Reversal of morphine anesthesia with naloxone

Abstract

Six hours after intravenous injection of morphine, 2 mg/kg, 7 healthy adults received a 10 hr intravenous infusion of naloxone (3.66 μg/kg loading dose plus 3.66 μg/kg/hr), totaling 40 μg/kg. Immediately before administration of naloxone, resting minute ventilation (VE) was 6.2 ± 0.4 (SE) l/min, end tidal CO2 tension (PETCO2) 65 ± 3 torr, and the CO2 response slope averaged only 0.5 ± 0.2 l/min/torr; in one subject VE decreased in response to CO2. Plasma morphine concentration was 654 ± 93 ng/ml and correlated poorly with respiratory depression or mental alertness. One hour after starting the naloxone infusion, resting VE was 6.8 ± 0.5 l/min, PETCO2 54 ± 1 torr, and CO2 response slope 1.2 ± 0.1 l/min/torr. Mental vigilance testing, by repetitive verbal challenges, showed 100 ± 0% correct responses during the control period, 50 ± 18% immediately before naloxone, and 86 ± 6% one hour later. VE, PETCO2, CO2 response slope and displacement, and mental vigilance improved progressively 4 and 8 hr after starting the naloxone infusion. 21.5 hr after morphine injection, plasma concentration was 39 ± 13 ng/ml. At this time resting ventilatory values did not differ from control, but the CO2 response curve remained significantly displaced. During naloxone infusion all subjects complained of bladder distention, and 5 vomited. Naloxone, 40 μg/kg/10 hr, as an antagonist to morphine, 2 mg/kg, adequately balances respiratory effects and emetic side effects.