Therapeutic trial of diazepam versus placebo in acute chloroquine intoxications of moderate gravity
- 77 Downloads
- 14 Citations
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.
Key words
Chloroquine poisoning Diazepam Membrane-stabilising effectPreview
Unable to display preview. Download preview PDF.
References
- 1.Guillion C, Le Bonniec Y (1982) Suicide mode d'emploi. Histoire, technique, actualité. Alan Moreau Editions, ParisGoogle Scholar
- 2.Tona L, Ng YC, Akera T, Brody TM (1990) Depressant effect of chloroquine on the isolated guinea-pig heart. Eur J Pharmacol 178: 293–301PubMedGoogle Scholar
- 3.Don Michael TA, Aiwazzadeh S (1970) The effects of acute chloroquine poisoning with special reference to the heart. Am Heart J 79: 831–842PubMedGoogle Scholar
- 4.Sofola OA (1979) The cardiovascular effect of chloroquine in anaesthetized dogs. Can J Pharmacol 58: 836–841Google Scholar
- 5.Sofola OA (1993) The effects of chloroquine on the electrocardiogram and heart rate in anaesthetized dogs. Clin Physiol 3: 75–82Google Scholar
- 6.Riou B, Barriot P, Rimailho A, Baud FJ (1988) Treatment of severe chloroquine poisoning. N Engl J Med 318: 1–6PubMedGoogle Scholar
- 7.Bondurand A, N'Dri K, Coffi S, Saracino E (1980) L'intoxication à la chloroquine au CHU d'Abidjan. Afr Méd 179: 239–242Google Scholar
- 8.Crouzette J, Vicaut E, Palombo S, Girre C, Fournier PE (1983) Experimental assessment of diazepam protecting activity on the acute toxicity of chloroquine. J Toxicol Clin Toxicol 20: 271–279PubMedGoogle Scholar
- 9.Koudogbo B, Asseko MC, Nguemby Mbina C, Laguerret-Atadou V (1986) Mode d'action antidotique du diazépam dans le traitement des intoxications à la chloroquine. J Toxicol Clin Exp 6: 307–312PubMedGoogle Scholar
- 10.Riou B, Rimailho A, Galliot M, Bourdon R, Huet Y (1988) Protective cardiovascular effect of diazepam in experimental acute chloroquine poisoning. Intensive Care Med 14: 610–616PubMedGoogle Scholar
- 11.Riou B, Lecarpentier Y, Barriot P, Viars P (1989) Diazepam does not improve the mechanical performance of rat cardiac papillary muscle exposed to chloroquine in vitro. Intensive Care Med 15: 390–395PubMedGoogle Scholar
- 12.Conférence de consensus (1988) Traitement de I'intoxication aiguë à la chloroquine. Réanim Soins Intens Méd Urg 4: 43–84Google Scholar
- 13.Monnet R, Boiteau H, Moussion C (1964) Identification et dosage de la chloroquine dans les milieux biologiques par spectrophotométrie dans I'ultra violet. Ann Biol Clin 22: 429–434Google Scholar
- 14.N'Dri KD, Palis R, Saracino E, Nyouma A, Bondurand A (1976) A propos de 286 cas d'intoxications à la chloroquine. Afr Méd 15: 103–105Google Scholar
- 15.Vitris M, Aubert M (1983) Intoxications à la chloroquine: notre expérience à propos de 80 cas. Dakar Méd 28: 593–602Google Scholar
- 16.Demazières J, Saissy JM, Vitris M, Seck M, Ndiaye M, Gaye M, Marcoux L (1992) Effets du diazépam sur la mortalité des intoxications aiguës par la chloroquine. Ann Fr Anesth Réanim 11: 164–167Google Scholar
- 17.Gnassounou JP, Advenier C (1988) Les effets antagonistes du diazépam et du RO5-4864 dans I'intoxication aiguë par la chloroquine chez le rat, sont-ils de nature centrale ou périphérique? Réanim Soins Intens Méd Urg 4: 61–62Google Scholar
- 18.Liu L, Katz Y, Weizman R, Rosenberg B, Pasternack GW, Gavish M (1991) Interactions of chloroquine with benzodiazepine, gamma-aminobutyric acid and opiate receptors. Biochem Pharmacol 41: 1534–1536PubMedGoogle Scholar
- 19.Charbonneau P (1988) Effect antiarythmique du diazépam lors des intoxications aiguës à la chloroquine. Apport de I'exploration isotopique. Réanim Soins Intens Méd Urg 4: 58–59Google Scholar
- 20.Clemessy J-L, Taboulet P, Hoffman JR, Hantson P, Barriot P, Bismuth C, Baud FJ (1996) Treatment of acute chloroquine poisoning: a 5 years' experience. Crit Care Med 24: 1189–1195PubMedGoogle Scholar