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The effect of acutely induced hepatic failure on remifentanil and fentanyl blood levels in a pig model

Published online by Cambridge University Press:  01 March 2006

G. Kostopanagiotou ,
S. L. Markantonis ,
N. Arkadopoulos ,
I. Andreadou ,
G. Charalambidis ,
J. Chondroudaki ,
C. Costopanagiotou  and
V. Smyrniotis
G. Kostopanagiotou
Affiliation:
University of Athens School of Medicine, Attikon Hospital, Second Department of Anaesthesiology, Haidari, Greece
S. L. Markantonis
Affiliation:
University of Athens School of Pharmacy, Laboratory of Biopharmaceutics and Pharmacokinetics, Athens, Greece
N. Arkadopoulos
Affiliation:
University of Athens School of Medicine, Second Department of Surgery, Athens, Greece
I. Andreadou
Affiliation:
University of Athens School of Pharmacy, Laboratory of Biopharmaceutics and Pharmacokinetics, Athens, Greece
G. Charalambidis
Affiliation:
University of Athens School of Pharmacy, Laboratory of Biopharmaceutics and Pharmacokinetics, Athens, Greece
J. Chondroudaki
Affiliation:
University of Athens School of Medicine, Attikon Hospital, Second Department of Anaesthesiology, Haidari, Greece
C. Costopanagiotou
Affiliation:
University of Athens School of Medicine, Attikon Hospital, Second Department of Anaesthesiology, Haidari, Greece
V. Smyrniotis
Affiliation:
University of Athens School of Medicine, Second Department of Surgery, Athens, Greece
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Extract

Summary

Background and objective: Opioids and especially fentanyl are widely used during the intensive care unit management of intracranial pressure in fulminant hepatic failure patients as well as during and after liver transplantation. The newer synthetic opioid remifentanil is also increasingly being used in critical care patients. Due to a lack of data relating to the influence of acute hepatic failure on remifentanil and fentanyl pharmacokinetics, this study was designed in order to determine the impact of this condition on the blood levels of these opioids using a pig model. Methods: Twenty pigs were randomly assigned to one of two groups: A group with surgically induced acute hepatic failure by hepatic devascularization (acute hepatic failure, n = 10) and a control group (SHAM, n = 10), subjected to a SHAM operation. Postoperatively, five animals in each group were administered remifentanil (1 μg kg−1 min−1) or fentanyl (0.2 μg kg−1 min−1) by continuous intravenous infusion. Blood samples for determination of drug concentrations were withdrawn at 0 h and 0.5, 1, 5, 7, 9 h after initiation of dosing. Results: Significantly higher blood concentrations were found in animals with acute hepatic failure compared to SHAM-operated animals receiving remifentanil at 5 h (P = 0.003), 7 h (P = 0.007) and 9 h (P = 0.004) and fentanyl at 7 h (P < 0.0005) and 9 h (P = 0.05). The small number and the great variability in drug concentrations did not allow a detailed kinetic analysis to be performed. Approximate clearance values were found to be greater for the SHAM compared with the acute hepatic failure animals for both fentanyl and remifentanil. Conclusions: Hepatic devascularization in our porcine acute hepatic failure model, appears to have significantly altered the disposition of fentanyl and unexpectedly remifentanil. These changes were thought to be brought about by severe disruption of blood flow and biotransformation in the liver, as well as by haemodynamic changes in the acute hepatic failure animals.

Keywords

ACUTE LIVER FAILURE, OPIOID ANALGESICS, fentanyl, remifentanilPHARMACOKINETICSPIG MODEL
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 23 , Issue 7 , July 2006 , pp. 598 - 604
Copyright
© 2006 European Society of Anaesthesiology

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References

Lee WM. Medical progress. Acute liver failure. New Engl J Med 1993; 329: 1862–1872.Google Scholar
Fingerote RJ, Bain VG. Fulminant hepatic failure. Am J Gastroenterol 1993; 88: 1000–1010.Google Scholar
Caraceni P, Van Thiel DH. Acute liver failure. Lancet 1995; 345: 163–169.Google Scholar
Munoz SJ. Difficult management problems in fulminant hepatic failure. Sem Liv Dis 1993; 13: 395–413.Google Scholar
Schiodt FV, Atillasoy E, Shakil AO et al. Etiology and outcome for 295 patients with acute liver failure in the United States. Liver Transpl Surg 1999; 5: 29–34.Google Scholar
Eisenhuber E, Madl C, Kramer L et al. Prognostic factors in acute liver failure. Wien Klin Wochenschr 1998; 110: 564–569.Google Scholar
Ascher NL, Lake JR, Emond JC, Roberts JP. Liver transplantation for fulminant hepatic failure. Arch Surg 1993; 128: 677–682.Google Scholar
Sakabe T, Nakakimura K. Effects of anesthetic agents and other drugs on cerebral blood flow, metabolism, and intracranial pressure. In: Cottrell JE, Smith DS, eds. Anaesthesia and Neurosurgery, 3rd edn. St. Louis: Mosby, 1997: 152–160.
Marks RM, Sachar EJ. Undertreatment of medical inpatients with narcotic agents. Ann Intern Med 1973; 78: 173–181.Google Scholar
Misfeldt BB, Jorgensen PB, Spotoft H, Ronde F. The effects of droperidol and fentanyl on intracranial pressure and cerebral perfusion pressure in neurosurgical patients. Br J Anaesth 1976; 48: 963–968.Google Scholar
Moss E, Powell D, Gibson RM, McDowall DG. Effects of fentanyl on intracranial pressure and cerebral perfusion pressure during hypocapnia. Br J Anaesth 1978; 50: 779–784.Google Scholar
Wendon J, Williams R. The practice of liver transplantation. In: Williams R, Portmann B, Tan KC, eds. Acute Liver Failure, Edinburgh: Churchill Livingstone, 1995: 93–103.
Boos DL, Stirt JA. Pharmacology. In: Sperry RJ, Stirt JA, Stone DJ, eds. Manual of Neuroanaesthesia Toronto: BC Decker, 1989: 37–66.
Tegeder I, Lotsch J, Geisslinger G. Pharmacokinetics of opioids in liver disease. Clin Pharmacokinet 1999; 37: 17–40.Google Scholar
Dershwitz M, Hoke JF, Rosow CE et al. Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease. Anaesthesiology 1996; 84: 812–820.Google Scholar
Navapurkar VU, Archer S, Gupta SK et al. Metabolism of remifentanil during liver transplantation. Br J Anaesth 1998; 81: 881–886.Google Scholar
Selinger K, Lanzo C, Sekut A. Determination of remifentanil in human and dog blood by HPLC with UV detection. J Pharm Biomed Anal 1994; 12: 243–248.Google Scholar
Gillespie TJ, Gandolfi AJ, Maiorino RM, Vaughan RW. Gas chromatographic determination of fentanyl and its analogues in human plasma. J Anal Toxicol 1981; 5: 133–137.Google Scholar
Haberer JP, Schoeffer P, Couderc E, Duvaldestin P. Fentanyl pharmacokinetics in anaesthetized patients with cirrhosis. Br J Anaesth 1982; 54: 1267–1270.Google Scholar
Hudson RJ, Tsomson IR, Cannon JE, Friesen RM, Meatherall RC. Pharmacokinetics of fentanyl in patients undergoing abdominal aortic surgery. Anaesthesiology 1986; 64: 334–338.Google Scholar
Chism JP, Rickert DE. The pharmacokinetics and extra-hepatic clearance of remifentanil, a short acting opioid agonist, in male beagle dogs during constant rate infusions. Drug Metab Dispos 1996; 24: 34–40.Google Scholar
Hoke JF, Cunningham F, James MK, Muir KT, Hoffman WE. Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs. J Pharmacol Exp Ther 1997; 281: 226–232.Google Scholar
Newsome PN, Plevris JN, Nelson LJ, Hayes PC. Animal models of fulminant hepatic failure: a critical evaluation. Liver Transplant 2000; 6: 21–31.Google Scholar
Hanid MA, MacKenzie RL, Jenner RE et al. Intracranial pressure in pigs with surgically induced acute liver failure. Gastroenterology 1979; 76: 123–131.Google Scholar
Kostopanagiotou G, Routsi C, Smyrniotis V et al. Alterations in bronchoalveolar lavage fluid during ischaemia-induced acute hepatic failure in the pig. Hepatology 2003; 37: 1130–1138.Google Scholar
Egan TD, Kuramkote S, Gong G, Zhang J, McJames SW, Bailey PL. Fentanyl pharmacokinetics in haemorrhagic shock: a porcine model. Anaesthesiology 1999; 91: 156–166.Google Scholar
Johnson KB, Kern SE, Hamber EA, McJames SW, Kohnstamm KM, Egan TD. Influence of haemorrhagic shock on remifentanil-A pharmacokinetic and pharmacodynamic analysis. Anaesthesiology 2001; 94: 322–332.Google Scholar