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.

Comparison of PLANE Technique versus Standard Echocardiography Guidance for Pediatric Pericardiocentesis.

Percutaneous pericardiocentesis remains a challenging and potentially dangerous procedure, particularly in small, critically ill patients. We present outcomes of the PLANE (pericardiocentesis using long-axis in-plane real-time echocardiography) technique for pediatric pericardiocentesis compared with a standard echocardiography (ECHO) guidance cohort. This was a retrospective chart review of all children undergoing percutaneous pericardiocentesis from March 2013 to February 2021 at a single center. A total of 78 procedures were performed, 52 utilizing PLANE technique and 26 utilizing standard ECHO-guidance technique. There was 100% technical success rate with only one minor complication for the entire cohort. Procedures were evenly split between the bedside intensive care unit and cardiac catheterization laboratory. PLANE technique was utilized in significantly younger (1.4 vs. 8.4 years, p = 0.008) and smaller (11.1 vs. 31.8 kg, p = 0.007) patients, as well as in most patients deemed high risk (postoperative < 7 days, extracorporeal membrane oxygenation (ECMO) support, and/or weight less than 5 kg; 19/22, p = 0.021). Other patient characteristics were similar between the two groups. There was a trend toward PLANE technique utilization by noncardiology trained operators. The PLANE technique for pediatric pericardiocentesis is safe and effective and can be effectively utilized in small and high-risk patient populations. The technical similarity to other long-axis ultrasound-guided procedures may facilitate adoption and mastery by critical care trained operators.

Deriving and validating a protocol to determine the need for prophylactic peritoneal dialysis in neonates after cardiopulmonary bypass surgery.

BACKGROUND: Prophylactic peritoneal dialysis (PD) in neonates undergoing cardiopulmonary bypass (CPB) is safe and improves outcomes. We sought to (1) derive the pre-operative characteristics of neonates who are most likely to benefit from PD after CPB and (2) validate a new prophylactic PD protocol based on our retrospective analysis. METHODS: First, we retrospectively evaluated neonates requiring cardiac surgery with CPB from October 2012 to June 2016. We categorized neonates as those who "needed PD" and those who "did not need PD" based on prior experience with neonates requiring kidney support therapy. Pre-operative serum creatinine ≥ 0.8 mg/dL, pre-operative weight ≤ 2.5 kg, or having an open chest post-operatively were independently associated with "needed PD." Next, beginning in March 2019, we implemented a new prophylactic PD protocol in which only those who met at least one of the three criteria derived in the retrospective analysis had a PD catheter placed in the OR. RESULTS: In Era 2, after the implementation of a new prophylactic PD protocol, 100% of neonates in the "needed PD" group had a PD catheter placed in the OR, which was more than in the prior era (Era 1 = 86.6%) (p = 0.05). Only 26.1% in the "did not need PD" group had a PD catheter placed in the OR which was less than in the prior era (Era 1 = 50.6%) (p < 0.01). CONCLUSIONS: We successfully developed and implemented an evidence-based prophylactic PD protocol that has improved our ability to provide prophylactic PD in neonates after CPB.

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.

Plasma proteoglycan 4: a novel biomarker for acute lung injury after pediatric cardiac surgery.

Background: Identification of biological molecules related to post cardiopulmonary bypass (CPB) lung injury could help diagnose, predict and potentially impact patient's clinical course after cardiac surgery. Proteoglycan 4 (PRG4) initially identified as potential biomarker for patients with prolonged mechanical ventilation following CPB in a prior study. To further validate these findings, we sought to understand the association of lower plasma PRG4 with prolonged mechanical ventilation and worse lung compliance in a larger cohort of pediatric patients post CPB. Methods: Retrospective chart review study. Pediatric Cardiac Intensive Care Unit, Tertiary Hospital. Infants <1 year old with tetralogy of Fallot, ventricular septal defect, or atrioventricular septal defect who underwent surgical repair 2012-2020 and had stored plasma samples in our biorepository were screened for inclusion. Patients with mechanical ventilation before surgery were excluded. Patients were divided into quartiles based on postoperative duration of mechanical ventilation (control <25th percentile, study >75th percentile). Preoperative and 48-hour postoperative samples for each cohort (20 patients each) were tested for PRG4 level using enzyme-linked immunosorbent assay (ELISA) technique. Results: Study group had lower lung compliance, higher mean airway pressure and higher oxygen need postoperative when compared to control group. Plasma PRG4 levels before surgery and 48 hours postoperative were lower in study group compared to control group (P=0.0232 preoperative; P=0.0016 postoperative). Plasma PRG4 levels were compared preoperative to PRG4 levels postoperative in both group, there was no statistically significant difference (study group: P=0.0869; control group: P=0.6500). Conclusions: Lower levels of plasma PRG4 is associated with longer duration of mechanical ventilation, worse ventilator compliance and higher oxygen requirement after cardiac surgery in our patient population. Further validation of this finding in a larger and more diverse patient population is necessary prior to its application at the bedside.

Risk factors for long post-operative hospital stays after cardiopulmonary bypass surgery in full-term neonates.

BACKGROUND: Long hospital stays for neonates following cardiac surgery can be detrimental to short- and long-term outcomes. Furthermore, it can impact resource allocation within heart centres' daily operations. We aimed to explore multiple clinical variables and complications that can influence and predict the post-operative hospital length of stay. METHODS: We conducted a retrospective observational review of the full-term neonates (<30 days old) who had cardiac surgery in a tertiary paediatric cardiac surgery centre - assessment of multiple clinical variables and their association with post-operative hospital length of stay. RESULTS: A total of 273 neonates were screened with a mortality rate of 8%. The survivors (number = 251) were analysed; 83% had at least one complication. The median post-operative hospital length of stay was 19.5 days (interquartile range 10.5, 31.6 days). The median post-operative hospital length of stay was significantly different among patients with complications (21.5 days, 10.5, 34.6 days) versus the no-complication group (14 days, 9.6, 19.5 days), p < 0.01. Among the non-modifiable variables, gastrostomy, tracheostomy, syndromes, and single ventricle physiology are significantly associated with longer post-operative hospital length of stay. Among the modifiable variables, deep vein thrombosis and cardiac arrest were associated with extended post-operative hospital length of stay. CONCLUSIONS: Complications following cardiac surgery can be associated with longer hospital stay. Some complications are modifiable. Deep vein thrombosis and cardiac arrest are among the complications that were associated with longer hospital stay and offer a direct opportunity for prevention which may be reflected in better outcomes and shorter hospital stay.

Does the standard medical procedure consent process meet the criteria required for informed consent? A concept analysis.

BACKGROUND: Informed consent is a complex process that is legally required before any surgical procedure. PURPOSE: The purpose of this manuscript was to perform a concept analysis of the informed consent process. METHODS: The use of dimensional analysis identified three separate yet related perspectives of the informed consent process: legal, health care, and patients. A database search using the Cumulative Index to Nursing and Allied Health Literature and PubMed were performed. FINDINGS: A total of 27 publications were reviewed. The legal perspective addresses the requirement of informed consent, which starts with the discussion between the health care provider and the patient undergoing the surgical procedure and ends with a signature on a piece of paper. The health care perspective also addresses the legal requirement but incorporates the goals and objectives of the individual initiating the informed consent discussion. The patients' perspectives also incorporate goals and objectives; however, they differ from that of the health care provider in that they go beyond what happens in the operating room or during hospitalization. DISCUSSION: Viewing informed consent through these different yet related perspectives provides insight into this complex process and may enhance the researcher's ability to understand and improve the informed consent process.

Impact of Management Strategy on Feeding and Somatic Growth in Neonates with Symptomatic Tetralogy of Fallot: Results from the Congenital Cardiac Research Collaborative.

OBJECTIVE: To evaluate early growth following primary or staged repair of neonatal symptomatic tetralogy of Fallot (sTOF). STUDY DESIGN: We performed a retrospective, multicenter cohort study of consecutive infants with sTOF who underwent initial intervention at age ≤30 days, from 2005 to 2017. Management strategies were either primary repair or staged repair (ie, initial palliation followed by complete repair). The primary outcome was change in weight-for-age z-score (ΔWAZ) from the initial intervention to age 6 ± 2 months. Secondary outcomes included method and mode of feeding, feeding-related medications, and feeding-related readmissions. Propensity score adjustment was used to account for baseline differences between groups. A secondary analysis was performed comparing patients stratified by the presence of adequate growth (6-month ΔWAZ > -0.5) or inadequate growth (6-month ΔWAZ ≤ -0.5), independent of treatment strategy. RESULTS: The study cohort included 143 primary repair subjects and 240 staged repair subjects. Prematurity was more common in the staged repair group. After adjustment, median ΔWAZ did not differ between treatment groups over the first 6 months of life (primary: -0.43 [IQR, -1.17 to 0.50]; staged: -0.31 [IQR, -1.31 to 0.71]; P = .55). For the entire cohort, ΔWAZ was negative (-0.36; IQR, -1.21 to 0.63). There were no between-group differences in the secondary outcomes. Secondary analysis revealed that the subjects with adequate growth were more likely to be orally fed at initial hospital discharge (P = .04). CONCLUSIONS: In neonates with sTOF, growth trajectory over the first 6 months of life was substandard, irrespective of treatment strategy. Those patients with adequate growth were more likely to be discharged from the index procedure on oral feeds.

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.

Palliation Strategy to Achieve Complete Repair in Symptomatic Neonates with Tetralogy of Fallot.

Neonates with symptomatic tetralogy of Fallot (sTOF) may undergo palliations with varying physiology, namely systemic to pulmonary artery connections (SPC) or right ventricular outflow tract interventions (RVOTI). A comparison of palliative strategies based on the physiology created is lacking. Consecutive sTOF neonates undergoing SPC or RVOTI from 2005-2017 were reviewed from the Congenital Cardiac Research Collaborative. The primary outcome was survival with successful complete repair (CR) by 18 months. A variety of secondary outcomes were assessed including overall survival, hospitalization-related comorbidities, and interstage reinterventions. Propensity score adjustment was utilized to compare treatment strategies. The cohort included 252 SPC (surgical shunt = 226, ductus arteriosus stent = 26) and 68 RVOTI (balloon pulmonary valvuloplasty = 48, RVOT stent = 11, RVOT patch = 9) patients. Genetic syndrome (29 [42.6%] v 75 [29.8%], p = 0.04), weight < 2.5 kg (28 [41.2%] v 68 [27.0%], p = 0.023), bilateral pulmonary artery Z-score < - 2 (19 [28.0%] v 36 [14.3%], p = 0.008), and pre-intervention antegrade flow (48 [70.6%] v 104 [41.3%], p < 0.001) were more common in RVOTI. Significant center differences were noted (p < 0.001). Adjusted survival to CR by 18 months (HR = 0.87, 95% CI = 0.63-1.21, p = 0.41) and overall survival (HR = 2.08, 95% CI = 0.93-4.65, p = 0.074) were similar. RVOTI had increased interstage reintervention (HR = 2.15, 95% CI = 1.36-3.99, p = 0.001). Total anesthesia (243 [213, 277] v 328 [308, 351] minutes, p < 0.001) and cardiopulmonary bypass times (117 [103, 132] v 151 [143, 160] minutes, p < 0.001) favored RVOTI. In this multicenter comparison of physiologic palliation strategies for sTOF, survival to successful CR and overall survival were similar; however, reintervention burden was significantly higher in RVOTI.

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.

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.

Early Versus Late Sternal Closure in Infants-Perioperative Associations and Outcomes.

BACKGROUND: Delayed sternal closure (DSC) has been used for patients who develop bleeding, chest wall edema, and malignant arrhythmia following cardiopulmonary bypass. Multiple factors can influence the timing of when to perform DSC. We aimed to describe our DSC experience in neonates and infants by comparing outcomes between patients undergoing early (<48 hours) versus late DSC (> 48 hours). We explored the associations between specific clinical and laboratory variables and the timing of DSC. METHODS: Retrospective chart review of neonates and infants (

Biomarkers for Adverse Lung Injury Following Pediatric Cardiopulmonary Bypass.

Cardiopulmonary bypass triggers systemic inflammation, resulting in lung injury, and frequently leads to prolonged mechanical ventilation. Biomarkers of systemic inflammation are required to predict the risk of such complications. We hypothesize that specific serum proteins can be used as biomarkers to predict the severity of lung injury following cardiac surgery. DESIGN: Retrospective chart review study. SETTING: Clinical variables were collected and used in conjuncture with unbiased proteomic analysis using mass spectrometry that was performed on frozen plasma samples from a study group (patients with mechanical ventilation > 48 hr post surgery) and a control group (patients with mechanical ventilation < 48 hr post surgery). SUBJECTS: Subjects included were infants who underwent cardiac surgery with similar complexity (Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery 3 or 4) using cardiopulmonary bypass. Patients in both groups were matched for their weight, age, and duration of cardiopulmonary bypass. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred eighty-three proteins were identified (99% minimum confidence and two peptides minimum, protein false discovery rate 0.1%) on proteomic analysis of four control and four study patients at precardiopulmonary bypass, 0, and 48 hours postcardiopulmonary bypass samples. Thirty-six of 178 proteins were significantly different (≥ 1.5-fold; p < 0.05) at precardiopulmonary bypass (top increased: tenascin; top decreased: tetranectin), 18 of 140 proteins at 0 hour (top increased: hemoglobin beta; top decreased: C8 beta), and 25 of 166 proteins at 48 hours post surgery (top increased: proteoglycan 4; top decreased: galectin-3-binding protein). The top pathway involved cytoskeleton remodeling. Other pathways involved immune response and blood coagulation. Proteoglycan 4 was validated by enzyme-linked immunosorbent assay in a different set of samples (n = 20/group; mean ± sd: 128 ± 67 vs 195 ± 160 ng/mL) (p = 0.037). CONCLUSIONS: Multiple proteomic biomarkers were associated with worse respiratory outcomes. Precardiopulmonary bypass biomarkers might indicate risk factors (e.g., abnormalities of coagulation), whereas those identified at 0 hour and post cardiopulmonary bypass may reflect mechanisms of ongoing pathobiology.

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.

Prophylactic Peritoneal Dialysis After the Arterial Switch Operation: A Retrospective Cohort Study.

BACKGROUND: Fluid overload contributes to poor outcomes after neonatal cardiac surgery. The optimal strategy to mitigate fluid overload related morbidity is unknown. The utility of prophylactic peritoneal dialysis remains controversial. We aimed to assess the impact of prophylactic peritoneal dialysis on outcomes and hypothesized that prophylactic dialysis would be associated with less fluid overload and improved outcomes in neonates undergoing the arterial switch operation. METHODS: A single-center retrospective analysis of 41 consecutive neonates between June 2010 and March 2016 undergoing the arterial switch operation was performed. Fluid balance and other outcomes were compared between those who received peritoneal dialysis (n = 25) and those who did not (n = 16). RESULTS: Demographics were similar between groups, except cardiopulmonary bypass duration, which was significantly longer in the dialysis group (125 ± 20 minutes) compared with the no dialysis group (109 ± 15 minutes; P = .01). Median time to dialysis initiation was 9.1 hours (interquartile range, 7 to 9.8) and median time to termination from cardiac intensive care unit admission was 58.7 hours (interquartile range, 44 to 76.1). Cumulative fluid balance in the dialysis group was significantly more negative compared with the no dialysis group across all 7 postoperative days. In the multivariable analysis, use of dialysis was associated with a 42% reduction in hours of mechanical ventilation (relative risk 0.58; 95% confidence interval, 0.4 to 0.85; P < .01) and a 34% reduction in intensive care unit length of stay (relative risk 0.66; 95% confidence interval, 0.47 to 0.94; P = .02). Utilization of dialysis was associated with lower hospital costs (P < .01). CONCLUSIONS: Prophylactic peritoneal dialysis after the arterial switch operation is associated with improved postoperative outcomes without increased hospital costs (Graphical Abstract).

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

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

Neonatal and Paediatric Heart and Renal Outcomes Network: design of a multi-centre retrospective cohort study.

BACKGROUND: Cardiac surgery-associated acute kidney injury is common. In order to improve our understanding of acute kidney injury, we formed the multi-centre Neonatal and Pediatric Heart and Renal Outcomes Network. Our main goals are to describe neonatal kidney injury epidemiology, evaluate variability in diagnosis and management, identify risk factors, investigate the impact of fluid overload, and explore associations with outcomes. METHODS: The Neonatal and Pediatric Heart and Renal Outcomes Network collaborative includes representatives from paediatric cardiac critical care, cardiology, nephrology, and cardiac surgery. The collaborative sites and infrastructure are part of the Pediatric Cardiac Critical Care Consortium. An acute kidney injury module was developed and merged into the existing infrastructure. A total of twenty-two participating centres provided data on 100-150 consecutive neonates who underwent cardiac surgery within the first 30 post-natal days. Additional acute kidney injury variables were abstracted by chart review and merged with the corresponding record in the quality improvement database. Exclusion criteria included >1 operation in the 7-day study period, pre-operative renal replacement therapy, pre-operative serum creatinine >1.5 mg/dl, and need for extracorporeal support in the operating room or within 24 hours after the index operation. RESULTS: A total of 2240 neonatal patients were enrolled across 22 centres. The incidence of acute kidney injury was 54% (stage 1 = 31%, stage 2 = 13%, and stage 3 = 9%). CONCLUSIONS: Neonatal and Pediatric Heart and Renal Outcomes Network represents the largest multi-centre study of neonatal kidney injury. This new network will enhance our understanding of kidney injury and its complications.

Furosemide Response Predicts Acute Kidney Injury After Cardiac Surgery in Infants and Neonates.

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

Acute Kidney Injury Biomarkers Predict an Increase in Serum Milrinone Concentration Earlier Than Serum Creatinine-Defined Acute Kidney Injury in Infants After Cardiac Surgery.

BACKGROUND: Milrinone, an inotropic agent used ubiquitously in children after cardiac surgery, accumulates in acute kidney injury (AKI). We assessed if urinary AKI biomarkers are predictive of an increase in milrinone concentrations in infants after cardiac surgery. METHODS: Multicenter prospective pilot study of infants undergoing cardiac surgery. Urinary AKI biomarkers were measured in the urine at specific time intervals after cardiopulmonary bypass initiation. AKI was defined using the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Serum milrinone concentrations were measured at specific intervals after drug initiation, dose changes, and termination. Excessive milrinone activity was defined as a 20% increase in serum concentration between 6 and 36 hours after initiation. The temporal relationship between urinary AKI biomarker concentrations and a 20% increase in milrinone concentration was assessed. RESULTS: AKI occurred in 31 (33%) of infants. Milrinone clearance was lower in patients with AKI (4.2 versus 5.6 L/h/70 kg; P = 0.02). Excessive milrinone activity was associated with development of serum creatinine-defined AKI [odds ratio (OR) 3.0; 95% confidence interval (CI), 1.21-7.39; P = 0.02]. Both tissue inhibitor metalloproteinase type 2 and insulin-like growth factor-binding protein type 7 (TIMP-2*IGFBP-7) ≥0.78 at 12 hours (OR 2.72; 95% CI, 1.01-7.38; P = 0.04) and kidney injury molecule 1 (KIM-1) ≥529.57 at 24 hours (OR 2.76; 95% CI, 1.06-7.17; P = 0.04) predicted excessive milrinone activity before a diagnosis of AKI. CONCLUSIONS: In this pilot study, urine TIMP-2*IGFBP-7 and KIM-1 were predictive of AKI and excessive milrinone activity. Future studies that include a pharmacodynamics assessment of patient hemodynamics, excessive milrinone activity, and AKI biomarker concentrations may be warranted to integrate this concept into clinical practice.