Cefuroxime pharmacokinetics in pediatric cardiovascular surgery patients undergoing cardiopulmonary bypass

Chad A. Knoderer, Sarah A. Saft, Scott G. Walker, Mark D. Rodefeld, Mark W. Turrentine, John W. Brown, Daniel P. Healy, Kevin M. Sowinski

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objectives: The objective of this study was to determine the pharmacokinetics of cefuroxime in children undergoing cardiopulmonary bypass (CPB) for cardiovascular surgery. Design: A prospective study. Setting: A tertiary pediatric teaching hospital. Participants: Infants and children undergoing CPB were enrolled in the study. Intervention: An initial dose (mean, 24.2 ± 1.6 mg/kg) of cefuroxime was administered before surgical incision, and a second dose (mean, 14.4 ± 7.9 mg/kg) was administered in the CPB prime solution. Serial blood samples were obtained before, during, and after the CPB process. Samples were shipped on dry ice to the analytic laboratory and concentrations determined by a validated high-performance liquid chromatography method. A 2-compartment pharmacokinetic model was fitted to the data using maximum a priori-Bayesian estimation, with weight as a covariate. Monte Carlo simulations of a single-dose (25 mg/kg pre-CPB) approach and a 2-dose (25 mg/kg pre- and 12.5-mg/kg prime solution dose) approach were performed. Measurements and Main Results: Fifteen subjects (9 males/6 females) were enrolled in the study, with median (range) age and weight of 11 (3-34) months and 9.5 (4.5-15.4) kg, respectively. The median (range) duration of CPB was 136 (71-243) minutes. Median and range cefuroxime pharmacokinetic parameters were as follows: maximum concentration (Cmax) dose, 1: 328 (150-512) μg/mL; systemic clearance, 0.050 (0.041-0.058) L/h/kg; steady-state volume of distribution, 0.213 (0.081-0.423) L/kg; volume of distribution in the central compartment, 0.081 (0.046-0.162) L/kg; and elimination half-life, 3.76 (1.03-6.81) hours. The median 8-hour post-dose-simulated cefuroxime concentrations were 26.5 and 16.0 mg/L for the 2-dose and single-dose regimens, respectively. Conclusion: Manufacturers recommend that pediatric doses of cefuroxime (25-50 mg/kg) can be used in infants and children undergoing CPB to maintain adequate serum concentrations for surgical-site infection prophylaxis. A second intraoperative dose, administered through the CPB circuit, provides no additional prophylactic advantage.

Original languageEnglish (US)
Pages (from-to)425-430
Number of pages6
JournalJournal of Cardiothoracic and Vascular Anesthesia
Volume25
Issue number3
DOIs
StatePublished - Jun 1 2011

Fingerprint

Cefuroxime
Cardiopulmonary Bypass
Pharmacokinetics
Pediatrics
Dry Ice
Surgical Wound Infection
Weights and Measures
Pediatric Hospitals
Tertiary Care Centers
Teaching Hospitals
Half-Life
High Pressure Liquid Chromatography
Prospective Studies

Keywords

  • cardiopulmonary bypass
  • cefuroxime
  • chromatography
  • liquid
  • pediatric
  • pharmacokinetics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Anesthesiology and Pain Medicine

Cite this

Cefuroxime pharmacokinetics in pediatric cardiovascular surgery patients undergoing cardiopulmonary bypass. / Knoderer, Chad A.; Saft, Sarah A.; Walker, Scott G.; Rodefeld, Mark D.; Turrentine, Mark W.; Brown, John W.; Healy, Daniel P.; Sowinski, Kevin M.

In: Journal of Cardiothoracic and Vascular Anesthesia, Vol. 25, No. 3, 01.06.2011, p. 425-430.

Research output: Contribution to journalArticle

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abstract = "Objectives: The objective of this study was to determine the pharmacokinetics of cefuroxime in children undergoing cardiopulmonary bypass (CPB) for cardiovascular surgery. Design: A prospective study. Setting: A tertiary pediatric teaching hospital. Participants: Infants and children undergoing CPB were enrolled in the study. Intervention: An initial dose (mean, 24.2 ± 1.6 mg/kg) of cefuroxime was administered before surgical incision, and a second dose (mean, 14.4 ± 7.9 mg/kg) was administered in the CPB prime solution. Serial blood samples were obtained before, during, and after the CPB process. Samples were shipped on dry ice to the analytic laboratory and concentrations determined by a validated high-performance liquid chromatography method. A 2-compartment pharmacokinetic model was fitted to the data using maximum a priori-Bayesian estimation, with weight as a covariate. Monte Carlo simulations of a single-dose (25 mg/kg pre-CPB) approach and a 2-dose (25 mg/kg pre- and 12.5-mg/kg prime solution dose) approach were performed. Measurements and Main Results: Fifteen subjects (9 males/6 females) were enrolled in the study, with median (range) age and weight of 11 (3-34) months and 9.5 (4.5-15.4) kg, respectively. The median (range) duration of CPB was 136 (71-243) minutes. Median and range cefuroxime pharmacokinetic parameters were as follows: maximum concentration (Cmax) dose, 1: 328 (150-512) μg/mL; systemic clearance, 0.050 (0.041-0.058) L/h/kg; steady-state volume of distribution, 0.213 (0.081-0.423) L/kg; volume of distribution in the central compartment, 0.081 (0.046-0.162) L/kg; and elimination half-life, 3.76 (1.03-6.81) hours. The median 8-hour post-dose-simulated cefuroxime concentrations were 26.5 and 16.0 mg/L for the 2-dose and single-dose regimens, respectively. Conclusion: Manufacturers recommend that pediatric doses of cefuroxime (25-50 mg/kg) can be used in infants and children undergoing CPB to maintain adequate serum concentrations for surgical-site infection prophylaxis. A second intraoperative dose, administered through the CPB circuit, provides no additional prophylactic advantage.",
keywords = "cardiopulmonary bypass, cefuroxime, chromatography, liquid, pediatric, pharmacokinetics",
author = "Knoderer, {Chad A.} and Saft, {Sarah A.} and Walker, {Scott G.} and Rodefeld, {Mark D.} and Turrentine, {Mark W.} and Brown, {John W.} and Healy, {Daniel P.} and Sowinski, {Kevin M.}",
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AU - Saft, Sarah A.

AU - Walker, Scott G.

AU - Rodefeld, Mark D.

AU - Turrentine, Mark W.

AU - Brown, John W.

AU - Healy, Daniel P.

AU - Sowinski, Kevin M.

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AB - Objectives: The objective of this study was to determine the pharmacokinetics of cefuroxime in children undergoing cardiopulmonary bypass (CPB) for cardiovascular surgery. Design: A prospective study. Setting: A tertiary pediatric teaching hospital. Participants: Infants and children undergoing CPB were enrolled in the study. Intervention: An initial dose (mean, 24.2 ± 1.6 mg/kg) of cefuroxime was administered before surgical incision, and a second dose (mean, 14.4 ± 7.9 mg/kg) was administered in the CPB prime solution. Serial blood samples were obtained before, during, and after the CPB process. Samples were shipped on dry ice to the analytic laboratory and concentrations determined by a validated high-performance liquid chromatography method. A 2-compartment pharmacokinetic model was fitted to the data using maximum a priori-Bayesian estimation, with weight as a covariate. Monte Carlo simulations of a single-dose (25 mg/kg pre-CPB) approach and a 2-dose (25 mg/kg pre- and 12.5-mg/kg prime solution dose) approach were performed. Measurements and Main Results: Fifteen subjects (9 males/6 females) were enrolled in the study, with median (range) age and weight of 11 (3-34) months and 9.5 (4.5-15.4) kg, respectively. The median (range) duration of CPB was 136 (71-243) minutes. Median and range cefuroxime pharmacokinetic parameters were as follows: maximum concentration (Cmax) dose, 1: 328 (150-512) μg/mL; systemic clearance, 0.050 (0.041-0.058) L/h/kg; steady-state volume of distribution, 0.213 (0.081-0.423) L/kg; volume of distribution in the central compartment, 0.081 (0.046-0.162) L/kg; and elimination half-life, 3.76 (1.03-6.81) hours. The median 8-hour post-dose-simulated cefuroxime concentrations were 26.5 and 16.0 mg/L for the 2-dose and single-dose regimens, respectively. Conclusion: Manufacturers recommend that pediatric doses of cefuroxime (25-50 mg/kg) can be used in infants and children undergoing CPB to maintain adequate serum concentrations for surgical-site infection prophylaxis. A second intraoperative dose, administered through the CPB circuit, provides no additional prophylactic advantage.

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KW - cefuroxime

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KW - pharmacokinetics

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