Target-achieved propofol concentration during on-pump cardiac surgery: a pilot dose-finding study.
OBJECTIVE
Propofol concentrations that produce laboratory-based cardioprotective effects are generally greater than those produced under routine anesthesia during cardiac surgery. It is unknown whether experimental cardioprotective propofol concentrations can routinely be achieved during cardiopulmonary bypass (CPB) using continuous infusion.


METHODS
Twenty-four patients scheduled for primary aortocoronary bypass grafting with CPB were allocated to receive one of three propofol infusion rates; 50, 100, or 150 microg x kg(-1) x min(-1) in an open-label pilot study. Data were described using a line of best fit to derive an experimental clinical maneuver predicted to produce a whole blood concentration of 5 microg x mL(-1) at reperfusion. A predetermined interim analysis of 30 patients who were receiving the derived maneuver in an ongoing study was used to evaluate the maneuver. Cardiac index (CI), systemic vascular resistance index (SVRI), and left ventricular stroke work index (LVSWI) were recorded.


RESULTS
The infusion rate-concentration curve had an equation of y = 0.215e (0.0279x ), where y represents the whole blood concentration and x represents the infusion rate (r (2) = 0.781). The predicted infusion rate to achieve a mean concentration of 5 microg x mL(-1) was 113 microg x kg(-1) x min(-1). The nearest practical rate is 120 microg x kg(-1) x min(-1), producing a concentration of 5.39 (1.45) microg x mL(-1). The values for CI, SVRI, and LVSWI were similar between groups at corresponding time periods.


CONCLUSIONS
An infusion rate of 120 microg x kg(-1) x min(-1) is clinically practical and capable of achieving experimental cardioprotective propofol concentrations at reperfusion.
Raedschelders
Koen
K
Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia, Rm 3200 3rd Floor, JPP. 910 West 10th Ave, Vancouver, BC V5Z 4E3, Canada.
Hui
Yu
Y
Laferlita
Bradley
B
Luo
Tao
T
Zhang
Hong
H
Chen
David D Y
DD
Ansley
David M
DM
D000368:Aged; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000097:blood*; D001794:Blood Pressure / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects; D001026:Coronary Artery Bypass / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015742:Propofol / Q000008:administration & dosage / Q000097:blood*; D015427:Reperfusion Injury / Q000517:prevention & control*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
D018686:Anesthetics, Intravenous; D015742:Propofol