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Value of forced diuresis in acute barbiturate poisoning.

1968; BMJ; Volume: 2; Issue: 5608 Linguagem: Inglês

10.1136/bmj.2.5608.790

0959-8138

G. E. Mawer, H. A. Lee,

Pharmacogenetics and Drug Metabolism

The therapeutic usefulness of forced diuresis in severe barbi turate poisoning has yet to be evaluated by a controlled clinical trial. In the absence of such a trial its usefulness can be judged only indirectly from urinary barbiturate excretion rates. Unfortunately, however, the rate of apparent barbiturate excre tion varies with the method of its measurement. The usual clinical laboratory procedures (Varley, 1967) depend on chloroform or ether extraction of barbiturate fol lowed by spectrophotometric estimation. When applied to bio logical fluids they estimate not only unchanged barbiturate hypnotic but also a proportion of the metabolic derivatives (Bloomer, 1967). The resultant error is small when plasma is extracted, for the concentrations of unchanged barbiturate hypnotic and metabolites are of the same order in plasma. When urine is extracted, however, the error may be large, for the concentrations of metabolites may be several times greater than the concentration of unchanged barbiturate. Using more selective methods, Bloomer (1965, 1966) found that the urinary excretion of unchanged pentobarbitone and quinalbarbitone during forced diuresis was only a minor factor in the elimination of these driigs. Linton, Luke, and Briggs (1967) described the results of forced diuresis in 110 patients with severe barbiturate poisoning. They concluded that the barbiturate excretion rates justified forced diuresis in cases of poisoning by long-acting barbiturates and by cyclobarbitone. They also concluded that forced diuresis was useful in cases of poisoning by intermediate-acting barbi turates if the blood level had reached 4 mg./100 ml. and that mannitol had no practical advantages over frusemide. How ever, these conclusions were based on a method of barbiturate estimation which is not specific for unchanged hypnotic. The present report describes the pattern of barbiturate excre tion in four pairs of patients poisoned by pentobarbitone, amylobarbitone, butobarbitone, and phenobarbitone. Forced diuresis was induced with mannitol and frusemide, and the following were determined: (1) the rate of excretion of speci fically identified unchanged barbiturate hypnotic; (2) the extent to which the excretion rate was exaggerated by a less specific assay technique; (3) the rate of excretion of derivatives of barbituric acid, both unchanged barbiturate hypnotic and metabolites; and (4) the relative effects of frusemide and mannitol on the urinary excretion of unchanged barbiturate hypnotic.