Effect of Membrane Oxygenators on Sufentanil Blood Levels During Cardiopulmonary Bypass

Durkan, W J; Lonergan, Margaret; Schwartz, Sorell L.; Fleming, Neal

doi:10.1213/00000539-198802001-00054

Cited by 3 publications

(2 citation statements)

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“…In vitro experiments have demonstrated that significant amounts of fentanyl ( 24–26) and alfentanil ( 25, 27) can be sequestered in bypass equipment ( Table 1), while sufentanil may also be taken up by oxygenators ( 28). However, Stone et al ( 29) could not demonstrate significant sufentanil loss by hemoconcentrators or cell savers, while cefazolin levels were unaffected by ultrafiltration during bypass ( 30).…”

Section: Factors During Cardiopulmonary Bypass Affecting Drug Pharmacmentioning

confidence: 99%

The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass

Mets

2000

Acta Anaesthesiol Scand

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The institution of cardiopulmonary bypass during cardiac surgery has profound effects on the plasma concentration of drugs and thus their therapeutic effectiveness. These changes occur through acute hemodilution, altered plasma protein binding, hypotension, as well as the use of hypothermia and heparin administration. Isolation of the lungs from the circulation and the possible sequestration of drugs in the bypass circuit also affect drug plasma concentrations on bypass. The individual characteristics of the drug in question are also important in determining the final plasma concentration: Lipid soluble drugs with a high volume of distribution may be more readily taken up by bypass equipment, but the initial fall in concentration at the start of cardiopulmonary bypass may be more readily counteracted by back diffusion into plasma, if large tissue stores have accumulated. The extent of the drug's plasma protein binding is of importance as the effective free fraction in plasma for highly bound drugs will be sensitive to changes in plasma protein binding brought on by factors such as hemodilution, heparin administration as well as alpha, acid-glycoprotein binding. Clearly the fate of drugs administered before or on bypass is complex and can only be accurately determined by specific studies evaluating drug plasma concentrations. This review updates the available data on anesthetics and drugs used during cardiac surgery in order that anesthetists may predict better the likely effect of drugs administered before or during cardiopulmonary bypass.

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Section: Factors During Cardiopulmonary Bypass Affecting Drug Pharmacmentioning

confidence: 99%

The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass

Mets

2000

Acta Anaesthesiol Scand

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“…1 Furthermore, the plastic components of the CPB system themselves have been shown to absorb drugs. [2][3][4][5][6][7] In the authors' institution, multiple experiments have been performed to determine in vitro drug recovery in extracorporeal membrane oxygenation (ECMO) systems. 8,9 Drug recovery has been defined as the concentration of drug present in the priming fluid after a certain amount of time has passed since addition of the drug to the CPB system.…”

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In Vitro Recovery of Sufentanil, Midazolam, Propofol, and Methylprednisolone in Pediatric Cardiopulmonary Bypass Systems

Saet

Zeilmaker-Roest

Hoeven

et al. 2020

Journal of Cardiothoracic and Vascular Anesthesia

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Objectives: To evaluate in vitro drug recovery in cardiopulmonary bypass (CPB) systems used for pediatric cardiac surgery. Design: Observational in vitro study. Setting: Single-center university hospital. Participants: In vitro CPB systems used for pediatric cardiac surgery. Interventions: Three full neonatal, infant, and pediatric CPB systems were primed according to hospital protocol and kept running for 6 hours. Midazolam, propofol, sufentanil, and methylprednisolone were added to the venous side of the systems in doses commonly used for induction of general anesthesia. Blood samples were taken from the postoxygenator side of the circuit immediately after injection of the drugs and after 2, 5, 7, 10, 30, 60, 180, and 300 minutes. Measurements and Main Results: Linear mixed model analyses were performed to assess the relationship between log-transformed drug concentration (dependent variable) and type of CPB system and sample time point (independent variables). The mean percentage of drug recovery after 60 and 180 minutes compared with T1 was 41.7% (95% confidence interval [CI] 35.9-47.4) and 23.0% (95% CI 9.2-36.8) for sufentanil, 87.3% (95% CI 64.9-109.7) and 82.0% (95% CI 64.6-99.4) for midazolam, 41.3% (95% CI 15.5-67.2) and 25.0% (95% CI 4.7-45.3) for propofol, and 119.3% (95% CI 101.89-136.78) and 162.0% (95% CI 114.09-209.91) for methylprednisolone, respectively. Conclusions: The present in vitro experiment with neonatal, infant, and pediatric CPB systems shows a variable recovery of routinely used drugs with significant differences between drugs, but not between system categories (with the exception of propofol). The decreased recovery of mainly sufentanil and propofol could lead to suboptimal dosing of patients during cardiac surgery with CPB.

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Population pharmacokinetic modeling of sufentanil in adult Korean patients undergoing cardiopulmonary bypass surgery

Khaowroongrueng,

Son,

Lee

et al. 2024

CPT Pharmacom & Syst Pharma

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Sufentanil is frequently used as an anesthetic agent in cardiac surgery owing to its cardiovascular safety and favorable pharmacokinetics. However, the pharmacokinetics profiles of sufentanil in patients undergoing cardiopulmonary bypass (CPB) surgery remain less understood, which is crucial for achieving the desired level of anesthesia and mitigating surgical complications. Therefore, this study aimed to develop a population pharmacokinetic model of sufentanil in patients undergoing CPB surgery and elucidate the clinical factors affecting its pharmacokinetic profile. Adult patients who underwent cardiac surgery with CPB and were administered sufentanil for anesthesia were enrolled. Arterial blood samples were collected to quantify plasma concentrations of sufentanil and clinical laboratory parameters, including inflammatory cytokines. A population pharmacokinetic model was established using nonlinear mixed‐effects modeling. Simulations were performed using the pharmacokinetic parameters of the final model. Overall, 20 patients were included in the final analysis. Sufentanil pharmacokinetics were modeled using a two‐compartment model, accounting for CPB effects. Sufentanil clearance increased 2.80‐fold during CPB and warming phases, while the central compartment volume increased 2.74‐fold during CPB. CPB was a significant covariate affecting drug clearance and distribution volume. No other significant covariates were identified despite increased levels of the inflammatory cytokines, including IL‐6, IL‐8, and TNF‐α during CPB. The simulation indicated a 30 μg loading dose and 40 μg/h maintenance infusion for target‐controlled infusion. Additionally, a bolus dose of 60 μg was added at CPB initiation to adjust for exposure changes during this phase. Considering the target sufentanil concentrations, a uniform dosing regimen was acceptable for effective analgesia.

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Effect of Membrane Oxygenators on Sufentanil Blood Levels During Cardiopulmonary Bypass

Cited by 3 publications

References 0 publications

The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass

The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass

In Vitro Recovery of Sufentanil, Midazolam, Propofol, and Methylprednisolone in Pediatric Cardiopulmonary Bypass Systems

Population pharmacokinetic modeling of sufentanil in adult Korean patients undergoing cardiopulmonary bypass surgery

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