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.

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.

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.

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

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

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.

Central ECMO cannulation for severe dihydropyridine calcium channel blocker overdose.

Calcium channel blocker (CCB) toxicity carries a high mortality and is the sixth most fatal drug class reported to US poison centers. Amlodipine overdose is characterized by a life-threatening arterial vasodilation that compromises organ perfusion. The management of CCB intoxication is focused on maintaining adequate organ perfusion. In cases refractory to medical therapies, hemodynamic support with extracorporeal membrane oxygenation (ECMO) is warranted necessitating higher flows than usual to compensate for the vasodilation and requiring central cannulation. We present a case of a 12-year-old with severe dihydropyridine CCB ingestion, refractory to medical management and successfully treated with central ECMO cannulation. The patient was discharged home with no significant disability. Central ECMO cannulation may be helpful to facilitate adequate flows in vasodilatory shock such as CCB overdose.

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

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

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

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

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

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

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

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

Does Extracorporeal Membrane Oxygenation Improve Survival in Pediatric Acute Respiratory Failure?

RATIONALE: Extracorporeal membrane oxygenation (ECMO) has supported gas exchange in children with severe respiratory failure for more than 40 years, without ECMO efficacy studies. OBJECTIVES: To compare the mortality and functional status of children with severe acute respiratory failure supported with and without ECMO. METHODS: This cohort study compared ECMO-supported children to pair-matched non-ECMO-supported control subjects with severe acute respiratory distress syndrome (ARDS). Both individual case matching and propensity score matching were used. The study sample was selected from children enrolled in the cluster-randomized RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) clinical trial. Detailed demographic and daily physiologic data were used to match patients. The primary endpoint was in-hospital mortality. Secondary outcomes included hospital-free days, ventilator-free days, and change in functional status at hospital discharge. MEASUREMENTS AND MAIN RESULTS: Of 2,449 children in the RESTORE trial, 879 (35.9%) non-ECMO-supported patients with severe ARDS were eligible to match to 61 (2.5%) ECMO-supported children. When individual case matching was used (60 matched pairs), the in-hospital mortality rate at 90 days was 25% (15 of 60) for both the ECMO-supported and non-ECMO-supported children (P > 0.99). With propensity score matching (61 matched pairs), the ECMO-supported in-hospital mortality rate was 15 of 61 (25%), and the non-ECMO-supported hospital mortality rate was 18 of 61 (30%) (P = 0.70). There was no difference between ECMO-supported and non-ECMO-supported patients in any secondary outcomes. CONCLUSIONS: In children with severe ARDS, our results do not demonstrate that ECMO-supported children have superior outcomes compared with non-ECMO-supported children. Definitive answers will require a rigorous multisite randomized controlled trial.

Aspiration After Congenital Heart Surgery.

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

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.

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.

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

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

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

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

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

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

Central Venous to Arterial CO2 Difference After Cardiac Surgery in Infants and Neonates.

OBJECTIVES: Venous to arterial CO2 difference correlates with cardiac output in critically ill adults, but its utility in pediatric patients is unclear. We sought to correlate venous to arterial CO2 difference with other cardiac output surrogates (arteriovenous oxygen saturation difference, central venous oxygen saturation, and lactate) and investigate its capacity to predict poor outcomes associated with low cardiac output (low cardiac output syndrome) in infants after cardiac surgery with cardiopulmonary bypass. DESIGN: Retrospective chart review. Poor outcome was defined as any inotrope score greater than 15; death, cardiac arrest, extracorporeal membrane oxygenation; and unplanned surgical reintervention. SETTING: Pediatric cardiovascular ICU. PATIENTS: One hundred thirty-nine infants less than 90 days who underwent cardiopulmonary bypass, from October 2012 to May 2015. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Two hundred ninety-six arterial and venous blood gas pairs from admission (n = 139), 6 (n = 62), 12 (n = 73), and 24 hours (n = 22) were included in analysis. For all pairs, venous to arterial CO2 difference was moderately correlated with arteriovenous oxygen saturation difference (R = 0.53; p < 0.01) and central venous oxygen saturation (R = -0.43; p < 0.01), but not lactate. At admission, venous to arterial CO2 difference was also moderately correlated with central venous oxygen saturation (R = -0.40; p < 0.01) and arteriovenous oxygen saturation difference (R = 0.55; p < 0.01), but not lactate. Thirty-four of 139 neonates (24.5%) had poor outcome. Median admission venous to arterial CO2 difference was 5.9 mm Hg (3.8-9.2 mm Hg). Patients with poor outcome had median admission venous to arterial CO2 difference 8.3 (5.6-14.9) versus 5.4 mm Hg (3.0-8.4 mm Hg) in those without poor outcome. Venous to arterial CO2 difference (area under the curve = 0.69; p < 0.01), serum lactate (area under the curve = 0.64; p = 0.02), and central venous oxygen saturation (area under the curve = 0.74; p < 0.01) were predictive of poor outcome. After controlling for covariates, admission venous to arterial CO2 difference remained significantly associated with poor outcome (odds ratio, 1.3; 95% CI, 1.1-1.45), including independent association with mortality (odds ratio, 1.2; 95% CI, 1.07-1.31). CONCLUSIONS: Venous to arterial CO2 difference is correlated with important surrogates of cardiac output, and is associated with poor outcome and mortality related to low cardiac output syndrome after cardiac surgery in infants. Prospective validation of these findings, including confirmation that venous to arterial CO2 difference can identify low cardiac output syndrome in real time, is warranted.

Early High-Frequency Oscillatory Ventilation in Pediatric Acute Respiratory Failure. A Propensity Score Analysis.

RATIONALE: The use of high-frequency oscillatory ventilation (HFOV) for acute respiratory failure in children is prevalent despite the lack of efficacy data. OBJECTIVES: To compare the outcomes of patients with acute respiratory failure managed with HFOV within 24-48 hours of endotracheal intubation with those receiving conventional mechanical ventilation (CMV) and/or late HFOV. METHODS: This is a secondary analysis of data from the RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) study, a prospective cluster randomized clinical trial conducted between 2009 and 2013 in 31 U.S. pediatric intensive care units. Propensity score analysis, including degree of hypoxia in the model, compared the duration of mechanical ventilation and mortality of patients treated with early HFOV matched with those treated with CMV/late HFOV. MEASUREMENTS AND MAIN RESULTS: Among 2,449 subjects enrolled in RESTORE, 353 patients (14%) were ever supported on HFOV, of which 210 (59%) had HFOV initiated within 24-48 hours of intubation. The propensity score model predicting the probability of receiving early HFOV included 1,064 patients (181 early HFOV vs. 883 CMV/late HFOV) with significant hypoxia (oxygenation index ≥ 8). The degree of hypoxia was the most significant contributor to the propensity score model. After adjusting for risk category, early HFOV use was associated with a longer duration of mechanical ventilation (hazard ratio, 0.75; 95% confidence interval, 0.64-0.89; P = 0.001) but not with mortality (odds ratio, 1.28; 95% confidence interval, 0.92-1.79; P = 0.15) compared with CMV/late HFOV. CONCLUSIONS: In adjusted models including important oxygenation variables, early HFOV was associated with a longer duration of mechanical ventilation. These analyses make supporting the current approach to HFOV less convincing.

Adrenal insufficiency in neonates after cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) may lead to adrenal insufficiency (AI). Emerging evidence supports association of AI with morbidity after cardiac surgery. AIMS: The aim of this study was to define AI incidence in neonates undergoing complex cardiac surgery with CPB and its association with intraoperative post-CPB outcomes. METHODS: Forty subjects enrolled in a prior randomized control trial who received preoperative methylprednisolone as part of our institutional neonatal bypass protocol were included. No intraoperative steroids were given. ACTH stimulation tests were performed: preoperatively and 1 h after separation from CPB. AI was defined as <9 µg·ml-1 increase in cortisol at 30 min post cosyntropin 1 mcg. Clinical outcomes were collected up to 90 min after CPB. RESULTS: 2/40 (5%) subjects had preoperative AI vs 13/40 (32.5%) post-CPB AI, P ≤ 0.001. No significant difference was observed in age, gestational age, weight, CPB time, circulatory arrest, or STAT category between subjects with or without post-CPB AI. ACTH decreased from preoperative values 127.3 vs 35 pcg·ml-1 [median difference = 81.8, 95% CI = 22.7-127.3], while cortisol increased from 18.9 vs 75 µg·dl-1 [median difference = 52.2, 95% CI = 36.3-70.9]. Post-CPB AI was associated with increased median colloid resuscitation, 275 vs 119 ml·kg-1 [median difference = 97.8, 95% CI = 7.1-202.2]; higher median peak lactate, 9.4 vs 6.9 mg·dl-1 [median difference = 3.2, 95% CI = 0.04-6.7]; median post-CPB lactate, 7.9 vs 4.3 mg·dl-1 , [median difference 3.6, 95% CI = 2.1-4.7], and median lactate on admission to CICU, 9.4 vs 6.0 mg·dl-1 [median difference = 3, 95% CI = 1.1-4.9]. No difference was observed in blood pressure or vasoactive inotrope score at any time point measured in operating room (OR). Higher initial post-CPB cortisol correlated with decreased cosyntropin response. CONCLUSIONS: Neonatal cardiac surgery with CPB and preoperative methylprednisolone leads to AI as determined by low-dose ACTH stimulation test in one-third of patients. AI is associated with increased serum lactate and colloid resuscitation in OR. Impact of preoperative methylprednisolone on results is not defined. Benefit of postoperative steroid administration in neonates with post-CPB AI warrants further investigation.