Effect of red blood cell storage time in pediatric cardiac surgery patients: A subgroup analysis of a randomized controlled trial.

Objective: This study aimed to determine whether or not transfusion of fresh red blood cells (RBCs) reduced the incidence of new or progressive multiple organ dysfunction syndrome compared with standard-issue RBCs in pediatric patients undergoing cardiac surgery. Methods: Preplanned secondary analysis of the Age of Blood in Children in Pediatric Intensive Care Unit study, an international randomized controlled trial. This study included children enrolled in the Age of Blood in Children in Pediatric Intensive Care Unit trial and admitted to a pediatric intensive care unit after cardiac surgery with cardiopulmonary bypass. Patients were randomized to receive either fresh (stored ≤7 days) or standard-issue RBCs. The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured up to 28 days postrandomization or at pediatric intensive care unit discharge, or death. Results: One hundred seventy-eight patients (median age, 0.6 years; interquartile range, 0.3-2.6 years) were included with 89 patients randomized to the fresh RBCs group (median length of storage, 5 days; interquartile range, 4-6 days) and 89 to the standard-issue RBCs group (median length of storage, 18 days; interquartile range, 13-22 days). There were no statistically significant differences in new or progressive multiple organ dysfunction syndrome between fresh (43 out of 89 [48.3%]) and standard-issue RBCs groups (38 out of 88 [43.2%]), with a relative risk of 1.12 (95% CI, 0.81 to 1.54; P = .49) and an unadjusted absolute risk difference of 5.1% (95% CI, -9.5% to 19.8%; P = .49). Conclusions: In neonates and children undergoing cardiac surgery with cardiopulmonary bypass, the use of fresh RBCs did not reduce the incidence of new or progressive multiple organ dysfunction syndrome compared with the standard-issue RBCs. A larger trial is needed to confirm these results.

The choice of perioperative inotropic support impacts the outcome of small infants undergoing complex cardiac surgery: an observational study.

BACKGROUND: Vaso-inotropic agents are frequently used to prevent and/or treat low cardiac output syndrome in infants undergoing surgery for congenital heart disease. Due to the lack of comparative studies, their use is largely dependent on physician- and center preferences. The aim was to assess the impact of two different inotropic regimens, milrinone-epinephrine versus dobutamine on postoperative morbi-mortality in young children undergoing complex cardiac surgery. METHODS: All consecutive children younger than one year of age admitted for complex cardiac surgery (Risk Adjustment in Congenital Heart Surgery-1 [RACHS-1] score ≥3) with cardiopulmonary bypass (CPB) from January 2008 to December 2018 were included. Children received either milrinone in association with low dose epinephrine (milrinone-epinephrine group) or dobutamine (dobutamine group) groups were matched and compared using a propensity score. Our primary outcome was a composite measure including either hospital death and/or the presence of at least two of the following events: respiratory failure, prolonged inotropic support, or renal failure. RESULTS: Two hundred and fifty patients were included in the analysis. Children in the milrinone-epinephrine group (N.=184) suffered more frequently from a cyanotic heart disease and had longer surgery, CPB, and aortic cross clamp times than those in the dobutamine group (N.=66). After matching, children in the milrinone-epinephrine group had a higher incidence of severe postoperative morbidity or mortality compared to those in the dobutamine group (27.4 versus 13.9%; P=0.016). Respiratory failure (28% vs. 12%), prolonged inotropic support (71% vs. 35%) and in-hospital death (3 vs. 0%) were more frequent in the milrinone-epinephrine group. CONCLUSIONS: In young infants undergoing complex cardiac surgery, milrinone combined with epinephrine is associated with a higher incidence of postoperative morbidity or mortality compared to dobutamine for perioperative inotropic support. Further prospective randomized studies are required to confirm this finding.

Fluid Overload in Pediatric Univentricular Patients Undergoing Fontan Completion.

BACKGROUND: Fluid overload (FO) is known to occur frequently after pediatric cardiac surgery and is associated with morbidity and mortality. Fontan patients are at risk to develop FO due to their critical fluid balance. Furthermore, they need an adequate preload in order to maintain adequate cardiac output. This study aimed to identify FO in patients undergoing Fontan completion and the impact of FO on pediatric intensive care unit (PICU) length of stay (LOS) and cardiac events, defined as death, cardiac re-surgery or PICU re-hospitalization during follow-up. METHODS: In this retrospective single center study, the presence of FO was assessed in 43 consecutive children undergoing Fontan completion. RESULTS: Patients with more than 5% maximum FO had an extended PICU LOS (3.9 [2.9-6.9] vs. 1.9 [1.0-2.6] days; p < 0.001) and an increased length of mechanical ventilation (21 [9-121] vs. 6 [5-10] h; p = 0.001). Regression analysis demonstrated that an increase of 1% maximum FO was associated with a prolonged PICU LOS of 13% (95% CI 1.042-1.227; p = 0.004). Furthermore, patients with FO were at higher risk to develop cardiac events. CONCLUSIONS: FO is associated with short-term and long-term complications. Further studies are needed to determine the impact of FO on the outcome in this specific population.

Does a balanced colloid decrease perioperative blood loss in paediatric cardiac surgery: A double-blinded randomized controlled trial?

BACKGROUND: Unbalanced fluid solutions cause metabolic acidosis and could be associated with impaired coagulation and increased blood loss. OBJECTIVE: To investigate whether the use of a balanced colloid compared with a saline colloid for peri-operative fluid therapy in children undergoing cardiac surgery is associated with decreased blood loss and exposure to blood products. DESIGN: Double-blinded randomised controlled trial. SETTING: Tertiary children's hospital from 2013 to 2016. PATIENTS: Children older than 29 days and younger than 3 years admitted for cardiac surgery with cardiopulmonary bypass (CPB). Exclusion criteria were emergency cardiac surgery, moribund (American Society of Anesthesiologists 5), Jehovah's witnesses, coagulopathy, renal failure, liver injury, intracranial haemorrhage and electrolyte disturbances. From the 128 patients eligible, 88 were included in the study. INTERVENTION: Random assignment of patients to either a saline colloid (6% hydroxyethyl starch 130/0.4 in 0.9% NaCl) or a balanced-electrolyte colloid (6% hydroxyethyl starch 130/0.4 in an isotonic solution) for CPB priming and intra- and postoperative fluid therapy during the first postoperative 48 h. MAIN OUTCOME MEASURE: The primary outcome measure was calculated blood loss until the third postoperative day (POD3). RESULTS: A total of 44 patients were included in each study arm. Calculated blood loss at POD3 was not significantly different between the groups (saline colloid 19.9 [IQR 13.8 to 26.1] ml kg-1 versus balanced colloid 15.9 [IQR 9.0 to 25.3 ml kg-1], P = 0.409). Secondary outcomes related to bleeding, exposure to blood products and coagulation were not different between groups. There was also no difference in length of mechanical ventilation, intensive care and hospital length of stay between groups. CONCLUSION: The use of a balanced colloid for peri-operative fluid therapy compared with a saline one is not associated with decreased blood loss or exposure to blood products. TRIAL REGISTRATION: EudraCT identifier: 2012-006034-17 and ClinicalTrial.gov identifier: NCT02584868.

How 217 Pediatric Intensivists Manage Anemia at PICU Discharge: Online Responses to an International Survey.

OBJECTIVE: To describe the management of anemia at PICU discharge by pediatric intensivists. DESIGN: Self-administered, online, scenario-based survey. SETTING: PICUs in Australia/New Zealand, Europe, and North America. SUBJECTS: Pediatric intensivists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Respondents were asked to report their decisions regarding RBC transfusions, iron, and erythropoietin prescription to children ready to be discharged from PICU, who had been admitted for hemorrhagic shock, cardiac surgery, craniofacial surgery, and polytrauma. Clinical and biological variables were altered separately in order to assess their effect on the management of anemia. Two-hundred seventeen responses were analyzed. They reported that the mean (± SEM) transfusion threshold was a hemoglobin level of 6.9 ± 0.09 g/dL after hemorrhagic shock, 7.6 ± 0.10 g/dL after cardiac surgery, 7.0 ± 0.10 g/dL after craniofacial surgery, and 7.0 ± 0.10 g/dL after polytrauma (p < 0.001). The most important increase in transfusion threshold was observed in the presence of a cyanotic heart disease (mean increase ranging from 1.80 to 2.30 g/dL when compared with baseline scenario) or left ventricular dysfunction (mean increase, 1.41-2.15 g/dL). One third of respondents stated that they would not prescribe iron at PICU discharge, regardless of the hemoglobin level or the baseline scenario. Most respondents (69.4-75.0%, depending on the scenario) did not prescribe erythropoietin. CONCLUSIONS: Pediatric intensivists state that they use restrictive transfusion strategies at PICU discharge similar to those they use during the acute phase of critical illness. Supplemental iron is less frequently prescribed than RBCs, and prescription of erythropoietin is uncommon. Optimal management of post-PICU anemia is currently unknown. Further studies are required to highlight the consequences of this anemia and to determine appropriate management.

Is a semi-elemental diet better than a polymeric diet after congenital heart surgery?

A retrospective observational study has been set up in order to compare feeding tolerance and energy delivery in children fed with a semi-elemental diet or a polymeric diet after congenital heart surgery. The study took place in the intensive care unit of a tertiary children's hospital. One hundred children were included: 56 received a semi-elemental diet and 44 received a polymeric diet. Patients were aged between 2 days and 6 years. Data from patients were obtained from medical files between February 2014 and May 2016. The feeding protocol was changed in March 2015 when a semi-elemental diet was substituted for the polymeric diet. Primary outcome was the feeding tolerance. Feeding intolerance occurs if the patient has more than two episodes of emesis or more than four liquid stools per day. Feeding tolerance in the semi-elemental and polymeric diet groups was comparable: emesis occurred in 14.3% versus 6.8% of patients, respectively (p = 0.338); diarrhea occurred in 3.6% versus 4.5% (p = 1000); post-pyloric feeding was necessary in 14% versus 9% (p = 0.542). Energy delivery was also comparable in the two groups: on postoperative day 2, the semi-elemental diet group reached 50% of the caloric target versus 52% in the polymeric diet group (p = 0.283); on day 5, 76% versus 85% (p = 0.429); and on day 10, 105% versus 125% (p = 0.397). Energy delivery was insufficient on postoperative days 2 and 5, but nutritional goals were achieved by day 10. No patient developed necrotizing enterocolitis in our population.Conclusion: the present study suggests that the feeding tolerance to a semi-elemental or a polymeric diet is similar after CHS.What is Known:•Nutrition can modify prognosis in PICU•Different types of diet have been tested in children with intestinal disorders or with congenital heart disease. None of these diets have shown to be superior in terms of feeding tolerance.What is New:•Semi elemental and polymeric diets seem to have the same feeding tolerance in PICU after cardiac surgery for congenital heart disease.

Aprotinin versus tranexamic acid in children undergoing cardiac surgery: an observational study.

OBJECTIVES: The upcoming release of aprotinin in paediatric cardiac surgery prompted a re-evaluation of its use in comparison to tranexamic acid (TXA) focusing on their effect on exposure to blood transfusions as well as severe postoperative morbidity or mortality. METHODS: This retrospective study was conducted in a tertiary children hospital from 2002 to 2015. Patients receiving aprotinin (Aprotinin group: 2002-2007) were compared with those receiving TXA group (2008-2015) using propensity score analysis. Primary outcome measures were 'exposure to blood products' and 'severe postoperative morbidity or mortality'. High-risk subgroups that included neonates, complex (Risk Adjusted Classification for Congenital Heart Surgery-1 ≥ 3) and redo surgery were also analysed. RESULTS: The study included 2157 patients, 1136 in the Aprotinin group and 1021 in the TXA group. Exposure to blood products was significantly higher in the Aprotinin group (78% vs 60%; P < 0.001) as well as in the complex and redo surgery subgroups. Incidence of mortality and/or severe morbidity was higher in the Aprotinin group (33% vs 28%; P = 0.007), as well as in the neonate group. However, cardiopulmonary bypass priming volume and intraoperative fluid balance were significantly decreased, and the use of modified ultrafiltration significantly increased in the TXA group. CONCLUSIONS: In our population, children receiving aprotinin were more frequently transfused and were at a higher risk of developing severe postoperative morbidity or mortality than those receiving TXA. Subgroups at high risk of bleeding or inflammation did not seem to benefit from aprotinin. These differences might be explained by a safer profile of TXA, but also attributed to major changes in our patient blood management strategies over years.

Cyanotic heart disease is an independent predicting factor for fresh frozen plasma and platelet transfusion after cardiac surgery.

OBJECTIVES: Cyanotic heart disease is associated with increased risk of bleeding in children undergoing cardiac surgery. We studied if the presence of a cyanotic heart disease was an independent predictive factor for fresh frozen plasma (FFP) and platelets transfusion in these patients. In children with ROTEM measurements, we also tried to characterize the coagulation profile between both groups. DESIGN: Retrospective observational study. SETTING: Tertiary university hospital; single center. PARTICIPANTS: All consecutive children admitted for cardiac surgery with cardiopulmonary bypass (CPB) from January 2006 to December 2014. Patients who received FFP in the CPB priming were excluded. Multivariate logistic regression was used to determine the predictive factors for FFP and platelet transfusions. INTERVENTION: none. MEASUREMENTS AND MAIN RESULTS: From the 1846 patients included for analysis: 1063 were acyanotic and 783 were cyanotic. The presence of cyanotic heart disease was an independent predicting factor for both FFP (OR: 2.09; 95%CI: 1.44-3.02) and platelets (OR:3.98; 95%CI: 2.28-6.70) transfusion. Cyanotic children exhibited also higher perioperative blood losses [Intraoperative: 31.1 (17.6-50.4) versus 26.7 (14.8-44.7); P < 0.001 and Postoperative: 31.2 (19.1-51.9) versus 16.9 (10.4-26.9); P < 0.001]. Thromboelastometry assays after separation from CPB and heparin reversal revealed more complex coagulation disturbances in cyanotic than acyanotic children. CONCLUSION: Children with a cyanotic heart disease are at higher risk of FFP and platelet transfusion after cardiac surgery. Intraoperative monitoring should be used to guide administration of blood and haemostatic product in this population at high risk of postoperative bleeding.

Consensus Recommendations for RBC Transfusion Practice in Critically Ill Children From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

OBJECTIVES: To date, there are no published guidelines to direct RBC transfusion decision-making specifically for critically ill children. We present the recommendations from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. DESIGN: Consensus conference series of multidisciplinary, international experts in RBC transfusion management of critically ill children. SETTING: Not applicable. INTERVENTION: None. SUBJECTS: Children with, or children at risk for, critical illness who receive or are at risk for receiving a RBC transfusion. METHODS: A panel of 38 content and four methodology experts met over the course of 2 years to develop evidence-based, and when evidence lacking, expert consensus-based recommendations regarding decision-making for RBC transfusion management and research priorities for transfusion in critically ill children. The experts focused on nine specific populations of critically ill children: general, respiratory failure, nonhemorrhagic shock, nonlife-threatening bleeding or hemorrhagic shock, acute brain injury, acquired/congenital heart disease, sickle cell/oncology/transplant, extracorporeal membrane oxygenation/ventricular assist/ renal replacement support, and alternative processing. Data to formulate evidence-based and expert consensus recommendations were selected based on searches of PubMed, EMBASE, and Cochrane Library from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. MEASUREMENTS AND RESULTS: The Transfusion and Anemia Expertise Initiative consensus conference developed and reached consensus on a total of 102 recommendations (57 clinical [20 evidence based, 37 expert consensus], 45 research recommendations). All final recommendations met agreement, defined a priori as greater than 80%. A decision tree to aid clinicians was created based on the clinical recommendations. CONCLUSIONS: The Transfusion and Anemia Expertise Initiative recommendations provide important clinical guidance and applicable tools to avoid unnecessary RBC transfusions. Research recommendations identify areas of focus for future investigation to improve outcomes and safety for RBC transfusion.

Heparin Reversal After Cardiopulmonary Bypass: Are Point-of-Care Coagulation Tests Interchangeable?

OBJECTIVE: Protamine is used to neutralize heparin after patient separation from cardiopulmonary bypass (CPB). Different bedside tests are used to monitor the adequacy of heparin neutralization. For this study, the interchangeability of the activated coagulation time (ACT) and thromboelastometry (ROTEM; Tem Innovations GmbH, Basel, Switzerland) clotting time (CT) ratios in children undergoing cardiac surgery was assessed. DESIGN: Single-center, retrospective, cohort study between September 2010 and January 2012. SETTING: University children's hospital. PARTICIPANTS: The study comprised children 0 to 16 years old undergoing elective cardiac surgery with CPB. Exclusion criteria were preoperative coagulopathy, Jehovah's witnesses, and children in a moribund condition (American Society of Anesthesiologists score 5). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After heparin neutralization with protamine, the ratio between ACT, with and without heparinase, and the CT measured with INTEM/HEPTEM (intrinsic test activated with ellagic acid was performed without heparinase [INTEM] and with heparinase [HEPTEM]) using tests of ROTEM were calculated. Agreement was evaluated using Cohen's kappa statistics, Passing-Bablok regression, and Bland-Altman analysis. Among the 173 patients included for analysis, agreement between both tests showed a Cohen's kappa statistic of 0.06 (95% CI: -0.02 to 0.14; p = 0.22). Bland-Altman analysis showed a bias of 0.01, with a standard deviation of 0.13, and limits of agreement between -0.24 and 0.26. Passing-Bablok regression showed a systematic difference of 0.40 (95% CI: 0.16-0.59) and a proportional difference of 0.61 (95% CI: 0.42-0.86). The residual standard deviation was 0.11 (95% CI: -0.22 to 0.22), and the test for linearity showed p = 0.10. CONCLUSION: ACT, with or without heparinase, and the INTEM/HEPTEM CT ratios are not interchangeable to evaluate heparin reversal after pediatric patient separation from CPB. Therefore, the results of these tests should be corroborated with the absence/presence of bleeding and integrated into center-specific treatment algorithms.

Impact of On-Bypass Red Blood Cell Transfusion on Severe Postoperative Morbidity or Mortality in Children.

BACKGROUND: Children undergoing cardiac surgery are frequently exposed to red blood cell (RBC) transfusions mainly in the case of hemorrhage or low oxygen transport. However, in this population, RBCs are sometimes added to the cardiopulmonary bypass (CPB) priming solution to maintain a predefined hematocrit on bypass. In this study, we investigated the impact of RBCs added to the CPB on severe postoperative morbidity or mortality. METHODS: This retrospective cohort study was conducted between 2006 and 2012 in a tertiary care level, children's hospital. Children receiving red cells only to prime the CPB (CPB transfusion) were compared with those receiving no RBCs during their entire hospital stay. The primary outcome was severe postoperative morbidity or mortality. Studied secondary outcomes were neurologic deficit, infection, length of mechanical ventilation, pediatric intensive care unit and hospital length of stay, and mortality. Both groups were compared with propensity score analysis where patients were matched via a genetic matching algorithm. In all analyses, applying a Bonferroni correction, a P value <.05/8 = .00625, was considered statistically significant. RESULTS: Among the 854 patients retained for this study, 439 (51.4%) received no RBC transfusion during their entire hospital stay and 415 (49.6%) received a CPB transfusion. Thirty-five (8.0%) patients in the no-transfusion group and 110 (26.5%) patients in the CPB transfusion group developed severe postoperative morbidity or died. This difference was statistically significant using univariate analysis (P < .001). Propensity score analysis showed that 79 (19.55%) patients developed severe postoperative morbidity or died in the no-transfusion group compared with 103 (25.50%) patients in the CPB transfusion group (P = .043). The relative risk and its Bonferroni-corrected confidence interval was 0.77 (0.53-1.10). All secondary outcomes were not significantly different between both groups, except the number of patients who developed infections (P < .001). CONCLUSIONS: In the condition of our study, adding RBCs to the CPB priming to maintain a predefined hematocrit does not seem to impact markedly severe postoperative morbidity or mortality in children undergoing cardiac surgery. Only the risk of infection was increased in the CPB transfusion group. Further studies are warranted to better understand the complex interaction among severity of illness, anemia, RBCs transfusion, and outcome in children undergoing cardiac surgery.

Effective tranexamic acid concentration for 95% inhibition of tissue-type plasminogen activator induced hyperfibrinolysis in children with congenital heart disease: A prospective, controlled, in-vitro study.

BACKGROUND: Although recent studies have assessed tranexamic acid (TXA) pharmacokinetics in different subgroups, the effective concentration of TXA required to completely inhibit fibrinolysis remains to be determined. OBJECTIVE: An in-vitro determination of the effective TXA concentration needed for 95% inhibition (EC95) of tissue-type plasminogen activator (t-PA) activated fibrinolysis, using an experimental model designed for thromboelastometry (ROTEM). DESIGN: A prospective interventional study. SETTING: Department of Anaesthesiology, Queen Fabiola Children's University Hospital and Laboratory of Haematology and Haemostasis, Brugmann University Hospital. Patients were enrolled between June 2013 and October 2014. PATIENTS AND VOLUNTEERS: Twenty children, aged between 1 and 10 years, undergoing elective cardiac catheterisation were included (10 with cyanotic and 10 with noncyanotic diseases). Exclusion criteria were child requiring a procedure in a moribund state. Ten adult volunteers were also included as controls. INTERVENTION: Citrated whole blood samples were obtained from children and volunteers. MAIN OUTCOMES MEASURES: The extrinsic coagulation pathway was activated by tissue factor using the EXTEM test on ROTEM. The degree of lysis measured 30 min (LI30) after the clotting time (CT), and clot amplitudes measured at different times were recorded at baseline, after addition of 1535 units t-PA ml(-1), and following the addition of increasing TXA concentrations in t-PA activated samples. RESULTS: The concentration-effect analysis performed with lysis index after 30 min (LI30) allowed the determination of TXA efficacy concentration 50% (EC50), and calculation of the EC95, which was significantly lower in cardiac surgery children than in adults [8.6 µg ml(-1); 95% confidence interval (95% CI) 6.9 to 14.9 versus 11.3 µg ml(-1); 95% CI 10.6 to 12.9, P < 0.001]. CONCLUSION: In this in-vitro study, we observed that the EC95 TXA concentration that completely inhibited t-PA induced hyperfibrinolysis in children with congenital heart was significantly lower than the concentration required in healthy adult volunteers. Further studies are needed to confirm that this plasma concentration can effectively inhibit fibrinolysis activation in children undergoing cardiac surgery.

Efficacy and safety of 6% hydroxyethyl starch 130/0.4 (Voluven) for perioperative volume replacement in children undergoing cardiac surgery: a propensity-matched analysis.

INTRODUCTION: Six percent hydroxyethyl starch (HES) 130/0.4 is considered an alternative to human albumin (HA) and crystalloids for volume replacement in children undergoing cardiac surgery. In this large propensity-matched analysis, we aimed to assess the efficacy and safety of replacing HA with HES for intraoperative volume therapy in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS: We retrospectively reviewed our database, including children who underwent cardiac surgery between January 2002 and December 2010. Four percent HA was used until 2005; it was replaced by HES thereafter. Demographic data, intra- and postoperative blood loss and blood component transfusions were recorded, together with the incidence of postoperative complications and mortality. We performed a propensity-matched analysis using 13 possible confounding factors to compare children who received either HES or HA intraoperatively. The primary objectives included the effects of both fluids on intraoperative fluid balance (difference between fluids in and fluids out (efficacy)) and blood loss and exposure to allogeneic blood products (safety). Secondary safety outcomes were mortality and the incidence of postoperative renal dysfunction. RESULTS: Of 1,832 children reviewed, 1,495 were included in the analysis. Intraoperative use of HES was associated with a less positive fluid balance. Perioperative blood loss, volume of red blood cells and fresh frozen plasma administered, as well as the number of children who received transfusions, were also significantly lower in the HES group. No difference was observed regarding the incidence of postoperative renal failure requiring renal replacement therapy or of morbidity and mortality. CONCLUSIONS: These results confirm that the use of HES for volume replacement in children during cardiac surgery with CPB is as safe as HA. In addition, its use might be associated with less fluid accumulation. Further large studies are needed to assess whether the reduction in fluid accumulation could have a significant impact on postoperative morbidity and mortality.

Experimental model of hyperfibrinolysis designed for rotational thromboelastometry in children with congenital heart disease.

We assessed an in-vitro model of hyperfibrinolysis using rotational thromboelastometry (ROTEM) by the addition of increasing concentrations of tissue-type plasminogen activator (t-PA) on whole blood obtained from children undergoing cardiac surgery. We assessed the relevance of this model by repeating the tests in the same population after tranexamic acid (TXA) infusion. In addition, we determined the sensitivity and specificity of ROTEM parameters to detect the different degrees of fibrinolysis. Blood samples obtained from 20 children were analyzed at two predefined timepoints: after induction of anesthesia, before TXA (baseline), and at the end of surgery during TXA infusion (end surgery). At baseline, an extrinsic activation with tissue factor (EXTEM) test was performed without and with increasing concentration of t-PA (102, 255, 512, 1024, 1535, and 2539 units t-PA/ml). At the end of surgery, a second EXTEM test was performed without and with two different t-PA concentrations (1535 and 2539 units t-PA/ml). At baseline, increasing t-PA concentrations in the EXTEM test induced a gradual increase of hyperfibrinolysis characterized by a reduction in clot firmness and stability parameters. In the presence of TXA, t-PA-induced hyperfibrinolysis was completely abolished. Lysis-onset time (LOT) and degree of fibrinolysis measured at 30 min (LI30) best assessed the degree of fibrinolysis. This in-vitro model of t-PA-induced hyperfibrinolysis using the EXTEM test of ROTEM may represent a promising tool to assess hyperfibrinolysis in the pediatric population. In addition, we observed that LOT and LI30 should be considered as the best parameters to detect different degrees of fibrinolysis.

Evaluation of dynamic parameters of thrombus formation measured on whole blood using rotational thromboelastometry in children undergoing cardiac surgery: a descriptive study.

BACKGROUND: Total thrombus formation velocity calculated using amplitude parameters obtained at different times could be used to estimate the amplification and the propagation phases observed during coagulation processes, and therefore might be useful to predict postoperative hemostatic products administration in pediatric patients. METHODS: We retrospectively analyzed data from 49 children <3 months of age who underwent cardiac surgery. Children ≤1 month of age routinely received fresh frozen plasma during bypass while children >1 month of age did not. The EXTEM parameters were used to calculate velocity curves using amplitudes obtained at different times, the area under the curve called total thrombus formation and the maximum rate of thrombus formation. These parameters were compared between children who received fresh frozen plasma and those who did not. Receiver operating characteristics curves were used to define variables that could be used to predict postoperative fresh frozen plasma transfusion. RESULTS: Total thrombus formation and maximum rate of thrombus formation significantly increased in children who received fresh frozen plasma compared to those who did not. Both total thrombus formation and maximum rate of thrombus formation have a better specificity to predict postoperative fresh frozen plasma transfusion compared to clotting time or maximal clot firmness. CONCLUSION: Based on this descriptive study, dynamic ROTEM(®) parameters of total thrombus formation could be used to estimate the amplification and the propagation phases of coagulation in children. These parameters might be used in further well-designed study to predict the need for hemostatic products in children undergoing cardiac surgery with cardiopulmonary bypass.

Development of a specific algorithm to guide haemostatic therapy in children undergoing cardiac surgery: a single-centre retrospective study.

BACKGROUND: Although rotational thromboelastometry (ROTEM) is increasingly used to guide haemostatic therapy in a bleeding patient, there is a paucity of data guiding its use in the paediatric population. OBJECTIVE: The objective of this study is to develop an algorithm on the basis of ROTEM values obtained in our paediatric cardiac population to guide the management of the bleeding child. DESIGN: A retrospective analysis. SETTING: Department of Anaesthesiology, Queen Fabiola Children's University Hospital. Data were collected between September 2010 and January 2012. PATIENTS: All children who underwent elective cardiac surgery requiring cardiopulmonary bypass (CPB) were reviewed. INTERVENTION: None. MAIN OUTCOME MEASURES: Significant postoperative bleeding was defined as blood loss more than 10% of the child's estimated blood volume within the first six postoperative hours, dividing our population according to high blood loss (HBL) or low blood loss (LBL). Factors independently associated with postoperative bleeding determined the bleeding probability. Receiving operating characteristics (ROC) curves were constructed with the aim of determining relevant ROTEM parameters (including clot amplitude 10 min after administration of protamine [A10]) to be used in our algorithm. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were determined for the developed algorithm. RESULTS: One-hundred and fifty children were included in our study. Univariate and multivariate logistic regression analysis revealed that preoperative weight (kg), presence of a cyanotic disease (yes/no) and wound closure duration (min) were independent predictors of postoperative bleeding. Analysis of our ROTEM parameters revealed that clotting time (CT) ≥ 111 s, A10 ≤ 38 mm measured on the EXTEM and A10 ≤ 3 mm obtained on the FIBTEM tests were the three relevant parameters to guide haemostatic therapy. If the ROTEM-based algorithm was applied according to the bleeding risk (n = 65), 27 out of 29 of the HBL and 24 out of 36 of the LBL group would have been treated. CONCLUSION: This study describes an algorithm starting with the detection of abnormal bleeding in which ROTEM could be used to guide haemostatic therapy in bleeding children after CPB. Further studies are needed to test the efficacy of this specific algorithm-based approach.

Predictive factors for red blood cell transfusion in children undergoing noncomplex cardiac surgery.

BACKGROUND: Red blood cell (RBC) transfusion is frequently required in pediatric cardiac surgery and is associated with altered outcome and increased costs. Determining which factors predict transfusion in this context will enable clinicians to adopt strategies that will reduce the risk of RBC transfusion. This study aimed to assess predictive factors associated with RBC transfusion in children undergoing low-risk cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Children undergoing surgery to repair ventricular septal defect or atrioventricular septal defect from 2006 to 2011 were included in this retrospective study. Demography, preoperative laboratory testing, intraoperative data, and RBC transfusion were reviewed. Univariate and multivariate logistic regression analysis were used to define factors that were able to predict RBC transfusion. Then, we employed receiver operating characteristic analysis to design a predictive score. RESULTS: Among the 334 children included, 261 (78%) were transfused. Age (<18 months), priming volume of the CPB (>43 mL/kg), type of oxygenator used, minimal temperature reached during CPB (<32°C), and preoperative hematocrit (<34%) were independently associated with RBC transfusion in the studied population. A predictive score 2 or greater was the best predictor of RBC transfusion. CONCLUSIONS: The present study identified several factors that were significantly associated with perioperative RBC transfusion. Based on these factors, we designed a predictive score that can be used to develop a patient-based blood management program with the aim of reducing the incidence of RBC transfusion.

Blood storage duration and morbidity and mortality in children undergoing cardiac surgery. A retrospective analysis.

BACKGROUND: Blood transfusion is frequently required in children undergoing cardiac surgery and is associated with altered postoperative outcome. This may be due to alterations in red blood cell properties related to the storage process. OBJECTIVE: To evaluate the effect of blood storage duration on postoperative morbidity and mortality in children undergoing cardiac surgery. DESIGN: A retrospective review of a paediatric cardiac surgery database. SETTING: Department of Anaesthesiology, Queen Fabiola Children's University Hospital, Brussels, Belgium. PARTICIPANTS: Children transfused with one or two units of blood in the perioperative period. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Storage duration was used to allocate children to the Group 'Young' or the Group 'Old' (cut-off = 7 days). The primary endpoint was a composite based on the incidence of hospital mortality and/or the incidence of at least one organ failure. RESULTS: From 1014 children in the database, 570 were included in the final analysis. One hundred and eighteen patients were included in the Group 'Young' [median (interquartile range, IQR) storage duration 6 (5 to 7) days] and 452 in the Group 'Old' [storage duration 14 (11 to 19) days]. No difference was found in mortality, length of ICU stay, mechanical ventilation duration, postoperative infection and major organ dysfunction. Duration of storage used as a continuous variable did not influence the incidence of the composite endpoint when evaluated by univariate or multivariate logistic regression analyses. CONCLUSION: Red blood cell storage duration did not influence postoperative morbidity and mortality in paediatric cardiac surgery patients transfused with one or two units of blood.