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

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 X 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 X kg-1) and H2 (cimetidine, 4 mg X kg-1) receptor antagonists administered 15 min before trimethaphan, 0.5 mg X kg-1, in the awake and anesthetized states. In Group 3 (n = 6), the effects of infusion of trimethaphan, 3 mg X 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 X ml-1 (P less than 0.01) and from 0.60 +/- 0.11 to 2.58 +/- 0.33 ng X ml-1 (P less than 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 less than 0.01) and anesthetized (from 82.6 +/- 3.7 to 57.3 +/- 2.5 mmHg; P less than 0.01) states, and was associated with increases in cardiac output and heart rate; stroke volume increased in the awake state only.(ABSTRACT TRUNCATED AT 250 WORDS)