Dokumentation avseende biverkningar med fatal utgång vid intravenös administrering av diazepam. Frå

Fråga: Dokumentation avseende biverkningar med fatal utgång vid intravenös administrering av diazepam. Frågan är ställd med anledning av dödsfall hos kvinna som erhållit 10 mg Valium intravenöst som premedicinering före intrakraniellt ingrepp (detaljerade kliniska data saknas).

Sammanfattning: Severe adverse reactions to intravenous diazepam are uncommon. Only single cases of fatal outcome after iv diazepam have been reported and in all cases there were predisposing factors such as hepatic decompensation, serious cardiac or pulmonary disease, raised intracranial pressure and concurrent therapy with other CNS depressant drugs. It has been pointed out in the literature that any intravenous sedative should be administered with caution to these patients.

Svar: Intravenous diazepam is the agent of choice in status epilepticus and is widely used as an introduction agent before anesthesia and as premedication for cardioversion and endoscopic procedures.

Diazepam, in an intravenous dose of 5 to 10 mg, can cause a slight decrease in respiration, blood pressure and left ventricular stroke work. Increase in heart rate and decrease in cardiac output can also occur (1).

Patients with hepatic failure are particularly prone to respiratory depression when treated with agents largely detoxicated in the liver, as diazepam. Elderly individuals often show a surprising susceptibility to sedatives (2).

Looking into the literature we have found single case reports describing apnea or hypotension following iv diazepam. In all these cases the patients were elderly, had serious underlying disease or received other central depressant drugs concurrently (3).

Greenblatt and Koch-Weser (1973; 4) reported adverse reactions in 6 of 173 hospitalized patients receiving iv diazepam. Three of these reactions were minor, three were life-threatening (apneas and coma in two patients, hypotension and coma in one). In all 6 cases the clinical situation was complicated by hepatic decompensation, hypoxia, congestive heart failure or concurrent treatment with other CNS depressant drugs (4).

Gatrod (1982; 5) described 7 cases of respiratory depression following iv diazepam in convulsing patients. Five of these had raised intercranial pressure that, according to the author, may make the respiratory centre more sensitive to the effects of iv diazepam (5). 1 Goodman and Gilman, The pharmacological basis of therapeutics, 1980; 6th ed: 438 2 Davies, Textbook of adverse drug reactions, 1981; 2nd ed: 171 3 Donaldson D, Gibson G: Systemic complications with intravenous diazepam. Oral Surg 1980; 49: 126-130 4 Greenblatt DJ, Koch-Weser YJ: Adverse reactions to intravenous diazepam. A report from the Boston Collaborative Drug Surveillance Program. Am J Med Sci 1973; 266: 261-266 6 Gatrad AR: Dangers of intravenous diazepam in controlling fits in patients with raised intracranial pressure. Br J Clin Pract 1982; 36: 189-191