Enhanced elimination in acute barbiturate poisoning – A systematic review

Abstract

Context. Despite a worldwide decline in barbiturate use, cases of acute poisoning with severe toxicity are still noted, particularly in developing countries. Severe poisonings often require prolonged admission to an intensive care unit, so enhanced elimination might be useful to hasten recovery. Information regarding the efficacy of these techniques for individual barbiturates is not available in standard textbooks. Objective. To determine the evidence supporting the effect of enhanced elimination and its role in the management of acute barbiturate poisoning. Methods. A systematic review was conducted using broad search criteria in three databases. All potentially relevant articles were obtained, and reference lists were manually reviewed. Ninety-four publications fulfilling inclusion criteria were located. Studies were classified as controlled or uncontrolled, and clinical and pharmacokinetic end points were manually extracted. If not directly stated, standard pharmacokinetic methods were used to calculate the clearance and efficiency of enhanced elimination techniques for each barbiturate and tabulated for direct comparison. Prospective controlled clinical trials. Two of the 94 publications were prospective controlled studies (only one stated that allocation was via blinded randomisation), and both assessed the effect of multiple-dose activated charcoal for acute phenobarbital poisoning. These studies demonstrated enhanced elimination with a decrease in elimination of half-life from approximately 80 to 40 h, but only one study reported clinical benefits. Uncontrolled series and single case reports. Sufficient data to determine the clearance due to enhanced elimination were available in only 52 of these papers. Barbiturate clearances by enhanced elimination varied markedly among studies. While extracorporeal modalities appeared to increase the direct clearance of many barbiturates, there was insufficient information to confirm a clinical benefit. Conclusions. There is limited evidence to support the use of enhanced elimination in the treatment of poisoning with most barbiturates. There is no role for urine alkalinisation, while multiple-dose activated charcoal may be useful for most phenobarbital and possibly primidone poisonings. Extracorporeal techniques appear to enhance elimination, but the clinical benefits, relative to the potential complications and cost, are poorly defined. Extracorporeal techniques such as haemodialysis and haemoperfusion can be considered for patients with life-threatening barbiturate toxicity such as refractory hypotension.

Keywords:

• Pentobarbital
• Phenobarbital
• Barbiturate
• Pharmacokinetics
• Dialysis