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Predicting Heparin Responsiveness in Children Before Cardiopulmonary Bypass: A Retrospective Cohort Study
Sayaka Nakamura1, Osami Honjo2, Lynn Crawford-Lean3
1From the Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Insights
Heparin responsiveness in children undergoing cardiopulmonary bypass (CPB) is difficult to predict. This study found that neither the Hemostasis Management System (HMS) Plus nor preoperative data reliably predicted heparin sensitivity index (HSI).
Area of Science:
- Pediatric Anesthesiology
- Cardiovascular Surgery
- Pharmacokinetics and Pharmacodynamics
Background:
- Unfractionated heparin dosing for cardiopulmonary bypass (CPB) requires careful management due to potential harm from inadequate or excess administration.
- Children exhibit age-dependent variations in heparin pharmacodynamics and pharmacokinetics, leading to unpredictable responses.
- Accurate heparin management is critical for patient safety during pediatric CPB procedures.
Purpose of the Study:
- To assess the correlation between predicted and observed heparin responsiveness in children before CPB using the Hemostasis Management System (HMS) Plus.
- To establish age-specific reference intervals for the heparin sensitivity index (HSI) in pediatric patients.
- To evaluate predictive models for HSI using preoperative clinical and laboratory data.
Main Methods:
- A retrospective cohort study included 1281 children (≤17 years) undergoing CPB, excluding those weighing ≥45 kg or height ≥142 cm.
- Heparin sensitivity index (HSI) was calculated as the difference in activated clotting time (ACT) post-heparinization and baseline, divided by heparin dose.
- Lin's concordance correlation coefficient and nonparametric regression analyses were employed to assess relationships between HSI and predictive factors.
Main Results:
- A moderate correlation (rho_c = 0.46) was observed between predicted and observed HSI using the HMS Plus system.
- Sixty-five percent of predicted HSI values were lower than observed values.
- Preoperative international normalized ratio, platelet count, and weight were the best predictors of HSI, but explained only 25% of the variance.
Conclusions:
- Heparin responsiveness in children before CPB cannot be reliably predicted by the HMS Plus system or standard preoperative data.
- Age-specific reference intervals for HSI are provided, which may assist in identifying heparin resistance.
- Further research is needed to improve the prediction of heparin requirements in pediatric CPB.
Background:
Inadequate or excess administration of unfractionated heparin for cardiopulmonary bypass (CPB) can cause significant harm. Age-dependent differences in the pharmacodynamics and pharmacokinetics of heparin contribute to increased variability of heparin responsiveness in children. The aims of the current study were to (1) examine the correlation between predicted and observed heparin responsiveness in children before CPB measured using the Hemostasis Management System (HMS) Plus (Medtronic, Minneapolis, MN), (2) describe age-specific reference intervals for heparin sensitivity index (HSI) observed in children, and (3) test predictive models of HSI using preoperative clinical and laboratory data.
Methods:
In this retrospective cohort study, children (ages ≤17 years) who required therapeutic heparinization for CPB in a 40-month period between September 2010 and December 2013 were investigated. Children weighing ≥45 kg or with a height ≥142 cm were excluded. HSI was defined as the difference between activated clotting time after heparin administration and the baseline activated clotting time divided by the heparin-loading dose (IU) per kilogram. Lin's concordance correlation coefficient was used for the primary analysis of the relationship between predicted and observed HSI. Reference intervals were calculated for HSI using medians and 2.5% and 97.5% percentiles according to established guidelines for clinical and laboratory standards. Nonparametric regression analyses were used to model the relationship between HSI (dependent variable) and preoperative covariates (independent variables).
Results:
A total of 1281 eligible children were included in the final analysis. Overall, there was a moderate correlation between predicted and observed HSI measured using HMS Plus System (rho_c = 0.46; 95% confidence interval, 0.41-0.50; P < .001). Sixty-five percent (829 of 1281) of predicted HSI values were less than observed. From adjusted regression models, HSI was best predicted by preoperative international normalized ratio, platelet count, and weight, but this model accounted for only 25% of the variance in HSI.
Conclusions:
In a large cohort of children, heparin responsiveness before CPB was not reliably predicted by either in vitro measurement using the HMS Plus System or commonly available preoperative clinical and laboratory data. We describe age-specific reference intervals for HSI in children, and we anticipate that these data will aid the identification of heparin resistance in this population.
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