Prediction of cardiac surgery associated acute kidney injury using response to loop diuretic and urine neutrophil gelatinase associated lipocalin.

BACKGROUND: Cardiac surgery associated acute kidney injury (CS-AKI) is common. Urine response to loop diuretic and urine neutrophil gelatinase associated lipocalin (uNGAL) are separately associated with CS-AKI. We aimed to determine whether urine response to loop diuretic and uNGAL together were associated with postoperative day 2-4 CS-AKI. METHODS: Two-center prospective observational study (ages 0-18 years). uNGAL (8-12 h after admission) (ng/mL) and urine response to loop diuretic (6 h for bolus furosemide and 12 h for infusion bumetanide) (mL/kg/hr) were measured. All diuretic doses were converted to furosemide equivalents. The primary outcome was day 2-4 CS-AKI. Patients were sub-phenotyped using a priori cutoffs (uNGAL + ≥ 100 ng/mL and UOP + < 1.5 mL/kg/hr) and optimal cutoffs (uNGAL + ≥ 127 ng/mL and UOP + ≤ 0.79 mL/kg/hr): 1) uNGAL-/UOP-, 2) uNGAL-/UOP + , 3) uNGAL + /UOP-, and 4) uNGAL + /UOP + . Multivariable regression was used to assess the association of uNGAL, UOP and each sub-phenotype with outcomes. RESULTS: 476 patients were included. CS-AKI occurred in 52 (10.9%). uNGAL was associated with 2.59-fold greater odds (95%CI: 1.52-4.41) of CS-AKI. UOP was not associated with CS-AKI. Compared with uNGAL + alone, uNGAL + /UOP + improved prediction of CS-AKI using a priori and optimal cutoffs respectively (AUC 0.70 vs. 0.75). Both uNGAL + /UOP + (IQR OR:4.63, 95%CI: 1.74-12.32) and uNGAL + /UOP- (IQR OR:5.94, 95%CI: 2.09-16.84) were associated with CS-AKI when compared with uNGAL-/UOP-. CONCLUSIONS: uNGAL is associated with CS-AKI. The sub-phenotype association was largely driven by uNGAL. Future studies standardizing diuretic dose and timing may be needed to refine the combined performance for clinical decision making.

Persistent acute kidney injury and fluid accumulation with outcomes after the Norwood procedure: report from NEPHRON.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CS-AKI) is common, but its impact on clinical outcomes is variable. Parsing AKI into sub-phenotype(s) and integrating pathologic positive cumulative fluid balance (CFB) may better inform prognosis. We sought to determine whether durational sub-phenotyping of CS-AKI with CFB strengthens association with outcomes among neonates undergoing the Norwood procedure. METHODS: Multicenter, retrospective cohort study from the Neonatal and Pediatric Heart and Renal Outcomes Network. Transient CS-AKI: present only on post-operative day (POD) 1 and/or 2; persistent CS-AKI: continued after POD 2. CFB was evaluated per day and peak CFB during the first 7 postoperative days. Primary and secondary outcomes were mortality, respiratory support-free and hospital-free days (at 28, 60 days, respectively). The primary predictor was persistent CS-AKI, defined by modified neonatal Kidney Disease: Improving Global Outcomes criteria. RESULTS: CS-AKI occurred in 59% (205/347) neonates: 36.6% (127/347) transient and 22.5% (78/347) persistent; CFB > 10% occurred in 18.7% (65/347). Patients with either persistent CS-AKI or peak CFB > 10% had higher mortality. Combined persistent CS-AKI with peak CFB > 10% (n = 21) associated with increased mortality (aOR: 7.8, 95% CI: 1.4, 45.5; p = 0.02), decreased respiratory support-free (predicted mean 12 vs. 19; p < 0.001) and hospital-free days (17 vs. 29; p = 0.048) compared to those with neither. CONCLUSIONS: The combination of persistent CS-AKI and peak CFB > 10% after the Norwood procedure is associated with mortality and hospital resource utilization. Prospective studies targeting intra- and postoperative CS-AKI risk factors and reducing CFB have the potential to improve outcomes.

Kinetics of Renin Concentrations in Infants Undergoing Congenital Cardiac Surgery.

BACKGROUND: Elevated renin has been shown to predict poor response to standard vasoactive therapies and is associated with poor outcomes in adults. Similarly, elevated renin was associated with mortality in children with septic shock. Renin concentration profiles after pediatric cardiac surgery are unknown. The purpose of this study was to characterize renin kinetics after pediatric cardiac surgery. METHODS: Single-center retrospective study of infants who underwent cardiac surgery with cardiopulmonary bypass (CPB) utilizing serum samples obtained in the perioperative period to measure plasma renin concentrations (pg/mL). Time points included pre-bypass and 1, 4, and 24 h after initiation of CPB. RESULTS: Fifty patients (65% male) with a median age 5 months (interquartile range (IQR) 3.5, 6.5) were included. Renin concentrations peaked 4 h after CPB. There was a significant difference in preoperative and 4 h post-CPB renin concentration (4 h post-CPB vs preoperative: mean difference 100.6, 95% confidence interval (CI) 48.9-152.4, P < .001). Median renin concentration at 24 h after CPB was lower than the preoperative baseline. CONCLUSIONS: We describe renin kinetics in infants after CPB. Future studies based on these data can now be performed to evaluate the associations of elevated renin concentrations with adverse outcomes.

Peritoneal catheters in neonates undergoing complex cardiac surgery: a multi-centre descriptive study.

BACKGROUND: The use of peritoneal catheters for prophylactic dialysis or drainage to prevent fluid overload after neonatal cardiac surgery is common in some centres; however, the multi-centre variability and details of peritoneal catheter use are not well described. METHODS: Twenty-two-centre NEonatal and Pediatric Heart Renal Outcomes Network (NEPHRON) study to describe multi-centre peritoneal catheter use after STAT category 3-5 neonatal cardiac surgery using cardiopulmonary bypass. Patient characteristics and acute kidney injury/fluid outcomes for six post-operative days are described among three cohorts: peritoneal catheter with dialysis, peritoneal catheter with passive drainage, and no peritoneal catheter. RESULTS: Of 1490 neonates, 471 (32%) had an intraoperative peritoneal catheter placed; 177 (12%) received prophylactic dialysis and 294 (20%) received passive drainage. Sixteen (73%) centres used peritoneal catheter at some frequency, including six centres in >50% of neonates. Four centres utilised prophylactic peritoneal dialysis. Time to post-operative dialysis initiation was 3 hours [1, 5] with the duration of 56 hours [37, 90]; passive drainage cohort drained for 92 hours [64, 163]. Peritoneal catheter were more common among patients receiving pre-operative mechanical ventilation, single ventricle physiology, and higher complexity surgery. There was no association with adverse events. Serum creatinine and daily fluid balance were not clinically different on any post-operative day. Mortality was similar. CONCLUSIONS: In neonates undergoing complex cardiac surgery, peritoneal catheter use is not rare, with substantial variability among centres. Peritoneal catheters are used more commonly with higher surgical complexity. Adverse event rates, including mortality, are not different with peritoneal catheter use. Fluid overload and creatinine-based acute kidney injury rates are not different in peritoneal catheter cohorts.

Biomarker-based risk model to predict persistent multiple organ dysfunctions after congenital heart surgery: a prospective observational cohort study.

BACKGROUND: Multiple organ dysfunction syndrome (MODS) is an important cause of post-operative morbidity and mortality for children undergoing cardiac surgery requiring cardiopulmonary bypass (CPB). Dysregulated inflammation is widely regarded as a key contributor to bypass-related MODS pathobiology, with considerable overlap of pathways associated with septic shock. The pediatric sepsis biomarker risk model (PERSEVERE) is comprised of seven protein biomarkers of inflammation and reliably predicts baseline risk of mortality and organ dysfunction among critically ill children with septic shock. We aimed to determine if PERSEVERE biomarkers and clinical data could be combined to derive a new model to assess the risk of persistent CPB-related MODS in the early post-operative period. METHODS: This study included 306 patients < 18 years old admitted to a pediatric cardiac ICU after surgery requiring cardiopulmonary bypass (CPB) for congenital heart disease. Persistent MODS, defined as dysfunction of two or more organ systems on postoperative day 5, was the primary outcome. PERSEVERE biomarkers were collected 4 and 12 h after CPB. Classification and regression tree methodology were used to derive a model to assess the risk of persistent MODS. RESULTS: The optimal model containing interleukin-8 (IL-8), chemokine ligand 3 (CCL3), and age as predictor variables had an area under the receiver operating characteristic curve (AUROC) of 0.86 (0.81-0.91) for differentiating those with or without persistent MODS and a negative predictive value of 99% (95-100). Ten-fold cross-validation of the model yielded a corrected AUROC of 0.75 (0.68-0.84). CONCLUSIONS: We present a novel risk prediction model to assess the risk for development of multiple organ dysfunction after pediatric cardiac surgery requiring CPB. Pending prospective validation, our model may facilitate identification of a high-risk cohort to direct interventions and studies aimed at improving outcomes via mitigation of post-operative organ dysfunction.

Assessment of fluid balance after neonatal cardiac surgery: a description of intake/output vs. weight-based methods.

BACKGROUND: Fluid overload associates with poor outcomes after neonatal cardiac surgery, but consensus does not exist for the most clinically relevant method of measuring fluid balance (FB). While weight change-based FB (FB-W) is standard in neonatal intensive care units, weighing infants after cardiac surgery may be challenging. We aimed to identify characteristics associated with obtaining weights and to understand how intake/output-based FB (FB-IO) and FB-W compare in the early postoperative period in this population. METHODS: Observational retrospective study of 2235 neonates undergoing cardiac surgery from 22 hospitals comprising the NEonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) database. RESULTS: Forty-five percent (n = 998) of patients were weighed on postoperative day (POD) 2, varying from 2 to 98% among centers. Odds of being weighed were lower for STAT categories 4 and 5 (OR 0.72; 95% CI 0.53-0.98), cardiopulmonary bypass (0.59; 0.42-0.83), delayed sternal closure (0.27; 0.19-0.38), prophylactic peritoneal dialysis use (0.58; 0.34-0.99), and mechanical ventilation on POD 2 (0.23; 0.16-0.33). Correlation between FB-IO and FB-W was weak for every POD 1-6 and within the entire cohort (correlation coefficient 0.15; 95% CI 0.12-0.17). FB-W measured higher than paired FB-IO (mean bias 12.5%; 95% CI 11.6-13.4%) with wide 95% limits of agreement (- 15.4-40.4%). CONCLUSIONS: Weighing neonates early after cardiac surgery is uncommon, with significant practice variation among centers. Patients with increased severity of illness are less likely to be weighed. FB-W and FB-IO have weak correlation, and further study is needed to determine which cumulative FB metric most associates with adverse outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Early postoperative weight-based fluid overload is associated with worse outcomes after neonatal cardiac surgery.

OBJECTIVES: Evaluate the association of postoperative day (POD) 2 weight-based fluid balance (FB-W) > 10% with outcomes after neonatal cardiac surgery. METHODS: Retrospective cohort study of 22 hospitals in the NEonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) registry from September 2015 to January 2018. Of 2240 eligible patients, 997 neonates (cardiopulmonary bypass (CPB) n = 658, non-CPB n = 339) were weighed on POD2 and included. RESULTS: Forty-five percent (n = 444) of patients had FB-W > 10%. Patients with POD2 FB-W > 10% had higher acuity of illness and worse outcomes. Hospital mortality was 2.8% (n = 28) and not independently associated with POD2 FB-W > 10% (OR 1.04; 95% CI 0.29-3.68). POD2 FB-W > 10% was associated with all utilization outcomes, including duration of mechanical ventilation (multiplicative rate of 1.19; 95% CI 1.04-1.36), respiratory support (1.28; 95% CI 1.07-1.54), inotropic support (1.38; 95% CI 1.10-1.73), and postoperative hospital length of stay (LOS 1.15; 95% CI 1.03-1.27). In secondary analyses, POD2 FB-W as a continuous variable demonstrated association with prolonged durations of mechanical ventilation (OR 1.04; 95% CI 1.02-1.06], respiratory support (1.03; 95% CI 1.01-1.05), inotropic support (1.03; 95% CI 1.00-1.05), and postoperative hospital LOS (1.02; 95% CI 1.00-1.04). POD2 intake-output based fluid balance (FB-IO) was not associated with any outcome. CONCLUSIONS: POD2 weight-based fluid balance > 10% occurs frequently after neonatal cardiac surgery and is associated with longer cardiorespiratory support and postoperative hospital LOS. However, POD2 FB-IO was not associated with clinical outcomes. Mitigating early postoperative fluid accumulation may improve outcomes but requires safely weighing neonates in the early postoperative period. A higher resolution version of the Graphical abstract is available as Supplementary information.

Inferior and Superior Vena Cava Saturation Monitoring After Neonatal Cardiac Surgery.

OBJECTIVES: Superior vena cava oxygen saturation (SVC O 2 ) monitoring is well described for early detection of hemodynamic deterioration after neonatal cardiac surgery but inferior vena cava vein oxygen saturation (IVC O 2 ) monitoring data are limited. DESIGN: Retrospective cohort study of 118 neonates with congenital heart disease (52 single ventricle) from February 2008 to January 2014. SETTING: Pediatric cardiac ICU. PATIENTS: Neonates (< 30 d) with concurrent admission IVC O 2 and SVC O 2 measurements after cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary aim was to correlate admission IVC O 2 and SVC O 2 . Secondary aims included: correlate flank or cerebral near-infrared spectroscopy with IVC O 2 and SVC O 2 , respectively, and exploratory analysis to evaluate associations between oximetry data and a composite adverse outcome defined as any of the following: increasing serum lactate or vasoactive support at 2 hours post-admission, cardiac arrest, or mortality. Admission IVC O 2 and SVC O 2 correlated ( r = 0.54; p < 0.001). However, IVC O 2 measurements were significantly lower than paired SVC O 2 (mean difference, -6%; 95% CI, -8% to -4%; p < 0.001) with wide variability in sample agreement. Logistic regression showed that each 12% decrease in IVC O 2 was associated with a 12-fold greater odds of the composite adverse outcome (odds ratio [OR], 12; 95% CI, 3.9-34; p < 0.001). We failed to find an association between SVC O 2 and increased odds of the composite adverse outcome (OR, 1.8; 95% CI, 0.99-3.3; p = 0.053). In an exploratory analysis, the area under the receiver operating curve for IVC O 2 and SVC O 2 , and the composite adverse outcome, was 0.85 (95% CI, 0.77-0.92) and 0.63 (95% CI, 0.52-0.73), respectively. Admission IVC O 2 had strong correlation with concurrent flank near-infrared spectroscopy value ( r = 0.74; p < 0.001). SVC O 2 had a weak association with cerebral near-infrared spectroscopy ( r = 0.22; p = 0.02). CONCLUSIONS: In postoperative neonates, admission IVC O 2 and SVC O 2 correlate. Lower admission IVC O 2 may identify a cohort of postsurgical neonates at risk for low cardiac output and associated morbidity.

Transient and persistent acute kidney injury phenotypes following the Norwood operation: a retrospective study.

BACKGROUND: Acute kidney injury is a common complication following the Norwood operation. Most neonatal studies report acute kidney injury peaking within the first 48 hours after cardiac surgery. The aim of this study was to evaluate if persistent acute kidney injury (>48 postoperative hours) after the Norwood operation was associated with clinically relevant outcomes. METHODS: Two-centre retrospective study among neonates undergoing the Norwood operation. Acute kidney injury was initially identified as developing within the first 48 hours after cardiac surgery and stratified into transient (≤48 hours) and persistent (>48 hours) using the neonatal modification of the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Severe was defined as stage ≥2. Primary and secondary outcomes were mortality and duration of ventilation and hospital length of stay. RESULTS: One hundred sixty-eight patients were included. Transient and persistent acute kidney injuries occurred in 24 and 17%, respectively. Cardiopulmonary bypass and aortic cross clamp duration, and incidence of cardiac arrest were greater among those with persistent kidney injury. Mortality was four times higher (41 versus 12%, p < 0.001) and mechanical ventilation duration 50 hours longer in persistent acute kidney injury patients (158 versus 107 hours; p < 0.001). In multivariable analysis, persistent acute kidney injury was not associated with mortality, duration of ventilation or length of stay. Severe persistent acute kidney injury was associated with a 59% increase in expected ventilation duration (aIRR:1.59, 95% CI:1.16, 2.18; p = 0.004). CONCLUSIONS: Future large studies are needed to determine if risk factors and outcomes change by delineating acute kidney injury into discrete timing phenotypes.

Epidemiology of Acute Kidney Injury After Neonatal Cardiac Surgery: A Report From the Multicenter Neonatal and Pediatric Heart and Renal Outcomes Network.

OBJECTIVES: Cardiac surgery-associated acute kidney injury occurs commonly following congenital heart surgery and is associated with adverse outcomes. This study represents the first multicenter study of neonatal cardiac surgery-associated acute kidney injury. We aimed to describe the epidemiology, including perioperative predictors and associated outcomes of this important complication. DESIGN: This Neonatal and Pediatric Heart and Renal Outcomes Network study is a multicenter, retrospective cohort study of consecutive neonates less than 30 days. Neonatal modification of The Kidney Disease Improving Global Outcomes criteria was used. Associations between cardiac surgery-associated acute kidney injury stage and outcomes (mortality, length of stay, and duration of mechanical ventilation) were assessed through multivariable regression. SETTING: Twenty-two hospitals participating in Pediatric Cardiac Critical Care Consortium. PATIENTS: Twenty-two-thousand forty neonates who underwent major cardiac surgery from September 2015 to January 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cardiac surgery-associated acute kidney injury occurred in 1,207 patients (53.8%); 983 of 1,657 in cardiopulmonary bypass patients (59.3%) and 224 of 583 in noncardiopulmonary bypass patients (38.4%). Seven-hundred two (31.3%) had maximum stage 1, 302 (13.5%) stage 2, 203 (9.1%) stage 3; prevalence of cardiac surgery-associated acute kidney injury peaked on postoperative day 1. Cardiac surgery-associated acute kidney injury rates varied greatly (27-86%) across institutions. Preoperative enteral feeding (odds ratio = 0.68; 0.52-0.9) and open sternum (odds ratio = 0.76; 0.61-0.96) were associated with less cardiac surgery-associated acute kidney injury; cardiopulmonary bypass was associated with increased cardiac surgery-associated acute kidney injury (odds ratio = 1.53; 1.01-2.32). Duration of cardiopulmonary bypass was not associated with cardiac surgery-associated acute kidney injury in the cardiopulmonary bypass cohort. Stage 3 cardiac surgery-associated acute kidney injury was independently associated with hospital mortality (odds ratio = 2.44; 1.3-4.61). No cardiac surgery-associated acute kidney injury stage was associated with duration of mechanical ventilation or length of stay. CONCLUSIONS: Cardiac surgery-associated acute kidney injury occurs frequently after neonatal cardiac surgery in both cardiopulmonary bypass and noncardiopulmonary bypass patients. Rates vary significantly across hospitals. Only stage 3 cardiac surgery-associated acute kidney injury is associated with mortality. Cardiac surgery-associated acute kidney injury was not associated with any other outcomes. Kidney Disease Improving Global Outcomes criteria may not precisely define a clinically meaningful renal injury phenotype in this population.

Development of Persistent Respiratory Morbidity in Previously Healthy Children After Acute Respiratory Failure.

OBJECTIVES: Acute respiratory failure is a common reason for admission to PICUs. Short- and long-term effects on pulmonary health in previously healthy children after acute respiratory failure requiring mechanical ventilation are unknown. The aim was to determine if clinical course or characteristics of mechanical ventilation predict persistent respiratory morbidity at follow-up. DESIGN: Prospective cohort study with follow-up questionnaires at 6 and 12 months. SETTING: Ten U.S. PICUs. PATIENTS: Two-hundred fifty-five children were included in analysis after exclusion for underlying chronic disease or incomplete data. One-hundred fifty-eight and 130 children had follow-up data at 6 and 12 months, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pulmonary dysfunction at discharge a priori defined as one of: mechanical ventilation, supplemental oxygen, bronchodilators or steroids at 28 days or discharge. Persistent respiratory morbidity a priori defined as a respiratory PedsQL, a pediatric quality of life measure, greater than or equal to 5 or asthma diagnosis, bronchodilator or inhaled steroids, or unscheduled clinical evaluation for respiratory symptoms. Multivariate backward stepwise regression using Akaike information criterion minimization determined independent predictors of these outcomes. Pulmonary dysfunction at discharge was present in 34% of patients. Positive bacterial respiratory culture predicted pulmonary dysfunction at discharge (odds ratio, 4.38; 95% CI, 1.66-11.56). At 6- and 12-month follow-up 42% and 44% of responders, respectively, had persistent respiratory morbidity. Pulmonary dysfunction at discharge was associated with persistent respiratory morbidity at 6 months, and persistent respiratory morbidity at 6 months was strongly predictive of 12-month persistent respiratory morbidity (odds ratio, 18.58; 95% CI, 6.68-52.67). Positive bacterial respiratory culture remained predictive of persistent respiratory morbidity in patients at both follow-up points. CONCLUSIONS: Persistent respiratory morbidity develops in up to potentially 44% of previously healthy children less than or equal to 24 months old at follow-up after acute respiratory failure requiring mechanical ventilation. This is the first study, to our knowledge, to suggest a prevalence of persistent respiratory morbidity and the association between positive bacterial respiratory culture and pulmonary morbidity in a population of only previously healthy children with acute respiratory failure.

Standardized Perioperative Feeding Protocol Improves Outcomes in Patients With d-Transposition of the Great Arteries Undergoing Arterial Switch Operation.

OBJECTIVE: To determine whether the presence of a standardized feeding protocol improves outcomes in a subset of neonates undergoing cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Cardiovascular ICU at a freestanding academic children's hospital. PATIENTS: Neonates with a diagnosis of d-transposition of the great arteries undergoing arterial switch operation from January 2007 to June 2017. INTERVENTIONS: Initiation of perioperative feeding protocols. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated before and after implementation of standardized perioperative feeding protocols in neonates with d-transposition of the great arteries undergoing arterial switch operation. Low-risk patients born after initiation of nurse-driven protocols were compared with a similar historical group. Data obtained included time to achievement of feeding goals, with primary outcome being weight gain at hospital discharge. Other measures analyzed included duration of mechanical ventilation and postoperative hospital length of stay. Overall, 33 patients in the protocol group were compared with 44 patients in the historical group. No significant baseline differences existed between the two cohorts. The protocol group achieved improved feeding outcomes in nearly all measured categories, including introduction to enteral feeds preoperatively (91% vs 59%; p < 0.01) and earlier attainment of postoperative full enteral feeds of 120 mL/kg/d (2 vs 5 d; p < 0.01). Protocol patients had significantly improved weight gain at the time of discharge (60 vs 1 g; p < 0.01), while achieving shorter postoperative length of stay (10.1 vs 12.6 d; p = 0.04). CONCLUSIONS: An aggressive, but safe, perioperative feeding protocol implemented in a homogenous low-risk neonatal cardiac surgical population improves feeding outcomes, including increased weight gain, as well as decreased postoperative length of stay. Consideration for perioperative feeding protocol implementation and further study should be given.

Positive Airway Pressure Versus High-Flow Nasal Cannula for Prevention of Extubation Failure in Infants After Congenital Heart Surgery.

OBJECTIVES: Compare the impact of initial extubation to positive airway pressure versus high-flow nasal cannula on postoperative outcomes in neonates and infants after congenital heart surgery. DESIGN: Retrospective cohort study with propensity-matched analysis. SETTING: Cardiac ICU within a tertiary care children's hospital. PATIENTS: Patients less than 6 months old initially extubated to either high-flow nasal cannula or positive airway pressure after cardiac surgery with cardiopulmonary bypass were included (July 2012 to December 2015). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 258 encounters, propensity matching identified 49 pairings of patients extubated to high-flow nasal cannula versus positive airway pressure. Extubation failure was 12% for all screened encounters. After matching, there was no difference in extubation failure rate between groups (positive airway pressure 16% vs high-flow nasal cannula 10%; p = 0.549). However, compared with high-flow nasal cannula, patients initially extubated to positive airway pressure experienced greater resource utilization: longer time to low-flow nasal cannula (83 vs 28 hr; p = 0.006); longer time to room air (159 vs 110 hr; p = 0.013); and longer postsurgical hospital length of stay (22 vs 14 d; p = 0.015). CONCLUSIONS: In this pediatric cohort, primary extubation to positive airway pressure was not superior to high-flow nasal cannula with respect to prevention of extubation failure after congenital heart surgery. Compared with high-flow nasal cannula, use of positive airway pressure was associated with increased hospital resource utilization. Prospective initiatives aimed at establishing best clinical practice for postoperative noninvasive respiratory support are needed.

Variation in Adjusted Mortality for Medical Admissions to Pediatric Cardiac ICUs.

OBJECTIVES: Pediatric cardiac ICUs should be adept at treating both critical medical and surgical conditions for patients with cardiac disease. There are no case-mix adjusted quality metrics specific to medical cardiac ICU admissions. We aimed to measure case-mix adjusted cardiac ICU medical mortality rates and assess variation across cardiac ICUs in the Pediatric Cardiac Critical Care Consortium. DESIGN: Observational analysis. SETTING: Pediatric Cardiac Critical Care Consortium clinical registry. PATIENTS: All cardiac ICU admissions that did not include cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was cardiac ICU mortality. Based on multivariable logistic regression accounting for clustering, we created a case-mix adjusted model using variables present at cardiac ICU admission. Bootstrap resampling (1,000 samples) was used for model validation. We calculated a standardized mortality ratio for each cardiac ICU based on observed-to-expected mortality from the fitted model. A cardiac ICU was considered a statistically significant outlier if the 95% CI around the standardized mortality ratio did not cross 1. Of 11,042 consecutive medical admissions from 25 cardiac ICUs (August 2014 to May 2017), the observed mortality rate was 4.3% (n = 479). Final model covariates included age, underweight, prior surgery, time of and reason for cardiac ICU admission, high-risk medical diagnosis or comorbidity, mechanical ventilation or extracorporeal membrane oxygenation at admission, and pupillary reflex. The C-statistic for the validated model was 0.87, and it was well calibrated. Expected mortality ranged from 2.6% to 8.3%, reflecting important case-mix variation. Standardized mortality ratios ranged from 0.5 to 1.7 across cardiac ICUs. Three cardiac ICUs were outliers; two had lower-than-expected (standardized mortality ratio <1) and one had higher-than-expected (standardized mortality ratio >1) mortality. CONCLUSIONS: We measured case-mix adjusted mortality for cardiac ICU patients with critical medical conditions, and provide the first report of variation in this quality metric within this patient population across Pediatric Cardiac Critical Care Consortium cardiac ICUs. This metric will be used by Pediatric Cardiac Critical Care Consortium cardiac ICUs to assess and improve outcomes by identifying high-performing (low-mortality) centers and engaging in collaborative learning.

Aspiration After Congenital Heart Surgery.

Dysphagia and vocal cord dysfunction are frequent complications after congenital heart surgery. Both are risk factors for aspiration, which can lead to pneumonia, progressive lung disease, and respiratory arrest. A protocol was implemented to promote early detection of aspiration in a high-risk cohort of patients. Retrospective data were collected on all patients under 120 days old who underwent the Norwood procedure, aortic arch repair, Blalock-Taussig shunt placement, or cervical cannulation for extracorporeal membrane oxygenation from 10/2012 to 05/2016 at a single institution. Patients underwent an assessment of symptoms, fiberoptic endoscopic evaluation of swallowing (FEES), and modified barium swallow (MBS) study in the postoperative period prior to initiating oral feeds. Patients with and without aspiration were compared. Of the 96 patients included in the study, one-third (33%) of patients had evidence of vocal cord dysfunction by FEES and just over half (51%) had evidence of aspiration by FEES or MBS. Most (73%) of the patients with aspiration were asymptomatic and a majority (53%) of patients with aspiration had normal vocal cord function. Aspiration is common after congenital heart surgery, and an assessment of vocal cord or swallow function in isolation may lead to underdiagnosis. A comprehensive protocol including MBS and FEES is necessary for the early detection of vocal cord dysfunction and aspiration and may prevent adverse outcomes in high-risk postoperative patients.

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 postoperative measurement of fibroblast growth factor 23 predicts severe acute kidney injury in infants after cardiac surgery
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AIMS: Acute kidney injury (AKI) occurs in 30 - 40% of children after cardiac surgery (CS) and is associated with poor prognosis. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone with a pivotal role in phosphorus and vitamin D metabolism. We assessed FGF23 as an early marker for severe AKI (sAKI) in infants after CS. MATERIALS AND METHODS: Samples were previously collected in a multicenter observational study from children after CS. Serum FGF23 (n = 41) and urine AKI biomarker levels (n = 35) were assessed 4 - 8 hours after bypass. sAKI was defined as ≥ 100% rise in serum creatinine over baseline. Non-parametric and ROC analyses were used to evaluate the association between FGF23, urine AKI markers, and sAKI in the week after CS. RESULTS: Serum FGF23, urine NGAL, and urine KIM1 were higher in sAKI patients. The AUC-ROC for urine NGAL (0.74, [0.49 - 0.99]), urine KIM1 (0.79, [0.68 - 0.98]), and serum FGF23 (0.74, [0.5 - 0.9]) showed fair prediction of sAKI. CONCLUSION: Early measurement of FGF23 has predictive ability in infants who develop sAKI after CS with cardiopulmonary bypass.
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Furosemide Response Predicts Acute Kidney Injury After Cardiac Surgery in Infants and Neonates.

OBJECTIVE: Cardiac surgery-induced acute kidney injury occurs frequently in neonates and infants and is associated with postoperative morbidity/mortality; early identification of cardiac surgery-induced acute kidney injury may be crucial to mitigate postoperative morbidity. We sought to determine if hourly or 6-hour cumulative urine output after furosemide in the first 24 hours after cardiopulmonary bypass could predict development of cardiac surgery-induced acute kidney injury and other deleterious outcomes. DESIGN: Retrospective chart review. SETTING: Pediatric cardiac ICU. PATIENTS: All infants younger than 90 days old admitted to the cardiac ICU from October 2012 to December 2015 who received at least one dose of furosemide in the first 24 hours after cardiopulmonary bypass surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ninety-nine patients met inclusion and exclusion criteria. In total, 45.5% developed cardiac surgery-induced acute kidney injury. Median time between cardiopulmonary bypass and furosemide was 7.7 hours (interquartile range, 4.4-9.5). Six-hour cumulative urine output was 33% lower (p = 0.031) in patients with cardiac surgery-induced acute kidney injury. Area under the curve for prediction of cardiac surgery-induced acute kidney injury was 0.69 (p = 0.002). Other models demonstrated urine output response to furosemide had significant area under the curves for prediction of peak fluid over load greater than 15% (0.68; p = 0.047), prolonged peritoneal dialysis (area under the curve, 0.79; p = 0.007), prolonged mechanical ventilation (area under the curve, 0.79; p < 0.001), prolonged hospitalization (area under the curve, 0.62; p = 0.069) and mortality (area under the curve, 0.72; p = 0.05). CONCLUSIONS: Urine output response to furosemide within 24 hours of cardiopulmonary bypass predicts cardiac surgery-induced acute kidney injury development and other important morbidity in children younger than 90 days old; prospective validation is warranted.

Correction to: Routine Sildenafil Does Not Improve Clinical Outcomes After Fontan Operation.

The original version of this article unfortunately contained a mistake. The presentation of Table 2 was incorrect .The corrected table is given below.

Impact of Hemolysis on Acute Kidney Injury and Mortality in Children Supported with Cardiac Extracorporeal Membrane Oxygenation.

Intravascular hemolysis with elevated plasma-free hemoglobin (PFH) complicates extracorporeal membrane oxygenation (ECMO). In 50 consecutive pediatric cardiac patients requiring ECMO, we sought to describe the relationship between PFH and clinical outcomes; primary outcomes were acute kidney injury (AKI) and prolonged (>14 days) renal replacement therapy (RRT). Median age was 35 days, median weight 3.9 kg, and median ECMO duration 4.2 days. Seventy-eight percent (39/50) weaned off ECMO; survival to discharge was 50% (25/50). Seventy percent (35/50) had AKI on ECMO. Seventy-seven percent (30/39) required RRT post-ECMO; median duration was 5.2 days (0, 14.2). Prolonged RRT was associated with higher daily PFH (67.5 mg/dL [54.1, 102.5] vs. 46.7 mg/dL [40, 72.6], p = .025) and higher peak PFH (120 mg/dL [90, 200] vs. 60 mg/dL [40, 135], p = .016). After adjusting for ECMO duration and oliguria/elevated creatinine on ECMO day 0, peak PFH >90 mg/dL was associated with prolonged RRT (operating room [OR] = 18, confidence interval [CI] 1.9-167.8). Patients who died had higher daily PFH (65 mg/dL [51.6, 111.7] vs. 42.5 mg/dL [37.5, 60], p = .0040). Adjusting for ECMO duration and blood product administration, daily PFH >53 mg/dL was associated with mortality (OR 4.8, CI 1.01-23.3). Elevated PFH during pediatric cardiac ECMO is associated with prolonged RRT and non-survival to discharge. Initiatives to decrease PFH burden may improve clinical outcomes.