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The clinical efficacy of different doses of the specific benzodiazepine antagonist flumazenil was studied in a total of 72 patients with benzodiazepine or ethanol overdose. In a randomized double-blind study, 18 patients (group 1) and eight patients (group 2) with suspected benzodiazepine overdose received 5 mg (group 1) or 1 mg (group 2) flumazenil or placebo, respectively. The stage of coma, heart rate, blood pressure and respiratory rate were monitored within the following 15 min. If no change in the stage of coma was observed, 5 mg (group 1) or 1 mg (group 2) flumazenil were given, and the stage of coma, heart rate and blood pressure were again monitored. In a similar way, the effect of 5 and 1 mg flumazenil was investigated in 13 patients (group 3) and four patients (group 4) with ethanol intoxication. In an open trial, the clinical efficacy of flumazenil for the diagnosis of benzodiazepine or ethanol overdose was studied in 29 patients (group 5). In all patients, a toxicological screening confirmed benzodiazepine or ethanol overdose. None of the patients receiving placebo showed effects on stage of coma, heart rate, blood pressure or respiratory rate. Patients with benzodiazepine overdose who received 5 mg flumazenil regained consciousness about 1-2 min after the end of injection. The effect of 1 mg flumazenil (group 2) on benzodiazepine-induced coma was less pronounced. In patients with ethanol overdose (group 3), ethanol-induced coma was reversed after 5 mg flumazenil more slowly than in patients of group 1. No effect of flumazenil on ethanol-induced coma was observed in group 4. In group 5, flumazenil proved to be useful for diagnosing benzodiazepine or ethanol intoxication. In one patient with coma due to carbamazepine overdose, flumazenil was also found to be effective. Additionally, a possible analytical interference of flumazenil and its metabolites with the identification of other benzodiazepines by a toxicological screening procedure was studied. Even after an oral dose of 200 mg flumazenil, no interference with immunological benzodiazepine assays (EMIT, TDX, and RIA) was found. A metabolite and an artifact of flumazenil could be identified in urine by gas chromatography/mass spectrometry.

21 patients with acute myocardial infarction and ventricular arrhythmia of Lown class II-IIIB of acute onset received a short infusion of (50 mg/5 min) ajmaline (Gilurytmal). 6 of the patients had normal kidney and liver function (Group 1), 4 patients had acute renal failure and hemodialysis treatment (Group 2), 4 patients had impaired hepatic function (Group 3), 3 patients had cardiogenic shock (Group 4), and 4 patients had been pretreated with phenobarbital for seizures for at least 5 days (Group 5). A distribution half-life of 6 +/- 1 min and an elimination half-life of 95 +/- 6 min was determined in Group 1. The total plasma clearance was significantly lower in patients with impaired liver or cardiac function and significantly higher in Group 5, whereas impaired renal function did not affect total plasma clearance. After short infusion, ventricular arrhythmia of Lown II-IIIB completely disappeared for at least 16 to 36 min (mean: 19 min), which was associated with an ajmaline plasma level of 0.1-0.45 micrograms/ml. Additionally, steady-state plasma levels of ajmaline were determined after continuous infusion of 10-50 mg/h to 16 patients (Group 6) with ventricular arrhythmia of acute onset (Lown class IVA-V). Ventricular arrhythmia completely disappeared or at least changed to lower Lown classes at ajmaline plasma levels of 0.4-2.0 micrograms/ml. The ajmaline plasma protein binding was 76 +/- 9%. Ajmaline had a special affinity to alpha 1-acid glycoprotein.

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