Longitudinal Follow-Up of Children With HLHS and Association Between Norwood Shunt Type and Long-Term Outcomes: The SVR III Study.

OBJECTIVE: In the SVR trial (Single Ventricle Reconstruction), newborns with hypoplastic left heart syndrome were randomly assigned to receive a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right ventricle-to-pulmonary artery shunt (RVPAS) at Norwood operation. Transplant-free survival was superior in the RVPAS group at 1 year, but no longer differed by treatment group at 6 years; both treatment groups had accumulated important morbidities. In the third follow-up of this cohort (SVRIII [Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type]), we measured longitudinal outcomes and their risk factors through 12 years of age. METHODS: Annual medical history was collected through record review and telephone interviews. Cardiac magnetic resonance imaging (CMR), echocardiogram, and cycle ergometry cardiopulmonary exercise tests were performed at 10 through 14 years of age among participants with Fontan physiology. Differences in transplant-free survival and complication rates (eg, arrhythmias or protein-losing enteropathy) were identified through 12 years of age. The primary study outcome was right ventricular ejection fraction (RVEF) by CMR, and primary analyses were according to shunt type received. Multivariable linear and Cox regression models were created for RVEF by CMR and post-Fontan transplant-free survival. RESULTS: Among 549 participants enrolled in SVR, 237 of 313 (76%; 60.7% male) transplant-free survivors (mBTTS, 105 of 147; RVPAS, 129 of 161; both, 3 of 5) participated in SVRIII. RVEF by CMR was similar in the shunt groups (RVPAS, 51±9.6 [n=90], and mBTTS, 52±7.4 [n=75]; P=0.43). The RVPAS and mBTTS groups did not differ in transplant-free survival by 12 years of age (163 of 277 [59%] versus 144 of 267 [54%], respectively; P=0.11), percentage predicted peak Vo2 for age and sex (74±18% [n=91] versus 72±18% [n=84]; P=0.71), or percentage predicted work rate for size and sex (65±20% versus 64±19%; P=0.65). The RVPAS versus mBTTS group had a higher cumulative incidence of protein-losing enteropathy (5% versus 2%; P=0.04) and of catheter interventions (14 versus 10 per 100 patient-years; P=0.01), but had similar rates of other complications. CONCLUSIONS: By 12 years after the Norwood operation, shunt type has minimal association with RVEF, peak Vo2, complication rates, and transplant-free survival. RVEF is preserved among the subgroup of survivors who underwent CMR assessment. Low transplant-free survival, poor exercise performance, and accruing morbidities highlight the need for innovative strategies to improve long-term outcomes in patients with hypoplastic left heart syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT0245531.

Reintervention Before Bidirectional Cavopulmonary Shunt and Intermediate Outcomes in Children with Single Ventricle Who Underwent Main Pulmonary Artery Banding.

Unplanned reinterventions following pulmonary artery banding (PAB) in single ventricle patients are common before stage 2 palliation (S2P) but associated risk factors are unknown. We hypothesized that reintervention is more common when PAB is placed at younger age and with a looser band, reflected by lower PAB pressure gradient. Retrospective single center study of single ventricle patients undergoing PAB between Jan 2000 and Dec 2020. The association with reintervention and successful S2P was modeled using exploratory cause-specific hazard regression. A multivariable model was developed adjusting for clinical and statistically relevant predictors. The cumulative proportion of patients undergoing reintervention were summarized using a competing risk model. 77 patients underwent PAB at median (IQR) 47 (24-66) days and 3.73 (3.2-4.5) kg. Within18 months of PAB, 60 (78%) reached S2P, 9 (12%) died, 1 (1%) transplanted and 7 (9%) were alive without S2P. Within 18 months of PAB 10 (13%) patients underwent reintervention related to pulmonary blood flow modification: PAB adjustment (n = 6) and conversion to Damus-Kaye-Stansel/Blalock-Taussig-Thomas shunt (n = 4). 6/10 (60%) reached S2P following reintervention. A trend toward higher intervention in patients with a genetic syndrome (p-0.06) and weight < 3 kg (p-0.057) at time of PAB was noted. Only genetic syndrome was a risk factor associated with poor outcome (p-0.025). PAB has a reasonable outcome in SV patients with unobstructed systemic and pulmonary blood flow, but with a high reintervention rate. Only a quarter of patients with genetic syndromes reach S2P and further study is required to explore the benefits from an alternative palliative strategy.

Standardisation of management after Norwood operation has not improved 1-year outcomes.

INTRODUCTION: Treatment of hypoplastic left heart syndrome varies across institutions. This study examined the impact of introducing a standardised programme. METHODS: This retrospective cohort study evaluated the effects of a comprehensive strategy on 1-year transplant-free survival with preserved ventricular and atrioventricular valve (AVV) function following a Norwood operation. This strategy included standardised operative and perioperative management and dedicated interstage monitoring. The post-implementation cohort (C2) was compared to historic controls (C1). Outcomes were assessed using logistic regression and Kaplan-Meier analysis. RESULTS: The study included 105 patients, 76 in C1 and 29 in C2. Groups had similar baseline characteristics, including percentage with preserved ventricular (96% C1 versus 100% C2, p = 0.28) and AVV function (97% C1 versus 93% C2, p = 0.31). Perioperatively, C2 had higher indexed oxygen delivery (348 ± 67 ml/minute/m2 C1 versus 402 ± 102ml/minute/m2 C2, p = 0.015) and lower renal injury (47% C1 versus 3% C2, p = 0.004). The primary outcome was similar in both groups (49% C1 and 52% C2, p = 0.78), with comparable rates of death and transplantation (36% C1 versus 38% C2, p = 0.89) and ventricular (2% C1 versus 0% C2, p = 0.53) and AVV dysfunction (11% C1 versus 11% C2, p = 0.96) at 1-year. When accounting for cohort and 100-day freedom from hospitalisation, female gender (OR 3.7, p = 0.01) increased and ventricular dysfunction (OR 0.21, p = 0.02) and CPR (OR 0.11, p = 0.002) or ECMO use (OR 0.15, p = 001) decreased the likelihood of 1-year transplant-free survival. CONCLUSIONS: Standardised perioperative management was not associated with improved 1-year transplant-free survival. Post-operative ventricular or AVV dysfunction was the strongest predictor of 1-year mortality.

Rapid Advancement in Enteral Nutrition Does Not Affect Systemic Inflammation and Insulin Homeostasis Following Pediatric Cardiopulmonary Bypass Surgery.

OBJECTIVES: To determine impact of enteral nutrition delivery on the relationship among inflammation, insulin resistance, and outcomes following pediatric cardiopulmonary bypass surgery. DESIGN: Pilot, randomized study analyzed according to intention-to-treat analysis. SETTING: Pediatric cardiac ICU. PATIENTS: Infants (≤ 6 mo) undergoing cardiopulmonary bypass. INTERVENTIONS: Patients randomly assigned to receive rapid escalation to enteral nutrition reaching goal feeds by 27 hours or standard feeding practice reaching goal feeds by 63 hours. Feeds were initiated on the first postoperative day. MEASUREMENTS AND MAIN RESULTS: Fifty patients were randomized equally to study arms. Patients were a median (interquartile range) of 16 days old (7-110 d old), undergoing biventricular surgery (88%) with a median cardiopulmonary bypass time of 125 minutes (105-159 min). Serial blood samples were drawn before and after cardiopulmonary bypass, cardiac ICU admission, and every 12 hours (up to 96 hr) for glucose, insulin, and cytokines (interleukin-1α, interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α) levels. Glucose-insulin ratio was calculated to quantify insulin resistance. Patient characteristics, time to enteral nutrition initiation, enteral nutrition interruptions, and insulin administration were similar across intervention arms. FF reached goal feeds at similar intervals as standard feeding (39 hr [30-60 hr] vs 60 hr [21-78 hr]; p = 0.75). No difference in cytokine, insulin, or glucose-insulin ratio was noted between groups. Higher inflammation was associated with increased glucose-insulin ratio and higher risk of adverse events. In multivariable models of interleukin-8, FF was associated with increased glucose-insulin ratio (estimate of effect [95% CI], 0.152 [0.033-0.272]; p = 0.013). Although higher interleukin-8 was associated with an elevated risk of adverse event, this relationship was possibly mitigated by FF (odds ratio [95% CI], 0.086 [0.002-1.638]; p = 0.13). CONCLUSIONS: A FF strategy was not associated with changes to early enteral nutrition delivery. Inflammation, insulin resistance, and morbidity were similar, but FF may modify the relationship between inflammation and adverse event. Multicenter nutrition studies are possible and necessary in this vulnerable population.

Extracorporeal Cardiopulmonary Resuscitation: One-Year Survival and Neurobehavioral Outcome Among Infants and Children With In-Hospital Cardiac Arrest.

OBJECTIVE: To describe neurobehavioral outcomes and investigate factors associated with survival and survival with good neurobehavioral outcome 1 year after in-hospital cardiac arrest for children who received extracorporeal cardiopulmonary resuscitation. DESIGN: Secondary analysis of the Therapeutic Hypothermia after Pediatric Cardiac Arrest In-Hospital trial. SETTING: Thirty-seven PICUs in the United States, Canada, and the United Kingdom. PATIENTS: Children (n = 147) resuscitated with extracorporeal cardiopulmonary resuscitation following in-hospital cardiac arrest. INTERVENTIONS: Neurobehavioral status was assessed using the Vineland Adaptive Behavior Scales, Second Edition, at prearrest baseline and 12 months postarrest. Norms for Vineland Adaptive Behavior Scales, Second Edition, are 100 (mean) ± 15 (SD). Higher scores indicate better functioning. Outcomes included 12-month survival, 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, decreased by less than or equal to 15 points from baseline, and 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, greater than or equal to 70. MEASUREMENTS AND MAIN RESULTS: Of 147 children receiving extracorporeal cardiopulmonary resuscitation, 125 (85.0%) had a preexisting cardiac condition, 75 (51.0%) were postcardiac surgery, and 84 (57.1%) were less than 1 year old. Duration of chest compressions was greater than 30 minutes for 114 (77.5%). Sixty-one (41.5%) survived to 12 months, 32 (22.1%) survived to 12 months with Vineland Adaptive Behavior Scales, Second Edition, decreased by less than or equal to 15 points from baseline, and 39 (30.5%) survived to 12 months with Vineland Adaptive Behavior Scales, Second Edition, greater than or equal to 70. On multivariable analyses, open-chest cardiac massage was independently associated with greater 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, decreased by less than or equal to 15 points and greater 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, greater than or equal to 70. Higher minimum postarrest lactate and preexisting gastrointestinal conditions were independently associated with lower 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, decreased by less than or equal to 15 points and lower 12-month survival with Vineland Adaptive Behavior Scales, Second Edition, greater than or equal to 70. CONCLUSIONS: About one third of children survived with good neurobehavioral outcome 1 year after receiving extracorporeal cardiopulmonary resuscitation for in-hospital arrest. Open-chest cardiac massage and minimum postarrest lactate were associated with survival with good neurobehavioral outcome at 1 year.

A randomized clinical trial of age and genotype-guided tacrolimus dosing after pediatric solid organ transplantation.

BACKGROUND: Tacrolimus pharmacokinetics are influenced by age and CYP3A5 genotype with CYP3A5 expressors (CYP3A5*1/*1 or *1/*3) being fast metabolizers. However, the benefit of genotype-guided dosing in pediatric solid organ transplantation has been understudied. OBJECTIVE: To determine whether age and CYP3A5 genotype-guided starting dose of tacrolimus result in earlier attainment of therapeutic drug concentrations. SETTING: Single hospital-based transplant center. METHODS: This was a randomized, semi-blinded, 30-day pilot trial. Between 2012 and 2016, pediatric patients listed for solid organ transplant were consented and enrolled into the study. Participants were categorized as expressors, CYP3A5*1/*1 or CYP3A5*1/*3, and nonexpressors, CYP3A5*3/*3. Patients were stratified by age (≤ or > 6 years) and randomized (2:1) after transplant to receive genotype-guided (n = 35) or standard (n = 18) starting dose of tacrolimus for 36-48 hours and were followed for 30 days. RESULTS: Median age at transplant in the randomized cohort was 2.1 (0.75-8.0) years; 24 (45%) were male. Participants in the genotype-guided arm achieved therapeutic concentrations earlier at a median (IQR) of 3.4 (2.5-6.6) days compared to those in the standard dosing arm of 4.7 (3.5-8.6) days (P = 0.049), and had fewer out-of-range concentrations [OR (95% CI) = 0.60 (0.44, 0.83), P = 0.002] compared to standard dosing, with no difference in frequency of adverse events between the two groups. CONCLUSIONS: CYP3A5 genotype-guided dosing stratified by age resulted in earlier attainment of therapeutic tacrolimus concentrations and fewer out-of-range concentrations.

Prelisting predictions of early postoperative survival in infant heart transplantation using classification and regression tree analysis.

Infants listed for heart transplantation experience high waitlist and early post-transplant mortality, and thus, optimal allocation of scarce donor organs is required. Unfortunately, the creation and validation of multivariable regression models to identify risk factors and generate individual-level predictions are challenging. We sought to explore the use of data mining methods to generate a prediction model. CART analysis was used to create a model which, at the time of listing, would predict which infants listed for heart transplantation would survive at least 3 months post-transplantation. A total of 48 infants were included; 13 died while waiting, and six died within 3 months of heart transplant. CART analysis identified RRT, blood urea nitrogen, and hematocrit as terminal nodes with alanine transaminase as an intermediate node predicting death. No patients listed on RRT (n = 10) survived and only three of 12 (25%) patients listed on ECLS survived >3 months post-transplant. CART analysis overall accuracy was 83%, with sensitivity of 95% and specificity 76%. This study shows that CART analysis can be used to generate accurate prediction models in small patient populations. Model validation will be necessary before incorporation into decision-making algorithms used to determine transplant candidacy.

Recommendations on RBC Transfusion in Infants and Children With Acquired and Congenital Heart Disease From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

OBJECTIVES: To present the recommendations and supporting literature for RBC transfusions in critically ill children with acquired and congenital heart disease developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. DESIGN: Consensus conference series of 38 international, multidisciplinary experts in RBC transfusion management of critically ill children. METHODS: Experts developed evidence-based and, when evidence was lacking, expert-based clinical recommendations and research priorities for RBC transfusions in critically ill children. The cardiac disease subgroup included three experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases 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. RESULTS: Twenty-one recommendations were developed and reached agreement. For children with myocardial dysfunction and/or pulmonary hypertension, there is no evidence that transfusion greater than hemoglobin of 10 g/dL is beneficial. For children with uncorrected heart disease, we recommended maintaining hemoglobin greater than 7-9.0 g/dL depending upon their cardiopulmonary reserve. For stable children undergoing biventricular repairs, we recommend not transfusing if the hemoglobin is greater than 7.0 g/dL. For infants undergoing staged palliative procedures with stable hemodynamics, we recommend avoiding transfusions solely based upon hemoglobin, if hemoglobin is greater than 9.0 g/dL. We recommend intraoperative and postoperative blood conservation measures. There are insufficient data supporting shorter storage duration RBCs. The risks and benefits of RBC transfusions in children with cardiac disease requires further study. CONCLUSIONS: We present RBC transfusion management recommendations for the critically ill child with cardiac disease. Clinical recommendations emphasize relevant hemoglobin thresholds, and research recommendations emphasize need for further understanding of physiologic and hemoglobin thresholds and alternatives to RBC transfusion in subpopulations lacking pediatric literature.

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.

Impact of prenatal diagnosis on the management and early outcome of critical duct-dependent cardiac lesions.

OBJECTIVE: The objective of this study was to compare the preoperative management and outcome of neonates with duct-dependent critical CHD with fetal versus postnatal diagnosis. METHODS: Patients referred with CHD to our centre from January 1, 2009 to December 31, 2010 were enrolled prospectively. Live births with a critical form of CHD, a gestational age ⩾36 weeks and a weight ⩾2 kg at birth, and the intention-to-treat were included in this sub-study. Excluded were neonates with lethal non-cardiac and/or genetic anomalies. RESULTS: In total, 129, 63 fetal and 66 postnatal, cases met the study inclusion criteria. All had received appropriate antenatal care, including a routine fetal anatomy scan. Both cohorts were comparable in weight, gestational age, and APGAR scores at birth. Unlike the postnatal cases, there were no deaths (0/63 versus 5/66; p=0.06) and no cardiac arrests (0/63 versus 9/63; p=0.003) before surgery or catheter intervention in those cases with a prenatal diagnosis of critical CHD. Moreover, newborns with fetal diagnoses were admitted earlier (median 0 (range 0-3) versus 2 (0-25) days; p<0.001) and were less likely to require preoperative ventilation (19/63 versus 31/61, p=0.03) and vasoactive medication (4/63 versus 15/61, p=0.006) than the postnatal cases. CONCLUSIONS: Prenatal diagnosis of critical CHD in this study was associated with significantly shorter time intervals from birth to neonatal admission and the absence of life-threatening or fatal preoperative cardiac events. Increased efforts should be made to improve rates of prenatal diagnosis.

Variation in care for infants undergoing the Stage II palliation for hypoplastic left heart syndrome.

BACKGROUND: The Single Ventricle Reconstruction trial randomised neonates with hypoplastic left heart syndrome to a systemic-to-pulmonary-artery shunt strategy. Patients received care according to usual institutional practice. We analysed practice variation at the Stage II surgery to attempt to identify areas for decreased variation and process control improvement. METHODS: Prospectively collected data were available in the Single Ventricle Reconstruction public-use database. Practice variation across 14 centres was described for 397 patients who underwent Stage II surgery. Data are centre-level specific and reported as interquartile ranges across all centres, unless otherwise specified. RESULTS: Preoperative Stage II median age and weight across centres were 5.4 months (interquartile range 4.9-5.7) and 5.7 kg (5.5-6.1), with 70% performed electively. Most patients had pre-Stage-II cardiac catheterisation (98.5-100%). Digoxin was used by 11/14 centres in 25% of patients (23-31%), and 81% had some oral feeds (68-84%). The majority of the centres (86%) performed a bidirectional Glenn versus hemi-Fontan. Median cardiopulmonary bypass time was 96 minutes (75-113). In aggregate, 26% of patients had deep hypothermic circulatory arrest >10 minutes. In 13/14 centres using deep hypothermic circulatory arrest, 12.5% of patients exceeded 10 minutes (8-32%). Seven centres extubated 5% of patients (2-40) in the operating room. Postoperatively, ICU length of stay was 4.8 days (4.0-5.3) and total length of stay was 7.5 days (6-10). CONCLUSIONS: In the Single Ventricle Reconstruction Trial, practice varied widely among centres for nearly all perioperative factors surrounding Stage II. Further analysis may facilitate establishing best practices by identifying the impact of practice variation.

Report of the National Heart, Lung, and Blood Institute Working Group: An Integrated Network for Congenital Heart Disease Research.

The National Heart, Lung, and Blood Institute convened a working group in January 2015 to explore issues related to an integrated data network for congenital heart disease research. The overall goal was to develop a common vision for how the rapidly increasing volumes of data captured across numerous sources can be managed, integrated, and analyzed to improve care and outcomes. This report summarizes the current landscape of congenital heart disease data, data integration methodologies used across other fields, key considerations for data integration models in congenital heart disease, and the short- and long-term vision and recommendations made by the working group.

Epidemiology of Noninvasive Ventilation in Pediatric Cardiac ICUs.

OBJECTIVE: To describe the epidemiology of noninvasive ventilation therapy for patients admitted to pediatric cardiac ICUs and to assess practice variation across hospitals. DESIGN: Retrospective cohort study using prospectively collected clinical registry data. SETTING: Pediatric Cardiac Critical Care Consortium clinical registry. PATIENTS: Patients admitted to cardiac ICUs at PC4 hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed all cardiac ICU encounters that included any respiratory support from October 2013 to December 2015. Noninvasive ventilation therapy included high flow nasal cannula and positive airway pressure support. We compared patient and, when relevant, perioperative characteristics of those receiving noninvasive ventilation to all others. Subgroup analysis was performed on neonates and infants undergoing major cardiovascular surgery. To examine duration of respiratory support, we created a casemix-adjustment model and calculated adjusted mean durations of total respiratory support (mechanical ventilation + noninvasive ventilation), mechanical ventilation, and noninvasive ventilation. We compared adjusted duration of support across hospitals. The cohort included 8,940 encounters from 15 hospitals: 3,950 (44%) received noninvasive ventilation and 72% were neonates and infants. Medical encounters were more likely to include noninvasive ventilation than surgical. In surgical neonates and infants, 2,032 (55%) received postoperative noninvasive ventilation. Neonates, extracardiac anomalies, single ventricle, procedure complexity, preoperative respiratory support, mechanical ventilation duration, and postoperative disease severity were associated with noninvasive ventilation therapy (p < 0.001 for all). Across hospitals, noninvasive ventilation use ranged from 32% to 65%, and adjusted mean noninvasive ventilation duration ranged from 1 to 4 days (3-d observed mean). Duration of total adjusted respiratory support was more strongly correlated with duration of mechanical ventilation compared with noninvasive ventilation (Pearson r = 0.93 vs 0.71, respectively). CONCLUSIONS: Noninvasive ventilation use is common in cardiac ICUs, especially in patients admitted for medical conditions, infants, and those undergoing high complexity surgery. We observed wide variation in noninvasive ventilation use across hospitals, though the primary driver of total respiratory support time seems to be duration of mechanical ventilation.

Management and Outcomes of Patients with Occlusive Thrombosis after Pediatric Cardiac Surgery.

OBJECTIVES: To evaluate management and outcomes of thrombosis after pediatric cardiac surgery and stratify thrombi according to risk of short- and long-term complications to better guide therapeutic choices. STUDY DESIGN: Retrospective review was performed of 513 thrombi (400 occlusive) diagnosed after 213 pediatric cardiac operations. Long-term outcomes over time were assessed with the use of parametric hazard regression models. RESULTS: Serious complications and/or high-intensity treatment occurred with 17%-24% of thrombi depending on location, most commonly in thrombi affecting the cardiac and cerebral circulation. Bleeding complications affected 13% of patients; associated factors included thrombolytics (OR 8.7, P < .001), greater daily dose of unfractionated heparin (OR 1.25 per 5 U/kg/day, P = .03), and extracorporeal support (OR 4.5, P = .007). Radiologic thrombus persistence was identified in 30% ± 3% at 12 months; associated factors included extracorporeal support (hazard ratio [HR] 1.9, P = .003), venous (HR 1.7, P = .003), and occlusive thrombi at presentation (HR 1.8, P = .001); greater oxygen saturation before surgery (HR 1.13/10%, P = .05) and thrombi in femoral veins (HR 1.9, P = .001) were associated with increased hazard of resolution. Freedom from postthrombotic syndrome was 83% ± 4% at 6 years, greater number of persistent vessel segment occlusions (HR 1.8/vessel, P = .001) and greater fibrinogen at diagnosis (HR 1.1 per g/L, P = .02) were associated with increased hazard. CONCLUSIONS: Thrombosis outcomes after pediatric cardiac surgery remain suboptimal. Given that more intensive treatment would likely increase the risk of bleeding, the focus should be on both thrombosis-prevention strategies, as well as in tailoring therapy according to a thrombosis outcome risk stratification approach.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Treatment of Acute Heart Failure.

OBJECTIVES: To provide an evidence-based review of pharmacotherapies to treat acute heart failure. To accomplish this objective, we will discuss circulatory physiology, vasoactive agents, and their indications in the management of acute heart failure. DATA SOURCE: A MEDLINE-baseline review of the literature. CONCLUSIONS: The optimal selection of vasoactive agents requires a consideration of circulatory physiology and the tailored application of pharmacotherapies to treat patients with acute heart failure.

Nutrition and Mesenteric Issues in Pediatric Cardiac Critical Care.

OBJECTIVES: The objectives of this review are to discuss the challenges of delivering adequate nutrition to children with congenital heart disease, including pre- and postoperative factors and the role of enteral and parenteral nutrition, as well as the evidence supporting current practices. DATA SOURCE: MEDLINE and PubMed. CONCLUSION: Providing adequate nutritional support is paramount for critically ill infants with congenital heart disease, a population at particular risk for malnutrition. Improved nutritional support has been associated with increased survival and reduction in overall morbidity. Further gains can be achieved by creating a clinical culture that emphasizes optimal perioperative nutritional support. Additional research is required to identify the specific nutrient composition, optimal mode, and timing of delivery to maximize clinical benefit.

Endocrinologic Diseases in Pediatric Cardiac Intensive Care.

OBJECTIVES: The objectives of this review are to discuss the pathophysiology, clinical impact and treatment of hyperglycemia, and disturbances in thyroid and adrenal function prior to and following cardiac surgery in children. DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: Disturbances in glucose metabolism and thyroid and adrenal function are common in critically ill children with cardiac disease and in particular in children undergoing cardiac surgery for complex congenital heart disease. An understanding of the pathophysiology, clinical impact and treatment of these disturbances is essential for the management of these at risk patients.

Outcomes in Patients with Persistent Ventricular Dysfunction After Stage I Palliation for Hypoplastic Left Heart Syndrome.

We sought to describe the clinical course for patients with hypoplastic left heart syndrome and persistent ventricular dysfunction and identify risk factors for death or transplantation before stage II palliation. 138 children undergoing stage I palliation from 2004 to 2011 were reviewed. Twenty-two (16 %) patients (seven Hybrid, 15 Norwood) with two consecutive echocardiograms reporting at least moderate dysfunction were included and compared to case-matched controls. Eleven of the 22 patients with dysfunction (50 %) underwent stage II, seven (32 %) were transplanted, and four (18 %) died prior to stage II. Of the patients who survived to hospital discharge (n = 17) following stage 1, 14 (82 %) required readmission for heart failure (HF) compared to only two (10 %) for controls (p < 0.001). Among patients with ventricular dysfunction, there was an increased use of ACE inhibitors or beta-blockers (82 vs. 25 %; p = 0.001), inotropes (71 vs. 15 %; p = 0.001), ventilation (58 vs. 10 %; p = 0.001), and ECMO (29 vs. 0 %; p = 0.014) for HF management post-discharge when compared to controls. There was a lower heart transplant-free survival at 7 months in patients with dysfunction compared to controls (50.6 vs. 90.9 %; p = 0.040). ECMO support (p = 0.001) and duration of inotropic support (p = 0.04) were significantly associated with death or transplantation before stage II palliation. Patients with ventricular dysfunction received more HF management and related admissions. Longer inotropic support should prompt discussion regarding alternative treatment strategies given its association with death or transplant.

Systemic inflammation increases energy expenditure following pediatric cardiopulmonary bypass.

OBJECTIVES: To examine the association between cardiopulmonary bypass-related systemic inflammation and resting energy expenditure in pediatric subjects following cardiac surgery. DESIGN: Single-center, prospective cohort study. SETTING: Pediatric cardiac critical care unit in Toronto, Canada. PATIENTS: Children with congenital heart disease undergoing cardiopulmonary bypass surgery. INTERVENTIONS: Resting energy expenditure was determined by indirect calorimetry and the modified Weir equation, using VO2 and VCO2 measured by in-line respiratory mass spectrometry. Measurements were taken at baseline and 6-hour intervals from separation from cardiopulmonary bypass for a maximum of 72 hours. Plasma interleukin-6, glucose delivery, feeding status, and cardiac output (calculated by Fick equation) were monitored at each resting energy expenditure measurement. MEASUREMENTS AND MAIN RESULTS: We studied 111 subjects at a median (interquartile range) age of 5.3 months (0.8-10.5 mo), weighing 5.7 kg (3.9-8.1 kg), of whom 88% underwent biventricular repair. Resting energy expenditure decreased from 51 kcal/kg/d to 45 kcal/kg/d during the study period. Resting energy expenditure was positively associated with increased plasma interleukin-6 (estimate variable, 1.76; p = 0.001) and inversely associated with preoperative methylprednisolone use (estimate variable, -6.7; p = 0.003) even after accounting for other predictors. Increase in cardiac output was also associated (estimate variable, 13.7; p < 0.0001) with higher resting energy expenditure. CONCLUSIONS: Resting energy expenditure ranges between 40 and 60 kcal/kg/d and decreases progressively in children following cardiopulmonary bypass surgery. It is directly associated with increased inflammation and higher cardiac output and inversely associated with anti-inflammatory strategies. Further studies are required to predict the appropriate caloric delivery in this cohort.

Clinical Epidemiology of Extubation Failure in the Pediatric Cardiac ICU: A Report From the Pediatric Cardiac Critical Care Consortium.

OBJECTIVE: To describe the clinical epidemiology of extubation failure in a multicenter cohort of patients treated in pediatric cardiac ICUs. DESIGN: Retrospective cohort study using prospectively collected clinical registry data. SETTING: Pediatric Cardiac Critical Care Consortium registry. PATIENTS: All patients admitted to the CICU at Pediatric Cardiac Critical Care Consortium hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analysis of all mechanical ventilation episodes in the registry from October 1, 2013, to July 31, 2014. The primary outcome of extubation failure was reintubation less than 48 hours after planned extubation. Repeated-measures analysis using generalized estimating equations to account for within patient and center correlation was performed to identify risk factors for extubation failure. Adjusted extubation failure rates for each hospital were calculated using logistic regression controlling for patient factors. Of 1,734 mechanical ventilation episodes (1,478 patients at eight hospitals) ending in a planned extubation, there were 100 extubation failures (5.8%). In multivariable analysis, only longer duration of mechanical ventilation was significantly associated with extubation failure (p = 0.01); the failure rate was 4% when ventilated less than 24 hours, 9% after 24 hours, and 13% after 7 days. For 503 patients intubated and extubated in the cardiac operating room, 15 patients (3%) failed extubation within 48 hours (12 within 24 hr). Case-mix-adjusted extubation failure rates ranged from 1.1% to 9.8% across hospitals. Patients failing extubation had greater median cardiac ICU length of stay (15 vs 3 d; p < 0.001) and in-hospital mortality (7.9 vs 1.2%; p < 0.001). CONCLUSIONS: Though extubation failure is uncommon overall, there may be opportunities to improve extubation readiness assessment in patients ventilated more than 24 hours. These data suggest that extubation in the operating room after cardiac surgery can be done with a low failure rate. We observed variation in extubation failure rates across hospitals, and future investigation must elucidate the optimal strategies of high-performing centers to reduce ventilation time while limiting extubation failures.