Halothane Increases Myocardial Sensitivity to Epinephrine-Induced Arrhythmias in Cirrhotic Rats
AbstractBackground: Cirrhotic patients are at a greater risk of different kinds of arrhythmias. Despite the well-known arrhythmogenic effects of halothane, developing countries continue to use halothane due to its low cost. This study was designed to investigate the pathophysiology of halothane untoward effects on heart rhythm moreover was aimed to explore the effect of halothane anesthesia on the threshold of epinephrine-induced arrhythmia in cirrhotic rats.Methods: Bile duct ligation was used to induce cirrhosis. The subjects were anesthetized with halothane or pentobarbital. Arrhythmia was induced by intravenous injections of increasing doses of epinephrine. Blood pressure and the electrocardiogram were monitored. The threshold doses of epinephrine for induction of premature ventricular contraction (PVC), ventricular tachycardia (VT) and ventricular fibrillation (VF) were determined.Results: Cirrhotic rats had longer QTc intervals in comparison with sham-operated animals. Halothane-anesthetized rats had significantly shorter QTc intervals than pentobarbital-anesthetized rats in both cirrhotic and sham-operated groups. Halothane significantly decreased the threshold dose of epinephrine for induction of PVC, VT and VF in cirrhotic rats. The BP of different experimental groups did not differ with each other.Conclusion: Cirrhosis intensifies halothane induced ventricular arrhythmia and our results raise concerns regarding the use of halothane in cirrhotic patients.
Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008; 371(9615):838-51.
Zambruni A, Trevisani F, Caraceni P, Bernardi M. Cardiac electrophysiological abnormalities in patients with cirrhosis. J Hepatol. 2006; 44(5):994-1002.
Bernardi M, Calandra S, Colantoni A, Trevisani F, Raimondo ML, Sica G, et al. Q-T interval prolongation in cirrhosis: prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors. Hepatology. 1998; 27(1):28-34.
Couderc JP, Lopes CM. Short and long QT syndromes: does QT length really matter? J Electrocardiol. 2010; 43:396-9.
Di Micoli A, Zambruni A, Bracci E, Benazzi B, Zappoli P, Berzigotti A, et al. "Torsade de pointes" during amiodarone infusion in a cirrhotic woman with a prolonged QT interval. Dig Liver Dis. 2009; 41(7):535-8.
Gundling F, Schmidtler F, Zelihic E, Seidl H, Haller B, Ronel J, et al. [Frequency of cardiac arrhythmia in patients with liver cirrhoses and evaluation of associated factors]. Z Gastroenterol. 2012; 50(11):1149-55.
Ingwersen W, Allen DG, Dyson DH, Pascoe PJ, O'Grady MR. Cardiopulmonary effects of a halothane/oxygen combination in healthy cats. Can J Vet Res. 1988; 52(3): 386–91.
Mahboobi N, Esmaeili S, Safari S, Habibollahi P, Dabbagh A, Alavian SM. Halothane: how should it be used in a developing country? East Mediterr Health J. 2012; 18(2):159-64.
Zoumenou E, Gbenou S, Assouto P, Ouro Bang'na Maman AF, Lokossou T, Hounnou G, et al. Pediatric anesthesia in developing countries: experience in the two main university hospitals of Benin in West Africa. Paediatr Anaesth. 2010; 20(8):741-7.
Crawford MW, Ho DS, Shams M, Gow R. Magnesium deficiency alters the threshold for epinephrine-induced arrhythmias during halothane or sevoflurane anesthesia in the rat. J Cardiothorac Vasc Anesth; 2004; 18(3):313-6.
Blayney MR, Malins AF, Cooper GM. Cardiac arrhythmias in children during outpatient general anaesthesia for dentistry: a prospective randomised trial. Lancet. 1999; 354(9193):1864-6.
Beyea SC, Hicks RW. Patient safety first alert--epinephrine and phenylephrine in surgical settings. AORN J. 2003; 77(4):743-7.
Namiranian K, Samini M, Mehr SE, Gaskari SA, Rastegar H, Homayoun H, et al. Mesenteric vascular bed responsiveness in bile duct-ligated rats: roles of opioid and nitric oxide systems. Eur J Pharmacol. 2001; 423(2-3):185-93.
Zorniak M, Mitrega K, Bialka S, Porc M, Krzeminski TF. Comparison of thiopental, urethane, and pentobarbital in the study of experimental cardiology in rats in vivo. J Cardiovasc Pharmacol. 2010; 56(1):38-44.
Roesch C, Haselby KA, Paradise RR, Krishna G, Dierdorf S, Wolfe TM, Rao CC. Comparison of cardiovascular effects of thiopental and pentobarbital at equivalent levels of CNS depression. Anesth Analg ; 1983; 62(8):749-53.
Bazett H. An analysis of the time-relations of electrocardiograms. Annals of Noninvasive Electrocardiology. 2006; 2(2):177-94.
Ebrahimkhani MR, Kiani S, Oakley F, Kendall T, Shariftabrizi A, Tavangar SM, et al. Naltrexone, an opioid receptor antagonist, attenuates liver fibrosis in bile duct ligated rats. Gut. 2006; 55(11):1606-16.
Henriksen JH, Bendtsen F, Hansen EF, Moller S. Acute non-selective beta-adrenergic blockade reduces prolonged frequency-adjusted Q-T interval (QTc) in patients with cirrhosis. J Hepatol. 2004; 40(2):239-46.
Henriksen JH, Fuglsang S, Bendtsen F, Christensen E, Moller S. Arterial compliance in patients with cirrhosis: stroke volume-pulse pressure ratio as simplified index. Am J Physiol Gastrointest Liver Physiol. 2001; 280(4):G584-94.
Moss AJ. Measurement of the QT interval and the risk associated with QTc interval prolongation: a review. Am J Cardiol. 1993; 72(6):23B-25B.
Himmel HM. Mechanisms involved in cardiac sensitization by volatile anesthetics: general applicability to halogenated hydrocarbons? Crit Rev Toxicol. 2008; 38(9):773-803.
Han J, Kim N, Kim E. Trifluoroacetic acid activates ATP-sensitive K(+) channels in rabbit ventricular myocytes. Biochem Biophys Res Commun; 2001; 285(5):1136-42.