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.

Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. DESIGN: Retrospective cohort. SETTING: Two large quarternary care pediatric hospitals. PATIENTS: Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. CONCLUSIONS: Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

Periods of low renal perfusion pressure are associated with acute kidney injury following paediatric cardiac surgery.

INTRODUCTION: Acute kidney injury is associated with worse outcomes after cardiac surgery. The haemodynamic goals to ameliorate kidney injury are not clear. Low post-operative renal perfusion pressure has been associated with acute kidney injury in adults. Inadequate oxygen delivery may also cause kidney injury. This study evaluates pressure and oximetric haemodynamics after paediatric cardiac surgery and their association with acute kidney injury. MATERIALS AND METHODS: Retrospective case-control study at a children's hospital. Patients were < 6 months of age who underwent a Society of Thoracic Surgery-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery categories ≥ 3. Low renal perfusion pressure was time and depth below several tested thresholds. The primary outcome was serum creatine-defined acute kidney injury in the first 7 days. RESULTS: Sixty-six patients (median age 8 days) were included. Acute kidney injury occurred in 36%. The time and depth of renal perfusion pressure < 42 mmHg in the first 24 hours was greater in acute kidney injury patients (94 versus 35 mmHg*minutes of low renal perfusion pressure/hour, p = 0.008). In the multivariable model, renal perfusion pressure < 42 mmHg was associated with acute kidney injury (aOR: 2.07, 95%CI: 1.25-3.82, p = 0.009). Mean arterial pressure, central venous pressure, and measures of inadequate oxygen delivery were not associated with acute kidney injury. CONCLUSION: Periods of low renal perfusion pressure (<42 mmHg) in the first 24 post-operative hours are associated with acute kidney injury. Renal perfusion pressure is a potential modifiable target that may mitigate the impact of acute kidney injury after paediatric cardiac surgery.

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.

A descriptive assessment of the informed consent document used by congenital cardiac surgery centres.

BACKGROUND: Informed consent for surgery is a complex process particularly in paediatrics. Complexity increases with procedures such as CHD surgery. Regulatory agencies outline informed consent contents for surgery. We assessed and described CHD surgical informed consent contents through survey dissemination to paediatric CHD centres across United States of America. METHODS: Publicly available email addresses for 125 paediatric cardiac clinicians at 70 CHD surgical centres were obtained. Nine-item de-identified survey assessing adherence to The Joint Commission informed consent standards was created and distributed via RedCap® 14 March, 2023. A follow-up email was sent 29 March, 2023. Survey link was closed 18 April, 2023. RESULTS: Thirty-seven surveys were completed. Results showed informed consent documents were available in both paper (25, 68%) and electronic (3, 8%) format. When both (9, 24%) formats were available, decision on which format to use was based on centre protocols (1, 11%), clinician personal preference (3, 33%), procedure being performed (1, 11%), or other (4, 45%). Five (13%) centres' informed consent documents were available only in English, with 32 (87%) centres also having a Spanish version. Review of informed consent documents demonstrated missing The Joint Commission elements including procedure specific risks, benefits, treatment alternatives, and expected outcomes. CONCLUSIONS: Informed consent for CHD surgery is a complex process with multiple factors involved. Majority of paediatric CHD surgical centres in the United States of America used a generic informed consent document which did not uniformly contain The Joint Commission specified information nor reflect time spent in discussion with families. Further research is needed on parental comprehension during the informed consent process.

Urine Quantification Following Furosemide for Severe Acute Kidney Injury Prediction in Critically Ill Children.

A standardized, quantified assessment of furosemide responsiveness predicts acute kidney injury (AKI) in children after cardiac surgery and AKI progression in critically ill adults. The purpose of this study was to determine if response to furosemide is predictive of severe AKI in critically ill children outside of cardiac surgery. We performed a multicenter retrospective study of critically ill children. Quantification of furosemide response was based on urine flow rate (normalized for weight) measurement 0 to 6 hours after the dose. The primary outcome was presence of creatinine defined severe AKI (Kidney Disease Improving Global Outcomes stage 2 or greater) within 7 days of furosemide administration. Secondary outcomes included mortality, duration of mechanical ventilation and length of stay. A total of 110 patients were analyzed. Severe AKI occurred in 20% ( n = 22). Both 2- and 6-hour urine flow rate were significantly lower in those with severe AKI compared with no AKI ( p = 0.002 and p < 0.001). Cutoffs for 2- and 6-hour urine flow rate for prediction of severe AKI were <4 and <3 mL/kg/hour, respectively. The adjusted odds of developing severe AKI for 2-hour urine flow rate of <4 mL/kg/hour was 4.3 (95% confidence interval [CI]: 1.33-14.15; p = 0.02). The adjusted odds of developing severe AKI for 6-hour urine flow rate of <3 mL/kg/hour was 6.19 (95% CI: 1.85-20.70; p = 0.003). Urine flow rate in response to furosemide is predictive of severe AKI in critically ill children. A prospective assessment of urine flow rate in response to furosemide for predicting subsequent severe AKI is warranted.

Acute Kidney Injury Defined by Fluid-Corrected Creatinine in Premature Neonates: A Secondary Analysis of the PENUT Randomized Clinical Trial.

Importance: Acute kidney injury (AKI) and disordered fluid balance are common in premature neonates; a positive fluid balance dilutes serum creatinine, and a negative fluid balance concentrates serum creatinine, both of which complicate AKI diagnosis. Correcting serum creatinine for fluid balance may improve diagnosis and increase diagnostic accuracy for AKI. Objective: To determine whether correcting serum creatinine for fluid balance would identify additional neonates with AKI and alter the association of AKI with short-term and long-term outcomes. Design, Setting, and Participants: This study was a post hoc cohort analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3, randomized clinical trial of erythropoietin, conducted at 19 academic centers and 30 neonatal intensive care units in the US from December 2013 to September 2016. Participants included extremely premature neonates born at less than 28 weeks of gestation. Data analysis was conducted in December 2022. Exposure: Diagnosis of fluid-corrected AKI during the first 14 postnatal days, calculated using fluid-corrected serum creatinine (defined as serum creatinine multiplied by fluid balance [calculated as percentage change from birth weight] divided by total body water [estimated 80% of birth weight]). Main Outcomes and Measures: The primary outcome was invasive mechanical ventilation on postnatal day 14. Secondary outcomes included death, hospital length of stay, and severe bronchopulmonary dysplasia (BPD). Categorical variables were analyzed by proportional differences with the χ2 test or Fisher exact test. The t test and Wilcoxon rank sums test were used to compare continuous and ordinal variables, respectively. Odds ratios (ORs) and 95% CIs for the association of exposure with outcomes of interest were estimated using unconditional logistic regression models. Results: A total of 923 premature neonates (479 boys [51.9%]; median [IQR] birth weight, 801 [668-940] g) were included, of whom 215 (23.3%) received a diagnosis of AKI using uncorrected serum creatinine. After fluid balance correction, 13 neonates with AKI were reclassified as not having fluid-corrected AKI, and 111 neonates previously without AKI were reclassified as having fluid-corrected AKI (ie, unveiled AKI). Therefore, fluid-corrected AKI was diagnosed in 313 neonates (33.9%). Neonates with unveiled AKI were similar in clinical characteristics to those with AKI whose diagnoses were made with uncorrected serum creatinine. Compared with those without AKI, neonates with unveiled AKI were more likely to require ventilation (81 neonates [75.0%] vs 254 neonates [44.3%] and have longer hospital stays (median [IQR], 102 [84-124] days vs 90 [71-110] days). In multivariable analysis, a diagnosis of fluid-corrected AKI was associated with increased odds of adverse clinical outcomes, including ventilation (adjusted OR, 2.23; 95% CI, 1.56-3.18) and severe BPD (adjusted OR, 2.05; 95% CI, 1.15-3.64). Conclusions and Relevance: In this post hoc cohort study of premature neonates, fluid correction increased the number of premature neonates with a diagnosis of AKI and was associated with increased odds of adverse clinical outcomes, including ventilation and BPD. Failing to correct serum creatinine for fluid balance underestimates the prevalence and impact of AKI in premature neonates. Future studies should consider correcting AKI for fluid balance. Trial Registration: ClinicalTrials.gov Identifier: NCT01378273.

Coronavirus Disease 2019 in Pediatric Oncology Patients: A Matched-Cohort Analysis of the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry.

BACKGROUND: There is a paucity of multicenter data describing the impact of coronavirus disease 2019 (COVID-19) on hospitalized pediatric oncology patients. Using a large, multicenter, Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness University Study (VIRUS) database, we aimed at assessing outcomes of COVID-19 infection in this population. METHOD: This is a matched-cohort study involving children below 18 years of age hospitalized with COVID-19 between March 2020 and January 2021. Using the VIRUS; COVID-19 Registry database, children with oncologic diseases were compared with propensity score matched (age groups, sex, race, and ethnicity) cohort of children without oncologic diseases for the prevalence of Multisystem Inflammatory Syndrome in Children (MIS-C), intensive care unit (ICU) admission, interventions, hospital, and ICU length of stay. RESULTS: The number of children in the case and control groups was 45 and 180, respectively. ICU admission rate was similar in both groups ([47.7 vs 51.7%], P =0.63). The proportion of children requiring noninvasive and invasive mechanical ventilation, and its duration were similar between groups, same as hospital mortality. Interestingly, MIS-C was significantly lower in the oncology group compared with the control (2.4 vs 24.6%; P =0.0002). CONCLUSIONS: In this study using a multicenter VIRUS database, ICU admission rate, interventions, and outcomes of COVID-19 were similar in children with the oncologic disease compared with control patients. The incidence of MIS-C is lower in oncologic patients.

Association of Fluid Balance With Short- and Long-term Respiratory Outcomes in Extremely Premature Neonates: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Extremely low gestational age neonates are at risk of disorders of fluid balance (FB), defined as change in fluid weight over a specific period. Few data exist on the association between FB and respiratory outcomes in this population. Objective: To describe FB patterns and evaluate the association of FB with respiratory outcomes in a cohort of extremely low gestational age neonates. Design, Setting, and Participants: This study is a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3 placebo-controlled randomized clinical trial of erythropoietin in extremely premature neonates conducted in 30 neonatal intensive care units in the US from December 1, 2013, to September 31, 2016. This analysis included 874 extremely premature neonates born at 24 to 27 weeks' gestation who were enrolled in the PENUT study. Secondary analysis was performed in November 2021. Exposures: Primary exposure was peak FB during the first 14 postnatal days. The FB was calculated as percent change in weight from birth weight (BW) as a surrogate for FB. Main Outcomes and Measures: The primary outcome was mechanical ventilation on postnatal day 14. The secondary outcome was a composite of severe bronchopulmonary dysplasia (BPD) or death. Results: A total of 874 neonates (449 [51.4%] male; mean [SD] BW, 801 [188] g; 187 [21.4%] Hispanic, 676 [77.3%] non-Hispanic, and 11 [1.3%] of unknown ethnicity; 226 [25.9%] Black, 569 [65.1%] White, 51 [5.8%] of other race, and 28 [3.2%] of unknown race) were included in this analysis. Of these 874 neonates, 458 (52.4%) received mechanical ventilation on postnatal day 14, and 291 (33.3%) had severe BPD or had died. Median peak positive FB was 11% (IQR, 4%-20%), occurring on postnatal day 13 (IQR, 9-14). A total of 93 (10.6%) never decreased below their BW. Neonates requiring mechanical ventilation at postnatal day 14 had a higher peak FB compared with those who did not require mechanical ventilation (15% above BW vs 8% above BW, P < .001). On postnatal day 3, neonates requiring mechanical ventilation were more likely to have a higher FB (5% below BW vs 8% below BW, P < .001). The median time to return to BW was shorter in neonates who received mechanical ventilation (7 vs 8 days, P < .001) and those with severe BPD (7 vs 8 days, P < .001). After adjusting for confounding variables, for every 10% increase in peak FB during the first 14 postnatal days, there was 103% increased odds of receiving mechanical ventilation at postnatal day 14 (adjusted odds ratio, 2.03; 95% CI, 1.64-2.51). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, peak FB was associated with mechanical ventilation on postnatal day 14 and severe BPD or death. Fluid balance in the first 3 postnatal days and time to return to BW may be potential targets to help guide management and improve respiratory outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT01378273.

Electrolyte derangements in critically ill children receiving balanced versus unbalanced crystalloid fluid resuscitation.

BACKGROUND: Adult studies have demonstrated potential harm from resuscitation with 0.9% sodium chloride (0.9%NaCl), resulting in increased utilization of balanced crystalloids like lactated ringers (LR). The sodium and potassium content of LR has resulted in theoretical safety concerns, although limited data exists in pediatrics. We hypothesized that use of LR for resuscitation would not be associated with increased electrolyte derangements compared to 0.9%NaCl. METHODS: A prospective, observational cohort study of critically ill children who received ≥ 20 ml/kg of fluid resuscitation and were admitted to two pediatric intensive care units from November 2017 to February 2020. Fluid groups included patients who received > 75% of fluids from 0.9%NaCl, > 75% of fluids from LR, and a mixed group. The primary outcome was incidence of electrolyte derangements (sodium, chloride, potassium) and acidosis. RESULTS: Among 559 patients, 297 (53%) received predominantly 0.9%NaCl, 74 (13%) received predominantly LR, and 188 (34%) received a mixture. Extreme hyperkalemia (potassium ≥ 6 mmol/L) was more common in 0.9%NaCl group (5.8%) compared to LR group (0%), p 0.05. Extreme acidosis (pH > 7.1) was more common in 0.9%NaCl group (11%) compared to LR group (1.6%), p 0.016. CONCLUSIONS: LR is associated with fewer electrolyte derangements compared to 0.9%NaCl. Prospective interventional trials are needed to validate these findings.

Filtering Down to Risks and Solutions: Risk Factors and Stratification After Pediatric Cardiac Surgery.

Acute kidney injury after cardiac surgery (CS-AKI) is common in neonatal and pediatric populations and is a risk factor for poor outcomes, such as mortality and increased hospital resource utilization. This review presents a summary of CS-AKI risk factors, integration of biomarkers, and the need to improve risk stratification for targeting future clinical trials. To date, studies examining CS-AKI risk factors cannot be generalized easily owing to variability in patient age, surgical complexity or population, AKI definition, and center-specific practices. However, certain risk associations, such as younger age at surgery, history of prematurity, cardiopulmonary bypass time, and surgical complexity, have been identified across multiple, but not all, studies. CS-AKI appears to have different severity and duration phenotypes, and serum creatinine is limited in its ability to identify CS-AKI early and predict CS-AKI course. Treatment strategies are largely supportive, and efforts are ongoing to use biomarkers and clinical features to risk-stratify patients, which in turn may facilitate differential CS-AKI phenotyping and management with supportive care bundles, clinical decision support techniques, and modulation of modifiable risk factors.

Infants Who Require Total Parenteral Nutrition and Paralytics at Time of Heart Transplant Experience Inferior Post-Transplant Mortality.

Background: Infants experience the worst one-year post-heart transplant (HTx) survival of any other pediatric group. Although mechanical ventilatory (MV) requirement at the time of transplant is an established predictor of post-transplant mortality, the impacts of commonly co-utilized support modalities such as total parenteral nutrition (TPN)-dependence and paralytics are understudied. Methods: All infant HTx recipients from 2003 to 2020 in both the United Network for Organ Sharing and Pediatric Health Information System databases were identified (n = 1344) and categorized depending upon support requirement at the time of transplant-none (59%), MV-only (10%), MV + Paralytics (2%), TPN-dependence-only (15%), MV + TPN (10%), and MV + Paralytics + TPN (4%). The primary study aim was to characterize the impact of TPN-dependence and paralytics on one-year post-transplant survival (PTS). Results: Compared to no-support, supported infants were generally at higher risk and more ill at transplant, with greater rates of congenital heart disease, renal and hepatic dysfunctions, and inotrope requirements. Post-transplant hospital outcomes were inferior among supported patients; all support groups experienced longer post-transplant MV, intensive care unit, and hospital lengths of stay (all P < .05 vs no-support). Upon multivariable analysis, each support modality independently predicted 1-year mortality (MV vs no-MV: 1.54 [1.10-2.14]; MV + Paralytics vs neither: 2.02 [1.25-3.27]; TPN vs no-TPN: 1.53 [1.10-2.13]; P < .01 for all), whereas no-support was protective (HR 0.66 [95% CI 0.48-0.91]). Conclusions: Infants who require paralytics and/or who are TPN-dependent at the time of HTx experience worse one-year PTS. Such knowledge can assist in risk-stratification, and the identification of patients who would benefit from pretransplant optimization.

Improving acute kidney injury diagnostic precision using biomarkers.

Acute kidney injury (AKI) is common in hospitalized patients of all ages and is associated with significant morbidity and mortality. Accurate prediction and early identification of AKI is of utmost importance because no therapy exists to mitigate AKI once it has occurred. Yet, serum creatinine lacks adequate sensitivity and specificity, and quantification of urine output is challenging in incontinent children without indwelling bladder catheters. Integration of clinically available biomarkers have the potential to delineate unique AKI phenotypes that could have important prognostic and therapeutic implications. Plasma Cystatin C, urine neutrophil gelatinase associated lipocalin (NGAL) and the urinary product of tissue inhibitor metalloproteinase (TIMP-2) and insulin growth factor binding protein-7 (IGFBP7) are clinically available. These biomarkers have been studied in heterogenous populations across the age spectrum and in a variety of clinical settings for prediction of AKI. The purpose of this review is to describe and discuss the clinically available AKI biomarkers including how they have been used to delineate AKI phenotypes.

Fluid Accumulation After Neonatal Congenital Cardiac Operation: Clinical Implications and Outcomes.

BACKGROUND: This study was conducted to determine the association between fluid balance metrics and mortality and other postoperative outcomes after neonatal cardiac operation in a contemporary multicenter cohort. METHODS: This was an observational cohort study across 22 hospitals in neonates (≤30 days) undergoing cardiac operation. We explored overall percentage fluid overload, postoperative day 1 percentage fluid overload, peak percentage fluid overload, and time to first negative daily fluid balance. The primary outcome was in-hospital mortality. Secondary outcomes included postoperative duration of mechanical ventilation and intensive care unit (ICU) and hospital length of stay. Multivariable logistic or negative binomial regression was used to determine independent associations between fluid overload variables and each outcome. RESULTS: The cohort included 2223 patients. In-hospital mortality was 3.9% (n = 87). Overall median peak percentage fluid overload was 4.9% (interquartile range, 0.4%-10.5%). Peak percentage fluid overload and postoperative day 1 percentage fluid overload were not associated with primary or secondary outcomes. Hospital resource utilization increased on each successive day of not achieving a first negative daily fluid balance and was characterized by longer duration of mechanical ventilation (incidence rate ratio, 1.11; 95% CI, 1.08-1.14), ICU length of stay (incidence rate ratio, 1.08; 95% CI, 1.03-1.12), and hospital length of stay (incidence rate ratio, 1.09; 95% CI, 1.05-1.13). CONCLUSIONS: Time to first negative daily fluid balance, but not percentage fluid overload, is associated with improved postoperative outcomes in neonates after cardiac operation. Specific treatments to achieve an early negative fluid balance may decrease postoperative care durations.

Modifying the Renal Angina Index for Predicting AKI and Related Adverse Outcomes in Pediatric Heart Surgery.

Background:Reliable prediction of severe acute kidney injury (AKI) and related poor outcomes has the potential to optimize treatment. The purpose of this study was to modify the renal angina index in pediatric cardiac surgery to predict severe AKI and related poor outcomes. Methods: We performed a multicenter retrospective study with the population divided into a derivation and validation cohort to assess the performance of a modified renal angina index assessed at 8 h after cardiac intensive care unit (CICU) admission to predict a complex outcome of severe day 3 AKI or related poor outcomes (ventilation duration >7 days, CICU length of stay >14 days, and mortality). The derivation sample was used to determine the optimal cut-off value. Results: There were 298 and 299 patients in the derivation and validation cohorts, respectively. The incidence of severe day 3 AKI and the complex outcome was 1.7% and 28% in the derivation and validation cohort. The sensitivity analysis for fulfillment of renal angina was a score >8 with a sensitivity of 63%, specificity of 73%, and negative predictive value of 83%. The cardiac renal angina index predicted the composite outcome with an area under the curve of 0.7 (95% confidence interval: 0.62-0.78). Renal angina patients had a significantly higher probability of the complex outcome when compared to individual risk and injury categories. Conclusions: We operationalized the renal angina index for use after cardiac surgery. Further revision and modification of the construct with integration of biomarkers in a prospective cohort are necessary to refine the prediction model.

Epidemiology of Neonatal Acute Kidney Injury After Cardiac Surgery Without Cardiopulmonary Bypass.

BACKGROUND: The purpose of this Neonatal and Pediatric Heart and Renal Outcomes Network study was to describe the epidemiology and outcomes of cardiac surgery-associated acute kidney injury (CS-AKI) after cardiac surgery without cardiopulmonary bypass (non-CPB). METHODS: We performed a retrospective study of neonates (≤30 days) who underwent non-CPB cardiac surgery at 22 centers affiliated with the Pediatric Cardiac Critical Care Consortium. CS-AKI was defined using the modified Kidney Disease: Improving Global Outcomes serum creatinine and urine output criteria from postoperative days 0 to 6. CS-AKI defined by serum creatinine was further subclassified into transient (resolved by postoperative day 3) and persistent/late (≥3 days). Multivariable regression analyses were used to determine risk factors for CS-AKI and associations with outcomes of ventilation hours and cardiac intensive care unit length of stay. RESULTS: Five hundred eighty-two neonates (median age at surgery, 9 days [interquartile range, 5-15], 25% functional single ventricle] were included. CS-AKI occurred in 38.3%: Rate and severity varied across centers. Aggregate daily CS-AKI prevalence peaked on postoperative day 1 (17.1%). No stage of CS-AKI was associated with ventilation hours or length of stay. Persistent/late CS-AKI occurred in 48 patients (8%). Prostaglandin use and single-ventricle surgery were associated with persistent/late CS-AKI. Higher baseline serum creatinine but not persistent/late CS-AKI was associated with longer ventilation duration and intensive care unit length of stay after adjusting for confounders. CONCLUSIONS: Kidney Disease: Improving Global Outcomes-defined CS-AKI occurred commonly in neonates undergoing non-CPB cardiac surgery. However most CS-AKI was transient, and no CS-AKI classification was associated with worse outcomes. Further work is needed to determine the CS-AKI definition that best associates with outcomes in this cohort.

Urine Biomarkers for the Assessment of Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Receiving Therapeutic Hypothermia.

OBJECTIVE: To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: We performed a multicenter prospective observational study of 64 neonates. Urine specimens were obtained at 12, 24, 48, and 72 hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin-18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor-binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO (Kidney Disease: Improving Global Outcomes) AKI criteria. RESULTS: AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use compared with those without AKI (median [IQR], 2 [0-5] days vs 0 [0-2] days; P = .026). Mortality was greater in neonates with AKI (25% vs 2%; P = .012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs yielded only a fair prediction. KIM-1 had the best predictive performance across time points, with an AUC (SE) of 0.79 (0.11) at 48 hours of life. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48 hours of life. CONCLUSIONS: Urine NGAL, KIM-1, and IL-18 levels were elevated in neonates with HIE receiving therapeutic hypothermia who developed AKI. However, wide variability and unclear cutoff levels make their clinical utility unclear.

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.