivnimi NSAR, zvečano. Zato moramo biti pri hkratni uporabi teh ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
133
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
zdravil skrajno previdni, potrebne so pogoste kontrole protrombinskega časa in prilagajanje odmerka kumarina, še bolje pa je če takih kombinacij zdravil ne uporabljamo.33 Pri jemalcih NSAR je klinično pomemben tudi učinek na zvečanje krvnega tlaka. Hipertenzivnim bolnikom, ki jih zaradi bolečine zdravimo z NSAR težje uredimo krvni tlak. Bolniki, ki niso bili hipertoniki pa lahko to postanejo. Tveganje za poslabšanje srčnega popuščanja pri starostnikih, se poveča že v prvem tednu po uvedbi zdravljenja z NSAR.34, 35 Koksibi bolj zvečajo sistolični krvni tlak kot diastoličnega, kar pomembno zveča tveganje za srčno-žilne dogodke, kot so dokazali v raziskavi Framingham.36 Med koksibi celekoksib manj zveča sistolični krvni tlak v primerjavi z rofekoksibom, ki so ga prav zaradi zvečanega tveganja za srčno-žilne zaplete (srčni infarkt) umaknili s tržišča. Celekoksib zavira karboanhidrazo in ima diuretični učinek, kar pojasni manjši vpliv na porast sistoličnega krvnega tlaka.37 Kerney s sodelavci je v metaanalizi analiziral tveganje za srčno-žilne dogodke (srčni infarkt, možgansko kap, srčno smrt) pri bolnikih zdravljenih s koksibi in neselektivnimi NSAR vsaj štiri tedne. Pri bolnikih zdravljenih s koksibi je ugotovil 42 % zvečanje relativnega tveganja za resne žilne zaplete, predvsem tveganje za srčni infarkt (class effect), podobno zvečanje tveganja so potrdili tudi za neselektivne NSAR (class effect), kot sta v visokih odmerkih ibuprofen in diklofenak. Takega tveganja pa niso potrdili pri bolnikih zdravljenih z naproksenom.38 Pri sulfonskih inhibitorjih ciklooksigenaze-2 (rofekoksib, etorikoksib) so potrdili zvečano tveganje za aterotrombotične dogodke zaradi pro-oksidativnega delovanja na oksidacijo LDL (zvečanja dovzetnosti bioloških lipidov za oksidativno modifikacijo z ne-encimskim procesom) in hkrati zmanjšanja antioksidantne kapacitete za vezavo kisikovih radikalov v plazmi. Nasprotno pa takega učinka pri sulfonamidnih selektivnih zaviralcih ciklooksigenaze-2 (celekoksibu, meloksikamu) in neselektivnih nesteroidnih antirevmatikih niso dokazali, kar razloži nekoliko manjše tveganje le teh za aterotrombotične dogodke v primerjavi z rofekoksibom.39 Dejavnik tveganja za okvaro izločevalne sposobnosti ledvic z NSAR pri starostnikih in tudi mlajših bolnikih so: zmanjšano uživanje tekočin s posledično dehidracijo, izguba vode s telesno vadbo, driska, bruhanje, krvavitev, hiponatremija, čezmerna diureza zaradi zdravil ali bolezni, kot je sladkorna bolezen, zmanjšanje krvnega volumna zaradi zastojne srčne odpovedi, jetrna ciroza, nefrotski sindrom in kronična ledvična odpoved.40 Koksibi sicer ne zmanjšajo glomerulne filtracije tako kot neselektivni NSAR, vendar povzročajo retenco natrija. Pri starejših bolnikih, ki uživajo hrano z malo soli (srčni bolniki, bolniki zdravljeni z diuretiki, bolniki z jetrno cirozo), pa koksibi, podobno kot neselektivni NSAR pomembno zmanjšajo glomerulno filtracijo.41 Tudi pri bolnikih z urtikarijo in angioedemom ter bronhialno hiperodzivnostjo moramo biti pri predpisovanju selektivnih zaviralcev in neselektivnih NSAR skrajno previdni oziroma teh zdravil tem bolnikom ne predpisujemo.42 Priporočila Angleškega revmatološkega združenja za obvladovanje bolečine pri bolnikih z RA niti ne omenjajo zdravljenja z opiati. Ta priporočila svetujejo čim popolnejše obvladovanje sklepnega vnetja s temeljnimi imunomodulatornimi zdravili (metotreksatom, leflunomidom, sulfasalazinom), intraartikularnimi in intramuskularnimi aplikacijami glukokortikoidov in v primeru neučinkovitosti zdravljenja s temi zdravili, zdravljenje z biološkimi zdravili. Če s tem pristopom dosežemo remisijo vnetja, bolnik večinoma ne potrebuje trajnega zdravljenja bolečine z analgetiki in nesteroidnimi antirevmatiki. Neselektivne NSAR ali selektivne zaviralce COX-2 naj zdravnik predpiše v nizkih odmerkih, za krajši čas. V primeru, da bolnik prejema aspirin, svetujejo lajšanje sklepnih bolečin z neselektivnim NSAR in zaščito z inhibitorjem protonske črpalke. Pri zdravljenju bolečine pri bolnikih z srčno-žilnim ali gastrointestinalnim tveganjem priporočajo posebno previdnost pri predpisovanju tako neselektivnih NSAR, kot selektivnih zaviralcev COX-2. Obeh skupin zdravil pa ne smemo uporabiti pri bolnikih z dokazano ishemično boleznijo srca.43 Opioidni analgetiki Tramadol, ki je uporaben za zdravljenje zmerne do hude bolečine, deluje kot šibek agonist opioidnih receptorjev mu v osrednjem živčevju, hkrati pa tudi zavira ponovni prevzem noradrenalina in serotonina. Protibolečinsko delovanje je okrepljeno ob sočasni uporabi paracetamola.44 Močno moramo biti previdni pri sočasnem predpisovanju selektivnih zaviralcev prevzema sero------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
134
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
tonina, zaradi nevarnosti krčev in/ali serotoninergičnega sindroma,45 pa tudi pri bolnikih, ki že prejemajo opioidne analgetike in druga zdravila, ki lahko povečajo nevarnost krčev. Odmerek tramadola moramo zmanjšati pri bolnikih z ledvično odpovedjo in/ali okvaro jeter. Odmerek tramadola moramo zmanjšati tudi pri starostnikih starejših od 75 let z normalno ledvično in jetrno funkcijo, ker so serumske koncentracije zmerno zvečane, razpolovni čas pa nekoliko podaljšan v primerjavi z osebami starimi 65–75 let.46 Pogosto je učinek zdravljenja kronične mišično-skeletne bolečine z enim analgetikom nezadosten. Izkazalo se je, da je zdravljenje bolečine pri bolniku z RA z večimi analgetiki hkrati pogosto učinkovitejše. Učinkovita je predvsem kombinacija paracetamola in tramadola, pa tudi kombinacije NSAR in tramadola ali NSAR in šibkih opioidov. Vendar je do danes objavljenih le malo kvalitetno izvedenih RCT raziskav, ki podpirajo te kombinacije. Šibki in močni opioidni analgetiki Pri bolnikih z RA je indicirano zdravljenje bolečine z opioidnimi analgetiki predvsem pri napredovali okvari sklepov in pri nevropatski bolečini. Čeprav je zdravljenje bolečine z šibkimi opioidnimi analgetiki, kot je kodein, pri bolnikih z RA podprto z redkimi dokazi, pa ta zdravila ne povzročajo resnih okvar organov, v kombinaciji s paracetamolom pa so klinično varna tudi pri dolgotrajnem zdravljenju.47 Z opioidnimi analgetiki lajšamo bolnikom z RA srednje hude do hude kronične bolečine (bolnikova ocena bolečine na lestvici VAS (visual analogue scale 4–10), če so bili vsi ostali načini zdravljenja bolečine preizkušeni (farmakološki, nefarmakološki in kirurški ukrepi) in neučinkoviti in če je poskus lajšanja bolečine z opioidi učinkovit (zmanjšanje VAS za 30–50 %). Za zdravljenje bolečine RA so primerni predvsem bolniki: • ki imajo po uporabi drugih zdravil za lajšanje bolečin ogrožajoče in neobvladljive neželene učinke; • ki zaradi spremljajočih bolezni ali zdravljenja ne smejo prejemati drugih zdravil za lajšanje bolečine; • ki zaradi spremljajočih bolezni ali zdravljenja niso primerni za operativne posege; • ki dlje časa čakajo na operativno zdravljenje (npr. vstavitev kolčne endoproteze pri koksartrozi). Bolnike, ki jih zaradi kontraindikacij ne moremo zdraviti z NSAR, in bolnike, ki teh zdravil ne prenašajo, ali če je kombinirano zdravljenje s šibkimi opioidi neučinkovito, lahko zdravimo z močnejšimi opioidnimi analgetiki (oksikodonom v večjih odmerkih, hidromorfonom, morfinom, fentanilom). Opioidno odzivnost na močne opioide ugotovimo s peroralno ali parenteralno uporabo majhnih odmerkov kratkodelujočih opioidov v nekaj dneh (ambulantno ali hospitalno v skladu s priporočili SZZB). Učinkovit odmerek opioida in s tem zmanjšanje neželenih učinkov lahko dosežemo s sočasnim zdravljenjem z nesteroidnimi antirevmatiki in paracetamolom, če ti niso kontraindicirani. Če je zdravilo učinkovito, vendar povzroča neželene učinke (npr. slabost, zaspanost), te učinke zdravimo in bolniku razložimo, da pričakujemo, da bodo ti izzveneli v naslednjih 4 tednih. Pri slabem analgetičnem učinku izbranega močnega opioida lahko do trikrat poskusimo z drugimi opioidi. Zdravljenje nadaljujemo izključno s peroralno ali transdermalno uporabo učinkovin s podaljšanim sproščanjem. Zdravljenje je učinkovito in varno le, če je odmerjanje redno. Nenadna prekinitev lahko privede do življenje ogrožajočega odtegnitvenega sindroma. Zdravljenje z močnimi opioidnimi analgetiki prenehamo, kadar:48, 49 • je odpravljen vzrok bolečine; • med zdravljenjem ne dosežemo izboljšanja simptomov in funkcionalnega statusa bolnika; • se pojavijo hudi in neobvladljivi neželeni učinki; • bolnik ne spoštuje dogovorjenih pogojev zdravljenja (glej spodnjo preglednico). Raziskave so pokazale, da opioidni analgetiki umirjajo bolečino pri vnetju sprva s svojim centralnim delovanjem, kasneje pa je protibolečinski učinek vse bolj posledica vezave na opioidne receptorje, ki se ob vnetju v večji meri izrazijo na perifernih senzoričnih nevronih in na celicah vnetnicah.50, 51 Zdravila κ-opioidi delujejo protivnetno in umirjajo sklepno vnetje z zmanjšanjem z lipopolisaharidi spodbujene tvorbe IL-6, protivnetno delujejo pri revmatoidnem artritisu tudi ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
135
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
endogeni endomorfini, lokalno spodbujanje njihove tvorbe bi bilo zato smiselno pri zdravljenju te bolezni.52, 53 Analiza zdravljenja kronične ne-maligne bolečine 15 RCT je pokazala, da je mogoče jakost nevropatske bolečine in mišično-skeletne bolečine zmanjšati v povprečju za 30 odstotkov.54 V raziskavi Solomona in sodelavcev so kronično jemanje opioidov opredelili kot vsaj šest 30-dnevnih odmerkov letno, kar je v Pensilvaniji jemalo 4 % bolnikov z RA (55). V obsežni metaanalizi 41 RCT-raziskav, ki so vključile 6019 bolnikov s kronično nemaligno bolečino (v 80 % nociceptivno bolečino) zdravljenih v povprečju 6 tednov peroralno ali s šibkimi opioidi (tramadol, propoksifen, kodein) ali z močnimi opioidi (morfin, oksikodon) se je pokazalo, da opioidni analgetiki v primerjavi s placebom zmanšajo bolečino in izboljšajo funkcijsko stanje bolnikov. Močni opioidi tudi učinkoviteje zmanjšajo bolečino v primerjavi z naproksenom, ne pa tudi funkcijsko stanje, katerega učinkoviteje izboljšajo drugi analgetiki. Nasprotno pa šibki opioidi niso učinkoviteje zmanjšali bolečino in izboljšali funkcijskega stanja bolnikov v primerjavi z nesteroidnimi antirevmatiki. Med sopojavi sta izstopala le zaprtje in navzea, vendar so raziskovalci opozorili, da so nujne dolgotrajnejše raziskave, ki bi lahko raziskale pogostnost stranskih učinkov kot so spolna disfunkcija in zasvojenost.56 Vendar je predpis opioidnih analgetikov starejšim bolnikom, ki jim jemanje teh zdravil ne nadzorujejo svojci, tudi tvegano, saj v ZDA po letu 1990 ugotavljajo pravo nacionalno epidemijo nezgodnih smrti starostnikov zaradi zastrupitev z opioidnimi analgetiki.57 Razvoj peroralnih in transdermalnih učinkovin s počasnim sproščanjem je sicer povečal varnost in uporabnost močnih opioidov tudi za zdravljenje kronične ne-maligne bolečine, vendar so pri starostnikih ugotovili, da v pomembnem odstotku ne upoštevajo navodil proizvajalca predvsem glede časovnih razmakov pri uporabi peroralnih učinkovin s počasnim sproščanjem in pri menjavi samolepilnih nalepk fentanila.58 Dolgotrajno zdravljenje z močnimi opioidi ostaja zaradi številnih stranskih učinkov, kot so zaprtje, omotičnost, zaspanost in zvečano tveganje za padce in zlome, pri kroničnih vnetnih revmatičnih boleznih predvsem pri starostnikih, kontroverzno. Vsekakor pa so ta zdravila ob upoštevanju pravil: začni zdravljenje z nizkim odmerkom in ga počasi večaj do zadovoljivega protibolečinskega učinka ali pojava stranskih učinkov, pretehtaj tveganja kot so: pridružene bolezni (kronična obstruktivna pljučna bolezen, ledvična odpoved), zloraba drog, vožnja vozil ali upravljanje s stroji, dovolj varna in učinkovita. Pri odločitvi za zdravljenje z opioidnim analgetikom je pomemben tudi podatek ali je imel bolnik v preteklosti pri zdravljenju s katerim koli opioidnim analgetikom resne stranske učinke, oziroma zdravila ni prenašal.59 Glukokortikoidi Zdravljenje z glukokortikoidi vpliva na bolečino pri RA z učinkom na aktivacijo celic glije. Posebno uporabni so glukokortikoidi, ki prehajajo hematoencefalno bariero (prednisolon, triamcinolon) , ki lahko preprečijo aktivacijo celic glie in posledično sproščanje citokinov ter okvaro nevronov. Seveda pa učinkujejo steroidi v vnetih sklepih tudi s svojim protivnetnim učinkom na zmanjšanje aktivacije perifernih bolečinskih receptorjev. Zaradi znanih stranskih učinkov na kostno premeno in razvoj osteoporoze, ter slabšega celjenja prelomov pa seveda to niso zdravila, ki bi jih bolniku z RA predpisovali za daljši čas samo zaradi bolečine, temveč jih uporabljamo predvsem za premostitveno zdravljenje ob uvedbi temeljnih zdravil, predno je dosežen njihov polni učinek. Intraartikularne injekcije glukokortikoida, lahko za daljši čas umirijo vnetje sklepa in vnetje sluzne vrečke ali kitne ovojnice. Skrb, da bi ob ponavljanju aplikacij prišlo do trajne poškodbe sklepnega hrustanca zadnje raziskave niso potrdile.60 Zdravljenje z biološkimi zdravili Citokini, kot so IL-1, IL-8 in TNF-α, ki se sproščajo pri vnetju, so molekule ki spodbujajo bolečino, saj stimulirajo tvorbo in sproščanje drugih vnetje spodbujajočih agensov, kot je na primer bradikinin. Pomembno pa je tudi njihovo neposredno delovanje na bolečinske receptorje. V kliničnih raziskavah so potrdili analgetično delovanje bioloških zdravil- zaviralcev TNF-α (etanercepta, adalimumaba, infliksimaba), seveda pa ta zdravila zmanjšajo bolečino tudi z učinkovitim ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
136
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
zmanjšanjem sklepnega vnetja.61 Teh zdravil seveda ne predpisujemo samo za zdravljenje bolečine, vendar s pridom izkoriščamo njihovo protibolečinsko delovanje, kadar je njihov predpis upravičen zaradi neobvladanja RA s temeljnimi zdravili (imunomodulirajočimi zdravili, ki spreminjajo naravni potek bolezni: sulfasalazinom, metotreksatom, leflunomidom, ciklosporinom A). Infliksimab (Remicade®) je humano/mišje (himerno) monoklonsko protitelo, usmerjeno proti TNF-alfa. Z veliko afiniteto se veže na topni in membranski TNF-alfa ter tako prepreči njegovo vezavo na receptor. Zdravilo uporabljamo za zdravljenje revmatoidnega artritisa, luskavičnega artritisa in ankilozirajočega spondilitisa.Njegova razpolovna doba je 9 dni. Že ena sama infuzija zdravila lahko izboljša simptome bolezni. Če zdravljenje ni uspešno ali če po začetnem izboljšanju pride do poslabšanja bolezni, lahko zvečamo odmerek zdravila ali pa skrajšamo čas med odmerki.Zaradi razvoja protiteles proti infliksimabu se priporoča sočasno zdravljenje z metotreksatom. Ta kombinacija tudi bolj učinkovito zavira napredovanje rentgensko vidnih sprememb, kot zdravljenje samo z metotreksatom. Etanercept (Enbrel®) je rekombinantni dvovalentni receptor za TNF-alfa, ki je vezan na Fc del IgG1. Vezava TNF-alfa na ta združeni protein kompetitivno prepreči njegovo vezavo na naravni, površinski celični receptor in s tem onemogoči njegovo delovanje. Zdravilo uporabljamo za zdravljenje revmatoidnega in psoriatičnega artritisa v kombinaciji z metotreksatom, ter kot monoterapijo pri ankilozirajočem spondilitisu. Razpolovna doba etanercepta je 4 dni. Dobri učinki zdravljenja se pokažejo že po dveh tednih in se nato pri nadaljevanju zdravljenja tudi vzdržujejo. Adalimumab (Humira®) je rekombinantno humano protitelo, ki se z veliko afiniteto veže na TNFalfa in s tem prepreči njegovo vezavo na naravni receptor, hkrati pa deluje citotoksično tudi na celice, ki na svoji površini izražajo TNF-alfa. Zdravilo uporabljamo za zdravljenje revmatoidnega artritisa. Razpolovna doba adalimumaba je 14 dni. Zdravljenje poteka v kombinaciji z metotreksatom. Sprva so v raziskavah ugotavljali, da zaviralci TNF-alfa skoraj nimajo resnih neželenih učinkov. Ob vse pogostejši uporabi pa so ta zdravila povezali s številnimi neželenimi učinki: okužbami, reakcijami na vbodnem mestu ali infuzijskimi reakcijami, malignimi boleznimi, krvnimi odkloni in sindromi, podobnimi avtoimunskim boleznim. Čeprav je opisanih več različnih okužb, povezanih s tem zdravljenjem, je verjetno najpomembnejša reaktivacija tuberkuloze. Običajno izbruhne med drugim in petim mesecem zdravljenja, pogostejša je zunajpljučna lokalizacija bolezni z neznačilno klinično sliko. Pri bolnikih je treba pred začetkom zdravljenja s skrbno anamnezo, kliničnim pregledom, rentgenskim slikanjem pljuč in Mantouxovim testom izključiti latentno tuberkulozno okužbo. Zaviralce TNF-alfa povezujejo s pogostejšim razvojem limfoma pri bolnikih z revmatoidnim artritisom. Zavedati se je treba, da je pojavnost limfoma pri bolnikih z revmatoidnim artritisom večja kot med splošno populacijo. Med zdravljenjem z zaviralci TNF-alfa se lahko tvorijo številna protitelesa, ne le nevtralizirajoča (usmerjena proti sami učinkovini), ampak tudi avtoprotitelesa. Njihov pomen ni povsem pojasnjen. Sistemski lupus eritematozus, povzročen s temi zdravili, se razvije zelo redko. Opisani so primeri poslabšanja prej umirjene multiple skleroze in pojav nove demielinizirajoče bolezni ob zdravljenju s temi zdravili. Previdnost je potrebna tudi pri zdravljenju bolnikov s srčnim popuščanjem. Anakinra (Kineret®) je rekombinantni antagonist receptorja za IL-1 in je trenutno na trgu edini zaviralec IL-1. Tega sproščajo monociti, makrofagi in nekatere specializirane sinovijske celice. IL-1 spodbuja vnetje predvsem z indukcijo IL-6 in COX-2. Pri bolnikih z revmatoidnim artritisom so v vnetih sklepih ugotovili manjše vrednosti naravnega zaviralca receptorja IL-1 od pričakovanih, kar je morda vzrok za kronično vnetje. Anakinra ima kratko razpolovno dobo 6 ur. Zdravilo se je izkazalo samo ali skupaj z metotreksatom za bolj učinkovito od placeba, pomembno pa upočasni tudi nastajanje rentgensko vidnih sklepnih sprememb. Najpogostejši neželeni učinek je omejena kožna reakcija na mestu vboda, ki je običajno blaga in izzveni v nekaj tednih. Pogostejše so tudi okužbe, predvsem bakterijske. Zaradi zmanjšanega števila nevtrofilcev in/ali krvnih ploščic, ki so ju ugotovili pri manjšem številu bolnikov, se ob zdravljenju s tem zdravilom priporoča občasni nadzor krvne slike.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
137
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Rituksimab (MabThera®) je z genskim inženiringom pridobljeno himerno mišje/humano monoklonsko protitelo; je glikoziliran imunoglobulin s humanim IgG1 konstantnim delom in mišjo lahko verigo v variabilnem delu. Domena rituksimaba Fab se veže na antigen CD20 na B-limfocitih in preko domene Fc sproži imunska dogajanja, ki privedejo do celične smrti z apoptozo. Rituksimab v kombinaciji z metotreksatom uporabljamo pri zdravljenju bolnikov z aktivnim revmatoidnim artritisom, kjer druga imunomodulirajoča zdravila, vključno z enim ali več zaviralci TNF, niso bila uspešna ali zdravil niso prenašali. Rituksimab zmanjša klinično in laboratorijsko aktivnost revmatoidnega artritisa in izboljša kakovost bolnikovega življenja. Zdravilo dajemo v dveh intravenskih infuzijah skozi poseben kanal. Razmak med obema infuzijama je 14-dnevni. Ob infuziji je potrebno skrbno opazovanje bolnika zaradi možnih reakcij na zdravilo, ki jih sproži sprostitev citokinov in/ali drugih kemičnih mediatorjev. Zato v premedikaciji vedno uporabljamo glukokortikoide, ki zmanjšajo pogostnost in resnost teh reakcij. Zdravljenje ponovimo v razmaku več kot 16 tednov. Kontraindikacije so preobčutljivost za zdravilno učinkovino ali pomožne snovi ali beljakovino glodalcev, dojenje in nosečnost, hude aktivne okužbe, hudo srčno popuščanje (IV. razred NYHA) in huda, neobvladljiva bolezen srca. Najpogostejši neželeni učinki rituksimaba so akutne reakcije, povezane z infuzijo, okužbe, predvsem zgornjih dihal in sečil, redkeje bronhospazem, nevtropenija, zelo redki pancitopenija, aplastična anemija in drugi neželeni učinki, povezani s posameznimi organskimi sistemi.62, 63 Zaključek Kljub napredku v razumevanju patogeneze bolečine vnetne revmatične bolezni kot je RA ostajajo številna vprašanja, predvsem temeljno in to je: kaj se dejansko dogaja bolečinskim receptorjem, da vzdržujejo kronično bolečino, nerešeno. Tako na primer ni jasno, zakaj je včasih bolečina vnetega sklepa epizodična, pri drugih bolnikih pa je kronična in stalna. Pomembno je, da z imunomodulirajočim zdravljenjem obvladamo vnetje, saj s tem zmanjšujemo ali odpravimo tudi bolečino vnetega sklepa. Bodočnost zdravljenja bolečine revmatoidnega artritisa in različnih drugih vnetnih revmatičnih bolezni je zdravljenje bolečine z bolj usmerjenimi, specifičnimi zdravili z učinkom na različne ionske kanale živcev in zdravili α-2 agonisti, ki spodbujajo inhibitorno nevronalno aktivnost v vnetem tkivu in hrbtnjačnem mozgu, ter zdravili z učinkom na prostaglandinske in opioidne receptorje v hrbtenjači. Literatura 1. Dray A. New Horizons in Pharmacologic treatment for Rheumatic Disease Pain. Rheum Dis Clin N Am 2008; 34: 481-505. 2. Fitzcharles MA, Shir Y. New concepts in rheumatic pain. Rheum Clin N Am 2008; 34: 267-83. 3. Wolfe F, Michaud K. Assessment of pain in rheumatoid arthritis: Minimal clinically significant diference, predictors, and the effect of anti-tumor necrosis factor therapy. J Rheumatol 2007; 34: 1674-83. 4. McDougall JJ. Arthritis and pain: Neurogenic origin of joint pain. Arthritis Research&Therapy 2006; 8: 220-9. 5. Gauldie SD, McQueen DS, Pertwee R, Chessell IP. Anandamide activates peripheral nociceptors in normal and arthritic rat knee joints. Br J Pharmacol 2001; 132: 617-21. 6. Bingham B, Ajit KS, Blake DR, Samad TA. The molecular basis of pain and its clinical implications in rheumatology. Nature Clin Practice Rheumatol 2009; 5: 28-36. 7. Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, et al. A TRP channel that senses cold stimuli and menthol. Cell 2002; 108: 705-15. 8. Caterina MJ, Schumacher MA, Tominaga M,Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat activated ion channel in the pain pathway. Nature 1997; 389: 816-24. 9. Dray A. New horizons in pharmacologic treatment for rheumatic disease pain. Rheum Dis Clin N Am 2008; 34: 481-505. 10. Omoigui S. The biochemical origin of pain: The origin of all pain is inflamation and the inflammatory response. Part 2 of 3 –Inflammatory profile of pain syndromes. Medical Hypotheses 2007; 69: 1169-78. 11. Kean WF, Rainsford KD, Kean IRL. Management of chronic musculosceletal pain in the elderly: Opinions on oral medication use. Review. Inflammopharmacology 2008; 16: 53-75. 12. Kidd BL. The expanding role of the nervous system in arthritis. EULAR Bull 1993; 4: 134-7. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
138
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
13. Shanahan F, Denburg JA, Fox J, Bienenstock J, Befus D. Mast cell heterogeneity: effects of neuroenteric peptides on histamine release. J Immunol 1985; 135: 1331-7. 14. Vergnolle N, Wallace JL, Bunnett NW, Hollenberg MD. Protease-activated receptors in inflammation, neuronal signaling and pain. Trends Pharmacol Sci 2001; 22: 146-52. 15. Cutolo M, Straub RH. Circadian rhytms in arthritis: Hormonal effects on the immune/inflammatory reaction. Autoimmunity Reviews 2008; 7. 223-8. 16. Li Z, Proud D, Zhang C, Wiehler S, McDougall JJ. Chronic arthritis downregulates peripheral mu-opioid receptor expression with concomitant loss of endomorfin-1 anti-nociception. Arthritis Rheum 2005; 52: 3210-9. 17. Coderre TJ, Katz J, Vaccarino AL, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 1999; 52: 259-85 18. Melzack R, Casey KL. Sensory, motivational and central control determinants of pain: a new conceptual model In: Kenshalo DR, editor. The skin senses. Spriengfield (IL). Charles C.Thomas; 1968: 423-43. 19. Peyron R, Laurent B, Garcia-Larrea L. Functional imaging of brain responses to pain: a review and metaanalysis (review). Neurophysiol Clin 2000; 30: 263-88. 20. Vogt. BA. Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci 2005; 6: 533-44. 21. Craig AD. Pain mechanisms: labeled lines versus convergence in central processing. Annu Rev Neurosci 2003; 26: 1-30. 22. Kulkari B, Bentley DE, Elliott R, Julyan RJ, Boeger E, Watson A, et al. Arthritic Pain is processed in brain areas concerned with emotions and fear. Arthritis Rheum 2007; 56: 1345-54. 23. GrahamGG, Scott KF. Mechanism of action of paracetamol. Am J Ther 2005; 12: 46-55. 24. Rainsford KD, Whitehouse MW. Paracetamol (acetaminophen)-induced gastrotoxicity: revealed by induced hyperacidity in combination with acute and chronic inflammation. Inflammopharmacology 2006; 14: 150-4. 25. Hungin AP, Kean WF. Nonsteroidal Anti-Inflammatory Drugs: Overused or uderused in osteoarthritis? Am J Med 2001; 110: (S-11S.) 26. Kean WF, Buchanan WW. The use of NSAIDs in rheumatic disorders 2005: A global perspective. Inflammopharmacology 2005; 13: 343-70. 27. Kos-Golja M. Zdravljenje revmatičnih bolezni z zdravili: Nesteroidni antirevmatiki. In: Kos-Golja M, Praprotnik S. Revmatološki priročnik za družinskega zdravnika. 3.dopolnjena izdaja. Lek 2007: 226-31. 28. Rainsford KD. New combinattions of anti-inflammatories for therapy of arthritic, neurological and malignant diseases. Inflammopharmacology 2004; 12: 211-3. 29. Hochberg MC, Altman RD, Brandt KD, Clark BM, Dieppe PA, Griffin MR, et al. Guidelines for medical management of osteoarthritis. Part I. Osteoarthritis of the hip. American College of Rheumatology. Arthritis Rheum 1995; 38: 1535-40. 30. Hochberg MC, Altman RD, Brandt KD, Clark BM, Dieppe PA, Griffin MR, et al. Guidelines for medical management of osteoarthritis. Part II. Osteoarthritis of the knee. American College of Rheumatology. Arthritis Rheum 1995; 38: 1541-6. 31. National Prescribing Centre. Cardiovascular and gastrointestinal safety of NSAIDs. MeReC Extra Issue 2007; No 30. 32. Rostom A, Muir K, Dubé C, Joliceuer E, Boucher M, Joyce J, et al. Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochran Collaboration systematic review. Clin Gastroenterol Hepatol 2007; 5 (7): 818-28. 33. Battistella M, Mamdami MM, Juurlink DN, Rabeneck L, Laupacis A. Risk of upper gastrointestinal hemorrhage in warfarin users treated with nonselective NSAIDs or COX-2 inhibitors. Arch Inter Med 2005; 165: 189-92. 34. Rossat J, Maillard M, Nussberger J, Brumner HR, Burnier M. Renal effects of selective cyclooxygenase-2 inhibition in normotensive salt depleted subjects. Clin Pharmacol Ther 1999; 66 (1): 76-84. 35. Page J, Henry D. consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognised public health problem. Arch inter med 2000; 160 (6): 777-84. 36. Kannel WB. Fifty years of Framingham Study contributions to understanding hypertension. J Hum Hypertens 2000; 14 (2): 83-90. 37. Fitzgerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001; 345 (6): 433-42. 38. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cycooxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 2006; 332 (7553): 1302-8. 39. Walter MF, Jacob RF, Day CA, Dahlborg R, Weng Y, Mason RP, et al. Sulfone COX-2 inhibitors increase susceptibility of human LDL and plasma to oxidative modification: Comparison to sulfonamide COX-2 inhibitors and NSAIDs. Atherosclerosis 2004; 177 (2): 235-43. 40. Patrono C, Dunn MJ. The clinical significance of renal prostaglandin synthesis. Kidney 1987; 32 (1): 1-12. 41. Swan SK, Rudy DW, Lasseter KC, Ryan CF, Buechel KL, Lambrecht LJ, et al. Effect of cyclooxigenase-2 inhibition on renal function in elderly person receiving a low-salt diet. A randomised, controlled trial. Ann Inter. Med 2000; 133 (1): 1-9. 42. Serrano C, Valero A, Picado C. Usefulness of montelucast to prevent adverse reactions to COX-2 selective inhibitors: A case report. J Invest Allergol Clin immunol 2005; 15 (2): 156-7. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
139
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
43. Raashid Luqmani, Hennell S, Estrach C,et al. On behalf of the British Society for Rheumatology and British Health Professionals in Rheumatology Standards, Guidelines and Audit Working Group. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for management of rheumatoid arthritis (after the first 2 years). Rheumatology 2009; 48 (4): 436-9. 44. Mullican WS, Lacy JR; TRAMAP-ANAG-006 Study Group: Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination capsules for the management of chronic pain: a comparative trial. Clin Ther 2001; 23: 1429-45. 45. Ripple MG, Pestaner JP, Levine BS, Smialek JE. Lethal combination of tramadol and multiple drugs affecting serotonin. Am J Forensic Med Pathol 2000; 21: 370-4. 46. Tramadol; www.medicinenet.com (Accessed March 20, 2007) 47. Langford RM. Pain management today-what have we learned? Clin Rheumatol 2006; 25: 2-8. 48. Praprotnik S. Zdravljenje revmatičnih bolezni z zdravili: Analgetiki. In: Kos-Golja M, Praprotnik S. Revmatološki priročnik za družinskega zdravnika. 3.dopolnjena izdaja. Lek 2007: 217-25. 49. Lahajnar Čavlovič S, Krčevski N, Stepanovič A, Čufer T. Priporočila za zdravljenje bolečine pri odraslem bolniku z rakom: Močni opioidi. Janssen-Cilag 2008: 15-27. 50. Siegel L, Piere M, Stein C, Baerwald C. Opioide bei muskulo-skelettalen Schmerzen. Z Rheumatol 2008; 67: 646-52. 51. Machelska H, Schopohl JK, Mousa SA, Labuz D, Schäfer M, Stein C. Different mechanisms of intrinsic pain inhibition in early and late inflammation. J Neuroimmunol 2003; 141: 30-9. 52. Walker JS. Anti-inflammatory effects of opioids. Adv Exp Med Biol 2003; 521: 148-50. 53. Straub RH, Wolff C, Fassold A, Hofbauer R, Chover-Gonzales A, Richards LJ, Jessop DS. Anti-inflammatory role of endorfins in osteoarthritis, rheumatoid arthritis and adjuvant-induced polyarthritis. Arthritis Rheum 2008; 58 (2): 456-66. 54. Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: Systematic review of efficacy and safety. Pain 2004; 112: 372-80. 55. Solomon DH, Avorn J, Wang PS, Xu X, Schein J, Vallow S, et al. Prescription opioid among older adults with arthritis or low back pain. Arthritis Rheum 2006; 55 (1): 35-41. 56. Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E. Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ 2006; 174 (II): 1589-94. 57. Paulozzi LJD, Budnitz DS, Xi Y. Opioid analgesics and rates of fatal drug poisoning in the United States. Am J Prev Med 2006; 31 (6): 506-11. 58. Ackerman SJ, Mordin M, Reblando J, Xu X, Schein J, Vallow S, et al. Patient- reported utilization patterns of fentanyl transdermal system and oxycodone hydrochloride controlled release among patients with chronic nonmalignant pain. J Manag Care Pharm 2003; 9 (3): 223-31. 59. Katz WA. Opioids for nonmalignant pain. Rheum Dis Clin N Am 2008; 34: 387-413. 60. Raynauld JP, Buckland-Wright C, Ward R, Choquette D, Haraoui BN, Martel-Pelleteir J. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis: A randomised trial. Arthritis Rheum 2003; 48; 370-77. 61. Kidd BL, Langford RM, Wodehouse T. Arthritis and pain.Current approaches in the treatment of arthritic pain. Arthritis Res Therapy 2007; 9 (3): 214. 62. Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Emery P, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2006. Ann Rheum Dis 2006; 65 Suppl III: iii2-iii15. doi: 10.1136/ard. 2006.061937. 63. Praprotnik S. Biološka zdravila. In: Kos-Golja M, Praprotnik S. Revmatološki priročnik za družinskega zdravnika. 3.dopolnjena izdaja. Lek 2007: 246-9.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
140
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
ZDRAVLJENJE TRADOVRATNIH GLAVOBOLOV IN NEVRALGIJE TROVEJNEGA ŽIVCA REFRACTORY HEADACHE AND TRIGEMINUS NEURALGIA TREATMENT Zvezdan Pirtošek, Bernard Meglič Department of Neurology, Neurology Division, University Medical Centre Ljubljana, Ljubljana, Slovenia
On refractory headaches There is currently no unanimously accepted definition of refractory headaches. Some proposals are currently worked on at the Refractory Headache Special Section of the American Headache Society. A headache can be labeled as refractory as the headache with no rebound, which has been unresponsive to multiple and combined symptomatic and preventive therapies in appropriate doses for a reasonable period of time, including trigger-point injections and medications such as antidepressants, calcium-channel blockers, beta blockers, triptans, and antiepileptics. Some would add that such a headache should be present a considerable time (e.g. at least 15 days per month), associated with disability, and that the diagnosis should be made by a headache specialist or a neurologist with headache expertise (minutes of the AHS). Also, there is little data on the prevalence which – in individual practices - may reach of 10% (minutes). However, the inability to relieve the pain often leads to desperation on the part of the patient and frustration on the part of the patient, his family as well as the physician. Pathophysiological mechanisms in various headaches differ but their understanding may be important for a logical therapeutic intervention in a specific form of headache. The pathophysiology of refractory headaches however remains unclear with the central sensitization being the most likely mechanism. Management of refractory headache often requires (a combination of) aggressive medications and therefore a specific organization of the service delivery. Organization of the service for management of refractory headaches Aggressive headache treatment should be delivered in a specialty headache clinic not in a usual emergency unit. Patients often need much wider range of effective and definitive treatments (as a rule not all of them available at the emergency unit) and as these treatments (e.g. various I.V. drugs) are often aggressive and potentially dangerous for the patient the environment of the speciality headache clinic should offer the patient a maximum of degree of safety at a more cost- and time-effective mode (Scott/Krusz et al 2005). An optimal clinic set up would include a comfortable room where patients can be treated with lights dimmed and where other members of staff (psychologists, other clinicians) may join in; a possibility for cervical and lumbar traction, a fluoroscopy room and an EEG room that can be used for IV treatments; pulse oximetry monitoring and nursing staff trained in IV therapy to start and monitor IV lines. Medications in refractory headaches MgSO4 (Magnesium Sulfate) – treatment of an intractable headache in a speciality clinic may start with Magnesium Sulfate IV. If MgSO4 alone is not beneficial, a combination with IV ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
141
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
steroids may work. There is a substantial literature on the use of magnesium intravenously for migraines and cluster headaches. Steroids – may be beneficial particularly for the cluster headache, status migrainosus, analgesic rebound (medication overuse) headaches, for refractory migraines, for helping the detoxification regimens, and for pain flare-ups. Dihydroergotamine (DHE) - can be given IV or IM and has a 10- to 14-hour half-life. It may be given every 8 hours with IV metochlopramide, 10mg, for two to three days. Valproate Sodium – apart from being used as an oral prophylactic in treating migraines in a prophylaxis manner. IV version of the valproate sodium may be used in intractable migraines. Propofol – selectively acting on subtypes of the GABA A receptors, propofol was - serendipitously – found to be one of the most effective IV agents, with a 95.4% success rate in reducing ongoing migraines (Scott-Krusz). The total dose was 120mg, given slowly by IV push 20mg at a time. Application needs pulse oxymetry. Lidocaine – the action of lidocaine, a Na+ channel blocker, is short lived (12–48 hours) and it may be used to buy time for the effect of other treatments. It should be initiated very slowly, so as to saturate the Na+ channels and obtain the best possible blockade. IV lidocaine may be part of a regimen of daily or nearly-daily IV treatments to break a cycle of headache. Although not the drug of the first choice, IV lidocaine may be particularly effective in a combination with MgSO4 (a Ca+ channel blockade), along with IV dexamethasone. Application needs pulse oxymetry. Tramadol - demonstrating opiate-like effects on the mu receptor, as well as weak presynaptic reuptake inhibition of norepinephrine and serotonin, the IV preparation of tramadol may be very efficacious in the treatment of refractory headaches with pain flare-ups. 50mg IV every 5-15 minutes may be given in the clinic and if efficacious the patient should continue on oral tramadol. Levetiracetam (Keppra™) – demonstrating a unique mechanism of blocking high-voltage Ca channels, levetiracetam IV is used in the treatment of refractory migraines, cluster headache flare-ups and trigeminal neuralgia. Many regard it as a powerful, non-toxic form of treatment for many difficult pain and headache flare-ups. Ketamine - an antagonist of NMDA-type glutamate receptors ketamine subcutaneously and intranasally was shown to decrease migraine attacks. Application needs pulse oxymetry. When intractable headache is accompanied by severe nausea, this can be relieved by IV droperidol, metochlopramide, promethazine, prochlorperazine, and ondansetron. Botulinum toxin (BT) in refractory headaches and trigeminal neuralgia Anecdotal reports in early years after the introduction of BT described the analgetic effect of the substance, particularly on migraines and different theories tried to explain the beneficial effect of botulinum toxin in relieving headache. The oldest theory proposed a reduction of muscular hyperactivity (Gobel et al 2001). The blockage of acetylcholine release from the presynaptic terminal would lead to a relaxation in the muscle. However, this theory fails to explain (i) why pain relief often occurs before the muscular relaxation; (ii) why pain relief occurs in areas that display no contraction or dystonia and this theory contradicts the theoretical view held by some that muscle overactivity is more likely a reflex central process, with pain leading to muscle activity, rather than opposite. Another theory involves the "normalization of excessive muscle spindle activity”. Rosales demonstrated botulinum induced inhibition of infrafusal muscle fibers along with a change in muscle spindle activity (Rosales et al 1996) resulting in less sensory information traveling from the 1a afferents from the muscle to the CNS, also from a domain outside of the directly involved pathway due to multiple reflex and centrally projecting pathways that are connected. Another proposed mechanism of botulinum action involves its possible entry into the CNS leading to pain modulation. Botulinum toxin was found to inhibit release of substance P from trigeminal nerve endings, activate ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
142
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
expression of substance P in the raphe nuclei (van den Bergh) and inhibite SNAP-25 thus blocking neurotransmitter exocystos and decreasing pain. BT was found in the dorsal root ganglia 2 days after injection, a time lag which correspondnds corresponds to pain relief (Binder). Another site of an analgesic action could be the postganglionic sympathetic nerve ending that uses norepinephrine and ATP as transmitters with norepinephrine increasing cases of chronic pain, and ATP acting as a stimulant of muscle nociceptors. If BT inhibits the release of these transmitters, it can then be analgesic in cases of sympathetically maintained pain ( e.g. the complex regional pain syndrome). BT induced decrease parasympathetic outflow would also explain its effect in headaches associated with the involvement of the trigemino-cervical complex and the pterygopalatine ganglion. These structures are integral in the autonomic symptoms and vasomotor control. Numerous studies have been published on the use of botulinum toxin for migraine and tension headache and much less for trigeminal neuralgia. For migraine, beneficial effects included decreased severity of migraines, less number of days utilizing migraine medications, and reduced migraine-associated vomiting (Silberstein et al 2000). In most studies, favourable response was reported to be about or above 50% (Silberstein et al 2000, Binder et al 2000). Several possible approaches with different protocols are described. Glabellar injections as well as combinations of frontalis, temporalis, and glabellar sites may lead to more complete relief. Optimal dosing of BTA remains an unresolved issue and it ranges widely. One multicenter double-blind study of 123 patients demonstrated that when a low dose (25 units of BOTOX) was compared to a higher dose (75 units BOTOX), the improvement was similar but there were significantly less fewer adverse events in the low dose (Silberstein). Early studies on botulinum toxin for tension headache have generally yielded less favourable results compared to those for migraine (Porto 1999, Relja 1999, Rollnik et al 2000, Smuts et al 1999). In one study where higher doses of BTA were utilized (80-150 units), 58% of those with CDH did achieve positive outcomes (Smuts et al 1999). In Shmuts’ double-blind, placebo-controlled, randomized study involving 40 patients with chronic tension-type headache the number of headache-free days was significantly increased in the BT group at 3 months post treatment, however, another (Rollnik et al 2000) double-blind, placebo-controlled and randomized revealed no significant differences through 12 weeks for chronic tension-type headache. Several studies suggest that botulinum toxin may represent a useful therapeutic tool in the management of patients with trigeminal neuralgia (Micheli et al 2002, Piovesan et al. 2005 and Borodic and Acquadro 2002). Borodic and Acquadro reported 11 cases of patients with trigeminal neuralgia, otherwise unresponsive to at least 3 drugs, treated with BT injections (Botox®) with doses ranging from 25 to 75 U. Eight out of eleven responded to treatment with a benefit duration ranging from 2 to 4 months. Piovesan and coworkers (2005) reported thirteen patients with trigeminal neuralgia treated with botulinum toxin type A injected transcutaneously among the trigeminal branches. All patients had benefit from this treatment, reducing significantly the visual analog scale pain score. Peak effect was reached 20 days after injection, lasting for more than 60 days in all patients. In Zuniga et al study (2008) ten of 12 patients reported a significant benefit from botulinum toxin injections, with reduction or even disappearance of pain, and remained pain free for as long as 60 days. At the Ljubljana UMC Department of Neurology Botulinum toxin is being used for dystonia, spasticity and cerebral palsy since 1987, for intractable headaches since 1999 and for trigeminal neuralgia since 2008. We are currently assessing the clinical effects of botulinum toxin type A injections in 17 patients with cranial painful syndrome, among them 9 patients with otherwise unresponsive trigeminal neuralgia, 4 with intractable migraine and 4 with painful jaw opening or jaw closing dystonia. For migraine we use glabellar, frontal, temporal and occasionally suboccipital sites. In our experience, lower doses are efficient in the frontal and temporal regions, but posterior, suboccipital muscles need larger doses. One sided injection is repeatedly effective in a patient with a well defined hemicrania. For patients with jaw closing and jaw opening dystonia the masseter and the lateral pterygoid muscles are infiltrated, respectively. Patients with trigeminal neuralgia are infiltrated with 3–6 units of Dysport per injection site. Injections are performed 10 mm apart to cover the painful anatomic region. The depth of the injection is appx. 1 to 3 mm. This double blind and cross-over ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
143
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
study has not been unblinded as yet and the preliminary results will be reported by the end of the year. Interesting and unexplained remains a possible extremely rapid action of pain control by the toxin in our series (within minutes) and shorter duration of analgetic effect compared to the motor effect which usually lasts between 3 and 6 months. In conclusion, botulinum toxin shows some benefit in the management of headache as recognized by the FDA. It is particularly effective for certain selected patients with migraine and probably effective for certain selected patients with trigeminal neuralgia. The efficacy is less convincing in patients with chronic daily headaches. The safety profile of botulinum toxin in the treatment of headaches has been well established and adverse effects rare and mild. Unresolved questions regarding the use of botulinum toxin in headache patients include delineation of the optimal sites and of the optimal doses of injection. References 1. Binder WJ, Brin MF, Blitzer A, Schoenrock LD, Pogoda JM. Botulinum toxin type A (Botox) for treatment of migraine headaches: an open-label study. Otolaryngol Head Neck Surg 2000; 123: 669-76. 2. Borodic GE, Acquadro MA. The use of botulinum toxin for the treatment of chronic facial pain. J Pain 2002; 3: 21-7. 3. Goadsby PJ, Zagami AS, Lambert GA. Neural processing of craniovascular pain: a synthesis of the central structures involved in migraine. Headache 1991; 31: 365-71. 4. Gobel H, Heinze A, Katja Heinze-Kuhn, Austermann K. Botulinum toxin A in the treatment of headache syndromes and pericranial pain syndromes. Pain. 2001.91: 195-9. 5. Micheli F, Scorticati MC, Raina G. Beneficial effects of botulinum toxin type a for patients with painful tic convulsif. Clin Neuropharmacol 2002; 25: 260-2. 6. Piovesan EJ, Teive HG,, Kowacs PA, Della Coletta MV, Werneck LC, Silberstein SD. An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology 2005;65: 1306-8. 7. Porto M. Botulinum toxin type A injections for myofascial pain syndrome and tension-type headache. Eur J Neurology 1999; 6 (suppl 4): S103-9. 8. Relja M. Botulinum toxin type A in the treatment of tension-type headache. Presented at the 9th World Congress on Pain, Vienna, Austria, August 22-27, 1999, and at the International Conference 1999: Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins, Orlando, FL, November 16-18, 1999. 9. Rollnik JD, Tannenberger O, Schubert M, Schneider U, Dengler R. Treatment of tension-type headache with botulinum toxin type A: A double-blind, placebo-controlled study. Headache 2000; 40: 300-5. 10. Rosales RL, Arimura K, Takenaga S, Osame M. Extrafusal and intrafusal muscle effects in experimental botulinum toxin-A injection. Muscle Nerve 1996: 19 (4): 488-96. 11. Scott-Krusz, V; Belanger, Jeanne, RN; Cagle, Jane, LVN; Krusz, John Claude. "Effectiveness of IV Therapy in the Headache Clinic for Refractory Migraines." Poster presentation to the annual conference of the European Federation of Neurologic Societies; Athens, Greece. September, 2005. 12. Smuts JA, Baker MK, Smuts HM, Rheta Stassen JM, Rossouw E, Barnard PWA. Prophylactic treatment of chronic tension-type headache using botulinum toxin type A. Eur J Neurology 1999; 6 (Suppl 4): S99-102. 13. Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type A as a migraine preventive treatment. Headache 2000; 40: 445-50. 14. Zúñiga, Sergio Díaz, Fabián Piedimonte, Federico Micheli. Beneficial effects of botulinum toxin type A in trigeminal neuralgia. Arq Neuropsiquiatr 2008; 66 (3-A): 500-3.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
144
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
COMPLEX REGIONAL PAIN SYNDROMES AND SIMILAR PAINFUL POSTTRAUMATIC STATES INVOLVING UPPER EXTREMITY Krunoslav Margić,1 Jelka Pirc2 1
Oddelek za plastično in rekonstruktivno kirurgijo, Kirurška služba in 2Oddelek za anestezijo in intenzivno medicino, Splošna bolnišnica Nova Gorica, Šempeter pri Gorici
Abstract. Complex regional pain syndrome (CRPS) is a heterogeneous disorder that develops secondary to injury or immobilization. Its pathophysiology and natural history are unknown. Some diffuse chronic posttraumatic reactions mimic CRPS. Since diffuse chronic pain states dynamically change during time and treatment, frequent team reevaluations are mainstay of differential diagnosis and treatment. Authors use simple working classification: borderline, pseudo-CRPS, CRPS-like and real CRPS group. There is no known therapeutic regime that can cure CRPS. Continuous regional analgesia (CRA) maintained for at least one week offers effective control of pain necessary to allow early active and painless physiotherapy. Outcomes, in the treatment of 30 patients with CRA were: eight excellent (completely normal hand), seventeen good (no spontaneous pain, at least 50% decrease of use-related pain and at last 50% mobility and strength) and five poor.
During Civil War in US Silas Weir Mitchell worked in the Turners Lane Hospital in Philadelphia specialized in nerve injuries. In the book Injuries of Nerves and Their Consequences published in 1872 he described the treatment of wounded soldiers with injuries of major peripheral nerves suffering from diffuse chronic and intractable pain and treated with rest and frequent hypodermic injections of morphine.1). From that time morphine and its derivates were frequently suggested in the treatment of the condition known as causalgia. Thirty years later and five years after Wilhelm Conrad Roentgen obtained the very first x-ray of human hand Paul Herman Martin Sudeck described acute inflammatory bone atrophy characterized by intensive pain, swelling, diminished mobility of wrist and fingers, rapid muscle atrophy and radiographic manifestations: diffuse osteoporosis with a severe patchy demineralization, especially of the periarticular regions, combined with a subperiostal bone resorption. Since severe disability resulted in majority of patients Sudeck suggested immobilization only of affected joints, elevation, massages and movement therapy as soon as possible.2 Up to date such clinical manifestations were known as Sudeck's syndrome. Spotty atrophy described by Sudeck is seen on plain radiographs weeks after the beginning of disease and can be demonstrated only when both hands are simultaneously exposed on the same film. These conventional bilateral radiographs were for years »golden standard« for diagnosing complex regional pain syndrome. In 1947 James A. Evans in article entitled Reflex Sympathetic Dystrophy stated that sympathetic dysfunction has the primary role in development of this chronic and disabling pain syndrome.3 Therefore sympathetic blockades were suggested as the treatment of choice. With time it was demonstrated that such blockades have diminished the pain only in a part of patients and cured only 29% of them.4, 5 Today the pain that depends on sympathetic dysfunction is referred as sympathetically maintained pain (SMP), others as sympathetically independent pain (SIP). In last century almost 40 terms were used to describe the same or similar painful conditions. Between them prevailed algodystrophy in Roman, morbus or syndrome Sudeck in German and RSD in Anglo-Saxon literature. To put some order in this chaos a new neutral term Complex Regional Pain Syndromes (CRPS) was introduced in 1992.6 While CRPS type I without evident peripheral nerve injury substitutes former terms as algodystrophy, syndrome Sudeck and RSD, CRPS typ II is used instead of causalgia. Finally, CRPS III or NOS (not otherwise specified) serves as a trash can for all others poorly defined and understood chronic post-traumatic painful conditions like: complex painful disorder, posttraumatic pain states, diffuse posttraumatic reaction, general posttraumatic pain states and so on.7 ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
145
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
During last century RSD/ s. Sudeck / algodystrophy was defined as chronic post-traumatic pain accompanied with triad of sensory, motor and sympathetic dysfunction. In 1992 at Second international congress on pain Task Force of International Association for the Study of Pain (IASP) proposed first criteria for the diagnosis of CRPS. They were: a.) the presence of an initial noxious event or immobilization, b.) continuing pain, allodynia or hyperalgesia disproportionate to any inciting event, c.) evidence at some time of edema, changes in skin blood flow or abnormal sudomotor activity in the affected region and d.) the diagnosis is excluded by the existence of conditions that would otherwise account for the degree of pain and dysfunction.6 It was pointed out that these criteria were not written in stone, rather they represented the temporary basis for further research. Indeed, subsequent studies demonstrated that these criteria have high sensitivity (0.98), low specificity (0.36) and only 40% probability of accurate diagnosis (8). Seven years later a multicentre study based on statistical grouping of signs and symptoms suggested that criteria could be improved by separating vasomotor and sudomotor dysfunction and edema, and that motor and trophic changes can be a distinct component of CRPS. Subsequent validations leaded to new criteria for diagnosis of CRPS consisting of continuing pain that is disproportionate to any inciting event (conditio sine qua non) and four categories of symptoms or signs: a.) sensory (hyperalgesia to pinprick and/or allodynia to light touch; b.) vasomotor (temperature and/or skin color changes and/or asymmetry; c.) sudomotor/edema (changes and/or asymmetry); d.) motor/trophic (decreased range of motion and/or dysfunction and/or trophic changes seen on hair, nails or skin). For diagnosis patient must report at least one symptom in each category or must display at least one sign in two or more categories. It is wise to combine new criteria with the first and last criterion of the older ones. The new criteria have 0.70 sensitivity, 0.94 specificity and 80% probability of accurate diagnosis.8 In other words there is 20% probability of misdiagnosis and overtreatment. Since, it was demonstrated that symptoms similar to CRPS can be seen after immobilization of healthy volunteers,9 and that in exaggerated posttraumatic reaction that mimic CRPS motor function is not affected,10 the authors think that the pain has to be more continuous and spontaneous and accompanied with decreased range of motion. Since new criteria for CRPS diagnosis, albeit decreased range of movements included various forms of motor dysfunction some patients with dystonia were included as CRPS/dystonia group. Some authors treating these CRPS/dystonia patients concluded that most of them are suffering of psychogenic pseudoneuropathy up to malingering. Ochoa makes a step forward denying even existence of CRPS .11–14 While some believe that CRPS is the condition psychiatrically manifested, no literature has shown psychological causation. It was said that myofascial trigger points and neglect like syndrome are frequently found in CRPS patients.15 Myofascial trigger points are defined as the presence of a palpable, tender, firm nodule or band in the affected muscle. As noted by others the authors have found and treated many painful points especially around shoulder (acromioclavicular joint, coracoid process, tendinoses, calcium deposits and so on) but rarely typical myofascial dysfunction.16–18 In neurological neglect-like syndrome the affected limb may feel foreign ("cognitive neglect") or directed mental and visual attention is needed to move the limb ("motor neglect"). Chronic pain and disuse combined with guarding-type response may involve reorganization of body schema resulting in longer time needed for recognizing and moving the affected limb.19,20 The diagnosis of complex regional pain syndrome is still based only on clinical signs and symptoms. It must be emphasized that CRPS is a reaction to injury or immobilization; but it is not an independent disease. Neurophysiological tests are useful in the differential diagnosis of CRPS I and II; however, the findings are not specific for the disease. Various laboratory tests or imaging procedures have been studied. While these tools can prove beneficial, for the early differentiation these diagnostic methods do not offer sufficient accuracy. Based on IASP criteria for diagnosis the authors use simple and useful subdivision of all patients with chronic posttraumatic pain and dysfunction: a.) real CRPS; b.) borderline group of patients that do not fulfill all criteria; c.) CRPS-like group with well known underlying pathology; and d.) pseudo-CRPS group with proven psychological/psychiatric disorders. It’s well known that ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
146
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
CRPS-like symptoms can overlay some entrapment neuropathies; carpal tunnel syndrome being most frequently quoted.21–23 Similarly, CRPS like dysfunctions were described combined with pathology around shoulder (so called shoulder-hand syndrome),16–18 after vigorous and painful physiotherapy24 and in our experience in misdiagnosed and overtreated patients. Psychological/psychiatric dysfunction may precede, accompany, or be a consequence of CRPS. In chronic CRPS depressive syndrome frequently develops, but there is no evidence that CRPS patients display more psychological distress than other chronic pain patients. Nevertheless, psychologic/psychiatric conditions may masquerade CRPS, between them conversion disorders, pseudoneurologic syndromes (pseudoparalysis, pseudosensory syndromes, psychogenic movement disorders etc.), work-related compensable disorders, chronic disability syndromes, deliberate exaggeration, malingering or simulation of illness. Some degree of exaggeration is common. Inappropriate physical signs, grimacing and grunting during examination are probably uncommon and represent a conscious reaction to the examination in an attempt to deceive doctors.25, 26 All our considerations are based on the assumption that the patient is honest, yet team approach is necessary to avoid needless and potentially harmful procedures on patients who may be better served with psychiatric or psychologic care. The clinical course of CRPS is commonly divided into three phases appearing in a variable chronology: acute or warm phase, dystrophic or cold phase characterized by fibrosis, and atrophic phase with disabling trophic symptoms. It must be stressed out that clinical presentation is dynamically changing. Inciting event is soon hidden with spreading of sensory, sympathetic and motor dysfunctions that with time and medical interventions change their nature and new leading painful disorders may appear. The diagnosis is still based on clinical signs and symptoms and therefore depends on the decision of treating physician. Since the CRPS is not an independent disease and usually develops as secondary complication of an injury or disease it is possible that signs accompanying unrecognized and longstanding sequelae/disease can be misinterpreted as pure CRPS. Therefore it’s our duty to regularly evaluate and reevaluate the diagnosis and results of treatment. As underlying pathophysiology of CRPS is unknown nowadays therapy is still symptomatic. IASP guidelines suggest simultaneous treatment of pain, physical therapy and psychological care.27, 28 Pain is a leading symptom in CRPS and may hinder functional recovery. Therefore only after the pain is effectively reduced physiotherapy should be increased. Vigorous painful physiotherapy while patient still suffer from severe pain is harmful and leads to deterioration. It must be remembered that pain relief, however it is achieved, is intended to facilitate participation in physical therapies.29 Morphine and derivates were tried from Mitchell’s times on. Sudeck has suggested rest, elevation and early active exercises. Pharmacologic therapy that should be effective may fail, and a trial-and-error approach to treatment is often mandatory. For a patient meaningful pain relief is achieved when it has diminished for at least 50% of its initial value.30 Conservative therapeutic methods (analgesics, rest and raised position) may take weeks before mild exercises can be started. Peripheral sensory nerve blocks can abruptly abolish nociceptive input to the central nervous system but subsequent recovery from such single block is frequently accompanied with increasing pain and discomfort deleting gained temporary improvement. This can be avoided with continuous regional analgesia (CRA) that can be maintained for weeks. While still controlling pain carefully titrated CRA allows motor recovery and painless early active exercises and functional therapy.
Authors’ experiences in the treatment of CRPS and similar disorders In our region almost all patients suffering from diffuse chronic pain involving upper extremity are sooner or later send to our team. Our first duty is to exclude all other possible causes, to find and block all leading painful points (2% lidocaine with betamethasone 1 : 1) and to suggest mild analgesics, rest, elevation and adequate painless physiotherapy. Majority of them are seen and reevaluated after two weeks. If there is no improvement, especially when there is spontaneous pain disturbing sleep and diminished range of movement we suggest hospitalization. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
147
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
In a retrospective study of 88 patients send to our team from other specialists (general practitioners, surgeons, orthopedics, neurologist, physiatrists, and pain clinics) with signs of CRPS involving upper extremity and applying IASP research criteria for diagnosis only 36 (41%) were accepted as “real” CRPS, five were separated as borderline group, 17 were classified as pseudo-CRPS and in 30 detailed reevaluation disclosed overlooked underlying pathology mimicking CRPS (CRPS-like group). A great percentage of CRPS III (borderline, pseudo-CRPS and CRPS-like group) is due to our acceptance of spontaneous pain disturbing sleep and diminished range of movement as obligatory criterions.31, 32 All hospitalized patients were initially treated with elevation, ice massages, active painless exercises and local blockades of all painful points. Thirty patients were classified as CRPS-like disorder. In 13 all signs disappeared in first 2–5 days. In others all signs of CRPS rapidly disappeared disclosing underlying pathology which was subsequently properly treated. The majority of patients in CRPS-like group were treated in first six months after inciting injury. Four patients were treated for 2–4 years by different specialists including surgeons, orthopedics, neurologist, physiatrists and in pain clinics. First of them was cured with one blockade of trigger thumb and carpal tunnel. In the second small neuroma of dorsal branch of digital nerve was implanted in bone. In the third one after three unsuccessful surgeries (cubital tunnel release and two revisions) a neuroma of cutaneous branch was implanted in bone and in the fourth combination of release of postoperative traction neuropathy of digital nerve and extirpation of the sesamoid bone of thumb revealed the problem. Seventeen patients were classified as pseudo-CRPS. Majority of them have had a long preexisting history of psychiatric disorders and psychiatric treatment was included in therapy. In few psychologic/psychiatric disorders have been disclosed during initial treatment of chronic pain of unknown origin like: self inflicting injury, conversion syndrome, work-related compensable disorders and psychogenic movement disorders (dystonia and clenched fist syndrome). If patients with “real “ CRPS after first three days of rest, elevation, ice massages, active painless exercises and local blockades refer important improvement we continue the same treatment for day or two and dismiss them with advices for further therapy and assured that they can come back if situation worsens. If this initial treatment was unsuccessful, catheter was inserted to the brachial plexus and a continuous regional analgesia started. Brachial plexus block was established with a bolus of local anesthetics (bupivacaine, ropivacaine) and then depending on the degree of motor blockade the concentration and volume of the anesthetic were adjusted to achieve good sensory blockade. Since the motor function was unaffected an active and painless exercise program was possible.33 On the seventh day the analgesia was withdrawn but the axillary catheter was left "in situ" and the program of elevation and active exercises were carried on. In this period some painful conditions were noted and immediately treated. If, on the tenth day there was a significant relief of pain and improvement of active range of movement (ROM) the catheter was removed and a few days later the patient was dismissed. At home elevation, cryotherapy and active exercises without pain were recommended. Patients were instructed to contact us if they notice any worsening; the first control was scheduled one to three months later. Surgery on the extremity affected with complex regional pain syndrome is generally avoided. In our study 14 patients were operated in acute stage or few months later. Majority were done in brachial plexus anesthesia followed by CRA. There was no worsening or recurrence. Authors believe that that all painful conditions should be treated immediately; therefore we do not hesitate to operate even in acute stage. The results of treatment are frequently reported as diminished pain and improved function without any quantification making any comparison impossible. Since for meaningful improvement the pain must decrease for at least 50%, the 50% is a lower limit for a satisfying result. Further problems arise in differentiation between expected sequels of inciting injury or accompanying disease and those due to CRPS. Authors believe that for a good result function of affected upper limb must reach at least 50% of normal hand. Based on these presumptions the results can be divided in: a.) excellent (completely normal hand); b.) good (no spontaneous pain, at ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
148
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
least 50% decrease of use-related pain and at least 50% of recovery of function measured as ROM and grip strength); and c.) poor (improved, unchanged, worsened). In the “real” CRPS group there were 36 patients (29 females and 7 males), the mean age was 58 (42–84) years, the mean interval between the inciting injury and our evaluation was 3.6 (range 1–48) months and the mean follow-up was 30 (9–75) months. Six patients have been treated conservatively (final results: one excellent, four good and one poor), and 30 with CRA (results: 8 excellent, 17 good and 5 poor). Overall results of treatment were 9 excellent, 21 good and 6 poor. During treatment in 21 patients one or more painful points were found and blocked. 8 patients were surgically treated during initial hospitalization and 6 few months later. In this surgically treated group no worsening or recurrences were noted. Conclusion CRPS appears secondary to injury or immobilization. Its pathophysiology and natural history are unknown and severe impairment is frequently reported. Since CRPS is a heterogeneous posttraumatic disorder with similar clinical pictures, authors suggest simple working classification in borderline, CRPS-like, pseudo-CRPS and CRPS group. No treatment has been shown to cure it, in fact patients reported to be cured by a treatment may be manifesting the natural history of their disease. Since chronic pain accompanied by allodynia or hyperalgesia maintains fear of movement, protective guarding and neglect like syndrome the pain must be abolished as soon as possible. Continuous regional analgesia offers abrupt and complete control of pain. We are aware that CRA is sensory and sympathetic blockade, yet our prime goal was not to find the difference between them but to eliminate the painful condition and allow painless active exercises as soon as possible. The fact that even painful surgical procedures executed during treatment have not caused any worsening suggests that CRA have important influence on underlying pathophysiology. References 1. Cervetti N. S. Weir Mitchell: The Early Years. APS Bulletin 2003; 13. http://www.ampainsoc.org/pub/bulletin/mar03 /hist1.htm 2. Sudeck P. On acute inflammatory bone atrophy. Translated Article. J Hand Surg 2005; 30E; 477-81. 3. Evans, JA. Reflex sympathetic dystrophy. Surg. Gynecol. Obstet. 1946; 82: 36-44. 4. Cepeda MS, Lau J, Carr DB. Defining the therapeutic role of local anesthetic sympathetic blockade in complex regional pain syndrome: a narrative and systematic review. Clin J Pain 2002; 18: 216-33. 5. 6. 7.
8.
9.
10. 11. 12. 13. 14.
Schott GD. Interrupting the sympathetic outflow in causalgia and reflex sympathetic dystrophy. A futile procedure for many patients. (Editorials). BMJ 1998; 316: 792-3. Merskey H, Bogduk N. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. 2nded. Seattle, IASP Press 1994, 40-3. Boas RA. Complex regional pain syndromes: symptoms, signs, and differential diagnosis. In: Jänig W, StantonHicks M, eds. Reflex sympathetic dystrophy: a reappraisal. Progress in pain research and management. Vol. 6. Seattle: IASP Press, 1996: 79-92. Bruehl S, Harden RN, Galer BS, Saltz S, Bertram M, Backonja M, Gayles R, Rudin N, Bhugra MK, StantonHicks M. External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria. International Association for the Study of Pain. Pain 1999; 81:147-54. Butler SH, Nyman M, Gordh T. Immobility in volunteers transiently produces signs and symptoms of complex regional pain syndrome. In: Devor M, Rowbotham MC, Wiesenfeld-Hallin Z. eds. Proceedings of the 9th world congress on pain, Progress in pain research and management. Seattle. IASP Press, 2000; 16: 657-60. Birklein F, Kunzel W, Sieweke N. Despite clinical similarities there are significant differences between acute limb trauma and complex regional pain syndrome I (CRPS I). Pain 2001; 93: 165-71. Verdugo RJ, Ochoa JL. Reversal of hypoaesthesia by nerve block, or placebo: a psychologically mediated sign in chronic pseudoneuropathic pain patients. J Neurol Neurosurg Psychiatry. 1998; 65: 196-203. Verdugo RJ, Ochoa JL. Abnormal movements in complex regional pain syndrome: assessment of their nature. Muscle Nerve 2000; 23: 198-205. Ochoa JL. ens review: Truths, errors, and lies around "reflex sympathetic dystrophy" and "complex regional pain syndrome". J Neurol 1999; 246: 875-9. Ochoa JL. Reflex sympathetic dystrophy: a disease of medical understanding. The Clin J Pain 1992; 8: 363-6.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
149
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
15. Rashiq S, Galer BS. Proximal myofascial dysfunction in complex regional pain syndrome: a retrospective prevalence study. Clin J Pain 1999; 15: 151-3. 16. Veldman PH, Goris RJ. Shoulder complaints in patients with reflex sympathetic dystrophy of the upper extremity. Arch Phys Med Rehabil 1995; 76: 239-42. 17. Zyluk A, Puchalski P, Zyluk B. [Shoulder pain and limited mobility in the course of algodystrophy of the hand] [Article in Polish] Chir Narzadow Ruchu Ortop Pol 2004; 69:273-7. 18. Taylor JG. Sudeck's atrophy and the shoulder-hand syndrome. Proc R Soc Med 1958; 51: 879-83. 19. Galer BS, Jensen M. Neglect-like symptoms in complex regional pain syndrome: results of a self-administered survey. J Pain Symptom Manage 1999; 18: 213-7 20. Moseley GL. Why do people with complex regional pain syndrome take longer to recognize their affected hand? Neurology 2004; 62: 2182-6. 21. Thimineur MA, Saberski L. Complex regional pain syndrome type I (RSD) or peripheral mononeuropathy? A discussion of three cases. Clin J Pain 1996; 12145-50. 22. Placzek JD, Boyer MI, Gelberman RH, Sopp B, Goldfarb CA. Nerve Decompression for Complex Regional Pain Syndrome Type II Following Upper Extremity Surgery. J Hand Surg 2005; 30A: 69–74 23. Grundberg AB, Reagan DS. Compression syndromes in reflex sympathetic dystrophy. J Hand Surg 1991; 16A: 731-6. 24. Zyluk A. Iatrogenic causes of post-traumatic reflex sympathetic dystrophy. In: Ege R.(ed). Proceedings of the 8th congress of the International federation of societies for surgery of the hand (IFSSH). Istambul, Turkey 10-14 June 2001; 781-4. 25. Aronoff GM, Livengood JM. Pain: psychiatric aspects of impairment and disability. Curr Pain Headache Rep. 2003; 7:105-15. 26. Driessens M, Blockx P, Geuens G, Dijs H, Verheyen G, Stassijns G. Pseudodystrophy. A conversion disorder mimicking reflex sympathetic dystrophy. Acta Orthop Belg 2002; 68: 330-6. 27. Stanton-Hicks M, Baron R, Boas R, Gordh T, Harden N, Hendler N, et al. Complex regional pain syndromes: guidelines for therapy. Consensus report. Clin J Pain 1998; 14: 155-66. 28. Chung OY, Bruehl SP. Complex Regional Pain Syndrome. Curr Treat Options Neurol 2003; 5: 499-511. 29. Berger P. The role of the physiotherapist in the treatment of complex peripheral pain syndromes. Pain Reviews 1999; 6: 211–232. 30. Forouzanfar T, Weber WE, Kemler M, van Kleef M. What is a meaningful pain reduction in patients with complex regional pain syndrome type 1? Clin J Pain 2003; 19: 281-5. 31. Birklein F, Riedl B, Sieweke N, Weber M, Neundorfer B. Neurological findings in complex regional pain syndromes--analysis of 145 cases. Acta Neurol Scand 2000; 101: 262-9. 32. Perez RS, Keijzer C, Bezemer PD, Zuurmond WW, de Lange JJ. Predictive value of symptom level measurements for complex regional pain syndrome type I. Eur J Pain 2005; 9: 49-56. 33. Margić K, Pirc J. The treatment of complex regional pain syndrome (CRPS) involving upper extremity with continuous sensory analgesia. Eur J Pain 2003; 7: 43-7.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
150
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
PRAVILNA IZBIRA ZDRAVILA ZA ZDRAVLJENJE BOLEČINE GLEDE NA JAKOST BOLEČINE – INDEKS OBVLADANOSTI BOLEČINE PRI BOLNIKIH NA ONKOLOŠKEM INŠTITUTU PROPER MEDICATION OF PAIN REGARDING ITS INTENSITY – PAIN MANAGEMENT INDEX AT THE LJUBLJANA INSTITUTE OF ONCOLOGY PATIENTS Slavica Lahajnar-Čavlovič Onkološki inštitut Ljubljana Izvleček. Bolečina je eden najbolj pogostih in motečih simptomov napredovalega raka. Kljub številnim zdravilom za zdravljenje bolečine, predvsem opioidom, ima veliko bolnikov neobvladano bolečino. Pri bolnikih, ki so hospitalizirani na Onkološkem inštitutu, smo poskušali ugotoviti, koliko jih ima neobvladano bolečino in, glede na jakost bolečine, predpisan prešibek analgetik. Za oceno slabo zdravljene bolečine smo uporabili indeks zdravljenja bolečine (PMI pain management index). 18,5 % vseh bolnikov je imelo neobvladano bolečino in zdravniki so 11 % teh bolnikov zdravili s prešibkimi analgetiki (negativen PMI). Rezultati v tej raziskavi so veliko boljši kot v podobni leta 2005, kar kaže na boljše zdravljenje bolečine bolnikom na Onkološkem inštitutu. Abstract. Pain is among the most common and unpleasant symptoms of advanced cancer. Despite numerous pain medications, mainly opioids, many patients still suffer from uncontrolled pain. We have tried to determine how many patients suffer from uncontrolled pain and how many were prescribed an analgesic that is not strong enough given the intensity of the pain among patients hospitalised at the Institute of Oncology. Insufficient pain management was evaluated by the Pain Management Index (PMI). Eighteen and a half percent of all patients suffered from uncontrolled pain and 11% of them were prescribed analgesics of an insufficient strength (negative PMI). The results of this study were considerably better than the results of a similar study from 2005; better pain management among patients at the Institute of Oncology is thus indicated.
Uvod Pri bolniku z rakom so prisotni številni simptomi, med katerimi je bolečina eden najbolj pogostih in obremenjujočih, tako za bolnika kot njegove bližnje. Opioidi so steber zdravljenja bolečine zaradi raka, ki je napredoval.1 Izdelana so priporočila za zdravljenje kronične bolečine, ki je posledica raka in na voljo so številni opioidi, vendar še veliko bolnikov trpi zaradi slabo zdravljene bolečine. Vzrok je, poleg neodkritega vzroka za bolečino, zdravljenja bolečine brez sočasnega lajšanja drugih simptomov bolezni, težav pri zdravljenju z opioidi, predvsem nepravilna izbira analgetika glede na jakost bolečine.2 Za slednjega so odgovorni zdravniki, ki ne predpisujejo opioidov ter bolniki, njegovi bližnji in družba, ki odklanjajo jemanje močnih opioidov. Izdelani so bili številni pripomočki za oceno učinkovitosti zdravljenja bolečine. PMI (pain management index) je od leta 1987 priznana metoda za oceno primernosti predpisanega analgetika glede na priporočila Svetovne zdravstvene organizacije.3 Le-ta je 1984 leta izdelala 3-stopenjsko lestvico zdravljenja bolečine, s katero je priporočila izbiro analgetika glede na jakost bolečine. Za zdravljenje blage bolečine so primerna zdravila neopioidi, za srednje močno šibki opioidi in za močno močni opioidi. V novih priporočilih za zdravljenje bolečine zaradi raka je vloga močnih opioidov še večja, saj jih priporočajo že pri zdravljenju srednje močne bolečine.4, 5 Med bolniki, ki so bili hospitalizirani na Onkološkem inštitutu smo po pregledu temperaturnih listov, kjer so podatki o predpisanih zdravilih za zdravljenje bolečine in bolnikovi oceni jakosti bolečine, ocenili primernost izbranega analgetika glede na jakost bolečine s pomočjo PMI. Podobno raziskavo smo opravili leta 2005, zato nas je zanimalo ali se je zdravljenje bolečine izboljšalo. K temu bi lahko pripomogla nova in posodobljena priporočila za zdravljenje bolečine pri odraslem bolniku z rakom, ki so bila izdana leta 2007, številna izobraževanja za zdravnike in medicinske sestre na Onkološkem inštitutu in po zdravstvenih domovih v Sloveniji ter beleženje bolnikove ocene jakosti bolečine, 5 vitalnega znaka, na temperaturnih listih bolnikov na Onkološkem inštitutu po letu 2004. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
151
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Material in metode Pregledali smo zapise na temperaturnih listih 250 hospitaliziranih bolnikov na internističnem, radioterapevtskem in paliativnem oddelku Onkološkega inštituta. Predmet naše raziskave je bila kronična bolečina, zato nismo obravnavali bolnikov na kirurškem oddelku, kjer ima večina bolnikov akutno bolečino po operaciji. Jakost predpisanega analgetika smo označili s števili od nič do tri (brez analgetika 0, neopioid 1, srednje močen opioid 2, močan opioid 3) in prav tako bolnikovo oceno jakosti povprečne bolečine (brez bolečine 0, blaga bolečina 1, srednje močna bolečina 2, močna bolečina 3). PMI smo izračunali tako, da smo od oznake analgetika odšteli oznako jakosti bolečine (razpredelnica 1). Razpredelnica 1. Izračun PMI Analgetiki
Jakost bolečine
PMI
VAS 7-10
0 1 2 3
3 3 3 3
-3 -2 -1 0
VAS 4-6
0 1 2 3
2 2 2 2
-2 -1 0 1
VAS 1-3
0 1 2 3
1 1 1 1
-1 0 1 2
VAS 0
0 1 2 3
0 0 0 0
0 1 2 3
VAS
neobvladana bolečina
VAS vizualna analogna skala PMI pain management index
Poskušali smo poiskati tudi druge vzroke za neobvladano bolečino, poleg neg PMI, to je nepredpisovanja močnih opioidov. Preverili smo ali imajo bolniki predpisan kratko delujoči opioid za titracijo in prebijajočo bolečino, odvajalo ali/in antiemetik za zdravljenje neželenih učinkov opioida, dodatna zdravila in postopke za zdravljenje nevropatske bolečine in stadij bolezni, predvsem prisotnost kostnih metastaz.
Rezultati in razpravljanje V raziskavo smo vključili 248 bolnikov, 124 moških in 126 žensk. Več kot tri četrtine bolnikov je bilo starejših od 50 let. Jakost bolečine in analgetiki Brez bolečine ali z obvladano bolečino, t.j. bolečino jakosti tri ali manj po VAS, je bilo 81,5 % bolnikov. Neobvladano bolečino, t.j. bolečino jakosti štiri ali več po VAS, je torej imelo 46 (18,5 %) bolnikov, kar je veliko manj kot v raziskavi 2005, ko je bilo takih bolnikov 45 %. Tudi bolnikov z močno bolečino, t.j. bolečino jakosti sedem do deset po VAS, je bilo manj (4 %, leta 2005 13 %). ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
152
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Od vseh bolnikov jih je imelo 70,5 % predpisana zdravila za zdravljenje bolečine, 15,5 % bolnikov neopioide, 29 % šibke opioide in 26 % močne opioide. Leta 2005 so bili večkrat predpisani neopioidi (45 % bolnikov) in šibki opioidi (41 % bolnikov) ter manjkrat močni opioidi (11 % bolnikov). Vsi bolniki z neobvladano bolečino, so imeli predpisane analgetike (nihče neopioide, 26 % šibke opioide in 74 % močne opioide), iz česar lahko sklepamo, da zdravniki sprašujejo bolnike o bolečini in jim predpisujejo analgetike. Leta 2005 četrtina bolnikov z neobvladano bolečino ni imela predpisanih analgetikov, več jih je imelo neopioide (36 %), predvsem nesteroidne antirevmatike in šibke opioide (42 %) ter manj močne opioide (samo 22 %). Vzrok za neobvladano bolečino ni to, da zdravniki ne predpisujejo analgetikov, pač pa nepravilna izbira analgetika glede na jakost bolečine, predvsem majhno predpisovanje močnih opioidov, kar smo poskušali pokazati z izračunom PMI. Indeks zdravljenja bolečine Negativni PMI (-1, -2, -3) pomeni, da so za zdravljenje bolečine, glede na jakost le-te, izbrani premalo močni analgetiki in je predvsem pokazatelj premajhnega predpisovanja močnih opioidov v skupini bolnikov z neobvladano bolečino (3). V naši raziskavi je bilo takih bolnikov 11 %, kar je veliko manj kot v raziskavi leta 2005 (56 %). Zdravniki torej samo pri 11 % bolnikov niso predpisali dovolj močan analgetik glede na jakost bolečine. PMI ni uporaben za oceno kakovosti obravnave posameznega bolnika z bolečino. Tudi bolniki s pozitivnim PMI (0, 1) imajo neobvladano bolečino, kar v klinični praksi obravnave posameznega bolnika lahko pomeni, da ta prejema primeren analgetik, na primer močan opioid, vendar v premajhnem odmerku, nima predpisanega kratko delujočega opioida za prebijajočo bolečino in titracijo, ima hujše neželene učinke opioidov in zato ne more jemati večjih odmerkov, nevropatsko bolečino, ki jo težko zdravimo samo z opioidi ali bolezen, ki je napredovala, kot so kostne metastaze, ki povzročajo prebijajočo bolečino, ki jo težko obvladamo s kratko delujočim morfinom, ki je edini pri nas registriran kratko delujoči opioid. Drugi vzroki za neobvladano bolečino Da bi poiskali druge vzroke za neobvladano bolečino, poleg ne-predpisovanja opioidov, smo 137 bolnikov, ki so imeli predpisane opioide razdelili v dve skupini t.j. 46 bolnikov z neobvladano bolečino in 91 bolnikov z obvladano bolečino. Proti pričakovanjem so imeli bolniki z neobvladano bolečino večkrat predpisan rešilni odmerek kratko delujočega opioida, odvajalo, zdravila in postopke za nevropatsko bolečino in med opioidi večkrat močne opioide kot bolniki z opioidi in obvladano bolečino (razpredelnica 2). Bolniki imajo torej predpisana zdravila in postopke za boljše zdravljenje bolečine in kljub temu še vedno neobvladano bolečino. Razpredelnica 2: Primerjava bolnikov, ki jemljejo opioide in imajo neobvladano ali obvladano bolečino
Kratko delujoči opioid Odvajalo Antiemetik Zdravila in postopki za nevropatsko bolečino Zdravila in postopki za kostne metastaze Kortikosteroid Lokalno napredovala bolezen ali/in kostne metastaze Šibak opioid Močan opioid
VAS ≥ 4 46 bolnikov
VAS ≤ 3 91 bolnikov
85 % 59 % 9%
78 % 27,5 % 13 %
19,5 %
12 %
13 %
15 %
6,5 %
9%
65 %
52 %
26 % 74 %
66 % 34 %
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
153
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
Med bolniki z rakom, ki je napredoval, t.j. z lokalnim progresom ali kostnimi metastazami, jih je bilo več z neobvladano kot obvladano bolečino. Bolnice z rakom dojke in bolniki z rakom sečil so imeli večkrat neobvladano kot obvladano bolečino, kljub jemanju opioidov. Bolniki z rakom pljuč so imeli večkrat obvladano, kot neobvladano bolečino in bolj pogosto so bili zdravljeni pri anesteziologu v ambulanti za zdravljenje bolečine. Razlike so bile tudi med oddelki. Med bolniki z opioidi je bilo na internističnih oddelkih več takih z neobvladano kot obvladano bolečino. Na radioterapevtskih oddelkih je bilo razmerje v prid bolnikov z obvladano bolečino in več bolnikov je bilo obravnavanih v ambulanti za zdravljenje bolečine. Enako je veljalo za paliativni oddelek. Internisti so imeli manj bolnikov z negativnim PMI, kot zdravniki iz drugih dveh oddelkov. Ker so imeli več bolnikov z neobvladano bolečino lahko sklepamo, da so predpisovali analgetike po priporočilih, niso pa uporabili dovolj velikih odmerkov. Zaključki Pri bolnikih v naši raziskavi je zdravljenje kronične bolečine zaradi raka boljše, kot v raziskavi leta 2005. Manj bolnikov ima neobvladano bolečino in manj močno bolečino. Več bolnikov ima predpisana zdravila za zdravljenje bolečine. Zmanjšala se je uporaba neopioidov in šibkih opioidov, povečalo pa predpisovanje močnih opioidov. Zdravniki predpisujejo analgetike po priporočilih WHO in posodobljenih priporočilih, ki so bila izdana v Sloveniji pred dvema letoma, zato smo negativen PMI izračunali le pri 5 (11 %) bolnikih z neobvladano bolečino. Vsi bolniki z neobvladano bolečino imajo predpisane opioide, tri četrtine močne opioide, večina kratko delujoči opioid za zdravljenje prebijajoče bolečine, več kot polovica odvajalo za zdravljenje zaprtja zaradi opioidov, petina ima predpisana zdravila in postopke za zdravljenje nevropatske bolečine, nekaj več kot 10 % bolnikov se obseva in/ali dobiva bifosfonate za zdravljenje bolečine pri kostnih metastazah. Glede na to, da se bolniki, ki jemljejo opioide in imajo obvladano bolečino, glede zgoraj naštetega, bistveno ne razlikujejo lahko sklepamo, da prvi jemljejo premajhne odmerke opioidov. Velikosti odmerkov nismo beležili, prav tako ne število rešilnih odmerkov in zamenjav opioidov, kar je slabost naše raziskave. Z rezultati raziskave smo lahko zadovoljni. K boljšemu rezultatu, glede na leto 2005, je največ pripomoglo ocenjevanje bolečine in zapis jakosti bolečine na temperaturnih listih bolnikov, s čimer smo bolečino naredili vidno. Pripomogla so tudi izobraževanja zdravnikov in medicinskih sester ter nova, posodobljena priporočila, ki priporočajo uvajanje močnih opioidov brez poprejšnje uporabe šibkih. Potrebno je osvestiti bolnike, naj večkrat vzamejo rešilne odmerke kratko delujočega morfina, če imajo neobvladano bolečino. Medicinske sestre bodo na temperaturne liste zapisale oceno jakosti bolečine tudi po tem, ko bo bolnik dobil rešilni odmerek opioida ali drug ukrep za zdravljenje bolečine. Zdravnike bomo še naprej izobraževali in jih spodbujali, naj čim prej začnejo zdraviti bolečino z močnimi opioidi in spremljajo učinkovitost zdravljenja ter po potrebi povečajo odmerek dolgo delujočega opioida ali ga zamenjajo, če bolniku povzroča hujše neželene učinke. Literatura 1. Fukshansky M, Are M, Burton A. The role of opioids in cancer pain management. Pain Practice 2005; 5: 43-54. 2. Deandrea S, Montanari M, Moja L, Apolone G. Prevalence of undertreatment of cancer pain. A review of published literature. Ann Oncol 2008; 19 (12): 1985-991. 3. Wit R, Dam F, Loonstra S, Zandbelt L, Buuren A, Heijden K et all. The Amsterdam pain management index compared to eight frequently used outcome measures to evaluate the adequacy of pain treatment in cancer patients with chronic pain. Pain 2001; 91: 339-49. 4. Marinangeli F, Ciccozzi A, Leonardis M et all. Use of strong opioids in advanced cancer pain: a randomized trial. J Pain Symptom Manage 2004, 27: 409-16. 5. Maltoni M, Scarpi E, Modonesi C, Passardi A, Calpona S, Turriziani A et al. A validation study of the WHO analgesic Ladder: a two-step vs three-step strategy. Support Care Cancer 2005; 13: 888-94. ------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
154
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
AVTORSKO KAZALO / AUTHORS INDEXS Ambrožič, D 114 Ammer, K 118 Andersen, OK 48 Arendt-Nielsen, L 48 Armentano, D 113 Bandić, D 99 Bekavac-Mišak, V 99 Bilić, A 105 Bitežnik, S 106 Bizilj, S 114 Cesar-Komar, M 54, 115 Cruccu, G 16, 71 Čelan, D 118 Ekart-Fakin, V 113 Fikfak, N 106 Gligorijevic, S 32 Golubović, V 68 Gregorič, MR 24 Jamnik, H 107 Junker, U 117 Kamenik, M 92 Karapandža, J 106 Kerimović, V 113 Kirkor, Z 39 Klopčič-Spevak, M 107 Kofler, M 40 Kogler, J 99 Krčevski-Škvarč, N 19 Lahajnar-Čavlovič, S 108, 114, 151
Likar, R 67 Lipovšek, S 37 Logar, D 127 Loughrey, J 17 Mahkovic-Hergouth, K 96 Majerić-Kogler, V 99 Manohin, A 52 Markić, A 72 Meglič, B 141 Meh, D 109, 110, 111 Novak-Jankovič, V 77 Pirc, J 114 Pirtošek, Z 141 Pišek-Šuta, K 113 Pišljar, M 111 Pleško-Mlakar, A 62 Praprotnik, S 127 Richardson, P 119 Rodi, Z 112 Sakan, S 99 Springer, C 112 Stepanovič, A 114 Šakić, K 72 Šarman, M 113 Štětkářová, I 45 Švigelj, V 86 Turk, Z 118 Vintar, N 80 Zajec, M 115
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
155
PREDAVANJA V SPOMIN DR. JANEZA FAGANELA IN SIMPOZIJI 1985–2009 Dr. JANEZ FAGANEL MEMORIAL LECTURES AND SYMPOSIA 1985–2009 1985
Brain Injury Satellite Symposium – BISS '85 P. D. Wall (London, Great Britain): Pain mechanisms
1986
Diagnostics in Neuromuscular Disorders K.-G. Henriksson (Linkøping, Sweden): Muscle pain in neuromuscular disorders and primary fibromyalgia
1987
2nd Yugoslav Symposium on Neurourology and Urodynamics J. K. Light (Houston, Texas, U.S.A.): Neurogenic bladder in patients with spinal cord injury
1988
Symposium on Quantitative Electromyography E. Stålberg (Uppsala, Sweden): Electromyography – reflection of motor unit's physiology in health and disease
1989
Symposium on Sensory Encephalography A. M. Halliday (London, Great Britain): The widening role of evoked potentials in clinical practice
1990
Symposium on Assessment of the Upper Motor Neuron Functions A. M. Sherwood (Houston, Texas, U.S.A.): Brain motor control assessment
1991
Symposium on Neurophysiological Monitoring V. Deletis (New York, N.Y., U.S.A.): Intraoperative monitoring of evoked potentials – current status and perspective
1992
International Symposium on Evaluation and Treatment of Severe Head Injury E. Rumpl (Klagenfurt, Austria): Neurophysiological evaluation of severe head injury patients
1993
Symposium on Neurophysiological Evaluation of the Visual System H. Ikeda (London, Great Britain): Mammalian retinal neurotransmitters – as seen through the eyes of a neurophysiologist
1994
Symposium on Extrapyramidal Disorders J. Jankovic (Houston, Texas, U.S.A.): New horizons in dystonia and The First Lecture of the Slovene Basal Ganglia Club: G. Stern (London, Great Britain): Amara lenta tempera risu
1995
Symposium on Multiple Sclerosis W. I. McDonald (London, Great Britain): The clinical and pathological dynamics of multiple sclerosis
1996
Symposium on Update in Neurogenetics L. P. Rowland (New York, N.Y., U.S.A.): Molecular genetics and clinical neurology
1997
Symposium on Cognitive Neuroscience G. Barrett (Farnborough, Great Britain): Cognitive neurophysiology, a tool for studying the breakdown of mental processes
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
156
1998
9th European Congress of Clinical Neurophysiology, Ljubljana J. Trontelj (Ljubljana, Slovenia): SFEMG – Sensitive optics in space and time
1999
Symposium on Electrophysiology of Hearing A. Starr (Irvine, California, U.S.A.): Mysteries of the cochlea
2000
Symposium on Movement Disorders, “The Alpine Basal Ganglia Club” A. J. Lees (London, Great Britain): The relevance of pleasure/reward dopamine circuits to Parkinson’s disease
2001
EC-IFCN Ljubljana 2001 Regional EMG Refresher Course E. Stålberg (Uppsala, Sweden): The role of conventional and advanced electromyography in clinical neurology
2002
International Symposium on Clinical and Electrophysiologic Diagnostics of Epilepsy P. Chauvel (Marseille, France): High-resolution electroencephalography in clinical neurophysiology: applications to epilepsy and evoked potentials
2003
Symposium on Intraoperative Neurophysiology V. E. Amassian (New York, N.Y., U.S.A): Essentials of neurophysiology of the motor system
2004
Symposium on Sleep Research M. Billiard (Montpellier, France): Excessive daytime sleepiness: clinical impression versus final diagnosis
2005
37th International Danube Symposium for Neurological Sciences and Continuing Education T. Prevec (Ljubljana, Slovenia): Sharp or kind stimulus to activate the sensory system?
2006
International Symposium on Spinal Cord Motor Control “From Denervated Muscles to Neurocontrol of Locomotion” G. Vrbová (London, Great Britain): Some observations on the biology of the neuromuscular system and their possible usefulness for recovery of impaired function
2007
XVIth International SFEMG and QEMG Course and IXth Quantitative EMG Conference J. Kimura (Kyoto, Japan): The use of late responses as a quantitative measure of nerve conduction and motor neuron excitability
2008
Symposium on Amyotrophic Lateral Sclerosis P. N. Leigh (London, Great Britain): ALS: Advances in the laboratory and in the clinic
2009
Symposium on Clinical Neurophysiology of Pain (in preparation for October) G. Cruccu (Rome, Italy): Clinical Neuropohysiology of Pain
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
157
VABILO NA LJUBLJANSKI NEVROFIZIOLOŠKI SIMPOZIJ 2010 INVITATION TO THE LJUBLJANA NEUROPHYSIOLOGICAL SYMPOSIUM 2010
We are pleased to announce the 2010 Symposium on Clinical Neurophysiology of Vision and on Eye Movements with the 26th of Dr Janez Faganel Memorial Lecture which are planned for 17-18 September 2010. The memorial lecture entitled ‘Face recognition-related potentials: EEG, MEG, and NIRS studies’ will be given by Professor Ryusuke Kakigi from Okazaki, Japan. Professor Kakigi is one of the world authorities in the field of evoked magnetic responses following visual and somatosensory stimuli. The symposium will be dedicated to the visual electrophysiology, covering the retina, the optic pathways and visual centres beyond it, and eye movements, as well. The topics will be covered from the research and clinical perspectives, hence interesting to both neurologists and ophthalmologists. You are warmly invited to participate in this traditional event, as well as to present the results of your original research. We will do our best to make your stay in Ljubljana enjoyable. Jelka Brecelj and Janez Zidar Chairpersons
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
158
------------------------- 1st Congress of the Slovenian Association for Pain Therapy and Symposium on Clinical Neurophysiology of Pain, Bled, 9–10 Oct 2009 -------------------------
ZAHVALA / ACKNOWLEDGEMENT Organizacijski odbor srečanja se najlepše zahvaljuje za pomoč pri organizaciji Javni agenciji za raziskovalno dejavnost RS in naslednjim podjetjem The congress organisers acknowledge the assistance granted by the Slovenian Research Agency and the following companies Zlati pokrovitelji / Golden Sponsors
Bronasta pokrovitelja / Bronze Sponsors
Razstavljalci / Exhibitors
ABBOTT LABORATORIES d.o.o.
MEDINOVA d.o.o.
AUREMIANA d.o.o.
MEDIS d.o.o.
BOEHRINGER INGELHEIM RCV GmbH & CO KG, Podružnica Ljubljana
NYCOMED GmbH, Podružnica Ljubljana
GRÜNENTHAL d.o.o.
PHARMAMED-MADO d.o.o.
HVM Co.
PHARMASWISS d.o.o.
JANSSEN - CILAG
PFIZER, Podružnica Ljubljana
KRKA, d.d., Novo mesto
THOMY F.E. d.o.o.
LEK d.d.
WÖRWAG PHARMA
Sponzorji predavanj, delavnic / Sponsors of lectures & workshops
Auremiana, Elmed, PharmaSwiss Kongresni organizator / Congress Agency Auditoria d.o.o.
------------------------------------------------------------------------------------------------------- PROCEEDINGS -------------------------------------------------------------------------------------------------------
