Histamine release with intravenous narcotics: protective effects of H1 and H2-receptor antagonists.

TLDR: It is demonstrated that morphine releases histamine in amounts which correlate with the hemodynamic changes seen, and prior administration of H1 and H2 histamine antagonists provide significant protection — more so than either alone.

Abstract: High dose narcotic anesthesia with fentanyl or morphine is not associated with significant direct myocardial depression. Morphine is reported to produce arteriolar dilatation and a decrease in SVR (probably due to histamine release) while fentanyl is not. Studies were undertaken to determine if morphine or fentanyl caused histamine release; if such a release correlated with hemodynamic changes, and if H1 and H2 antagonists could provide protection. In a randomized double blind study of 40 patients in 4 groups, patients who received morphine (1 mg/kg) demonstrated significant increases in plasma histamine (880±163 to 7,437±2,684 pg/ml−p<0.01) accompanied by an increase in CI (2.4±0.2 to 3.0±0.2 l/min/m2−p<0.01) and decreases in\(\overline {BP} \) (88±4 to 61±4 torr−p<0.01) and SVR (15.5±1 to 9.0±1 torr-l-min−1p<0.01). The prior administration of H1 (dyphenhydramine 1 mg/kg) and H2 (cimetidine 4 mg/kg) antagonists provided significant protection (SVR 17.4±1 to 14.6±1 torr-l-min−1−p<0.05) although histamine increased comparably (1,059±22 to 7,653±4,242 pg/ml−p<0.05). In a separate study, seven patients receiving fentanyl 50 µg/kg showed no histamine changes (935±51 to 685±51 pg/ml) and no significant hemodynamic response. Eight patients receiving morphine 1 mg/kg again showed significant increases in plasma histamine (880±163 to 7,480±2,230 pg/ml−p<0.05) which collelated with the decrease in SVR (r=0.81). These data demonstrate that morphine releases histamine in amounts which correlate with the hemodynamic changes seen. Prior administration of H1 and H2 histamine antagonists provide significant protection — more so than either alone. Fentanyl produced no histamine release which may account for much of the cardiovascular stability reported with this drug.