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Richard W Melchior,1 Steven W Sutton,2 William Harris,3 Heidi J Dalton4,5 1Department of Perfusion Services, The Children's Hospital of Philadelphia, Philadelphia, PA, 2Cardiovascular Support Services, Inc., Dallas, TX, 3Department of Perfusion Services, Ochsner Clinic Foundation, New Orleans, LA, 4Alaskan Native Tribal Health Consortium, Anchorage, AK, 5Department of Child Health, University of Arizona-College of Medicine, Phoenix, AZ, USAAbstract: The development of the membrane oxygenator for pediatric cardiopulmonary bypass has been an incorporation of ideology and technological advancements with contributions by many investigators throughout the past two centuries. With the pursuit of this technological achievement, the ability to care for mankind in the areas of cardiac surgery has been made possible. Heart disease can affect anyone within the general population, but one such segment that it can affect from inception includes children. Currently, congenital heart defects are the most common birth defects nationally and worldwide. A large meta-analysis study from 1930 to 2010 was conducted in review of published medical literature totaling 114 papers with a study population of 24,091,867 live births, and divulged a staggering incidence of congenital heart disease involving 164,396 subjects with diverse cardiac illnesses. The prevalence of these diseases increased from 0.6 per 1,000 live births from 1930–1934 to 9.1 per 1,000 live births after 1995. These data reveal an emphasis on a growing public health issue regarding congenital heart disease. This discovery displays a need for heightened awareness in the scientific and medical industrial community to accelerate investigative research on emerging cardiovascular devices in an effort to confront congenital anomalies. One such device that has evolved over the past several decades is the pediatric membrane oxygenator. The pediatric membrane oxygenator, in conjunction with the heart lung machine, assists in the repair of most congenital cardiac defects. Numerous children born with congenital heart disease with or without congestive heart failure have experienced improved clinical outcomes in quality of life, survival, and mortality as a result of the inclusion of this technology during their cardiac surgical procedure. The purpose of this review is to report a summary of the published medical and scientific literature related to development of the pediatric membrane oxygenator from its conceptual evolutionary stages to artificially supporting whole body perfusion in the modern pediatric cardiac surgical setting. Keywords: cardiovascular perfusion, pediatric cardiac surgery, extracorporeal technological advancement

Introduction: Absence of pre-hospital coagulation tests challenges prompt management of hemostasis after trauma. The Viscoelastic Coagulation Monitor (VCM, Entegrion, Durham, NC) is a hand-held coagulation test for point-of-care. We evaluated VCM in a translational swine polytrauma model, hypothesizing that VCM correlates with a laboratory reference method, the TEG 5000 (Haemonetics, Boston, MA), and can identify coagulopathic phenotypes relevant to trauma. Our secondary hypothesis was that pre-warming of VCM disposable test cartridges using a heating plate versus pre-warming of cartridges by carrying the cartridge in the user's pocket does not significantly alter results., Materials and Methods: This study was conducted in tandem with a parent study involving anesthetized, mechanically ventilated swine (n = 20; 54 ± 5 kg) that encountered traumatic brain injury, pulmonary contusion and hemorrhage, or combination/polytrauma injury. Blood was collected at baseline, post-injury, post-shock, post-transfusion, and 6-, 24-, and 48 h post-injury to perform VCM at point-of-care. Within-group effect of time was assessed. Spearman correlation examined linear relations between VCM and standard laboratory-based coagulation tests; as well as lactate, ionized calcium, and body temperature. Logistic regression examined predictiveness of VCM to identify coagulopathic phenotypes, with receiver operator characteristic curves generated to assess diagnostic capability. At a subset of timepoints, necessity of pre-warming the VCM test cartridge using a heating plate versus pre-warming the cartridge by placement in the user's pocket was assessed by conducting simultaneous tests on two separate instruments, with results analyzed by paired t-test with crossover design., Results: VCM revealed time-dependent changes in clotting time, clot formation time (CFT), alpha, maximum clot firmness (MCF), and lysis index (LI30). All VCM metrics correlated with the respective TEG 5000 metrics, with strongest correlation for VCM MCF with TEG MA (rhos = 0.77, P < .0001) and VCM LI30 with TEG LY30 (rhos = -0.76, P < .0001). VCM demonstrated good (area under the curve >0.70) to excellent (area under the curve >0.90) diagnostic accuracy in detection of low platelet count (MCF), low hematocrit (clotting time, clot formation time, alpha, and MCF), low fibrinogen (MCF), and high fibrinogen (alpha, MCF). There was no statistically or clinically relevant effect of cartridge warming method on results., Conclusions: In a trauma model, VCM detected significant changes in coagulation at point-of-care in a simplified portable form factor. VCM could enable informed hemostasis management in pre-hospital settings where coagulations tests are unavailable, pending further validation in clinical trials., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support., Methods: These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels., Results: We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts., Conclusions: The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI., (© 2024. The Author(s).)

Objective: The outcomes of COVID-19 patients on venovenous extracorporeal membrane oxygenation (VV-ECMO) varied. We aim to investigate the variability concerning location and timeframe. We conducted a retrospective analysis of data from 351 institutions in 53 countries. The primary outcome was survival to hospital discharge or death up to 90 days from ECMO start. The associations between calendar time (month and year) of ECMO initiation and the primary outcome were examined by Cox regression modeling. Multivariable survival analyses were adjusted for the time of ECMO start, age, body mass index, APACHE II, SOFA, and the duration of mechanical ventilation before ECMO., Results: 1060 adult COVID-19 patients enrolled in the COVID-19 Critical Care Consortium (COVID Critical) international registry and required VV-ECMO support. The study period is from January 2020 to December 2021. The median age was 51 years old, and 70% were male patients. Most patients were from Europe (39.3%) and North America (37.4%). The in-hospital mortality of the entire cohort was 47.12%. In North America and Europe, there was an increased probability of death from May 2020 through February 2021. Latin America showed a steady rate of survival until late in the study. South Asia, the Middle East, and Africa showed an increased chance of mortality around May 2020. In the Asian-Pacific region, after February 2021, there was an increased probability of death. The time of ECMO initiation and advanced patient age were associated with increased mortality., Conclusion: Variability in the outcomes of COVID-19 patients on VV-ECMO existed within different regions. This variability reflects the differences in resources, policies, patient selection, management, and possibly COVID-19 virus subtypes. Our findings might help guide global response in the future by early adoption of patient selection protocols, worldwide policies, and delivery of resources., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Gianluigi Li Bassi is a recipient of the BITRECS fellowship; the “BITRECS” project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 754,550 and from the “La Caixa” Foundation (ID 100010434), under the agreement LCF/PR/GN18/50310006. Jacky Y Suen is funded by the Advance Queensland fellowship program. Sung-Min Cho is funded by NIH (1K23HL157610) and serves as a consultant for Hyperfine. Peta Alexander is funded by U.S. DoD PRMRP Clinical Trial Award #W81XWH2210301, NIH (R13HD104432) and FDA UCSF-Stanford Center of Excellence in Regulatory Sciences and Innovation (U01FD004979/U01FD005978). Peta Alexander is Treasurer of ELSO Board of Directors.

Objectives: To derive systematic-review informed, modified Delphi consensus regarding the medications used for anticoagulation for pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE (PEACE)., Data Sources: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021., Study Selection: Included studies assessed anticoagulation used in pediatric ECMO., Data Extraction: Two authors reviewed all citations independently, with a third reviewer adjudicating any conflicts. Eighteen references were used for data extraction as well as for creation of recommendations. 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-informed recommendations and, when evidence was lacking, expert-based consensus statements, or good practice statements for anticoagulation during pediatric ECMO. A web-based modified Delphi process was used to build consensus via the Research and Development/University of California Appropriateness Method. Consensus was based on a modified Delphi process with agreement defined as greater than 80%. Two recommendations, two consensus statements, and one good practice statement were developed, and, in all, agreement greater than 80% was reached., Conclusions: There is insufficient evidence to formulate optimal anticoagulation therapy during pediatric ECMO. Additional high-quality research is needed to inform evidence-based practice for anticoagulation during pediatric ECMO., Competing Interests: The Executive Committee (Drs. Alexander, Muszynski, Bembea, Cheifetz, Steiner, and Barbaro) served as arbitrators for conflict of interest management. Dr. Alexander’s institution received funding from Novartis (ProspectiveTrial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF [PANORAMA-HF]). Dr. Sloan commenced employment with CSL Behring after the consensus process was complete. Dr. Patregnani discloses consultation payments from MNK Pharmaceuticals and Pfizer. Dr. Dalton discloses she is a consultant for Innovative Extracorporeal Membrane Oxygenation Concepts, Hemocue Entegrion, and Medtronic. Dr. Ryerson received an honorarium from the Instrumentation Laboratory for consultation work. Drs. Brandão, Monagle, Ryerson, Alexander, and Dalton disclosed the off-label product use of direct thrombin inhibitors for pediatric ECMO anticoagulation. Dr. Muszynski’s institution received funding from the National Institutes of Health (NIH). Drs. Muszynski and Alexander received support for article research from the NIH. Dr. Alexander’s institution received funding from the National Institute of Child Health and Human Development (R13HD104432), ELSO, and Novartis. Dr. Dalton received funding from Innovative ECMO Concepts, Entegrion, and Hemocue. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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., Competing Interests: Drs. Alexander’s and Muszynski’s institutions received funding from the National Institutes of Health (NIH). Drs. Alexander, Bembea, Himebauch, Barbaro, and Muszynski received support for article research from the NIH. Drs. Alexander’s and Bembea’s institutions received funding from the Extracorporeal Life Support Organization (ELSO). Dr. Alexander’s institution received funding from Novartis (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF [PANORAMA-HF]). Dr. Alexander disclosed that she is Treasurer of the Board of Directors of ELSO, past Co-Chair of Pediatric Extracorporeal Membrane Oxygenation (Pedi-ECMO). Dr. Bembea’s institution received funding from the National Institute of Neurologic Disorders and Stroke and a Grifols Investigator Sponsored Research Grant. Dr. Cheifetz received funding from UptoDate. Dr. Dalton received funding from Innovative Extracorporeal Membrane Oxygenation (ECMO) Concepts, Medtronic, Entegrion, and Hemocue. Drs. Dalton, Ozment, Barbaro, Almond, Brandão, Baumann Kreuziger, Paden, and Ryerson disclosed the off-label product use of pediatric ECMO-related medications for anticoagulation. Dr. Himebauch’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI) (K23HL153759). Drs. Karam’s and Nellis’s institutions received funding from the NHBLI (R34HL159119). Dr. Ozment received funding from Kaufman & Canoles, Social Cascade, and Wiseman Ashworth Law Group. Dr. Steiner’s institution received funding from the Department of Defense (DoD); she received funding from Medtronic and Octapharma; she disclosed that she is a Pumps for Kids, Infantsand Neonates (PumpKIN) trial Data Safety and Monitoring Board member. Dr. Alexander’s and Thiagarajan’s institution received funding from the DoD Clinical Trial Award for Trial of Indication-Based Transfusion of RBCs in ECMO trial (W81XWH2210301). Dr. Thiagarajan received funding from Society of Critical Care Medicine and ELSO. Dr. Zantek disclosed that she is a Board Member and Vice President of the North American Specialized Coagulation Laboratory Association and Board Member of the American Society for Apheresis, the External Quality Assurance in Thrombosis and Hemostasis, and Blood Network subgroup of Pediatric Acute Lung Injury and Sepsis Investigators groups; she disclosed that her spouse is an employee of Boston Scientific and owns stock in Endo International PLC. Dr. Barbaro’s institution received funding from the NHLBI (R01 HL153519 and K12 HL138039); he disclosed that he is ELSO Board of Directors and Pedi-ECMO Co-Chair. Dr. Emani received funding from Chiesi Pharma. Dr. Hyslop disclosed he is Co-Chair of ELSO Registry Database Development Committee and Coordinator Liaison to ELSO Steering Committee. Dr. Baumann Kreuziger received funding from the Health Resources and Services Administration Vaccine Injury Compensation Program. Dr. Paden disclosed that he is past president and board member of ELSO. Dr. Ryerson received an honorarium from Instrumentation Laboratory for consultation work. Dr. Sloan commenced employment with CSL Behring after the consensus process was complete. Dr. Patregnani received funding from Mallinckrodt; he discloses consultation payments from MNK pharmaceuticals and Pfizer. The Executive Committee (Drs. Alexander, Muszynski, Bembea, Cheifetz, Steiner, and Barbaro) served as arbitrators for conflict-of-interest management. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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., Competing Interests: Drs. Muszynski and Alexander’s institutions received funding from the National Institutes of Health (NIH). Drs. Muszynski, Bembea, Himebauch, Barbaro, and Alexander received support for article research from the NIH. Dr. Bembea’s institution received funding from the National Institute of Neurologic Disorder and Stroke (R01NS106292) and a Grifols Investigator Sponsored Research Grant. Drs. Bembea, Steiner, and Thiagarajan’s institutions received funding from the Department of Defense. Dr. Cheifetz received funding from UptoDate. Dr. Dalton received funding from Innovative Extracorporeal Membrane Oxygenation (ECMO) Concepts, Entegrion, and Hemocue; she disclosed the off-label product use of ECMO equipment and drugs for anticoagulation. Dr. Himebauch receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K23HL153759. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr. Said acknowledges research support from the Children’s Discovery Institute Faculty Development Award at Washington University in St. Louis. Dr. Ozment received funding from Kaufman & Canoles Law Firm, Wiseman Ashworth Law Group, and Social Cascade; she disclosed the off-label product use of Heparin and bivalirudin use in neonatal and pediatric patients on ECMO. Dr. Steiner received funding from Octapharma, MedTronic, and PumpKIN DSMB; she disclosed the off-label product use of rFVIIA, TXA, Amicar, Kcentra. Dr. Thiagarajan received funding from the Society of Critical Care Medicine and the Extracorporeal Life Support Organization (ELSO). Dr. Zantek received funding from the North American Specialized Coagulation Laboratory Association (NASCOLA), the American Society for Apheresis (ASFA), and BloodNet; she disclosed that she is a Board Member of External Quality Assurance in Thrombosis and Hemostasis, a committee member of NASCOLA, ASFA, the Association for the Advancement of Blood and Biotherapies, the College of American Pathologists, and the International Society for Laboratory Hematology; she disclosed that her spouse is an employee of Boston Scientific and has a financial interest in Boston Scientific and Endo International. Dr. Barbaro’s institution received funding from the NIH (R01 HL153519 and K12 HL138039); he disclosed that he is a Board Member for ELSO and Co-Chair for Pedi-ECMO. Dr. Alexander’s institution received funding from ELSO and Novartis. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: In refractory respiratory failure, extracorporeal membrane oxygenation (ECMO) is a rescue therapy to prevent ventilator-induced lung injury. Optimal ventilator parameters during ECMO remain unknown. Our objective was to describe the association between mortality and ventilator parameters during ECMO for neonatal and pediatric respiratory failure., Methods: We performed a secondary analysis of the Bleeding and Thrombosis on ECMO dataset. Ventilator parameters included breathing frequency, tidal volume, peak inspiratory pressure, PEEP, dynamic driving pressure, pressure support, mean airway pressure, and F IO 2 . Parameters were evaluated before cannulation, on the calendar day of ECMO initiation (ECMO day 1), and the day before ECMO separation., Results: Of 237 included subjects analyzed, 64% were neonates, of whom 36% had a congenital diaphragmatic hernia. Of all the subjects, 67% were supported on venoarterial ECMO. Overall in-hospital mortality was 35% ( n = 83). The median (interquartile range) PEEP on ECMO day 1 was 8 (5.0-10.0) cm H 2 O for neonates and 10 (8.0-10.0) cm H 2 O for pediatric subjects. By multivariable analysis, higher PEEP on ECMO day 1 in neonates was associated with lower odds of in-hospital mortality (odds ratio 0.77, 95% CI 0.62-0.92; P = .01), with a further amplified effect in neonates with congenital diaphragmatic hernia (odds ratio 0.59, 95% CI 0.41-0.86; P = .005). No ventilator type or parameter was associated with mortality in pediatric subjects., Conclusions: Avoiding low PEEP on ECMO day 1 for neonates on ECMO may be beneficial, particularly those with a congenital diaphragmatic hernia. No additional ventilator parameters were associated with mortality in either neonatal or pediatric subjects. PEEP is a modifiable parameter that may improve neonatal survival during ECMO and requires further investigation., Competing Interests: Dr Dalton is a consultant to industry of Entegrion, Hemocue, is the medical director of Innovative ECMO Concepts, and is on the advisory board for BREATHE-Oxi 1 (Abiomed), Medtronic. The other authors have disclosed no conflicts of interest., (Copyright © 2023 by Daedalus Enterprises.)

Background: Acute brain injury (ABI) remains common after extracorporeal cardiopulmonary resuscitation (ECPR). Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO 2 ) and carbon dioxide (PaCO 2 ) on ABI occurrence., Methods: We retrospectively analyzed adult (≥18 years old) ECPR patients in the Extracorporeal Life Support Organization registry from 1/2009 through 12/2020. Composite ABI included ischemic stroke, intracranial hemorrhage (ICH), seizures, and brain death. The registry collects 2 blood gas data pre- (6 hours) and post- (24 hours) cannulation. Blood gas parameters were classified as: hypoxia (<60mm Hg), normoxia (60-119mm Hg), and mild (120-199mm Hg), moderate (200-299mm Hg), and severe hyperoxia (≥300mm Hg); hypocarbia (<35mm Hg), normocarbia (35-44mm Hg), mild (45-54mm Hg) and severe hypercarbia (≥55mm Hg). Missing values were handled using multiple imputation. Multivariable logistic regression analysis was used to assess the relationship of PaO 2 and PaCO 2 with ABI., Results: Of 3,125 patients with ECPR intervention (median age=58, 69% male), 488 (16%) experienced ABI (7% ischemic stroke; 3% ICH). In multivariable analysis, on-ECMO moderate (aOR=1.42, 95%CI: 1.02-1.97) and severe hyperoxia (aOR=1.59, 95%CI: 1.20-2.10) were associated with composite ABI. Additionally, severe hyperoxia was associated with ischemic stroke (aOR=1.63, 95%CI: 1.11-2.40), ICH (aOR=1.92, 95%CI: 1.08-3.40), and in-hospital mortality (aOR=1.58, 95%CI: 1.21-2.06). Mild hypercarbia pre-ECMO was protective of composite ABI (aOR=0.61, 95%CI: 0.44-0.84) and ischemic stroke (aOR=0.56, 95%CI: 0.35-0.89)., Conclusions: Early severe hyperoxia (≥300mm Hg) on ECMO was a significant risk factor for ABI and mortality. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: To systematically review and assimilate literature on children receiving extracorporeal membrane oxygenation (ECMO) support in pediatric acute respiratory distress syndrome (PARDS) with the goal of developing an update to the Pediatric Acute Lung Injury Consensus Conference recommendations and statements about clinical practice and research., Data Sources: Electronic searches of MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost)., Study Selection: The search used a medical subject heading terms and text words to capture studies of ECMO in PARDS or acute respiratory failure. Studies using animal models and case reports were excluded from our review., Data Extraction: Title/abstract review, full-text review, and data extraction using a standardized data collection form., Data Synthesis: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. There were 18 studies identified for full-text extraction. When pediatric data was lacking, adult and neonatal data from randomized clinical trials and observational studies were considered. Six clinical recommendations were generated related to ECMO indications, initiation, and management in PARDS. There were three good practice statements generated related to ECMO indications, initiation, and follow-up in PARDS. Two policy statements were generated involving the impact of ECMO team organization and training in PARDS. Last, there was one research statement., Conclusions: Based on a systematic literature review, we propose clinical management, good practice and policy statements within the domains of ECMO indications, initiation, team organization, team training, management, and follow-up as they relate to PARDS., Competing Interests: Dr. Barbaro’s institution received funding from the National Institutes of Health (NIH) (ARDS in Children and ECMO initiation strategies impact on Neuro-Development [ASCEND] R01 HL153519 and K12 HL138039); he disclosed that he is the Extracorporeal Life Support Organization Registry Chair; and he received support for article research from the NIH. Dr. Dalton received funding from Innovative Extracorporeal Membrane Oxygenation Concepts, Entegrion, Hemocue, and a Department of Defense grant U21-11-4603. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed., Design: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science., Setting: Not applicable., Patients: Patients with or at risk for PARDS., Interventions: None., Measurements and Main Results: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%., Conclusions: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients., Competing Interests: Dr. Barbaro is currently receiving grant support (R01 HL153519; R01 HD015434) from the National Institutes of Health (NIH); he is currently Chair of the Extracorporeal Life Support Organization Registry. Dr. Bembea receives research funding to her institution from the NIH/National Institute of Neurological Disorders and Stroke (R01NS106292) and the Grifols Investigator Sponsored Research Grant. She serves as Chair of the Scientific Committee of the Pediatric Acute Lung Injury and Sepsis Investigators Research Network. Dr. Cheifetz is a medical consultant for Phillips and Medtronic. His institution receives research grant funding from the NIH. Dr. Cruces received funding from the Chilean Ministry of Sciences (Fondecyt 1220322). Dr. Curley received funding from the NIH (UH3HL141736, R01HD098269, R01HL149910, R01HL153519, R01HD104618). Dr. Dahmer received funding from the NIH (National Institute of Child Health and Human Development [NICHD], R21 HD097387; National Heart, Lung and Blood Institute [NHLBI] R01 HL149910). Dr. Dalton received funding from the Department of Defense (No. 13363072). She is a consultant for Innovative Extracorporeal Membrane Oxygenation Concepts, Hemocue, Entegrion, Medtronic, and advisory board member for Abiomed. Dr. Emeriaud’s research program is supported by the Fonds de Recherche du Québec-Santé and the Quebec Respiratory Health Network. Dr. Emeriaud is leading a study, which is financially supported by Maquet. Dr. Jouvet’s research program and salary is supported by the Fonds de Recherche du Québec-Santé and the Quebec Respiratory Health Network. Dr. Jouvet is leading studies, which is financially supported by VitalTracer, Dymedso and public financial agencies (Canadian Foundation for innovation, Institut TransMedTech, Quebec Ministry of Health, Sainte-Justine Hospital). Dr. Killien received funding from the NIH (NICHD K23HD100566). Dr. Kneyber received research funding from the NIH/NICHD (UG3 HL141736-01/U24 HL141723-01) and ZorgOnderzoek Nederland and the area Medical (848041002), Stichting Vrienden Beatrix Kinderziekenhuis, Fonds NutsOhra, University Medical Center Groningen, VU University Medical Center, and the Royal Academy of Dutch Sciences (TerMeulen stipend). Dr. Kneyber’s research program is technically supported by Vyaire, Applied Biosignals, and Timpl. Dr. Kneyber received honoraria from Vyaire. Dr. Kneyber serves as consultant for Metran and served as consultant for Vyaire. Dr. Kudchadkar received funding to her institution from the NIH/NICHD (R01HD103811 & R21HD093369) and the Donaghue Foundation. Dr. López-Fernández is funded by an academic grant from the Instituto de Salud Carlos III, Madrid, Spain (PI19/00141). Dr. Maddux received funding to her institution from the NIH/NICHD (K23HD096018). Dr. Morrow has received honoraria for Continuing Medical Education presentations from EduPro Health. Her research is part-funded by the National Research Foundation of South Africa, through the Incentive Funding for Rated Researchers program. Dr. Nadkarni receives unrestricted research grants to his institution from the NIH, U.S. Department of Defense, Agency for Healthcare Research and Quality, Laerdal Foundation, RQI Partners, Zoll Medical, Defibtech, HeartHero, and Nihon-Kohden. Dr. Nadkarni is an elected member of the Executive Committee (Council) of the Society of Critical Care Medicine. Dr. Napolitano research and consulting relationships with: Drager, Timpel, VERO-Biotech, Actuated Medical, and Philips/Respironics. Dr. Pons has been on the speaker’s bureau of Philips, ResMed and Fisher & Paykel; Hospital Sant Joan de Déu has received disposable material from these companies. Dr. Randolph receives funding from the Centers for Disease Control and Prevention, NIH (National Institute of Allergy and Infectious Diseases AI154470). Dr. Rowan receives funding from the NHLBI (NHLBI K23HL150244). Dr. Sanchez-Pinto received funding from the NIH (NICHD R01 HD105939). Dr. Sauthier research program and salary is supported by the Fonds de Recherche du Québec-Santé. Dr. Takeuchi receives funding from Japan Society for the Promotion of Science grant (KAKENHI 21K09063). Dr. Tse receives research funding to her institution from the Canadian Institute of Health Research and salary support from the Fonds de Recherche du Québec—Santé. Dr. Watson receives research funding to his institution from the NIH. Dr. Zimmerman received research funding from NIH and Biomedical Advanced Research and Development Authority; royalties from Elsevier Publishing. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Extracorporeal carbon dioxide removal (ECCO 2 R) is a form of extracorporeal life support (ECLS) largely aimed at removing carbon dioxide in patients with acute hypoxemic or acute hypercapnic respiratory failure, so as to minimize respiratory acidosis, allowing more lung protective ventilatory settings which should decrease ventilator-induced lung injury. ECCO 2 R is increasingly being used despite the lack of high-quality evidence, while complications associated with the technique remain an issue of concern. This review explains the physiological basis underlying the use of ECCO 2 R, reviews the evidence regarding indications and contraindications, patient management and complications, and addresses organizational and ethical considerations. The indications and the risk-to-benefit ratio of this technique should now be carefully evaluated using structured national or international registries and large randomized trials., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries., Methods: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria., Results: A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10))., Conclusion: Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis., Methods: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression., Results: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0-25) and 25 (IQR 7-26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0-87) and 87 (IQR 0-88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177)., Conclusions: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting., (© 2022. The Author(s).)

Objectives: Extracorporeal membrane oxygenation (ECMO) involves complex coagulation management and frequent hemostatic complications. ECMO practice between centers is variable. To compare results between coagulation studies, standardized definitions and clear documentation of ECMO practice is essential. We assessed how study population, outcome definitions, and ECMO-, coagulation-, and transfusion-related parameters were described in pediatric ECMO studies., Data Sources: Embase, Medline, Web of Science, Cochrane Library and Google Scholar., Study Selection: English original studies of pediatric ECMO patients describing hemostatic tests or outcome., Data Extraction: Eligibility was assessed following PRISMA guidelines. Study population, outcome and ECMO-, coagulation, and transfusion parameters were summarized., Data Synthesis: A total of 107 of 1312 records were included. Study population parameters most frequently included (gestational) age (79%), gender (60%), and (birth) weight (59%). Outcomes, including definitions of bleeding (29%), thrombosis (15%), and survival (43%), were described using various definitions. Description of pump type, oxygenator and cannulation mode occurred in 49%, 45%, and 36% of studies, respectively. The main coagulation test (53%), its reference ranges (49%), and frequency of testing (24%) were the most prevalent reported coagulation parameters. The transfusion thresholds for platelets, red blood cells, and fibrinogen were described in 27%, 18%, and 18% of studies, respectively., Conclusions: This systematic review demonstrates a widespread lack of detail or standardization of several parameters in coagulation research of pediatric ECMO patients. We suggest several parameters that might be included in future coagulation studies. We encourage the ECMO community to adopt and refine this list of parameters and to use standardized definitions in future research., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: Research evaluating hemostatic agents for the treatment of clinically significant bleeding has been hampered by inconsistency and lack of standardized primary clinical trial outcomes. Clinical trials of hemostatic agents in both cardiac surgery and mechanical circulatory support, such as extracorporeal membrane oxygenation and ventricular assist devices, are examples of studies that lack implementation of universally accepted outcomes., Methods: A subgroup of experts convened by the National Heart, Lung, and Blood Institute and the US Department of Defense developed consensus recommendations for primary outcomes in cardiac surgery and mechanical circulatory support., Results: For cardiac surgery the primary efficacy endpoint of total allogeneic blood products (units vs mL/kg for pediatric patients) administered intraoperatively and postoperatively through day 5 or hospital discharge is recommended. For mechanical circulatory support outside the perioperative period the recommended primary outcome for extracorporeal membrane oxygenation is a 5-point ordinal score of thrombosis and bleeding severity adapted from the Common Terminology Criteria for Adverse Events version 5.0. The recommended primary endpoint for ventricular assist device is freedom from disabling stroke (Common Terminology Criteria for Adverse Events AE ≥ grade 3) through day 180., Conclusions: The proposed composite risk scores could impact the design of upcoming clinical trials and enable comparability of future investigations. Harmonizing and disseminating global consensus definitions and management guidelines can also reduce patient heterogeneity that would confound standardized primary outcomes in future research., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The study investigated the impact of prone positioning during venovenous extracorporeal membrane oxygenation support for coronavirus disease 2019 acute respiratory failure on the patient outcome., Design: An observational study of venovenous extracorporeal membrane oxygenation patients. We used a multistate survival model to compare the outcomes of patients treated with or without prone positioning during extracorporeal membrane oxygenation, which incorporates the dynamic nature of prone positioning and adjusts for potential confounders., Setting: Seventy-two international institutions participating in the Coronavirus Disease 2019 Critical Care Consortium international registry., Patients: Coronavirus disease 2019 patients who were supported by venovenous extracorporeal membrane oxygenation during the study period., Intervention: None., Measurements and Main Results: There were 232 coronavirus disease 2019 patients at 72 participating institutions who were supported with venovenous extracorporeal membrane oxygenation during the study period from February 16, 2020, to October 31, 2020. Proning was used in 176 patients (76%) before initiation of extracorporeal membrane oxygenation and in 67 patients (29%) during extracorporeal membrane oxygenation. Survival to hospital discharge was 33% in the extracorporeal membrane oxygenation prone group versus 22% in the extracorporeal membrane oxygenation supine group. Prone positioning during extracorporeal membrane oxygenation support was associated with reduced mortality (hazard ratio, 0.31; 95% CI, 0.14-0.68)., Conclusions: Our study highlights that prone positioning during venovenous extracorporeal membrane oxygenation support for refractory coronavirus disease 2019-related acute respiratory distress syndrome is associated with reduced mortality. Given the observational nature of the study, a randomized controlled trial of prone positioning on venovenous extracorporeal membrane oxygenation is needed to confirm these findings., Competing Interests: Dr. Jacobs received funding from SpecialtyCare and the American Academy of Dermatology. Dr. Heinsar received funding via PhD scholarship from the University of Queensland. Dr. Bassi’s institution received funding from Fisher & Paykel. Dr. Dalton received funding from Innovative Extracorporeal Membrane Oxygenation (ECMO) Concepts; she disclosed the off-label product use of ECMO equipment. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Bleeding is a common complication of extracorporeal membrane oxygenation (ECMO) for pediatric cardiac patients. We aimed to identify anticoagulation practices, cardiac diagnoses, and surgical variables associated with bleeding during pediatric cardiac ECMO by combining two established databases, the Collaborative Pediatric Critical Care Research Network (CPCCRN) Bleeding and Thrombosis in ECMO (BATE) and the Extracorporeal Life Support Organization (ELSO) Registry. Methods: All children (<19 years) with a primary cardiac diagnosis managed on ECMO included in BATE from six centers were analyzed. ELSO Registry criteria for bleeding events included pulmonary or intracranial bleeding, or red blood cell transfusion >80 ml/kg on any ECMO day. Bleeding odds were assessed on ECMO Day 1 and from ECMO Day 2 onwards with multivariable logistic regression. Results: There were 187 children with 114 (61%) bleeding events in the study cohort. Biventricular congenital heart disease (94/187, 50%) and cardiac medical diagnoses (75/187, 40%) were most common, and 48 (26%) patients were cannulated directly from cardiopulmonary bypass (CPB). Bleeding events were not associated with achieving pre-specified therapeutic ranges of activated clotting time (ACT) or platelet levels. In multivariable analysis, elevated INR and fibrinogen were associated with bleeding events (OR 1.1, CI 1.0-1.3, p = 0.02; OR 0.77, CI 0.6-0.9, p = 0.004). Bleeding events were also associated with clinical site (OR 4.8, CI 2.0-11.1, p < 0.001) and central cannulation (OR 1.75, CI 1.0-3.1, p = 0.05) but not with cardiac diagnosis, surgical complexity, or cannulation from CPB. Bleeding odds on ECMO day 1 were increased in patients with central cannulation (OR 2.82, 95% CI 1.15-7.08, p = 0.023) and those cannulated directly from CPB (OR 3.32, 95% CI 1.02-11.61, p = 0.047). Conclusions: Bleeding events in children with cardiac diagnoses supported on ECMO were associated with central cannulation strategy and coagulopathy, but were not modulated by achieving pre-specified therapeutic ranges of monitoring assays., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ankola, Bailly, Reeder, Cashen, Dalton, Dolgner, Federman, Ghassemzadeh, Himebauch, Kamerkar, Koch, Kohne, Lewen, Srivastava, Willett and Alexander.)

Thromboelastography (TEG) evaluates viscoelastic properties of blood clot formation. The TEG 5000 analyzer is commonly used but prone to errors related to vibration or operator error. The TEG 6s was developed to overcome these limitations. Performance of TEG 6s compared with TEG 5000 has not been reported in extracorporeal membrane oxygenation (ECMO). We compared the agreement between devices via a single-center prospective observational study in hospitalized adult patients on ECMO. Data for both devices were collected daily for 3 days after ECMO initiation. Standard tests for method comparison were used. Thirty-four matching samples were available for analysis. Minimal bias was noted; however, the limit of agreement was wide for TEG parameters. Visually, agreement was better for values within the reference ranges of the tests. Lin's coefficients demonstrated moderate correlation for reaction time and alpha angle (0.58; 95% confidence interval [CI], 0.31-0.76 and 0.63; 95% CI, 0.40-0.78, respectively). Excellent correlation was demonstrated for kinetic time and maximum amplitude (0.88; 95% CI, 0.79-0.94 and 0.89; 95% CI, 0.79-0.94). The TEG 6s device may represent an acceptable surrogate for the TEG 5000 in patients on ECMO. However, limitations in reliability were noted, and the devices may not be interchangeable when results fall outside of the reference values., Competing Interests: Disclosure: H.J.D. serves as a consultant to Innovative ECMO Concepts Inc. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Factors associated with mortality in coronavirus disease 2019 patients on invasive mechanical ventilation are still not fully elucidated., Objectives: To identify patient-level parameters, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation or coronavirus disease 2019., Design Setting and Participants: Prospective observational cohort study by the global Coronavirus Disease 2019 Critical Care Consortium. Patients with laboratory-confirmed coronavirus disease 2019 requiring invasive mechanical ventilation from February 2, 2020, to May 15, 2021., Main Outcomes and Measures: Patient characteristics and clinical data were assessed upon ICU admission, the commencement of invasive mechanical ventilation and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day invasive mechanical ventilation mortality., Results: One-thousand five-hundred eighty-seven patients were included in the survival analysis; 588 patients died in hospital within 28 days of commencing invasive mechanical ventilation (37%). Cox-regression analysis identified associations between the hazard of 28-day invasive mechanical ventilation mortality with age (hazard ratio, 1.26 per 10-yr increase in age; 95% CI, 1.16-1.37; p < 0.001), positive end-expiratory pressure upon commencement of invasive mechanical ventilation (hazard ratio, 0.81 per 5 cm H 2 O increase; 95% CI, 0.67-0.97; p = 0.02). Time-dependent parameters associated with 28-day invasive mechanical ventilation mortality were serum creatinine (hazard ratio, 1.28 per doubling; 95% CI, 1.15-1.41; p < 0.001), lactate (hazard ratio, 1.22 per doubling; 95% CI, 1.11-1.34; p < 0.001), Paco 2 (hazard ratio, 1.63 per doubling; 95% CI, 1.19-2.25; p < 0.001), pH (hazard ratio, 0.89 per 0.1 increase; 95% CI, 0.8-14; p = 0.041), Pao 2 /Fio 2 (hazard ratio, 0.58 per doubling; 95% CI, 0.52-0.66; p < 0.001), and mean arterial pressure (hazard ratio, 0.92 per 10 mm Hg increase; 95% CI, 0.88-0.97; p = 0.003)., Conclusions and Relevance: This international study suggests that in patients with coronavirus disease 2019 on invasive mechanical ventilation, older age and clinically relevant variables monitored at baseline or sequentially during the course of invasive mechanical ventilation are associated with 28-day invasive mechanical ventilation mortality hazard. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes., Competing Interests: Dr. Li Bassi received research support from Fisher & Paykel outside the submitted work. Dr. Dalton consults with Innovative Extracorporeal Membrane Oxygenation Concepts, Abiomed, and Instrumentation Laboratory, which does not affect the current work. Dr. Brodie receives research support from ALung Technologies, and he has been on the medical advisory boards for Baxter, Abiomed, Xenios, and Hemovent. Dr. Fan reports personal fees from ALung Technologies, Baxter, Fresenius Medical Care, Getinge, and MC3 Cardiopulmonary outside the submitted work. Dr. Laffey reports consulting fees from Baxter and Cala Medical, both outside the submitted work. Dr. Nichol is supported by a Health Research Board of Ireland Award (CTN-2014-012). Dr. Fraser receives research support from Fisher & Paykel outside the submitted work. Dr. Grasselli reports personal fees from Draeger Medical, Biotest, Getinge, Fisher & Paykel, and Merck Sharp & Dohme outside the submitted work. Dr. Hodgson is funded by the National Health and Medical Research Council Grant. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

The history of cardiopulmonary resuscitation and the Society of Critical Care Medicine have much in common, as many of the founders of the Society of Critical Care Medicine focused on understanding and improving outcomes from cardiac arrest. We review the history, the current, and future state of cardiopulmonary resuscitation., Competing Interests: Dr. Dalton received funding from Innovative ECMO Concepts, Inc; she disclosed the off-label product use of new resuscitative tools and monitoring equipment. Dr. Tisherman disclosed that he is the coauthor of a patent for “Emergency Preservation and Resuscitation Method”; he disclosed the off-label product use of normal saline and cardiopulmonary bypass equipment; he is supported by U.S. Army Medical Acquisition Activity (W81XWH1810601). Dr. Thiagarajan’s institution received funding from Bristol Myers Squibb and Pfizer; he received funding from Advocate Children’s Hospital. Dr. Alexander’s institution received funding from Novartis; she received finding from Instrumentation Laboratories; she disclosed the off-label product use of extracorporeal membrane oxygenation under extracorporeal cardiopulmonary resuscitation conditions. Dr. Kochanek received funding from Pediatric Critical Care Medicine for serving as the Editor-in-Chief, the National Institutes of Health, and the U.S. Army; he disclosed he is a patent holder for the United States Invention Disclosure, “Method to improve neurologic outcomes in temperature managed patients” (No. 62/164,205), the United States Invention Disclosure, “Small Molecule Inhibitors of RNA Binding MOTIF Proteins for the Treatment of Acute Cellular Injury” and the United States Patent 8,628,512 B2, “Method of Inducing EPR Following Cardiopulmonary Arrest”. Dr. Kochanek is supported by NS105721 from the National Institutes of Neurologic Disorders and Stroke/the National Institutes of Health, and the American Heart Association (18TPA34170553). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)