Agents Actions, Special Conference Issue (1992) 0065-4299/92/02C238-04 $1.50+ 0.20/0 9 1992 Birkh/iuserVerlag, Basel Therapeutic efficacy of combined H I- + H2-receptor-antagonists on severe histamine-induced cardiovascular reactions in humans M. Tryba, M. Zenz and H. Thole Abstract Histamine is a well known causal factor in a variety of clinical events and complications, especially in allergic and anaphylactoid reactions. We therefore investigated whether a dose-dependent therapeutic effect of H1 + H2-antagonists (dimethindene maleate+ cimetidine) could be shown in the treatment of a histamine-induced cardiovascular reactions in humans. 6 healthy male volunteers participated in a randomized single-blind crossover-study. A histamine dosage leading to a decrease of the mean arterial pressure to 60 mmHg within 2 min was continuously infused over a period of 15 min on two occasions. The volunteers received either histamine + saline or histamine + treatment first. Treatment started 3 min after the start of the histamine infusion (4 mg dimethindene maleate + 200 mg cimetidine i.v.) and was repeated every 2 min until the cardiovascular baseline values were reached or 15 rain were completed. Statistical analysis of the treatment effect was performed on an intraindividual basis (ANOVA) with p < 0.05 In both treatment courses mean MAP decreased to about 60 mmHg. While in the saline group MAP remained at this low level during the time of histamine infusion, all volunteers quickly responded to treatment with dimethindene maleate + cimetidine. After 8 mg dimethindene maleate + 400 mg cimetidine MAP reached baseline values in all volunteers (p <0.01). Mean HR increased to 119 bpm in the saline group after 3 rain. Treatment with dimethindene maleate+cimetidine showed similar efficacy against histamine-induced tachycardia (p <0.01). It may thus be concluded that usual dosages of H 1- and H 2- receptor-antagonists are effective in the treatment of histamine-induced cardiovascular reactions. Introduction Anaphylactoid reactions are a common cause of anesthetic complications occurring in 1-5% of all anesthetic procedures. About 10% of these ana- phylactoid reactions are life-threatening [9]. Severe bronchospasm or hypotension are the main clinical symptoms. Histamine has been shown to be a Address for correspondence: Tryba, Dept. Anesthesiology, In- tensive Care Medicine and Pain Therapie, University Hospital Bergmannsheil, Gilsingstr. 14, D-4630 Bochum, Germany. causal factor of anaphylactoid reactions in a variety of clinical situations. It is not only derived from release reactions of allergic and pseudoallergic nature due to drugs, but also from pathophysi- ological events, from surgical procedures, and from the infusion of free histamine during transfusion of blood [4, 9, 11, 13, 15, 16]. The observed histamine-induced clinical reactions are mediated by the activation of Ha- and H2- receptors. Numerous experimental and clinical studies have shown that non-lethal as well as potentially lethal cardiovascular reactions can be