Effect of H₁- and H₂-receptor antagonists on the hemodynamic changes induced by the intravenous administration of ketamine in sevoflurane-anesthetized cats

Abstract.

Objective: The anesthetic ketamine has been reported to cause both an increase of the plasma histamine concentration, notably in cats, and a cardiovascular depression. The latter has been described in humans and in other species. However the relevance of the histamine fluctuation for the ketamine-induced hemodynamic changes has not been determined.

Subjects and treatment: We studied the contribution of histamine to the hemodynamic effects induced by IV ketamine (7 mg/kg) in 12 sevoflurane anesthetized cats, of which half had been pre-treated with combined H₁- and H₂ -receptor antagonists.

Methods: The mean arterial pressure (MAP) and the heart rate (HR) from both untreated (group C) and pre-treated (group AH) cats were recorded before and after the ketamine administration. The plasma histamine concentration was also measured.

Results: Plasma histamine fluctuations in the control and the antihistamine-treated group followed a similar pattern (no statistical differences); an initial rise that peaked 2 min after ketamine injection (from 0.63 ± 0.11 ng/ml to 2.22 ± 0.69 ng/ml in the C group, and from 0.71 ± 0.10 ng/ml to 1.09 ± 0.28 ng/ml in the AH group) followed by an immediate decrease in plasma concentrations. As for the hemodynamic variables under analysis, in the control group ketamine administration was followed by an early 30.3 ± 8.1% reduction (p < 0.005) in the MAP with no associated changes in the HR. In the antihistamine pre-treated group, ketamine caused a further decrease of the MAP (41.7 ± 2.3%), and a significant (p < 0.01) 11.6 ± 2.9% reduction of the HR.

Conclusion: Ketamine in anesthetized cats triggers histamine release and induces cardiovascular depression. The depression is more pronounced under the blockade of histamine activity through histamine receptor antagonists.