Combined H1 and H2 receptor blockade attenuates the cardiovascular effects of high dose atracurium in rabbits.

Large doses of atracurium (1.5 mg/kg) (six times the ED95) have been reported to provide adequate conditions for rapid sequence endotracheal intubation within 60 seconds in humans. However, this dose can result in significant histamine release and systemic hypotension. We therefore studied the efficacy of histamine receptor blockade in attenuating this response. Four groups of five rabbits were pretreated as follows: 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 rabbits were anesthetized and then 1.8 mg/kg (six times the rabbit ED95) atracurium was administered. Group I rabbits experienced a decrease in MAP of 12.2 mmHg after one minute, a change that was significantly greater than Group IV in which MAP decreased by 0.8 mmHg (p less than 0.001). H1 or H2 receptor blockade alone was associated with intermediate changes in MAP not significantly different from control. We conclude that combined H1 and H2 receptor blockade attenuates the cardiovascular effects associated with large doses of atracurium in the rabbit and that this combination of antagonist drugs might have similar effectiveness in humans.