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OBJECTIVE The Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) program is a multicenter, quality improvement initiative that identifies patients at risk for nephrotoxic medication-associated acute kidney injury (NTMx-AKI). The purpose of this study was to (1) evaluate the prevalence and types of NTMx exposures and (2) determine the prevalence of NTMx-AKI categorized by service. Exploratory analysis evaluated potential associations between hospital measures and NTMx-AKI. METHODS This is a single-center, retrospective chart review of NTMx exposures from January 2019 to June 2020 in noncritically ill children. High NTMx exposures were defined as ≥3 simultaneous nephrotoxins or ≥3 days of either intravenous vancomycin or aminoglycoside. Prevalence of high NTMx and NTMx-AKI rate were normalized to 1000 patient days. A retrospective case-control analysis assessed for potential associations with development of NTMx-AKI. RESULTS There were 609 NTMx exposures in 565 patients and 44 (7.2%) episodes of NTMx-AKI. The NTMx prevalence rate per 1000 patient days was highest among liver, neurosurgery, and gastroenterology services. The most commonly used NTMx were vancomycin, intravenous contrast, and nonsteroidal antiinflammatory drugs. The NTMx-AKI rate in exposed patients ranged from 0% to 14% across service lines. AKI was most often attributable to vancomycin. Univariable analyses suggest type and duration of NTMx exposure are associated with development of NTMx-AKI but not with severity. CONCLUSIONS NTMx exposures and NTMx-AKI are variable across services. Partnerships with antimicrobial stewardship and multicenter studies are needed to modify NTMx-AKI risk. Ongoing surveillance is needed in patients who do not have normalization of creatinine before discharge.

Quality improvement initiatives to decrease rates of nephrotoxic medication exposure have reduced rates of acute kidney injury (AKI) in noncritically ill children. The objective of our study was to analyze the implementation of a similar program in critically ill children and to measure important balancing measures including opioid and benzodiazepine exposure.Prospective quality improvement study.PICU at Children's Hospital Colorado between 2018 and 2020.All children admitted to PICU.Quality improvement initiative called Nephrotoxic Injury Negated by Just-In-Time Action (NINJA).Eight thousand eight hundred thirty-three PICU patient admissions were included. Mean rates of nephrotoxic medication exposure/1,000 PICU patient days decreased from 46 to 26, whereas rates of nephrotoxic AKI/1,000 PICU patient days did not change. Nonsteroidal anti-inflammatory drug dispenses per 1,000 patient days were reduced from 521 to 456. Similarly, opioid and benzodiazepine exposures per 1,000 patient days were reduced from 812 to 524 and 441 to 227, respectively, during the study observation period.The NINJA intervention was efficaciously implemented in our single-center PICU. Nephrotoxic exposure is a modifiable factor that did not inadvertently increase exposure to opioids and benzodiazepines.

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.

Objective To determine the association of dysnatremia in the first postnatal week and risk of acute kidney injury (AKI) and mortality. Study design A secondary analysis of 1979 neonates in the AWAKEN cohort evaluated the association of dysnatremia with (1) AKI in the first postnatal week and (2) mortality, utilizing time-varying Cox proportional hazard models. Result Dysnatremia developed in 50.2% of the cohort and was not associated with AKI. Mortality was associated with hyponatremia (HR 2.15, 95% CI 1.07-4.31), hypernatremia (HR 4.23, 95% CI 2.07-8.65), and combined hypo/hypernatremia (HR 6.39, 95% CI 2.01-14.01). In stratified models by AKI-status, hypernatremia and hypo/hypernatremia increased risk of mortality in neonates without AKI. Conclusion Dysnatremia within the first postnatal week was associated with increased risk of mortality. Hypernatremia and combined hypo/hypernatremia remained significantly associated with mortality in neonates without AKI. This may reflect fluid strategies kidney injury independent of creatinine and urine-output defined AKI, and/or systemic inflammation.

Mechanical ventilation prior to pediatric heart transplantation predicts inferior post-transplant survival, but the impact of ventilation duration on survival is unclear.Data from the United Network for Organ Sharing and Pediatric Health Information System were used to identify pediatric (18 years) heart transplant recipients from 2003 to 2020. Patients ventilated pretransplant were first compared to no ventilation, then ventilation durations were compared across quartiles of ventilation (≤1 week, 8 days-5 weeks,5 weeks).At transplant, 11% (511/4506) of patients required ventilation. Ventilated patients were younger, had more congenital heart disease, more urgent listing-status, and greater rates of nephropathy, TPN-dependence, and inotrope and ECMO requirements (p .001 for all). Post-transplant, previously ventilated patients experienced longer ventilation durations, ICU and hospital stays, and inferior survival (all p .001). Hospital outcomes and survival worsened with longer pretransplant ventilation. One-year and overall survival were similar between the no-ventilation and ≤1 week groups (p = .703p = .433, respectively) but were significantly worse for ventilation durations1 week (p .001). On multivariable analysis, ventilation ≤1 week did not predict mortality (HR 0.98 [95% CI 0.85-1.43]), whereas ventilation1 week did (HR: 1.18 [1.01-1.39]).Longer pretransplant ventilation portends worse outcomes, although only ventilation1 week predicts mortality. These findings can inform pretransplant prognostication.

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

Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery in children and is associated with adverse outcomes including increased risk of death. The purpose of this review is to discuss the contemporary prevention and management considerations for children with critical cardiac disease who are at risk for and have experienced AKI. Despite numerous clinical trials, there has been little success in preventing or treating AKI. In adults and children, implementation of electronic health care alerts and care bundles have been shown to reduce AKI incidence, but the effect on long-term outcomes is variable. Follow-up with nephrology after an episode of AKI may reduce the risk for long-term complications. Prevention and treatment of AKI are paramount to reducing the risk for long-term complications which may be improved by primary, secondary, and tertiary prevention strategies. Follow-up clinics should become routine across pediatric centers to survey the development of chronic kidney disease and implement measures to mitigate progression.

Objective To examine incidence of acute kidney injury (AKI), antenatal and postnatal predictors, and impact of AKI on outcomes in infants with congenital diaphragmatic hernia (CDH). Study design Single center retrospective study of 90 CDH infants from 2009–2017. Baseline characteristics, CDH severity, possible AKI predictors, and clinical outcomes were compared between infants with and without AKI. Result In total, 38% of infants developed AKI, 44% stage 1, 29% stage 2, 27% stage 3. Lower antenatal lung volumes and liver herniation were associated with AKI. Extracorporeal life support (ECLS), diuretics, abdominal closure surgery, hypotension, and elevated plasma free hemoglobin were associated with AKI. Overall survival was 79%, 47% with AKI, and 35% with AKI on ECLS. AKI is associated with increased mechanical ventilation duration and length of stay. Conclusion AKI is common among CDH infants and associated with adverse outcomes. Standardized care bundles addressing AKI risk factors may reduce AKI incidence and severity.

Acute kidney injury (AKI), fluid overload (FO), and mortality are common in pediatric patients supported by extracorporeal membrane oxygenation (ECMO). The aim of this study is to evaluate if using a fluid management algorithm reduced AKI and mortality in children supported by ECMO. We performed a retrospective study of pediatric patients aged birth to 25 years requiring ECMO at a quaternary level children's hospital from 2007 to 2019 In October 2017, a fluid management algorithm was implemented for protocolized fluid removal after deriving a daily fluid goal using a combination of diuretics and ultrafiltration. Daily algorithm compliance was defined as ≥ 12 h on the algorithm each day. The primary and secondary outcomes were AKI and mortality, respectively, and were assessed in the entire cohort and the sub-analysis of children from the era in which the algorithm was implemented. Two hundred and ninety-nine (median age 5.3 months; IQR: 0.2, 62.3; 45% male) children required ECMO (venoarterial in 85%). The fluid algorithm was applied in 74 patients. The overall AKI rate during ECMO was 38% (26% severe-stage 2/3). Both AKI incidence and mortality were significantly lower in patients managed on the algorithm (p = 0.02 and p = 0.05). After adjusting for confounders, utilization of the algorithm was associated with lower odds of AKI (aOR: 0.40, 95%CI: 0.21, 0.76; p = 0.005) but was not associated with a reduction in mortality. In the sub-analysis, algorithm compliance of 80-100% was associated with a 54% reduction in mortality (ref: 60% compliant; aOR:0.46, 95%CI:0.22-1.00; p = 0.05). Conclusion: Among the entire cohort, the use of a fluid management algorithm reduced the odds of AKI. Better compliance on the algorithm was associated with lower mortality. Multicenter studies that implement systematic fluid removal may represent an opportunity for improving ECMO-related outcomes. What is Known: • Acute kidney injury and fluid overload are associated with morbidity and mortality in children supported by extracorporeal membrane oxygenation. What is New: • A systematic and protocolized approach to fluid removal in children supported by extracorporeal membrane oxygenation reduces acute kidney injury incidence. • Greater adherence to a protocolized fluid removal algorithm is associated with a reduction in mortality.

Preclinical models and emerging translational data suggest that acute kidney injury (AKI) has far reaching effects on all other major organ systems in the body. Common in critically ill children and adults, AKI is independently associated with worse short and long term morbidity, as well as mortality, in these vulnerable populations. Evidence exists in adult populations regarding the impact AKI has on life course. Recently, non-renal organ effects of AKI have been highlighted in pediatric AKI survivors. Given the unique pediatric considerations related to somatic growth and neurodevelopmental consequences, pediatric AKI has the potential to fundamentally alter life course outcomes. In this article, we highlight the challenging and complex interplay between AKI and the brain, heart, lungs, immune system, growth, functional status, and longitudinal outcomes. Specifically, we discuss the biologic basis for how AKI may contribute to neurologic injury and neurodevelopment, cardiac dysfunction, acute lung injury, immunoparalysis and increased risk of infections, diminished somatic growth, worsened functional status and health related quality of life, and finally the impact on young adult health and life course outcomes.

Background:Milrinone is a phosphodiesterase type 3 inhibitor that results in a positive inotropic effect in the heart through an increase in cyclic adenosine monophosphate. The purpose of this study was to evaluate circulating cyclic adenosine monophosphate and milrinone concentrations in milrinone treated paediatric patients undergoing congenital heart surgery.Methods:Single-centre prospective observational pilot study from January 2015 to December 2017 including children aged birth to 18 years. Milrinone and circulating cyclic adenosine monophosphate concentrations were measured at four time points through the first post-operative day and compared between patients with and without low cardiac output syndrome, defined using clinical and laboratory criteria.Results:Fifty patients were included. Nine (18%) developed low cardiac output syndrome. For all patients, 22% had single ventricle heart disease. The density and distribution of cyclic adenosine monophosphate concentrations varied between those with and without low cardiac output syndrome but were not significantly different. Milrinone concentrations increased in all patients. Paired t-tests demonstrated an increase in circulating cyclic adenosine monophosphate concentrations during the post-operative period among patients without low cardiac output syndrome.Conclusions:In this prospective observational study, circulating cyclic adenosine monophosphate concentrations increased in those without low cardiac output syndrome during the first 24 post-operative hours and milrinone concentrations increased in all patients. Further study of the utility of cyclic adenosine monophosphate concentrations in milrinone treated patients is necessary.

Background: Describe the incidence and associated outcomes of gastrointestinal (GI) manifestations of acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in hospitalized children (MIS-C). Methods: Retrospective review of the Viral Infection and Respiratory Illness Universal Study registry, a prospective observational, multicenter international cohort study of hospitalized children with acute COVID-19 or MIS-C from March 2020 to November 2020. The primary outcome measure was critical COVID-19 illness. Multivariable models were performed to assess for associations of GI involvement with the primary composite outcome in the entire cohort and a subpopulation of patients with MIS-C. Secondary outcomes included prolonged hospital length of stay defined as being >75th percentile and mortality. Results: Of the 789 patients, GI involvement was present in 500 (63.3%). Critical illness occurred in 392 (49.6%), and 18 (2.3%) died. Those with GI involvement were older (median age of 8 yr), and 18.2% had an underlying GI comorbidity. GI symptoms and liver derangements were more common among patients with MIS-C. In the adjusted multivariable models, acute COVID-19 was no associated with the primary or secondary outcomes. Similarly, despite the preponderance of GI involvement in patients with MIS-C, it was also not associated with the primary or secondary outcomes. Conclusions: GI involvement is common in hospitalized children with acute COVID-19 and MIS- C. GI involvement is not associated with critical illness, hospital length of stay or mortality in acute COVID-19 or MIS-C.

Understanding physiologic water balance and homeostasis mechanisms in the neonate is critical for clinicians in the NICU as pathologic fluid accumulation increases the risk for morbidity and mortality. In addition, once this process occurs, treatment is limited. In this review, we will cover fluid homeostasis in the neonate, explain the implications of prematurity on this process, discuss the complexity of fluid accumulation and the development of fluid overload, identify mitigation strategies, and review treatment options.

With the adoption of standardized neonatal acute kidney injury (AKI) definitions over the past decade and the concomitant surge in research studies, the epidemiology of and risk factors for neonatal AKI have become much better understood. Thus, there is now a need to focus on strategies designed to improve AKI care processes with the goal of reducing the morbidity and mortality associated with neonatal AKI. The 22nd Acute Dialysis/Disease Quality Improvement (ADQI) report provides a framework for such quality improvement in adults at risk for AKI and its sequelae. While many of the concepts can be translated to neonates, there are a number of specific nuances which differ in neonatal AKI care. A group of experts in pediatric nephrology and neonatology came together to provide neonatal-specific responses to each of the 22nd ADQI consensus statements.

This review sought to highlight the current paradigms and emerging treatment options for two common and serious problems after congenital cardiac surgery: low cardiac output syndrome (LCOS) and vasoplegia. Low cardiac output syndrome and vasoplegia remain prevalent after congenital cardiac surgery. Recent studies on adjunctive agents for LCOS have not shown consistent improvements in patient outcomes. Recent studies of targeted vasoconstrictors, adjunctive nitric oxide antagonists, and perioperative corticosteroids have limitations precluding their routine use in pediatric patients after congenital cardiac surgery. The treatment of LCOS is predicated on approaches that improve cardiac output by augmentation of heart rate, contractility, preload, and minimization of afterload. Strategies that minimize tissue oxygen demand can also be helpful to restore matching of tissue oxygen delivery and demand. The hallmark of vasoplegia treatment is augmentation of systemic vascular tone. A variety of emerging therapies are under investigation for their role in LCOS and vasoplegia after congenital cardiac surgery, but none are ready for routine use.

OBJECTIVES Evaluate the independent and synergistic associations of fluid overload and acute kidney injury with outcome in critically ill pediatric patients. DESIGN Secondary analysis of the Acute Kidney Injury in Children Expected by Renal Angina and Urinary Biomarkers (NCT01735162) prospective observational study. SETTING Single-center quaternary level PICU. PATIENTS One-hundred forty-nine children 3 months to 25 years old with predicted PICU length of stay greater than 48 hours, and an indwelling urinary catheter enrolled (September 2012 to March 2014). Acute kidney injury (defined by creatinine or urine output on day 3) and fluid overload (≥ 20% on day 3) were used as outcome variables and risk factors for ICU endpoints assessed at 28 days. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Acute kidney injury and fluid overload occurred in 19.4% and 24.2% respectively. Both acute kidney injury and fluid overload were associated with longer ICU length of stay but neither maintained significance after multivariate regression. Delineation into unique fluid overload/acute kidney injury classifications demonstrated that fluid overload patients experienced a longer ICU and hospital length of stay and higher rate of mortality compared with fluid overload patients, regardless of acute kidney injury status. Fluid overload/acute kidney injury patients had increased odds of death (p = 0.013). After correction for severity of illness, ICU length of stay remained significantly longer in fluid overload/acute kidney injury patients compared with patients without both classifications (17.4; 95% CI, 11.0-23.7 vs 8.8; 95% CI, 7.3-10.9; p = 0.05). Correction of acute kidney injury classification for net fluid balance led to acute kidney injury class switching in 29 patients and strengthened the association with increased mechanical ventilation and ICU length of stay on bivariate analysis, but reduced the increased risk conferred by fluid overload for mortality. CONCLUSIONS The current study suggests the effects of significant fluid accumulation may be delineable from the effects of acute kidney injury. Concurrent fluid overload and acute kidney injury significantly worsen outcome. Correction of acute kidney injury assessment for net fluid balance may refine diagnosis and unmask acute kidney injury associated with deleterious downstream sequelae. The unique effects of fluid overload and acute kidney injury on outcome in critically ill patients warrant further study.

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

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.

PURPOSE OF REVIEW: Acute kidney injury (AKI) and fluid overload affect a large number of children undergoing cardiac surgery, and confers an increased risk for adverse complications and outcomes including death. Survivors of AKI suffer long-term sequelae. The purpose of this narrative review is to discuss the short and long-term impact of cardiac surgery associated AKI and fluid overload, currently available tools for diagnosis and risk stratification, existing management strategies, and future management considerations. RECENT FINDINGS: Improved risk stratification, diagnostic prediction tools and clinically available early markers of tubular injury have the ability to improve AKI-associated outcomes. One of the major challenges in diagnosing AKI is the diagnostic imprecision in serum creatinine, which is impacted by a variety of factors unrelated to renal disease. In addition, many of the pharmacologic interventions for either AKI prevention or treatment have failed to show any benefit, while peritoneal dialysis catheters, either for passive drainage or prophylactic dialysis may be able to mitigate the detrimental effects of fluid overload. SUMMARY: Until novel risk stratification and diagnostics tools are integrated into routine practice, supportive care will continue to be the mainstay of therapy for those affected by AKI and fluid overload after pediatric cardiac surgery. A viable series of preventative measures can be taken to mitigate the risk and severity of AKI and fluid overload following cardiac surgery, and improve care.

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.

Background: Early warning systems that utilize dense physiologic data and machine learning may aid prediction of decompensation after congenital heart surgery (CHS). The Compensatory Reserve Index (CRI) analyzes changing features of the pulse waveform to predict hemodynamic decompensation in adults, but it has never been studied after CHS. This study sought to understand the feasibility, safety, and potential utility of CRI monitoring after CHS with cardiopulmonary bypass (CPB). Methods: A single-center prospective pilot cohort of patients undergoing pulmonary valve replacement was studied. Compensatory Reserve Index was continuously measured from preoperative baseline through the first 24 postoperative hours. Average CRI values during selected procedural phases were compared between patients with an intensive care unit (ICU) length of stay (LOS) Results: Twenty-three patients were enrolled. On average, 17,445 (±3,152) CRI data points were collected and 0.33% (±0.40) of data were missing per patient. There were no adverse events related to monitoring. Five (21.7%) patients had an ICU LOS ≥3 days. Compared to the ICU LOS Conclusions: Compensatory Reserve Index monitoring after CHS with CPB seems feasible and safe. Early changes in CRI may precede meaningful clinical outcomes, but this requires further study.

Supplemental Digital Content is available in the text., OBJECTIVES: To compare clinical characteristics and outcomes of children admitted to the PICU for severe acute respiratory syndrome coronavirus 2–related illness with or without multisystem inflammatory syndrome in children. The secondary objective was to identify explanatory factors associated with outcome of critical illness defined by a composite index of in-hospital mortality and organ system support requirement. DESIGN: Retrospective cohort study. SETTING: Thirty-eight PICUs within the Viral Infection and Respiratory Illness Universal Study registry from March 2020 to January 2021. PATIENTS: Children less than 18 years with severe acute respiratory syndrome coronavirus 2–related illness with or without multisystem inflammatory syndrome in children. MEASUREMENTS AND MAIN RESULTS: Of 394 patients, 171 (43.4%) had multisystem inflammatory syndrome in children. Children with multisystem inflammatory syndrome in children were more likely younger (2–12 yr vs adolescents; p < 0.01), Black (35.6% vs 21.9%; p < 0.01), present with fever/abdominal pain than cough/dyspnea (p < 0.01), and less likely to have comorbidities (33.3% vs 61.9%; p < 0.01) compared with those without multisystem inflammatory syndrome in children. Inflammatory marker levels, use of inotropes/vasopressors, corticosteroids, and anticoagulants were higher in multisystem inflammatory syndrome in children patients (p < 0.01). Overall mortality was 3.8% (15/394), with no difference in the two groups. Diagnosis of multisystem inflammatory syndrome in children was associated with longer duration of hospitalization as compared to nonmultisystem inflammatory syndrome in children (7.5 d[interquartile range, 5–11] vs 5.3 d [interquartile range, 3–11 d]; p < 0.01). Critical illness occurred in 164 patients (41.6%) and was more common in patients with multisystem inflammatory syndrome in children compared with those without (55.6% vs 30.9%; p < 0.01). Multivariable analysis failed to show an association between critical illness and age, race, sex, greater than or equal to three signs and symptoms, or greater than or equal to two comorbidities among the multisystem inflammatory syndrome in children cohort. Among nonmultisystem inflammatory syndrome in children patients, the presence of greater than or equal to two comorbidities was associated with greater odds of critical illness (odds ratio 2.95 [95% CI, 1.61–5.40]; p < 0.01). CONCLUSIONS: This study delineates significant clinically relevant differences in presentation, explanatory factors, and outcomes among children admitted to PICU with severe acute respiratory syndrome coronavirus 2–related illness stratified by multisystem inflammatory syndrome in children.

OBJECTIVE To describe the impact of obesity on disease severity and outcomes of coronavirus disease 2019 (COVID-19) among hospitalized children. METHODS This retrospective cohort study from the Society of Critical Care Medicine Viral Respiratory Illness Universal Study registry included all children hospitalized with COVID-19 from March 2020 to January 2021. Obesity was defined by Centers for Disease Control and Prevention BMI or World Health Organization weight for length criteria. Critical illness definition was adapted from National Institutes of Health criteria of critical COVID. Multivariate mixed logistic and linear regression was performed to calculate the adjusted odds ratio of critical illness and the adjusted impact of obesity on hospital length of stay. RESULTS Data from 795 patients (96.4% United States) from 45 sites were analyzed, including 251 (31.5%) with obesity and 544 (68.5%) without. A higher proportion of patients with obesity were adolescents, of Hispanic ethnicity, and had other comorbidities. Those with obesity were also more likely to be diagnosed with multisystem inflammatory syndrome in children (35.7% vs 28.1%, P = .04) and had higher ICU admission rates (57% vs 44%, P < .01) with more critical illness (30.3% vs 18.3%, P < .01). Obesity had more impact on acute COVID-19 severity than on multisystem inflammatory syndrome in children presentation. The adjusted odds ratio for critical illness with obesity was 3.11 (95% confidence interval: 1.8–5.3). Patients with obesity had longer adjusted length of stay (exponentiated parameter estimate 1.3; 95% confidence interval: 1.1–1.5) compared with patients without obesity but did not have increased mortality risk due to COVID-19 (2.4% vs 1.5%, P = .38). CONCLUSION In a large, multicenter cohort, a high proportion of hospitalized children from COVID-19 had obesity as comorbidity. Furthermore, obesity had a significant independent association with critical illness.

OBJECTIVE: The aim of this study was to characterize continuous renal replacement therapy (CRRT) utilization on extracorporeal membrane oxygenation (ECMO) and to determine the association of both fluid overload (FO) at CRRT initiation and fluid removal during CRRT with mortality in a large multicenter cohort. METHODS: Retrospective chart review of all children < 18 years of age concurrently treated with ECMO and CRRT from January 1, 2007 to December 31, 2011 at 6 tertiary care children’s hospital. Children treated with hemodialysis or peritoneal dialysis were excluded from the FO analysis. MEASUREMENTS AND MAIN RESULTS: A total of 756 of the 1009 children supported with ECMO during the study period had complete FO data. Of these, 357 (47.2%) received either CRRT or were treated with an in-line filter and thus entered into the final analysis. Survival to ECMO decannulation was 66.4% and survival to hospital discharge was 44.3%. CRRT initiation occurred at median of 1 day (IQR 0, 2) after ECMO initiation. Median FO at CRRT initiation was 20.1% (IQR 5, 40) and was significantly lower in ECMO survivors vs. non-survivors (15.3% vs. 30.5% p= 0.005) and in hospital survivors vs. non-survivors (13.5% vs. 25.9%, p= 0.004). Median FO at CRRT discontinuation was significantly lower in ECMO survivors (23% vs. 37.6% p= 0.002) and hospital survivors vs. non-survivors (22.6% vs. 36.1%, p=0.002). In ECMO survivors, after adjusting for pH at CRRT initiation, non-renal complications, ECMO mode, support type, center, patient age and AKI, FO at CRRT initiation (p = 0.01), and FO at CRRT discontinuation (p = 0.0002) were independently associated with duration of ECMO. In a similar multivariable analysis, FO at CRRT initiation (adjusted adds ratio [aOR] 1.09, 95% CI 1.00–1.18, p=0.045) and at CRRT discontinuation (aOR 1.11, 95% CI 1.03–1.19, p=0.01) were independently associated with hospital mortality. CONCLUSIONS: In a multicenter pediatric ECMO cohort, this study demonstrates that severe FO was very common at CRRT initiation. We found an independent association between the degree of FO at CRRT initiation with adverse outcomes including mortality and increased duration of ECMO support. The results suggest intervening prior to the development of significant FO may be a clinical therapeutic target and warrants further evaluation.

Children who undergo cardiac surgery with cardiopulmonary bypass are a unique population at high risk for postoperative acute kidney injury (AKI) and fluid overload. Fluid management is important in the postoperative care of these children as fluid overload is associated with increased morbidity and mortality. Peritoneal dialysis catheters are an important tool in the armamentarium of a cardiac intensivist and are used for passive drainage for fluid removal or dialysis for electrolyte and uremia control in AKI. Prophylactic placement of a peritoneal catheter is a safe method of fluid removal that is associated with few major complications. Early initiation of peritoneal dialysis has been associated with improved clinical markers and outcomes such as early achievement of a negative fluid balance, lower vasoactive medication needs, shorter duration of mechanical ventilation, and decreased mortality. In this review, we discuss the safety and potential benefits of peritoneal catheters for dialysis or passive drainage in children following cardiopulmonary bypass.

Background:Both the Norwood procedure and acute kidney injury (AKI) are associated with significant morbidity and mortality. The impact of AKI by measured and fluid corrected serum creatinine on outcomes after the Norwood procedure has not been previously studied. The purpose of this study was to (1) identify the incidence of AKI, (2) determine AKI risk factors, and (3) evaluate outcomes in patients with AKI using both measured and fluid corrected serum creatinine.Methods:Single-center retrospective chart review from 2009 to 2015 including neonates who underwent the Norwood procedure. Acute kidney injury was defined by the Kidney Disease Improving Global Outcomes staging criteria using both measured and fluid corrected serum creatinine. Multivariable logistic regression analysis was performed to determine the risk factors associated with AKI.Results:Ninety-five neonates underwent the Norwood procedure. Correcting for fluid overload increased the incidence of AKI from 40% to 44%, increased AKI severity in 15 patients, and improved the identification of adverse outcomes associated with AKI. Patients palliated with the modified Blalock-Taussig shunt (mBTS) had a 9.4 greater odds of fluid corrected AKI compared to those palliated with a right ventricle to pulmonary artery conduit (95% confidence interval [95% CI]: 1.68-52.26, P = .01). A higher vasoactive inotrope score (VIS) on postoperative day (POD) 0 was associated with fluid corrected AKI (odds ratio: 1.20, 95% CI: 1.06-1.35; P = .003).Conclusions:Acute kidney injury is common after the Norwood procedure. Correcting creatinine for fluid balance revealed new cases of AKI. Use of an mBTS and higher VIS on POD 0 were associated with increased risk of AKI.

BACKGROUND: Acute kidney injury (AKI) and infection are common complications after pediatric cardiac surgery. No pediatric study has evaluated for an association between postoperative AKI and infection. The objective of this study was to determine if AKI in neonates after cardiopulmonary bypass was associated with the development of a postoperative infection. METHODS: We performed a single center retrospective chart review from January 2009 to December 2015 of neonates (age ≤ 30 days) undergoing the Norwood procedure. AKI was defined by the modified neonatal Kidney Disease Improving Global outcomes serum creatinine criteria using (1) measured serum creatinine and (2) creatinine corrected for fluid balance on postoperative days 1–4. Infection, (culture positive or presumed), must have occurred after a diagnosis of AKI and within 60 days of surgery. RESULTS: Ninety-five patients were included, of which postoperative infection occurred in 42 (44%). AKI occurred in 38 (40%) and 42 (44%) patients by measured serum creatinine and fluid overload corrected creatinine, respectively, and was most commonly diagnosed on postoperative day 2. The median time to infection from the time of surgery and AKI was 7 days (IQR 5–14 days) and 6 days (IQR 3–13 days), respectively. After adjusting for confounders, the odds of a postoperative infection were 3.64 times greater in patients with fluid corrected AKI (95% CI, 1.36–9.75; p = 0.01). CONCLUSIONS: Fluid corrected AKI was independently associated with the development of a postoperative infection. These findings support the notion that AKI is an immunosuppressed state that increases the risk of infection.

The optimal fluid management in critically ill children is currently under investigation with several studies suggesting that hyperchloremia, chloride load, and the use of chloride-rich fluids contribute to worse outcomes. This is a single-center retrospective cohort study of Pediatric Intensive Care Unit patients from 2008 to 2016 requiring continuous renal replacement therapy (CRRT). Patients were excluded if they had end-stage renal disease, a disorder of chloride transport, or concurrent provision of extracorporeal membrane oxygenation therapy. Patients (n = 66) were dichotomized into two groups (peak chloride (Cl) ≥ 110 mmol/L vs. peak Cl

Serum chloride derangements are associated with poor clinical outcomes, including acute kidney injury (AKI) and mortality. We sought to determine the association between persistent hyperchloremia and renal recovery in critically ill children with AKI.We performed a retrospective cohort study of all patients with day 2 AKI admitted to a large academic pediatric intensive care unit from January 2014 to December 2015. After applying exclusion criteria, 348 patients were categorized as (1) hyperchloremia on both day 2 and day 7 (PersistentCl), (2) hyperchloremia on day 2 with normochloremia on day 7 (RecoveredCl), (3) normochloremia on day 2 with hyperchloremia on day 7 (DelayedCl), and (4) no hyperchloremia on day 2 nor day 7 (NormalCl). Hyperchloremia was defined as ≥ 110 mEq/L. The primary outcome was renal recovery on day 7, defined as the absence of AKI criteria. Secondary outcomes included discharge renal recovery, mortality, duration of mechanical ventilation, and hospital length of stay.Day 7 renal recovery rates for PersistentCl, RecoveredCl, DelayedCl, and NormalCl were 37%, 66%, 71%, and 52% respectively. PersistentCl had lower odds of day 7 renal recovery (aOR = 0.29; 95% CI, 0.14 to 0.60; p = 0.0009), lower odds of discharge renal recovery (aOR = 0.22; 95% CI, 0.11 to 0.48; p = 0.0001), and higher odds of mortality (aOR = 3.50; 95% CI, 1.11 to 11.10; p = 0.03) when compared with RecoveredCl after adjusting for confounders.Persistent hyperchloremia is independently associated with impaired renal recovery as well as higher mortality. Prospective studies are indicated to determine if serum chloride represents a modifiable risk factor for poor outcomes. Graphical abstract.

BACKGROUND: We evaluated the epidemiology of fluid balance (FB) over the first postnatal week and its impact on outcomes in a multi-center cohort of premature neonates from the AWAKEN study. METHODS: Retrospective analysis of infants

Acute kidney injury (AKI) is a common occurrence among hospitalized children and leads to increased mortality and prolonged length of stay (LOS) in critically ill patients. Few studies have examined the impact of AKI on LOS for common pediatric conditions. We hypothesized that a diagnosis of AKI would be associated with a longer hospital LOS and increased exposure to nephrotoxic medications for all patients. We performed a multicenter retrospective cross-sectional analysis of 34 children’s hospitals in the Pediatric Health Information System (PHIS) database from 1/2009 through 12/2013. Patients were grouped based on primary discharge diagnosis, number of days spent in an intensive care unit, and assignment of a secondary diagnostic code for AKI. Median LOS was compared among different patient groupings. Exposure to commonly used nephrotoxic medications was collected for each admission. A total of 588,884 admissions from 423,337 patients were included in the analysis. The median LOS among non-critically ill patients with and without AKI was 5 days [95% CI 3–10] versus 2 days [95% CI 1–4], respectively. Among critically ill patients, median LOS for those with and without AKI was 12 days [95% CI 7–20] versus 4 days [95% CI 2–7], respectively. Patients who developed AKI were more likely to have significant nephrotoxic exposure. Development of AKI was associated with longer hospital length of stay and increased nephrotoxic medication exposure for all diagnostic categories. Non-critically ill children with AKI were hospitalized the same length or longer than critically ill children without AKI.

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.

Determine the risk factors for repeated episodes of acute kidney injury in children who undergo multiple cardiac surgical procedures.Single-center retrospective chart review.Cardiac ICU at a quaternary pediatric care center.Birth to 18 years who underwent at least two cardiac surgical procedures with cardiopulmonary bypass.None.One-hundred eighty patients underwent two cardiac surgical procedures and 89 underwent three. Acute kidney injury was defined by the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Acute kidney injury frequency was 26% (n = 46) after surgery 1, 20% (n = 36) after surgery 2, and 24% (n = 21) after surgery 3, with most acute kidney injury occurring on postoperative days 1 and 2. The proportion of patients with severe acute kidney injury increased from surgery 1 to surgery 3. Patients with acute kidney injury had a significantly longer duration of ventilation and length of stay after each surgery. The odds of acute kidney injury after surgery 3 was 2.40 times greater if acute kidney injury was present after surgery 1 or 2 (95% CI, 1.26-4.56; p = 0.008) after adjusting for confounders. The time between surgeries was not significantly associated with acute kidney injury (p = 0.85).In a heterogeneous population of pediatric patients with congenital heart disease undergoing multiple cardiopulmonary bypass surgeries, odds of acute kidney injury after a third surgery was increased by the presence of acute kidney injury after prior procedures. Time between surgery did not play a role in increasing odds of acute kidney injury. Further studies in a larger multicenter investigation are necessary to confirm these findings.

Background There are several limitations when using creatinine to estimate glomerular filtration rate, especially in children with chronic medical conditions who are at high risk of kidney dysfunction. Cystatin C has been the recent focus of research as a replacement biomarker for creatinine. Our objective was to compare the 2 biomarkers in pediatric single-ventricle heart disease patients who have undergone the Fontan operation. We hypothesized that there would be poor correlation and agreement between the 2 estimates of renal function. Methods This was a single center retrospective chart review of 20 patients who had previously undergone Fontan operation. Demographic and clinical data were collected from medical records. Blood samples were collected as part of routine clinical care and simultaneously measured for serum creatinine and cystatin C. Glomerular filtration rate was calculated using the creatinine-based bedside Schwartz formula and cystatin C-based Zapatelli equation. Spearman correlation and Bland-Altman analysis were used to assess correlation and agreement. Results The median Schwartz-derived estimated glomerular filtration rate was 98.94 mL/min/1.73 m2 while the median Zappitelli-derived estimated glomerular filtration rate was 84.76 mL/min/1.73 m2 . The mean difference was -19.27 suggesting poor agreement. There was weak to moderate correlation between the Schwartz and cystatin C estimated glomerular filtration rate. Conclusion The bedside Schwartz formula may be an overestimate of glomerular filtration rate in pediatric single-ventricle heart disease patients who have undergone the Fontan operation. While larger studies are necessary, cystatin C is a promising biomarker to replace creatinine and better estimate kidney function in this population.

Renal near-infrared spectroscopy is known to be predictive of acute kidney injury in children following cardiac surgery using a series of complex equations and area under the curve. This study was performed to determine if a greater than or equal to 20% reduction in renal near-infrared spectroscopy for 20 consecutive minutes intraoperatively or within the first 24 postoperative hours is associated with 1) acute kidney injury, 2) increased acute kidney injury biomarkers, or 3) other adverse clinical outcomes in children following cardiac surgery.Prospective single center observational study.Pediatric cardiac ICU.Children less than or equal to age 4 years who underwent cardiac surgery with the use of cardiopulmonary bypass during the study period (June 2011-July 2012).None.A reduction in near-infrared spectroscopy was not associated with acute kidney injury. Nine of 12 patients (75%) with a reduction in renal near-infrared spectroscopy did not develop acute kidney injury. The remaining three patients had mild acute kidney injury (pediatric Risk, Injury, Failure, Loss, End stage-Risk). A reduction in renal near-infrared spectroscopy was associated with the following adverse clinical outcomes: 1) a longer duration of mechanical ventilation (p = 0.05), 2) longer intensive care length of stay (p = 0.05), and 3) longer hospital length of stay (p0.01). A decline in renal near-infrared spectroscopy in combination with an increase in serum interleukin-6 and serum interleukin-8 was associated with a longer intensive care length of stay, and the addition of urine interleukin-18 to this was associated with a longer hospital length of stay.In this cohort, the rate of acute kidney injury was much lower than anticipated thereby limiting the evaluation of a reduction in renal near-infrared spectroscopy as a predictor of acute kidney injury. A greater than or equal to 20% reduction in renal near-infrared spectroscopy was significantly associated with adverse outcomes in children following cardiac surgery. The addition of specific biomarkers to the model was predictive of worse outcomes in these patients. Thus, real-time evaluation of renal near-infrared spectroscopy using the specific levels of change of a 20% reduction for 20 minutes may be useful in predicting prolonged mechanical ventilation and other adverse outcomes in children undergoing cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is common in neonatal encephalopathy (NE) and is associated with worse outcomes. Our objectives were to determine the incidence, risk factors, and outcomes of AKI in infants with NE. METHODS: We performed a retrospective analysis of infants ≥ 34 weeks’ gestational age with a diagnosis of NE from the AWAKEN (Analysis of Worldwide Acute Kidney injury Epidemiology in Neonates) database. AKI was defined using the modified Kidney Disease Improving Global Outcomes criteria. Perinatal and postnatal factors were evaluated. Multivariate logistic and linear regression were performed. RESULTS: 113 patients with NE were included. 41.6% (47) developed AKI. Being born outside the admitting institution (OR 4.3; 95% CI:1.2 – 14.8; p = 0.02), intrauterine growth restriction (OR: 10.3, 95% CI:1.1 – 100.5; p = 0.04) and meconium at delivery (OR: 2.8, 95% CI:1.04 – 7.7; p = 0.04) conferred increased odds of AKI. After controlling for confounders, infants with AKI stayed in the hospital an average of 8.5 days longer than infants without AKI (95% CI: 0.79 – 16.2 days; p = 0.03). CONCLUSIONS: In this multi-national analysis, several important perinatal factors were associated with AKI and infants with both NE and AKI had longer length of stay than NE alone. Future research aimed at early AKI detection, renoprotective management strategies, and understanding the long-term renal consequences are warranted in this high-risk group of patients.

Pediatric cardiac intensive care continues to evolve, with rapid advances in knowledge and improvement in clinical outcomes. In the past, the Board of Directors of the Pediatric Cardiac Intensive Care Society created and subsequently updated a list of sentinel references focused on the care of critically ill children with congenital and acquired heart disease. The objective of this article is to provide clinicians with a compilation and brief summary of updated and useful references that have been published since 2012.Pediatric Cardiac Intensive Care Society members were solicited via a survey sent out between March 20, 2017, and April 28, 2017, to provide important references that have impacted clinical care. The survey was sent to approximately 523 members. Responses were received from 45 members, of which some included multiple references.Following review of the list of references, and removing editorials, references were compiled by the first and last author. The final list was submitted to members of the society's Research Briefs Committee, who ranked each publication.Rankings were compiled and the references with the highest scores included. Research Briefs Committee members ranked the articles from 1 to 3, with one being highly relevant and should be included and 3 being less important and should be excluded. Averages were computed, and the top articles included in this article. The first (K.C.U.) and last author (K.M.G.) reviewed and developed summaries of each article.This article contains a compilation of useful references for the critical care of children with congenital and acquired heart disease published in the last 5 years. In conjunction with the prior version of this update in 2012, this article may be used as an educational reference in pediatric cardiac intensive care.

Background Neonatal acute kidney injury (AKI) occurs in 40 to 70% of critically ill neonatal intensive care admissions. This study explored the differences in perceptions and practice variations among neonatologists and pediatric nephrologists in diagnostic criteria, management, and follow-up of neonatal AKI. Methods A survey weblink was emailed to nephrologists and neonatologists in Australia, Canada, New Zealand, India, and the United States. Questions consisted of demographic and unit practices, three clinical scenarios assessing awareness of definitions of neonatal AKI, knowledge, management, and follow-up practices. Results Many knowledge gaps among neonatologists, and to a lesser extent, pediatric nephrologists were identified. Neonatologists were less likely to use categorical definitions of neonatal AKI (p Conclusion Neonatal AKI is underappreciated, particularly among neonatologists. A lack of evidence on neonatal AKI contributes to this variation in response. Therefore, dissemination of current knowledge and areas for research should be the priority.

Background: The purpose of this study was to characterize tachyarrhythmias in children following the Norwood procedure. Methods: This is a single-center retrospective study including all children who underwent stage I Norwood procedure (n = 98; January 2003-September 2011). The primary outcome measure is the development of tachyarrhythmia during hospitalization after the Norwood procedure. Secondary aims include quantification of mortality in patients with tachyarrhythmias and evaluation of potential risk factors for the development of tachyarrhythmia. Results: Tachyarrhythmia occurred in 33 (34%) of 98 patients. The median time to onset of tachyarrhythmia was ten days (0-47 days). Tachyarrhythmia conferred no increase in overall mortality ( P = .45), including operative mortality ( P = .37) or interstage mortality ( P = 1.00). There was no significant difference in the incidence of arrhythmia based on demographic, anatomic, or surgical variables, including shunt type ( P = .23) except that patients with tachyarrhythmias were slightly larger (median weight 3.2 kg) at the time of stage I than those without tachyarrhythmia (median weight 2.93 kg; P = .02]. The odds of arrhythmia in males were 8.7 times higher than that in females (95% confidence interval 2.9-31.3; P < .0001). Conclusions: Postoperative tachyarrhythmia is common, occurring in 34% of patients after the Norwood operation. Onset of tachyarrhythmia occurred later after the Norwood operation than reported previously, and male gender is a risk factor. Further studies to elucidate the etiology and the timing of tachyarrhythmias after the Norwood procedure are necessary.

Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) are cell-cycle arrest biomarkers that have been shown to be predictive of acute kidney injury (AKI) in critically ill adults. AKI affects a large proportion (40%) of children following cardiac surgery. The aim of this study was to describe the kinetics of TIMP-2*IGFBP-7 and test its ability to predict AKI in infants following cardiac surgery. A multicenter prospective study was performed in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) from October 2013 to January 2015. Urine samples were obtained at baseline and at 2, 6, 12, 24, 48 and 72 h after CPB initiation. TIMP-2*IGFBP-7 concentration was measured in urine samples using the Astute 140® meter to determine a risk score for AKI. This risk score is the product of TIMP-2 (ng/mL) and IGFBP-7 (ng/mL) divided by 1000. A total of 94 infants with a mean age of 154.2 ± 85.7 days were enrolled in the study, of whom 31 (33%) subsequently developed AKI. The mean time to AKI diagnosis was 25 ± 7 h after CPB initiation. The concentration of TIMP-2*IGFBP-7 was significantly higher in patients with AKI at 12 h after CPB initiation relative to baseline (p = 0.006). At 12 h after CPB initiation patients with a TIMP-2*IGFBP-7 concentration of ≥0.78 had a threefold higher odds of developing AKI than those with a TIMP-2*IGFBP-7 concentration of

The original version of this article unfortunately contained a mistake. The collaborators of the Neonatal Kidney Collaborative (NKC) were not named individually. The list of all collaborators is given below.

In paediatric pulmonary embolism, cardiac findings and thromboembolic outcomes are poorly defined. We conducted a mixed retrospective-prospective cohort study of paediatric pulmonary embolism at the Children's Hospital Colorado between March, 2006 and January, 2011. A total of 58 consecutive children – age less than or equal to 21 years – with acute pulmonary embolism were enrolled. Data collection included clinical and laboratory characteristics, treatments, serial echocardiographic and electrocardiographic findings, and outcomes of pulmonary embolism non-resolution and recurrence. The median age was 16.5 years ranging from 0 to 21 years. The most prevalent clinical risk factors were oral contraceptive pill use (52% of female patients), presence of a non-infectious inflammatory condition (21%), and trauma (21%). Thrombophilias included heterozygous factor V Leiden in 21%; antiphospholipid antibody syndrome was established in 31% overall. Proximal pulmonary artery involvement was present in 34%. At presentation, nearly half of the patients had hypoxaemia and 37% had tachycardia. The classic electrocardiographic finding of S1Q3T3 was present in 12% acutely; tricuspid regurgitation greater than 3 metres per second, septal flattening, and right ventricular dilation were each present on acute echocardiogram in 25%. Nearly all patients received therapeutic anticoagulation, with initial systemic tissue plasminogen activator administered in 16% for occlusive iliofemoral deep venous thrombosis and/or massive pulmonary embolism. Pulmonary embolism resolution was observed in 82% by 6 months. Recurrent pulmonary embolism occurred in 9%. There were no pulmonary embolism-related deaths. Right ventricular dysfunction was rare in follow-up. These data indicate that acute heart strain is common, but chronic cardiac dysfunction is rare, following aggressive management of acute pulmonary embolism in children.

We compared the neurodevelopmental outcome of extremely premature, surfactant-deficient infants who received either prophylactic surfactant at birth, "rescue" surfactant after the clinical diagnosis of respiratory distress syndrome was established, or placebo. Infants studied were participants in a randomized, bicenter (San Diego, Calif., and Helsinki, Finland), controlled trial of human surfactant therapy. One hundred fifty infants (prophylaxis group, 63 infants; rescue group, 57; placebo group, 30) were prospectively enrolled at 38 weeks of gestational age. There were no neonatal intergroup differences in the incidence or severity of sonographic central nervous system abnormality or retinopathy. One hundred forty-five infants were alive at 1 year of adjusted age, at which time growth, neurosensory, and neurologic outcome were similar in all three treatment groups at both centers. Cerebral palsy occurred in 20% overall. Five infants (3.5%) were functionally blind. However, infants treated at birth had lower mean mental and motor scores on the Bayley Scales of Infant Development compared with those of infants rescued with surfactant after the onset of respiratory distress syndrome (Mental Development Index: 78 vs 96, p = 0.02; Psychomotor Development Index: 73 vs 87, p = 0.04). Chronic lung disease occurred more frequently in the prophylactically treated group and contributed to the subjects' neurologic and developmental morbidity. Because prophylactic surfactant treatment offered no neurodevelopmental advantage and may contribute to poorer outcome, we currently recommend early surfactant replacement only for those infants who have postnatal evidence of respiratory distress syndrome.