Cefuroxime Pharmacokinetics in Pediatric Cardiovascular Surgery Patients Undergoing Cardiopulmonary Bypass

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

doi:10.1053/j.jvca.2010.07.022

Cefuroxime Pharmacokinetics in Pediatric Cardiovascular Surgery Patients Undergoing Cardiopulmonary Bypass

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

Research output: Contribution to journal › Article › peer-review

Abstract

<p> <h4 id="x-x-x-absSec_1"> Objectives </h4> <p id="x-x-x-sp0040"> The objective of this study was to determine the pharmacokinetics of cefuroxime in children undergoing cardiopulmonary bypass (CPB) for cardiovascular surgery. <h4 id="x-x-x-absSec_2"> Design </h4> <p id="x-x-x-sp0045"> A prospective study. <h4 id="x-x-x-absSec_3"> Setting </h4> <p id="x-x-x-sp0050"> A tertiary pediatric teaching hospital. <h4 id="x-x-x-absSec_4"> Participants </h4> <p id="x-x-x-sp0055"> Infants and children undergoing CPB were enrolled in the study. <h4 id="x-x-x-absSec_5"> Intervention </h4> <p id="x-x-x-sp0060"> 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. <h4 id="x-x-x-absSec_6"> Measurements and Main Results </h4> <p id="x-x-x-sp0065"> 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. <h4 id="x-x-x-absSec_7"> Conclusion </h4> <p id="x-x-x-sp0070"> 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. </p> </p> </p> </p> </p> </p> </p></p>

Original language	American English
Journal	Scholarship and Professional Work – COPHS
Volume	25
Issue number	3
DOIs	https://doi.org/10.1053/j.jvca.2010.07.022
State	Published - Jan 1 2011

Keywords

cardiopulmonary bypass
cefuroxime
chromatography
liquid
pediatric
pharmacokinetics

Disciplines

Cardiology
Pediatrics
Pharmacy and Pharmaceutical Sciences

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Cefuroxime Pharmacokinetics in Pediatric Cardiovascular Surgery PFinal published version, 625 KBLicense: Unspecified

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@article{7236af0c4ae740bb967d7565e8db1d56,

title = "Cefuroxime Pharmacokinetics in Pediatric Cardiovascular Surgery Patients Undergoing Cardiopulmonary Bypass",

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, \{Markl D.\} and Turrentine, \{Mark W.\} and Brown, \{John W.\} and Healy, \{Daniel P.\} and Sowinski, \{Kevin M.\}",

year = "2011",

month = jan,

day = "1",

doi = "10.1053/j.jvca.2010.07.022",

language = "American English",

volume = "25",

journal = "Scholarship and Professional Work – COPHS",

number = "3",

}

TY - JOUR

T1 - Cefuroxime Pharmacokinetics in Pediatric Cardiovascular Surgery Patients Undergoing Cardiopulmonary Bypass

AU - Knoderer, Chad A.

AU - Saft, Sarah A.

AU - Walker, Scott G.

AU - Rodefeld, Markl D.

AU - Turrentine, Mark W.

AU - Brown, John W.

AU - Healy, Daniel P.

AU - Sowinski, Kevin M.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - 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.

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.

KW - cardiopulmonary bypass

KW - cefuroxime

KW - chromatography

KW - liquid

KW - pediatric

KW - pharmacokinetics

UR - https://digitalcommons.butler.edu/cophs_papers/53

U2 - 10.1053/j.jvca.2010.07.022

DO - 10.1053/j.jvca.2010.07.022

M3 - Article

VL - 25

JO - Scholarship and Professional Work – COPHS

JF - Scholarship and Professional Work – COPHS

IS - 3

ER -

Cefuroxime Pharmacokinetics in Pediatric Cardiovascular Surgery Patients Undergoing Cardiopulmonary Bypass

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