Population pharmacokinetics of cefazolin before, during and after cardiopulmonary bypass to optimize dosing regimens for children undergoing cardiac surgery

Cock, Pieter De; Mulla, Hussain; Desmet, Sarah; Somer, Filip De; McWhinney, Brett; Ungerer, Jacobus P.J.; Moerman, Annelies T.; Commeyne, Sabrina; Walle, Johan Vande; François, Katrien; Hasselt, J. G. Coen van; Paepe, Peter De

doi:10.1093/jac/dkw496

Cited by 26 publications

(32 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… who found a fluctuation of CXM protein binding less than 2% during adult cardiac surgery. Even the variation of the highly protein‐bound antibiotic cefazolin with a subsequently higher susceptibility to changes in plasma proteins was minimal (28% ± 3%) in a group of children similar to ours using a reconstituted blood prime on CPB , with a negligible effect of varying albumin concentrations on PTA .…”

Section: Discussionsupporting

confidence: 68%

Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery

Gertler

Gruber

Wiesner

et al. 2018

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 68%

Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery

Gertler

Gruber

Wiesner

et al. 2018

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…This may also affect the cefazolin plasma concentration and account for the more profound decrease in the larger CPB system. Recently, De Cock et al published in vivo data on cefazolin plasma concentration during and after pediatric cardiac surgery . The authors collected blood samples from children undergoing cardiac surgery and concentration‐time profiles were analyzed using population pharmacokinetic modeling .…”

Section: Discussionmentioning

confidence: 99%

“…To date, no uniform guidelines for the dosing of antibiotic prophylaxis in children are available. Also, potentially increased risks of SSI after cardiac surgery are not incorporated in current dosing advice . Several procedural risk factors, such as the use of a bladder catheter, longer duration of CPB or prolonged surgery time, may increase the risk of SSI in pediatric cardiac surgery patients .…”

Section: Discussionmentioning

confidence: 99%

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

“…Caffarellie et al also reported that the traditional dosing protocol of cefazolin was unable to maintain drug concentrations above 8 μg mL −1 in 50% of the patients when surgical time was longer than 120 minutes. De Cock et al performed population pharmacokinetic analysis on total and unbound plasma cefazolin concentrations in 54 children undergoing cardiac surgery with CPB. They concluded that an additional bolus dose at the start of CPB may improve the probability of target attainment from 59% to >94% in a typical pediatric patient.…”

Section: Discussionmentioning

confidence: 99%

“…To establish an effective antimicrobial prophylaxis regimen with cefazolin for patients undergoing cardiothoracic surgery with CPB, we should develop a pharmacokinetic model that describes the disposition of plasma unbound drug during operation. The pharmacokinetics of plasma unbound cefazolin during CPB may be influenced by complex physiological changes associated with the procedure (including low serum albumin levels, transient increase in volume of distribution by connecting the CPB circuit to systemic circulation, changes in circulating volume by infusion and blood loss, and changes in liver and kidney perfusion) . The disposition of cefazolin may be particularly susceptible to alteration associated with CPB‐induced physiological changes, since the drug has a small volume of distribution (0.19 L kg −1 or 11.4 L per 60 kg) and binds extensively to albumin (80%‐86%) .…”

Section: Discussionmentioning

confidence: 99%

Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery

Asada

Nagata

Mizuno

et al. 2018

Pharmacology Res & Perspec

View full text Add to dashboard Cite

The aim of the study was to evaluate the disposition of plasma unbound cefazolin in patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB). Adult patients undergoing cardiothoracic surgery with CPB were enrolled in the study. Cefazolin sodium was given intravenously before skin incision (1 g) and at the beginning of CPB (2 g). Thereafter, an additional dose (1 g) was given every 4 hours. Seven to ten blood samples were collected before and during surgery. Plasma total and unbound (ultrafiltrated) cefazolin concentrations were analyzed using an HPLC‐UV method. Plasma protein binding was analyzed with the Langmuir model. Twenty‐seven patients (aged 70 ± 12 years, body weight 62 ± 12 kg, mean ± SD) with GFR >30 mL min−1 completed the study. There was a significant (P < 0.001) increase in median plasma unbound fraction of cefazolin from 21% before skin incision to 45% during CPB (P < 0.001), which was accompanied by a significant (P < 0.001) reduction in median plasma albumin concentration from 36 to 27 g L−1. Plasma concentrations of unbound cefazolin exceeded the assumed target thresholds of 2 μg mL−1 in all samples and of 8 μg mL−1 in all but one of 199 samples. The increased plasma unbound fraction of cefazolin would be attributable to dilutional reduction of serum albumin at the beginning of CPB and to saturable plasma protein binding of cefazolin. These data reveal CPB may alter the plasma protein binding and possibly distribution of cefazolin. Further studies are warranted to reappraise the protocol of antimicrobial prophylaxis with cefazolin in patients undergoing surgery with CPB.

show abstract

Population pharmacokinetics of cefazolin before, during and after cardiopulmonary bypass to optimize dosing regimens for children undergoing cardiac surgery

Abstract: We propose an optimized dosing regimen for cefazolin during cardiac surgery in paediatric patients to avoid treatment failure due to inadequate antibiotic prophylaxis.

Cited by 26 publications

References 46 publications

Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery

Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems

Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery

Contact Info

Product

Resources

About