Protective cardiovascular effects of diazepam in experimental acute chloroquine poisoning

Abstract

To assess the effects of diazepam in chloroquine poisoning, we studied pentobarbital anesthetized and mechanically ventilated pigs. All the pigs received 50 mg.kg-1 chloroquine given intravenously for 25 min. Eight pigs acted as control (group C). Another 7 were treated with diazepam given intravenously 5 min after the end of chloroquine infusion: 2 mg.kg-1 of diazepam for 2 min, then 1 mg.kg.h-1 for 25 min (group D). Thereafter, all pigs were sacrificed. In both groups the chloroquine infusion induced a large fall in arterial pressure, a decrease in heart rate, and an increase in QRS duration. No difference was observed between the 2 groups for weight, systolic and diastolic arterial pressures, heart rate, QRS and QT durations before diazepam. After diazepam, systolic and diastolic arterial pressures, heart rate, urine volume, urinary excretion of chloroquine, plasma and blood cell chloroquine levels were higher, whereas QRS duration was lower, in group D compared to group C. No difference was observed between the 2 groups for urinary concentration of chloroquine, the ratio between plasma and blood cell chloroquine levels, hepatic, cardiac, and skeletal muscle chloroquine levels, and QT duration. After diazepam, the slope of the regression curve between QRS duration and plasma chloroquine levels was reversed in group D compared to group C. We conclude that diazepam counteracts some haemodynamic and electrocardiographic changes, and increases urinary excretion of chloroquine, in acute experimental chloroquine poisoning.

Massive hydroxychloroquine overdose

“…The suggestion of using diazepam for a hydroxychloroquine overdose is based on observations from patients overdosed with chloroquine and coingestion of diazepam who did not develop cardiovascular toxicity (8). Additionally, regarding a chloroquine overdose, Crouzette and Riou showed experimentally that high-dose diazepam decreased mortality in rats and provided protective cardiovascular effects in pigs (9,10). A case of severe hydroxychloroquine overdose was reported by Pruchnicki, and in this case high doses of diazepam (1 mg kg À1 ) were administered and this appeared to reverse the potential cardiovascular toxicity of the hydroxychloroquine (4).…”

Acute Chloroquine Poisoning: A Case Report

“…(5) Diazepam is a valuable therapeutic agent in experimental chloroquine poisoning, it counteracts some hemodynamic and electrocardiographic changes, and increased urinary excretion of chloroquine in experimental chloroquine poisoning, but diazepam cannot be considered as an antidote against chloroquine. (1,2) The management of severe chloroquine intoxication involves control of airway, breathing and circulation, prevention of further absorption, stabilizing the cardiovascular system and aggressively managing hypokalemia. Activated charcoal absorbs chloroquine very effectively from the gastrointestinal tract (GIT), and should be administered as soon as possible in known or suspected chloroquine poisoning.…”

“…(1,2) Gastric lavage was performed, and he received activated charcoal when he was haemodynamically stable. His ECG was initially abnormal and the QRS complex was 0.14 sec.…”

Hydroxychloroquine overdose: case report and recommendations for management

“…The use of diazepam to treat dysrhythmias and hypotension is a unique use of this drug in an overdose situation [12]. Animal studies have shown that high doses of diazepam decreased mortality significantly [13] and also improved cardiovascular parameters and increased excretion of chloroquine [14]. In the absence of good human studies, the use of diazepam can be recommended when significant toxicity is noted from hydroxychloroquine overdose, given these findings.…”