Challenges in determining death by neurologic criteria in extracorporeal membrane oxygenation - A single center experience.

INTRODUCTION: Apnea test (AT) in patients on extracorporeal membrane oxygenation (ECMO) support is challenging, leading to variation in determining death by neurologic criteria (DNC). We aim to describe the diagnostic criteria and barriers for DNC in adults on ECMO in a tertiary care center. METHODS: A retrospective review of a prospective observational standardized neuromonitoring study was conducted in adult VA- and VV-ECMO patients at a tertiary center from June 2016 to March 2022. Brain death was defined according to the 2010 American Academy of Neurology guidelines and following the 2020 World Brain Death Project recommendations for performing AT in ECMO patients. RESULTS: Eight (2.7%) ECMO patients (median age = 44 years, 75% male, 50% VA-ECMO) met criteria for DNC, six (75%) of whom were determined with AT. In the other two patients who did not undergo AT due to safety concerns, ancillary tests (transcranial doppler and electroencephalography) were consistent with DNC. An additional seven (2.3%) patients (median age = 55 years, 71% male, 86% VA-ECMO) were noted to have absent brainstem reflexes but failed to complete determination of DNC as they underwent withdrawal of life-sustaining treatment (WLST) before a full evaluation was completed. In these patients, AT was never performed, and ancillary tests were inconsistent with either neurological exam findings and/or neuroimaging supporting DNC, or with each other. CONCLUSION: AT was used safely and successfully in 6 of the 8 ECMO patients diagnosed with DNC and was always consistent with the neurological exam and imaging findings, as opposed to ancillary tests alone.

Critically Ill Patients Treated for Chimeric Antigen Receptor-Related Toxicity: A Multicenter Study.

OBJECTIVES: To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. DESIGN: Retrospective cohort study. SETTING: Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative. PATIENTS: Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019. INTERVENTIONS: Demographics, toxicities, specific interventions, and outcomes were collected. RESULTS: One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3-4 toxicities (66.7%); 15.2% had grade 3-4 cytokine release syndrome and 64% grade 3-4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64-not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival. CONCLUSIONS: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.

Review of the published literature to characterise clinical excellence in COVID-19 care.

COVID-19 continues to be a major source of global morbidity and mortality. It abruptly stressed healthcare systems early in 2020 and the pressures continue. Devastating hardships have been endured by individuals, families and communities; the losses will be felt for years to come. As healthcare professionals and organisations stepped up to respond to the overwhelming number of cases, it is understandable that the focus has been primarily on coping with the quantity of the demand. During a pandemic, it is not surprising that few papers have drawn attention to the quality of the care delivered to those afflicted with illness. Despite the challenges, clinicians caring for patients with COVID-19 have risen to the occasion. This manuscript highlights aspirational examples from the published literature of thoughtful and superb care of patients with COVID-19 using an established framework for clinical excellence (formulated by the Miller-Coulson Academy of Clinical Excellence).

Pathophysiology of Brain Injury and Neurological Outcome in Acute Respiratory Distress Syndrome: A Scoping Review of Preclinical to Clinical Studies.

Acute respiratory distress syndrome (ARDS) has been associated with secondary acute brain injury (ABI). However, there is sparse literature on the mechanism of lung-mediated brain injury and prevalence of ARDS-associated secondary ABI. We aimed to review and elucidate potential mechanisms of ARDS-mediated ABI from preclinical models and assess the prevalence of ABI and neurological outcome in ARDS with clinical studies. We conducted a systematic search of PubMed and five other databases reporting ABI and ARDS through July 6, 2020 and included studies with ABI and neurological outcome occurring after ARDS. We found 38 studies (10 preclinical studies with 143 animals; 28 clinical studies with 1175 patients) encompassing 9 animal studies (n = 143), 1 in vitro study, 12 studies on neurocognitive outcomes (n = 797), 2 clinical observational studies (n = 126), 1 neuroimaging study (n = 15), and 13 clinical case series/reports (n = 15). Six ARDS animal studies demonstrated evidence of neuroinflammation and neuronal damage within the hippocampus. Five animal studies demonstrated altered cerebral blood flow and increased intracranial pressure with the use of lung-protective mechanical ventilation. High frequency of ARDS-associated secondary ABI or poor neurological outcome was observed ranging 82-86% in clinical observational studies. Of the clinically reported ABIs (median age 49 years, 46% men), the most common injury was hemorrhagic stroke (25%), followed by hypoxic ischemic brain injury (22%), diffuse cerebral edema (11%), and ischemic stroke (8%). Cognitive impairment in patients with ARDS (n = 797) was observed in 87% (range 73-100%) at discharge, 36% (range 32-37%) at 6 months, and 30% (range 25-45%) at 1 year. Mechanisms of ARDS-associated secondary ABI include primary hypoxic ischemic injury from hypoxic respiratory failure, secondary injury, such as lung injury induced neuroinflammation, and increased intracranial pressure from ARDS lung-protective mechanical ventilation strategy. In summary, paucity of clinical data exists on the prevalence of ABI in patients with ARDS. Hemorrhagic stroke and hypoxic ischemic brain injury were commonly observed. Persistent cognitive impairment was highly prevalent in patients with ARDS.

Critical Care Management of Toxicities Associated With Targeted Agents and Immunotherapies for Cancer.

OBJECTIVES: To describe the most common serious adverse effects and organ toxicities associated with emerging therapies for cancer that may necessitate admission to the ICU. DATA SOURCES AND STUDY SELECTION: PubMed and Medline search of relevant articles in English on the management of adverse effects of immunotherapy for cancer. DATA EXTRACTION AND DATA SYNTHESIS: Targeted therapies including tyrosine kinase inhibitors, monoclonal antibodies, checkpoint inhibitors, and immune effector cell therapy have improved the outcome and quality of life of patients with cancer. However, severe and life-threatening side effects can occur. These toxicities include infusion or hypersensitivity reactions, cytokine release syndrome, pulmonary, cardiac, renal, hepatic, and neurologic toxicities, hemophagocytic lymphohistiocytosis, opportunistic infections, and endocrinopathies. Cytokine release syndrome is the most common serious toxicity after administration of monoclonal antibodies and immune effector cell therapies. Most of the adverse events from immunotherapy results from an exaggerated T-cell response directed against normal tissue, resulting in the generation of high levels of proinflammatory cytokines. Toxicities from targeted therapies are usually secondary to "on target toxicities." Management is largely supportive and may include discontinuation of the specific agent, corticosteroids, and other immune suppressing agents for severe (grade 3 or 4) immune-related adverse events like neurotoxicity and pneumonitis. CONCLUSIONS: The complexity of toxicities associated with modern targeted and immunotherapeutic agents for cancer require a multidisciplinary approach among ICU staff, oncologists, and organ specialists and adoption of standardized treatment protocols to ensure the best possible patient outcomes.

Performance of Critical Care Outcome Prediction Models in an Intermediate Care Unit.

BACKGROUND: Intermediate care units (IMCUs) are heterogeneous in design and operation, which makes comparative effectiveness studies challenging. A generalizable outcome prediction model could improve such comparisons. However, little is known about the performance of critical care outcome prediction models in the intermediate care setting. The purpose of this study is to evaluate the performance of the Acute Physiology and Chronic Health Evaluation version II (APACHE II), Simplified Acute Physiology Score version II (SAPS II) and version 3 (SAPS 3), and Mortality Probability Model version III (MPM0III) in patients admitted to a well-characterized IMCU. MATERIALS AND METHODS: In the IMCU of an academic medical center (July to December 2012), the discrimination and calibration of each outcome prediction model were evaluated using the area under the receiver-operating characteristic and Hosmer-Lemeshow goodness-of-fit test, respectively. Standardized mortality ratios (SMRs) were also calculated. RESULTS: The cohort included data from 628 unique IMCU admissions with an inpatient mortality rate of 8.3%. All models exhibited good discrimination, but only the SAPS II and MPM0III were well calibrated. While the APACHE II and SAPS 3 both markedly overestimated mortality, the SMR for the SAPS II and MPM0III were 0.91 and 0.91, respectively. CONCLUSIONS: The SAPS II and MPM0III exhibited good discrimination and calibration, with slight overestimation of mortality. Each model should be further evaluated in multicenter studies of patients in the intermediate care setting.

Mechanical Ventilation Management during Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome. An International Multicenter Prospective Cohort.

Rationale: Current practices regarding mechanical ventilation in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown.Objectives: To report current practices regarding mechanical ventilation in patients treated with ECMO for severe acute respiratory distress syndrome (ARDS) and their association with 6-month outcomes.Methods: This was an international, multicenter, prospective cohort study of patients undergoing ECMO for ARDS during a 1-year period in 23 international ICUs.Measurements and Main Results: We collected demographics, daily pre- and per-ECMO mechanical ventilation settings and use of adjunctive therapies, ICU, and 6-month outcome data for 350 patients (mean ± SD pre-ECMO PaO2/FiO2 71 ± 34 mm Hg). Pre-ECMO use of prone positioning and neuromuscular blockers were 26% and 62%, respectively. Vt (6.4 ± 2.0 vs. 3.7 ± 2.0 ml/kg), plateau pressure (32 ± 7 vs. 24 ± 7 cm H2O), driving pressure (20 ± 7 vs. 14 ± 4 cm H2O), respiratory rate (26 ± 8 vs. 14 ± 6 breaths/min), and mechanical power (26.1 ± 12.7 vs. 6.6 ± 4.8 J/min) were markedly reduced after ECMO initiation. Six-month survival was 61%. No association was found between ventilator settings during the first 2 days of ECMO and survival in multivariable analysis. A time-varying Cox model retained older age, higher fluid balance, higher lactate, and more need for renal-replacement therapy along the ECMO course as being independently associated with 6-month mortality. A higher Vt and lower driving pressure (likely markers of static compliance improvement) across the ECMO course were also associated with better outcomes.Conclusions: Ultraprotective lung ventilation on ECMO was largely adopted across medium- to high-case volume ECMO centers. In contrast with previous observations, mechanical ventilation settings during ECMO did not impact patients' prognosis in this context.

Management of the Critically Ill Adult Chimeric Antigen Receptor-T Cell Therapy Patient: A Critical Care Perspective.

OBJECTIVES: Chimeric antigen receptor T-cell therapy, a type of immune effector therapy for cancer, has demonstrated encouraging results in clinical trials for the treatment of patients with refractory hematologic malignancies. Nevertheless, there are toxicities specific to these treatments that, if not recognized and treated appropriately, can lead to multiple organ failure and death. This article is a comprehensive review of the available literature and provides, from a critical care perspective, recommendations by experienced intensivists in the care of critically ill adult chimeric antigen receptor T-cell patients. DATA SOURCES: PubMed and Medline search of articles published from 2006 to date. STUDY SELECTION: Clinical studies, reviews, or guidelines were selected and reviewed by the authors. DATA EXTRACTION: Not available. DATA SYNTHESIS: Not available. CONCLUSIONS: Until modifications in chimeric antigen receptor T-cell therapy decrease their toxicities, the intensivist will play a leading role in the management of critically ill chimeric antigen receptor T-cell patients. As this novel immunotherapeutic approach becomes widely available, all critical care clinicians need to be familiar with the recognition and management of complications associated with this treatment.

Red blood cell transfusion triggers in acute leukemia: a randomized pilot study.

BACKGROUND: Red blood cell (RBC) transfusion thresholds have yet to be examined in large randomized trials in hematologic malignancies. This pilot study in acute leukemia uses a restrictive compared to a liberal transfusion strategy. STUDY DESIGN AND METHODS: A randomized (2:1) study was conducted of restrictive (LOW) hemoglobin (Hb) trigger (7 g/dL) compared to higher (HIGH) Hb trigger (8 g/dL). The primary outcome was feasibility of conducting a larger trial. The four requirements for success required that more than 50% of the eligible patients could be consented, more than 75% of the patients randomized to the LOW arm tolerated the transfusion trigger, fewer than 15% of patients crossed over from the LOW arm to the HIGH arm, and no indication for the need to pause the study for safety concerns. Secondary outcomes included fatigue, bleeding, and RBCs and platelets transfused. RESULTS: Ninety patients were consented and randomly assigned to LOW to HIGH. The four criteria for the primary objective of feasibility were met. When the number of units transfused was compared, adjusting for baseline Hb, the LOW arm was transfused on average 8.0 (95% confidence interval [CI], 6.9-9.1) units/patient while the HIGH arm received 11.7 (95% CI, 10.1-13.2) units (p = 0.0003). There was no significant difference in bleeding events or neutropenic fevers between study arms. CONCLUSION: This study establishes feasibility for trial of Hb thresholds in leukemia through demonstration of success in all primary outcome metrics and a favorable safety profile. This population requires further study to evaluate the equivalence of liberal and restrictive transfusion thresholds in this unique clinical setting.

Postoperative Critical Care of the Adult Cardiac Surgical Patient. Part I: Routine Postoperative Care.

OBJECTIVES: Cardiac surgery, including coronary artery bypass, cardiac valve, and aortic procedures, is among the most common surgical procedures performed in the United States. Successful outcomes after cardiac surgery depend on optimum postoperative critical care. The cardiac intensivist must have a comprehensive understanding of cardiopulmonary physiology and the sequelae of cardiopulmonary bypass. In this concise review, targeted at intensivists and surgeons, we discuss the routine management of the postoperative cardiac surgical patient. DATA SOURCE AND SYNTHESIS: Narrative review of relevant English-language peer-reviewed medical literature. CONCLUSIONS: Critical care of the cardiac surgical patient is a complex and dynamic endeavor. Adequate fluid resuscitation, appropriate inotropic support, attention to rewarming, and ventilator management are key components. Patient safety is enhanced by experienced personnel, a structured handover between the operating room and ICU teams, and appropriate transfusion strategies.

Postoperative Critical Care of the Adult Cardiac Surgical Patient: Part II: Procedure-Specific Considerations, Management of Complications, and Quality Improvement.

OBJECTIVES: The armamentarium of cardiac surgery continues to expand, and the cardiac intensivist must be familiar with a broad spectrum of procedures and their specific management concerns. In the conclusion of this two-part review, we will review procedure-specific concerns after cardiac surgery and the management of common complications. We also discuss performance improvement and outcome assurance. DATA SOURCE AND SYNTHESIS: Narrative review of relative English language peer-reviewed medical literature. CONCLUSIONS: Knowledge of procedure-specific sequelae informs anticipation and prevention of many complications after cardiac surgery. Most complications after cardiac surgery fall into a limited number of categories. Familiarity with common complications combined with a structured approach to management facilitates response to even the most complicated postoperative situations. Standardized care and constant self-examination are essential for programmatic improvement and consistent high-quality care.

Protein kinase G increases antioxidant function in lung microvascular endothelial cells by inhibiting the c-Abl tyrosine kinase.

Oxidant injury contributes to acute lung injury (ALI). We previously reported that activation of protein kinase GI (PKGI) posttranscriptionally increased the key antioxidant enzymes catalase and glutathione peroxidase 1 (Gpx-1) and attenuated oxidant-induced cytotoxicity in mouse lung microvascular endothelial cells (MLMVEC). The present studies tested the hypothesis that the antioxidant effect of PKGI is mediated via inhibition of the c-Abl tyrosine kinase. We found that activation of PKGI with the cGMP analog 8pCPT-cGMP inhibited c-Abl activity and decreased c-Abl expression in wild-type but not PKGI(-/-) MLMVEC. Treatment of wild-type MLMVEC with atrial natriuretic peptide also inhibited c-Abl activation. Moreover, treatment of MLMVEC with the c-Abl inhibitor imatinib increased catalase and GPx-1 protein in a posttranscriptional fashion. In imatinib-treated MLMVEC, there was no additional effect of 8pCPT-cGMP on catalase or GPx-1. The imatinib-induced increase in antioxidant proteins was associated with an increase in extracellular H2O2 scavenging by MLMVEC, attenuation of oxidant-induced endothelial barrier dysfunction, and prevention of oxidant-induced endothelial cell death. Finally, in the isolated perfused lung, imatinib prevented oxidant-induced endothelial toxicity. We conclude that cGMP, through activation of PKGI, inhibits c-Abl, leading to increased key antioxidant enzymes and resistance to lung endothelial oxidant injury. Inhibition of c-Abl by active PKGI may be the downstream mechanism underlying PKGI-mediated antioxidant signaling. Tyrosine kinase inhibitors may represent a novel therapeutic approach in oxidant-induced ALI.

Palliative Care Utilization in Patients Requiring Extracorporeal Membrane Oxygenation: An Observational Study.

Palliative care (PC) is a model of care centered around improving the quality of life for individuals with life-limiting illnesses. Few studies have examined its impact in patients on extracorporeal membrane oxygenation (ECMO). We aimed to describe demographics, clinical characteristics, and complications associated with PC consultation in adult patients requiring ECMO support. We analyzed data from an ECMO registry, including patients aged 18 years and older who have received either venoarterial (VA)- or venovenous (VV)-ECMO support between July 2016 and September 2021. We used analysis of variance and Fisher exact tests to identify factors associated with PC consultation. Of 256, 177 patients (69.1%) received VA-ECMO support and 79 (30.9%) received VV-ECMO support. Overall, 115 patients (44.9%) received PC consultation while on ECMO. Patients receiving PC consultation were more likely to be non-white (47% vs. 53%, p = 0.016), have an attending physician from a medical versus surgical specialty (65.3% vs. 39.6%), have VV-ECMO (77.2% vs. 30.5%, p < 0.001), and have longer ECMO duration (6.2 vs. 23.0, p < 0.001). Patients were seen by the PC team on an average of 7.6 times (range, 1-35), with those who died having significantly more visits (11.2 vs. 5.6, p < 0.001) despite the shorter hospital stay. The average time from cannulation to the first PC visit was 5.3 ± 5 days. Congestive heart failure in VA-ECMO, coronavirus disease 2019 infection in VV-ECMO, and non-white race and longer ECMO duration for all patients were associated with PC consultation. We found that despite the benefits of PC, it is underused in this population.

Extracorporeal membrane oxygenation in adults receiving haematopoietic cell transplantation: an international expert statement.

Combined advances in haematopoietic cell transplantation (HCT) and intensive care management have improved the survival of patients with haematological malignancies admitted to the intensive care unit. In cases of refractory respiratory failure or refractory cardiac failure, these advances have led to a renewed interest in advanced life support therapies, such as extracorporeal membrane oxygenation (ECMO), previously considered inappropriate for these patients due to their poor prognosis. Given the scarcity of evidence-based guidelines on the use of ECMO in patients receiving HCT and the need to provide equitable and sustainable access to ECMO, the European Society of Intensive Care Medicine, the Extracorporeal Life Support Organization, and the International ECMO Network aimed to develop an expert consensus statement on the use of ECMO in adult patients receiving HCT. A steering committee with expertise in ECMO and HCT searched the literature for relevant articles on ECMO, HCT, and immune effector cell therapy, and developed opinion statements through discussions following a Quaker-based consensus approach. An international panel of experts was convened to vote on these expert opinion statements following the Research and Development/University of California, Los Angeles Appropriateness Method. The Appraisal of Guidelines for Research and Evaluation statement was followed to prepare this Position Paper. 36 statements were drafted by the steering committee, 33 of which reached strong agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and expert panel, and rephrased before an additional round of voting. At the conclusion of the process, 33 statements received strong agreement and three weak agreement. This Position Paper could help to guide intensivists and haematologists during the difficult decision-making process regarding ECMO candidacy in adult patients receiving HCT. The statements could also serve as a basis for future research focused on ECMO selection criteria and bedside management.

Incidence and Outcomes of Respiratory Failure after Nonmyeloablative Related Haploidentical Blood or Marrow Transplantation.

Respiratory failure is a devastating complication of allogenic blood or marrow transplantation (BMT). Prior data suggest that respiratory failure occurs in 20% of BMT recipients and acute respiratory distress syndrome (ARDS) occurs in 15%. Nonmyeloablative (NMA) haploidentical BMT allows donor pool expansion and may decrease complications. Incidence, outcomes, and risk factors for respiratory failure after NMA haploidentical BMT are unknown. This study aimed to determine the incidence of respiratory failure after NMA haploidentical BMT and explore outcomes and risk factors for respiratory failure. In this single-center, retrospective study of all patients age >18 years undergoing NMA haploidentical BMT between 2004 and 2016, the primary outcome was respiratory failure, marked by the use of high-flow nasal cannula oxygen, noninvasive ventilation (NIV), or invasive mechanical ventilation (IMV) within 2 years after BMT. Respiratory failure incidence is reported as incidence rate ratio (IRR) with 95% confidence interval (CI). Unadjusted and multivariable Cox proportional hazards models with adjustment for a priori identified patient-level characteristics were used. Results are presented as hazard ratio (HR) with 95% CI. A total of 520 patients underwent NMA haploidentical BMT, of whom 82 (15.8%) developed respiratory failure (IRR, 0.114/person-year) at a median of 0.34 year (interquartile range, 0.06 to 0.75 year) after BMT. Older age (HR, 1.04; 95% CI, 1.02 to 1.07), transplantation for myelodysplastic syndrome (MDS) (HR, 1.99; 95% CI, 1.07 to 3.72), and parent donor (HR, 3.49; 95% CI, 1.32 to 9.26) were associated with an increased risk of respiratory failure, whereas higher pretransplantation lung diffusion capacity of carbon monoxide (DLCO; % of predicted) was associated with lower risk (HR, 0.98; 95% CI, 0.77 to 0.99). Sixty-one patients (11.7%) required IMV, and 30 were successfully extubated. Only 37 patients (7%) had ARDS. Of the 82 patients with respiratory failure, 43 (52.4%) died during index hospitalization and 61 (77.2%) died by 2 years post-transplantation. Only 40 (49%) had nonrelapse mortality. The incidence of respiratory failure and ARDS after NMA haploidentical BMT is modest at 15% by 2 years post-transplantation. Despite successful extubation in >50% of patients, respiratory failure, regardless of cause, is associated with a high rate of death by 2 years from both relapse and nonrelapse causes. Age, BMT for MDS, parental donor, and pretransplantation DLCO are risk factors for respiratory failure.

Multisite implementation of a workflow-integrated machine learning system to optimize COVID-19 hospital admission decisions.

Demand has outstripped healthcare supply during the coronavirus disease 2019 (COVID-19) pandemic. Emergency departments (EDs) are tasked with distinguishing patients who require hospital resources from those who may be safely discharged to the community. The novelty and high variability of COVID-19 have made these determinations challenging. In this study, we developed, implemented and evaluated an electronic health record (EHR) embedded clinical decision support (CDS) system that leverages machine learning (ML) to estimate short-term risk for clinical deterioration in patients with or under investigation for COVID-19. The system translates model-generated risk for critical care needs within 24 h and inpatient care needs within 72 h into rapidly interpretable COVID-19 Deterioration Risk Levels made viewable within ED clinician workflow. ML models were derived in a retrospective cohort of 21,452 ED patients who visited one of five ED study sites and were prospectively validated in 15,670 ED visits that occurred before (n = 4322) or after (n = 11,348) CDS implementation; model performance and numerous patient-oriented outcomes including in-hospital mortality were measured across study periods. Incidence of critical care needs within 24 h and inpatient care needs within 72 h were 10.7% and 22.5%, respectively and were similar across study periods. ML model performance was excellent under all conditions, with AUC ranging from 0.85 to 0.91 for prediction of critical care needs and 0.80-0.90 for inpatient care needs. Total mortality was unchanged across study periods but was reduced among high-risk patients after CDS implementation.

Calculated Plasma Volume Status Is Associated With Mortality in Acute Respiratory Distress Syndrome.

The optimal method to assess fluid overload in acute respiratory distress syndrome is not known, and current techniques have limitations. Plasma volume status has emerged as a noninvasive method to assess volume status and is defined as the percentage alteration from ideal plasma volume. We hypothesized that plasma volume status would suggest the presence of significant excess volume and therefore correlate with mortality in acute respiratory distress syndrome. DESIGN AND SETTING: This is a retrospective cohort study of subjects enrolled in four previously completed National Heart Lung and Blood Institute-sponsored acute respiratory distress syndrome trials, using data from the National Institutes of Health Biologic Specimen and Data Repository Information Coordinating Center repository. PATIENTS: Study subjects included 3,165 patients with acute respiratory distress syndrome previously enrolled in National Heart Lung and Blood Institute-sponsored acute respiratory distress syndrome trials. MEASUREMENTS AND MAIN RESULTS: The exposure variable of interest was plasma volume status, calculated as the percentage alteration of actual plasma volume calculated on the basis of weight and hematocrit using sex-specific constants. We performed Kaplan-Meier survival analysis and univariable and adjusted Cox proportional hazard models to determine the association of plasma volume status with 60-day mortality. The median age of subjects was 52 years (interquartile range, 40-63 yr). Median plasma volume status was 5.9% (interquartile range, -2.4% to 13.6%), and overall, 68% of subjects had positive plasma volume status suggesting plasma volume higher than ideal plasma volume. In adjusted models, plasma volume status greater than median was associated with 38% greater risk for mortality (hazard ratio, 1.38; 95% CI, 1.20-1.59; p < 0.001). Each interquartile range increase in plasma volume status was associated with greater mortality in adjusted models (hazard ratio, 1.24 per interquartile range increase; 95% CI, 1.13-1.36; p < 0.001). Plasma volume status greater than median was associated with fewer ventilator-free days (18 vs 19 d; p = 0.0026) and ICU-free days (15 vs 17 d; p = 0.0001). CONCLUSIONS: Plasma volume status is independently associated with mortality, ICU-free days, and ventilator-free days among subjects with acute respiratory distress syndrome. Plasma volume status could be considered for risk-stratification and to direct therapy, particularly fluid management.

Operational Recommendations for Scarce Resource Allocation in a Public Health Crisis.

The coronavirus disease 2019 pandemic may require rationing of various medical resources if demand exceeds supply. Theoretical frameworks for resource allocation have provided much needed ethical guidance, but hospitals still need to address objective practicalities and legal vetting to operationalize scarce resource allocation schemata. To develop operational scarce resource allocation processes for public health catastrophes, including the coronavirus disease 2019 pandemic, five health systems in Maryland formed a consortium-with diverse expertise and representation-representing more than half of all hospitals in the state. Our efforts built on a prior statewide community engagement process that determined the values and moral reference points of citizens and health-care professionals regarding the allocation of ventilators during a public health catastrophe. Through a partnership of health systems, we developed a scarce resource allocation framework informed by citizens' values and by general expert consensus. Allocation schema for mechanical ventilators, ICU resources, blood components, novel therapeutics, extracorporeal membrane oxygenation, and renal replacement therapies were developed. Creating operational algorithms for each resource posed unique challenges; each resource's varying nature and underlying data on benefit prevented any single algorithm from being universally applicable. The development of scarce resource allocation processes must be iterative, legally vetted, and tested. We offer our processes to assist other regions that may be faced with the challenge of rationing health-care resources during public health catastrophes.