PARACETAMOL OVERDOSE WITH LIVER FAILURE BENEFITS FROM N-ACETYLCYSTEINE

Clinical Bottom Line: In pts with fulminant hepatic failure after paracetamol overdose, N-acetylcysteine decreases the risk of death.

Appraised by: S Straus 13 March 1997

Three-part Question:
In pts with hepatic failure following paracetamol overdose, does N-acetylcysteine decrease the risk of death?

Search Terms: paracetamol and overdose in MEDLINE

The Study:
Single-blinded randomised controlled trial. Consecutive pts admitted with fulminant hepatic failure after paracetamol overdose and who had not already received n-acetylcysteine
Control group (N=25): conventional intensive liver care which included intravascular monitoring, inotropes, dialysis and intubation as necessary + IV D5W as placebo
Experimental group (N=25): conventional intensive liver care and IV N-AC 150 mg/kg in 200 cc D5W over 15 minutes, then 50 mg/kg in 500 cc over 4 hrs, followed by 100 mg/kg in 1 L D5W until death or recovery from encephalopathy

The Evidence:

Outcome	Control Event Rate	Time to Outcome	RRR	ARR	NNT
death	0.8	21 days	35%	0.28	4
	95% CI		4% to 66%	0.029 to 0.531	2 to 34
cerebral oedema	0.68	21 days	41%	0.28	4
	95% CI		2% to 80%	0.015 to 0.545	2 to 67
death in pts with cerebral edema	1.0	21 days	20%	0.20	5
	95% CI		4% to 36%	0.043 to 0.357	3 to 23

Comments:

1. mean of 54 hrs between overdose and admission to liver unit where randomisation and administration of N-AC occurred - no information about when N-AC given once admitted
2. pts in N-AC group had lower mean PT at start (115 vs 140) but no other differences in severity at baseline
3. no difference in PT and encephalopathy between groups during the trial.
4. 2 pts in treatment group referred for Orthotopic Liver Transplant (OLT) and included in analysis as dead - no mention if any others were referred for OLT or how this decision was made
5. no mention of side effects of N-AC
6. theorised that N-AC improves tissue oxygen extraction in fulminant hepatic failure

Expiry date: March 1998

References:

1. Keays R et al. BMJ 1991;303:1026-9.

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