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.

Diuretic response after neonatal cardiac surgery: a report from the NEPHRON collaborative.

BACKGROUND: Multicenter early diuretic response (DR) analysis of single furosemide dosing following neonatal cardiac surgery is lacking to inform whether early DR predicts adverse clinical outcomes. METHODS: We performed a retrospective cohort study utilizing data from the NEPHRON registry. Random forest machine learning generated receiver operating characteristic-area under the curve (ROC-AUC) and odds ratios for mechanical ventilation (MV) and respiratory support (RS). Prolonged MV and RS were defined using ≥ 90th percentile of observed/expected ratios. Secondary outcomes were prolonged CICU and hospital length of stay (LOS) and kidney failure (stage III acute kidney injury (AKI), peritoneal dialysis, and/or continuous kidney replacement therapy on postoperative day three) assessed using covariate-adjusted ROC-AUC curves. RESULTS: A total of 782 children were included. Cumulative urine output (UOP) metrics were lower in prolonged MV and RS patients, but DR poorly predicted prolonged MV (highest AUC 0.611, OR 0.98, sensitivity 0.67, specificity 0.53, p = 0.006, 95% OR CI 0.96-0.99 for cumulative 6-h UOP) and RS (highest AUC 0.674, OR 0.94, sensitivity 0.75, specificity 0.54, p < 0.001, 95% CI 0.91-0.97 UOP between 3 and 6 h). Secondary outcome results were similar. DR had fair discrimination for kidney failure (AUC 0.703, OR 0.94, sensitivity 0.63, specificity 0.71, 95% OR CI 0.91-0.98, p < 0.001, cumulative 6-h UOP). CONCLUSIONS: Early DR poorly discriminated patients with prolonged MV, RS, and LOS in this cohort, though it may identify severe postoperative AKI phenotype. Future work is warranted to determine if early DR or late postoperative DR later, in combination with other AKI metrics, may identify a higher-risk phenotype.

Neonatal Chylothorax and Early Fluid Overload After Cardiac Surgery: Retrospective Analysis of the Neonatal and Pediatric Heart and Renal Outcomes Network Registry (2015-2018).

OBJECTIVES: To evaluate the association between postoperative cumulative fluid balance (FB) and development of chylothorax in neonates after cardiac surgery. DESIGN: Multicenter, retrospective cohort identified within the Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) Registry. SETTING: Twenty-two hospitals were involved with NEPHRON, from September 2015 to January 2018. PATIENTS: Neonates (< 30 d old) undergoing index cardiac operation with or without cardiopulmonary bypass (CPB) entered into the NEPHRON Registry. Postoperative chylothorax was defined in the Pediatric Cardiac Critical Care Consortium as lymphatic fluid in the pleural space secondary to a leak from the thoracic duct or its branches. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 2240 NEPHRON patients, 4% ( n = 89) were treated for chylothorax during postoperative day (POD) 2-21. Median (interquartile range [IQR]) time to diagnosis was 8 (IQR 6, 12) days. Of patients treated for chylothorax, 81 of 89 (91%) had CPB and 68 of 89 (76%) had Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery Congenital Heart Surgery 4-5 operations. On bivariate analysis, chylothorax patients had higher POD 1 FB (3.2 vs. 1.1%, p = 0.014), higher cumulative POD 2 FB (1.5 vs. -1.5%, p < 0.001), achieved negative daily FB by POD 1 less often (69% vs. 79%, p = 0.039), and had lower POD 1 urine output (1.9 vs. 3. 2 mL/kg/day, p ≤ 0.001) than those without chylothorax. We failed to identify an association between presence or absence of chylothorax and peak FB (5.2 vs. 4.9%, p = 0.9). Multivariable analysis shows that higher cumulative FB on POD 2 was associated with greater odds (odds ratio [OR], 95% CI) of chylothorax development (OR 1.5 [95% CI, 1.1-2.2]). Further multivariable analysis shows that chylothorax was independently associated with greater odds of longer durations of mechanical ventilation (OR 5.5 [95% CI, 3.7-8.0]), respiratory support (OR 4.3 [95% CI, 2.9-6.2]), use of inotropic support (OR 2.9 [95% CI, 2.0-4.3]), and longer hospital length of stay (OR 3.7 [95% CI, 2.5-5.4]). CONCLUSIONS: Chylothorax after neonatal cardiac surgery for congenital heart disease (CHD) is independently associated with greater odds of longer duration of cardiorespiratory support and hospitalization. Higher early (POD 2) cumulative FB is associated with greater odds of chylothorax. Contemporary, prospective studies are needed to assess whether early fluid mitigation strategies decrease postoperative chylothorax development.

Cardiac Surgery-Associated Acute Kidney Injury in Neonates Undergoing the Norwood Operation: Retrospective Analysis of the Multicenter Neonatal and Pediatric Heart and Renal Outcomes Network Dataset, 2015-2018.

OBJECTIVES: Cardiac surgery-associated acute kidney injury (CS-AKI) is associated with adverse outcomes. Single-center studies suggest that the prevalence of CS-AKI is high after the Norwood procedure, or stage 1 palliation (S1P), but multicenter data are lacking. DESIGN: A secondary analysis of the Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) multicenter cohort who underwent S1P. Using neonatal modification of Kidney Disease Improving Global Outcomes (KDIGO) criteria, perioperative associations between CS-AKI with morbidity and mortality were examined. Sensitivity analysis, with the exclusion of prophylactic peritoneal dialysis (PD) patients, was performed. SETTING: Twenty-two hospitals participating in the Pediatric Cardiac Critical Care Consortium (PC 4 ) and contributing to NEPHRON. PATIENTS: Three hundred forty-seven neonates (< 30 d old) with S1P managed between September 2015 and January 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 347 patients, CS-AKI occurred in 231 (67%). The maximum stages were as follows: stage 1, in 141 of 347 (41%); stage 2, in 51 of 347 (15%); and stage 3, in 39 of 347 (11%). Severe CS-AKI (stages 2 and 3) peaked on the first postoperative day. In multivariable analysis, preoperative feeding was associated with lower odds of CS-AKI (odds ratio [OR] 0.48; 95% CI, 0.27-0.86), whereas prophylactic PD was associated with greater odds of severe CS-AKI (OR 3.67 [95% CI, 1.88-7.19]). We failed to identify an association between prophylactic PD and increased creatinine (OR 1.85 [95% CI, 0.82-4.14]) but cannot exclude the possibility of a four-fold increase in odds. Hospital mortality was 5.5% ( n = 19). After adjusting for risk covariates and center effect, severe CS-AKI was associated with greater odds of hospital mortality (OR 3.67 [95% CI, 1.11-12.16]). We failed to find associations between severe CS-AKI and respiratory support or length of stay. The sensitivity analysis using PD failed to show associations between severe CS-AKI and outcome. CONCLUSIONS: KDIGO-defined CS-AKI occurred frequently and early postoperatively in this 2015-2018 multicenter PC 4 /NEPHRON cohort of neonates after S1P. We failed to identify associations between resource utilization and CS-AKI, but there was an association between severe CS-AKI and greater odds of mortality in this high-risk cohort. Improving the precision for defining clinically relevant neonatal CS-AKI remains a priority.

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.

Unplanned Extubation During Pediatric Cardiac Intensive Care: U.S. Multicenter Registry Study of Prevalence and Outcomes.

OBJECTIVES: The epidemiology of unplanned extubations (UEs) and associated adverse outcomes in pediatric cardiac ICUs (CICU). DESIGN: Registry data (August 2014 to October 2020). SETTING: Forty-five Pediatric Cardiac Critical Care Consortium hospitals. PATIENTS: Patients receiving mechanical ventilation (MV) via endotracheal tube (ETT). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-six thousand five hundred eight MV courses occurred in 36,696 patients, with a crude UE rate of 2.8%. In cardiac surgical patients, UE was associated with longer duration of MV, but we failed to find such association in medical patients. In both cohorts, UE was associated with younger age, being underweight, and airway anomaly. In multivariable logistic regression, airway anomaly was associated with UE in all patients. Younger age, higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score category, longer duration of MV, and initial oral rather than nasal ETT are associated with UE in the surgical group, but we failed to find such associations in the medical group. UE was associated with a higher reintubation rate compared with elective extubation (26.8 vs 4.8%; odds ratio [OR], 7.35; 95% CI, 6.44-8.39; p < 0.0001) within 1 day of event. After excluding patients having redirection of care, UE was associated with at least three-fold greater odds for each of ventilator-associated pneumonia (VAP), cardiac arrest, and use of mechanical circulatory support (MCS). However, we failed to identify an association between UE and greater odds of mortality (1.2 vs 0.8%; OR, 1.48; 95% CI, 0.86-2.54; p = 0.15), but uncertainty remains. CONCLUSIONS: UE in CICU patients is associated with greater odds of cardiac arrest, VAP, and MCS. Cardiac medical and surgical patients in the CICU appear to have different explanatory factors associated with UE, and perhaps these may be modifiable and tested in future collaborative population research.

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.

Critical Care Unit Organizational and Personnel Factors Impact Cardiac Arrest Prevention and Rescue in the Pediatric Cardiac Population.

OBJECTIVES: Patient-level factors related to cardiac arrest in the pediatric cardiac population are well understood but may be unmodifiable. The impact of cardiac ICU organizational and personnel factors on cardiac arrest rates and outcomes remains unknown. We sought to better understand the association between these potentially modifiable organizational and personnel factors on cardiac arrest prevention and rescue. DESIGN: Retrospective analysis of the Pediatric Cardiac Critical Care Consortium registry. SETTING: Pediatric cardiac ICUs. PATIENTS: All cardiac ICU admissions were evaluated for cardiac arrest and survival outcomes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Successful prevention was defined as the proportion of admissions with no cardiac arrest (inverse of cardiac arrest incidence). Rescue was the proportion of patients surviving to cardiac ICU discharge after cardiac arrest. Cardiac ICU organizational and personnel factors were captured via site questionnaires. The associations between organizational and personnel factors and prevention/rescue were analyzed using Fine-Gray and multinomial regression, respectively, accounting for clustering within hospitals. We analyzed 54,521 cardiac ICU admissions (29 hospitals) with 1,398 cardiac arrest events (2.5%) between August 1, 2014, and March 5, 2019. For both surgical and medical admissions, lower average daily cardiac ICU occupancy was associated with better cardiac arrest prevention. Better rescue for medical admissions was observed for higher registered nursing hours per patient day and lower proportions of "part time" cardiac ICU physician staff (< 6 service weeks/yr). Increased registered nurse experience was associated with better rescue for surgical admissions. Increased proportion of critical care certified nurses, full-time intensivists with critical care fellowship training, dedicated respiratory therapists, quality/safety resources, and annual cardiac ICU admission volume were not associated with improved prevention or rescue. CONCLUSIONS: Our multi-institutional analysis identified cardiac ICU bed occupancy, registered nurse experience, and physician staffing as potentially important factors associated with cardiac arrest prevention and rescue. Recognizing the limitations of measuring these variables cross-sectionally, additional studies are needed to further investigate these organizational and personnel factors, their interrelationships, and how hospitals can modify structure to improve cardiac arrest outcomes.

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.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

BACKGROUND: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

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.

A Novel Model Demonstrates Variation in Risk-Adjusted Mortality Across Pediatric Cardiac ICUs After Surgery.

OBJECTIVE: To develop a postoperative mortality case-mix adjustment model to facilitate assessment of cardiac ICU quality of care, and to describe variation in adjusted cardiac ICU mortality across hospitals within the Pediatric Cardiac Critical Care Consortium. DESIGN: Observational analysis. SETTING: Multicenter Pediatric Cardiac Critical Care Consortium clinical registry. PARTICIPANTS: All surgical cardiac ICU admissions between August 2014 and May 2016. The analysis included 8,543 admissions from 23 dedicated cardiac ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed a novel case-mix adjustment model to measure postoperative cardiac ICU mortality after congenital heart surgery. Multivariable logistic regression was performed to assess preoperative, intraoperative, and immediate postoperative severity of illness variables as candidate predictors. We used generalized estimating equations to account for clustering of patients within hospital and obtain robust SEs. Bootstrap resampling (1,000 samples) was used to derive bias-corrected 95% CIs around each predictor and validate the model. The final model was used to calculate expected mortality at each hospital. We calculated a standardized mortality ratio (observed-to-expected mortality) for each hospital and derived 95% CIs around the standardized mortality ratio estimate. Hospital standardized mortality ratio was considered a statistically significant outlier if the 95% CI did not include 1. Significant preoperative predictors of mortality in the final model included age, chromosomal abnormality/syndrome, previous cardiac surgeries, preoperative mechanical ventilation, and surgical complexity. Significant early postoperative risk factors included open sternum, mechanical ventilation, maximum vasoactive inotropic score, and extracorporeal membrane oxygenation. The model demonstrated excellent discrimination (C statistic, 0.92) and adequate calibration. Comparison across Pediatric Cardiac Critical Care Consortium hospitals revealed five-fold difference in standardized mortality ratio (0.4-1.9). Two hospitals had significantly better-than-expected and two had significantly worse-than-expected mortality. CONCLUSIONS: For the first time, we have demonstrated that variation in mortality as a quality metric exists across dedicated cardiac ICUs. These findings can guide efforts to reduce mortality after cardiac surgery.

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.