Cardiopulmonary Bypass and the Pharmacokinetics of Drugs

Buylaert, W. A.; Herregods, Luc; Mortier, Éric; Bogaert, Marc G.

doi:10.2165/00003088-198917010-00002

Cited by 119 publications

(74 citation statements)

References 63 publications

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“…The decrease in protein binding upon initiation of the bypass could result in potentionally greater transfer of antibiotic to the tissue. In addition, decreased clearance and enhanced volume of distribution for the cephalosporins have been described 26,27 . From a practical point of view, we used a standard dose of cefuroxime for each patient regardless of bodyweight.…”

Section: Discussionmentioning

confidence: 99%

Tissue and Plasma Concentrations of Antibiotic During Cardiac Surgery With Cardiopulmonary Bypass - Microdialysis Study

Pojar

Mandak²,

Maláková³

et al. 2008

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aim: Surgical-site infections are very serious complications of cardiac operations. Use of cardiopulmonary bypass (CPB) is associated with profound physiological changes, which aff ects the pharmacokinetic behaviour of prophylactic antibiotics. The aim of this study was to monitor tissue concentrations of cefuroxime in peripheral tissue (skeletal muscle) during cardiac surgery using CPB by means of a microdialysis.Methods: Eleven adult patients operated on using CPB were included in the study. Cefuroxime was the prophylactic antibiotic and study drug given. Microdialysis was performed by probe CMA 60 inserted into the patient's left deltoid muscle. Samples of dialysates were collected at intervals: before CPB, each 30 minutes of CPB and at the end of CPB. Samples of blood were collected at intervals: incision, start of CPB, each 30 minutes of CPB, at the end of CPB and at the end of surgery.

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Section: Discussionmentioning

confidence: 99%

Tissue and Plasma Concentrations of Antibiotic During Cardiac Surgery With Cardiopulmonary Bypass - Microdialysis Study

Pojar

Mandak²,

Maláková³

et al. 2008

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…39,45,46 Due to our small sample size and the apparent bimodal distribution observed in our patients during the pre-CPB period, it was impossible to identify a general trend in the relative changes in Cl during the post-CPB period.…”

Section: Resultsmentioning

confidence: 88%

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children

Withington

Ménard

Harris

et al. 2000

Can J Anesth/J Can Anesth

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Purpose: To determine the effect of moderate and deep hypothermic cardiopulmonary bypass (CPB) on the pharmacokinetic and pharmacodynamic behaviour of vecuronium in infants and children. Methods:We studied 12 patients undergoing surgery for congenital heart disease under narcotic-nitrous oxide anesthesia. Neuromuscular blockade was maintained constant (T1 4-10% by Datex electromyograph) by adjusting a vecuronium infusion. Plasma vecuronium concentrations (Cpss) were analysed by HPLC to describe a pseudosteadystate during each of the pre-CPB, CPB and post-CPB phases. Paired arterial blood samples were taken 20 min apart after at least 20 min of constant infusion.Results: Nine cases were analysed, mean age 20 mo, mean weight 9 kg. Three patients had deep and six moderate hypothermia. In the pre-CPB phase Cpss fell into two groups (mean ± SD: 330 ± 42 ng·ml -1 ; 127 ± 27 ng·ml -1 ; P < 0.001); similarly the clearances showed a bimodal distribution (mean ± SD: 5.08 ± 0.94; 11.51 ± 0.2 ml·min -1 ·kg -1 P < 0.001), although in different patients. During CPB this bimodal distribution disappeared. Vecuronium infusion rate (VIR) decreased by 84% and 92% from pre-CPB to CPB phase in deep and moderate hypothermia groups respectively (P < 0.05), paralleled by decreases in Cpss of 36% (P > 0.05) and 52% (P < 0.05). Conclusion: Changes in vecuronium requirements and plasma concentrations during CPB demonstrate that vecuronium pharmacokinetics and pharmacodynamics are both affected by hypothermic CPB in infants. The finding of bimodal distributions for plasma vecuronium and vecuronium clearance highlights the need for individual monitoring of neuromuscular blockade in this age group.Objectif: Déterminer l'effet d'une circulation extracorporelle (CEC) avec hypothermie modérée ou profonde sur les paramètres pharmacocinétiques et pharmacodynamiques du vécuronium chez des nourrissons et des enfants.Méthode : Nous avons étudié 12 patients opérés pour cardiopathie congénitale sous anesthésie avec un mélange de narcotique et de protoxyde d'azote. Le blocage neuromusculaire a été maintenu constant (T1 4-10 % avec un élec-tromyographe Datex) en ajustant une perfusion de vécuronium. Les concentrations plasmatiques de vécuronium (Cpss) ont été analysées par chromatographie liquide haute performance (CLHP) afin de définir l'état pseudo-équilibre pendant chacune des étapes pré-CEC, CEC et post-CEC. Des échantillons appariés de sang artériel ont été prélevés à intervalles de 20 min, après au moins 20 min de perfusion constante.Résultats: Neuf cas ont été analysés, âgés de 20 ms et pesant 9 kg en moyenne. Trois patients avaient une hypothermie profonde et six, une modérée. Pendant la pré-CEC, les Cpss se séparent en deux groupes (moyenne ± écart type : 330 ± 42 ng·ml -1 ; 127 ± 27 ng·ml -1 ; P < 0,001); les clairances ont affiché une distribution bimodale (moyenne ± écart type : 5,08 ± 0,94; 11,51 ± 0,2 ml·min -1 ·kg -1 P < 0,001), chez différents patients cependant. Pendant la CEC, cette distribution bimodale a disparu. La vitesse de perfus...

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“…The drug concentrations may be profoundly altered during CPB, albeit mainly as a result of changed V d and k e , resulting in underdosing. 15) In this study, the pharmacokinetic parameters of ampicillin were compared before and after CPB. The V d of after CPB was slightly increased compared to that observed before CPB.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Prophylactic Ampicillin–Sulbactam and Dosing Optimization in Patients Undergoing Cardiovascular Surgery with Cardiopulmonary Bypass

Yokoyama

Matsumoto

Ikawa

et al. 2015

Biological & Pharmaceutical Bulletin

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Antibiotic concentrations must be maintained at an adequate level throughout cardiovascular surgery to prevent surgical site infection. This study aimed to determine the most appropriate timing for intraoperative repeated dosing of ampicillin-sulbactam, a commonly used antibiotic prophylaxis regimen, to maintain adequate concentrations throughout the course of cardiovascular surgery with cardiopulmonary bypass (CPB). The total plasma concentrations of ampicillin were monitored in 8 patients after ampicillin (1 g)-sulbactam (0.5 g) administration via initial intravenous infusion and subsequent CPB priming. Pharmacokinetic parameters were estimated and used to predict the free plasma concentrations of ampicillin. The mean values for the volume of distribution, elimination rate constant, elimination half-life, and total clearance of ampicillin were 15.8 4.1 L, 0.505 0.186 h 1 , 1.52 0.47 h, and 7.72 2.72 L/h, respectively. When ampicillin (1 g)-sulbactam (0.5 g) was intravenously administered every 3, 4, 6, and 12 h after the start of CPB, the predicted free trough plasma concentrations of ampicillin were 15.20, 8.25, 2.74, and 0.13 µg/mL, respectively. Therefore, an every-6-h regimen was needed to maintain the free ampicillin concentration at more than 2 µg/mL during cardiovascular surgery with CPB. We suggest that the dose and dosing interval for ampicillin-sulbactam should be adjusted to optimize the efficacy and safety of treatment, according to the minimum inhibitory concentrations for methicillin-sensitive Staphylococcus aureus isolates at each institution. Registration number: UMIN000007356.Key words ampicillin; sulbactam; cardiovascular surgery; prophylaxis; cardiopulmonary bypass The United States Centers for Disease Control National Nosocomial Infections Surveillance system demonstrated that surgical site infection (SSI) is the most frequently reported nosocomial infection, accounting for 14-16% of such infections among hospitalized patients and 38% in surgical patients.1) According to the Japan Nosocomial Infections Surveillance Open Report 2013, the incidence of SSI in cardiovascular surgery was 1.5-4.8%. 2)Postoperative SSIs are a major cause of postoperative morbidity and mortality in patients undergoing cardiac surgery. SSIs of the sternal wound and underlying mediastinum occur in 0.4-4% of cardiac surgical operations.3) The administration of antibiotic prophylaxis in patients treated with cardiothoracic operations can reduce the rate of SSI, and placebo-controlled trials of cardiothoracic antibiotic prophylaxis have found a benefit in preventing postoperative wound infections. 4)Cardiopulmonary bypass (CPB) is a technique that is nearly exclusively used by cardiac surgeons and has profound effects on the volume of distribution (V d , L) and elimination kinetics for a variety of drugs, including commonly used antibiotic prophylaxis agents.3) Antibiotic prophylaxis should be selected according to the type of surgery, with administration starting within 60 min of the skin incision. When the duration of...

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Cardiopulmonary Bypass and the Pharmacokinetics of Drugs

Cited by 119 publications

References 63 publications

Tissue and Plasma Concentrations of Antibiotic During Cardiac Surgery With Cardiopulmonary Bypass - Microdialysis Study

Tissue and Plasma Concentrations of Antibiotic During Cardiac Surgery With Cardiopulmonary Bypass - Microdialysis Study

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children

Pharmacokinetics of Prophylactic Ampicillin–Sulbactam and Dosing Optimization in Patients Undergoing Cardiovascular Surgery with Cardiopulmonary Bypass

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