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

Barbosa RA, Santos SR, White PF, Pereira VA, Silva Filho CR, Malbouisson LM, Carmona MJ - Clinics (Sao Paulo) (2009)

Bottom Line: Data were analyzed using ANOVA, considering p<0.05 as significant.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).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.

View Article: PubMed Central - PubMed

Affiliation: Serviço de Anestesiologia e Terapia Intensiva Cirúrgica, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo - São Paulo/SP, Brazil. navajasbarbosa@superig.com.br

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.

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Related in: MedlinePlus

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
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f1-12-oa-0209: 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

Mentions: A total of 520 blood samples were analyzed for plasma propofol concentration in the CABG (290 samples) and OPCAB (230 samples) groups. The groups did not differ with respect to total propofol doses infused during surgery (1452 ± 256 mg vs. 1408 ± 289 mg in the CABG and OPCAB groups, respectively, p=0.648), or with respect to the total propofol doses infused from the end of surgery to the time of tracheal extubation (144 ± 81 mg vs. 95 ± 68 mg in the CABG and OPCAB groups, respectively, p=0.26). The actual plasma propofol concentrations in CABG and OPCAB groups over time are displayed in figure 1. Plasma propofol concentrations did not differ between the groups throughout the study, except during the moments corresponding to cardiopulmonary bypass in the CPB group, during which the plasma concentration was higher in the OPCAB group. When the propofol PK parameters were analyzed for time points after CPB up to the time of observation in the CPB group and for corresponding time points in the OPCAB group, we observed that the fast elimination rate constant in the CPB group was double that of the OPCAB group (p <0.01), while the biological half-life was 50% lower (p <0.01) (Table 2). Patients undergoing CPB exhibited a higher terminal elimination half-life (p <0.01) and higher total plasma clearance (p <0.01) when compared to patients in the OPCAB group. Figure 2 shows plasma propofol concentration measures plotted against respective Bispectral Index values after the end of coronary grafting until the end of blood sampling in both groups.


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

Barbosa RA, Santos SR, White PF, Pereira VA, Silva Filho CR, Malbouisson LM, Carmona MJ - Clinics (Sao Paulo) (2009)

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
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2666455&req=5

f1-12-oa-0209: 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
Mentions: A total of 520 blood samples were analyzed for plasma propofol concentration in the CABG (290 samples) and OPCAB (230 samples) groups. The groups did not differ with respect to total propofol doses infused during surgery (1452 ± 256 mg vs. 1408 ± 289 mg in the CABG and OPCAB groups, respectively, p=0.648), or with respect to the total propofol doses infused from the end of surgery to the time of tracheal extubation (144 ± 81 mg vs. 95 ± 68 mg in the CABG and OPCAB groups, respectively, p=0.26). The actual plasma propofol concentrations in CABG and OPCAB groups over time are displayed in figure 1. Plasma propofol concentrations did not differ between the groups throughout the study, except during the moments corresponding to cardiopulmonary bypass in the CPB group, during which the plasma concentration was higher in the OPCAB group. When the propofol PK parameters were analyzed for time points after CPB up to the time of observation in the CPB group and for corresponding time points in the OPCAB group, we observed that the fast elimination rate constant in the CPB group was double that of the OPCAB group (p <0.01), while the biological half-life was 50% lower (p <0.01) (Table 2). Patients undergoing CPB exhibited a higher terminal elimination half-life (p <0.01) and higher total plasma clearance (p <0.01) when compared to patients in the OPCAB group. Figure 2 shows plasma propofol concentration measures plotted against respective Bispectral Index values after the end of coronary grafting until the end of blood sampling in both groups.

Bottom Line: Data were analyzed using ANOVA, considering p<0.05 as significant.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).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.

View Article: PubMed Central - PubMed

Affiliation: Serviço de Anestesiologia e Terapia Intensiva Cirúrgica, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo - São Paulo/SP, Brazil. navajasbarbosa@superig.com.br

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.

Show MeSH
Related in: MedlinePlus