Continuous infusion of ketamine and midazolam for prolonged sedation in the intensive care unit]

The clinical effects and pharmacokinetics of ketamine and midazolam, administered continuously for prolonged sedation were studied in 7 critically ill patients under mechanical ventilation. Initially ketamine 1 mg.kg-1 and midazolam 0.1 mg.kg-1 were administered intravenously and these were followed by infusion at a rate of 1.0 mg.kg-1.hr-1 of ketamine and 0.05 mg.kg-1.hr-1 of midazolam. The infusion rate was changed every 30 minute with increments of 0.5 mg.kg-1.hr-1 of ketamine and 0.05 mg.kg-1.hr-1 of midazolam until the sedative score by Ramsy RAE reached rank 4 (i.e. slow response to loud verbal commands). The plasma concentrations of ketamine were analyzed using high performance liquid chromatography and those of midazolam using gas chromatography. The mean maintenance doses of ketamine and midazolam were 2.25 +/- 0.61 mg.kg-1.hr-1 and 0.11 +/- 0.05 mg.kg-1.hr-1 (mean +/- SD), respectively. There were no significant changes in blood pressure or heart rate before and after the injection of ketamine and midazolam in all the patients. The plasma concentrations of ketamine and midazolam were 2.98 +/- 0.20 micrograms.ml-1 and 494.1 +/- 66.7 ng.ml-1, respectively. The time to clear response to verbal commands after cessation of the continuous infusion was 168 +/- 109 min. The plasma concentrations of ketamine and midazolam decreased rapidly, and plasma half-life of ketamine was about 1 hour and for midazolam less than 2 hours. In conclusion, continuous infusion of ketamine and midazolam was very useful to sedate critically ill patients under mechanical ventilation, with minimal effect on the cardiovascular system and rapid recovery of consciousness.