In vivo measurement of pediatric extracorporeal oxygenator insensible losses; a single center pilot study.

Introduction: Fluid overload on Extracorporeal Membrane Oxygenation (ECMO) is associated with worse outcomes. Previous in vitro studies have attempted to quantify oxygenator-related insensible losses, as failure to account for this fluid loss may lead to inaccurate fluid balance assessment and potentially harmful clinical management, such as unnecessary exposure to diuretics, slow continuous ultrafiltration (SCUF), or continuous kidney replacement therapy (CKRT). We performed a novel in vivo study to measure insensible fluid losses in pediatric ECMO patients. Methods: Pediatric ECMO patients were approached over eleven months in the pediatric and cardiac intensive care units. The water content of the oxygenator inflow sweep gas and exhaust gas were calculated by measuring the ambient temperature and relative humidity at frequent intervals and various sweep flow. Results and discussion: Nine subjects were enrolled, generating 431 data points. The cohort had a median age of 11 years IQR [0.83, 13], weight of 23.2 kg IQR [6.48, 44.28], and body surface area of 0.815 m2 IQR [0.315, 1.3725]. Overall, the cohort had a median sweep of 2.5 L/min [0.9, 4], ECMO flow of 3.975 L/m2/min [0.75, 4.51], and a set ECMO temperature of 37 degrees Celsius [36.6, 37.2]. The calculated net water loss per L/min of sweep was 75.93 ml/day, regardless of oxygenator size or patient weight. There was a significant difference in median documented vs. calculated fluid balance incorporating the insensible fluid loss, irrespective of oxygenator size (pediatric oxygenator: 7.001 ml/kg/day [-12.37, 28.59] vs. -6.11 ml/kg/day [-17.44, 13.01], respectively, p = 0.005 and adult oxygenator: 14.36 ml/kg/day [1.54, 25.77] and 9.204 ml/kg/day [-1.28, 22.05], respectively, p = <0.001). We present this pilot study of measured oxygenator-associated insensible fluid losses on ECMO. Our results are consistent with prior in vitro methods and provide the basis for future studies evaluating the impact of incorporating these fluid losses into patients' daily fluid balance on patient management and outcomes.

Major Adverse Kidney Events in Pediatric Continuous Kidney Replacement Therapy.

Importance: Continuous kidney replacement therapy (CKRT) is increasingly used in youths with critical illness, but little is known about longer-term outcomes, such as persistent kidney dysfunction, continued need for dialysis, or death. Objective: To characterize the incidence and risk factors, including liberation patterns, associated with major adverse kidney events 90 days after CKRT initiation (MAKE-90) in children, adolescents, and young adults. Design, Setting, and Participants: This international, multicenter cohort study was conducted among patients aged 0 to 25 years from The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry treated with CKRT for acute kidney injury or fluid overload from 2015 to 2021. Exclusion criteria were dialysis dependence, concurrent extracorporeal membrane oxygenation use, or receipt of CKRT for a different indication. Data were analyzed from May 2 to December 14, 2023. Exposure: Patient clinical characteristics and CKRT parameters were assessed. CKRT liberation was classified as successful, reinstituted, or not attempted. Successful liberation was defined as the first attempt at CKRT liberation resulting in 72 hours or more without return to dialysis within 28 days of CKRT initiation. Main Outcomes and Measures: MAKE-90, including death or persistent kidney dysfunction (dialysis dependence or ≥25% decline in estimated glomerular filtration rate from baseline), were assessed. Results: Among 969 patients treated with CKRT (529 males [54.6%]; median [IQR] age, 8.8 [1.7-15.0] years), 630 patients (65.0%) developed MAKE-90. On multivariable analysis, cardiac comorbidity (adjusted odds ratio [aOR], 1.60; 95% CI, 1.08-2.37), longer duration of intensive care unit admission before CKRT initiation (aOR for 6 days vs 1 day, 1.07; 95% CI, 1.02-1.13), and liberation pattern were associated with MAKE-90. In this analysis, patients who successfully liberated from CKRT within 28 days had lower odds of MAKE-90 compared with patients in whom liberation was attempted and failed (aOR, 0.32; 95% CI, 0.22-0.48) and patients without a liberation attempt (aOR, 0.02; 95% CI, 0.01-0.04). Conclusions and Relevance: In this study, MAKE-90 occurred in almost two-thirds of the population and patient-level risk factors associated with MAKE-90 included cardiac comorbidity, time to CKRT initiation, and liberation patterns. These findings highlight the high incidence of adverse outcomes in this population and suggest that future prospective studies are needed to better understand liberation patterns and practices.

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.

Long-term kidney outcomes in pediatric continuous-flow ventricular assist device patients.

BACKGROUND: Continuous-flow ventricular assist devices (CF-VADs) are used increasingly in pediatric end-stage heart failure (ESHF) patients. Alongside common risk factors like oxidant injury from hemolysis, non-pulsatile flow constitutes a unique circulatory stress on kidneys. Post-implantation recovery after acute kidney injury (AKI) is commonly reported, but long-term kidney outcomes or factors implicated in the evolution of chronic kidney disease (CKD) with prolonged CF-VAD support are unknown. METHODS: We studied ESHF patients supported > 90 days on CF-VAD from 2008 to 2018. The primary outcome was CKD (per Kidney Disease Improving Global Outcomes (KDIGO) criteria). Secondary outcomes included AKI incidence post-implantation and CKD evolution in the 6-12 months of CF-VAD support. RESULTS: We enrolled 134 patients; 84/134 (63%) were male, median age was 13 [IQR 9.9, 15.9] years, 72/134 (54%) had preexisting CKD at implantation, and 85/134 (63%) had AKI. At 3 months, of the 91/134 (68%) still on a CF-VAD, 34/91 (37%) never had CKD, 13/91 (14%) developed de novo CKD, while CKD persisted or worsened in 49% (44/91). Etiology of heart failure, extracorporeal membrane oxygenation use, duration of CF-VAD, AKI history, and kidney replacement therapy were not associated with different CKD outcomes. Mortality was higher in those with AKI or preexisting CKD. CONCLUSIONS: In the first multicenter study to focus on kidney outcomes for pediatric long-term CF-VAD patients, preimplantation CKD and peri-implantation AKI were common. Both de novo CKD and worsening CKD can happen on prolonged CF-VAD support. Proactive kidney function monitoring and targeted follow-up are important to optimize outcomes.

Programs and processes for advancing pediatric acute kidney support therapy in hospitalized and critically ill children: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

Pediatric acute kidney support therapy (paKST) programs aim to reliably provide safe, effective, and timely extracorporeal supportive care for acutely and critically ill pediatric patients with acute kidney injury (AKI), fluid and electrolyte derangements, and/or toxin accumulation with a goal of improving both hospital-based and lifelong outcomes. Little is known about optimal ways to configure paKST teams and programs, pediatric-specific aspects of delivering high-quality paKST, strategies for transitioning from acute continuous modes of paKST to facilitate rehabilitation, or providing effective short- and long-term follow-up. As part of the 26th Acute Disease Quality Initiative Conference, the first to focus on a pediatric population, we summarize here the current state of knowledge in paKST programs and technology, identify key knowledge gaps in the field, and propose a framework for current best practices and future research in paKST.

Early postoperative weight-based fluid overload is associated with worse outcomes after neonatal cardiac surgery.

OBJECTIVES: Evaluate the association of postoperative day (POD) 2 weight-based fluid balance (FB-W) > 10% with outcomes after neonatal cardiac surgery. METHODS: Retrospective cohort study of 22 hospitals in the NEonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) registry from September 2015 to January 2018. Of 2240 eligible patients, 997 neonates (cardiopulmonary bypass (CPB) n = 658, non-CPB n = 339) were weighed on POD2 and included. RESULTS: Forty-five percent (n = 444) of patients had FB-W > 10%. Patients with POD2 FB-W > 10% had higher acuity of illness and worse outcomes. Hospital mortality was 2.8% (n = 28) and not independently associated with POD2 FB-W > 10% (OR 1.04; 95% CI 0.29-3.68). POD2 FB-W > 10% was associated with all utilization outcomes, including duration of mechanical ventilation (multiplicative rate of 1.19; 95% CI 1.04-1.36), respiratory support (1.28; 95% CI 1.07-1.54), inotropic support (1.38; 95% CI 1.10-1.73), and postoperative hospital length of stay (LOS 1.15; 95% CI 1.03-1.27). In secondary analyses, POD2 FB-W as a continuous variable demonstrated association with prolonged durations of mechanical ventilation (OR 1.04; 95% CI 1.02-1.06], respiratory support (1.03; 95% CI 1.01-1.05), inotropic support (1.03; 95% CI 1.00-1.05), and postoperative hospital LOS (1.02; 95% CI 1.00-1.04). POD2 intake-output based fluid balance (FB-IO) was not associated with any outcome. CONCLUSIONS: POD2 weight-based fluid balance > 10% occurs frequently after neonatal cardiac surgery and is associated with longer cardiorespiratory support and postoperative hospital LOS. However, POD2 FB-IO was not associated with clinical outcomes. Mitigating early postoperative fluid accumulation may improve outcomes but requires safely weighing neonates in the early postoperative period. A higher resolution version of the Graphical abstract is available as Supplementary information.

Assessment of fluid balance after neonatal cardiac surgery: a description of intake/output vs. weight-based methods.

BACKGROUND: Fluid overload associates with poor outcomes after neonatal cardiac surgery, but consensus does not exist for the most clinically relevant method of measuring fluid balance (FB). While weight change-based FB (FB-W) is standard in neonatal intensive care units, weighing infants after cardiac surgery may be challenging. We aimed to identify characteristics associated with obtaining weights and to understand how intake/output-based FB (FB-IO) and FB-W compare in the early postoperative period in this population. METHODS: Observational retrospective study of 2235 neonates undergoing cardiac surgery from 22 hospitals comprising the NEonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) database. RESULTS: Forty-five percent (n = 998) of patients were weighed on postoperative day (POD) 2, varying from 2 to 98% among centers. Odds of being weighed were lower for STAT categories 4 and 5 (OR 0.72; 95% CI 0.53-0.98), cardiopulmonary bypass (0.59; 0.42-0.83), delayed sternal closure (0.27; 0.19-0.38), prophylactic peritoneal dialysis use (0.58; 0.34-0.99), and mechanical ventilation on POD 2 (0.23; 0.16-0.33). Correlation between FB-IO and FB-W was weak for every POD 1-6 and within the entire cohort (correlation coefficient 0.15; 95% CI 0.12-0.17). FB-W measured higher than paired FB-IO (mean bias 12.5%; 95% CI 11.6-13.4%) with wide 95% limits of agreement (- 15.4-40.4%). CONCLUSIONS: Weighing neonates early after cardiac surgery is uncommon, with significant practice variation among centers. Patients with increased severity of illness are less likely to be weighed. FB-W and FB-IO have weak correlation, and further study is needed to determine which cumulative FB metric most associates with adverse outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children: A Modified Delphi Consensus Statement.

Importance: Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge. Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy. Evidence Review: At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations. Findings: The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy. Conclusions and Relevance: Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.

Impact of Continuous Renal Replacement Therapy on Bivalirudin Dosing in Pediatric Extracorporeal Membrane Oxygenation.

There is an increasing interest in the use of bivalirudin for pediatric extracorporeal membrane oxygenation (ECMO) anticoagulation. However, dosing is not well described in those requiring continuous renal replacement therapy (CRRT). We aimed to determine whether CRRT affects bivalirudin dosing in pediatric ECMO patients. Children ≤18 years of age placed on ECMO and anticoagulated with bivalirudin for ≥24 hours from January 2019 to May 2020 were included. Bivalirudin doses were collected for 144 hours from initiation of bivalirudin or CRRT. Analysis was performed to determine whether CRRT, age, or weight affected bivalirudin dosing. Thirty-one children were included, and 11 (35%) required concomitant CRRT. There was no difference in age (median 9.1 versus 3.2 months, p = 0.15) or days on ECMO (median 11 versus 9, p = 0.7) between those who did or did not receive CRRT. The mean bivalirudin dosing was similar in patients who did or did not require CRRT (median and IQR: 0.13 mg/kg/hour [0.08-0.26] versus 0.15 mg/kg/hour [0.11-0.22], respectively, p = 0.13). Younger age ( p < 0.001) and lower weight ( p < 0.001) were associated with higher bivalirudin dosing. In our study, bivalirudin dosing did not differ if the patient required CRRT while on ECMO.

Systemic Hypertension in Pediatric Veno-Venous Extracorporeal Membrane Oxygenation.

Systemic hypertension (HTN) is a recognized complication of veno-venous (VV) extracorporeal membrane oxygenation (ECMO) in children. We sought to determine the prevalence and associated features of HTN in a retrospective cohort of children (>1 year old) supported with VV ECMO from January 2015 to July 2019 at our institution. Patient and ECMO-related characteristics were reviewed, including intensive care unit (ICU) length of stay (LOS), ECMO duration, corticosteroids and nephrotoxic medication exposure, acute kidney injury (AKI), overall fluid balance, and transfusion data. We analyzed 23 children (43% female) with a median age of 8.5 years (interquartile range [IQR] = 4-14.5). Median ICU LOS was 26 days (IQR = 15-47) with a median ECMO duration of 288 hours (IQR = 106-378) and a mortality rate of 35%. HTN was diagnosed in 87% subjects at a median of 25 ECMO hours (IQR = 9-54) of whom 55% were hypertensive >50% of their ECMO duration. AKI and fluid overload were documented in >50% of cohort. All but two subjects received at least one nephrotoxic medication, and nearly all received corticosteroids. Our data demonstrate that HTN is present in a preponderance of children supported with VV ECMO and appears within the first 3 days of cannulation. Underlying etiology is likely multifactorial.

Identifying Risk for Acute Kidney Injury in Infants and Children Following Cardiac Arrest.

OBJECTIVES: Our goal was to identify risk factors for acute kidney injury in children surviving cardiac arrest. DESIGN: Retrospective analysis of a public access dataset. SETTING: Fifteen children's hospitals associated with the Pediatric Emergency Care Applied Research Network. PATIENTS: Two hundred ninety-six subjects between 1 day and 18 years old who experienced in-hospital or out-of-hospital cardiac arrest between July 1, 2003, and December 31, 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our primary outcome was development of acute kidney injury as defined by the Acute Kidney Injury Network criteria. An ordinal probit model was developed. We found six critical explanatory variables, including total number of epinephrine doses, postcardiac arrest blood pressure, arrest location, presence of a chronic lung condition, pH, and presence of an abnormal baseline creatinine. Total number of epinephrine doses received as well as rate of epinephrine dosing impacted acute kidney injury risk and severity of acute kidney injury. CONCLUSIONS: This study is the first to identify risk factors for acute kidney injury in children after cardiac arrest. Our findings regarding the impact of epinephrine dosing are of particular interest and suggest potential for epinephrine toxicity with regard to acute kidney injury. The ability to identify and potentially modify risk factors for acute kidney injury after cardiac arrest may lead to improved morbidity and mortality in this population.

Surfactant treatment of an infant with acute idiopathic pulmonary hemorrhage.

OBJECTIVE: To describe the successful use of surfactant for treatment of respiratory distress refractory to conventional mechanical ventilation in a 4-wk-old with pulmonary hemorrhage. DESIGN: Case report. SETTING: Tertiary care center pediatric intensive care unit. PATIENT: Four-week-old infant. MAIN RESULT: Clinical improvement of respiratory distress as evidenced by 50% reduction in oxygenation index and subsequent extubation. CONCLUSION: Pulmonary hemorrhage is a rare but potentially fatal condition in children. Previously described therapeutic approaches include high-frequency oscillation ventilation and extracorporeal membrane oxygenation. Infants with pulmonary hemorrhage and respiratory distress may benefit from a trial of surfactant before escalating care.