Therapeutic trial of diazepam versus placebo in acute chloroquine intoxications of moderate gravity

Abstract

Objective: Acute chloroquine intoxication is responsible for a membrane-stabilising effect which results in electrocardiographic (ECG) and hemodynamic disturbances. Diazepam is used in acute chloroquine intoxication on the basis of clinical and experimental observations, but its utility alone, in man, remains unproven. The goal of this study was to verify whether diazepam alone has an effect on the membrane-stabilising effect observed in moderately severe chloroquine intoxications.

Design: Prospective, multi-center, double-blind, placebo-controlled study.

Setting: Prehospital mobile intensive care units (Paris) and hospital intensive care units (paris and Dakar).

Patients and participants: Adults with moderately severe intoxication defined as: a suspected ingested dose of 2 or more but less than 4 g, systolic blood pressure (SBP) higher than 80 mmHg, QRS duration less than 0.12 s and the absence of dysrhythmia at inclusion.

Interventions: Patients received either a loading dose of 0.5 mg/kg diazepam followed by an infusion of 1 mg/kg over 24 h or an equivalent volume of placebo.

Measurements and results: Outcome was measured by serial assessments of SBP, ECG (QRS and QT segments) and clinical deterioration. There were no significant differences observed in the initial or serial ECG or SBP measurements. There were no deaths and no patient had to be removed from the study due to clinical deterioration.

Conclusions: Diazepam, at the dose studied, does not appear to reverse the chloroquine-induced membrane-stabilising effect in acute moderately severe chloroquine intoxication. Supportive intensive care of these intoxications appears to be all that is necessary.