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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.

Background Children with congenital heart defects (CHD) have quantitative and qualitative differences in coagulation compared with healthy children. Secondary to polycythemia and increased deformability of red blood cells, cyanosis may be an important confounding factor for altered whole-blood coagulation in this population with potential implications for interpreting intraoperative thromboelastometry (TEM) for children with CHD undergoing major surgery. The primary aim of the study was to evaluate the association between cyanosis in children with CHD and measures of whole-blood coagulation determined using TEM (ROTEM [Tem International, GmbH, Munich, Germany]). Methods In this retrospective cohort study, children who underwent congenital cardiac surgery in a 12-month period between April 2014 and 2015 were investigated. Children who were receiving antiplatelet or anticoagulant medications in the preoperative period were excluded. Eligible children were categorized by the presence of cyanosis, defined as an oxyhemoglobin concentration ≤85%. Multivariable linear regression analyses were used to determine the relationship between cyanosis and TEM outcomes (primary outcome, fibrinogen/fibrin polymerization [FibTEM] maximal clot firmness [MCF]) adjusting for potential confounding factors. Results Three hundred forty-five TEM profiles from 320 children were included in the cohort for analysis. Twenty-two percent (76/345) of children had cyanotic CHD. Clot firmness measured using the FibTEM assay was decreased in cyanotic children compared with noncyanotic children, median difference (95% confidence interval) interim [2 (0-3) mm; P = .01], and maximal [2 (1-3) mm; P = .01] clot firmness. The association between cyanosis and fibrinogen/fibrin polymerization clot firmness was not significant (A10, P = .7; MCF, P = .7) after adjusting for confounding factors (hematocrit, platelet count, and sex). There was a significant association between cyanosis and intrinsically activated clot firmness (A10, P = .03; MCF, P = .02), but not other TEM outcomes, after adjusting for confounding factors. Conclusions Cyanotic children had decreased clot firmness in the fibrinogen/fibrin polymerization component of the clot compared with noncyanotic children, but the association between cyanosis and clot firmness was accounted for by differences in hematocrit, platelet count, and sex between groups. These findings will help guide the identification and treatment of coagulopathy in this vulnerable population.

The negative effects of long-term storage of allogeneic red blood cells (RBCs) on outcomes in adult cardiac surgery have been established, but evidence of a similar effect in pediatric cardiac surgery is limited.The weighted average duration of storage for RBC units used in 1,225 pediatric cardiac operations was determined. Operations were divided into high RBC use (more than 4 units or more than 150 mL/kg) or low RBC use. For both categories, associations between storage duration and surgical outcomes, adjusted for relevant patient characteristics, were evaluated.High RBC use was associated with higher surgical complexity. Storage duration for patients who received low RBC volumes was not associated with surgical outcomes. For patients with high RBC transfusion volumes, longer storage duration (per day) was associated with higher odds of bleeding complications (odds ratio 1.029, p=0.07), renal insufficiency (odds ratio 1.085, p=0.001), higher inotrope score after surgery (12 to 24 hours +0.08, p=0.002; 24 to 48 hours +0.07, p0.001), greater chest tube drainage (24 hours +1.5 mL/kg, p0.001), longer postoperative hospitalization (+0.3 days p=0.02), and increased in-hospital mortality (odds ratio 1.054, p=0.03). Effects of RBC transfusions on postoperative bleeding were greatest for storage duration longer than 14 days.The freshest RBC units available should be used for pediatric cardiac operations expected to require more than 4 units or more than 150 mL/kg of allogeneic RBC transfusions, with no units more than 14 days old being transfused whenever possible.

We sought to determine whether the use of specific unfractionated heparin brands during cardiopulmonary bypass for pediatric cardiac surgery was associated with differences in postoperative outcomes, especially regarding the incidence of bleeding and thromboembolic complications.We compared postoperative outcomes for pediatric cardiac surgeries performed with Hepalean (Organon Teknika) to those performed with PPC heparin (Pharmaceutical Partners of Canada). Differences in clinical outcomes were determined in multivariable logistic and linear regression models adjusted for patients and surgery characteristics.In all, 903 operations were reviewed, 289 (32%) using Hepalean and 614 (68%) using PPC heparin. Patient demographics and surgical variables were comparable between groups. In multivariable regression models, adjusted for patients' characteristics, heparin use and choice of antifibrinolytic agents, the use of PPC heparin was associated with greater use of red blood cell transfusions in the first 48 postoperative hours (estimates +1.6 mL/kg, p0.001), increased odds of bleeding complications (odds ratio 3.8, p=0.04), thromboembolic complications (odds ratio 4.7, p=0.01), early unplanned reoperation (odds ratio 6.9, p=0.03), longer postoperative intensive care unit stay (estimate +3.2 days, p0.001), and longer hospital stay (estimate +3.6 days, p0.001).Brand of unfractionated heparin used during cardiopulmonary bypass for pediatric cardiac surgery was associated with bleeding complications and clinical outcomes. Different brands of unfractionated heparin should not be considered equivalent without proper validation in formal trials.

Objective This study compared the effects of reconstituted fresh whole blood against standard blood component therapy in neonates undergoing cardiac surgery. Methods Patients less than 1 month of age were randomized to receive either reconstituted fresh whole blood (n = 31) or standard blood component therapy (n = 33) to prime the bypass circuit and for transfusion during the 24 hours after cardiopulmonary bypass. Primary outcome was chest tube drainage; secondary outcomes included transfusion needs, inotrope score, ventilation time, and hospital length of stay. Results Patients who received reconstituted fresh whole blood had significantly less postoperative chest tube volume loss per kilogram of body weight (7.7 mL/kg vs 11.8 mL/kg; P = .03). Standard blood component therapy was associated with higher inotropic score (6.6 vs 3.3; P = .002), longer ventilation times (164 hours vs 119 hours; P = .04), as well as longer hospital stays (18 days vs 12 days; P = .006) than patients receiving reconstituted fresh whole blood. Of the different factors associated with the use of reconstituted fresh whole blood, lower platelet counts at 10 minutes and at the end of cardiopulmonary bypass, older age of cells used in the prime and throughout bypass, and exposures to higher number of allogeneic donors were found to be independent predictors of poor clinical outcomes. Conclusions Reconstituted fresh whole blood used for the prime, throughout cardiopulmonary bypass, and for all transfusion requirements within the first 24 hours postoperatively results in reduced chest tube volume loss and improved clinical outcomes in neonatal patients undergoing cardiac surgery.

ObjectivesWe sought to determine whether infants (younger than 1 year old) had similar clinical benefits with individualized anticoagulation management as older children and adult undergoing cardiopulmonary bypass (CPB).BackgroundIndividualized heparin and protamine management in older children and adults undergoing CPB has been associated with improved clinical outcomes.MethodsNinety infants younger than 1 year of age undergoing CPB were enrolled in a randomized, controlled trial comparing weight-based anticoagulation management using activated clotting time (ACT) to individualized management with Hemostasis Management System Plus. Manufacturer's guidelines were followed for the first 33 patients. A modified protocol was used for the last 57 patients with adjustments for coagulation system immaturity and hemodilution on CPB.ResultsThe hemostasis management system (HMS) device consistently underestimated plasma anti-Xa levels, leading to an overestimated required heparin dose. After a blinded interim analysis revealed poor outcomes in the experimental HMS group using manufacturer guidelines, the safety committee suspended the study pending protocol modifications. The use of the HMS device following the modified protocol resulted in more stable anti-Xa levels during CPB with improved post-operative outcomes including reduced need for transfusions (71 ml/kg vs. 80 ml/kg; p = 0.003), ventilation time (33 h vs. 49 h; p = 0.04), intensive care (88 h vs. 99 h; p = 0.003), and hospital length of stay (192 h vs. 216 h; p < 0.001), compared with the weight-based protocol.ConclusionsThis study supports the use of the HMS device, with a modified protocol for infants younger than 1 year of age, for anticoagulation management during CPB. Clinical guidelines for the use of the HMS device should be modified for infants younger than 1 year of age.