KONTROLA BOLI U HIRURGIJI MALIH ŢIVOTINJA PAIN MANAGEMENT IN SMALL ANIMAL SURGERY
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1 KONTROLA BOLI U HIRURGIJI MALIH ŢIVOTINJA PAIN MANAGEMENT IN SMALL ANIMAL SURGERY Filipović Selma, Maksimović A., Nurkić Maša, Sinanović N., ObhoĊaš M. 10 Abstract The field of pain management has profoundly evolved over the last decade. The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. Adequate pain management should be a priority in veterinary surgery in terms of ethics, animal welfare, and reduce of morbidity and mortality. In veterinary medicine, scoring systems for pain rely on interpreting or measuring the consequences of pain. Results of numerous studies on pain support two treatment concepts, preventive and multimodal analgesia. Preventive analgesia includes analgesic application before occurrence of pain stimuli. Multimodal approach involves application of combination of two or more analgesics. Key words: pain, pain management, preventive analgesia, multimodal analgesia Kratki sadrţaj Internacionalna asocijacija za studiju boli definiše bol kao neţeljeno senzorno i emocionalno iskustvo povezano s aktualnim ili prijetećim oštećenjem tkiva, ili opisano u uvjetima takvog oštećenja. Sa stanovišta etike i dobrobiti ţivotinja, te u svrhu reduciranja morbiditeta i mortaliteta sprovoċenje adekvatne kontrole boli predstavlja prioritet u veterinarskoj hirurgiji. S obzirom da ţivotinje nisu sposobne verbalno opisati intenzitet boli, odreċivanje stepena bolnosti zasniva se na ocjeni reakcija izazvanih pojavom boli. Na osnovu rezultata brojnih studija o boli razvila su se dva osnovna koncepta kontrole boli: preventivna i multimodalna analgezija. Preventivna analgezija podrazumijeva aplikaciju analgetika prije nastanka bolnog stimulusa. Multimodalni pristup podrazumijeva primjenu kombinacije dva ili više analgetika. 10 Dr. sc. Filipović Selma, DVM, docent; mr. sc. Maksimović Alan, DVM, asistent; Nurkić Maša, DVM, asistent, Katedra za hirurgiju; dr. sc. Sinanović Nasir, DVM, docent, Katedra za ambulantnu kliniku; ObhoĊaš Muamer, vet. tehn., Katedra za hirurgiju, Veterinarski fakultet, Univerzitet u Sarajevu. 2 Filipović Selma, DVM, PhD, Assistant Professor; Maksimović Alan, DVM, MSc, Assistant; Nurkić Maša, DVM, Assistant, Department of Surgery; Sinanović Nasir, DVM, PhD, Assistant Professor, Department of Ambulatory Clinic; ObhoĊaš Muamer, Vet. Technician, Department of Surgery, Veterinary Faculty, University of Sarajevo. Veterinaria 59 (1-4), 85-91, Sarajevo
2 Kljuĉne rijeĉi: bol, preventivna analgezija, multimodalna analgezija Uvod U posljednje vrijeme sve se više paţnje posvećuje znaĉaju kontrole boli kao neizostavnog dijela veterinarske hirurgije. Benefit kontrole boli u humanoj hirurgiji podrazumijeva pad morbiditeta i mortaliteta, ubrzan oporavak i umanjenost potreba za hospitalizacijom (1, 2, 17, 20). Sliĉni rezultati su registrovani i u veterinarskoj hirurgiji. Stoga nije iznenaċujuće da se teţi inkorporaciji tehnika kontrole boli u svakodnevnu veterinarsku praksu (10). MeĊunarodno društvo za istraţivanje boli (IASP- International Association for the Study of Pain) definiše bol kao neţeljeno senzorno i emocionalno iskustvo povezano s aktualnim ili prijetećim oštećenjem tkiva, ili opisano u uvjetima takvog oštećenja (5, 23). OdreĊivanje stepena bolnosti moguće je precizno izvršiti samo kod verbalnih humanih pacijenata. S obzirom da ţivotinje nemaju sposobnost govora, odreċivanje stepena bolnosti zasniva se na ocjeni posljediĉnih reakcija na bol, kao što su uskraćivanje pokretljivosti udova (hromost), vokalizacija, socijalna povuĉenost, ubrzanost srĉanog rada ili povećanje koncentracije kortizola (1, 7, 17, 22). Sposobnost i uvjeţbanost ustanovljavanja stepena bolnosti veoma je bitna, jer ukoliko nismo sposobni ustanoviti intenzitet boli, onda se ne moţe procijeniti ni efikasnost mjera kontrole boli. Kontrola boli u veterinarskoj medicini nameće pitanje kako sa sigurnošću znamo da smo postigli adekvatnu analgeziju?. Najjednostavniji odgovor je da ukoliko ţivotinja postoperativno moţe ugodno spavati, analgezija je adekvatno sprovedena. Kompleksniji odgovor je da se na osnovu odreċivanja specifiĉnih varijabli (srĉani i respiratorni ritam, voljnost za interakciju sa njegovateljem, vokalizacija, odgovor na palpaciju i manipulaciju mjesta operativnog zahvata, voljnost za samostalno kretanje) moţe izvršiti pocjena efikasnosti analgezije (10). Preventivna analgezija Aplikacija analgetika prije, tokom i nakon bolnog stimulusa (hirurški zahvat) znatno reducira potrebnu dozu analgetika u odnosu na situaciju ukoliko se analgetik aplicira samo poslije hirurškog zahvata (8, 22, 27). Najbolje objašnjenje navedene observacije je da bolni stimulus uzrokuje promjene u putevima prijenosa boli, a s tim i naĉin transmisije boli i doţivljavanja boli od strane pacijenta (25, 31). Ukoliko analgetike ne apliciramo preoperativno nervi kojima se prenosi bol su pod neprekidnom stimulacijom, što rezultira povećanjem intenziteta transmisije boli. Nasuprot tome ukoliko analgetike apliciramo prije bolnog stimulusa, transmisija boli je reducirana ili blokirana i putevi prijenosa boli ostaju nepromijenjeni (31). Multimodalna (kombinovana) analgezija Princip multimodalnog pristupa terapiji bola evoluirao je tokom protekle decenije (29). Za razliku od jednog analgetika, primjena kombinacije dva ili više analgetika (multimodalna analgezija) znatno efikasnije reducira transmisiju boli zato što razliĉite familije analgetika djeluju kroz razliĉte receptore i na razliĉitim mjestima 86
3 prijenosa boli (19, 26). Prisutna su brojna mjesta na putu prijenosa boli gdje moţe nastati modifikacija transmisije (24). Na primjer, opioidi djeluju centralno i periferno, kako bi prigušili transmisiju boli duţ aferentnih nervnih vlakana i modulirali otpuštanje neurotransmitera duţ sinapsi dorzalnih rogova spinalne moţdine. Nasuprot tome, NSAID (nesteroidni aniinflamatorni lijekovi) iako djeluju periferno i na spinalno uţe, reduciraju nastajanje prostaglandina, koji kao medijatori upale povećavaju ekscitatornost senzornih i simpatiĉkih nervnih vlakana i izazivaju senzibilizaciju perifernih nociceptora, što rezultira povećanjem odgovora na bolni stimulus (primarna hiperalgezija) (31). TakoĊer, analgetici aplicirani u kombinaciji imaju dodatni ili sinergistiĉki efekt, što dovodi do smanjenja doze svakog pojedinaĉno, rezultirajući smanjenjem ispoljavanja neţeljenih efekata i dalje osiguravajući adekvatnu analgeziju (31, 26). Lijekovi koji se koriste u kontroli boli Opioidi se već dugi niz godina primjenjuju kao najefikasniji analgetici, meċutim, što se duţe primjenjuju i u većim dozama, to je veća mogućnost nastanka tolerantnosti, što rezultira povećanjem potrebne doze i redukcijom efikasnosti. Danas se u terapiji akutne boli sve više uvode neopioidni analgetici, primjenjuje se regionalna i blok anestezija ili se analgetici apliciraju na mjestu aktivnosti kako bi reducirali koliĉinu opioida (31). Najĉešća sredstva koja se danas rutinski primjenjuju u reţimu analgezije pasa i maĉaka su ketamin, medetomidin, lidokain, NSAID preparati i opioidni analgetici. Ketamin Iako se ketamin dugo koristi za indukciju i odrţavanje opšte anestezije, tek nedavno je prikazan kao veoma koristan postoperativni analgetik. Aplikacija ketamina u subanestetiĉkim dozama (0,1 1,0 mg/kg i.v., i.m.) obezbjeċuje analgeziju djelujući kao antagonist na N-methyl-D-aspartat (NMDA) receptore (31). TakoĊer, ketamin potencira antinociceptorni efekt opioida i α 2 adrenergiĉnih agonista, tako da se simultanom aplikacijom ketamina sa nekim od navedenih lijekova postiţe bolji analgetski efekt. Koristan je i za reverziju tolerantnosti opioida nastalu uslijed dugotrajne aplikacije istih (9). Ukoliko se ketamin primjenjuje u malim dozama (0,6 mg/kg/h) u vidu tzv. infuzije konstantnog protoka (CRI - constant rate infusion), veoma je bitno prije prekida aplikacije postepeno smanjivati brzinu infuzije, kako bi smo prevenirali hipersenzibilizaciju koja moţe nastati ukoliko naglo prekinemo aplikaciju (19). U lijekove koji djeluju na iste receptore kao i ketamin spadaju dekstrometorfan i amantadin, ali se oni primjenjuju peroralno (31). Medetomidin Medetomidin kao i ksilazin je α 2 adrenergiĉnih agonista i primijenjen u niskim dozama (1-2 μg/kg) ima mjerljiv analgetski efekt sa blaţe izraţenim kardiovaskularnim sporednim efektima od onih koji se javljaju kod aplikacije većih doza (17, 28). Kao i ketamin, medetomidin je najefikasniji u kombinaciji sa opioidima u perioperativnom Veterinaria 59 (1-4), 85-91, Sarajevo
4 periodu. TakoĊer se moţe aplicirati infuzijom konstantnog protoka (1,5 μg/kg/sat ) i to kroz više sati, u kombinaciji sa drugim analgeticima kako bi reducirali bol, stres i anksioznost u posttraumatskoj ili postoperativnoj hospitalizaciji (31). Neţeljeni efekti navedene infuzione primjene medetomidina su hemodinamiĉnog karaktera, gdje dolazi do elevacije arterijskog pritiska, bradikardije, redukcije srĉanog indeksa i oksigenacije tkiva (17). Lidokain Primjena lokalnih anestetika metodama blokade nerava i regionalne infiltrativne anestezije predstavlja jednu od prvih metoda anestezije i anelgezije primijenjenih u modernoj veterinarskoj medicini. MeĊutim, navedene metode su istovremeno bile veoma teško izvodive na budnim pacijentima, te su brzo napuštene u korist opće anestezije. Danas se zna da lokalna anestezija nervnim blokom i infiltrativna anestezija kod pacijenata induciranih u opću anesteziju predstavlja jednu od najefikasnijih i najjeftinijih metoda blokade transmisije boli (31). Na mjestu lokalnog oštećenja tkiva lokalna anestezija smanjuje direktnu aktivaciju nociceptora (24). Lidokain apliciran sistemski u antiaritmiĉnim dozama (50-80 μg/kg/min) obezbjeċuje analgeziju, uklanja slobodne radikale i povećava gastrointestinalni (GI) motilitet (31). U humanoj medicini je potvrċeno da lidokain apliciran u obliku infuzionog rastvora u dozi od 5 mg/kg/sat djeluje analgetski kod neuropatija (30). NSAID Preoperativna primjena NSAID-a, naroĉito selektivnih COX-2 inhibitora, reducira upalnu reakciju i bolnost nastale hirurškim zahvatom (17, 18). Mogu se peroralno primijeniti šest do osam sati prije operativnog zahvata ili parenteralno neposredno prije zahvata, jer nemaju znaĉajan uticaj na hemostazu. TakoĊer, preporuĉena je njihova primjena u postoperativnom periodu tokom tri do pet dana sa svrhom redukcije mediatora upale (31). Iako postoje brojne indikacije preoperativne primjene NSAID lijekova, ĉesto su razmatrani njihovi efekti na funkciju bubrega i jetre sa aspekta hipotenzije, koja se javlja kod mnogih pacijenata u općoj anesteziji. MeĊutim, sprovedena istraţivanja efekata selektivnih COX-2 inhibitora na bubreţnu funkciju zdravih i oboljelih anesteziranih pacijenata nisu pokazala neţeljene efekte (4, 6). S obzirom da nisu sprovedena sliĉna istraţivanja sa aspekta funkcije jetre, dok se ista ne sprovedu i ne dokaţu suprotno, kod pacijenata kojima se preoperativno apliciraju NSAID lijekovi potreban je monitoring krvnog pritiska i tretman hipotenzije, ukoliko je prisutna (31). NSAID lijekovi, koji se najĉešće primjenjuju su karprofen, ketoprofen i acetilsalicilna kiselina (tab.1) (21). 88
5 Tabela 1. Doziranje NSAID za kontrolu akutne i hroniĉne boli Table 1. NSAID dosing regimen for acute and chronic pain Naziv preparata Indikacija Vrsta ţivotinje, doza, naĉin aplikacije Ketoprofen Hirurška bol Pas 2,0 mg/kg, IV, IM, SC Maĉka 2,0 mg/kg, SC Pas i maĉka 1,0 mg/kg Frekventost aplikacije Pre ili postoperativno Ponoviti za 24 h Hroniĉna bol Pas i maĉka 2,0 mg/kg, PO 1,0 mg/kg Inicijalno Ponoviti za 24 h Karprofen Hirurška bol Hroniĉna bol Pas i maĉka 4,0 mg/kg, IV,IM,SC 2,2 mg/kg Pas i maĉka 2,2 mg/kg, PO Jedanokratno Ponoviti po potrebi za 12 h Svakih 12 h Acetilsalicilna kiselina Hroniĉna bol Pas: mg/kg, PO Maĉka: 10 mg/kg, PO Svakih 8 h Svaka 72 h LITERATURA 1. Anand KJS, Hickey PR. Pain and its effects in the human neonate and fetus. N. Eng. J. Med., 1987;317: Anand KJS, Phil D, Hickey PR. Halothane morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in cardiac surgery. N. Eng. J. Med., 1992; 326: Anand KJS, Sippell WG, Aynsley-Green A. Randomized trial of fentanyl anesthesia in preterm babies undergoing surgery: effects on the stress response. Lancet 1987;1: Bergmann HML, Nolte IJA, Kramer S. Effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing surgery for fracture repair. Am. J. Vet. Res., 2005; 66: Bonica JJ. Definitions and taxonomy of pain. Izvod iz: Bonica J.J, Management of pain. Philadelphia: Lea & Febiger, 1990; Bostrom IM, Nyman G, Hoppe A, Lord P. Effects of meloxicam on renal function in dogs with hypotension during anesthesia. Vet. Anaesth. Analg. 2006; 33: Conzemius MG, Brockman DJ, King LG i saradnici. Analgesia in dogs after intercostal thoracotomy: a clinical trial comparing intravenous buprenorphine and intrapleural bupivacaine. Vet. Surg. 1994;23: Veterinaria 59 (1-4), 85-91, Sarajevo
6 8. Dickenson AH, Sullivan AF. Subcutaneous formalin-induced activity of dorsal horn neurons in the rat: differential response to an intrathecal opiate administered pre or post formalin. Pain 1987; 30: Eilers H, Philip LA, Bickler PE i saradnici. The reversal of fentanyl-induced tolerance by administration of "small dose" ketamine. Anesth. Analg. 2001; 93: Elizabeth MH, Andrew EK. Paint management in the small animal patient. izvod iz: Bojrab MJ, Ellison WG, Slocum B, Current techniques in small animal surgery, fourth edition.1996; 3: FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N. Engl. J. Med. 2001; 345: Fox SM, Mellor DJ, Firth EC i saradnici. Changes in plasma cortisol concentrations before, during and after analgesia, anaesthesia, and anaesthesia plus ovariohysterectomy in bitches. Res. Vet. Sci. 1994; 5: Gajraj NM. Cyclooxygenase-2 inhibitors. Anesth. Analg. 2003; 96: Grimm KA, Tranquilli WJ, Gross DR, i saradnici. Cardiopulmonary effects of fentanyl in conscious dogs and dogs sedated with a continuous rate infusion of medetomidine. Am. J. Vet. Res. 2005; 66: Howard-Jensen N, Cioms A. Ethical cod for animal experimentation, WHO Chron., 1985; 39: Joshi GP. Multimodal analgesia techniques and postoperative rehabilitation. Anesthesiol. Clin. North America., 2005; 23(1): Kehlet HD. Analgesia benefit postinjury outcome, izvod iz: Parker MM, Saphiro MJ, Porembka DT, Critical care state of the art, Anaheim CA: Society of Critical Care Medicine, 1995; 15: Kissin I. Preemptive analgesia. Anesthesiol. 2000; 93: Lamont LA, Tranquilli WJ, Mathews KA. Adjunctive analgesic therapy. Vet. Clin. North. Am. Small. Anim. Pract., 2000; 30: Liu S, Carpenter RL, Neal JM. Epidural anesthesia and analgesia: their role in posoperative outcome, Anesthesiol., 1995; 82: Mathews KA. Nonsteroidal anti-inflammmatory analgesics in pain management in dogs and cats, Can. Vet. J., 1996; 37: McGrath PJ, Johnson J, Goodman JT, i saradnici. CHEOPS: A behavioral scale for rating postoperative pain in children, Advances in pein reasrch and therapy. New York, Raven press, 1985; 9: Merskey H, Bogduk N. Part III: Pain Terms, A Current List with Definitions and Notes on Usage. izvod iz: IASP Task Force on Taxonomy, IASP Press, Seattle, 1994; Meyr AJ, Steinberg JS. The Physiology of the Acute Pain Pathway. Clin Podiatr. Med. Surg., 2008; 25:
7 25. Millar AY, Mansfield MD, Kinsella J. Influence of timing of morphine administration on postoperative pain and analgesic consumption. Br. J. Anaesth., 1998; 81: Mugabure BB, Tranque BI, González SS, i saradnici. Multimodal approaches to postoperative pain management and convalescence. Rev. Esp. Anestesiol. Reanim., 2007; 54(1): Ong CK-S, Lirk P, Seymour RA, i saradnici. The efficacy of preemptive analgesia for acute postoperative pain management: A meta-analysis. Anesth. Analg., 2005; 100: Pascoe PJ, Raekallio M, Kuusela E, i saradnici. Changes in the minimum alveolar concentration of isoflurane and some cardiopulmonary measurements during three continuous rate infusion rates of dexmedetomidine in dogs. Vet. Anaesth. Analg., 2006; 33: Rueben SS, Buvanendran A. Preventing the development of chronic pain after orthopedic surgery with preventative multimodal analgesic techniques. J. Bone Joint Surg. Am., 2007;89: Tremont-Lukats IW, Challapalli V, McNicol ED, i saradnici. Systemic administration of local anesthetics to relieve neuropathic pain: A systematic review and meta-analysis. Anesth. Analg., 2005; 101: Wetmore LA. Options for Analgesia in Dogs. izvod iz: Gleed RD, Ludders JW, Recent Advances in Veterinary Anesthesia and Analgesia: Companion Animals. International Veterinary Information Service, Ithaca, NY ( Uredništvo primilo rukopis Veterinaria 59 (1-4), 85-91, Sarajevo
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