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

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.

SUBMITTER: Barbosa RA

PROVIDER: S-EPMC2666455 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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

Barbosa Ricardo Antonio G RA Santos Silvia Regina C Jorge SR White Paul F PF Pereira Valéria A VA Silva Filho Carlos R CR Malbouisson Luiz M S LM Carmona Maria José C MJ

Clinics (Sao Paulo, Brazil) 20090101 3

<h4>Purpose</h4>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.<h4>Methods</h4>Twenty patients scheduled for on-pump coronary artery bypass graft (group, n=10) or off-pump coronary artery bypas ...[more]

PMID: 19330248

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Project description:As methicillin-resistant Staphylococcus aureus (MRSA) becomes more prevalent, vancomycin is becoming increasingly used as a prophylaxis against surgical-site infections for cardiothoracic surgeries. However, vancomycin administration can be challenging, and the pharmacokinetics of alternative antibiotics in this setting are poorly understood. The primary objective of this investigation was to describe the pharmacokinetics of daptomycin in patients undergoing coronary artery bypass graft surgery. We enrolled 15 patients undergoing coronary artery bypass surgery requiring cardiopulmonary bypass. Each subject was administered a single open-label dose of daptomycin (8 mg/kg of body weight) for surgical prophylaxis. Fourteen daptomycin plasma samples were collected. Safety outcomes between subjects who received daptomycin and 15 control subjects who received the standard-of-care antibiotic were compared. The mean maximal concentration of daptomycin (C(max)) was 84.4 ± 27.1 ?g/ml; the mean daptomycin concentration during the cardiopulmonary bypass procedure was 33.2 ± 11.4 ?g/ml and was 30.9 ± 12.7 ?g/ml at sternum closure. Mean daptomycin concentrations at 12, 18, 24, and 48 h were 22.7 ± 9.7, 16.2 ± 8.2, 12.0 ± 4.7, and 3.5 ± 2.3 ?g/ml, respectively. Mean daptomycin concentrations were consistently above the MIC at which 90% of the tested isolates are inhibited (MIC??) for S. aureus and S. epidermidis during the cardiopulmonary bypass procedure. Daptomycin was not associated with surgical-site infections or differences in adverse events compared to findings for control subjects. We found that a single dose of daptomycin at 8 mg/kg was well tolerated and achieved adequate plasma concentrations against common pathogens associated with surgical-site infections after cardiothoracic surgery. Daptomycin may be considered an alternative surgical prophylaxis antibiotic for patients undergoing cardiothoracic bypass surgery who are unable to receive vancomycin.

Project description:ObjectiveMetabolism management plays an essential role during cardiopulmonary bypass (CPB). There are different metabolic management devices integrated to heart-lung machines; the most commonly used and accepted metabolic target is indexed oxygen delivery (DO2i) (280 mL/min/m2) and cardiac index (CI) (2.4 L/min/m2), which can be managed independently or according to other metabolic parameters. Our objective was to compare lactate production during CPB procedures using different metabolic management: DO2i in relation to indexed oxygen extraction ratio (O2ERi) and CI in relation to mixed venous oxygen saturation (SvO2).MethodsData on 500 CPB procedures were retrospectively collected in a specialized regional tertiary cardiac surgery center in Italy between September and 2012 and November 2019. In group A, the DO2i with 280 mL/min/m2 target in relation to O2ERi 25% was used; in group B, CI with 2.4 L/min/m2 target in relation to SvO2 75% was used. During CPB, serial arterial blood gas analyses with blood lactate and glucose determinations were obtained. Hyperlactatemia (HL) was defined as a peak arterial blood lactate concentration >3 mmol/L. The postoperative outcome of patients with or without HL was compared.ResultsEight pre- and intraoperative factors were found to be significantly associated with peak blood lactate level during CPB at univariate analysis. HL (>3 mmol/L) was detected in 15 (6%) patients of group A and in 42 (16.8%) patients of group B (P = .022); hyperglycemia (>160 mg/dL) was found in 23 (9.2%) patients of group A and in 53 (21.2%) patients of group B (P = .038). Patients with HL during CPB had a significant increase in serum creatinine value, higher rate of prolonged mechanical ventilation time and intensive care unit stay. A cutoff of DO2i <270 mL/min/m2 in relation to O2ERi >35% in group A and a cutoff of CI <2.4 L/min/m2 in relation to SvO2 <65% in group B were found to have a positive predictive value of 80% and 75% for HL, respectively. A cutoff of DO2i >290 mL/min/m2 in relation to O2ERi 24% in group A and a cutoff of CI >2.4 L/min/m2 in relation to SvO2 >75% in group B were found to have a negative predictive value of 78% and 62% for HL, respectively.ConclusionsThis retrospective observational analysis showed that management of DO2i in relation to O2ERi was 16% more specific in terms of negative predictive value for HL during CPB compared with the use of CI in relation to SvO2. Group A reported a significant reduction in the incidence of intraoperative lactate peak, correlated with postoperative reduction of serum creatinine value, mechanical ventilation time, and intensive care unit stay, compared with group B.

Project description:Introduction: To our knowledge, methylprednisolone pharmacokinetics and plasma concentrations have not been comprehensively investigated in children with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass. It is unknown whether there is a significant influence of cardiopulmonary bypass on the plasma concentrations of methylprednisolone and whether this may be an explanation for the limited reported efficacy of steroid administration in cardiac surgery with cardiopulmonary bypass. Methods: The study was registered in the Dutch Trial Register (NTR3579; https://www.trialregister.nl/trial/3428). Methylprednisolone 30 mg/kg was administered as an intravenous bolus after induction of anesthesia. Methylprednisolone concentration was measured with liquid chromatography tandem mass spectrometry and analyzed using linear mixed-effects modeling. Results: Thirty-nine patients were included in the study, of which three were excluded. There was an acute decrease in observed methylprednisolone plasma concentration on initiation of cardiopulmonary bypass (median = 26.8%, range = 13.9-48.14%, p < 0.001). We found a lower intercept (p = 0.02), as well as a less steep slope of the model predicted methylprednisolone concentration vs. time curve for neonates (p = 0.048). A lower intercept (p = 0.01) and a less steep slope (p = 0.0024) if the volume of cell saver blood processed was larger than 91 ml/kg were also found. Discussion: We report similar methylprednisolone plasma concentrations as earlier studies performed in children undergoing cardiopulmonary bypass, and we confirmed the large interindividual variability in achieved methylprednisolone plasma concentrations with weight-based methylprednisolone administration. A larger volume of distribution and a lower clearance of methylprednisolone for neonates were suggested. The half-life of methylprednisolone in our study was calculated to be longer than 6 h for neonates, 4.7 h for infants, 3.6 h for preschool children and 4.7 h for school children. The possible influence of treatment of pulmonary hypertension with sildenafil and temperature needs to be investigated further.

Dataset Information

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

Publications

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

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