Effects of Cardiopulmonary Bypass on Propofol Pharmacokinetics and Bispectral Index During Coronary Surgery

Abstract

Barbosa RAG, Santos SRCJ, White PF, Pereira VA, Silva Filho CR, Malbouisson LMS. Effects of cardiopulmonary bypass on propofol pharmacokinetics and bispectral index during coronary surgery. Clinics. 2009;64(3):215-21. PURPOSE:Cardiopulmonary bypass is known to alter propofol pharmacokinetics in patients undergoing cardiac surgery. However, few studies have evaluated the impact of these alterations on postoperative pharmacodynamics. This study was designed to test the hypothesis that changes in propofol pharmacokinetics increase hypnotic effects after cardiopulmonary bypass. METHODS: Twenty patients scheduled for on-pump coronary artery bypass graft (group, n=10) or off-pump coronary artery bypass graft (group, n=10) coronary artery bypass grafts were anesthetized with sufentanil and a propofol target controlled infusion (2.0 µg/mL). Depth of hypnosis was monitored using the bispectral index. Blood samples were collected from the induction of anesthesia up to 12 hours after the end of propofol infusion, at predetermined intervals. Plasma propofol concentrations were measured using high-performance liquid chromatography, followed by a non-compartmental propofol pharmacokinetic analysis. Data were analyzed using ANOVA, considering p<0.05 as significant. RESULTS: After cardiopulmonary bypass, despite similar plasma propofol concentrations in both groups, bispectral index values were lower in the on-pump coronary artery bypass graft group. Time to extubation after the end of propofol infusion was greater in the on-pump coronary artery bypass graft group (334 ± 117 vs. 216 ± 85 min, p = 0.04). Patients undergoing cardiopulmonary bypass had shorter biological (1.82 ± 0.5 vs. 3.67 ± 1.15h, p < 0.01) and terminal elimination (6.27 ± 1.29 vs. 10.5h ± 2.18, p < 0.01) half-life values, as well as higher total plasma clearance (28.36 ± 11.40 vs.18.29 ± 7.67 mL/kg/min, p = 0.03), compared to patients in the off-pump coronary artery bypass graft group. CONCLUSION: Aside from the increased sensitivity of the brain to anesthetics after cardiopulmonary bypass, changes in propofol pharmacokinetics may contribute to its central nervous system effects.

Patients and surgery-related factors that affect time to recovery of consciousness in adult patients undergoing elective cardiac surgery

“…22 Barbosa et al reported pharmacokinetics of propofol modified by the CPB, may contribute to an increase in hypnotic effects after cardiac surgery. 23 In our clinical practice, fentanyl and dormicum infusion continued to be administrated during the CPB and we speculate that the effects of the CPB on these anesthetic drugs may be related to our finding.…”

Brain Monitoring with Electroencephalography and the Electroencephalogram-Derived Bispectral Index During Cardiac Surgery

“…43 Furthermore, the unbound propofol fraction increases during CPB, which might decrease the blood propofol concentration required to maintain anesthesia during CPB. 44 Closed-loop anesthesia using BIS during cardiac surgery has been shown to decrease propofol administration and to increase hemodynamic stability compared to dosing controlled manually by anesthesiologists based upon the BIS reading.…”

Brain Monitoring With Electroencephalography and the Electroencephalogram-Derived Bispectral Index During Cardiac Surgery

“…42 Apart from altering pharmacokinetics, CPB is hypothesized to increase the sensitivity of the brain to anesthesia. 43 Furthermore, the unbound propofol fraction increases during CPB, which might decrease the blood propofol concentration required to maintain anesthesia during CPB. 44 Closed-loop anesthesia using BIS during cardiac surgery has been shown to decrease propofol administration and to increase hemodynamic stability compared to dosing controlled manually by anesthesiologists based upon the BIS reading.…”