In Vitro Adsorption of Analgosedative Drugs in New Extracorporeal Membrane Oxygenation Circuits

Raffaeli, Genny; Allegaert, Karel; Koch, Birgit C. P.; Cavallaro, Giacomo; Mosca, Fabio; Tibboel, Dick; Wildschut, Enno D.

doi:10.1097/pcc.0000000000001484

Cited by 28 publications

(40 citation statements)

References 37 publications

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“…[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. 8,9 Previous publications have used the term absorption to indicate the decrease in concentration of drug in the priming fluid.…”

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confidence: 99%

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

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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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confidence: 99%

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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“…Sequestration in these systems is expected for lipophilic drugs, such as sufentanil or midazolam. 13 As shown by Shekar et al 14 in ECMO circuits, drugs with a LogP greater than 2.3 have a significantly higher decrease in the concentration compared to less lipophilic or hydrophilic drugs. As both cefazolin and clindamycin have a lower LogP they are not expected to sequester in the CPB systems (see Table 5).…”

Section: Discussionmentioning

confidence: 93%

“…Hydrophilic drugs such as clindamycin are not known to sequester in CPB systems. Sequestration in these systems is expected for lipophilic drugs, such as sufentanil or midazolam . As shown by Shekar et al in ECMO circuits, drugs with a LogP greater than 2.3 have a significantly higher decrease in the concentration compared to less lipophilic or hydrophilic drugs.…”

Section: Discussionmentioning

confidence: 97%

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems

et al. 2020

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Cardiopulmonary bypass (CPB) is often necessary for congenital cardiac surgery, but CPB can alter drug pharmacokinetic parameters resulting in underdosing. Inadequate plasma levels of antibiotics could lead to postoperative infections with increased morbidity. The influence of pediatric CPB systems on cefazolin and clindamycin plasma levels is not known. We have measured plasma levels of cefazolin and clindamycin in in vitro pediatric CPB systems. We have tested three types of CPB systems. All systems were primed and spiked with clindamycin and cefazolin. Samples were taken at different time points to measure the recovery of cefazolin and clindamycin. Linear mixed model analyses were performed to assess if drug recovery was different between the type of CPB system and sampling time point. The experiments were conducted at a tertiary university hospital. 81 samples were analyzed. There was a significant difference in the recovery over time between CPB systems for cefazolin and clindamycin (P < .001). Cefazolin recovery after 180 minutes was 106% (95% CI: 91‐123) for neonatal, 99% (95% CI: 85‐115) for infant, and 77% (95% CI: 67‐89) for pediatric systems. Clindamycin recovery after 180 minutes was 143% (95% CI: 116‐177) for neonatal, 111% (95% CI: 89‐137) for infant, and 120% (95% CI: 97‐149) for pediatric systems. Clindamycin recovery after 180 minutes compared to the theoretical concentration was 0.4% for neonatal, 1.2% for infants, and 0.6% for pediatric systems. The recovery of cefazolin was high in the neonatal and infant CPB systems and moderate in the pediatric system. We found a large discrepancy between the theoretical and measured concentrations of clindamycin in all tested CPB systems.

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“…However, in vitro data reported that mechanisms behind changed CL are not clear yet -it depends on drug lipophilicity, but also on the bindingsite saturation. [5][6][7][8] Phenobarbital, phenytoin and fos-phenytoin are anticonvulsive drugs used in neonates and infants undergoing ECMO to treat seizures (18-20%) and withdrawal symptoms. [8][9][10] There is insufficient data on the potential impact of ECMO on the PK of phenobarbital.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8] Phenobarbital, phenytoin and fos-phenytoin are anticonvulsive drugs used in neonates and infants undergoing ECMO to treat seizures (18-20%) and withdrawal symptoms. [8][9][10] There is insufficient data on the potential impact of ECMO on the PK of phenobarbital. 11 A number of publications reported serum concentrations of phenobarbital after the loading dose (LD) to be decreased (24 hours) due to the large Vd, while concentrations measured during the maintenance dose (MD) regimen were still within the therapeutic range and the calculated t 1/2 was similar to neonates receiving phenobarbital without ECMO.…”

Section: Introductionmentioning

confidence: 99%

Phenobarbital pharmacokinetics in neonates and infants during extracorporeal membrane oxygenation

et al. 2018

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In Vitro Adsorption of Analgosedative Drugs in New Extracorporeal Membrane Oxygenation Circuits

Cited by 28 publications

References 37 publications

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

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

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems

Phenobarbital pharmacokinetics in neonates and infants during extracorporeal membrane oxygenation

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