The Influence of the Extracorporeal Membrane Oxygenation Circuit and Components on Anticoagulation Management: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding the influence of extracorporeal membrane oxygenation (ECMO) circuit components on anticoagulation practices for pediatric ECMO for the Pediatric ECMO Anticoagulation CollaborativE. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: Management of ECMO anticoagulation in the setting of different ECMO circuit components. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twenty-nine references were used for data extraction and informed recommendations, evidence-based consensus statements, and good practice statements. Evidence tables were constructed using a standardized data extraction form. DATA SYNTHESIS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements or good practice statements for the influence of ECMO circuit and components on anticoagulation management. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One good practice statement, 2 weak recommendations, and 2 consensus statements are presented. CONCLUSIONS: The incorporation of new component technologies into clinical practice has outpaced clinical investigations of anticoagulation strategies for pediatric ECMO. Future investigations should leverage academic and industrial collaborations, translational platforms, and modern biostatistical methods to improve patient outcomes.

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference.

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference. DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill children. DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements. CONCLUSIONS: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials.

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.

Extracorporeal membrane oxygenation for COVID-19: evolving outcomes from the international Extracorporeal Life Support Organization Registry.

BACKGROUND: Over the course of the COVID-19 pandemic, the care of patients with COVID-19 has changed and the use of extracorporeal membrane oxygenation (ECMO) has increased. We aimed to examine patient selection, treatments, outcomes, and ECMO centre characteristics over the course of the pandemic to date. METHODS: We retrospectively analysed the Extracorporeal Life Support Organization Registry and COVID-19 Addendum to compare three groups of ECMO-supported patients with COVID-19 (aged ≥16 years). At early-adopting centres-ie, those using ECMO support for COVID-19 throughout 2020-we compared patients who started ECMO on or before May 1, 2020 (group A1), and between May 2 and Dec 31, 2020 (group A2). Late-adopting centres were those that provided ECMO for COVID-19 only after May 1, 2020 (group B). The primary outcome was in-hospital mortality in a time-to-event analysis assessed 90 days after ECMO initiation. A Cox proportional hazards model was fit to compare the patient and centre-level adjusted relative risk of mortality among the groups. FINDINGS: In 2020, 4812 patients with COVID-19 received ECMO across 349 centres within 41 countries. For early-adopting centres, the cumulative incidence of in-hospital mortality 90 days after ECMO initiation was 36·9% (95% CI 34·1-39·7) in patients who started ECMO on or before May 1 (group A1) versus 51·9% (50·0-53·8) after May 1 (group A2); at late-adopting centres (group B), it was 58·9% (55·4-62·3). Relative to patients in group A2, group A1 patients had a lower adjusted relative risk of in-hospital mortality 90 days after ECMO (hazard ratio 0·82 [0·70-0·96]), whereas group B patients had a higher adjusted relative risk (1·42 [1·17-1·73]). INTERPRETATION: Mortality after ECMO for patients with COVID-19 worsened during 2020. These findings inform the role of ECMO in COVID-19 for patients, clinicians, and policy makers. FUNDING: None.

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.

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.

Catheter-Directed Pharmacologic Thrombolysis for Acute Submassive and Massive Pulmonary Emboli in Children and Adolescents-An Exploratory Report.

OBJECTIVES: The objective of this study is to report a single-center experience of the safety and efficacy of pulmonary artery catheter-directed thrombolysis for both massive and submassive pulmonary emboli in the pediatric and adolescent population. DESIGN: A 22-month retrospective review of the electronic medical record and picture archiving and communication system was performed of patients less than 21 years old, presenting with massive or submassive pulmonary emboli treated with pulmonary artery catheter-directed thrombolysis at a single, tertiary care pediatric hospital. Multiple variables were analyzed including indications, technical success, clinical efficacy, and complications. SETTING: A single, tertiary care pediatric hospital. PATIENTS: Nine patients (mean 13.9 yr; range 6-19 yr) with massive and/or submassive pulmonary emboli who underwent pulmonary artery catheter-directed thrombolysis met inclusion criteria. INTERVENTIONS: Catheter-directed thrombolysis. MEASUREMENTS AND MAIN RESULTS: Pulmonary emboli was diagnosed by CT angiography in all cases. Catheter-directed thrombolysis alone was clinically successful (defined as improved cardiopulmonary function following catheter-directed thrombolysis) in seven patients (78%) with two patients not improving following catheter-directed thrombolysis. There were no immediate bleeding complications from catheter-directed thrombolysis therapy. All patients were maintained on anticoagulation treatment following catheter-directed thrombolysis. Catheter-directed thrombolysis was technically successful (defined as successful placement of pulmonary artery infusion catheters with full or partial resolution of thrombus) in all cases. Follow-up pulmonary angiography at the cessation of catheter-directed thrombolysis revealed complete thrombus resolution in four patients (44%) and partial resolution in five patients (55%). Mean pulmonary artery pressures decreased in all patients (mean precatheter-directed thrombolysis pulmonary artery pressure = 37 ± 11 mm Hg; mean postcatheter-directed thrombolysis pulmonary artery pressure = 28 ± 10 mm Hg; p = 0.0164). CONCLUSIONS: Pulmonary artery catheter-directed thrombolysis is a technically feasible therapeutic option for children and adolescents with submassive and massive pulmonary emboli.

Epidemiology of therapeutic apheresis with a multidisciplinary approach at a high volume pediatric center.

INTRODUCTION: Therapeutic apheresis (TA) is used inconsistently in pediatric populations. We seek to define our multidisciplinary institutional practice. METHODS: We conducted a retrospective chart review of patients receiving TA from January 1, 2012 through October 31, 2015. Data collected included demographics, American Society of Apheresis (ASFA) indication, complications, and mortality. RESULTS: Over 46 months, 1198 TA procedures were conducted on 289 patients ranging in age from 5 months to 21 years with weights ranging from 4.76 to 170.3 kg (16 procedures in patients <10 kg). The procedures were 86% therapeutic plasma exchange, 10% red blood cell exchange, 4% extracorporeal photopheresis, and 5 leukocytapheresis procedures. TA was initiated in different clinical environments: 41% outpatient, 37% intensive care, 15% general inpatient, and 7% operating room. The ASFA category (6th edition) indications for the 1198 procedures included: 44% category I, 25% category II, 23% category III, a single category IV procedure, and the remainder (8%) uncategorized by ASFA. The rate of procedure failure and procedure-related mortality are 1 and 0%, respectively. Case mortality rate was 4%. CONCLUSION: At a large volume pediatric hospital, TA is commonly used and can be performed safely in a variety of settings by a multidisciplinary team. This demographic review catalogs the number and type of procedures performed as a second-line therapy or on the basis of limited evidence. Additional collaborative investigation is needed to evaluate unique implications of TA in pediatrics to maximize efficacy while preserving safety.

The Impact of Fluid Overload on Outcomes in Children Treated With Extracorporeal Membrane Oxygenation: A Multicenter Retrospective Cohort Study.

OBJECTIVE: To characterize the epidemiology of fluid overload and its association with mortality and duration of extracorporeal membrane oxygenation in children treated with extracorporeal membrane oxygenation. DESIGN: Retrospective cohort study. SETTING: Six tertiary children's hospital ICUs. PATIENTS: Seven hundred fifty-six children younger than 18 years old treated with extracorporeal membrane oxygenation for greater than or equal to 24 hours from January 1, 2007, to December 31, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall survival to extracorporeal membrane oxygenation decannulation and hospital discharge was 74.9% (n = 566) and 57.7% (n = 436), respectively. Median fluid overload at extracorporeal membrane oxygenation initiation was 8.8% (interquartile range, 0.3-19.2), and it differed between hospital survivors and non survival, though not between extracorporeal membrane oxygenation survivors and non survivors. Median peak fluid overload on extracorporeal membrane oxygenation was 30.9% (interquartile range, 15.4-54.8). During extracorporeal membrane oxygenation, 84.8% had a peak fluid overload greater than or equal to 10%; 67.2% of patients had a peak fluid overload of greater than or equal to 20% and 29% of patients had a peak fluid overload of greater than or equal to 50%. The median peak fluid overload was lower in patients who survived on extracorporeal membrane oxygenation (27.2% vs 44.4%; p < 0.0001) and survived to hospital discharge (24.8% vs 43.3%; p < 0.0001). After adjusting for acute kidney injury, pH at extracorporeal membrane oxygenation initiation, nonrenal complications, extracorporeal membrane oxygenation mode, support type, center and patient age, the degree of fluid overload at extracorporeal membrane oxygenation initiation (p = 0.05), and the peak fluid overload on extracorporeal membrane oxygenation (p < 0.0001) predicted duration of extracorporeal membrane oxygenation in survivors. Multivariable analysis showed that peak fluid overload on extracorporeal membrane oxygenation (adjusted odds ratio, 1.09; 95% CI, 1.04-1.15) predicted mortality on extracorporeal membrane oxygenation; fluid overload at extracorporeal membrane oxygenation initiation (adjusted odds ratio, 1.13; 95% CI, 1.05-1.22) and peak fluid overload (adjusted odds ratio, 1.18; 95% CI, 1.12-1.24) both predicted hospital morality. CONCLUSIONS: Fluid overload occurs commonly and is independently associated with adverse outcomes including increased mortality and increased duration of extracorporeal membrane oxygenation in a broad pediatric extracorporeal membrane oxygenation population. These results suggest that fluid overload is a potential target for intervention to improve outcomes in children on extracorporeal membrane oxygenation.

Development and Validation of the Neonatal Risk Estimate Score for Children Using Extracorporeal Respiratory Support.

OBJECTIVE: To develop and validate the Neonatal Risk Estimate Score for Children Using Extracorporeal Respiratory Support, which estimates the risk of in-hospital death for neonates prior to receiving respiratory extracorporeal membrane oxygenation (ECMO) support. STUDY DESIGN: We used an international ECMO registry (2008-2013); neonates receiving ECMO for respiratory support were included. We divided the registry into a derivation sample and internal validation sample, by calendar date. We chose candidate variables a priori based on published evidence of association with mortality; variables independently associated with mortality in logistic regression were included in this parsimonious model of risk adjustment. We evaluated model discrimination with the area under the receiver operating characteristic curve (AUC), and we evaluated calibration with the Hosmer-Lemeshow goodness-of-fit test. RESULTS: During 2008-2013, 4592 neonates received ECMO respiratory support with mortality of 31%. The development dataset contained 3139 patients treated in 2008-2011. The Neo-RESCUERS measure had an AUC of 0.78 (95% CI 0.76-0.79). The validation cohort had an AUC = 0.77 (0.75-0.80). Patients in the lowest risk decile had an observed mortality of 7.0% and a predicted mortality of 4.4%, and those in the highest risk decile had an observed mortality of 65.6% and a predicted mortality of 67.5%. CONCLUSIONS: Neonatal Risk Estimate Score for Children Using Extracorporeal Respiratory Support offers severity-of-illness adjustment for neonatal patients with respiratory failure receiving ECMO. This score may be used to adjust patient survival to assess hospital-level performance in ECMO-based care.

The Incidence of Acute Kidney Injury and Its Effect on Neonatal and Pediatric Extracorporeal Membrane Oxygenation Outcomes: A Multicenter Report From the Kidney Intervention During Extracorporeal Membrane Oxygenation Study Group.

OBJECTIVE: In a population of neonatal and pediatric patients on extracorporeal membrane oxygenation; to describe the prevalence and timing of acute kidney injury utilizing a consensus acute kidney injury definition and investigate the association of acute kidney injury with outcomes (length of extracorporeal membrane oxygenation and mortality). DESIGN: Multicenter retrospective observational cohort study. SETTING: Six pediatric extracorporeal membrane oxygenation centers. PATIENTS: Pediatric patients (age, < 18 yr) on extracorporeal membrane oxygenation at six centers during a period of January 1, 2007, to December 31, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Complete data were analyzed for 832 patients on extracorporeal membrane oxygenation. Sixty percent of patients had acute kidney injury utilizing the serum creatinine Kidney Disease Improving Global Outcomes criteria (AKI) and 74% had acute kidney injury using the full Kidney Disease Improving Global Outcomes criteria including renal support therapy (AKI). Of those who developed acute kidney injury, it was present at extracorporeal membrane oxygenation initiation in a majority of cases (52% AKI and 65% AKI) and present by 48 hours of extracorporeal membrane oxygenation support in 86% (AKI) and 93% (AKI). When adjusted for patient age, center of support, mode of support, patient complications and preextracorporeal membrane oxygenation pH, the presence of acute kidney injury by either criteria was associated with a significantly longer duration of extracorporeal membrane oxygenation support (AKI, 152 vs 110 hr; AKI, 153 vs 99 hr) and increased adjusted odds of mortality at hospital discharge (AKI: odds ratio, 1.77; 1.22-2.55 and AKI: odds ratio, 2.50; 1.61-3.90). With the addition of renal support therapy to the model, acute kidney injury was associated with a longer duration of extracorporeal membrane oxygenation support (AKI, 149 vs 121 hr) and increased risk of mortality at hospital discharge (AKI: odds ratio, 1.52; 1.04-2.21). CONCLUSION: Acute kidney injury is present in 60-74% of neonatal-pediatric patients supported on extracorporeal membrane oxygenation and is present by 48 hours of extracorporeal membrane oxygenation support in 86-93% of cases. Acute kidney injury has a significant association with increased duration of extracorporeal membrane oxygenation support and increased adjusted odds of mortality at hospital discharge.

Association of hospital-level volume of extracorporeal membrane oxygenation cases and mortality. Analysis of the extracorporeal life support organization registry.

RATIONALE: Recent pediatric studies suggest a survival benefit exists for higher-volume extracorporeal membrane oxygenation (ECMO) centers. OBJECTIVES: To determine if higher annual ECMO patient volume is associated with lower case-mix-adjusted hospital mortality rate. METHODS: We retrospectively analyzed an international registry of ECMO support from 1989 to 2013. Patients were separated into three age groups: neonatal (0-28 d), pediatric (29 d to <18 yr), and adult (≥18 yr). The measure of hospital ECMO volume was age group-specific and adjusted for patient-level case-mix and hospital-level variance using multivariable hierarchical logistic regression modeling. The primary outcome was death before hospital discharge. A subgroup analysis was conducted for 2008-2013. MEASUREMENTS AND MAIN RESULTS: From 1989 to 2013, a total of 290 centers provided ECMO support to 56,222 patients (30,909 neonates, 14,725 children, and 10,588 adults). Annual ECMO mortality rates varied widely across ECMO centers: the interquartile range was 18-50% for neonates, 25-66% for pediatrics, and 33-92% for adults. For 1989-2013, higher age group-specific ECMO volume was associated with lower odds of ECMO mortality for neonates and adults but not for pediatric cases. In 2008-2013, the volume-outcome association remained statistically significant only among adults. Patients receiving ECMO at hospitals with more than 30 adult annual ECMO cases had significantly lower odds of mortality (adjusted odds ratio, 0.61; 95% confidence interval, 0.46-0.80) compared with adults receiving ECMO at hospitals with less than six annual cases. CONCLUSIONS: In this international, case-mix-adjusted analysis, higher annual hospital ECMO volume was associated with lower mortality in 1989-2013 for neonates and adults; the association among adults persisted in 2008-2013.

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.

Recovery of renal function and survival after continuous renal replacement therapy during extracorporeal membrane oxygenation.

OBJECTIVE: To assess the outcome of pediatric patients supported by concomitant extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). DESIGN, SETTING, AND PATIENTS: Acute kidney injury is associated with mortality in ECMO patients. CRRT in patients on ECMO provides an efficient and potentially beneficial method of acute kidney injury management. Concern that concomitant CRRT use increases the risk of developing anuria and chronic renal failure limits its use in some centers. We hypothesized that development of chronic renal failure is rare with concurrent ECMO and CRRT. We evaluated the outcomes of 154 ECMO/CRRT patients cared for over 10 yrs at a referral pediatric medical center. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 68 (44%) ECMO/CRRT survivors, 45 were assigned a pediatric risk, injury, failure, loss and end-stage (referred to as "pRIFLE") score at CRRT initiation. Seventeen (38%) patients met the criteria for Risk, 15 (33%) for Injury, and 10 (22%) for Failure. Two Failure patients later met End stage criteria. Of all survivors, 18 (26%) required ongoing renal replacement therapy (15 required continuous veno-venous hemofiltration, two required peritoneal dialysis, and one patient required intermittent hemodialysis) post ECMO discontinuation. Renal recovery occurred in 65 (96%) of 68 patients before discharge. One neonatal patient had sepsis-induced renal injury on transfer, but had normal creatinine 1 month later. Two pediatric patients with vasculitis and primary renal disease at presentation (both meeting Failure criteria) developed end-stage renal disease. One received peritoneal dialysis and subsequent renal transplant. The other has diminished function without need for renal replacement therapy. CONCLUSION: In the absence of primary renal disease, chronic renal failure did not occur after concurrent use of CRRT with ECMO. Concern for precipitating chronic renal failure by using CRRT during ECMO is not substantiated by this large single-center experience. Consistent with previous reports, mortality is higher in patients receiving concomitant CRRT and ECMO compared with those receiving ECMO alone. Mortality is similar to patients requiring CRRT who are not on ECMO. Additional studies are warranted to determine the optimal role of CRRT use in ECMO patients.

Thrombolysis in Children: A Case Report and Review of the Literature.

Thromboembolism (TE), including venous thromboembolism (VTE), arterial TE, arterial ischemic stroke (AIS), and myocardial infarction (MI), is considered a relatively rare complication in the pediatric population. Yet, the incidence is rising, especially in hospitalized children. The vast majority of pediatric TE occurs in the setting of at least one identifiable risk factor. Most recently, acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) have demonstrated an increased risk for TE development. The mainstay for the management pediatric TE has been anticoagulation. Thrombolytic therapy is employed more frequently in adult patients with ample data supporting its use. The data for thrombolysis in pediatric patients is more limited, but the utilization of this therapy is becoming more commonplace in tertiary care pediatric hospitals. Understanding the data on thrombolysis use in pediatric TE and the involved risks is critical before initiating one of these therapies. In this paper, we present the case of an adolescent male with acute fulminant myocarditis and cardiogenic shock likely secondary to MIS-C requiring extracorporeal life support (ECLS) who developed an extensive thrombus burden that was successfully resolved utilizing four simultaneous catheter-directed thrombolysis (CDT) infusions in addition to a review of the literature on the use of thrombolytic therapy in children.

Use of the Selective Cytopheretic Device in Critically Ill Children.

INTRODUCTION: Critically ill children with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT) are at increased risk of death. The selective cytopheretic device (SCD) promotes an immunomodulatory effect when circuit ionized calcium (iCa2+) is maintained at <0.40 mmol/l with regional citrate anticoagulation (RCA). In a randomized trial of adult patients on CRRT, those treated with the SCD maintaining an iCa2+ <0.40 mmol/l had improved survival/dialysis independence. We conducted a US Food and Drug Administration (FDA)-sponsored study to evaluate safety and feasibility of the SCD in 16 critically ill children. METHODS: Four pediatric intensive care units (ICUs) enrolled children with AKI and multiorgan dysfunction receiving CKRT to receive the SCD integrated post-CKRT membrane. RCA was used to achieve a circuit iCa2+ level <0.40 mmol/l. Subjects received SCD treatment for 7 days or CKRT discontinuation, whichever came first. RESULTS: The FDA target enrollment of 16 subjects completed the study from December 2016 to February 2020. Mean age was 12.3 ± 5.1 years, weight was 53.8 ± 28.9 kg, and median Pediatric Risk of Mortality II was 7 (range 2-19). Circuit iCa2+ levels were maintained at <0.40 mmol/l for 90.2% of the SCD therapy time. Median SCD duration was 6 days. Fifteen subjects survived SCD therapy; 12 survived to ICU discharge. All ICU survivors were dialysis independent at 60 days. No SCD-related adverse events (AEs) were reported. CONCLUSION: Our data demonstrate that SCD therapy is feasible and safe in children who require CKRT. Although we cannot make efficacy claims, the 75% survival rate and 100% renal recovery rate observed suggest a possible favorable benefit-to-risk ratio.

Extracorporeal Membrane Oxygenation for COVID-19: Updated 2021 Guidelines from the Extracorporeal Life Support Organization.

DISCLAIMER: This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19-related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19-related ARDS, myocarditis, or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.