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Objective: Several studies have suggested that the cardioprotective effects of halogenated anesthetics in cardiac surgery result in reduced cardiac biomarker release compared with total intravenous anesthesia (TIVA). These findings came from relatively small randomized clinical trials and meta-analyses. The authors of this study hypothesized that the beneficial effects of volatile anesthetics translate into a reduced length of hospital stay after coronary artery bypass grafting surgery (CABG) with cardiopulmonary bypass., Design: A randomized controlled trial., Setting: Two university hospitals., Participants: Adult patients undergoing elective CABG surgery with cardiopulmonary bypass., Interventions: Patients were assigned randomly to 2 following groups: propofol-based TIVA group (n = 431) and sevoflurane group (n = 437)., Measurements and Main Results: The primary endpoint was hospital length of stay, and the secondary endpoint included postoperative troponin T and N-terminal pro-brain natriuretic peptide release and mortality. In the sevoflurane group, a reduced length of hospital stay was observed compared with the propofol-based TIVA group (10 [9-11] days v 14 [10-16], p<0.001) as were reductions in cardiac troponin T release (0.18 ng/mL v 0.57 ng/mL at 24 hours, p<0.001), in N-terminal pro-brain natriuretic peptide release (633 pg/mL v 878 pg/mL at 24 hours, p<0.001; 482 pg/mL v 1,036 pg/mL at 48 hours, p<0.001), and in mortality at 1-year follow up (17.8% v 24.8%, p = 0.03)., Conclusions: Anesthesia with sevoflurane reduced cardiac biomarker release and length of hospital stay after CABG with cardiopulmonary bypass surgery compared with propofol-based TIVA with a possible reduction in 1-year mortality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Because of the lack of data regarding the impact of obesity on propofol pharmacokinetics in patients undergoing cardiac surgery using hypothermic cardiopulmonary bypass (CPB), the authors sought to explore propofol pharmacokinetics and develop a predictive pharmacokinetic model that characterizes and predicts propofol pharmacokinetics in this population., Design: A prospective, observational study., Setting: A teaching hospital., Participants: The study comprised 17 obese and 17 control (nonobese) patients undergoing hypothermic CPB., Intervention: None., Measurements and Main Results: Patients mainly underwent valve surgery. On initiation of hypothermic CPB (28°C-32°C), patients received a propofol (1%) bolus (1 mg/kg) immediately followed by a 2 mg/kg/h infusion. Blood samples were withdrawn at the following times: before dosing; 1, 3, 5, and 7 minutes after the propofol bolus dose; every 20 minutes during infusion; just before discontinuation of the infusion; and at 1, 3, 5, 7, 10, 20, 30, and 60 minutes after discontinuation of the infusion. The plasma propofol concentration was determined using high-performance liquid chromatography, and then data were imported into Monolix (Lixoft, Antony, France) for population pharmacokinetic modeling and pharmacokinetic parameters estimation. A 2-compartment pharmacokinetic model with age as a covariate on the peripheral volume of distribution (V2) best described the pooled data. The pooled data was internally evaluated successfully to describe and predict propofol pharmacokinetics in the addressed population. Propofol clearance, intercompartmental clearance, and central volume of distribution were 805 mL/min, 1140 mL/min and 18.8 L, respectively. V2 was calculated as 9.86×exp.(1.88×[age/40]) L., Conclusion: Propofol pharmacokinetic parameters were similar in obese and nonobese patients undergoing hypothermic CPB. Age was the major determinant of propofol V2 in the obese population., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To compare the effects of propofol, sevoflurane, and the combination of the 2 on circulating lymphocytes in patients undergoing off-pump coronary artery bypass graft (OPCAB) surgery., Design: A prospective, randomized study., Setting: A university hospital., Participants: One hundred five patients undergoing elective OPCAB surgery., Interventions: Participants were randomized to receive sevoflurane (group S), propofol (group P), or coadministration (group C) of sevoflurane- and propofol-maintained anesthesia., Measurements and Main Results: Blood samples were obtained before, during, and after surgery. Caspase-3 and apoptosis-inducing factor in lymphocytes were evaluated by Western blot. During surgery, 5 minutes after revascularization of the left anterior descending artery, 5 minutes after all anastomoses (T4), and after the sternal closure (T5), caspase-3 expression of group S was higher than that of group P (p = 0.02) and group C (p = 0.02). At T4 and T5, expression of active apoptosis-inducing factor in group S was higher than that in the other 2 groups (p = 0.03 and p = 0.04, respectively). 24 hours after surgery, the lymphocyte count of group S (0.55/nL) was lower than that of group P (0.73/nL, p = 0.02) and group C (0.73/nL, p = 0.03). Intensive care unit stay of group S (3.0 days) was longer than that of the other 2 groups (2.2 days, p = 0.02 and 2.1 days, p = 0.01)., Conclusions: OPCAB surgery was associated with postoperative lymphopenia. Regarding a protective effect for circulating lymphocytes, propofol and the combination of sevoflurane- and propofol-maintained anesthesia were both superior to sevoflurane-maintained anesthesia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate the ability of the Schnider pharmacokinetic model to predict plasma propofol concentration during target-controlled propofol infusion in patients with impaired left ventricular function and to investigate the predictive value of the bispectral index (BIS) to indicate deep sedation in this patient group., Design: Prospective, observational study., Participants: Thirty-four patients (mean left ventricular ejection fraction 31% +/- 9%) undergoing the implantation of a cardioverter-defibrillator during deep sedation., Interventions: None., Measurements and Main Results: Predicted and measured propofol plasma concentrations and BIS were assessed during steady-state conditions with the propofol infusion rate constant for at least 20 minutes. The plasma propofol concentration was significantly underestimated by the pharmacokinetic model used (mean percentage prediction error 37% +/- 49%). The 50% probability of deep sedation was calculated at a predicted propofol concentration of 2.09 (95% confidence interval [CI], 2.04-2.14) mug/mL and at a measured propofol concentration of 2.70 (95% CI, 2.62-2.78) mug/mL. BIS values showed a marked variability among individuals during deep sedation (5th-95th percentiles: 25-81)., Conclusions: The pharmacokinetic model used markedly underestimated propofol plasma levels in the patient group studied. The large variability among patients suggests that BIS monitoring is not suitable for indicating an exact endpoint corresponding to deep sedation.

Objectives: To determine if anesthesia with sevoflurane or target-controlled propofol reduced the time to tracheal extubation after coronary artery bypass graft surgery compared with isoflurane anesthesia., Design: A 3-arm (isoflurane, sevoflurane, or propofol), randomized, controlled trial with patients and intensive care staff blinded to the drug allocation., Setting: A single, tertiary referral hospital affiliated with the University of Melbourne., Participants: Three hundred sixty elective coronary artery surgery patients., Interventions: Patients received either isoflurane (control group, 0.5%-2% end-tidal concentration), sevoflurane (1%-4% end-tidal concentration), or target-controlled infusion of propofol (1-8 microg/mL plasma target concentration) as part of a balanced, standardized anesthetic technique including 15 microg/kg of fentanyl., Measurements and Main Results: The primary outcome was time to tracheal extubation. The median time to tracheal extubation for the propofol group was 10.25 hours (interquartile range [IQR] 8.08-12.75), the sevoflurane group 9.17 hours (IQR 6.25-11.25), and the isoflurane group 7.67 hours (IQR 6.25-9.42). Intraoperatively, the propofol group required less vasopressor (p = 0.002) and more vasodilator therapy (nitroglycerin p = 0.01, nitroprusside p = 0.002). There was no difference among the groups in time to intensive care unit discharge., Conclusions: The median time to tracheal extubation was significantly longer for the target-controlled propofol group. A significantly greater number in this group required the use of a vasodilator to control intraoperative hypertension.

Objective: To examine the effects of cardiopulmonary bypass (CPB) on total and unbound plasma concentrations of propofol and midazolam when administered by continuous infusion during cardiac surgery., Design: Prospective clinical study., Setting: University hospital., Participants: Twenty-four adult patients undergoing cardiac surgery., Interventions: Patients received either propofol or midazolam to supplement fentanyl anesthesia. Twelve patients received a propofol bolus (1 mg/kg) followed by an infusion of 3 mg/kg/hr. A second group received midazolam, 0.2 mg/kg bolus, followed by an infusion of 0.07 mg/kg/hr., Measurements and Main Results: Blood sample were collected from the radial artery cannula at 0, 2, 4, 8, 8, 10, 15, 20 minutes and then every 10 minutes before CPB, at 1, 2, 3, 4, 6, 10, 15, 20 minutes and then each 10 minutes during CPB. On weaning from CPB samples were collected at 0, 5, 10 and 20 minutes. Plasma binding, total and unbound propofol and midazolam concentrations were determined by ultrafiltration and high-pressure liquid chromatography (HPLC). CPB resulted in a fall in total propofol and midazolam plasma concentrations, but the unbound concentrations remained stable. The propofol unbound fraction increased from 0.22 +/- 0.06% to 0.41 +/- 0.17%. The midazolam unbound fraction increased from 5.6 +/- 1.0% to 11.2 +/- 2.1%., Conclusions: Unbound concentrations of propofol and midazolam are not affected by cardiopulmonary bypass. Total intravenous anesthesia algorithms do not need to be changed to achieve stable unbound plasma concentrations when initiating CPB.

Objective: In the current study, the use of a target-controlled infusion of low-dose propofol was combined with a continuous infusion of sufentanil for patients undergoing mitral valve surgery. The purpose of the study was to evaluate the hemodynamic stability, the time to awakening and spontaneous ventilation, and the feasibility in an early extubation setting of a total intravenous anesthetic technique., Design: Prospective study., Setting: University hospital., Participants: Fifteen patients scheduled for elective mitral valve surgery., Interventions: Induction of anesthesia consisted of sufentanil (1 microgram/kg), propofol (1 microgram/mL) target plasma concentration achieved over 3 minutes, and atracurium (0.5 mg/kg). The propofol target-controlled infusion was maintained at 1 microgram/mL throughout surgery and stopped at skin closure. A continuous infusion of sufentanil at 1.8 micrograms/kg/hr was started after induction and reduced to 0.9 microgram/kg/hr at the start of cardiopulmonary bypass and stopped at the end of bypass. Atracurium was infused at a rate of 0.5 mg/kg/hr up to sternal closure. No inhalation agents were used., Measurements and Main Results: Hemodynamic data were within normal limits. Six patients (40%) responded to verbal commands within 15 minutes postoperatively, 10 (67%) within the first hour, and all patients recovered within 2 hours. Four patients (27%) resumed spontaneous ventilation within the first 15 postoperative minutes. The time to successful spontaneous ventilation was 169 +/- 42 minutes. Spontaneous ventilation was associated with a 21% increase in cardiac index. Total sufentanil dose was 328 +/- 28 micrograms (4.6 +/- 0.2 microgram/kg), whereas total propofol dose was 862 +/- 44 mg (13.1 +/- 1.2 mg/kg). No patient required reintubation., Conclusion: The simplicity of the method with only one change in infusion rate is a major advantage. The technique permits predictable recovery and return to spontaneous ventilation in all patients. Its use in patients entering early extubation protocols is appealing for its reproducibility, simplicity, and safety.

Objective: To document changes in serum lipids and glucose with a propofol infusion technique for cardiac surgery., Design: Prospective cohort., Setting: University teaching hospital., Participants: 22 elective cardiac surgical patients., Interventions: Frequent venous blood sampling., Measurements and Main Results: Serum lipids and glucose were measured at 10 time periods perioperatively, from preinduction until 4 hours post-cardiopulmonary bypass. Plasma propofol concentrations were also measured in 10 of these patients. There was a significant increase in glucose (P < 0.0005) and decreases in cholesterol (P < 0.0005), high-density lipoprotein (P = 0.004), and low-density lipoprotein (P < 0.0005); there was no significant change in triglycerides (P = 0.39). The propofol infusion resulted in acceptable plasma levels throughout the procedure and allowed early extubation in the intensive care unit, after a mean (SD) of 7.14 (5.9) hours. There was a strong correlation between triglyceride and propofol levels at most time periods (r = 0.38 to 0.98)., Conclusions: This study demonstrates that a propofol infusion technique does not result in elevation of serum lipids and supports its increased popularity in maintenance of anesthesia for cardiac surgery.

Total intravenous anesthesia (TIVA) using alfentanil and propofol was used in 10 patients undergoing coronary artery bypass grafting. In an attempt to diminish unwanted side effects, lower doses were chosen than if either drug had been used alone. Anesthesia was induced with alfentanil, 75 micrograms/kg, followed by a sleep dose of propofol (mean dose 0.5 mg/kg). Maintenance in the precardiopulmonary bypass (CPB) period was achieved by infusions of propofol (6 mg/kg/h) and alfentanil (100 micrograms/kg/h). These were decreased by two thirds on commencement of CPB, and increased to half the initial rate on rewarming to 32 degrees C. Additional boluses of alfentanil were used to control breakthrough hypertension. The mean arterial pressure (MAP) and left ventricular stroke work index (LVSWI) fell significantly on induction. MAP but not LVSWI returned to baseline levels at skin incision. The cardiac index (CI) was maintained. A degree of myocardial depression was suggested by a fall in LVSWI despite maintaining preload, and by the failure of CI to increase in the presence of a reduced SVR. Anesthesia was satisfactory in all but one patient who developed breakthrough hypertension on sternotomy with transient ST segment depression, and awareness after CPB despite a plasma alfentanil concentration of 450 ng/mL. Mean time to wakening was 55 minutes. The study indicated that TIVA using propofol and alfentanil in the dosages described provides satisfactory basal anesthesia for coronary artery bypass surgery in patients with good left ventricular function, but requires additional pharmacologic manipulation, particularly with boluses of alfentanil, to control breakthrough hypertension.