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. 1991 Oct 26;303(6809):1026–1029. doi: 10.1136/bmj.303.6809.1026

Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial.

R Keays 1, P M Harrison 1, J A Wendon 1, A Forbes 1, C Gove 1, G J Alexander 1, R Williams 1
PMCID: PMC1671790  PMID: 1954453

Abstract

OBJECTIVE--To see whether intravenous acetylcysteine would improve outcome in patients with fulminant hepatic failure after paracetamol overdose. DESIGN--A prospective randomised controlled study. SETTING--The Institute of Liver Studies, King's College Hospital, London. PATIENTS--50 consecutive patients (21 male) aged 16-60 with fulminant hepatic failure after paracetamol overdose who had not previously received acetylcysteine. INTERVENTIONS--Conventional intensive liver care plus either acetylcysteine (25 patients) in the same dose regimen as used early after a paracetamol overdose, except that the infusion was continued until recovery from encephalopathy or death, or an equivalent volume of 5% dextrose (25 patients). MAIN OUTCOME MEASURES--Survival; incidence of cerebral oedema, renal failure, and hypotension requiring inotropic support; liver function as assessed by prolongation of the prothrombin time; and degree of encephalopathy. RESULTS--The rate of survival was significantly higher in the acetylcysteine treated group than in the controls (48% (12/25 patients) v 20% (5/25); p = 0.037, 95% confidence interval for difference in proportions surviving 3% to 53%). Acetylcysteine treated patients had a lower incidence of cerebral oedema (40% (10/25) v 68% (17/25); p = 0.047, 95% confidence interval for difference in incidence 2% to 54%), and fewer developed hypotension requiring inotropic support (48% (12/25) v 80% (20/25); p = 0.018, 95% confidence interval 7% to 57%). Rates of deterioration and recovery of liver function, however, were similar in the two groups. No adverse reactions to acetylcysteine were seen. CONCLUSIONS--Acetylcysteine is safe and effective in fulminant hepatic failure after paracetamol overdose.

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Selected References

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  1. Artman M., Olson R. D., Boucek R. J., Jr, Boerth R. C. Depression of contractility in isolated rabbit myocardium following exposure to iron: role of free radicals. Toxicol Appl Pharmacol. 1984 Feb;72(2):324–332. doi: 10.1016/0041-008x(84)90317-x. [DOI] [PubMed] [Google Scholar]
  2. Aruoma O. I., Halliwell B., Hoey B. M., Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med. 1989;6(6):593–597. doi: 10.1016/0891-5849(89)90066-x. [DOI] [PubMed] [Google Scholar]
  3. Banda P. W., Quart B. D. The use of N-acetylcysteine long after an acetaminophen overdose in mice. Toxicol Lett. 1987 Mar;36(1):89–94. doi: 10.1016/0378-4274(87)90045-2. [DOI] [PubMed] [Google Scholar]
  4. Bihari D. J., Gimson A. E., Williams R. Cardiovascular, pulmonary and renal complications of fulminant hepatic failure. Semin Liver Dis. 1986 May;6(2):119–128. doi: 10.1055/s-2008-1040595. [DOI] [PubMed] [Google Scholar]
  5. Braganza J. M., Holmes A. M., Morton A. R., Stalley L., Ku R., Kisher R. Acetylcysteine to treat complications of pancreatitis. Lancet. 1986 Apr 19;1(8486):914–915. doi: 10.1016/s0140-6736(86)91017-2. [DOI] [PubMed] [Google Scholar]
  6. Harrison P. M., Keays R., Bray G. P., Alexander G. J., Williams R. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. Lancet. 1990 Jun 30;335(8705):1572–1573. doi: 10.1016/0140-6736(90)91388-q. [DOI] [PubMed] [Google Scholar]
  7. Harrison P. M., O'Grady J. G., Keays R. T., Alexander G. J., Williams R. Serial prothrombin time as prognostic indicator in paracetamol induced fulminant hepatic failure. BMJ. 1990 Oct 27;301(6758):964–966. doi: 10.1136/bmj.301.6758.964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Harrison P. M., Wendon J. A., Gimson A. E., Alexander G. J., Williams R. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med. 1991 Jun 27;324(26):1852–1857. doi: 10.1056/NEJM199106273242604. [DOI] [PubMed] [Google Scholar]
  9. Knaus W. A., Draper E. A., Wagner D. P., Zimmerman J. E. Prognosis in acute organ-system failure. Ann Surg. 1985 Dec;202(6):685–693. doi: 10.1097/00000658-198512000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Miners J. O., Drew R., Birkett D. J. Mechanism of action of paracetamol protective agents in mice in vivo. Biochem Pharmacol. 1984 Oct 1;33(19):2995–3000. doi: 10.1016/0006-2952(84)90599-9. [DOI] [PubMed] [Google Scholar]
  11. Modig J., Sandin R. Haematological, physiological and survival data in a porcine model of adult respiratory distress syndrome induced by endotoxaemia. Effects of treatment with N-acetylcysteine. Acta Chir Scand. 1988 Mar;154(3):169–177. [PubMed] [Google Scholar]
  12. O'Grady J. G., Alexander G. J., Hayllar K. M., Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989 Aug;97(2):439–445. doi: 10.1016/0016-5085(89)90081-4. [DOI] [PubMed] [Google Scholar]
  13. O'Grady J. G., Gimson A. E., O'Brien C. J., Pucknell A., Hughes R. D., Williams R. Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterology. 1988 May;94(5 Pt 1):1186–1192. doi: 10.1016/0016-5085(88)90011-x. [DOI] [PubMed] [Google Scholar]
  14. O'Grady J. G., Williams R. Acute liver failure. Baillieres Clin Gastroenterol. 1989 Jan;3(1):75–89. doi: 10.1016/0950-3528(89)90047-x. [DOI] [PubMed] [Google Scholar]
  15. O'Grady J. G., Williams R. Management of acute liver failure. Schweiz Med Wochenschr. 1986 Apr 26;116(17):541–544. [PubMed] [Google Scholar]
  16. Parker D., White J. P., Paton D., Routledge P. A. Safety of late acetylcysteine treatment in paracetamol poisoning. Hum Exp Toxicol. 1990 Jan;9(1):25–27. doi: 10.1177/096032719000900106. [DOI] [PubMed] [Google Scholar]
  17. Prescott L. F., Donovan J. W., Jarvie D. R., Proudfoot A. T. The disposition and kinetics of intravenous N-acetylcysteine in patients with paracetamol overdosage. Eur J Clin Pharmacol. 1989;37(5):501–506. doi: 10.1007/BF00558131. [DOI] [PubMed] [Google Scholar]
  18. Prescott L. F., Illingworth R. N., Critchley J. A., Stewart M. J., Adam R. D., Proudfoot A. T. Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. Br Med J. 1979 Nov 3;2(6198):1097–1100. doi: 10.1136/bmj.2.6198.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rumack B. H., Peterson R. C., Koch G. G., Amara I. A. Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment. Arch Intern Med. 1981 Feb 23;141(3 Spec No):380–385. doi: 10.1001/archinte.141.3.380. [DOI] [PubMed] [Google Scholar]
  20. Tirmenstein M. A., Nelson S. D. Acetaminophen-induced oxidation of protein thiols. Contribution of impaired thiol-metabolizing enzymes and the breakdown of adenine nucleotides. J Biol Chem. 1990 Feb 25;265(6):3059–3065. [PubMed] [Google Scholar]

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