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.

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.

Optimal Fat-Modified Diet Duration for the Treatment of Postoperative Chylothorax in Children.

BACKGROUND: Dietary modification is the mainstay of treatment for postoperative chylothorax in children. However, optimal fat-modified diet (FMD) duration to prevent recurrence is unknown. Our aim was to determine the association between FMD duration and chylothorax recurrence. METHODS: Retrospective cohort study conducted across 6 pediatric cardiac intensive care units within the United States. Patients aged <18 years who developed chylothorax within 30 days after cardiac surgery between January 2020 and April 2022 were included. Patients with a Fontan palliation, who died, or were lost to follow-up or within 30 days of resuming a regular diet were excluded. FMD duration was defined as the first day of a FMD when chest tube output was <10 mL/kg/d without increasing until the resumption of a regular diet. Patients were classified into 3 groups (<3 weeks, 3-5 weeks, >5 weeks) based on FMD duration. RESULTS: A total of 105 patients were included: <3 weeks (n = 61) 3-5 weeks (n = 18), and >5 weeks (n = 26). Demographic, surgical, and hospitalization characteristics were not different across groups. In the >5 weeks group, chest tube duration was longer compared with the <3 weeks and 3-5 weeks groups (median, 17.5 days [interquartile range, 9-31] vs 10 and 10.5 days; P = .04). There was no recurrence of chylothorax within 30 days once chylothorax was resolving regardless of FMD duration. CONCLUSIONS: FMD duration was not associated with recurrence of chylothorax, suggesting that FMD duration can safely be shortened to at least <3 weeks from time of resolving chylothorax.

Nuclear Cell-Free DNA Predicts Adverse Events After Pediatric Cardiothoracic Surgery.

BACKGROUND: Preoperative risk stratification in cardiac surgery includes patient and procedure factors that are used in clinical decision-making. Despite these tools, unidentified factors contribute to variation in outcomes. Identification of latent physiologic risk factors may strengthen predictive models. Nuclear cell-free DNA (ncfDNA) increases with tissue injury and drops to baseline levels rapidly. The goal of this investigation is to measure and to observe ncfDNA kinetics in children undergoing heart operations with cardiopulmonary bypass (CPB), linking biomarkers, organ dysfunction, and outcomes. METHODS: This is a prospective observational study of 116 children <18 years and >3 kg undergoing operations with CPB. Plasma ncfDNA samples were collected and processed in a stepwise manner at predefined perioperative time points. The primary outcome measure was occurrence of postoperative cardiac arrest or extracorporeal membrane oxygenation. RESULTS: Data were available in 116 patients (median age, 0.9 years [range, 0-17.4 years]; median weight, 7.8 kg [range, 3.2-98 kg]). The primary outcome was met in 6 of 116 (5.2%). Risk of primary outcome was 2% with ncfDNA <20 ng/mL and 33% with ncfDNA >20 ng/mL (odds ratio, 25; CI, 3.96-158; P = .001). Elevated ncfDNA was associated with fewer hospital-free days (P < .01). CONCLUSIONS: This study analyzes ncfDNA kinetics in children undergoing operations with CPB for congenital heart disease. Elevated preoperative ncfDNA is strongly associated with postoperative arrest and extracorporeal membrane oxygenation. Further studies are needed to validate this technology as a tool to predict morbidity in children after cardiac surgical procedures.

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.

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.

Interventions Associated With Treatment of Low Cardiac Output After Stage 1 Norwood Palliation.

BACKGROUND: Mortality after stage 1 palliation of hypoplastic left heart syndrome remains significant. Both cardiac output (CO) and systemic vascular resistance (SVR) contribute to hemodynamic vulnerability. Simultaneous measures of mean arterial pressure and somatic regional near infrared spectroscopy saturation can classify complex hemodynamics into 4 distinct states, with a low-CO state of higher risk. We sought to identify interventions associated with low-CO state occupancy and transition. METHODS: Perioperative data were prospectively collected in an institutional review board-approved database. Hemodynamic state was classified as high CO, high SVR, low SVR, and low CO using bivariate analysis. Associations of static and dynamic support levels and state classifications over 48 postoperative hours were tested between states and across transitions using mixed regression methods in a quasi-experimental design. RESULTS: Data from 10,272 hours in 214 patients were analyzed. A low-CO state was observed in 142 patients for 1107 hours. Both low CO and extracorporeal membrane oxygenation had increased mortality risk. The low-CO state was characterized by lower milrinone but higher catecholamine dose. Successful transition out of low CO was associated with increased milrinone dose and hemoglobin concentration. Increasing milrinone and hemoglobin levels predicted reduced risk of low CO in future states. CONCLUSIONS: Bivariate classification objectively defines hemodynamic states and transitions with distinct support profiles. Maintaining or increasing inodilator and hemoglobin levels were associated with improved hemodynamic conditions and were predictive of successful future transitions from the low-CO state.

Identification of Time-Dependent Risks of Hemodynamic States After Stage 1 Norwood Palliation.

BACKGROUND: Mortality after stage 1 palliation of hypoplastic left heart syndrome remains significant. Hemodynamic changes result from interaction of cardiac output (CO) and systemic vascular resistance (SVR). We sought to identify time-dependent changes in postoperative hemodynamic states and their associations with mortality. METHODS: Perioperative data were prospectively collected in an institutional review board-approved database. Hemodynamic state was classified as high CO, high SVR, low SVR, and low CO using bivariate analysis of mean arterial pressure and somatic regional near-infrared spectroscopic oximetry saturation. State classifications over 48 postoperative hours were modelled using multinomial logistic regressions for association with mortality. RESULTS: Data from 9614 of 10,272 hours in 214 patients were analyzed. Operative survival was 91%. The predominant state was high CO (46% time). Low CO state without extracorporeal membrane oxygenation (ECMO) was found in 52% of patients for 9.7% time. ECMO was employed in 24 (11.2%) patients for 10.4% time. State stability was 33%, with high SVR the least stable (17%) and high CO the most stable (53%). Transition from high CO increased in hours 1 to 12, mainly to low SVR. Transition to low CO was 18.4%, increasing in hours 1 to 12, mainly from high SVR. The transition risk to ECMO was 0.32%, and 0.74% during hours 1 to 12, only from low CO. Both low CO and ECMO had increased mortality risk. CONCLUSIONS: Bivariate classification defines hemodynamic states with distinct physiologic, transition, and mortality risk profiles. High SVR state was unstable. Transition to ECMO occurred only from low CO, while the low SVR and high CO states were safest.

Chest tube removal algorithm is associated with decreased chest tube duration in pediatric cardiac surgical patients.

OBJECTIVE: Management of chest tubes in adult and pediatric patients is highly variable. There are no published guidelines for pediatric cardiac surgical patients. Our center undertook a quality improvement project aimed at reducing chest tube duration and length of stay in postsurgical pediatric cardiac patients. METHODS: A work group identified 2 opportunities for reducing chest tube duration: standardizing removal criteria and increasing frequency of assessment for removal. An algorithm was created, and chest tube assessments were increased to twice daily. All postsurgical cardiac patients were managed according to the algorithm. Outcome measure reporting was limited to patients age 1 month to 18 years with a biventricular surgical procedure. Outcome measures included chest tube duration, cardiac intensive care unit and hospital length of stay, and cost of hospitalization. Process measure was documentation of chest tube assessments. The balancing measure was chest tube reinsertions. RESULTS: Between April 2016 and July 2018, 126 patients aged 1 month to 18 years underwent a biventricular surgical procedure. Mean chest tube duration decreased from 61 to 47 hours. Cardiac intensive care unit length of stay decreased from 141 hours to 89 hours, hospital length of stay decreased from 266 to 156 hours, and average hospitalization cost decreased from $75,881 to $48,118. There was no increase in chest tube reinsertions. CONCLUSIONS: Implementation of a chest tube removal algorithm for pediatric cardiac surgery patients resulted in decreased chest tube duration and was associated with decreased length of stay and costs without an increase in reinsertions. More significant impact may be attainable with more aggressive approach to removal.

Reclassifying by highest complexity operation rather than first operation influences mortality after pediatric heart surgery.

OBJECTIVE: To evaluate the effect on mortality of reclassifying patients undergoing pediatric heart reoperations of varying complexity by operation of highest complexity instead of by first operation. METHODS: Data from the Virtual Pediatric Systems Database on children aged < 18 years who underwent heart surgery (with or without cardiopulmonary bypass) were included (2009-2015). Only patients who underwent reoperations during the same hospitalization were included. Patients were classified based on the first cardiovascular operation (the index operation), and on the complexity of the operation (the operation with the highest Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery [STAT] mortality category of each hospital admission) performed. RESULTS: Of 51,047 patients (73 centers), 22,393 met inclusion criteria. Using index operation as the classifying operation, the number of patients classified in the STAT 1 category increased by approximately 2.5 times compared with the highest-complexity operation (index, 7,077 and highest complexity, 2,654). In contrast, when the highest-complexity classification was used, we noted an increase in the number of patients in other STAT categories. We also noted higher mortality in all STAT categories when patients were classified by index operation instead of by highest complexity (index vs highest STAT category 1, 0.6% vs 0.2%; category 2, 2.4% vs 0.8%; category 3, 3.1% vs 2.1%; category 4, 5.8% vs 5.6%; and category 5, 16.7% vs 16.5%). CONCLUSIONS: This study demonstrates differences in the reported number of patients and reported mortality in each STAT category among children undergoing various heart reoperations during the same hospitalization by classifying patients based on index operation compared with the operation of highest complexity.