Variability of plasma aprotinin concentrations in pediatric patients undergoing cardiac surgery

William C. Oliver, David N. Fass, Gregory A. Nuttall, Joseph A. Dearani, Lisa M. Schrader, Darrell R. Schroeder, Mark H. Ereth, Francisco J. Puga

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objectives: Infants and children undergoing cardiopulmonary bypass for repair of congenital heart defects are at substantial risk for excessive bleeding, contributing greatly to morbidity and mortality. Aprotinin significantly reduces bleeding and transfusion requirements in adults but is of indeterminate value for pediatric patients. The aim of this study was to determine plasma aprotinin concentrations in these patients with a functional aprotinin assay. Methods: Thirty patients less than 16 years of age scheduled for cardiac surgery with aprotinin were enrolled. Aprotinin was administered as a 25,000 KIU/kg bolus, 35,000 KIU/kg cardiopulmonary bypass prime, and 12,500 KIU · kg-1 · h-1 continuous infusion. Blood samples for aprotinin concentrations (kallikrein-inhibiting units/milliliter) were obtained before aprotinin; 5 minutes post-bolus; 5 minutes after cardiopulmonary bypass initiation; 30 and 60 minutes on cardiopulmonary bypass; on discontinuation of aprotinin; 1 hour after aprotinin discontinuation; and 4 hours after permanent separation from cardiopulmonary bypass. For analysis, patients were grouped according to weight (< 10 kg, 10-20 kg, >20 kg). Differences between weight groups were assessed using an exact test for categoric variables and 1-way analysis of variance for continuous variables. Results: Aprotinin concentrations differed significantly across weight groups. Five minutes after aprotinin bolus and initiation of cardiopulmonary bypass, there was significant correlation between weight and aprotinin concentration (r = .57, P = .003; r = .69, P = .001, respectively). Conclusion: A functional assay reveals significant variability in aprotinin concentration for pediatric patients using current weight-based aprotinin dosing. Additional investigation is necessary to determine target aprotinin concentration dosing regimens to provide better efficacy.

Original languageEnglish (US)
Pages (from-to)1670-1677
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume127
Issue number6
DOIs
StatePublished - Jun 2004

Fingerprint

Aprotinin
Thoracic Surgery
Pediatrics
Cardiopulmonary Bypass
Weights and Measures
Hemorrhage
Kallikreins
Congenital Heart Defects

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Oliver, W. C., Fass, D. N., Nuttall, G. A., Dearani, J. A., Schrader, L. M., Schroeder, D. R., ... Puga, F. J. (2004). Variability of plasma aprotinin concentrations in pediatric patients undergoing cardiac surgery. Journal of Thoracic and Cardiovascular Surgery, 127(6), 1670-1677. https://doi.org/10.1016/j.jtcvs.2003.10.029

Variability of plasma aprotinin concentrations in pediatric patients undergoing cardiac surgery. / Oliver, William C.; Fass, David N.; Nuttall, Gregory A.; Dearani, Joseph A.; Schrader, Lisa M.; Schroeder, Darrell R.; Ereth, Mark H.; Puga, Francisco J.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 127, No. 6, 06.2004, p. 1670-1677.

Research output: Contribution to journalArticle

Oliver, WC, Fass, DN, Nuttall, GA, Dearani, JA, Schrader, LM, Schroeder, DR, Ereth, MH & Puga, FJ 2004, 'Variability of plasma aprotinin concentrations in pediatric patients undergoing cardiac surgery', Journal of Thoracic and Cardiovascular Surgery, vol. 127, no. 6, pp. 1670-1677. https://doi.org/10.1016/j.jtcvs.2003.10.029
Oliver, William C. ; Fass, David N. ; Nuttall, Gregory A. ; Dearani, Joseph A. ; Schrader, Lisa M. ; Schroeder, Darrell R. ; Ereth, Mark H. ; Puga, Francisco J. / Variability of plasma aprotinin concentrations in pediatric patients undergoing cardiac surgery. In: Journal of Thoracic and Cardiovascular Surgery. 2004 ; Vol. 127, No. 6. pp. 1670-1677.
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AU - Oliver, William C.

AU - Fass, David N.

AU - Nuttall, Gregory A.

AU - Dearani, Joseph A.

AU - Schrader, Lisa M.

AU - Schroeder, Darrell R.

AU - Ereth, Mark H.

AU - Puga, Francisco J.

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N2 - Objectives: Infants and children undergoing cardiopulmonary bypass for repair of congenital heart defects are at substantial risk for excessive bleeding, contributing greatly to morbidity and mortality. Aprotinin significantly reduces bleeding and transfusion requirements in adults but is of indeterminate value for pediatric patients. The aim of this study was to determine plasma aprotinin concentrations in these patients with a functional aprotinin assay. Methods: Thirty patients less than 16 years of age scheduled for cardiac surgery with aprotinin were enrolled. Aprotinin was administered as a 25,000 KIU/kg bolus, 35,000 KIU/kg cardiopulmonary bypass prime, and 12,500 KIU · kg-1 · h-1 continuous infusion. Blood samples for aprotinin concentrations (kallikrein-inhibiting units/milliliter) were obtained before aprotinin; 5 minutes post-bolus; 5 minutes after cardiopulmonary bypass initiation; 30 and 60 minutes on cardiopulmonary bypass; on discontinuation of aprotinin; 1 hour after aprotinin discontinuation; and 4 hours after permanent separation from cardiopulmonary bypass. For analysis, patients were grouped according to weight (< 10 kg, 10-20 kg, >20 kg). Differences between weight groups were assessed using an exact test for categoric variables and 1-way analysis of variance for continuous variables. Results: Aprotinin concentrations differed significantly across weight groups. Five minutes after aprotinin bolus and initiation of cardiopulmonary bypass, there was significant correlation between weight and aprotinin concentration (r = .57, P = .003; r = .69, P = .001, respectively). Conclusion: A functional assay reveals significant variability in aprotinin concentration for pediatric patients using current weight-based aprotinin dosing. Additional investigation is necessary to determine target aprotinin concentration dosing regimens to provide better efficacy.

AB - Objectives: Infants and children undergoing cardiopulmonary bypass for repair of congenital heart defects are at substantial risk for excessive bleeding, contributing greatly to morbidity and mortality. Aprotinin significantly reduces bleeding and transfusion requirements in adults but is of indeterminate value for pediatric patients. The aim of this study was to determine plasma aprotinin concentrations in these patients with a functional aprotinin assay. Methods: Thirty patients less than 16 years of age scheduled for cardiac surgery with aprotinin were enrolled. Aprotinin was administered as a 25,000 KIU/kg bolus, 35,000 KIU/kg cardiopulmonary bypass prime, and 12,500 KIU · kg-1 · h-1 continuous infusion. Blood samples for aprotinin concentrations (kallikrein-inhibiting units/milliliter) were obtained before aprotinin; 5 minutes post-bolus; 5 minutes after cardiopulmonary bypass initiation; 30 and 60 minutes on cardiopulmonary bypass; on discontinuation of aprotinin; 1 hour after aprotinin discontinuation; and 4 hours after permanent separation from cardiopulmonary bypass. For analysis, patients were grouped according to weight (< 10 kg, 10-20 kg, >20 kg). Differences between weight groups were assessed using an exact test for categoric variables and 1-way analysis of variance for continuous variables. Results: Aprotinin concentrations differed significantly across weight groups. Five minutes after aprotinin bolus and initiation of cardiopulmonary bypass, there was significant correlation between weight and aprotinin concentration (r = .57, P = .003; r = .69, P = .001, respectively). Conclusion: A functional assay reveals significant variability in aprotinin concentration for pediatric patients using current weight-based aprotinin dosing. Additional investigation is necessary to determine target aprotinin concentration dosing regimens to provide better efficacy.

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