Combined H1 and H2 receptor blockade attenuates the cardiovascular effects of high-dose atracurium for rapid sequence endotracheal intubation

Large doses of atracurium (1.5 mg/kg) (six times the ED95) can result in significant histamine release, resulting in systemic hypotension. The efficacy of histamine receptor blockade in attenuating atracurium induced hypotension was therefore studied. Four groups of seven patients each were studied: group I, control; group II, H1 blockade (1 mg/kg diphenhydramine); group III, H2 blockade (cimetidine 4 mg/kg); and group IV, H1 and H2 blockade (diphenhydramine 1 mg/kg and cimetidine 4 mg/kg). All patients were anesthetized with an intravenous narcotic-nitrous oxide technique and then given 1.5 mg/kg atracurium. In group I, mean arterial pressure (MAP) decreased 30 mm Hg after 2 minutes and remained 25 mm Hg below baseline at 3 minutes, a change significantly greater than that in group IV, in which MAP decreased 8 and 7 mm Hg, respectively. H1 receptor blockade was associated with no significant attenuation of changes in MAP. H2 receptor blockade alone was associated with significant decreases in MAP, possibly secondary to enhanced release of histamine via an antagonist effect on recently described H3 receptors. Plasma histamine levels increased significantly 2 minutes after atracurium administration and correlated with hemodynamic changes. It is concluded that combined H1 and H2 receptor blockade attenuates cardiovascular effects associated with large doses of atracurium in humans. Histamine-releasing agents may be contraindicated in patients subject to chronic H2 receptor blockade.