Intravenous morphine and nalbuphine increase histamine and catecholamine release without accompanying hemodynamic changes*

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Abstract
Patients receiving intravenous morphine at doses of 0.3 and 1.0 mg/kg for general anesthesia have been reported to show significant elevations in plasma histamine that are associated with hemodynamic changes. We undertook a prospective, randomized, double-blind trial in which 0.15 mg/kg morphine or 0.3 mg/kg nalbuphine was administered intravenously to normal volunteers. Thirteen of 15 subjects receiving morphine and 10 of 14 subjects receiving nalbuphine had elevations in plasma histamine levels and symptoms of histamine release within 5 minutes of drug administration. Six subjects in the morphine group and five in the nalbuphine group exhibited levels of plasma histamine > 2.0 ng/ml, but these levels were not associated with hemodynamic changes and occurred 10 to 15 minutes after drug administration. Our study suggests that the opiate-induced elevation of plasma histamine derives from cutaneous mast cells.