Acute Kidney Injury, Fluid Overload, and Renal Replacement Therapy Differ by Underlying Diagnosis in Neonatal Extracorporeal Support and Impact Mortality Disparately.

INTRODUCTION: We aimed to characterize acute kidney injury (AKI), fluid overload (FO), and renal replacement therapy (RRT) utilization by diagnostic categories and examine associations between these complications and mortality by category. METHODS: To test our hypotheses, we conducted a retrospective multicenter, cohort study including 446 neonates (categories: 209 with cardiac disease, 114 with congenital diaphragmatic hernia [CDH], 123 with respiratory disease) requiring extracorporeal membrane oxygenation (ECMO) between January 1, 2007, and December 31, 2011. RESULTS: AKI, FO, and RRT each varied by diagnostic category. AKI and RRT receipt were most common in those neonates with cardiac disease. Subjects with CDH had highest peak %FO (51% vs. 28% cardiac vs. 32% respiratory; p < 0.01). Hospital survival was 55% and varied by diagnostic category (45% cardiac vs. 48% CDH vs. 79% respiratory; p < 0.001). A significant interaction suggested risk of mortality differed by diagnostic category in the presence or absence of AKI. In its absence, diagnosis of CDH (vs. respiratory disease) (OR 3.04, 95% CL 1.14-8.11) independently predicted mortality. In all categories, peak %FO (OR 1.20, 95% CL 1.11-1.30) and RRT receipt (OR 2.12, 95% CL 1.20-3.73) were independently associated with mortality. DISCUSSION/CONCLUSIONS: Physiologically distinct ECMO diagnoses warrant individualized treatment strategies given variable incidence and effects of AKI, FO, and RRT by category on mortality.

Predicting Infection in Very Preterm Infants: A Study Protocol.

BACKGROUND: Neonatal sepsis causes morbidity and mortality in preterm infants. Clinicians need a predictive tool for the onset of neonatal infection to expedite treatment and prevent morbidity. Abnormal thermal gradients, a central-peripheral temperature difference (CPtd) of >2°C or <0°C, and elevated heart rate characteristic (HRC) scores are associated with infection. OBJECTIVE: This article presents the protocol for the Predictive Analysis Using Temperature and Heart Rate Study. METHODS: This observational trial will enroll 440 very preterm infants to measure abdominal temperature and foot temperature every minute and HRC scores hourly for 28 days to compare infection data. Time with abnormal thermal gradients (Model 1) and elevated HRC scores (Model 2) will be compared to the onset of infections. For data analysis, CPtd (abdominal temperature - foot temperature) will be investigated as two derived variables, high CPtd (number/percentage of minutes with CPtd of >2°C) and low CPtd (number/percentage of minutes with CPtd of <0°C). In the infant-level model, the outcome yi will be an indicator of whether the infant was diagnosed with an infection in the first 28 days of life, and the high CPtd and low CPtd variables will be the average over the entire observation period, logit(yi) = ß0 + xiß1 + ziγ. For the day-level model, the outcome yit will be an indicator of whether the ith infant was diagnosed with an infection on the tth day from t = 4 through t = 28 or the day that infection is diagnosed (25 possible repeated measures), logit(yit) = ß0 + xitß1 + zitγ. It will be determined whether a model with only high CPtd or only low CPtd is superior in predicting infection. Also, the correlation of abnormal HRC scores with high CPtd and low CPtd values will be assessed. DISCUSSION: Study results will inform the design of an interventional study using temperatures and/or heart rate as a predictive tool to alert clinicians of cardiac and autonomic instability present with infection.

Nephrotoxic medications and acute kidney injury risk factors in the neonatal intensive care unit: clinical challenges for neonatologists and nephrologists.

Neonatal acute kidney injury (AKI) is common. Critically ill neonates are at risk for AKI for many reasons including the severity of their underlying illnesses, prematurity, and nephrotoxic medications. In this educational review, we highlight four clinical scenarios in which both the illness itself and the medications indicated for their treatment are risk factors for AKI: sepsis, perinatal asphyxia, patent ductus arteriosus, and necrotizing enterocolitis. We review the available evidence regarding medications commonly used in the neonatal period with known nephrotoxic potential, including gentamicin, acyclovir, indomethacin, vancomycin, piperacillin-tazobactam, and amphotericin. We aim to illustrate the complexity of decision-making involved for both neonatologists and pediatric nephrologists when managing infants with these conditions and advocate for ongoing multidisciplinary collaboration in the development of better AKI surveillance protocols and AKI mitigation strategies to improve care for these vulnerable patients.

Fluid overload and fluid removal in pediatric patients on extracorporeal membrane oxygenation requiring continuous renal replacement therapy: a multicenter retrospective cohort study.

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 six 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 that intervening prior to the development of significant FO may be a clinical therapeutic target and warrants further evaluation.

Acute Kidney Injury Guidelines Are Associated With Improved Recognition and Follow-up for Neonatal Patients.

BACKGROUND: Studies demonstrate that neonatal acute kidney injury (AKI) is associated with increased morbidity and mortality. Acute kidney injury survivors are at risk for renal dysfunction and chronic kidney disease and require long-term follow-up. PURPOSE: To maximize identification of AKI and ensure referral, we created guidelines for diagnosis, evaluation, and management of AKI. METHODS/SEARCH STRATEGY: Retrospective cohort study of neonatal intensive care unit patients treated before guideline implementation (cohort 1; n = 175) and after (cohort 2; n = 52). Outcome measures included AKI incidence, documented diagnosis, and pediatric nephrology consultation. Statistical methods included t tests, Fisher exact tests, and Wilcoxon rank sum tests. FINDINGS/RESULTS: We found 68 AKI episodes in 52 patients in cohort 1 and 15 episodes in 12 patients in cohort 2. Diagnosis and documentation of AKI improved after guideline implementation (C1:24/68 [35%], C2: 12/15 [80%]; P = .003) as did pediatric nephrology consultation (C1:12/68 [18%]; C2: 12/15 [80%]; P < .001) and outpatient referral (C1: 3/47 [6%], C2:5/8 [63%]; P < .01). IMPLICATIONS FOR PRACTICE: Neonatal AKI guideline implementation was associated with improvements in recognition, diagnosis, and inpatient and outpatient nephrology consultation. Early recognition and diagnosis along with specialist referral may improve outcomes among neonatal AKI survivors, ensuring appropriate future monitoring and long-term follow-up. IMPLICATIONS FOR RESEARCH: Future research should continue to determine the long-term implications of early diagnosis of AKI and appropriate subspecialty care with follow-up.

Early continuous renal replacement therapy during infant extracorporeal life support is associated with decreased lung opacification.

Lung opacification on chest radiography (CXR) is common during extracorporeal life support (ECLS), often resulting from pulmonary edema or inflammation. Concurrent use of continuous renal replacement therapy (CRRT) during ECLS is associated with improved fluid balance and cytokine filtration; through modification of these pathologic states, CRRT may modulate lung opacification observed on CXRs. We hypothesize that early CRRT use during infant ECLS decreases lung opacification on CXR. We conducted a retrospective cohort study comparing CXRs from infants receiving ECLS and early CRRT (n = 7) to matched infants who received ECLS alone (n = 7). The CXR obtained prior to ECLS, all CXRs obtained within the first 72 h of ECLS, and daily CXRs for the remainder of the ECLS course were analyzed. The outcome measure was the degree of opacification, determined by independent assessment of two, blinded pediatric radiologists using a modified Edwards et al.'s lung opacification scoring system (from Score 0: no opacification to Score 5: complete opacification). 220 CXRs were assessed (cases: 93, controls: 127). Inter-rater reliability was established (Cohen's weighted к = 0.74; p < 0.0001, good agreement). At baseline, the mean opacification score difference between cases and controls was 1 point (cases: 1.8, controls 2.8; p = 0.049). Using mixed modeling analysis for repeated measures accounting for differences at baseline, the average overall opacification score was 1.2 points lower in cases than controls (cases: 2.1, controls: 3.3; p < 0.0001). The overall distribution of scores was lower in cases than controls. Early CRRT utilization during infant ECLS was associated with decreased lung opacification on CXR.

Implementing a practice change: early initiation of continuous renal replacement therapy during neonatal extracorporeal life support standardizes care and improves short-term outcomes.

PURPOSE: We hypothesized that a standardized approach to early continuous renal replacement therapy (CRRT) during neonatal extracorporeal life support (ECLS) results in greater homogeneity of CRRT initiation times with improvements in fluid balance and outcomes. METHODS: Retrospective analysis of data (2007-2015) obtained from neonates treated prior to (E1; n = 32) and after (E2; n = 31) a 2011 practice change: CRRT initiation within 48 h of ECLS. RESULTS: Birthweight, gestational age, ECLS mode, and age at ECLS initiation were similar to each epoch. Survival [E1: median 75%, E2: 71%] and length of ECLS [E1: median 221 h, E2: 180 h] were comparable. During E2, 100% of infants received CRRT (vs. E1: 37%; p < 0.001) and 97% of infants initiated CRRT within 48 h of ECLS (vs. E1: 13%; p < 0.001). Control charts demonstrate reduced practice variation. Elapsed time from ECLS to CRRT differed between Epochs [E1: median 105 h, E2: 9 h; p < 0.001] as did weight at CRRT initiation [E1: 4.13 kg (29% above baseline), E2: 3.19 kg (0%); p < 0.001]. Significant differences in weight change were noted on days 6 and 7 (E1: 14%, E2: 2%; raw data comparison yielded p < 0.05) and curves were different (p < 0.05). CONCLUSIONS: We successfully implemented a practice change, initiating CRRT within 48 h of ECLS cannulation, leading to decreased practice variation and improved short-term outcomes including decreased weight gain at CRRT initiation and faster return to baseline weight during the first 7 days of ECLS. We did not demonstrate changes in duration of ECLS, invasive ventilation, or survival.

Early Continuous Renal Replacement Therapy Improves Nutrition Delivery in Neonates During Extracorporeal Life Support.

OBJECTIVE: Optimizing nutrition in neonatal patients as soon as possible after extracorporeal life support (ECLS) initiation is imperative as malnutrition can worsen both short- and long-term outcomes. Fluid restriction, used to manage the fluid overload that commonly complicates neonatal ECLS, severely impairs nutrition delivery. Continuous renal replacement therapy (CRRT) can be used to help manage fluid overload. We hypothesize that early CRRT utilization ameliorates the need for fluid restriction and allows providers to prescribe higher parenteral nutrition (PN) volumes leading to better nutrition delivery. DESIGN: The design of the study was a retrospective chart review, and the setting was a single, level III neonatal intensive care unit. SUBJECTS: Neonatal patients (n = 42) treated with ECLS between January 1, 2008, and December 31, 2013. INTERVENTIONS: Comparisons were made between 2 groups: neonates who received ECLS without early CRRT initiation (group 1; n = 23) and with early CRRT initiation (group 2; n = 19). MAIN OUTCOME MEASURES: The main outcome measures were goal total fluid intake, prescribed PN volume, protein, glucose infusion rate, intralipid, and kilocalories. RESULTS: Infants who received early CRRT were prescribed higher mean total fluid intake goals (group 1: 99 mL/kg/day vs. group 2: 119 mL/kg/day, P < .001) and higher mean volumes of PN (group 1: 61 mL/kg/day vs. group 2: 81 mL/kg/day, P < .001) over the first 72 hours of ECLS compared with infants who did not receive early CRRT. Early CRRT receivers also were prescribed greater mean amounts of protein during the first 72 hours of ECLS (group 1: 2.7 g/kg/day vs. group 2: 3 g/kg/day, P = 0.03). There were no significant changes noted in prescribed glucose infusion rates, intralipid, or total kilocalories. CONCLUSIONS: Institution of early CRRT in neonates on ECLS allows for administration of greater volumes of PN with improved protein delivery. This study characterizes one benefit of early CRRT initiation in neonates on ECLS and suggests these patients could experience improved nutritional outcomes.

Resident Workshop Standardizes Patient Handoff and Improves Quality, Confidence, and Knowledge.

OBJECTIVES: Residency programs are required to instruct residents in handoff; however, a handoff curriculum endorsed by the Accreditation Council for Graduate Medical Education does not exist. Although curricula are available, we preferred to use a curriculum that could be taught quickly, was easy to implement, and used a mnemonic that resembled current practices at our institution. We designed and implemented a novel handoff educational workshop intended to improve resident confidence and performance. METHODS: In this observational study, pediatric residents across postgraduate training years during winter 2014-spring 2015 participated in two study segments: a handoff workshop with questionnaires and handoff observations. Co-investigators developed and led an interactive workshop for residents that emphasized a standardized approach using the SIGNOUT mnemonic (see text for definition). The effect of workshop participation on handoff abilities was evaluated using a validated, handoff evaluation tool administered before and after the workshop. Qualitative feedback was obtained from residents using pre- and postworkshop surveys. RESULTS: Forty-three residents participated in the workshop; 41 residents completed handoff observations. Improvements were noted in clinical judgment (P = 0.02) and organization/communication (P = 0.005). Pre- and postworkshop surveys demonstrated self-perceived increases in confidence, comfort, and knowledge (P < 0.001). CONCLUSIONS: Improvements in handoffs, particularly in clinical judgment and organization/communication domains, suggest that a more standardized handoff approach is beneficial, especially for postgraduate year 1 residents. The novel, interactive workshop we developed can be taught quickly, is easy to implement, is appropriate for all resident training levels, and improves resident confidence and skill. This workshop can be implemented by training programs across all disciplines, possibly leading to improved patient safety.

Urinary Tract Dilation in the Fetus and Neonate.

Urinary tract dilation (UTD), previously known as hydronephrosis, is the most common congenital condition identified on prenatal ultrasonography. UTD can be physiologic and resolve spontaneously or can be caused by various congenital anomalies of the urinary tract, which can lead to renal failure if not treated properly. In 2014, a multidisciplinary consensus group established UTD definitions, a classification system, and a standardized scheme for perinatal evaluation. Various imaging modalities are available to help diagnose the cause of UTD in fetuses and neonates and to help identify those patients who may benefit from fetal or early postnatal intervention. In this article, we will review the diagnosis and quantification of antenatal and postnatal UTD based on the UTD classification system, outline the imaging studies available to both evaluateUTD and determine its cause, briefly review the most common causes of UTD in the fetus and neonate, outline management strategies for UTD including the role for fetal intervention and prophylactic antibiotics, and report on the outcome and prognosis in patients with UTD.

Fluid Balance Management Informs Renal Replacement Therapy Use During Pediatric Extracorporeal Membrane Oxygenation: A Survey Report From the Kidney Intervention During Extracorporeal Membrane Oxygenation Group.

Fluid overload (FO) and acute kidney injury (AKI) occur commonly in children supported with extracorporeal membrane oxygenation (ECMO). Continuous renal replacement therapy (CRRT) may be used to manage AKI and FO in children on ECMO. In 2012, our group surveyed ECMO centers to begin to understand the practice patterns around CRRT and ECMO. Since then, more centers are initiating ECMO for increasingly diverse indications and an increased volume of research quantifies the detrimental impacts of AKI and FO. We, therefore, investigated practice patterns of CRRT utilization during ECMO in children. A multi-point survey instrument was distributed to 116 international neonatal and pediatric ECMO centers. Sixty of 116 (51.7%) international neonatal and pediatric ECMO centers responded. All reports using CRRT on ECMO, compared with 75% from the 2012 survey. Eighty-five percent use CRRT to treat or prevent FO, an increased from 59%. The modality of CRRT therapy differed between in-line (slow continuous ultrafiltration, 84.4%) and machine-based (continuous venovenous hemodiafiltration, 87.3%) methods. Most (65%) do not have protocols for fluid management, AKI, or CRRT on ECMO. Trialing off CRRT is dictated by physician preference in 90% (54/60), with varying definitions of success. In this survey study, we found that CRRT use during pediatric ECMO has increased since 2012 with fluid management representing the predominant indication for initiation. Despite the expanded utilization of CRRT with ECMO, there remains significant practice variation in terms of method, modality, indication, the timing of initiation, fluid management, and discontinuation.

Acute Kidney Injury and Fluid Overload in Pediatric Extracorporeal Cardio-Pulmonary Resuscitation: A Multicenter Retrospective Cohort Study.

Acute kidney injury (AKI) and fluid overload (FO) are common complications of extracorporeal membrane oxygenation (ECMO). The purpose of this study was to characterize AKI and FO in children receiving extracorporeal cardiopulmonary resuscitation (eCPR). We performed a multicenter retrospective study of children who received eCPR. AKI was assessed during ECMO and FO defined as <10% [FO-] vs. ≥10% [FO+] evaluated at ECMO initiation and discontinuation. A composite exposure, defined by a four-group discrete phenotypic classification [FO-/AKI-, FO-/AKI+, FO+/AKI-, FO+/AKI+] was also evaluated. Primary outcome was mortality and hospital length of stay (LOS) among survivors. 131 patients (median age 29 days (IQR:9, 242 days); 51% men and 82% with underlying cardiac disease) were included. 45.8% survived hospital discharge. FO+ at ECMO discontinuation, but not AKI was associated with mortality [aOR=2.3; 95% CI: 1.07-4.91]. LOS for FO+ patients was twice as long as FO- patients, irrespective of AKI status [(FO+/AKI+ (60 days; IQR: 49-83) vs. FO-/AKI+ (30 days, IQR: 19-48 days); P = 0.01]. FO+ at ECMO initiation and discontinuation was associated with an adjusted 66% and 50% longer length of stay respectively. Prospective studies that target timing and strategy of fluid management, including its removal in children receiving ECPR are greatly needed.

Nutrition Considerations in Neonatal Extracorporeal Life Support.

Extracorporeal life support (ECLS) is a life-saving therapy, but neonates who require ECLS have unique nutritional needs and require aggressive, early nutritional support. These critically ill neonates are at increased risk for long-term feeding difficulties, malnutrition, and growth failure with associated increased morbidity and mortality. Unfortunately, few studies specific to this population exist. Clinical guidelines published by the American Society for Parenteral and Enteral Nutrition are specific to this population and available to aid clinicians in appropriate nutrition regimens, but studies to date suggest that nutrition provision varies greatly from center to center and often is inadequate. Though enteral feedings are becoming more common, aggressive parenteral nutrition is still needed to ensure nutrition goals are met, including the goal of increased protein provision. Long-term complications, including the need for tube feedings and growth failure, are common in neonatal ECLS survivors, particularly those with congenital diaphragmatic hernia. Oral aversion with poor feeding and growth failure must be anticipated and recognized early if present. The nutritional implications associated with the development of acute kidney injury, fluid overload, or the use of continuous renal replacement therapy must be recognized. In this state-of-the-art review, we examine aspects of nutrition for neonates receiving ECLS including nutritional requirements, nutrition provision, current practices, long-term outcomes, and special population considerations.

Fluid Balance in the Critically Ill Child Section: "How Bad Is Fluid in Neonates?"

Fluid overload (FO) in neonates is understudied, and its management requires nuanced care and an understanding of the complexity of neonatal fluid dynamics. Recent studies suggest neonates are susceptible to developing FO, and neonatal fluid balance is impacted by multiple factors including functional renal immaturity in the newborn period, physiologic postnatal diuresis and weight loss, and pathologies that require fluid administration. FO also has a deleterious impact on other organ systems, particularly the lung, and appears to impact survival. However, assessing fluid balance in the postnatal period can be challenging, particularly in extremely low birth weight infants (ELBWs), given the confounding role of maternal serum creatinine (Scr), physiologic weight changes, insensible losses that can be difficult to quantify, and difficulty in obtaining accurate intake and output measurements given mixed diaper output. Although significant FO may be an indication for kidney replacement therapy (KRT) in older children and adults, KRT may not be technically feasible in the smallest infants and much remains to be learned about optimal KRT utilization in neonates. This article, though not a meta-analysis or systematic review, presents a comprehensive review of the current evidence describing the effects of FO on outcomes in neonates and highlights areas where additional research is needed.

Neonatal Extracorporeal Life Support: A Review of Nutrition Considerations.

Critically ill neonates who require extracorporeal life support have particular nutrition needs. These infants require prescription of aggressive, early nutrition support by knowledge providers. Understanding the unique metabolic demands and nutrition requirements of these fragile patients is paramount, particularly if additional therapies such as aggressive diuretic regimens or continuous renal replacement therapy are used concurrently. Although the American Society for Parenteral and Enteral Nutrition has published guidelines for this population, a review of each nutrition component is warranted because few studies exist specific to this population. Long-term complications in survivors of neonatal extracorporeal life support, particularly in patients with select diagnoses such as congenital diaphragmatic hernia, can be significant and must be recognized and anticipated. This review focuses on recognizing the nutrition needs of neonatal patients requiring extracorporeal life support, appraising the available data to guide selection of an appropriate mode of nutrition delivery, and describing the anticipated long-term nutrition implications of extracorporeal life support provision during the neonatal period.