Study Of The Interactions Between Propofol And Ketamine In Anesthesia Induction By Isobolographic Analysis

Object Using isobolographic analysis to prove the interactions between propofol and ketamine on the effects of hypnosis and anesthesia , and the different effects of each drug and their combination.Methods 75 patients undergoing upper abdominal operations were randomly assigned into three groups(group p , k , p/k ) ,then divided into five subgroups separately. Before induction .the each group of ketamine (kl~k5)received 0.32, 0.40, 0.50, 0.63, 0.78 dose(mg/kg) separately; the each group of propofol(pl~p5) received 0.80> 1.00, 1.25 , 1.56, 1.95 dose(mg/kg) respectively; the each group of combination (p/kl~p/k5) received 0.45/0.15, 0.60/0.20,0.80/0.27, 1.05/0.35, 1.41/0.47 dose( mg/kg) of propofol / ketamine injection individually . Each drug was diluted in normal saline(NS) to 10ml i.v. in 15 seconds . The incidence of apnea, arterial pressure, heart rate, oxygen saturation of pulse, BIS changed during first 5 min were recorded. At 2 min after administration , two endpoints were assessed. First, loss of response to verbal commond (hypnosis) and then, in those who failed to respond to this endpoint, loss of response to a 5-s transcutaneous tetanus stimulation (anesthesia). The interactions were analyzed in terms of isobolographic analysis. All datas were analyzed by SPSS 10.0.Result At the hypnotic endpoints, the EDsos were 1.15mg/kg for propofol (95% CIs 0.95-1.40), 0.40 mg/kg for ketamine (95% CIs 0.34~0.47),and the ED50for the combination was 0.65/0.22 mg/kg for group p/k (95% CIs 0.55/0.18-0.78/0.26).At the anesthetic endpoint , the ED50s were 1.88mg/kg forpropofol (95%CIs 1.60-2.22), 0.72mg/kg for ketamine (95% CIs 0.61-0.86), and 1.19 70.40 mg/kg for the combination group (95% CIs 0.95/0.32-1.48/0.49). The effects of the combination were additive at both endpoints. The ED^s for apnea were 1.61 mg/kg for propofol (95%CIs 1.39-1.92), 1.43/ 0.48 mg/kg for combination group (95%CIs 1.20/0.40-1.70/0.57). In the group p and k, SBP and DBF after administration at 1 and 2 min, were significantly decreased and increased respectively. In group p, incidences of apnea were higher than other two groups. Ketamine could not reduce the incidences of apnea caused by propofol. Except group k, the other two groups had a decline in BIS than their own basic values.Conclusion At hypnotic -. anesthetic and apneic endpointSjED s of propofol were 1.15 1.89 1.61 mg/kg, ED50s of combination were 0.65/0.22 x 1.19/0.40 1.43/0.48 respectively. At hypnotic x anesthetic endpoints, ED50s of ketamine were 0.40 0.72 mg/kg. By isobolographic analysis, the combination of propofol and ketamine showed additive effect at hypnotic and anesthetic endpoints.