BACKGROUND:Blood transfusion and hemorrhage control procedures can be unreliable surrogates for bleeding requiring intervention in children. Some receive unnecessary blood transfusions or lack intraoperative findings for hemorrhage, while others die before an intervention occurs. Standardized criteria for adjudicating the presence of actionable hemorrhage are needed. We aimed to define expert consensus criteria for retrospectively identifying actionable hemorrhage within 6 hours of emergency department (ED) arrival. METHODS:Experts from six specialties involved in pediatric trauma care participated in a modified Delphi study. Panelists were prompted to consider "actionable hemorrhage" as "severe bleeding or injuries at risk of progression to class III or IV shock without prompt intervention." In Round 1, panelists answered five free-response questions identifying criteria for actionable hemorrhage, including indicators for transfusion and hemorrhage control procedures, postmortem findings, and other relevant factors. Responses were consolidated and rated on a five-point strength-of-indication scale in subsequent rounds. Consensus was defined a priori as ≥70% agreement among panelists. Stability of consensus ( p >0.05) between rounds was assessed using the Wilcoxon Signed-Rank Test. RESULTS:Three Delphi rounds were required to achieve a stable consensus. Twenty-nine of 32 participating panelists participated in all three rounds. Thirteen statements achieved stable consensus as strong indicators of actionable hemorrhage. Criteria with the highest agreement included partial/total resection of intrathoracic/abdominal bleeding solid organs (96.4%), hemoglobin<6 g/dL (93.1%), and resuscitative thoracotomy/sternotomy with hilar or thoracic/abdominal aortic cross-clamp, cardiac massage, or cardiorrhaphy (92.9%). No statements reached a stable consensus as weak indicators of actionable hemorrhage. CONCLUSIONS:We established expert consensus criteria for adjudication of actionable hemorrhage in injured children within 6 hours of ED arrival. These criteria reflect strong indicators that an intervention or death was due to an actionable hemorrhage. Prospective validation of these criteria is needed. ( J Trauma Acute Care Surg . 2026;101: 415-422. Copyright © 2026 Wolters Kluwer Health, LLC. All rights reserved.). LEVEL OF EVIDENCE:Diagnostic Test/Criteria; Level III.

Importance:Patients undergoing cardiac surgery with cardiopulmonary bypass often require platelet transfusions for bleeding. Platelets are routinely stored at room temperature (20-24 °C) for up to 5 to 7 days; however, cold storage (1-6 °C) may allow for increased storage duration without loss of hemostatic function. Objective:To determine the maximum cold-storage duration, up to 21 days, for which cold-stored platelets (CSPs) are noninferior or superior in hemostatic efficacy to room-temperature platelets (RTPs) when transfused in actively bleeding patients undergoing cardiac surgery with cardiopulmonary bypass. Design, Setting, and Participants:A phase 3, multicenter, randomized, partially blinded, adaptive, noninferiority, storage duration-ranging trial conducted in pediatric and adult patients undergoing cardiac surgery with planned cardiopulmonary bypass at 27 sites in the US and Australia from December 2021 to March 2025. Statistical analysis was conducted from September 9 to October 3, 2025. Intervention:Patients were randomized 2:1 to receive CSPs with a maximum of 21 days of storage vs RTPs with a maximum of 7 days of storage. Main Outcomes and Measures:The primary outcome was a hemostatic efficacy score with values ranging from 1 to 5 and higher values indicating greater bleeding. The noninferiority margin was 1 point. The success criterion was met if at least 1 cold-storage duration of 7 days or more had a posterior probability of noninferiority of at least 97.5%. The secondary outcome was 24-hour chest tube output. Results:Of the 1000 patients who underwent platelet transfusion, 989 were included in the primary analysis (650 CSPs and 339 RTPs). The cohort had a mean (SD) age of 42.1 (30.1) years and 67.8% were male. CSPs were noninferior to RTPs for the primary outcome, with a probability of greater than 99.9% for all cold-storage durations. Pooled across storage durations, CSPs had a mean difference from RTPs of 0.09 (95% credible interval, -0.06 to 0.23). Median (IQR) chest tube output at 24 hours (8.9 mL/kg [5.2-15.4] for CSPs vs 8.4 mL/kg [5.5-15.9] for RTPs; difference in medians, 0.4 [95% CI, -1.0 to 1.5]) was not statistically different between study groups. In a post hoc analysis, as all storage durations were noninferior, considering the CSPs as a single group, the hemostatic efficacy score was similar between both groups: mean (SD) of 3.08 (1.15) CSPs vs 2.99 (1.10) RTPs. There were no differences in venous or arterial thrombotic events, transfusion-associated adverse events, acute respiratory distress syndrome, kidney failure, septic shock, and mortality between the study groups, except for increased reexploration rates in the CSP group. Conclusions and Relevance:For patients undergoing cardiac surgery, CSPs stored up to 21 days are noninferior to RTPs for the control of active surgical bleeding. Use of CSPs may allow for increased availability of platelets by reducing wastage and shortages and may allow for incorporation of platelets into inventory at locations where platelets cannot be maintained due to the 5- to 7-day shelf life of RTPs. Trial Registration:ClinicalTrials.gov Identifier: NCT04834414.

Importance Patients undergoing cardiac surgery with cardiopulmonary bypass often require platelet transfusions for bleeding. Platelets are routinely stored at room temperature (20-24 °C) for up to 5 to 7 days; however, cold storage (1-6 °C) may allow for increased storage duration without loss of hemostatic function. Objective To determine the maximum cold-storage duration, up to 21 days, for which cold-stored platelets (CSPs) are noninferior or superior in hemostatic efficacy to room-temperature platelets (RTPs) when transfused in actively bleeding patients undergoing cardiac surgery with cardiopulmonary bypass. Design, Setting, and Participants A phase 3, multicenter, randomized, partially blinded, adaptive, noninferiority, storage duration–ranging trial conducted in pediatric and adult patients undergoing cardiac surgery with planned cardiopulmonary bypass at 27 sites in the US and Australia from December 2021 to March 2025. Statistical analysis was conducted from September 9 to October 3, 2025. Intervention Patients were randomized 2:1 to receive CSPs with a maximum of 21 days of storage vs RTPs with a maximum of 7 days of storage. Main Outcomes and Measures The primary outcome was a hemostatic efficacy score with values ranging from 1 to 5 and higher values indicating greater bleeding. The noninferiority margin was 1 point. The success criterion was met if at least 1 cold-storage duration of 7 days or more had a posterior probability of noninferiority of at least 97.5%. The secondary outcome was 24-hour chest tube output. Results Of the 1000 patients who underwent platelet transfusion, 989 were included in the primary analysis (650 CSPs and 339 RTPs). The cohort had a mean (SD) age of 42.1 (30.1) years and 67.8% were male. CSPs were noninferior to RTPs for the primary outcome, with a probability of greater than 99.9% for all cold-storage durations. Pooled across storage durations, CSPs had a mean difference from RTPs of 0.09 (95% credible interval, −0.06 to 0.23). Median (IQR) chest tube output at 24 hours (8.9 mL/kg [5.2-15.4] for CSPs vs 8.4 mL/kg [5.5-15.9] for RTPs; difference in medians, 0.4 [95% CI, −1.0 to 1.5]) was not statistically different between study groups. In a post hoc analysis, as all storage durations were noninferior, considering the CSPs as a single group, the hemostatic efficacy score was similar between both groups: mean (SD) of 3.08 (1.15) CSPs vs 2.99 (1.10) RTPs. There were no differences in venous or arterial thrombotic events, transfusion-associated adverse events, acute respiratory distress syndrome, kidney failure, septic shock, and mortality between the study groups, except for increased reexploration rates in the CSP group. Conclusions and Relevance For patients undergoing cardiac surgery, CSPs stored up to 21 days are noninferior to RTPs for the control of active surgical bleeding. Use of CSPs may allow for increased availability of platelets by reducing wastage and shortages and may allow for incorporation of platelets into inventory at locations where platelets cannot be maintained due to the 5- to 7-day shelf life of RTPs. Trial Registration ClinicalTrials.gov Identifier: NCT04834414

The past year has yielded important advances in coagulation and transfusion practice across cardiothoracic and vascular care. Patient blood management remains central, with growing evidence supporting restrictive transfusion thresholds, structured anemia screening and treatment, and multidisciplinary bleeding protocols. Ultra-permissive anemia strategies in selected cardiac surgery populations appear feasible, while registry and prospective data reinforce the importance of preoperative hematocrit optimization. Four-factor prothrombin complex concentrate has been established as a preferred alternative to fresh frozen plasma for vitamin K antagonist reversal and management of post-cardiopulmonary bypass coagulopathic bleeding, demonstrating reduced transfusion requirements without increased thromboembolic risk. Hemadsorption techniques show promise for intraoperative drug removal of direct oral anticoagulants in urgent cardiac surgery, although evidence remains limited and largely investigational. Advances in viscoelastic testing enhance early identification of coagulation deficits, as well as monitoring of residual heparin effect, and support personalized, viscoelastic testing-guided transfusion algorithms. Heparin resistance and postoperative thrombocytopenia-including heparin-induced thrombocytopenia-require structured diagnostic and therapeutic approaches, with increasing use of direct thrombin inhibitors in cardiopulmonary bypass and extracorporeal support. Antithrombotic therapy research emphasizes careful escalation and de-escalation strategies to balance bleeding and thrombosis risk, including aspirin withdrawal in selected mechanical circulatory support patients and individualized approaches after valve interventions and coronary bypass surgery. Extracorporeal membrane oxygenation remains associated with increased rates of bleeding and thrombosis. Emerging data on platelet thresholds, direct thrombin inhibitors, and novel factor-targeted agents highlight the complexity of extracorporeal membrane oxygenation-associated coagulopathy. Collectively, recent studies underscore a continued shift toward individualized, viscoelastic testing-guided hemostatic management across adult and pediatric populations.

IntroductionBleeding and thrombosis are major causes of morbidity and mortality in pediatric extracorporeal membrane oxygenation (ECMO), yet their evolving, time-dependent risks remain poorly defined. This study evaluated clinical predictors of bleeding and thrombotic events using time-to-event analysis.MethodsA retrospective cohort study was conducted using the Pediatric ECMO Outcomes Registry (PEDECOR) from October 2011 to September 2024. Patients aged ≤18 years undergoing their first ECMO run were included. Two time-varying Cox proportional hazards models assessed associations between prior complications and time to first bleed or thrombosis, adjusting for clinical and ECMO-related variables.ResultsAmong 1444 patients, median age was 0.4 years (IQR: 0.0-4.4), and 53.6% were male. Bleeding occurred in 65% and thrombosis in 28%. Time to first bleeding events had a median of 2 days (IQR: 0-4) while time to first thrombosis had a median of 3 days (IQR: 2-6). Prior thrombosis was associated with lower early bleeding risk (HR: 0.39, 95% CI: 0.25-0.62, p < 0.001), which reversed over time (interaction HR: 1.44, 95% CI: 1.08-1.92, p = 0.013; crossover at 12.4 days). Similarly, prior bleeding was associated with reduced early thrombosis risk (HR: 0.49, 95% CI: 0.34-0.71, p < 0.001), but reversed over time (interaction HR: 1.63, 95% CI: 1.26-2.11, p < 0.001; crossover at 4.3 days). Central cannulation, cardiac surgery, and non-pulmonary indications were associated with bleeding; sepsis was associated with thrombosis. Anticoagulant type and sex were not significant.ConclusionsBleeding and thrombosis are common and time-dependent in pediatric ECMO. These findings support dynamic anticoagulation strategies tailored to evolving risk.

Randomized trials reported no benefit from transfusion of red blood cell (RBC) units stored for shorter durations compared to standard care. However, there was insufficient evidence to exclude harms at extremes of storage age or explore subgroup differences. We therefore performed an individual patient data meta-analysis to determine the effect of fresher vs. older RBC transfusion on 28-day mortality in hospitalized adults. Individual patient data was sought from clinical trials that randomized more than 1000 adult patients. For the meta-analysis, we used a logistic regression model with a trial-specific fixed effect. Four studies provided individual data from 33,549 patients enrolled from March 2009 through December 2016 from 12 countries. After exclusions, 32,959 (98.2%) patients were included in the analysis. Patients received a median (IQR) of 2 (1 – 4) RBC units with a storage duration of 10 (7 – 15) days in the fresh and 23 (16 – 30) days in the older group. Death occurred in 1,446 of 12,236 patients (11.8%) in the fresher and 1,984 of 20,572 patients (9.6%) in the older group (odds ratio 1.06; 95% CI 0.98 to 1.14; p=0.124). No significant subgroup differences were identified. We found an association between receiving one and two or more RBCs ≤7 days and higher mortality (odds ratio 1.18, 95%CI 1.02 to 1.35; p=0.024 and 1.17, 95% CI 1.04 to 1.32; p=0.015, respectively), but not with any RBC ≥35 days. Adjusted analyses confirmed these findings. Our findings support current blood inventory management policies and are applicable to most hospitalized adults.ClinicalTrials.gov: NCT05482737

OBJECTIVES:To characterize the epidemiology and management of massive bleeding events in children with cancer and/or hematopoietic cell transplant (HCT). DESIGN:Multicenter, retrospective cohort study. SETTING:Nineteen pediatric hospitals in Europe and United States. SUBJECTS:Children ages 0-21 years old with malignancy and/or HCT and massive bleeding admitted from January 1, 2017, to December 31, 2021. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Demographics, oncologic history, laboratory values, interventions, and PICU outcomes were collected. One hundred fifty-two bleeding episodes from 135 patients were analyzed. The median (interquartile range [IQR]) age was 7 years (2-14 yr). Forty-three percent (58/135) were female sex. Nineteen percent of children (26/135) had death attributable to hemorrhage. Forty percent had solid tumors and one-third had undergone at least one HCT. The majority of bleeding events occurred in the PICU (81/152, 53%). The median (IQR) platelet count at time of bleeding was 52 × 10 9 /L (24-115 × 10 9 /L), prothrombin time 18.5 seconds (15.2-24.8 s), activated partial thromboplastin time 42.2 seconds (33.2-56.0 s), and international normalized ratio 1.51 (1.21-2.11). To treat these bleeding events, 99% (148/152) of the time children received RBC transfusions, 84% (126/152) of the time plasma transfusions, 88% (132/152) of the time platelet transfusions, and less than one-fifth hemostatic medications. Half (77/152, 52%) of the time the children received high plasma ratios and half (73/152, 49%) received high platelet ratios. Pulmonary bleeding, oral/nasal bleeding, and receipt of prothrombin complex concentrate were each associated with greater odds of death attributed to hemorrhage: odds ratio (95% CI), respectively: 5.44 (2.250-13.171; p < 0.001); 3.30 (1.20-9.09; p = 0.021); and 3.24 (1.18-8.93; p = 0.023). CONCLUSIONS:Children with malignancy and/or HCT have a high mortality rate from hemorrhage despite being hospitalized at the time of their bleeding event. The majority of children received balanced resuscitation. Definitive trials are needed to determine optimal hemostatic resuscitation practice in this population.

IntroductionThis study aimed to characterize the severity of bleeding and its association with short-term neurologic outcomes in pediatric ECMO.MethodsMulticenter retrospective cohort study of pediatric ECMO patients at 10 centers utilizing the Pediatric ECMO Outcomes Registry (PEDECOR) database from December 2013-February 2019. Subjects excluded were post-cardiac surgery patients and those with neonatal pathologies. A novel ECMO bleeding scale was utilized to categorize daily bleeding events. Poor short-term neurologic outcome was defined as an unfavorable Pediatric Cerebral Performance Category (PCPC) or Pediatric Overall Performance Category (POPC) (score of >3) at hospital discharge.ResultsThis study included 283 pediatric ECMO patients with a median (interquartile range [IQR]) age of 1.3 years [0.1, 9.0], ECMO duration of 5 days [3.0, 9.5], and 44.1% mortality. Unfavorable PCPC and POPC were observed in 48.4% and 51.3% of patients at discharge, respectively. Multivariable logistic regression analysis included patient's age, cannulation type, duration of ECMO, need for cardiopulmonary resuscitation, acute kidney injury, new infection, and vasoactive-inotropic score. As the severity of bleeding increased, there was a corresponding increase in the likelihood of poor neurologic recovery, shown by increasing odds of unfavorable neurologic outcome (PCPC), with an adjusted odds ratio (aOR) of 0.77 (confidence interval [CI] 0.36-1.62), 1.87 (0.54-6.45), 2.97 (1.32-6.69), and 5.56 (0.59-52.25) for increasing bleeding severity (grade 1 to 4 events, respectively). Similarly, unfavorable POPC aOR (CI) was 1.02 (0.48-2.17), 2.05 (0.63-6.70), 5.29 (2.12-13.23), and 5.11 (0.66-39.64) for bleeding grade 1 to 4 events.ConclusionShort-term neurologic outcomes in pediatric ECMO are proportional to the severity of bleeding events. Strategies to mitigate bleeding events could improve neurologic recovery in pediatric ECMO.

Postoperative bleeding in the pediatric intensive care unit patient can result in significant morbidity or mortality. Differentiation between surgical and nonsurgical/coagulopathic bleeding is an important element of bleeding management. Recent definitions of bleeding severity are reviewed. Developmental hemostasis, patient age, and size are special considerations in pediatric bleeding management as are special surgical sites within small or contained areas vulnerable to even small extravascular blood volumes. Hemostatic control other than through blood product administration can be achieved through mechanical or other pharmaceutical adjuncts and a reference table is provided. Collaboration with interventional radiology should be explored in appropriate bleeding situations. An algorithm for resuscitation and management of the bleeding patient including communication prior to any reoperation is presented.

IntroductionRetrospective data suggest that pediatric hematopoietic cell transplant (HCT) patients placed on non-invasive ventilation (NIV) prior to intubation have increased risk of mortality compared to patients who are intubated earlier in their course. The HCT-CI subgroup of the PALISI Network set out to gain a better understanding of factors that influence clinician’s decisions surrounding timing of intubation of pediatric HCT patients.MethodsWe validated and distributed a brief survey exploring potential factors that may influence clinician’s decisions around timing of intubation of pediatric HCT patients with acute lung injury (ALI).ResultsOne hundred and four of the 869 PALISI Network’s members responded to the survey; 97 of these respondents acknowledged caring for HCT patients and were offered the remainder of the survey. The majority of respondents were PICU physicians (96%), with a small number of Advanced Practice Providers and HCT physicians. As expected, poor prognosis categories were perceived as a factors that delay timing to intubation whereas need for invasive procedures was perceived as a factor shortening timing to intubation. Concerns for oxygen toxicity or NIV-associated lung injury were not believed to influence timing of intubation.DiscussionOur survey indicates increased risk of ALI from prolonged NIV and oxygen toxicity in HCT patients are not a concern for most clinicians. Further education of pediatric ICU clinicians around these risk factors could lead to improvement in outcomes and demands further study. Additionally, clinicians identified concerns for the patient’s poor prognosis as a common reason for delayed intubation.

During extracorporeal membrane oxygenation (ECMO) support, the high shear stress in the ECMO circuit results in increased proteolysis of von Willebrand factor (VWF), loss of VWF high-molecular-weight multimers, and impaired ability to bind to platelets and collagen. These structural changes in VWF are consistent with acquired von Willebrand syndrome (AVWS) type 2A and may contribute to the bleeding diathesis frequently observed in ECMO patients. We performed a systematic review of all clinical studies evaluating the prevalence and associated outcomes of AVWS in ECMO patients. Our findings suggest that almost all ECMO patients develop partial or complete loss of VWF high-molecular-weight multimers within a few hours of device implantation. The AVWS persists as long as the patient is supported by ECMO. Weaning from ECMO rapidly and completely resolves the AVWS. Nevertheless, few studies have reported bleeding outcomes in ECMO patients with AVWS, and the extent to which AVWS contributes to the bleeding diathesis during ECMO support cannot be determined by current evidence. Data supporting the use of VWF concentrates to prevent bleeding complications in ECMO patients remain limited.

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.

Few data describe pediatric patients who receive massive transfusion for life-threatening hemorrhage (LTH) while on extracorporeal membrane oxygenation (ECMO). We present a retrospective secondary analysis of a multicenter prospective observational study to describe resource utilization and mortality in pediatric patients with LTH while on ECMO. Children who were on ECMO during an LTH were compared to children with LTH who were not on ECMO. Primary outcomes were volumes of blood products administered and 28 day mortality. Comparisons were assessed by two-sided Fisher's exact test or Wilcoxon rank sum test. A total of 449 children, including 36 on ECMO, were included. Compared to those not on ECMO, children on ECMO received a higher volume of blood products (110 [50-223] vs. 59 [28-113]) ml/kg, p = 0.002) and were more likely to receive antifibrinolytic therapy (39% vs. 10%, p < 0.001). Blood product ratios were similar. Extracorporeal membrane oxygenation patients had higher 28 day mortality (64% vs. 35%, p = 0.001), although 24 hour mortality was similar (17% vs. 23%, p = 0.5). In conclusion, children on ECMO with LTH experience high resource utilization and 28 day mortality. Studies are needed to identify children at risk for LTH and to evaluate ECMO-specific treatment strategies.

( Anesthesiology. 2023; 138:535–560) This clinical review explored coagulopathy in severely bleeding patients after major surgery (eg, cardiac surgery with cardiopulmonary bypass or CPB), serious trauma, and postpartum hemorrhage. There are a multitude of surgical and nonsurgical factors, or a mix of both, that can cause perioperative bleeding in patients. This includes fibrinolysis, metabolic acidosis, platelet impairment, thrombocytopenia, coagulation factor deficiency, activation of inflammatory pathways, hemodilution, hypothermia, and hypovolemia. Bleeding patients can often have previous hemostatic issues because of oral anticoagulants or antiplatelet therapy.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multi-organ involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong antibody production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 weeks after infection. Therefore, we hypothesized that dysfunctional cell-mediated antibody responses downstream of antibody production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, while natural killer (NK) cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function in vitro. Together, our results reveal dysregulation in antibody-mediated cellular responses unique to MIS-C that likely contribute to the immune pathology of this disease.

OBJECTIVES: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus. DATA SOURCES: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill neonates and children. DATA EXTRACTION: Within each of the eight subgroups, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: Following the systematic review of MEDLINE, EMBASE, and Cochrane Library databases from January 1988 to May 2021, and the consensus process for clinical recommendations and consensus statements, PEACE panel experts constructed research priorities using the Child Health and Nutrition Research Initiative methodology. Twenty research topics were prioritized, falling within five domains (definitions and outcomes, therapeutics, anticoagulant monitoring, protocolized management, and impact of the ECMO circuit and its components on hemostasis). CONCLUSIONS: We present the research priorities identified by the PEACE expert panel after a systematic review of existing evidence informing clinical care of neonates and children managed with ECMO. More research is required within the five identified domains to ultimately inform and improve the care of this vulnerable population.

Background The role of hypothermia in post-arrest neuroprotection is controversial. Animal studies suggest potential benefits with lower temperatures, but high-fidelity ECPR models evaluating temperatures below 30 °C are lacking. Objectives To determine whether rapid cooling to 24 °C initiated upon reperfusion reduces brain injury compared to 34 °C in a swine model of ECPR. Methods Twenty-four female pigs had electrically induced VF and mechanical CPR for 30 min. Animals were cannulated for VA-ECMO and cooled to either 34 °C for 4 h (n = 8), 24 °C for 1 h with rewarming to 34 °C over 3 h (n = 7), or 24 °C for 4 h without rewarming (n = 9). Cooling was initiated upon VA-ECMO reperfusion by circulating ice water through the oxygenator. Brain temperature and cerebral and systemic hemodynamics were continuously monitored. After four hours on VA-ECMO, brain tissue was obtained for examination. Results Target brain temperature was achieved within 30 min of reperfusion (p = 0.74). Carotid blood flow was higher in the 24 °C without rewarming group throughout the VA-ECMO period compared to 34 °C and 24 °C with rewarming (p < 0.001). Vasopressin requirement was higher in animals treated with 24 °C without rewarming (p = 0.07). Compared to 34 °C, animals treated with 24 °C with rewarming were less coagulopathic and had less immunohistochemistry-detected neurologic injury. There were no differences in global brain injury score. Conclusions Despite improvement in carotid blood flow and immunohistochemistry detected neurologic injury, reperfusion at 24 °C with or without rewarming did not reduce early global brain injury compared to 34 °C in a swine model of ECPR.

Background Extracorporeal cardiopulmonary resuscitation improves outcomes after out‐of‐hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in‐hospital mortality. Methods and Results Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out‐of‐hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96–0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P <0.001) though bleeding was not significantly associated with in‐hospital death (aHR, 0.81 [95% CI. 0.55–1.19]). A thrombotic event occurred in 23.5% (47/200) of patients. Venous thromboembolism occurred in 11% (22/200) and arterial thrombi in 15.5% (31/200). Clinical characteristics were comparable between groups. In adjusted analyses, no risk factors for thrombosis were identified. Thrombosis was not associated with in‐hospital death (aHR, 0.65 [95% CI, 0.42–1.03]). Conclusions Bleeding is a frequent complication of extracorporeal cardiopulmonary resuscitation that is associated with decreased fibrinogen levels on admission whereas thrombosis is less common. Neither bleeding nor thrombosis was significantly associated with in‐hospital mortality.