The cardiovascular effects of mivacurium chloride (BW B1090U) in patients receiving nitrous oxide-opiate-barbiturate anesthesia

Abstract

The dose-effect relationship of mivacurium chloride on arterial blood pressure, heart rate, and plasma histamine was determined in 97 consenting ASA physical status I-II patients receiving nitrous oxide-oxygen-opiate-barbiturate anesthesia. In the absence of surgical stimulation during steady state anesthetic conditions with controlled ventilation, average maximum change in tachograph-counted heart rate was 7% or less after 10-15-s injection of mivacurium at all does from 0.03 to 0.30 mg/kg. Average peak change in mean arterial pressure measured via radial arterial catheter was 7% or less after all doses from 0.03 to 0.15 mg/kg. Transient (0.2-4.5 min) decreases in arterial blood pressure were noted after 10-15-s injection in some patients at 0.20, 0.25, and 0.30 mg/kg. When they occurred, these changes were usually accompanied by facial erythema lasting 2-5 min and were correlated with increases in plasma histamine level (P < 0.001). Facial erythema, decrease in blood pressure, and elevation of histamine level were all accentuated by increasing the dose of mivacurium and by more rapid injection of the drug. For example, mean blood pressure decreased an average of 13% after injection of mivacurium 0.25 mg/kg over 10-15s. In contrast, during administration over 30 and 60 s of this dose, arterial pressure decreased 7.6 and 1.5%, respectively (P < 0.001, 10-15 s vs. 60-s injection). Average peak histamine level, which increased to 132% of control after administration of 0.25 mg/kg over 10-15 s, did not change after injection over 60 s. The cardiovascular response to mivacurium shows tachyphylaxis: the average decrease in mean blood pressure was significantly greater after first doses of 0.20 or 0.25 mg/kg (18 and 13%, respectively) than after identical second doses (2 and 8%). The authors conclude that the cardiovascular response to mivacurium in health patients is minimal at dosages up to and including 2 X ED95. Blood pressure may decrease in some people after injection over 10-15 s of initial doses greater than 2 X ED95. This response likely results from the release of histamine. The dose-ratio (ED50 for histamine-related events/ED95 for neuromuscular blockade) after rapid injection is 0.24/0.08 mg/kg, or 3.0. This safety ratio may be increased by slowing the rate of injection of mivacurium.