Concentrations of remifentanil, propofol, fentanyl, and midazolam during rewarming from therapeutic hypothermia

Background The clearance of sedatives and analgesics may be reduced by therapeutic hypothermia. However, little is known about the concentrations of such drugs during rewarming. The aim of this study was to describe the serum concentrations of sedatives and analgesics during rewarming from therapeutic hypothermia. Methods Blood samples were collected for quantification of drug concentrations in 22 patients given analgesia/sedation with either remifentanil/propofol or fentanyl/midazolam during rewarming from therapeutic hypothermia (33-34 degrees C) after cardiac arrest. Samples for were drawn before (-2h) and during rewarming (0-8h). Linear mixed effects models were used to describe serum concentrations and adjust for rates of infusion during rewarming from therapeutic hypothermia. Results Subjects with samples analyzed were remifentanil (n=8), propofol (n=14), fentanyl (n=8), and midazolam (n=8). Age, body mass index, and simplified acute physiology score II [mean (standard deviation)] were 64 (14.2) years, 27.3 (3.7) kg/m2, and 69 (13.2), respectively. While the concentration of fentanyl was not significantly affected by temperature, concentrations of remifentanil, propofol, and midazolam decreased with core temperature by 16%, 12%, and 11% (mean values) from 33 degrees C to 37 degrees C after adjusting for rates of infusion, respectively. Conclusion Concentrations of remifentanil, propofol, and midazolam decreased during rewarming from therapeutic hypothermia when adjusting for rates of infusion. No changes were demonstrated for fentanyl.