Activation of renal epithelial Na+ channels (ENaC) in infants with congenital heart disease.

Introduction: This study was designed to measure the concentration and activity of urinary proteases that activate renal epithelial sodium channel (ENaC) mediated Na+ transport in infants with congenital heart disease, a potential mechanism for fluid retention. Methods: Urine samples from infants undergoing cardiac surgery were collected at three time points: T1) pre-operatively, T2) 6-8 h after surgery, and T3) 24 h after diuretics. Urine was collected from five heathy infant controls. The urine was tested for four proteases and whole-cell patch-clamp testing was conducted in renal collecting duct M-1 cells to test whether patient urine increased Na+ currents consistent with ENaC activation. Results: Heavy chain of plasminogen, furin, and prostasin were significantly higher in cardiac patients prior to surgery compared to controls. There was no difference in most proteases before and after surgery. Urine from cardiac patients produced a significantly greater increase in Na+ inward currents compared to healthy controls. Conclusion: Urine from infants with congenital heart disease is richer in proteases and has the potential to increase activation of ENaC in the nephron to enhance Na+ reabsorption, which may lead to fluid retention in this population.

Epinephrine dosing strategies during pediatric extracorporeal cardiopulmonary resuscitation reveal novel impacts on survival: A multicenter study utilizing time-stamped epinephrine dosing records.

OBJECTIVES: To describe epinephrine dosing distribution using time-stamped data and assess the impact of dosing strategy on survival after ECPR in children. METHODS: This was a retrospective study at five pediatric hospitals of children <18 years with an in-hospital ECPR event. Mean number of epinephrine doses was calculated for each 10-minute CPR interval and compared between survivors and non-survivors. Patients were also divided by dosing strategy into a frequent epinephrine group (dosing interval of ≤5 min/dose throughout the first 30 minutes of the event), and a limited epinephrine group (dosing interval of ≤5 min/dose for the first 10 minutes then >5 min/dose for the time between 10 and 30 minutes). RESULTS: A total of 191 patients were included. Epinephrine was not evenly distributed throughout ECPR, with 66% of doses being given during the first half of the event. Mean number of epinephrine doses was similar between survivors and non-survivors the first 10 minutes (2.7 doses). After 10 minutes, survivors received fewer doses than non-survivors during each subsequent 10-minute interval. Adjusted survival was not different between strategy groups [OR of survival for frequent epinephrine strategy: 0.78 (95% CI 0.36-1.69), p = 0.53]. CONCLUSIONS: Survivors received fewer doses than non-survivors after the first 10 minutes of CPR and although there was no statistical difference in survival based on dosing strategy, the findings of this study question the conventional approach to EPCR analysis that assumes dosing is evenly distributed.

Impact of Extubation Time on Feeding Outcomes after Neonatal Cardiac Surgery: A Single-Center Study.

This study aimed to examine the impact of timing of extubation on feeding outcomes in neonates after surgery for congenital heart disease. This was a single-center retrospective study between December 2014 and June 2020. Patients were divided into three categories: extubated in the OR (immediate), extubated in the intensive care unit (ICU) between 0 and 3 days post-procedure (early), and extubated >3 days post-procedure (delayed). Comparing the immediate and early groups, we found no difference in time to first enteral feed (1.3 days (1.0-3.4) vs. 2.3 days (1.1-3.3), p = 0.27). There was no difference in time to first oral feed (2.0 days (1.1-4.5) vs. 3.1 days (1.8-4.4), p = 0.34) and time to goal feed (6.0 days (3.2-8.3) vs. 6.9 days (5.0-9.0), p = 0.15)). There was no difference in all oral feeds at one year: 88% vs. 98%, p = 0.16. The delayed extubation group performed significantly worse on all measures. Immediate and early extubation displayed no differences in feeding outcomes and length of stay in this study, while delayed extubation performed worse on all measures. Thus, we believe that clinicians should emphasize extubation within 3 days post-surgery to improve feeding outcomes while minimizing time hospitalized.

Antibiotic use in nonintubated children with bronchiolitis in the intensive care unit.

INTRODUCTION: Antibiotic use may shorten mechanical ventilation duration and length of stay for patients with bronchiolitis that require intubation. The goals of this study were to describe antibiotic use in previously healthy children with bronchiolitis admitted to the intensive care unit (ICU) for noninvasive respiratory support and to describe associations of early antibiotic use with clinical outcomes. METHODS: The Pediatric Health Information Systems database was queried for children <2 years of age without significant comorbidities admitted to the ICU for bronchiolitis. Children requiring mechanical ventilation on the first ICU day were excluded. Two groups were analyzed: those patients receiving antibiotics on the first day of their ICU stay (early antibiotics), and those receiving no antibiotics on their first ICU day (no antibiotics). Primary outcome was the length of ICU stay. RESULTS: A total of 11,029 admissions met criteria, 2522 (22.9%) in the early antibiotic group, and 8507 (77.1%) in the no antibiotic group. The use of early antibiotics varied by center from 10% to 54%. In multivariate analysis, the early antibiotic group had similar ICU length of stay compared to the no antibiotic group (relative risk, RR [95% confidence interval, CI] 1.01 [0.98-1.05]). For patients on noninvasive ventilation, the first ICU day early antibiotics did not impact ICU length of stay (RR [95% CI] 0.97 [0.92-1.02]) or need for intubation (RR [95% CI] 1.11 [0.77-1.58]). CONCLUSION: Early antibiotic use was common with significant variation between centers. Early antibiotic use was not associated with improved clinical outcomes in children admitted to the ICU for noninvasive respiratory support for bronchiolitis.

Preventing Cardiac Arrest in the Pediatric Cardiac Intensive Care Unit Through Multicenter Collaboration.

Importance: Preventing in-hospital cardiac arrest (IHCA) likely represents an effective strategy to improve outcomes for critically ill patients, but feasibility of IHCA prevention remains unclear. Objective: To determine whether a low-technology cardiac arrest prevention (CAP) practice bundle decreases IHCA rate. Design, Setting, and Participants: Pediatric cardiac intensive care unit (CICU) teams from the Pediatric Cardiac Critical Care Consortium (PC4) formed a collaborative learning network to implement the CAP bundle consistent with the Institute for Healthcare Improvement framework; 15 hospitals implemented the bundle voluntarily. Risk-adjusted IHCA incidence rates were analyzed across 2 time periods, 12 months (baseline) and 18 months after CAP implementation (intervention) using difference-in-differences (DID) regression to compare 15 CAP and 16 control PC4 hospitals that chose not to participate in CAP but had IHCA rates tracked in the PC4 registry. Patients deemed at high risk for IHCA, based on a priori evidence-based criteria and empirical hospital-specific criteria, were selected to receive the CAP bundle. Data were collected from July 2018 to December 2019, and data were analyzed from March to August 2020. Interventions: CAP bundle included 5 elements developed to promote increased situational awareness and communication among bedside clinicians to recognize and mitigate deterioration in high-risk patients. Main Outcomes and Measures: Risk-adjusted IHCA incidence rate across all CICU admissions (IHCA events divided by all admissions). Results: The bundle was activated in 2664 of 10 510 CAP hospital admissions (25.3%); admission characteristics were similar across study periods. There was a 30% relative reduction in risk-adjusted IHCA incidence rate at CAP hospitals (intervention period: 2.6%; 95% CI, 2.2-2.9; baseline: 3.7%; 95% CI, 3.1-4.0), but no change at control hospitals (intervention period: 2.7%; 95% CI, 2.3-2.9; baseline: 2.7%; 95% CI, 2.2-3.0). DID analysis confirmed significantly reduced odds of IHCA among all admissions at CAP hospitals compared with control hospitals during the intervention period vs baseline (odds ratio, 0.72; 95% CI, 0.56-0.91; P = .01). DID odds ratios were 0.72 (95% CI, 0.53-0.98) for the surgical subgroup, 0.74 (95% CI, 0.48-1.14) for the medical subgroup, and 0.72 (95% CI, 0.50-1.03) for the high-risk admission subgroup at CAP hospitals after intervention. All-cause risk-adjusted mortality rate did not change after intervention. Conclusions and Relevance: Implementation of this CAP bundle led to significant IHCA reduction across multiple pediatric CICUs. Future studies may determine if this bundle can be effective in other critically ill populations.

Postoperative Breath-Holding Spells Requiring Cardiopulmonary Resuscitation After Cardiopulmonary Bypass.

Breath-holding spells are common in childhood and can be associated with bradycardia and pulselessness. This report details severe breath-holding spells complicating postoperative management after atrial septal defect closure. The patient required cardiopulmonary resuscitation despite the use of a temporary pacemaker to prevent bradycardia. After multiple episodes of chest compressions, the decision was made to not intervene immediately to pulselessness and the patient was able to recover without further intervention.

Enteral Sodium Chloride Supplementation and Fluid Balance in Children Receiving Diuretics.

The use of sodium chloride (NaCl) supplementation in children being prescribed diuretics is controversial due to concerns that supplementation could lead to fluid retention. This is a single-center retrospective study in which fluid balance and diuretic dosing was examined in children prescribed enteral NaCl supplements for hyponatremia while receiving loop diuretics. The aim of this study was to determine whether significant fluid retention occurred with the addition of NaCl. Fifty-five patients with 68 events were studied. The median age was 5.2 months, and 82% were hospitalized for cardiac disease. Daily fluid balance the seven days prior to NaCl supplementation was lower than the seven days after, with measurement of: median 17 mL/kg/day (7-26) vs. 22 mL/kg/day (13-35) (p = 0.0003). There was no change in patient weight after supplementation (p = 0.63). There was no difference in the median loop diuretic dose before and after supplementation, with the diuretic dose in furosemide equivalents of 3.2 mL/kg/day (2.3-4.4) vs. 3.2 mL/kg/day (2.2-4.7) (p = 0.50). There was no difference in the proportion of patients receiving thiazide diuretics after supplementation (56% before vs. 50% after (p = 0.10)). NaCl supplementation in children receiving loop diuretics increased calculated fluid balance, but weight was unchanged, and this was not associated with an increase in diuretic needs, suggesting clinicians did not consider the increase in fluid balance to be clinically significant.

Trends and Variation in Care and Outcomes for Children Hospitalized With Acute Gastroenteritis.

OBJECTIVES: Assess trends in inpatient acute gastroenteritis (AGE) management across children's hospitals and identify elements of AGE management associated with resource use. METHODS: We examined inpatient stays for children 6 months to 18 years hospitalized with AGE from 2009 to 2018 using the Pediatric Health Information System database. We characterized demographics, hospital-level resource use (ie, medications, laboratories, and imaging), and outcomes (ie, cost per case, 14-day revisit rates, and length of stay [LOS]). We compared demographic characteristics and resource use between 2009 to 2013 and 2014 to 2018 using χ2 and Wilcoxon rank-sum tests. We grouped hospitals on the basis of 2009 use of each resource and trended use over time using logistic regression. Annual change in mean cost and LOS were estimated by using models of log-transformed data. RESULTS: Across 32 354 hospitalizations at 38 hospitals, there was a high use of electrolyte testing (85.4%) and intravenous fluids (84.1%) without substantial changes over time. There were significant reductions in the majority of laboratory, medication, and imaging resources across hospitals over the study period. The most notable reductions were for rotavirus and stool testing. Many hospitals saw a decrease in LOS, with only 3 noting an increased revisit rate. Reductions in cost per case over time were most associated with decreases in imaging, laboratory testing, and LOS. CONCLUSIONS: Significant variation in resource use for children hospitalized with AGE coupled with high use of resources discouraged in AGE guidelines highlights potential opportunities to improve resource use that may be addressed in future AGE guidelines and quality improvement initiatives.

Association Between Postoperative Dexmedetomidine Use and Arrhythmias in Infants After Cardiac Surgery.

BACKGROUND: Dexmedetomidine has been suggested as an arrhythmia prophylactic agent after surgery for congenital heart disease due to its heart rate lowering effect, though studies are conflicting. We sought to study the effect of dexmedetomidine in infants that are at highest risk for arrhythmias. METHODS: Retrospective cohort study of infants less than six months of age undergoing cardiopulmonary bypass for congenital heart disease. The arrhythmia incidence in the first 48 hours after surgery in infants receiving dexmedetomidine for sedation was compared to those that did not receive dexmedetomidine. RESULTS: A total of 309 patients were included, 206 patients who did not receive dexmedetomidine and 103 patients who did. The incidence of tachyarrhythmias was similar between the non-DEX group and the DEX group (19% vs 15%, P = .34). When adjusted for baseline differences, the non-DEX group did not have an increased risk of postoperative tachyarrhythmias (odds ratio [OR]: 1.4, 95% confidence interval [CI]: 0.5-3.8). The non-DEX group had an increased need for treatment for arrhythmias (18% vs 8%, P = .012). The three lesions with baseline higher risk for arrhythmias (tetralogy of Fallot, transposition of the great arteries, and complete atrioventricular canal) had an increased incidence of tachyarrhythmias in the non-DEX group (34% vs 6%, P = .027). This risk was not significant in multivariate analysis (OR: 2.5, 95% CI: 0.4-15.5). CONCLUSIONS: High-risk infants had decreased incidence of tachyarrhythmias when receiving dexmedetomidine, though this was not significant after accounting for baseline differences between groups.

Perioperative serum albumin and its influence on clinical outcomes in neonates and infants undergoing cardiac surgery with cardiopulmonary bypass: a multi-centre retrospective study.

Hypoalbuminemia is associated with morbidity and mortality in critically ill children. In this multi-centre retrospective study, we aimed to determine normative values of serum albumin in neonates and infants with congenital heart disease, evaluate perioperative changes in albumin levels, and determine if low serum albumin influences post-operative outcomes. Consecutive eligible neonates and infants who underwent cardiac surgery with cardiopulmonary bypass at one of three medical centres, January 2012-August 2013, were included. Data on serum albumin levels from five data points (pre-operative, 0-24, 24-48, 48-72, 72 hours post-operative) were collected. Median pre-operative serum albumin level was 2.5 g/dl (IQR, 2.1-2.8) in neonates versus 4 g/dl (IQR, 3.5-4.4) in infants. Hypoalbuminemia was defined as <25th percentile of these values. A total of 203 patients (126 neonates, 77 infants) were included in the study. Post-operative hypoalbuminemia developed in 12% of neonates and 20% of infants; 97% occurred in the first 48 hours. In multivariable analysis, perioperative hypoalbuminemia was not independently associated with any post-operative morbidity. However, when analysed as a continuous variable, lower serum albumin levels were associated with increased post-operative morbidity. Pre-operative low serum albumin level was independently associated with increased odds of post-operative hypoalbuminemia (OR, 3.67; 95% CI, 1.01-13.29) and prolonged length of hospital stay (RR, 1.40; 95% CI, 1.08-1.82). Lower 0-24-hour post-operative serum albumin level was independently associated with an increased duration of mechanical ventilation (RR, 1.35; 95% CI, 1.12-1.64). Future studies should further assess hypoalbuminemia in this population, with emphasis on evaluating clinically meaningful cut-offs and possibly the use of serum albumin levels in perioperative risk stratification models.

Early Mobilization of Infants Intubated for Acute Respiratory Failure.

BACKGROUND: Early mobility in the intensive care unit is being promoted as a way to improve outcomes but has not been studied in young infants. OBJECTIVE: To determine the safety of a holding intervention for infants intubated for respiratory failure. METHODS: Infants less than 6 months of age intubated for respiratory failure underwent a holding intervention in which a caretaker held the infant at least twice a day once the infant was medically stabilized. Rates of adverse events were compared with historical controls matched by age and Pediatric Index of Mortality 2 score. Vital signs before and during holding were recorded to assess for physiologic tolerance. RESULTS: Twenty-four infants with a total of 158 holding interventions were studied. Mean holding duration was 99 minutes. Twenty holding interventions were terminated early, most commonly because of agitation. The 24 historical controls had 1 unplanned extubation and 2 arterial catheter removals. The intervention group had no unplanned extubations, inadvertent central catheter removals, or urinary catheter removals and had 1 arterial catheter removal that was not associated with holding. Vital signs before and during holding were similar. There were no differences between the control and intervention groups in duration of intubation (7.3 vs 6.0 days, P = .98), length of intensive care unit stay (9.1 vs 9.0 days, P = .52), or length of hospital stay (11.5 vs 12.5 days, P = .28). CONCLUSIONS: Holding intubated infants in the intensive care unit was well tolerated, without an increase in adverse events.

Outcomes of Tracheostomy in Children Requiring Surgery for Congenital Heart Disease.

Outcomes after discharge in children requiring tracheostomy after cardiac surgery have not been fully described. A retrospective, single-center study was performed on all children <18 years of age requiring both tracheostomy and surgery for congenital heart disease from January 2002 to May 2015. Forty-six tracheostomies were placed after surgery and four before. Single-ventricle anatomy was present in 12 (33%) patients. Incidence of tracheostomy after heart surgery increased from 0.8% the first half of the study period to 2% the second half. Median time between cardiac surgery and tracheostomy was 58 days. The most common indication for tracheostomy was multifactorial (30%) followed by airway malacia (22%). Median length to follow-up for survivors was 3.9 years (range 0.4-11.8 years). Survival to hospital discharge was 72%, and intermediate survival was 48%. Survival in those with systemic to pulmonary artery shunts at the time of tracheostomy was 22% compared to 59% for those with biventricular anatomy. Heart failure and multiple indications for tracheostomy were associated with worse outcome. There was no difference in survival for those discharged with a ventilator compared to those that were not. The most common cause of death after discharge was tracheostomy tube dislodgement/obstruction, accounting for 5 of 11 that died. Survival with a tracheostomy after cardiac surgery is poor, and children with systemic to pulmonary artery shunts are at especially high risk of death.

Outcomes after in-hospital cardiac arrest in children with cardiac disease: a report from Get With the Guidelines--Resuscitation.

BACKGROUND: Small studies suggest that children experiencing a cardiac arrest after undergoing cardiac surgery have better outcomes than other groups of patients, but the survival outcomes and periarrest variables of cardiac and noncardiac pediatric patients have not been compared. METHODS AND RESULTS: All cardiac arrests in patients <18 years of age were identified from Get With the Guidelines-Resuscitation from 2000 to 2008. Cardiac arrests occurring in the neonatal intensive care unit were excluded. Of 3323 index cardiac arrests, 19% occurred in surgical-cardiac, 17% in medical-cardiac, and 64% in noncardiac (trauma, surgical-noncardiac, and medical-noncardiac) patients. Survival to hospital discharge was significantly higher in the surgical-cardiac group (37%) compared with the medical-cardiac group (28%; adjusted odds ratio, 1.8; 95% confidence interval, 1.3-2.5) and the noncardiac group (23%; adjusted odds ratio, 1.8; 95% confidence interval, 1.4-2.4). Those in the cardiac groups were younger and less likely to have preexisting noncardiac organ dysfunction, but were more likely to have ventricular arrhythmias as their first pulseless rhythm, to be monitored and hospitalized in the intensive care unit at the time of cardiac arrest, and to have extracorporeal cardiopulmonary resuscitation compared with those in the noncardiac group. There was no survival advantage for patients in the medical-cardiac group compared with those in the noncardiac group when adjusted for periarrest variables. CONCLUSION: Children with surgical-cardiac disease have significantly better survival to hospital discharge after an in-hospital cardiac arrest compared with children with medical-cardiac disease and noncardiac disease.

Use of near-infrared spectroscopy for estimation of renal oxygenation in children with heart disease.

We evaluated whether near-infrared spectroscopy (NIRS) measurement from the flank correlates with renal vein saturation in children undergoing cardiac catheterization. Thirty-seven patients <18 years of age were studied. A NIRS sensor was placed on the flank, and venous oxygen saturations were measured from the renal vein and the inferior vena cava (IVC). There was a strong correlation between flank NIRS values (rSO(2)) and renal vein saturation (r = 0.821, p = 0.002) and IVC saturation (r = 0.638, p = 0.004) in children weighing ≤ 10 kg. In children weighing > 10 kg, there was no correlation between rSO(2) and renal vein saturation (r = 0.158, p = 0.57) or IVC saturation (r = -0.107, p = 0.67). Regional tissue oxygenation as measured by flank NIRS correlates well with both renal vein and IVC oxygen saturations in children weighing <10 kg undergoing cardiac catheterization, but not in larger children.

Coma in a 20-month-old child from an ingestion of a toy containing 1,4-butanediol, a precursor of gamma-hydroxybutyrate.

Ingestion of plastic toys is common in children and usually does not result in harm. We report a case of coma in a 20-month-old child after an ingestion of a toy containing 1,4-butanediol, an industrial solvent used to manufacture plastics. When ingested, 1,4-butanediol is metabolized to gamma-hydroxybutyrate, which can have significant systemic effects including death. Health care providers should suspect the possibility of a toxic component when a presumed nontoxic object causes unusual symptoms.