OBJECTIVES:A temperature control strategy is strongly recommended for comatose in-hospital cardiac arrest (IHCA) survivors. We aimed to investigate variation in adherence to this recommendation and associations with outcomes, which have not been comprehensively assessed for IHCA. DESIGN:Prospective observational cohort study with data collected from October 2023 to June 2024. SETTING:Multicenter, international (24 hospital systems, 46 enrolling hospitals). PATIENTS:Adults who suffered IHCA, survived initial resuscitation, and remained comatose and eligible for temperature control. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:The main exposure was documentation of a temperature control strategy in the first 24 hours after arrest. Outcomes were survival to hospital discharge (primary), use of temperature control therapy, fever (temperature ≥ 38°C), favorable functional outcome (modified Rankin Scale ≤ 3), and favorable neurologic outcome (Cerebral Performance Category score ≤ 2). Among 1006 enrolled patients, 615 (61.1%) remained comatose and were eligible for temperature control; of those, 273 (44.4%) had a documented temperature control strategy. A documented strategy was associated with higher adjusted odds of receiving a temperature control therapy (adjusted odds ratio [aOR], 21.3; 95% CI, 12.3-36.7; p < 0.01), and lower adjusted odds of fever in the first 24 hours after resuscitation (aOR, 0.63; 95% CI, 0.43-0.92; p = 0.02). Having a strategy, compared with not, had no statistically significant association with survival (32.6% vs. 28.1%; aOR, 1.19; 95% CI, 0.79-1.80; p = 0.42), favorable functional outcome (9.9% vs. 10.5%; aOR, 1.14; 95% CI, 0.53-2.42; p = 0.74), or favorable neurologic outcome (12.8% vs. 12.3%; aOR, 1.15; 95% CI, 0.63-2.12; p = 0.65). Hospital system specific proportions of temperature control strategy ranged from 0% to 100%. CONCLUSIONS:Among comatose IHCA survivors, more than half received no documented temperature control strategy. Those with a strategy were less likely to have a fever and more likely to receive temperature control directed therapy, but showed no difference in survival, functional, or neurologic outcomes.

Rationale: The WHO describes patient blood management as a system- and evidence-based, patient-focused approach to improving patient care by limiting unnecessary blood and blood product transfusion. This retrospective study describes the effectiveness of an enterprise-wide patient blood management program in improving adherence to international society guidelines and reducing healthcare costs.Methods: This is a retrospective descriptive analysis of the effectiveness of a patient blood management initiative instituted at an 18-hospital healthcare enterprise in December 2019. Data from January 2020 to April 2024 was analyzed. The initiative identifies clinical leaders and creates multidisciplinary committees that use iterative transfusion data to promote awareness, educate clinicians on internationally recognized transfusion thresholds, and provide targeted feedback on clinical practice. Targeted packed red blood cell (pRBC) transfusion goals included increasing the percentage of transfusions performed for patients with hemoglobin less than 7 g/dL, decreasing the percentage of transfusions for patients with a hemoglobin greater than 8 g/dL, and increasing the percentage of single-unit transfusions.Results: Data collected between January 2020 and April 2024 shows a significant inverse relationship between the duration of the patient blood management program and the use of pRBCs per 100 patient days within the enterprise r(50) = 0.82, p < 0.001. Over this time frame, there was an increase in the percentage of pRBC transfusions for patients with hemoglobin less than 7 g/dL, 73% to 81%, a decrease in the percentage of transfusions for patients with hemoglobin greater than 8 g/dL, from 8% to 6%, and an increase in the percentage of single unit transfusion orders from 84% to 90%. Cost analysis using an estimated cost of $1500 for the transfusion of a single unit of pRBC leads to an estimated cost savings of $5460 per 100 patient days for the enterprise and a total cost savings of $11.3 million per year.Conclusions: Using EMR overlays, focused education, and proactive decision support, our healthcare system was able to reduce blood product use and the associated healthcare costs. The intensity of interventions varied based on the local champions, but these focused interventions had sustained results. This project could be expanded to improve the protection of a limited resource or highlight patient-related outcomes dependent on reduced transfusions. The primary goal of this study was to show that a multi-disciplinary effort can effect change and sustainably reduce healthcare costs.

IMPORTANCE: In-hospital cardiac arrest (IHCA) is a significant public health burden. Rates of return of spontaneous circulation (ROSC) have been improving, but the best way to care for patients after the initial resuscitation remains poorly understood, and improvements in survival to discharge are stagnant. Existing North American cardiac arrest databases lack comprehensive data on the post-resuscitation period, and we do not know current post-IHCA practice patterns. To address this gap, we developed the Discover In-Hospital Cardiac Arrest (Discover IHCA) study, which will thoroughly evaluate current post-IHCA care practices across a diverse cohort. OBJECTIVES: Our study collects granular data on post-IHCA treatment practices, focusing on temperature control and prognostication, with the objective of describing variation in current post-IHCA practice. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter, prospectively collected, observational cohort study of patients who have suffered IHCA and have been successfully resuscitated (achieved ROSC). There are 24 enrolling hospital systems (23 in the United States) with 69 individual enrolling hospitals (39 in the United States). We developed a standardized data dictionary, and data collection began in October 2023, with a projected 1000 total enrollments. Discover IHCA is endorsed by the Society of Critical Care Medicine. INTERVENTIONS, OUTCOMES, AND ANALYSIS: The study collects data on patient characteristics including pre-arrest frailty, arrest characteristics, and detailed information on post-arrest practices and outcomes. Data collection on post-IHCA practice was structured around current American Heart Association and European Resuscitation Council guidelines. Among other data elements, the study captures post-arrest temperature control interventions and post-arrest prognostication methods. Analysis will evaluate variations in practice and their association with mortality and neurologic function. CONCLUSIONS: We expect this study, Discover IHCA, to identify variability in practice and outcomes following IHCA, and be a vital resource for future investigations into best-practice for managing patients after IHCA.

1Sidney Kimmel Medical College at Thomas Jefferson University 2Thomas Jefferson University Hospital 3Thomas Jefferson University Hospital, Philadlphia, PA

Severely ill patients with COVID-19 are challenging to sedate and often require high-dose sedation and analgesic regimens. Ketamine can be an effective adjunct to facilitate sedation of critically ill patients but its effects on sedation level and inflammation in COVID-19 patients have not been studied. This retrospective, observational cohort study evaluated the effect of ketamine infusions on inflammatory biomarkers and clinical outcomes in mechanically ventilated patients with SARS-CoV-2 infection. A total of 186 patients were identified (47 received ketamine, 139 did not). Patients who received ketamine were significantly younger than those who did not (mean (standard deviation) 59.2 (14.2) years versus 66.3 (14.4) years; P = 0.004), but there was no statistically significant difference in body mass index ( P = 0.25) or sex distribution ( P = 0.91) between groups. Mechanically ventilated patients who received ketamine infusions had a statistically significant reduction in Richmond Agitation-Sedation Scale score (–3.0 versus –2.0, P < 0.001). Regarding inflammatory biomarkers, ketamine was associated with a reduction in ferritin ( P = 0.02) and lactate ( P = 0.01), but no such association was observed for C-reactive protein ( P = 0.27), lactate dehydrogenase ( P = 0.64) or interleukin-6 ( P = 0.87). No significant association was observed between ketamine administration and mortality (odds ratio 0.971; 95% confidence interval 0.501 to 1.882; P = 0.93). Ketamine infusion was associated with improved sedation depth in mechanically ventilated COVID-19 patients and provided a modest anti-inflammatory benefit but did not confer benefit with respect to mortality or intensive care unit length of stay.

The Cooling to Help Injured Lungs (CHILL) trial is an open label, two group, parallel design multicenter, randomized phase IIB clinical trial assessing the efficacy and safety of targeted temperature management with combined external cooling and neuromuscular blockade to block shivering in patients with early moderate-severe acute respiratory distress syndrome (ARDS). This report provides the background and rationale for the clinical trial and outlines the methods using the Consolidated Standards of Reporting Trials guidelines. Key design challenges include: [1] protocolizing important co-interventions; [2] incorporation of patients with COVID-19 as the cause of ARDS; [3] inability to blind the investigators; and [4] ability to obtain timely informed consent from patients or legally authorized representatives early in the disease process. Results of the Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial informed the decision to mandate sedation and neuromuscular blockade only in the group assigned to therapeutic hypothermia and proceed without this mandate in the control group assigned to a usual temperature management protocol. Previous trials conducted in National Heart, Lung, and Blood Institute ARDS Clinical Trials (ARDSNet) and Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks informed ventilator management, ventilation liberation and fluid management protocols. Since ARDS due to COVID-19 is a common cause of ARDS during pandemic surges and shares many features with ARDS from other causes, patients with ARDS due to COVID-19 are included. Finally, a stepwise approach to obtaining informed consent prior to documenting critical hypoxemia was adopted to facilitate enrollment and reduce the number of candidates excluded because eligibility time window expiration.

INTRODUCTION:Systemic inflammatory response syndrome (SIRS) is frequently observed following decannulation from extracorporeal membrane oxygenation (ECMO). Differentiating cytokine release due to infection from endothelial injury from cannula removal and/or discontinuation from the ECMO circuit has been shown to impact treatment and outcomes. This response, however, may be complicated in COVID-19 patients due to prevalent glucocorticoid and immune modulator use. It remains unclear whether COVID-19 infection and/or associated immune modulator use impact the incidence of SIRS following decannulation.OBJECTIVES:The aim of this study is to investigate the incidence of the SIRS phenomenon and associated outcomes in patients with COVID-19 after ECMO decannulation.METHODS:An IRB-approved retrospective chart review of all patients who survived ECMO between June 31, 2010 and July 7, 2021 was done to identify patients who experienced SIRS within 48 hours of decannulation from ECMO support. Patients with COVID-19 were confirmed by a positive reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV2. SIRS was confirmed when two out of three of the following criteria were met: fever, leukocytosis, and/or initiation/escalation of vasopressors. Patients who developed post-ECMO SIRS were then distinguished based on the presence of infection. Infection was defined by the presence of either a new or positive culture following decannulation. We compared the incidence of SIRS and infection within 48 hours of decannulation in patients with and without COVID-19.RESULTS:We identified 227 eligible patients who survived ECMO. Twenty-eight patients (12%) had COVID-19. Of these patients, ten patients with COVID-19 (36%) experienced post-ECMO SIRS, including those with true SIRS (n=3) and associated infections (n=7). Five of the ten patients with COVID-19 who experienced post-ECMO SIRS were exposed to immune modulators within two weeks of decannulation. Ninety-five (42%) patients without COVID-19 developed post-ECMO SIRS. Thirty-day survival in COVID patients who experienced post-ECMO SIRS compared to COVID patients who did not experience post-ECMO SIRS was 73% vs. 94%. (p=0.11).CONCLUSION:Post-ECMO SIRS is common. The incidence of SIRS following decannulation was similar when historically compared to non-COVID patients who survived ECMO in a previously reported cohort from our institution. Immune-modulation exposure within two weeks of decannulation did not affect the incidence of SIRS in patients with COVID-19.

Giraffes have long been a subject of study for scientists due to the physiological anomaly their anatomical design can present. The study of the species helps aid in understanding of clinically relevant processes. The long trachea of a giraffe presents the dilemma of exaggerated dead space; however, this physiological problem is surmounted by a narrow trachea when compared to mammals of similar size, thus decreasing potential dead space. As COVID-19 patients in the hospital and ICU can develop COVID-19 associated acute respiratory distress syndrome, limiting excess dead space in COVID-19 patients is favorable. Removing additional tubing for a patient with an endotracheal tube in a ventilator circuit could help lower the patient's PaCO2 and raise their pH.

OBJECTIVES: The multifaceted long-term impairments resulting from critical illness and COVID-19 require interdisciplinary management approaches in the recovery phase of illness. Operational insights into the structure and process of recovery clinics (RCs) from heterogeneous health systems are needed. This study describes the structure and process characteristics of existing and newly implemented ICU-RCs and COVID-RCs in a subset of large health systems in the United States. DESIGN: Cross-sectional survey. SETTING: Thirty-nine RCs, representing a combined 156 hospitals within 29 health systems participated. PATIENTS: None. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: RC demographics, referral criteria, and operating characteristics were collected, including measures used to assess physical, psychologic, and cognitive recoveries. Thirty-nine RC surveys were completed (94% response rate). ICU-RC teams included physicians, pharmacists, social workers, physical therapists, and advanced practice providers. Funding sources for ICU-RCs included clinical billing (n = 20, 77%), volunteer staff support (n = 15, 58%), institutional staff/space support (n = 13, 46%), and grant or foundation funding (n = 3, 12%). Forty-six percent of RCs report patient visit durations of 1 hour or longer. ICU-RC teams reported use of validated scales to assess psychologic recovery (93%), physical recovery (89%), and cognitive recovery (86%) more often in standard visits compared with COVID-RC teams (psychologic, 54%; physical, 69%; and cognitive, 46%). CONCLUSIONS: Operating structures of RCs vary, though almost all describe modest capacity and reliance on volunteerism and discretionary institutional support. ICU- and COVID-RCs in the United States employ varied funding sources and endorse different assessment measures during visits to guide care coordination. Common features include integration of ICU clinicians, interdisciplinary approach, and focus on severe critical illness. The heterogeneity in RC structures and processes contributes to future research on the optimal structure and process to achieve the best postintensive care syndrome and postacute sequelae of COVID outcomes.

OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN: Retrospective observational study. SETTING: Multicenter, international COVID-19 registry. Subjects: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001). CONCLUSIONS: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.

INTRODUCTION:Immunosuppressed hosts represent a growing group of patients who suffer acute respiratory failure and may be considered for therapies such as extracorporeal membrane oxygenation (ECMO). OBJECTIVES:We conducted this retrospective study to determine whether acutely or chronically immunosuppressed patients placed on ECMO for cardiac and/or respiratory failure in our institution have different outcomes than immunocompetent patients placed on ECMO in our institution. METHODS:Adult patients placed on ECMO between June 31, 2010 and July 7, 2021 were identified within an IRB-approved database. Data was retrospectively extracted from the database and patients' medical records. Patients who survived ECMO decannulation were sub-grouped by the presence of acute or chronic immunosuppression, defined by the use of high-dose steroids or immunosuppressive agents for greater than four weeks prior to ECMO initiation. We analyzed and compared baseline characteristics and clinical outcomes using chi-squared tests for categorical variables and a one-way analysis of variance (ANOVA) for continuous variables. RESULTS:385 patients were included in this study, with 39 identified as chronically immunosuppressed, 49 as acutely immunosuppressed, and 297 as immunocompetent. There was no statistical difference in ECMO survival (respectively 54%, 59%, 65% p = 0.359) or 30-day survival (33%, 51%, 48% p = 0.149) for chronically immunosuppressed, acutely immunosuppressed, and immunocompetent, respectively. There were significant differences in rates of pre-ECMO COVID infection (p<0.001), coronary artery disease (p<0.001), smoking (p = 0.003), and acute kidney injury (p = 0.032). Acutely immunosuppressed patients had the highest rates of new infections during ECMO (p = 0.006). CONCLUSION:When compared to immunocompetent patients, both acutely and chronically immunosuppressed patients had no significant difference in ECMO survival or 30-day survival. Acutely immunosuppressed patients had less comorbidities than chronically immunosuppressed patients, but they were more commonly infected during ECMO. ECMO may still be a valuable tool in appropriately selected patients with refractory respiratory or cardiac failure.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) has been used to treat refractory acute respiratory distress syndrome (ARDS) due to COVID-19.This study was conducted to explore outcomes of ECMO as a rescue therapy for ARDS due to COVID-19, focusing on the outcome differences between the first wave and the second wave. METHODS:All adult patients with ARDS due to COVID-19 that were placed on ECMO between April 2020 and March 2021 were identified within an IRB-approved database and included in this study.The patients were stratified as first wave patients (ECMO started on 04/2020 -09/2020) and second wave patients (ECMO started on 11/2020 -03/2021), as no ECMO was initiated during October 2020.Clinical characteristics and outcomes were compared between the two groups.RESULTS: A total of 41 COVID-19 ECMO patients were identified.All ECMO was performed with veno-venous ECMO; no veno-arterial ECMO was performed.Among them, 28 patients (median age 52 years, male 68%) were stratified to the first wave and 13 patients (median age 45 years, male 69%) were stratified to the second wave.Pre-ECMO comorbidities were not significantly different between the two groups; however, pre-ECMO immunomodulators were more often given in the second wave (steroids 54% vs. 100%, p¼0.003; remdesivir 39% vs. 85%, p¼0.007), and second wave patients were more often placed in prone position before ECMO (11% vs. 85%, p<0.001).The median length of ECMO was 14 days in first wave patients vs. 20 days in second wave patients (p¼0.728).ECMO mortality was greater in second wave patients compared to first wave patients (9/28, 32% in first wave vs. 9/13, 69% in second wave, p¼0.026).Other complications observed during ECMO included acute renal failure (39% vs. 38%, p¼0.960), sepsis (32% vs. 23%, p¼0.553), bacterial pneumonia (11% vs. 8%, p¼0.762), gastrointestinal bleed (21% vs. 15%, p¼0.650) and cerebral vascular accident (4% vs. 23%, p¼0.050).CONCLUSIONS: Despite improved pre-ECMO treatment, second wave COVID-19 patients experienced higher mortality on ECMO than first wave patients.CLINICAL IMPLICATIONS: More strict inclusion/exclusion criteria for ECMO may be necessary to improve outcomes.

Purpose: Extracorporeal membrane oxygenation (ECMO) is a refractorytreatment for acute respiratory distress syndrome (ARDS) due toinfluenza and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2, also referred to as COVID-19). We conducted this study tocompare the outcomes of influenza patients treated with veno-venous-ECMO(VV-ECMO) to COVID-19 patients treated with VV-ECMO, during the firstwave of COVID-19. Materials and Methods: Patients in our institutionwith ARDS due to COVID-19 or influenza who were placed on ECMO betweenAugust 1, 2010 and September 15, 2020 were included in this comparative,retrospective study. To improve homogeneity, only VV -ECMO patients wereanalyzed. The clinical characteristics and outcomes were extracted andanalyzed. Results: 28 COVID-19 patients and 17 influenza patients wereidentified and included. ECMO survival rates were 68% (19/28) inCOVID-19 patients and 94% (16/17) in influenza patients (p=0.04).30-day survival rates after ECMO decannulation were 54% (15/28) inCOVID-19 patients and 76% (13/17) in influenza patients (p=0.13).COVID-19 patients spent a longer time on ECMO compared to flu patients(21 days vs. 12 days, p=0.025), and more COVID-19 patients (26/28 vs.2/17) were on immunomodulatory therapy prior to ECMO initiation(p<0.001). COVID-19 patients had higher rates of newinfections during ECMO (50% vs. 18%, p=0.03) and bacterial pneumonia(36% vs 6%, p=0.024). Conclusions: COVID-19 patients who were treatedin our institution with VV-ECMO had statistically lower ECMO survivalrates than influenza patients. It is possible that COVID-19immunomodulation therapies may increase the risk of other superimposedinfections.

Modern extracorporeal life-support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH); however, reports in the literature remain scarce. We sought to pool existing evidence to better characterize ECLS use in these patients. An electronic search was conducted to identify all studies in the English literature reporting the use of ECLS for DAD/DAH. Thirty-two articles consisting of 38 patients were selected, and patient-level data were extracted and pooled for analysis. Median patient age was 36 [IQR: 27, 48] years, and the majority (63.2%) were female. Most common etiological factors included granulomatosis with polyangiitis (8/38, 21.1%), systemic lupus erythematosus (8/38, 21.1%), Goodpasture's syndrome (4/38, 10.5%), and microscopic polyangiitis (4/38, 10.5%). Immunologic markers included anti-neutrophil cytoplasmic antibody (ANCA) in 15/38 (39.5%), anti-nuclear antibody (ANA) in 6/38 (15.8%), and anti-glomerular basement membrane (anti-GBM) antibodies in 4/38 (10.5%). DAH was present in 32/38 (84.2%) of cases and DAD without evidence of DAH was present in 6/38 (15.8%) of cases. ECLS strategies included extracorporeal membrane oxygenation of veno-venous type (VV-ECMO) in 28/38 (73.7%), veno-arterial type (VA-ECMO) in 5/38 (13.2%), and one case of right ventricular assist device with oxygenator (RVAD-ECMO). Heparin was utilized in 18/38 (47.4%) of cases with no difference in use between DAH versus no DAH (P = .46) or VA- versus VV-ECLS (P = 1). Median duration of ECLS was 10 [5, 14] days. Pre- versus post-ECLS comparison of blood gases showed improvement in median PaO2 (49 [45, 59] mm Hg vs. 80 [70, 99] mm Hg, P < .001), PaO2:FiO2 ratio (48.2 [41.4, 54.8] vs. 182.0 [149.4, 212.2], P < .01), and pulse oximetry values (76% [72, 80] vs. 96% [94, 97], P = .086). Overall, 94.7% (36/38) of patients survived to decannulation while 30-day mortality was 10.5% (4/38) with no differences between VA- and VV-ECMO (P = 1 and P = .94, respectively). DAD/DAH occurs in a younger, predominantly female population, and tends to be associated with systemic autoimmune processes. ECLS, independent of its type, appears to result in favorable short-term survival.