Effects of trimethaphan on arterial blood histamine and systemic hemodynamics in humans

Abstract

Because of lack of direct evidence of histamine release by trimethaphan, the authors determined serum histamine levels and hemodynamic responses to trimethaphan administration in 19 consecutive patients. Group 1 patients (n = 7) received a single intravenous injection of trimethaphan, 0.5 mg.kg-1, while awake and again during stable halothane-nitrous oxide anesthesia. Group 2 patients (n = 6) were pretreated with intravenous H1 (chlorpheniramine, 0.1 mg.kg-1) and H2 (cimetidine, 4 mg.kg-1) receptor antagonists administered 15 min before trimethaphan, 0.5 mg.kg-1, in the awake and anesthetized states. In Group 3 (n = 6), the effects of infusion of trimethaphan, 3 mg.min-1 for 15 min, were studied during halothane-nitrous oxide anesthesia. In Group 1, bolus doses of trimethaphan were associated with maximal increases in serum histamine from 0.56 ± 0.14 to 2.56 ± 0.35 ng.ml-1 (P < 0.01) and from 0.60 ± 0.11 to 2.58 ± 0.33 ng.ml-1 (P < 0.01) 2 min after drug administration in the awake and anesthetized states, respectively; there were also clinical manifestations of histamine release. Mean arterial pressure decreased maximally after 5 min in the awake (from 92.0 ± 3.4 to 69.9 ± 2.2 mmHg; P < 0.01) and anesthetized (from 82.6 ± 3.7 to 57.3 ± 2.5 mmHg; P < 0.01) states, and was associated with increases in cardiac output and heart rate; stroke volume increased in the awake state only. Pretreatment with H1 and H2 receptor antagonists did not modify the hemodynamic response to trimethaphan, despite increases in serum histamine levels comparable to Group 1. In contrast to Group 1, although trimethaphan infusion caused a significant (P < 0.05) increase in serum histamine concentration from 0.72 ± 0.1 to 1.1 ± 0.1 ng.ml-1, the hypotension achieved was not associated with significant alterations in heart rate or cardiac output. In all patients, trimethaphan-induced hypotension was associated with a significant decrease in systemic vascular resistance, an effect that probably was related to the ganglionic blocking, direct vasodilating and alpha-adrenergic blocking action of trimethaphan. The authors conclude that histamine release by trimethaphan does not play an important role in the hemodynamic effects of the drug in humans.