Effects of cardiopulmonary bypass on propofol pharmacokinetics and bispectral index during coronary surgery

Ricardo Antonio G Barbosa, Silvia Regina C Jorge Santos, Paul F White, Valéria A Pereira, Carlos R Silva Filho, Luiz M S Malbouisson, Maria José C Carmona, Ricardo Antonio G Barbosa, Silvia Regina C Jorge Santos, Paul F White, Valéria A Pereira, Carlos R Silva Filho, Luiz M S Malbouisson, Maria José C Carmona

Abstract

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 microg/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 +/- 1.15 h, 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.

Trial registration: ClinicalTrials.gov NCT00622791.

Figures

Figure 1
Figure 1
Plasma propofol concentrations as a function of time after the induction of anesthesia. Closed circles represent the coronary artery bypass graft (CABG) group and open circles represent the off-pump coronary artery bypass (OPCAB) group. Data reported as mean values ± standard error * p ≤ 0.05
Figure 2
Figure 2
Plasma propofol concentration measures plotted against respective bispectral index values after the end of coronary grafting up to the end of blood sampling. Closed circles represent the coronary artery bypass graft (CABG) group and open circles represent the off-pump coronary artery bypass (OPCAB) group
Figure 3
Figure 3
Time course of changes in bispectral index (BIS) values. Closed circles represent coronary artery bypass graft (CABG) group and open circles represent off-pump coronary artery bypass (OPCAB) group. After discontinuation of the propofol infusion, time “0” represents the point at which the BIS values were higher in the OPCAB group as compared to the CABG group. Data reported as mean ± standard error * p

Figure 4

Pharmacokinetic-pharmacodynamic modeling using sigmoid E…

Figure 4

Pharmacokinetic-pharmacodynamic modeling using sigmoid E MAX model of plasma propofol concentration and bispectral…

Figure 4
Pharmacokinetic-pharmacodynamic modeling using sigmoid EMAX model of plasma propofol concentration and bispectral index (BIS) values during and after surgery
Figure 4
Figure 4
Pharmacokinetic-pharmacodynamic modeling using sigmoid EMAX model of plasma propofol concentration and bispectral index (BIS) values during and after surgery

References

    1. White PF. Intravenous anesthesia and analgesia: what is the role of target-controlled infusion? J Clin Anesth. 1996;8:26S–28S.
    1. Olivier P, Sirieix D, Dassier P, D’Attellis N, Baron JF. Continuous infusion of remifentanil and target-controlled infusion of propofol for patients undergoing cardiac surgery: a new approach for scheduled early extubation. J Cardiothorac Vasc Anesth. 2000;14:29–35.
    1. Holley FO, Ponganis KV, Stanski DR. Effect of cardiopulmonary bypass on the pharmacokinetics of drugs. Clin Pharmacokinet. 1982;7:234–51.
    1. Mets B. The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass. Acta Anaesthesiol Scand. 2000;44:261–73.
    1. Takizawa E, Hiraoka H, Takizawa D, Goto F. Changes in the effect of propofol in response to altered plasma protein binding during normothermic cardiopulmonary bypass. Br J Anaesth. 2006;96:179–85.
    1. Lundell JC, Scuderi PE, Butterworth JFt. Less isoflurane is required after than before cardiopulmonary bypass to maintain a constant bispectral index value. J Cardiothorac Vasc Anesth. 2001;15:551–4.
    1. Buylaert WA, Herregods LL, Mortier EP, Bogaert MG. Cardiopulmonary bypass and the pharmacokinetics of drugs. An update. Clin Pharmacokinet. 1989;17:10–26.
    1. Hiraoka H, Yamamoto K, Okano N, Morita T, Goto F, Horiuchi R. Changes in drug plasma concentrations of an extensively bound and highly extracted drug, propofol, in response to altered plasma binding. Clin Pharmacol Ther. 2004;75:324–30.
    1. Bailey JM, Mora CT, Shafer SL. Pharmacokinetics of propofol in adult patients undergoing coronary revascularization. The Multicenter Study of Perioperative Ischemia Research Group. Anesthesiology. 1996;84:1288–97.
    1. Lee HS, Khoo YM, Chua BC, Ng AS, Tan SS, Chew SL. Pharmacokinetics of propofol infusion in Asian patients undergoing coronary artery bypass grafting. Ther Drug Monit. 1995;17:336–41.
    1. Massey NJ, Sherry KM, Oldroyd S, Peacock JE. Pharmacokinetics of an infusion of propofol during cardiac surgery. Br J Anaesth. 1990;65:475–9.
    1. Hammaren E, Yli-Hankala A, Rosenberg PH, Hynynen M. Cardiopulmonary bypass-induced changes in plasma concentrations of propofol and in auditory evoked potentials. Br J Anaesth. 1996;77:360–4.
    1. Marsh B, White M, Morton N, Kenny GN. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth. 1991;67:41–8.
    1. Yeganeh MH, Ramzan I. Determination of propofol in rat whole blood and plasma by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 1997;691:478–82.
    1. Knibbe CA, Koster VS, Deneer VH, Stuurman RM, Kuks PF, Lange R. Determination of propofol in low-volume samples by high-performance liquid chromatography with fluorescence detection. J Chromatogr B Biomed Sci Appl. 1998;706:305–10.
    1. Mora CT, Dudek C, Torjman MC, White PF. The effects of anesthetic technique on the hemodynamic response and recovery profile in coronary revascularization patients. Anesth Analg. 1995;81:900–10.
    1. Yang H, Homi HM, Smith BE, Grocott HP. Cardiopulmonary bypass reduces the minimum alveolar concentration for isoflurane. J Cardiothorac Vasc Anesth. 2004;18:620–3.
    1. Yoshitani K, Kawaguchi M, Takahashi M, Kitaguchi K, Furuya H. Plasma propofol concentration and EEG burst suppression ratio during normothermic cardiopulmonary bypass. Br J Anaesth. 2003;90:122–6.
    1. Hall RI, Poole L, Murphy JT, Moffitt EA. A randomized study of changes in serum cholesterol, triglycerides, high density lipoproteins, and cortisol during cardiac surgery in patients anaesthetised with propofol-sufentanil vs enflurane-sufentanil. Cardiac Anaesthesia Research Group. Can J Anaesth. 1990;37:S76.
    1. Neumeister MW, Li G, Williams G, Doak G, Sullivan JA, Hall RI. Factors influencing MAC reduction after cardiopulmonary bypass in dogs. Can J Anaesth. 1997;44:1120–6.
    1. Dawson PJ, Bjorksten AR, Blake DW, Goldblatt JC. The effects of cardiopulmonary bypass on total and unbound plasma concentrations of propofol and midazolam. J Cardiothorac Vasc Anesth. 1997;11:556–61.
    1. Lysakowski C, Dumont L, Pellegrini M, Clergue F, Tassonyi E. Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of consciousness and bispectral index during propofol induction of anaesthesia. Br J Anaesth. 2001;86:523–7.
    1. Hudson RJ, Thomson IR, Jassal R. Effects of cardiopulmonary bypass on sufentanil pharmacokinetics in patients undergoing coronary artery bypass surgery. Anesthesiology. 2004;101:862–71.
    1. Barakat AR, Sutcliffe N, Schwab M. Effect site concentration during propofol TCI sedation: a comparison of sedation score with two pharmacokinetic models. Anaesthesia. 2007;62:661–6.

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