Related Experiment Videos
Age-related differences in heparin sensitivity and heparin-protamine interactions in cardiac surgery patients
C D'Errico1, J R Shayevitz, S J Martindale
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, USA.
Insights
Children and adults exhibit varying sensitivity to heparin during cardiopulmonary bypass (CPB). Younger children require higher heparin doses, while adults need a greater protamine-to-heparin ratio for effective anticoagulation management.
Area of Science:
- Cardiovascular Surgery
- Anesthesiology
- Pharmacology
Background:
- Heparin and protamine are critical for anticoagulation and reversal during cardiopulmonary bypass (CPB).
- Understanding age-related differences in heparin sensitivity and protamine interactions is crucial for optimizing patient safety during cardiac surgery.
Purpose of the Study:
- To investigate age-specific differences in heparin sensitivity and heparin-protamine interactions in pediatric and adult patients undergoing cardiac surgery with CPB.
- To inform optimal dosing strategies for heparin and protamine in diverse age groups.
Main Methods:
- Prospective study involving 90 patients (2 months to 72 years) undergoing cardiac or aortic arch surgery with CPB.
- Utilized the Medtronic Hemotec Hepcon Hemostasis Management System to generate ex vivo heparin dose-response curves and perform heparin-protamine titrations.
- Determined target heparin concentration (THC) for an activated coagulation time (ACT) of ≥480 seconds and calculated protamine-to-heparin ratios.
Main Results:
- Preschool children (1-5 years) required higher initial heparin doses (477 ± 159 U/kg) compared to school-age children (327 ± 57 U/kg) and adults (332 ± 64 U/kg).
- Infants (<1 year) showed the lowest target heparin concentration (3.3 ± 0.7), while preschool children had the highest (4.0 ± 1.1).
- Adults and school-age children exhibited significantly higher protamine-to-heparin ratios (1.4 ± 0.5 and 1.3 ± 0.6, respectively) than younger children.
Conclusions:
- Preschool children demonstrate reduced sensitivity to heparin and a wider range of response.
- Current recommendations support 300 U/kg heparin for patients ≥5 years undergoing CPB.
- Younger pediatric patients may require up to 500 U/kg of heparin to achieve adequate anticoagulation, necessitating individualized dosing adjustments.
Objective:
The present study was conducted to determine how children and adults differ (it at all) with respect to sensitivity to heparin activity and heparin-protamine interactions during cardiac surgery requiring cardiopulmonary bypass (CPB).
Design:
A prospective study of both children and adults undergoing CPB.
Setting:
A tertiary care academic medical center between July 1992 and October 1994.
Participants:
Ninety patients who had cardiac or aortic arch surgery using CPB. The median age of the entire study sample was 15.8 years (range 2 months to 72 years).
Intervention:
Data were obtained using the Medtronic Hemotec Hepcon Hemostasis Management System (Englewood, CO). An ex vivo heparin dose-response (HDR) curve was generated for each patient before skin incision to determine the target heparin concentration (THC) needed to achieve an activated coagulation time (ACT) of at least 480 seconds. Protamine dose was determined on the basis of whole blood heparin concentration estimated by means of a heparin-protamine titration.
Measurements And Main Results:
The study population was divided into four groups based on age: infants (< 1 year), preschool (1 to 5 years), school-age (5 to 14 years) and adults (> 14 years). The mean +/- SD THC for the preschool group was 4.0 +/- 1.1; for infants, 3.3 +/- 0.7; for school-age, 3.1 +/- 0.7; and for adults, 3.4 +/- 0.7. The initial dose of heparin needed to achieve this THC (mean +/- SD) was significantly higher in infants (578 +/- 220 U/kg) and preschool children (477 +/- 159 U/kg) than in school-age children (327 +/- 57 U/kg) and adults (332 +/- 64 U/kg). The ratio of protamine to heparin was significantly higher in adults (1.4 +/- 0.5) and school-age children (1.3 +/- 0.6) than in infants (1.1 +/- 0.7) and preschool children (1.1 +/- 0.4).
Conclusions:
Pre-school children are less sensitive to heparin but also display a wider range of sensitivity. The data in this study support the use of 300 U/kg of heparin before CPB in patients > or = 5 years but suggest that heparin requirements may be greater in the younger patient who may require as much as 500 U/kg to achieve what is believed to be an appropriate target heparin concentration for initiating CPB.