Tekrarlanan halotan, izofluran ve sevofluran anestezisinin fare karaciğeri üzerine histopatolojik etkileri

Bu çalışmada halotan, izofluran ve sevofluranın fare karaciğeri üzerine olan histopatolojik etkileri araştırıldı. Karışık yetiştirilmiş Mus musculus Swiss-albino farelerden ortalama ağırlıkları 25-30 g olan toplam 80 fare çalışmada kullanıldı. Deney hayvanları (n=80) rasgele dört eşit gruba ayrıldılar; G I'e halotan, G II'ye izofluran ve G III'e sevofluran, (1'er MAC) verildi. G IV'e (kontrol) ise herhangi bir anestezik ajan verilmedi. Çalışma gruplarına on gün süre ile her gün ikişer saat olmak üzere %100 O2 içinde anestezik gazlar uygulandı. Çalışma sonunda farelerin karaciğerleri H-E (Hematoxylen-Eozin) ile boyandıktan sonra ışık mikroskobu ile portal ve sinüzoidal infiltrasyon (akut ve kronik iltihabı infiltrasyon), portal ve parankimal fibrozis, hepatositlerde hidropik dejenerasyon, mikro ve makroveziktiler yağlanma, apopitoz ve nükleer değişiklikler (nuklueslarda pleomorfizm, çift nükleus, şeffaf nükleus, inklüzyonlar) ve fokal nekroz, köprüleşme nekrozu, submasif ve masif nekroz ile portal ve intrahepatik safra stazı ve Kupffer hücre değişiklikleri (sayı ve şekil değişiklikleri) açısından değerlendirme yapılarak karaciğer hasarı histopatolojik olarak incelendi. Kontrol grubunda 3 farenin karaciğerlerinde çok hafif sel lüle r hasar vardı, diğerlerinde ise tamamen normal sellüler yapı saptandı. Halotan grubundaki bütün farelerin karaciğerlerinde hasar saptanırken, izofluran grubunda 17, sevofluran grubunda ise 13 farenin karaciğerinde hasar saptandı. Halotan grubundaki histopatolojik değişikliklerin derecesi izofluran grubuna göre daha fazla olmasına karşın, bu fark istatistiksel olarak anlamsız bulundu. Halotan ile sevofluran grupları arasındaki fark anlamlı idi (p

The histopathologic effect of repeated halothane, isoflurane and sevoflurane anesthesia on mice liver

In this study effects of halothane, isoflurane and sevoflurane were investigated on the liver cells in mice. Eigthy Mus musculus Swiss-albino mice weighing between 25-30 g grown heterogenously were included in this study. The animals were randomly divided into four groups: G I was received halothane, G II was received isoflurane and G III was received sevoflurane. G IV (control) was not received any anesthetic agent. The study groups were ventilated for 2 hour with 100% O<sub>2</sub> and appropriate inhalation agent for 10 days. After 10th day, histopathologic studies were performed on livers (portal and sinusoidal infiltration, portal and parenchymal fibrosis, focal necrosis, bridge necrosis, submassive and massive necrosis, portal and intrahepatic biliary stasis, hydropic degeneration, micro and macrovesicular fat, apoptosis and nuclear change). In control group three livers had very little cellular disconfiguration, while remaining livers were normal. Although necrotic tissues were seen in all of the mice in the halothane group, necrotic tissues were determined in 17 and 13 mice in the isoflurane and sevoflurane groups, respectively. Histopathologic grades and severity of lesions were higher in halothane group when compared with the isoflurane group, but differences were not significant. The difference between halothane and sevoflurane was determined significant (p<0.05), but it- was insignificant between isoflurane and sevoflurane groups. In halothane, isoflurane and sevoflurane groups histopathologic differences were regarded rather significant compared with the control group (p<0.001). We suggested that sevoflurane may be preferred during anesthesia especially in patients with liver disease.

___

  • 1. Harris B, Moody E. lnhalational anaesthetics. In: Weinberg GL(ed). Basic Science Review of Anesthesiology, Chicago. McGraw-Hill 1997: 8-15
  • 2. Burnell R. Brown. Inhalation anaesthesia and hepatic injury In: Gravenstem N, Kirby RR. (eds.). Complications in Anesthesiology, Philadelphia, Lippincott-Raven 1996: 701-710.
  • 3. EsenerZ. Genel Anestezi. İn: EsenerZ. Klinik Anestezi. İstanbul, Logos Yayıncılık 1991:43-101
  • 4. Ray DC, Drumond GB. Halothane hepatitis. Br J Anaesth 1991:67: 84-99.
  • 5. Smith G. lnhalational anaesthetic agents. In: Aitkenhead AR, Smith G. (eds.) Textbook Of Anaesthesia, Avon, Churchill Livingstone 1994: 153-173.
  • 6. Carrigan TW, Staughen WJ, A report of hepatic necrosis and death following isoflurane anesthesia. Anesthesiology 1987: 67:581-3.
  • 7. Cherng CH, Ho ST. Kuo WS, Yaııg CY, Chang CL. Akut hepatitis in an uremic patient following isoflurane anesthesia. Ma Tsui Hsueh Tsa Chi 1998: 26 (Abstract): 239-42.
  • 8. Gregoire S, Smiley RK. Acute hepatitis in a patient with mild factor IX deficiency after anaesthesia wiih isoflurane. Can Med Association J 1986; 1.35: 645-6.
  • 9. Holaday DA, Smith FR. Clinical characteristics and biotransformation of sevoflurane in healthv human volunteers. Anesthesiology 1981: 54: 100-6.
  • 10. Shichinohe Y, Masuda Y, Takahashi H et al. A case of postoperative hepatic injurv after sevaflurane anesthesia. Masui 1992: 41 (Abstract): 1802-5.
  • 11. Flecknell PA. Anaesthesia, in: Fleeknell PA. Laboratory Animal Anaesthesia. London, Academic Press 1987: 26-27.
  • 12. Crawford MW, Lerman J, Pilato M, Orrego H, Saldiva V, Carmichael FJ. Hameodynamic and organ blood flow responses to sevoflurane during spontaneous ventilation in the rat: a dose-response study. Can J Anaeslh 1992; 39: 270-5.
  • 13. Nishiyama 1. Yokoyama T, Hanaoka K. Liver function after sevoflurane or isoflurane anaesthesia in neurosurgical patients. Caıı J Anaeslh 1998;45:753-6.
  • 14. Tsujimoto S, Kato H, Minamoto Y, Miki H, Kitamura R. Comparison of postoperative liver dysfunction following halothane and sevoflurane anesthesia in women undergoing mastectomy for cancer. J Anesth 1995: 9:129-34.
  • 15. Hussey AJ, Aldridge LM, Paul D, Ray DC, Beckett GJ, Allan LG. Plasma glutathione S-transferase concentration as a measure of hepatocellular integrity following a single general anaesthetic with halothane, enflurane or isoflurane. Br J Anaesth 1988;60:130-5.
  • 16. laizzo PA, Seewald MJ, Powis G, Phil D, Van Dyke RA. The effects of volatile anesthetics on Ca++ mobilization in rat he-patocytes. Anesthesiology 1990: 72:504-9.
  • 17. Baden JM, Rice SA. Metabolism and toxicity. In: Miller RD (ed.) Anesthesia, New York, Churchill Livingstone 1994; 157-179.
  • 18. Collins VJ. Genel Anesthesia-Fundamental Consideratons In: Principles of Anesthesiology. Philadelphia, Lea & Febiger 1993; 314-360.
  • 19. Elliot RH, Strunin L. Hepatotoxicity of volatile anaesthetics. Br J Anaesth 1993; 70 (3): 339-49.
  • 20. Brunt EM, White H, Marsh JW, Holtmann B, Peters MG. Fluminant hepatic failure after repeated exposure to isoflurane anesthesia: acase report. Hepatology 1991; 13:1017-21.
  • 21. Weitz J, Kienle P, Bohrer H, Hofmann W, Theilmann L, Otto G. Fatal hepatic necrosis after isoflurane anaesthesia. Anaesthesia 1997; 52:892-5.
  • 22. Watanabe K, Hatakerıaka S, Ikemune K. A case of suspected liver dysfunction induced by sevoflurane anesthesia. Jpn J Anesthesiol 1993;42:902-5.
  • 23. Hitt BA, Mazze Rl, Cousins MJ, Edmunds HN, Barr G A, Tru-dell JR. Metabolism of isoflurane in Fischer 344 rais and man. Anesthesiology 1974; 40(Abstract):62-7.
  • 24. Goldfarb G, Debaene B, Ang ET, Roulot D, Jolis P, Lebrec D. Hepatic blood flow in humans during isoflurane - N20 and halothane - N20 anesthesia. Anesth Analg 1990; 71:349-53.
  • 25. Fujita Y, Kimura K, Hamada H, Takaori M. Comparative effects of halothane, isoflurane, and sevoflurane on the liver with hepatic artery ligation in the beagle. Anesthesiology 1991;75:313-8.
  • 26. Manohar M, Parks CM. Porcine systemic and regional organ blood flow during 1.0 and 1.5 minimum alveolar concentrations of sevoflurane anesthesia without and with 50% nitrous oxide. J Pharmacol Exp Ther 1984; 231 (Abslraet):640-8.
  • 27. Bernard JM, Doursout MF, Wouters P, Hartley CJ, Merin RG, Chelly JE. Effects of sevoflurane and isoflurane on hepatic circulation in the chronically instrumented dog. Anesthesiology 1992:77:541-5.
  • 28. Serin S, Gönüllü M, Özbilirıı G. Halotan ve izofluranın insan karaciğeri üzerine histopatoiojik etkileri. Türk Anest Rean Cem Mec 1995; 23: 281-7.
  • 29. Goldfarb G, Rogier E, Gebauer C, el al. Comparative effects of halothane and isofluraııe anesthesia oıı the ultrastructure of human hepatic cells. Anesth Analg 1989; 69: 491-5.
  • 30. Uslu S, Yakıt R, Yüksek MŞ. Halotan ve izofluranın karaciğer üzerine etkisi. Türk Aııest Rean Cem Mec 1995: 23: 325-8.
  • 31. Sameshima T. Hepatotoxicity of halogenated inhalational anesthetics studied in rats hepatocytes. Masui 1994; 43 (Abstract): 454-66.
  • 32. Van Dyke RA. Hepatic centrilobular necrosis in rats after exposure to halothane, enflurane or isoflurane. Anesth Analg 1982;61:812-9.
  • 33. Eger EI, Johnson BH. Strum DP, Ferell LD. Studies of the toxicity of 1-653, halothane and isoflurane in enzyme induced hypoxic rats. Anesth Analg 1987; 66:1227-9.
  • 34. Gelman S, Riverman V, Fowler KC, Bishop SP, Bradley EL. The effect of halothane. isoflurane and blood loss on hepatotoxicity and hepalic oxygen availability in phenobarbital pre treated hypoxic rats. Anesth Analg 1984: 63:965-72.
  • 35. Schlieble TM, Costa AK, Heffel DF, Trudell JR. Comparative toxicity of halothane, isoflurane and phenobarbital induction in monolayer cultures of rat hepatocytes. Anesthesiology 1988; 68:485-94.
  • 36. Ghantus HN, Fernando J, Gandolfi AJ, Brendel K. Toxicity of halothane in guinea pig liver slices. Toxicology 1990; 62: 59-69.
  • 37. Ghantus HN, Fernando J, Gandolfi AJ, Brendel K. Sevoflurane is biotamsformed by guinea pig liver slices but causes minimal cytotoxicity. Anesth Analg 1992; 75: 36-40.
  • 38. Kharasch ED. Metabolism and toxicity of the new anesthetic agents. Acta Anaesthesiol Belg 1996; 47: 7-14.
  • 39. Fee JP, Thomson GH. Comparative tolerability profiles of the inhaled anaesthetics. Drug Safety 1997; 16 (Abstract): 157-70.
  • 40. Frink EJ, Isner RJ, Malan TP, Morgan SE, Brown EA, Brown BR Jr. Sevoflurane degradation product concentrations with soda lime during prolonged anesthesia. J Clin Anesth 1994; 6:239-42.
  • 41. Hasting KL, Thomas C, Hubbart AK, Gandolfi AJ. Serening for antibodies associated with halothane hepatits. Br J Anaesth 1991:67:722-5.
  • 42. Kenna JG, Neuberger J, Williams R. Specific antibodies to halothane induced liver antigens in halothane associated hepatitis. Br J Anaesth 1987; 59:1286-90.
Anestezi Dergisi-Cover
  • ISSN: 1300-0578
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 1993
  • Yayıncı: Betül Kartal
Sayıdaki Diğer Makaleler

Çocuklarda sevofluran ve halotanla anestezi indüksiyonunun göziçi hemodinamiye etkileri

idil TEKİN, Handan ALINCAK, Koray ERBÜYÜN

İntrakraniyal cerrahide kullanılan anestezi yöntemlerinin immün-enflamatuar yanıt üzerine etkileri

Nusa TUNA, Metin TUNA, Demet KOCA, Şebnem ATICI, Anış ARIBOĞAN, Geylan IŞIK

Kısa süreli cerrahi girişimlerde "Kaflı orofaringeal havayolu" ve "Laringeal maske" uygulaması

MESUT ŞENER, Elif A. AKPEK, Gülnaz ARSLAN

Marfan sendromlu olguda anestezi: İki olgu nedeniyle

Ayşegül CEYHAN, Ferah DÖNMEZ, Hatice YAĞMURDUR, Altuğ NARLI, Nurten ÜNAL

Propofol enjeksiyon ağrısını önlemede ondansetron ve lidokain kullanılması

Santral venöz katetere bağlı infeksiyonların tanısında endolüminal fırça tekniğinin yeri

Döndü İYİCAN, Esragül AKINCI, Pınar DURAK, Özcan ERDEMLİ, Mehmet KARAHAN

Koroner arter cerrahisi anestezisinde rokuronyum ve pankuronyumun hemodinamik etkilerinin karşılaştırılması

Suna GÖREN, Gülsen KORFALI, Nuray KAPLAN, Şükran ŞAHİN

Duchenne tipi musküler distrofili olguda anestezik yaklaşım

Hilal GÜNAL, Canan ÜN, Tülin BİLGİLİ, Mehtap S. TUNÇ, Eser ŞAVKILIOĞLU

Omurga cerrahisinde wake-up testi uygulamasında propofol ve sevofluranın karşılaştırılması

Ahmet EROĞLU, Cenk ERKILINÇOĞLU, Mine SOLAK

Tekrarlanan halotan, izofluran ve sevofluran anestezisinin fare karaciğeri üzerine histopatolojik etkileri

Cengiz Bekir DEMİREL, Mustafa KÖSEM, İsmail KATI, HANEFİ ÖZBEK, Ürfettin A. HÜSEYİNOĞLU, HASAN KOÇOĞLU