Methylprednisolone for Heart Surgery in Infants - A Randomized, Controlled Trial.

BACKGROUND: Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown. METHODS: We conducted a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes. The infants were randomly assigned to receive prophylactic methylprednisolone (30 mg per kilogram of body weight) or placebo, which was administered into the cardiopulmonary-bypass pump-priming fluid. The primary end point was a ranked composite of death, heart transplantation, or any of 13 major complications. Patients without any of these events were assigned a ranked outcome based on postoperative length of stay. In the primary analysis, the ranked outcomes were compared between the trial groups with the use of odds ratios adjusted for prespecified risk factors. Secondary analyses included an unadjusted odds ratio, a win ratio, and safety outcomes. RESULTS: A total of 1263 infants underwent randomization, of whom 1200 received either methylprednisolone (599 infants) or placebo (601 infants). The likelihood of a worse outcome did not differ significantly between the methylprednisolone group and the placebo group (adjusted odds ratio, 0.86; 95% confidence interval [CI], 0.71 to 1.05; P = 0.14). Secondary analyses (unadjusted for risk factors) showed an odds ratio for a worse outcome of 0.82 (95% CI, 0.67 to 1.00) and a win ratio of 1.15 (95% CI, 1.00 to 1.32) in the methylprednisolone group as compared with the placebo group, findings suggestive of a benefit with methylprednisolone; however, patients in the methylprednisolone group were more likely than those in the placebo group to receive postoperative insulin for hyperglycemia (19.0% vs. 6.7%, P<0.001). CONCLUSIONS: Among infants undergoing surgery with cardiopulmonary bypass, prophylactic use of methylprednisolone did not significantly reduce the likelihood of a worse outcome in an adjusted analysis and was associated with postoperative development of hyperglycemia warranting insulin in a higher percentage of infants than placebo. (Funded by the National Center for Advancing Translational Sciences and others; STRESS ClinicalTrials.gov number, NCT03229538.).

Timing of surgical repair and resource utilisation in infants with complete atrioventricular septal defect.

INTRODUCTION: Variation exists in the timing of surgery for balanced complete atrioventricular septal defect repair. We sought to explore associations between timing of repair and resource utilisation and clinical outcomes in the first year of life. METHODS: In this retrospective single-centre cohort study, we included patients who underwent complete atrioventricular septal defect repair between 2005 and 2019. Patients with left or right ventricular outflow tract obstruction and major non-cardiac comorbidities (except trisomy 21) were excluded. The primary outcome was days alive and out of the hospital in the first year of life. RESULTS: Included were 79 infants, divided into tertiles based on age at surgery (1st = 46 to 137 days, 2nd = 140 - 176 days, 3rd = 178 - 316 days). There were no significant differences among age tertiles for days alive and out of the hospital in the first year of life by univariable analysis (tertile 1, median 351 days; tertile 2, 348 days; tertile 3, 354 days; p = 0.22). No patients died. Fewer post-operative ICU days were used in the oldest tertile relative to the youngest, but days of mechanical ventilation and hospitalisation were similar. Clinical outcomes after repair and resource utilisation in the first year of life were similar for unplanned cardiac reinterventions, outpatient cardiology clinic visits, and weight-for-age z-score at 1 year. CONCLUSIONS: Age at complete atrioventricular septal defect repair is not associated with important differences in clinical outcomes or resource utilisation in the first year of life.

Calcium Chloride Infusions are Not Associated with Improved Outcomes in Neonates Undergoing Cardiac Operations.

Neonatal cardiac performance is dependent on calcium delivery to the myocardium. Little is known about the use and impact of calcium chloride infusions in neonates who undergo cardiac surgery. We hypothesized that the use of calcium chloride infusions would decrease the doses required of traditional inotropic and vasoactive medications by supporting cardiac output in this patient population. We performed a single-institution, retrospective, cohort study. All neonates (≤ 30 days old) undergoing cardiac surgery from 06/01/2015 through 12/31/2018 were included. Patients were divided into two groups: those who received postoperative calcium chloride infusions (calcium group) and those who did not (control group). The primary outcome was the occurrence of a maximum Vasoactive Inotropic Score (VIS) > 15 in the first 24 h following surgery. One hundred and thirty-five patients met inclusion criteria. Sixty-six patients received postoperative calcium infusions and 69 patients did not. Gestational age, weight at surgery, age at surgery, surgical complexity and cardiopulmonary bypass times were similar between groups. Forty-two (70%) patients receiving calcium had a postoperative maximum VIS > 15 compared with 38 (55%) patients not on a calcium infusion (p = 0.08). There were no differences in postoperative length of ventilation, time to enteral feeding, hospital LOS, or operative mortality between groups. Calcium chloride infusions in neonates who underwent cardiac surgery did not decrease exposure to other inotropic and vasoactive agents in the first 24 post-operative hours or improve patient outcomes.

Improved outcomes after implementation of a specialized pediatric cardiac rapid response team.

INTRODUCTION: The efficacy of a specialized pediatric cardiac rapid response team is unknown. We hypothesized that a specialized cardiac rapid response team would facilitate team-wide communication between the cardiac stepdown unit and cardiac intensive care unit (ICU) teams and improve patient care. MATERIALS AND METHODS: A specialized pediatric cardiac rapid response team was implemented in June 2015. All pediatric cardiac rapid response team activations and outcomes from implementation through December 2018 were reviewed. Cardiac arrests and unplanned transfers to the cardiac ICU were indexed to 1000 patient-days to account for inpatient volume trends and evaluated over time. RESULTS: There were 202 cardiac rapid response team activations in 108 unique patients during the study period. After implementation of the pediatric cardiac rapid response team, unplanned transfers from the cardiac stepdown unit to the cardiac ICU decreased from 16.8 to 7.1 transfers per 1000 patient days (p = 0.012). The stepdown unit cardiac arrest rate decreased from 1.2 to 0.0 arrests per 1000 patient-days (p = 0.015). There was one death on the cardiac stepdown unit in the 5 years since the implementation of the cardiac rapid response team, compared to four deaths in the previous 5 years. CONCLUSIONS: A reduction in unplanned cardiac ICU transfers, cardiac arrests, and mortality on the cardiac stepdown unit has been observed since the implementation of a specialized pediatric cardiac rapid response team. A specialized cardiac rapid response team may improve communication and empower the interdisciplinary care team to escalate care for patients experiencing clinical decline.

Overcoming underpowering: Trial simulations and a global rank end point to optimize clinical trials in children with heart disease.

BACKGROUND: Randomized controlled trials (RCTs) in children with heart disease are challenging and therefore infrequently performed. We sought to improve feasibility of perioperative RCTs for this patient cohort using data from a large, multicenter clinical registry. We evaluated potential enrollment and end point frequencies for various inclusion cohorts and developed a novel global rank trial end point. We then performed trial simulations to evaluate power gains with the global rank end point and with use of planned covariate adjustment as an analytic strategy. METHODS: Data from the Society of Thoracic Surgery-Congenital Heart Surgery Database (STS-CHSD, 2011-2016) were used to support development of a consensus-based global rank end point and for trial simulations. For Monte Carlo trial simulations (n = 50,000/outcome), we varied the odds of outcomes for treatment versus placebo and evaluated power based on the proportion of trial data sets with a significant outcome (P < .05). RESULTS: The STS-CHSD study cohort included 35,967 infant index cardiopulmonary bypass operations from 103 STS-CHSD centers, including 11,411 (32%) neonatal cases and 12,243 (34%) high-complexity (Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality category ≥4) cases. In trial simulations, study power was 21% for a mortality-only end point, 47% for a morbidity and mortality composite, and 78% for the global rank end point. With covariate adjustment, power increased to 94%. Planned covariate adjustment was preferable to restricting to higher-risk cohorts despite higher event rates in these cohorts. CONCLUSIONS: Trial simulations can inform trial design. Our findings, including the newly developed global rank end point, may be informative for future perioperative trials in children with heart disease.

Rationale and design of the STeroids to REduce Systemic inflammation after infant heart Surgery (STRESS) trial.

For decades, physicians have administered corticosteroids in the perioperative period to infants undergoing heart surgery with cardiopulmonary bypass (CPB) to reduce the postoperative systemic inflammatory response to CPB. Some question this practice because steroid efficacy has not been conclusively demonstrated and because some studies indicate that steroids could have harmful effects. STRESS is a randomized, placebo-controlled, double-blind, multicenter trial designed to evaluate safety and efficacy of perioperative steroids in infants (age < 1 year) undergoing heart surgery with CPB. Participants (planned enrollment = 1,200) are randomized 1:1 to methylprednisolone (30 mg/kg) administered into the CPB pump prime versus placebo. The trial is nested within the existing infrastructure of the Society of Thoracic Surgeons Congenital Heart Surgery Database. The primary outcome is a global rank score of mortality, major morbidities, and hospital length of stay with components ranked commensurate with their clinical severity. Secondary outcomes include several measures of major postoperative morbidity, postoperative hospital length of stay, and steroid-related safety outcomes including prevalence of hyperglycemia and postoperative infectious complications. STRESS will be one of the largest trials ever conducted in children with heart disease and will answer a decades-old question related to safety and efficacy of perioperative steroids in infants undergoing heart surgery with CPB. The pragmatic "trial within a registry" design may provide a mechanism for conducting low-cost, high-efficiency trials in a heretofore-understudied patient population.

Influence of Early Extubation Location on Outcomes Following Pediatric Cardiac Surgery.

OBJECTIVES: Early extubation following pediatric cardiac surgery is common, but debate exists whether location affects outcome, with some centers performing routine early extubations in the operating room (odds ratio) and others in the cardiac ICU. We aimed to define early extubation practice variation across hospitals and assess impact of location on hospital length-of-stay and other outcomes. DESIGN: Secondary analysis of the Pediatric Cardiac Critical Care Consortium registry. SETTING: Twenty-eight Pediatric Cardiac Critical Care Consortium hospitals. PATIENTS: Patients undergoing Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality category 1-3 operations between August 2014 and February 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined early extubation as extubation less than 6 hours after postoperative admission. Hospitals were categorized based on the proportion of their early extubation patients who underwent an odds ratio extubation. Categories included low- (< 50% of early extubation, n = 12), medium- (50%-90%, n = 8), or high- (> 90%, n = 8) frequency odds ratio early extubation centers. The primary outcome of interest was postoperative hospital length-of-stay. We analyzed 16,594 operations (9,143 early extubation, 55%). Rates of early extubation ranged from 16% to 100% across hospitals. Odds ratio early extubation rates varied from 16% to 99%. Patient characteristics were similar across hospital odds ratio early extubation categories. Early extubation rates paralleled the hospital odds ratio early extubation rates-77% patients underwent early extubation at high-frequency odds ratio extubation centers compared with 39% at low-frequency odds ratio extubation centers (p < 0.001). High- and low-frequency odds ratio early extubation hospitals had similar length-of-stay, cardiac arrest rates, and low mortality. However, high-frequency odds ratio early extubation hospitals used more noninvasive ventilation than low-frequency hospitals (15% vs. 9%; p < 0.01), but had fewer extubation failures (3.6% vs. 4.5%; p = 0.02). CONCLUSIONS: Considerable variability exists in early extubation practices after low- and moderate-complexity pediatric cardiac surgery. In this patient population, hospital length-of-stay did not differ significantly between centers with different early extubation strategies based on location or frequency.

Central Venous Catheter Utilization and Complications in the Pediatric Cardiac ICU: A Report From the Pediatric Cardiac Critical Care Consortium (PC4).

OBJECTIVES: Current central venous catheter utilization in patients within pediatric cardiac ICUs is not well elucidated. We aim to describe current use of central venous catheters in a multi-institutional cohort and to explore the prevalence and risk factors for central line-associated thrombosis and central line-associated bloodstream infections. DESIGN: Observational analysis. SETTING: Pediatric Cardiac Critical Care Consortium hospitals. PATIENTS: Hospitalizations with at least one cardiac ICU admission from October 2013 to July 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 17,846 hospitalizations and 69% included greater than or equal to one central venous catheter. Central venous catheter use was higher in younger patients (86% neonates). Surgical hospitalizations included at least one central venous catheter 88% of the time compared with 35% of medical hospitalizations. The most common location for central venous catheters was internal jugular (46%). Central venous catheters were in situ a median of 4 days (interquartile range, 2-10). There were 248 hospitalizations (2% overall, 1.8% medical, and 2.1% surgical) with at least one central line-associated thrombosis (271 total thromboses). Thrombosis was diagnosed at a median of 7 days (interquartile range, 4-14) after catheter insertion. There were 127 hospitalizations (1% overall, 1.4% medical, and 1% surgical) with at least one central line-associated bloodstream infection (136 total infections) with no association with catheter type or location. Central line-associated bloodstream infection was diagnosed at a median of 19 days (interquartile range, 8-36) after catheter insertion. Significant risk factors for central line-associated thrombosis and central line-associated bloodstream infection were younger age, greater surgical complexity, and total catheter days. CONCLUSIONS: Utilization of central venous catheters in pediatric cardiac ICUs differs according to indication for hospitalization. Although thrombosis and central line-associated bloodstream infection are infrequent complications of central venous catheter use in cardiac ICU patients, these events can have important short- and long-term consequences for patients. Total central venous catheter line days were the only modifiable risk factor identified. Future study must focus on understanding central venous catheter practices in high-risk patient subgroups that reduce the prevalence of thrombosis and central line-associated bloodstream infection.

Plasma Neutrophil Gelatinase-Associated Lipocalin Is Associated With Acute Kidney Injury and Clinical Outcomes in Neonates Undergoing Cardiopulmonary Bypass.

OBJECTIVES: Acute kidney injury is a frequent complication following neonatal cardiac surgery and is associated with significant morbidity and mortality. The objectives of this study were to determine if plasma neutrophil gelatinase-associated lipocalin levels were associated with acute kidney injury and clinical outcomes in neonates with congenital heart disease undergoing cardiopulmonary bypass. DESIGN: Retrospective single-center observational study. SETTING: A pediatric cardiac ICU within a tertiary-care academic hospital. PATIENTS: Patients age less than 30 days undergoing cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma neutrophil gelatinase-associated lipocalin peaked at 12 hours postcardiopulmonary bypass and more than doubled compared with preoperative levels. Higher preoperative and 24-hour postoperative neutrophil gelatinase-associated lipocalin levels were associated with acute kidney injury (r = 0.30, r = 0.49), longer duration of mechanical ventilation (r = 0.40, r = 0.51), ICU (r = 0.32, r = 0.33) and hospital lengths of stay (r = 0.28, r = 0.32), and total hospital charges (r = 0.35, r = 0.30; all p values < 0.05). CONCLUSIONS: Both preoperative and 24-hour postoperative plasma neutrophil gelatinase-associated lipocalin levels are associated with acute kidney injury and worse clinical outcomes in neonates undergoing cardiac surgery. Plasma neutrophil gelatinase-associated lipocalin levels may have a role in risk stratification for predicting postoperative renal dysfunction as well as providing a potential clinical trajectory in the postoperative period.

Lessons learned in the use of clinical registry data in a multi-centre prospective study: the Pediatric Heart Network Residual Lesion Score Study.

BACKGROUND: Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology. OBJECTIVES: We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders' perspectives, and provide recommendations to guide future studies using this methodology. METHODS: The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff. RESULTS: Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes. CONCLUSIONS: Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.

The Pediatric Heart Network Scholar Award programme: a unique mentored award embedded within a multicentre network.

BACKGROUND: The Pediatric Heart Network designed a career development award to train the next generation of clinician scientists in paediatric-cardiology-related research, a historically underfunded area. We sought to identify the strengths/weaknesses of the programme and describe the scholars' academic achievements and the network's return on investment. METHODS: Survey questions designed to evaluate the programme were sent to applicants - 13 funded and 19 unfunded applicants - and 20 mentors and/or principal investigators. Response distributions were calculated. χ2 tests of association assessed differences in ratings of the application/selection processes among funded scholars, unfunded applicants, and mentors/principal investigators. Scholars reported post-funding academic achievements. RESULTS: Survey response rates were 88% for applicants and 100% for mentor/principal investigators. Clarity and fairness of the review were rated as "clear/fair" or "very clear/very fair" by 98% of respondents, but the responses varied among funded scholars, unfunded applicants, and mentors/principal investigators (clarity χ2=10.85, p=0.03; fairness χ2=16.97, p=0.002). Nearly half of the unfunded applicants rated feedback as "not useful" (47%). "Expanding their collaborative network" and "increasing publication potential" were the highest-rated benefits for scholars. Mentors/principal investigators found the programme "very" valuable for the scholars (100%) and the network (75%). The 13 scholars were first/senior authors for 97 abstracts and 109 manuscripts, served on 22 Pediatric Heart Network committees, and were awarded $9,673,660 in subsequent extramural funding for a return of ~$10 for every scholar dollar spent. CONCLUSIONS: Overall, patient satisfaction with the Scholar Award was high and scholars met many academic markers of success. Despite this, programme challenges were identified and improvement strategies were developed.

Clinical epidemiology and centre variation in chylothorax rates after cardiac surgery in children: a report from the Pediatric Cardiac Critical Care Consortium.

Introduction Chylothorax after paediatric cardiac surgery incurs significant morbidity; however, a detailed understanding that does not rely on single-centre or administrative data is lacking. We described the present clinical epidemiology of postoperative chylothorax and evaluated variation in rates among centres with a multicentre cohort of patients treated in cardiac ICU. METHODS: This was a retrospective cohort study using prospectively collected clinical data from the Pediatric Cardiac Critical Care Consortium registry. All postoperative paediatric cardiac surgical patients admitted from October, 2013 to September, 2015 were included. Risk factors for chylothorax and association with outcomes were evaluated using multivariable logistic or linear regression models, as appropriate, accounting for within-centre clustering using generalised estimating equations. RESULTS: A total of 4864 surgical hospitalisations from 15 centres were included. Chylothorax occurred in 3.8% (n=185) of hospitalisations. Case-mix-adjusted chylothorax rates varied from 1.5 to 7.6% and were not associated with centre volume. Independent risk factors for chylothorax included age <1 year, non-Caucasian race, single-ventricle physiology, extracardiac anomalies, longer cardiopulmonary bypass time, and thrombosis associated with an upper-extremity central venous line (all p<0.05). Chylothorax was associated with significantly longer duration of postoperative mechanical ventilation, cardiac ICU and hospital length of stay, and higher in-hospital mortality (all p<0.001). CONCLUSIONS: Chylothorax after cardiac surgery in children is associated with significant morbidity and mortality. A five-fold variation in chylothorax rates was observed across centres. Future investigations should identify centres most adept at preventing and managing chylothorax and disseminate best practices.

Intraoperative Steroid Use and Outcomes Following the Norwood Procedure: An Analysis of the Pediatric Heart Network's Public Database.

OBJECTIVE: Data supporting the use of perioperative steroids during cardiac surgery are conflicting, and most pediatric studies have been limited by small sample sizes and/or diverse cardiac diagnoses. The objective of this study was to determine if intraoperative steroid administration improved outcomes following the Norwood procedure. DESIGN: A retrospective analysis was performed on the 549 neonates who underwent a Norwood procedure in the publicly available datasets from the Pediatric Heart Network's Single Ventricle Reconstruction trial. Groups were compared to determine if outcomes differed between intraoperative steroid recipients (n = 498, 91%) and nonrecipients (n = 51, 9%). SETTING: Fifteen North American centers. SUBJECTS: Infants enrolled in the Single Ventricle Reconstruction trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics and intraoperative variables were similar between groups with the exception of a shorter duration of cross clamp and cardiopulmonary bypass time in the group that received steroids. Subjects who did not receive intraoperative steroids had improved hospital survival (94% vs 83%, p = 0.03) but longer ICU stays (16 d; interquartile range, 12-33 vs 14 d; interquartile range, 9-28; p = 0.04) and hospital stays (29 d; interquartile range, 21-50 vs 23 d; interquartile range, 15-40; p = 0.01) than steroid recipients. In multivariate analysis, lengths of stay associations were no longer significant, but hospital survival trended toward favoring the nonsteroid group with an odds ratio of 3.52 (95% CI, 0.98-12.64; p = 0.054). CONCLUSIONS: In the large multicentered Single Ventricle Reconstruction trial, there was widespread use of intraoperative steroids. Intraoperative steroid administration was not associated with an improvement in outcomes and may be associated with a reduction in hospital survival in neonates undergoing the Norwood procedure. This study highlights the need for a randomized control trial.

Feasibility and Efficacy of Defatted Human Milk in the Treatment for Chylothorax After Cardiac Surgery in Infants.

Chylothorax is a well-described complication after cardiothoracic surgery in children. Medical nutritional therapy for chylothorax includes medium-chain triglyceride (MCT) formulas and reduction in enteral long-chain triglyceride intake to reduce chyle production. Human milk is usually eliminated from the diet of infants with chylothorax because of its high long-chain triglyceride content. However, given the immunologic properties of human milk, young infants with chylothorax may benefit from using human milk over human milk substitutes. We performed a retrospective cohort study to describe the feasibility and efficacy of defatted human milk (DHM) for the treatment for chylothorax in infants after cardiac surgery and to compare growth outcomes between infants treated with DHM (n = 14) versus MCT formula (n = 21). There were no differences in mortality or length of hospital stay between the DHM and MCT formula treatment groups. The DHM treatment group had a significantly higher weight-for-age z-score at hospital discharge compared to the MCT formula group with median z-scores of -1 (-2 to 0.5) and -1.5 (-2 to 0), respectively (p = 0.02). In infants with chylothorax after cardiac surgery, DHM is a safe and feasible medical nutritional treatment and may have potential benefits for improved nutrition and growth.

Randomized Clinical Trial of Preoperative Feeding to Evaluate Intestinal Barrier Function in Neonates Requiring Cardiac Surgery.

OBJECTIVES: To evaluate intestinal barrier function in neonates undergoing cardiac surgery using lactulose/mannitol (L/M) ratio measurements, and to determine correlations with early breast milk feeding. STUDY DESIGN: This was a single-center, prospective, randomized pilot study of 27 term-born neonates (≥ 37 weeks gestation) requiring cardiac surgery who were randomized to 1 of 2 preoperative feeding groups: nil per os (NPO) or trophic (10 mL/kg/day) breast milk feeds. At 3 time points (preoperative [preop], postoperative [postop] day 7, and postop day 14), subjects were administered an oral L/M solution, after which urine L/M ratios were measured using gas chromatography, with higher ratios indicative of increased intestinal permeability. Trends over time in the mean urine L/M ratios for each group were estimated using a general linear mixed model. RESULTS: There were no adverse events related to preoperative trophic feeding. In the NPO group (n = 13), the mean urine L/M ratio was 0.06 at preop, 0.12 at postop day 7, and 0.17 at postop day 14. In the trophic breast milk feeds group (n = 14), the mean urine L/M ratio was 0.09 at preop, 0.19 at postop day 7, and 0.15 at postop day 14. In both groups, L/M ratios were significantly higher at postop day 7 and postop day 14 compared with preop (P < .05). CONCLUSION: Neonates have increased intestinal permeability after cardiac surgery extending to at least postop day 14. This pilot study was not powered to detect differences in benefit or adverse events comparing the NPO and trophic breast milk feeds groups. Further studies to identify mechanisms of intestinal injury and therapeutic interventions are warranted. TRIAL REGISTRATION: Registered with ClinicalTrials.gov: NCT01475357.

Perioperative feeding management of neonates with CHD: analysis of the Pediatric Cardiac Critical Care Consortium (PC4) registry.

UNLABELLED: Introduction The optimal perioperative feeding strategies for neonates with CHD are unknown. In the present study, we describe the current feeding practices across a multi-institutional cohort. METHODS: Inclusion criteria for this study were as follows: all neonates undergoing cardiac surgery admitted to the cardiac ICU for ⩾24 hours preoperatively between October, 2013 and July, 2014 in the Pediatric Cardiac Critical Care Consortium registry. RESULTS: The cohort included 251 patients from eight centres. The most common diagnoses included the following: hypoplastic left heart syndrome (17%), coarctation/aortic arch hypoplasia (18%), and transposition of the great arteries (22%); 14% of the patients were <37weeks of gestational age. The median total hospital length of stay was 21 days (interquartile range (IQR) 14-35) and overall mortality was 8%. Preoperative feeding occurred in 133 (53%) patients. The overall preoperative feeding rates across centres ranged from 29 to 79%. Postoperative feeds started on median day 2 (IQR 1-4); for patients with hypoplastic left heart syndrome postoperative feeds started on median day 4. Postoperative feeds were initiated in 89 (35%) patients before extubation (range across centres: 21-61%). The median cardiac ICU discharge feeding volume was 108 cc/kg/day, varying across centres. The mean discharge weight was 280 g above birth weight, ranging from +100 to 430 g across centres. A total of 110 (44%) patients had discharge feeding tubes, ranging from 6 to 80% across centres, and 40/110 patients had gastrostomy/enterostomy tubes placed. In addition, eight (3.2%) patients developed necrotising enterocolitis - three preoperatively and five postoperatively. CONCLUSION: In this cohort, neonatal feeding practices and outcomes appear to vary across diagnostic groups and institutions. Only half of the patients received preoperative enteral nutrition; almost half had discharge feeding tubes. Multi-institutional collaboration is necessary to determine feeding strategies associated with best clinical outcomes.

Factors associated with neurodevelopment for children with single ventricle lesions.

OBJECTIVE: To measure neurodevelopment at 3 years of age in children with single right-ventricle anomalies and to assess its relationship to Norwood shunt type, neurodevelopment at 14 months of age, and patient and medical factors. STUDY DESIGN: All subjects in the Single Ventricle Reconstruction Trial who were alive without cardiac transplant were eligible for inclusion. The Ages and Stages Questionnaire (ASQ, n = 203) and other measures of behavior and quality of life were completed at age 3 years. Medical history, including measures of growth, feeding, and complications, was assessed through annual review of the records and phone interviews. The Bayley Scales of Infant Development, Second Edition (BSID-II) scores from age 14 months were also evaluated as predictors. RESULTS: Scores on each ASQ domain were significantly lower than normal (P < .001). ASQ domain scores at 3 years of age varied nonlinearly with 14-month BSID-II. More complications, abnormal growth, and evidence of feeding, vision, or hearing problems were independently associated with lower ASQ scores, although models explained <30% of variation. Type of shunt was not associated with any ASQ domain score or with behavior or quality-of-life measures. CONCLUSION: Children with single right-ventricle anomalies have impaired neurodevelopment at 3 years of age. Lower ASQ scores are associated with medical morbidity, and lower BSID-II scores but not with shunt type. Because only a modest percentage of variation in 3-year neurodevelopmental outcome could be predicted from early measures, however, all children with single right-ventricle anomalies should be followed longitudinally to improve recognition of delays.

Perioperative exposure to volatile organic compounds in neonates undergoing cardiac surgery.

OBJECTIVE: Volatile organic compounds (VOCs) are used in the sterilization and manufacture of medical equipment. These compounds have high vapor pressures with low water solubility and are emitted as gases from solids or liquids. They can be mutagenic, neurotoxic, genotoxic, and/or carcinogenic. Safe limits of exposure are not known for neonates. This study examined determinants of exposure in newborns undergoing cardiac surgery. METHODS: Twenty metabolites of 16 VOCs (eg, xylene, cyanide, acrolein, acrylonitrile, N, N-dimethylformamide, 1,3-butadiene, styrene, and benzene) were measured as metabolites in daily urine samples collected from 10 neonates undergoing cardiac operations (n = 150 samples). Metabolites were quantified using reversed-phase ultra-high performance liquid chromatography and electrospray ionization tandem mass spectrometry. Repeated measures analysis of covariance was performed for each metabolite to examine associations with use of medical devices. RESULTS: At least 3 metabolites were detected in every sample. The median number of metabolites detected in each sample was 14 (range, 3-15). In a model controlling for other factors, the use of extracorporeal membrane oxygenation was associated with significantly (P ≤ .05) greater metabolite levels of acrolein, acrylonitrile, ethylene oxide, propylene oxide, styrene, and ethylbenzene. Patients breathing ambient air had greater levels of metabolites of acrolein, xylene, N,N-dimethylformamide, methyl isocyanate, cyanide, 1,3-butadiene (all P ≤ .05). CONCLUSIONS: Exposure to volatile organic compounds is pervasive in newborns undergoing cardiac surgery. Sources of exposure likely include medical devices and inhalation from the air in the intensive care unit. The contribution of VOC exposure during cardiac surgery in newborns to adverse outcomes warrants further evaluation.

Evaluating registry-based trial economics: Results from the STRESS clinical trial.

Background: Registry-based trials have the potential to reduce randomized clinical trial (RCT) costs. However, observed cost differences also may be achieved through pragmatic trial designs. A systematic comparison of trial costs across different designs has not been previously performed. Methods: We conducted a study to compare the current Steroids to Reduce Systemic inflammation after infant heart surgery (STRESS) registry-based RCT vs. two established designs: pragmatic RCT and explanatory RCT. The primary outcome was total RCT design costs. Secondary outcomes included: RCT duration and personnel hours. Costs were estimated using the Duke Clinical Research Institute's pricing model. Results: The Registry-Based RCT estimated duration was 31.9 weeks greater than the other designs (259.5 vs. 227.6 weeks). This delay was caused by the Registry-Based design's periodic data harvesting that delayed site closing and statistical reporting. Total personnel hours were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design (52,488 vs 29,763 vs. 24,480 h, respectively). Total costs were greatest for the Explanatory design followed by the Pragmatic design and the Registry-Based design ($10,140,263 vs. $4,164,863 vs. $3,268,504, respectively). Thus, Registry-Based total costs were 32 % of the Explanatory and 78 % of the Pragmatic design. Conclusion: Total costs for the STRESS RCT with a registry-based design were less than those for a pragmatic design and much less than an explanatory design. Cost savings reflect design elements and leveraging of registry resources to improve cost efficiency, but delays to trial completion should be considered.