Additive interactions between propofol and ketamine when used for anesthesia induction in female patients

Propofol and ketamine may be paired for anesthesia induction and for total intravenous anesthesia. The nature of any sedative interactions occurring between propofol and ketamine are unknown. The combination when used for anesthesia induction in female patients was studied.

Quantal dose-response curves were determined in 180 female patients to whom the drugs were administered individually and in combination. Two minutes after administering the drugs, two endpoints were assessed. First, loss of response to verbal command (hypnosis) and then, in those who failed to respond to this endpoint, loss of response to a 5-s transcutaneous tetanus (anesthesia). Interactions were analyzed by fitting the data to a mathematical model in which response was analyzed in terms of the doses of the two drugs and an additional term included to describe nonadditive interactions. The incidences of apnea, arterial pressure, and heart rate changes during the first 5 min were recorded.

At the hypnotic endpoint, the ED50s were 1.10 mg/kg propofol (95% CIs 0.93-1.27), 0.39 mg/kg ketamine (95% CIs 0.27-0.46), and the combination of 0.63 mg/kg propofol and 0.21 mg/kg ketamine (95% CIs 0.53/0.18-0.73/0.24). At the anesthetic endpoint, the ED50s were 1.85 mg/kg propofol (95% CIs 1.58-2.36) 0.66 mg/kg ketamine (95% CIs 0.58-0.77), and the combination of 1.05 mg/kg propofol and 0.35 mg/kg ketamine (95% CIs 0.88/0.29-1.27/0.42). The effects were additive at both endpoints; there was no evidence of an interaction. The ED50s for apnea were 1.61 mg/kg propofol (95% CIs 1.39-1.94), greater than 0.85 mg/kg ketamine and for the combination 1.50 mg/kg propofol and 0.50 mg/kg ketamine (95% CIs 1.15/0.38-3.09/1.03). The addition of ketamine did not significantly alter the ED50 for apnea of propofol. There was a significant difference in the arterial pressures among the three groups (P < 0.001). Using the combination, the cardiostimulant effects of ketamine balanced the cardiodepressant effects of propofol. There was no change in arterial pressure or heart rate after the noxious stimulus.

When using the combination, doses were additive at hypnotic and anesthetic endpoints. Ketamine had no influence on the incidence of apnea after propofol, and the net hemodynamic effects were minimal.