Managing the kidney - The role of continuous renal replacement therapy in neonatal and pediatric ECMO.

Extracorporeal membrane oxygenation (ECMO) represents a lifesaving therapy utilized in in the most critically ill neonates and children with reversible cardiopulmonary failure. As a result of the severity of their critical illness these patients are among the highest risk populations for developing acute kidney injury (AKI) and disorders of fluid balance including the pathologic state of fluid overload (FO). In multiple studies AKI has been shown to occur commonly in 60-80% children treated with ECMO and is associated with adverse outcomes. In early studies evaluating ECMO in neonatal respiratory populations, the importance of fluid balance and the development of FO was recognized as an important contributor to adverse outcomes. Multiple single center studies and multicenter work have confirmed that FO occurs commonly across ECMO populations and is consistently associated with adverse outcomes. As a result of the high rates of AKI and the high rates of FO, continuous renal replacement therapy (CRRT) is increasingly utilized in neonatal and pediatric ECMO. In this state-of-the-art review, we cover the definitions, pathophysiology, incidence, and impact of AKI and FO in neonates and children supported with ECMO and summarize and appraise the evidence regarding the use of CRRT concurrently with ECMO. This review will cover the appropriate timing of this initiation, the options for providing CRRT with ECMO, overview of CRRT prescription, and the long-term implications of kidney support therapy in this population.

Trends in Neonatal Extracorporeal Membrane Oxygenation During a Venovenous Cannula Shortage.

OBJECTIVES: To report temporal trends in venovenous extracorporeal membrane oxygenation (ECMO) use for neonatal respiratory failure in U.S. centers before and after functional venovenous cannula shortage due to withdrawal of one dual lumen venovenous cannula from the market in 2018. DESIGN: Retrospective cohort study. SETTING: ECMO registry of the Extracorporeal Life Support Organization. PATIENTS: Infants who received neonatal (cannulated prior to 29 d of age) respiratory ECMO at a U.S. center and had a record available in the ECMO registry from January 1, 2010 to July 20, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was receipt of venovenous ECMO (vs venoarterial or other), and secondary outcomes were survival to hospital discharge and adverse neurologic outcomes. Using an interrupted time series design, we fit multivariable mixed effects logistic regression models with receipt of venovenous ECMO as the dependent variable, treatment year modeled as a piecewise linear variable using three linear splines (pre shortage: 2010-2014, 2014-2018; shortage: 2018-2021), and adjusted for center clustering and multiple covariates. We evaluated trends in venovenous ECMO use by primary diagnosis including congenital diaphragmatic hernia, meconium aspiration, pulmonary hypertension, and other. Annual neonatal venovenous ECMO rates decreased after 2018: from 2010 to 2014, adjusted odds ratio (aOR) for yearly trend 0.98 (95% CI 0.92-1.04), from 2014 to 2018, aOR for yearly trend 0.90 (95% CI 0.80-1.01), and after 2018, aOR for yearly trend 0.46 (95% CI 0.37-0.57). We identified decreased venovenous ECMO use after 2018 in all diagnoses evaluated, and we failed to identify differences in temporal trends between diagnoses. Survival and adverse neurologic outcomes were unchanged across the study periods. CONCLUSIONS: Venovenous ECMO for neonatal respiratory failure in U.S. centers decreased after 2018 even after accounting for temporal trends, coincident with withdrawal of one of two venovenous cannulas from the market.

Synergistic association of fluid overload and acute kidney injury on outcomes in pediatric cardiac ECMO: a retrospective analysis of the KIDMO database.

BACKGROUND: Acute kidney injury (AKI) and fluid overload (FO) are associated with poor outcomes in children receiving extracorporeal membrane oxygenation (ECMO). Our objective is to evaluate the impact of AKI and FO on pediatric patients receiving ECMO for cardiac pathology. METHODS: We performed a secondary analysis of the six-center Kidney Interventions During Extracorporeal Membrane Oxygenation (KIDMO) database, including only children who underwent ECMO for cardiac pathology. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria. FO was defined as < 10% (FO-) vs. ≥ 10% (FO +) and was evaluated at ECMO initiation, peak during ECMO, and ECMO discontinuation. Primary outcomes were mortality and length of stay (LOS). RESULTS: Data from 191 patients were included. Non-survivors (56%) were more likely to be FO + than survivors at peak ECMO fluid status and ECMO discontinuation. There was a significant interaction between AKI and FO. In the presence of AKI, the adjusted odds of mortality for FO + was 4.79 times greater than FO- (95% CI: 1.52-15.12, p = 0.01). In the presence of FO + , the adjusted odds of mortality for AKI + was 2.7 times higher than AKI- [95%CI: 1.10-6.60; p = 0.03]. Peak FO + was associated with a 55% adjusted relative increase in LOS [95%CI: 1.07-2.26, p = 0.02]. CONCLUSIONS: The association of peak FO + with mortality is present only in the presence of AKI + . Similarly, AKI + is associated with mortality only in the presence of peak FO + . FO + was associated with LOS. Studies targeting fluid management have the potential to improve LOS and mortality outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Use of Antifactor Xa Assays in a Comprehensive Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Protocol is Associated with Increased Survival and Significant Blood Product Cost-Savings.

We augmented our standard extracorporeal membrane oxygenation laboratory protocol to include antifactor Xa assays, thromboelastography, and antithrombin measurements. We performed a retrospective chart review to determine outcomes for patients placed on extracorporeal membrane oxygenation (ECMO) prior to and after the initiation of our anticoagulation laboratory protocol. A total of 663 consecutive ECMO runs were evaluated from January 1, 2007 to June 30, 2018. Of these patients, 252 were on ECMO prior to initiation of the anticoagulation laboratory protocol on September 1, 2011, and 411 patients were on ECMO after initiation of the protocol. There were no major changes to our extracorporeal membrane oxygenation circuit or changes to our transfusion threshold during this continuous study period. Transfusion utilization data revealed statistically significant decreases in almost all blood components, and a savings in blood component inflation-adjusted acquisition costs of 31% bringing total blood product cost-savings to $309,905 per year. In addition, there was an increase in survival to hospital discharge from 45 to 56% associated with the initiation of the protocol ( p = 0.004). Our data indicate that implementation of a standardized ECMO anticoagulation protocol, which titrates unfractionated heparin infusions based on antifactor Xa assays, is associated with reduced blood product utilization, significant blood product cost savings, and increased patient survival. Future prospective evaluation is needed to establish an antifactor Xa assay-driven ECMO anticoagulation strategy as both clinically superior and cost-effective.

Extracorporeal Life Support Organization Guidelines for Fluid Overload, Acute Kidney Injury, and Electrolyte Management.

DISCLAIMER: This guideline for extracorporeal membrane oxygenation (ECMO) fluid and electrolyte management for all patient populations is intended for educational use to build the knowledge of physicians and other health professionals in assessing the conditions and managing the treatment of patients undergoing extracorporeal life support (ECLS)/ECMO and describe what are believed to be useful and safe practice for ECLS/ECMO, but these are not necessarily consensus recommendations. The aim of clinical guidelines is to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Ultimately, healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge, and expertise. These guidelines do not take the place of physicians' and other health professionals' judgment in diagnosing and treatment of particular patients. These guidelines are not intended to and should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment must be made by the physician and other health professionals and the patient in light of all the circumstances presented by the individual patient, and the known variability and biologic behavior of the clinical condition. These guidelines reflect the data at the time the guidelines were prepared; the results of subsequent studies or other information may cause revisions to the recommendations in these guidelines to be prudent to reflect new data, but Extracorporeal Life Support Organization (ELSO) is under no obligation to provide updates. In no event will ELSO be liable for any decision made or action taken in reliance upon the information provided through these guidelines.

Flexible Bronchoscopy in Pediatric Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: Pediatric patients with ARDS will on occasion need venovenous extracorporeal membrane oxygenation (VV-ECMO) for organ support. As these patients recover, they may benefit from lung recruitment maneuvers including flexible bronchoscopy (FB). The objective of this study was to assess the clinical course of patients who underwent FB while on VV-ECMO for ARDS. METHODS: This was a secondary analysis of a retrospective multi-center cohort at 10 United States pediatric academic quaternary care centers. Data were collected on 204 subjects age 14 d-18 y on VV-ECMO. RESULTS: 271 FBs were performed on 129 (63%) subjects. Pre-FB tidal volume was 1.8 mL/kg compared to 2.22 mL/kg following FB (P = .007). Dynamic compliance also improved from pre-FB to post-FB (2.23 vs 3.04 mL/cm H2O, P = .005). There was a low incidence of complications following FB (3.1%). Subjects in the FB group had fewer ECMO-free days (EFDs) (17.9 vs 22.1 d, P < .001), fewer ventilator-free days (VFDs) (40.0 vs 46.5 d, P = .001), and longer ICU length of stay (LOS) (18 vs 32 d, P < .001). Subjects in the early versus late FB group had more EFDs (19.4 vs 15.2 d, P = .003), more VFDs (43.0 vs 34.0 d, P = .004), and shorter ICU LOS (27.5 vs 35.5 d, P = .045). Mortality in the subjects who had at least one FB was 27.1% compared to 40% in the subjects who did not have a FB while on VV-ECMO (P = .057). CONCLUSIONS: FB can be performed on patients while anticoagulated on VV-ECMO with a low incidence of complications. FB may be beneficial especially when performed early in the course of VV-ECMO.

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.

Extracorporeal Life Support for Respiratory Failure in Patients With Electronic Cigarette or Vaping Product Use-Associated Lung Injury.

OBJECTIVES: Electronic cigarette or vaping product use-associated lung injury is a clinical entity that can lead to respiratory failure and death. Despite the severity of electronic cigarette or vaping product use-associated lung injury, the role of extracorporeal life support in its management remains unclear. Our objective was to describe the clinical characteristics and outcomes of patients with electronic cigarette or vaping product use-associated lung injury who received extracorporeal life support. DESIGN: We performed a retrospective review of records of electronic cigarette or vaping product use-associated lung injury patients who received extracorporeal life support. Standardized data were collected via direct contact with extracorporeal life support centers. Data regarding presentation, ventilatory management, extracorporeal life support details, and outcome were analyzed. SETTING: This was a multi-institutional, international case series with patients from 10 different institutions in three different countries. PATIENTS: Patients who met criteria for confirmed electronic cigarette or vaping product use-associated lung injury (based on previously reported diagnostic criteria) and were placed on extracorporeal life support were included. Patients were identified via literature review and by direct contact with extracorporeal life support centers. MEASUREMENTS AND MAIN RESULTS: Data were collected for 14 patients ranging from 16 to 45 years old. All had confirmed vape use within 3 months of presentation. Nicotine was the most commonly used vaping product. All patients had respiratory symptoms and radiographic evidence of bilateral pulmonary opacities. IV antibiotics and corticosteroids were universally initiated. Patients were intubated for 1.9 days (range, 0-6) prior to extracorporeal life support initiation. Poor oxygenation and ventilation were the most common indications for extracorporeal life support. Five patients showed evidence of ventricular dysfunction on echocardiography. Thirteen patients (93%) were placed on venovenous extracorporeal life support, and one patient required multiple rounds of extracorporeal life support. Total extracorporeal life support duration ranged from 2 to 37 days. Thirteen patients survived to hospital discharge; one patient died of septic shock. CONCLUSIONS: Electronic cigarette or vaping product use-associated lung injury can cause refractory respiratory failure and hypoxemia. These data suggest that venovenous extracorporeal life support can be an effective treatment option for profound, refractory respiratory failure secondary to electronic cigarette or vaping product use-associated lung injury.

Tracheostomy and long-term mechanical ventilation in children after veno-venous extracorporeal membrane oxygenation.

OBJECTIVE: Our objective is to characterize the incidence of tracheostomy placement and of new requirement for long-term mechanical ventilation after extracorporeal membrane oxygenation (ECMO) among children with acute respiratory failure. We examine whether an association exists between demographics, pre-ECMO and ECMO clinical factors, and the placement of a tracheostomy or need for long-term mechanical ventilation. METHODS: A retrospective multicenter cohort study was conducted at 10 quaternary care pediatric academic centers, including children supported with veno-venous (V-V) ECMO from 2011 to 2016. RESULTS: Among 202 patients, 136 (67%) survived to ICU discharge. All tracheostomies were placed after ECMO decannulation, in 22 patients, with 19 of those surviving to ICU discharge (14% of survivors). Twelve patients (9% of survivors) were discharged on long-term mechanical ventilation. Tracheostomy placement and discharge on home ventilation were not associated with pre-ECMO severity of illness or pre-existing chronic illness. Patients who received a tracheostomy were older and weighed more than patients who did not receive a tracheostomy, although this association did not exist among patients discharged on home ventilation. ECMO duration was longer in those who received a tracheostomy compared with those who did not, as well as for those discharged on home ventilation, compared to those who were not. CONCLUSION: The 14% rate for tracheostomy placement and 9% rate for discharge on long-term mechanical ventilation after V-V ECMO are important patient-centered findings. This study informs anticipatory guidance provided to families of patients requiring prolonged respiratory ECMO support, and lays the foundation for future research.

Veno-Venous Extracorporeal Membrane Oxygenation for Children With Cancer or Hematopoietic Cell Transplant: A Ten Center Cohort.

We performed a multicenter retrospective cohort study of children with 14 days to 18 years of age in the United States from 2011 to 2016 with cancer or hematopoietic cell transplant (HCT) who were supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO). We compared the outcomes of children with oncological diagnoses or HCT supported with V-V ECMO to other children who have received V-V ECMO support. In this cohort of 204 patients supported with V-V ECMO, 30 (15%) had a diagnosis of cancer or a history of HCT. There were 21 patients who had oncological diagnoses without HCT and 9 children were post-HCT. The oncology/HCT group had a higher overall ICU mortality (67% vs. 28%, P < 0.001), mortality on ECMO (43% vs. 21%, P < 0.01), and ICU mortality among ECMO survivors (35% vs. 8%, P < 0.01). The oncology/HCT group had a higher rate of conversion to veno-arterial (V-A) ECMO (23% vs. 9%, P = 0.02) (RR, 2.5; 95% CI, 1.1-5.6). Children with cancer or HCT were older (6.6 vs. 2.9 years, P = 0.02) and had higher creatinine levels (0.65 vs. 0.4 mg/dL, P = 0.04) but were similar to the rest of the cohort for other pre-ECMO variables. For post-HCT patients, survival was significantly worse for those whose indication for HCT was cancer or immunodeficiency (0/6) as compared to other nonmalignant indications (3/3) (P = 0.01).

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.

Extracorporeal Membrane Oxygenation Support for Pediatric Burn Patients: Is It Worth the Risk?

OBJECTIVES: Examine the outcomes of pediatric burn patients requiring extracorporeal membrane oxygenation to determine whether extracorporeal membrane oxygenation should be considered in this special population. DESIGN: Retrospective cohort study. SETTING: All extracorporeal membrane oxygenation centers reporting to the Extracorporeal Life Support Organization. SUBJECTS: Pediatric patients (birth to younger than 18 yr) who were supported with extracorporeal membrane oxygenation with a burn diagnosis between 1990 and 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 113 patients were identified from the registry by inclusion criteria. Patients cannulated for respiratory failure had the highest survival (55.7%, n = 97) compared to those supported for cardiac failure (33.3%, n = 6) or extracorporeal cardiopulmonary resuscitation (30%, n = 10). Patients supported on venovenous extracorporeal membrane oxygenation for respiratory failure had the best overall survival at 62.2% (n = 37). Important for the burn population, rates of surgical site bleeding were similar to other surgical patients placed on extracorporeal membrane oxygenation at 22.1%. Cardiac arrest prior to cannulation was associated with increased hospital mortality (odds ratio, 3.41; 95% CI, 0.16-1.01; p = 0.048). Following cannulation, complications including the need for inotropes (odds ratio, 2.64; 95% CI, 1.24-5.65; p = 0.011), presence of gastrointestinal hemorrhage (p = 0.049), and hyperglycemia (glucose > 240 mg/dL) (odds ratio, 3.42; 95% CI, 1.13-10.38; p = 0.024) were associated with increased mortality. Of patients with documented burn percentage of total body surface area (n = 19), survival was 70% when less than 60% total body surface area was involved. CONCLUSIONS: Extracorporeal membrane oxygenation could be considered as an additional level of support for the pediatric burn population, especially in the setting of respiratory failure. Additional studies are necessary to determine the optimal timing of cannulation and other patient characteristics that may impact outcomes.

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.

Mechanical Ventilation in Children on Venovenous ECMO.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is used when mechanical ventilation can no longer support oxygenation or ventilation, or if the risk of ventilator-induced lung injury is considered excessive. The optimum mechanical ventilation strategy once on ECMO is unknown. We sought to describe the practice of mechanical ventilation in children on VV-ECMO and to determine whether mechanical ventilation practices are associated with clinical outcomes. METHODS: We conducted a multicenter retrospective cohort study in 10 pediatric academic centers in the United States. Children age 14 d through 18 y on VV-ECMO from 2011 to 2016 were included. Exclusion criteria were preexisting chronic respiratory failure, primary diagnosis of asthma, cyanotic heart disease, or ECMO as a bridge to lung transplant. RESULTS: Conventional mechanical ventilation was used in about 75% of children on VV-ECMO; the remaining subjects were managed with a variety of approaches. With the exception of PEEP, there was large variation in ventilator settings. Ventilator mode and pressure settings were not associated with survival. Mean ventilator FIO2 on days 1-3 was higher in nonsurvivors than in survivors (0.5 vs 0.4, P = .009). In univariate analysis, other risk factors for mortality were female gender, higher Pediatric Risk Estimate Score for Children Using Extracorporeal Respiratory Support (Ped-RESCUERS), diagnosis of cancer or stem cell transplant, and number of days intubated prior to initiation of ECMO (all P < .05). In multivariate analysis, ventilator FIO2 was significantly associated with mortality (odds ratio 1.38 for each 0.1 increase in FIO2 , 95% CI 1.09-1.75). Mortality was higher in subjects on high ventilator FIO2 (≥ 0.5) compared to low ventilator FIO2 (> 0.5) (46% vs 22%, P = .001). CONCLUSIONS: Ventilator mode and some settings vary in practice. The only ventilator setting associated with mortality was FIO2 , even after adjustment for disease severity. Ventilator FIO2 is a modifiable setting that may contribute to mortality in children on VV-ECMO.

Acute kidney injury risk-based screening in pediatric inpatients: a pragmatic randomized trial.

BACKGROUND: Pediatric acute kidney injury (AKI) is common and associated with increased morbidity, mortality, and length of stay. We performed a pragmatic randomized trial testing the hypothesis that AKI risk alerts increase AKI screening. METHODS: All intensive care and ward admissions of children aged 28 days through 21 years without chronic kidney disease from 12/6/2016 to 11/1/2017 were included. The intervention alert displayed if calculated AKI risk was > 50% and no serum creatinine (SCr) was ordered within 24 h. The primary outcome was SCr testing within 48 h of AKI risk > 50%. RESULTS: Among intensive care admissions, 973/1909 (51%) were randomized to the intervention. Among those at risk, more SCr tests were ordered for the intervention group than for controls (418/606, 69% vs. 361/597, 60%, p = 0.002). AKI incidence and severity were the same in intervention and control groups. Among ward admissions, 5492/10997 (50%) were randomized to the intervention, and there were no differences between groups in SCr testing, AKI incidence, or severity of AKI. CONCLUSIONS: Alerts based on real-time prediction of AKI risk increased screening rates in intensive care but not pediatric ward settings. Pragmatic clinical trials provide the opportunity to assess clinical decision support and potentially eliminate ineffective alerts.

Acute Kidney Injury, Fluid Overload, and Outcomes in Children Supported With Extracorporeal Membrane Oxygenation for a Respiratory Indication.

This study seeks to evaluate the association between acute kidney injury (AKI), fluid overload (FO), and mortality in children supported with extracorporeal membrane oxygenation (ECMO) for refractory respiratory failure. This retrospective observational cohort study was performed at six tertiary care children's hospital intensive care units, studying 424 patients < 18 years of age supported with ECMO for ≥ 24 hours for a respiratory indication from January 1, 2007, to December 31, 2011. In a multivariate analysis, FO level at ECMO initiation was not associated with hospital mortality, whereas peak FO level during ECMO was associated with hospital mortality. For every 10% increase in peak FO during ECMO, the odds of hospital mortality were approximately 1.2 times higher. Every 10% increase in peak FO during ECMO resulted in a significant relative change in the duration of ECMO hours by a factor of 1.08. For hospital survivors, every 10% increase in peak FO level during ECMO resulted in a significant relative change in the duration of mechanical ventilation hours by a factor of 1.13. In this patient population, AKI and FO are associated with increased mortality and should be considered targets for medical interventions including judicious fluid management, diuretic use, and renal replacement therapy.

Adjunctive Therapies During Extracorporeal Membrane Oxygenation to Enhance Multiple Organ Support in Critically Ill Children.

Since the advent of extracorporeal membrane oxygenation (ECMO) over 40 years ago, there has been increasing interest in the use of the extracorporeal circuit as a platform for providing multiple organ support. In this review, we will examine the evidence for the use of continuous renal replacement therapy, therapeutic plasma exchange, leukopheresis, adsorptive therapies, and extracorporeal liver support in conjunction with ECMO.