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Background: A recent ICU telemedicine research consensus conference identified the need for reliable methods of measuring structural features and processes of critical care delivery in the domains of organizational context and characteristics of ICU teams, ICUs, hospitals, and of the communities supported by an ICU.Methods: The American College of Chest Physicians Critical Care Institute developed and conducted a survey of ICU telemedicine practices. A 32-item survey was delivered electronically to leaders of 311 ICUs, and 11 domains were identified using principal components analysis. Survey reliability was judged by intraclass correlation among raters, and validity was measured for items for which independent assessment was available.Results: Complete survey information was obtained for 170 of 311 ICUs sent invitations. Analysis of a subset of surveys from 45 ICUs with complete data from more than one rater indicated that the survey reliability was in the excellent to nearly perfect range. Coefficients for measures of external validation ranged from 0.63 to 1.0. Analyses of the survey revealed substantial variation in the practice of ICU telemedicine, including ICU telemedicine center staffing patterns; qualifications of providers; case sign-out, ICU staffing models, leadership, and governance; intensivist review for new patients; adherence to best practices; use of quality and safety information; and ICU physician sign out for their patients.Conclusions: The American College of Chest Physicians ICU telemedicine survey is a reliable tool for measuring variation among ICUs with regard to staffing, structure, processes of care, and ICU telemedicine practices. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the evolving role, patterns of use, and costs of critical care medicine in the United States from 2000 to 2005.Design: Retrospective study of data from the Hospital Cost Report Information System (Centers for Medicare and Medicaid Services, Baltimore, Maryland).Setting: Nonfederal, acute care hospitals with critical care medicine beds in the United States.Subjects: None.Interventions: None.Measurements and Main Results: We analyzed hospital and critical care medicine beds, bed types, days, occupancy rates, payer mix (Medicare and Medicaid), and costs. Critical care medicine costs were compared with national cost indexes. Between 2000 and 2005, the total number of U.S. hospitals with critical care medicine beds decreased by 12.2% (from 3,586 to 3,150). Although the number of hospital beds decreased by 4.2% (from 655,785 to 628,409), both hospital days and occupancy rates increased by 5.1% (from 145.1 to 152.5 million) and 13.7% (from 59% to 67%), respectively. Critical care medicine beds increased by 6.5% (from 88,252 to 93,955), days by 10.6% (from 21.0 to 23.2 million), and occupancy rates by 4.5% (from 65% to 68%). The majority (90%) of critical care medicine beds were classified as intensive care, premature/neonatal, and coronary care unit beds. The percentage of critical care medicine days used by Medicare decreased by 3.8% (from 37.9% to 36.5%) compared with an increase of 15.5% (from 14.5% to 16.8%) by Medicaid. From 2000 to 2005, critical care medicine costs per day increased by 30.4% (from $2698 to $3518). Although annual critical care medicine costs increased by 44.2% (from $56.6 to $81.7 billion), the proportion of hospital costs and national health expenditures allocated to critical care medicine decreased by 1.6% and 1.8%, respectively. However, the proportion of the gross domestic product used by critical care medicine increased by 13.7%. In 2005, critical care medicine costs represented 13.4% of hospital costs, 4.1% of national health expenditures, and 0.66% of the gross domestic product.Conclusions: Critical care medicine continues to grow in a shrinking U.S. hospital system. The critical care medicine payer mix is evolving, with Medicaid increasing in its percentage of critical care medicine use. Critical care medicine is more cost controlled than other healthcare indexes, but is still using an increasing percentage of the gross domestic product. Our updated and comprehensive critical care medicine use and cost analysis provides a contemporary benchmark for the strategic planning of critical care medicine services within the U.S. healthcare system. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze the relationship of intrahospital transport patterns with patient throughput and outcomes in an oncological intensive care unit. We retrospectively reviewed all patients admitted to a closed medical-surgical intensive care unit at a cancer center between January 1, 2004 and December 31, 2005. We compared the clinical characteristics and outcomes of patients with and without transport and analyzed all intrahospital transports in relation to intensive care unit occupancy, length of stay, and intensive care unit and hospital outcomes. Transport patterns were also assessed by day of week, time of day, timing of the first transport to intensive care unit admission, and destination. Transported patients (n = 413, 43.5%) had significantly higher severity of illness scores on intensive care unit admission, greater use of vasopressors and mechanical ventilation, and longer intensive care unit and hospital length of stay and higher hospital mortality than nontransported patients (n = 535, 56.5%). Multiple transports (!2) occurred in 45% of the transported patients. The number of transports was directly proportional to intensive care unit length of stay. The highest transport rates and nearly half of all first transports occurred during the first 24 hours of intensive care unit admission. Transports were most common during weekdays and on afternoon and evening hours and most frequently to the computed tomography suite. Our study shows that intrahospital transport of the critically ill is a multifaceted process with important implications for intensive care unit resource analysis, workload and throughput. [ABSTRACT FROM AUTHOR]

Objective: A comparison of federal Medicare databases to identify critical care medicine (CCM) use, cost discrepancies, and their possible causes.Design: A 6-yr (1995-2000) retrospective analysis of Medicare hospital and CCM use and cost, comparing the Hospital Cost Report Information System (HCRIS) with Medicare Provider Analysis and Review File (MedPAR) supplemented when necessary by Health Care Information System (HCIS) (identified herein as MedPAR/HCIS).Setting: All nonfederal U.S. hospitals.Subjects: None.Interventions: None.Measurements and Main Results: Data are presented as days (M = million) and costs ($; B = Billion) for both hospitals and CCM. Between 1995 and 2000, the number of hospital days decreased in both databases: HCRIS (-13.2%; 78M to 67.7M) and MedPAR/HCIS (-14.1%; 82.8M to 71.1M). CCM days decreased in HCRIS (-4.6%; 8.3M to 7.9M). In contrast, CCM days increased in MedPAR/HCIS (7.2%; 13.9M to 14.9M). The discrepancy in CCM days between HCRIS and MedPAR/HCIS increased from 40% (5.6M days) in 1995 to 47% (7M days) in 2000. Two CCM billing codes (intensive care unit and coronary care unit 'post/intermediate') used in MedPAR/HCIS were responsible for 73% on average per year, over the study period, for this CCM discrepancy. The use of these two codes progressively increased (44%; 3.9M to 5.6M days) by the end of the study. The cumulative 6-yr discrepancy in CCM days between HCRIS and MedPAR/HCIS (37.3M days) had a calculated cost of $92.3B.Conclusions: We have identified major, and progressively increasing, discrepancies between two U.S. federal databases tabulating hospital and CCM use and cost for Medicare beneficiaries. Two CCM 'post/intermediate' billing codes in MedPAR/HCIS were predominantly responsible for the CCM discrepancy. To accurately assess Medicare CCM use and cost, either HCRIS, or MedPAR/HCIS without the 'post/intermediate' codes, should be used. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the relationship between hospital size and changes in the number of critical care medicine (CCM) beds, proportion of hospital beds allocated to CCM, and CCM occupancy in acute care hospitals in the United States from 1985 to 2000. DESIGN: A 16-yr (1985 to 2000) retrospective analysis was performed using the Hospital Cost Report Information System (Centers for Medicare and Medicaid Services, Baltimore, MD) on U.S. acute care hospitals that provided CCM. Hospitals were stratified into four groups (small, 1-100 beds; medium, 101-300 beds; large 301-500 beds; and extra large, >500 beds). SETTING: Nonfederal, acute care hospitals with CCM units in the United States. SUBJECTS: None. INTERVENTIONS: None. MEASUREMENTS: Changes in the number of hospitals, non-CCM and CCM beds, the proportion of CCM to hospital beds, and their occupancy rates. MAIN RESULTS: Between 1985 and 2000, the number of hospitals providing CCM decreased overall (4,150 to 3,581, -13.7%). The greatest decreases were seen in large (-39%) and extra-large (-40%) hospitals. Small hospitals increased minimally (3.3%). The number of non-CCM beds decreased (820,300 to 566,900, -30.9%), most prominently in large (-44.2%) and extra-large (-46.1%) hospitals. In contrast, CCM beds increased overall (69,300 to 87,400, 26.1%), especially in small (27%) and medium (44.2%) hospitals. The proportion of total hospital beds assigned to CCM increased (71.8%), most markedly in large (93.5%) and extra-large (85.7%) hospitals. Non-CCM occupancy decreased (-6.4%), particularly in small (-7.5%) and extra-large (-5.8%) hospitals. However, regardless of hospital size, CCM occupancy changed negligibly (0.4%). At every time point studied, CCM occupancy was greater than non-CCM occupancy within each size group. As hospital size increased, occupancy rates increased. CONCLUSIONS: Across hospitals of all sizes, CCM bed numbers are increasing, whereas non-CCM bed numbers are decreasing. Although the CCM bed capacity is increasing at a greater percentage rate in smaller hospitals, the assignment of hospital beds to CCM remains higher in the larger hospitals. In addition, CCM bed occupancy is greater in larger institutions. These findings may help guide the future development of hospital size-based CCM benchmarking standards and guidelines. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVES: To describe the frequency and outcome of patients with acute lung injury (ALI) and ARDS who require mechanical ventilation (MV) after lung resection, and to analyze preoperative and perioperative variables associated with mortality. METHODS: We retrospectively reviewed the case records of all patients who underwent lung resection and acquired ALI and/or ARDS and required invasive MV and ICU admission at a tertiary-care cancer center from January 1, 2002, to December 31, 2004. Preoperative and perioperative information including ICU-specific variables and outcome data were analyzed. Data are presented as median (range). RESULTS: During the study period, 2,039 patients underwent a total of 2,192 lung resections. ALI/ARDS developed in 50 patients (2.45%). The prevalence of ALI/ARDS by procedure was as follows: pneumonectomy, 7.9% (10 cases in 126 procedures); lobectomy/bilobectomy, 2.96% (31 cases in 1,047 procedures); and sublobar resection, 0.88% (9 cases in 1,019 procedures). There were 28 men (56%) and 22 women (44%). Median age was 68.5 years (range, 44 to 88 days). Median time of presentation to the ICU with ALI/ARDS following surgery was 4 days (range, 1 to 22 days). Median ICU length of stay was 10 days (range, 2 to 43 days), and median hospital LOS was 26.5 days (range, 6 to 93 days). During hospitalization, 20 of the 50 patients (40%) died: 16 in the ICU and 4 after ICU discharge. The mortality rate was highest after pneumonectomy (50%), followed by lobectomy (42%) and sublobar resections (22%). Although increased age was associated with a higher ICU mortality, none of the preoperative and perioperative variables were significantly associated with hospital mortality. There was a marginally significant association between mortality and time of presentation to the ICU after surgery (p = 0.06). CONCLUSIONS: Our results confirm that ALI/ARDS after lung resection is associated with a high mortality in patients who require invasive MV and ICU care. [ABSTRACT FROM AUTHOR]

Objective: To report the development of the Brugada electrocardiographic (ECG) pattern in the immediate postoperative setting.Design: Case report.Setting: Postanesthesia care unit at Memorial Sloan-Kettering Cancer Center.Patient: A 51-yr-old white male who developed new ST-segment elevation in leads V(1)-V(3) typical of the ECG changes of the Brugada syndrome immediately after undergoing head and neck surgery for cancer. The patient was asymptomatic, and the cardiac enzymes and echocardiogram were normal; therefore, electrophysiologic study was not performed.Conclusions: We postulated that the Brugada ECG abnormalities were induced primarily by an increase in parasympathetic tone resulting from vagal nerve manipulation during deep neck dissection and partially by the fever he developed during the postoperative period. In addition to the more common causes of ST-segment elevation, the Brugada ECG pattern or syndrome should be considered in patients undergoing deep neck dissection who develop characteristic ECG changes in association with normal cardiac enzymes and echocardiogram. [ABSTRACT FROM AUTHOR]

Diffuse alveolar hemorrhage (DAH) is a serious pulmonary complication that occurs in patients undergoing hematopoietic stem-cell transplantation (HSCT). Current management strategies are limited to corticosteroids, platelet transfusions, and mechanical ventilator support to treat acute respiratory failure. Recombinant factor VIIa (rFVIIa) is an approved agent for the treatment of bleeding in patients with hemophilia A or B and the presence of inhibitors. We report a case of DAH after allogeneic HSCT that failed standard therapy and was then successfully treated with rFVIIa. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is a prevalent condition associated with many comorbidities. However, establishing the independent impact of OSA on specific health outcomes can be challenging without access to a substantial patient cohort. This study aimed to investigate whether a diagnosis of OSA was independently associated with venous thromboembolism (VTE) after total knee arthroplasty (TKA)., Methods: In this retrospective cohort study, we interrogated the TriNetX Analytics Research Network, a large database comprising the billing claims and electronic health record-derived data of >117 million patients. Using Current Procedural Terminology (CPT) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, we identified US adult patients who underwent TKA between January 1, 2013 and January 1, 2023, with and without preexisting OSA (and ≥2 OSA occurrences overall). We then analyzed the 1-month postoperative incidence of VTE as a composite outcome of deep vein thrombosis (DVT) and pulmonary embolism (PE) incidence, as well as cerebrovascular accident (CVA), myocardial infarction (MI), and DVT and PE individually. Baseline demographic and comorbidity covariates were incorporated into a 1:1 propensity score-matched analysis to clarify the independent effect of OSA., Results: During the 10-year study period, a total of 197,460 patients underwent TKA. Of these, 27,976 met the criteria for inclusion in the OSA cohort, while 150,830 had no documented history of OSA. In the initial analysis, OSA was significantly associated with the primary outcome (DVT/PE) as well as all secondary outcomes (CVA, MI, and individually with DVT and PE) at 1 month postsurgery. After generating propensity score matched cohorts, DVT/PE remained significantly associated with OSA, with an absolute risk difference of 0.7% (odds ratio [OR], 1.19, confidence interval [CI], 1.1-1.3, P < .001), as were the secondary outcomes of DVT (OR, 1.11, CI, 1.0-1.2, P = .030) and PE (OR, 1.41, CI, 1.2-1.6, P < .001)., Conclusions: In this study encompassing a nationally representative sample of TKA patients, OSA was associated with increased incidence of VTE at 1 month postoperatively, an association that persisted after the generation of matched cohorts. While limitations related to the lack of patient-level data, disease severity, and therapy adherence should be acknowledged, our large sample size enabled us to factor many baseline characteristics into our analysis, reinforcing the association of these findings. Prospective work is needed on the impact of modulating factors such as anticoagulation regimen and positive airway pressure therapy on these outcomes., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 International Anesthesia Research Society.)

Rationale: New evidence is available examining the use of corticosteroids in sepsis, acute respiratory distress syndrome (ARDS) and community-acquired pneumonia (CAP), warranting a focused update of the 2017 guideline on critical illness-related corticosteroid insufficiency., Objectives: To develop evidence-based recommendations for use of corticosteroids in hospitalized adults and children with sepsis, ARDS, and CAP., Panel Design: The 22-member panel included diverse representation from medicine, including adult and pediatric intensivists, pulmonologists, endocrinologists, nurses, pharmacists, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. We followed Society of Critical Care Medicine conflict of interest policies in all phases of the guideline development, including task force selection and voting., Methods: After development of five focused Population, Intervention, Control, and Outcomes (PICO) questions, we conducted systematic reviews to identify the best available evidence addressing each question. We evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach and formulated recommendations using the evidence-to-decision framework., Results: In response to the five PICOs, the panel issued four recommendations addressing the use of corticosteroids in patients with sepsis, ARDS, and CAP. These included a conditional recommendation to administer corticosteroids for patients with septic shock and critically ill patients with ARDS and a strong recommendation for use in hospitalized patients with severe CAP. The panel also recommended against high dose/short duration administration of corticosteroids for septic shock. In response to the final PICO regarding type of corticosteroid molecule in ARDS, the panel was unable to provide specific recommendations addressing corticosteroid molecule, dose, and duration of therapy, based on currently available evidence., Conclusions: The panel provided updated recommendations based on current evidence to inform clinicians, patients, and other stakeholders on the use of corticosteroids for sepsis, ARDS, and CAP., Competing Interests: Dr. Balk received funding from Dompe Pharmaceuticals, Merck, and BioMerieux. Dr. Sarwal’s institution receives funding from Biogen, Bard, Novartis, CVR Global, Lung Pacer, the National Institute on Aging (R01 AG066910-01), Shaltout, and Butterfly. Dr. Gershengorn disclosed that she served as an advisory board member for Gilead Sciences. Dr. Menon received funding from the Canadian Institutes of Health Research. Dr. Jayaprakash disclosed that she was the site principal investigator for sponsored trials through Abbott Laboratories and BioCogniV. Dr. Russell reports patents owned by the University of British Columbia (UBC) that are related to the use of PCSK9 inhibitor(s) in sepsis and related to the use of vasopressin in septic shock and a patent owned by Ferring for use of selepressin in septic shock. Dr. Russell is an inventor of these patents. Dr. Russell was a founder, Director and shareholder in Cyon Therapeutics and is a shareholder in Molecular You Corp. Dr. Russell is no longer actively consulting for any industry. Dr. Russell reports receiving consulting fees in the last 3 years from: 1) SIB Therapeutics LLC (developing a sepsis drug). 2) Ferring Pharmaceuticals (manufactures vasopressin and developing selepressin). 3) Dr. Russell was a funded member of the Data and Safety Monitoring Board of a National Institutes of Health-sponsored trial of plasma in COVID-19 (PASS-IT-ON) (2020–2021). 4) PAR Pharma (sells prepared bags of vasopressin). Dr. Russell reports having received an investigator-initiated grant from Grifols (entitled “Is HBP a mechanism of albumin’s efficacy in human septic shock?”) that was provided to and administered by UBC. Dr. Russell was a nonfunded Science Advisor and member of the Government of Canada COVID-19 Therapeutics Task Force (June 2020 to 2021). Dr. Asehnoune received funding from LFB and Edwards Lifesciences Baxter. Dr. Spencer-Segal received funding from Camurus AB, Chiasma, and Recordati Rare Diseases. Dr. Esper received funding from Honeywell. Dr. Annane has been involved with research relating to this guideline, in particular with multiple randomized control trials examining the use of corticosteroids in sepsis. He participated in the discussion for corticosteroids in sepsis but abstained from voting on final recommendations pertaining to corticosteroids in sepsis and septic shock. Dr. Menon is funded by a Canadian Institute of Health Research grant for The Stress Hydrocortisone in Pediatric Septic Shock trial. The remaining authors have disclosed that they do not have any potential conflicts of interest. The 22-member panel included diverse representation from medicine, including adult and pediatric intensivists, pulmonologists, endocrinologists, nurses, pharmacists, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. We followed Society of Critical Care Medicine conflict of interest policies in all phases of the guideline development, including task force selection and voting., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Competing Interests: Dr. Balk received funding from Dompe Pharmaceuticals, Merck, and BioMerieux. Dr. Sarwal’s institution receives funding from Biogen, Bard, Novartis, CVR Global, Lung Pacer, the National Institute on Aging (R01 AG066910-01), Shaltout, and Butterfly. Dr. Gershengorn disclosed that she served as an advisory board member for Gilead Sciences. Dr. Menon received funding from the Canadian Institutes of Health Research. Dr. Jayaprakash disclosed that she was the site principle investigator for sponsored trials through Abott Laboratories and BioCogniV. Dr. Russell reports patents owned by the University of British Columbia (UBC) that are related to the use of PCSK9 inhibitor(s) in sepsis and related to the use of vasopressin in septic shock and a patent owned by Ferring for use of selepressin in septic shock. Dr. Russell is an inventor on these patents. Dr. Russell was a founder, Director and shareholder in Cyon Therapeutics and is a shareholder in Molecular You Corp. Dr. Russell is no longer actively consulting for any industry. Dr. Russell reports receiving consulting fees in the last 3 years from: 1) SIB Therapeutics LLC (developing a sepsis drug). 2) Ferring Pharmaceuticals (manufactures vasopressin and developing selepressin). 3) Dr. Russell was a funded member of the Data and Safety Monitoring Board of an NIH-sponsored trial of plasma in COVID-19 (PASS-IT-ON) (2020–2021). 4) PAR Pharma (sells prepared bags of vasopressin). Dr. Russell reports having received an investigator-initiated grant from Grifols (entitled “Is HBP a mechanism of albumin’s efficacy in human septic shock?”) that was provided to and administered by UBC. Dr. Russell was a nonfunded Science Advisor and member, Government of Canada COVID-19 Therapeutics Task Force (June 2020 to 2021). Dr. Asehnoune received funding from LFB and Edwards Lifecience Baxter. Dr. Spencer-Segal received funding from Camurus AB, Chiasma, and Recordati Rare Diseases. Dr. Esper received funding from Honeywell. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Objectives: We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). By pooling data across all trials that have examined corticosteroids in these three acute conditions, we aim to examine the side effects of corticosteroid use in critical illness., Data Sources: We performed a comprehensive search of MEDLINE, Embase, Centers for Disease Control and Prevention library of COVID research, CINAHL, and Cochrane center for trials., Study Selection: We included randomized controlled trials (RCTs) that compared corticosteroids to no corticosteroids or placebo in patients with sepsis, ARDS, and CAP., Data Extraction: We summarized data addressing the most described side effects of corticosteroid use in critical care: gastrointestinal bleeding, hyperglycemia, hypernatremia, superinfections/secondary infections, neuropsychiatric effects, and neuromuscular weakness., Data Synthesis: We included 47 RCTs ( n = 13,893 patients). Corticosteroids probably have no effect on gastrointestinal bleeding (relative risk [RR], 1.08; 95% CI, 0.87-1.34; absolute risk increase [ARI], 0.3%; moderate certainty) or secondary infections (RR, 0.97; 95% CI, 0.89-1.05; absolute risk reduction, 0.5%; moderate certainty) and may have no effect on neuromuscular weakness (RR, 1.22; 95% CI, 1.03-1.45; ARI, 1.4%; low certainty) or neuropsychiatric events (RR, 1.19; 95% CI, 0.82-1.74; ARI, 0.5%; low certainty). Conversely, they increase the risk of hyperglycemia (RR, 1.21; 95% CI, 1.11-1.31; ARI, 5.4%; high certainty) and probably increase the risk of hypernatremia (RR, 1.59; 95% CI, 1.29-1.96; ARI, 2.3%; moderate certainty)., Conclusions: In ARDS, sepsis, and CAP, corticosteroids are associated with hyperglycemia and probably with hypernatremia but likely have no effect on gastrointestinal bleeding or secondary infections. More data examining effects of corticosteroids, particularly on neuropsychiatric outcomes and neuromuscular weakness, would clarify the safety of this class of drugs in critical illness., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: To determine the risk difference of arterial and venous thromboembolic events between patients with upper gastrointestinal bleeding (UGIB) who received and did not receive tranexamic acid., Design: Retrospective cohort study., Setting: The TriNetX Analytics (Cambridge, MA) Research Network, a deidentified mixed electronic health record and claims-derived database with over 110 million patients, primarily located in the United States., Patients: A total of 2,016,763 patients diagnosed with hematemesis or melena between October 31, 2003, and October 31, 2023., Interventions: Receipt of tranexamic acid within 7 days of a UGIB diagnosis., Measurements and Main Results: We measured the incidence of thromboembolic events, both venous (deep venous thrombosis [DVT] and pulmonary embolism [PE]) and arterial (cerebrovascular accident [CVA] and myocardial infarction [MI]), within either 7 days of tranexamic acid (for recipients) or 7 days of UGIB diagnosis (for nonrecipients). Subsequently, we developed similar subcohorts using propensity score matching (PSM) for demographic and comorbidity data and reexamined the incidence of thromboembolic events, both before and after excluding any patients with any prior episodes of the outcomes. In all analyses, tranexamic acid recipients experienced significantly more adverse thromboembolic outcomes, with the post-PSM cohorts' risk difference generating an odds ratio of 1.4 for MI (95% CI, 1.2-1.7), 1.6 in CVA (95% CI, 1.3-1.9), 1.8 in PE (95% CI, 1.5-2.3), and 2.1 in DVT (95% CI, 1.8-2.5); all p values of less than 0.001., Conclusions: Leveraging data from a large, multi-institutional database, we identified a correlation between tranexamic acid use in patients with UGIB and the occurrence of both venous and arterial thromboembolic events. Although the former is well-attested in the literature, the latter finding is more novel, underscoring the need for further prospective research to better characterize the risk-benefit profile of tranexamic acid in the management of gastrointestinal bleeding., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: To perform a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with sepsis., Data Sources: We searched PubMed, Embase, and the Cochrane Library, up to January 10, 2023., Study Selection: We included randomized controlled trials (RCTs) comparing corticosteroids with placebo or standard care with sepsis., Data Extraction: The critical outcomes of interest included mortality, shock reversal, length of stay in the ICU, and adverse events., Data Analysis: We performed both a pairwise and dose-response meta-analysis to evaluate the effect of different corticosteroid doses on outcomes. We used Grading of Recommendations Assessment, Development and Evaluation to assess certainty in pooled estimates., Data Synthesis: We included 45 RCTs involving 9563 patients. Corticosteroids probably reduce short-term mortality (risk ratio [RR], 0.93; 95% CI, 0.88-0.99; moderate certainty) and increase shock reversal at 7 days (RR, 1.24; 95% CI, 1.11-1.38; high certainty). Corticosteroids may have no important effect on duration of ICU stay (mean difference, -0.6 fewer days; 95% CI, 1.48 fewer to 0.27 more; low certainty); however, probably increase the risk of hyperglycemia (RR, 1.13; 95% CI, 1.08-1.18; moderate certainty) and hypernatremia (RR, 1.64; 95% CI, 1.32-2.03; moderate certainty) and may increase the risk of neuromuscular weakness (RR, 1.21; 95% CI, 1.01-1.45; low certainty). The dose-response analysis showed a reduction in mortality with corticosteroids with optimal dosing of approximately 260 mg/d of hydrocortisone (RR, 0.90; 95% CI, 0.83-0.98) or equivalent., Conclusions: We found that corticosteroids may reduce mortality and increase shock reversal but they may also increase the risk of hyperglycemia, hypernatremia, and neuromuscular weakness. The dose-response analysis indicates optimal dosing is around 260 mg/d of hydrocortisone or equivalent., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Abstract: Brain natriuretic peptide (BNP) is a well-established biomarker for heart failure (HF). However, its diagnostic utility can be limited in patients with comorbidities that independently elevate serum BNP levels, including chronic renal failure and sepsis. We describe a rare occurrence of significantly elevated serum BNP levels in a patient with metastatic urothelial cancer without HF or obvious signs of sepsis. The report highlights the need for considering alternative causes for increased serum BNP levels, especially in the presence of malignancy., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2023 American Association of Nurse Practitioners.)

Rationale: Fever is frequently an early indicator of infection and often requires rigorous diagnostic evaluation., Objectives: This is an update of the 2008 Infectious Diseases Society of America and Society (IDSA) and Society of Critical Care Medicine (SCCM) guideline for the evaluation of new-onset fever in adult ICU patients without severe immunocompromise, now using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology., Panel Design: The SCCM and IDSA convened a taskforce to update the 2008 version of the guideline for the evaluation of new fever in critically ill adult patients, which included expert clinicians as well as methodologists from the Guidelines in Intensive Care, Development and Evaluation Group. The guidelines committee consisted of 12 experts in critical care, infectious diseases, clinical microbiology, organ transplantation, public health, clinical research, and health policy and administration. All task force members followed all conflict-of-interest procedures as documented in the American College of Critical Care Medicine/SCCM Standard Operating Procedures Manual and the IDSA. There was no industry input or funding to produce this guideline., Methods: We conducted a systematic review for each population, intervention, comparison, and outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as best-practice statements., Results: The panel issued 12 recommendations and 9 best practice statements. The panel recommended using central temperature monitoring methods, including thermistors for pulmonary artery catheters, bladder catheters, or esophageal balloon thermistors when these devices are in place or accurate temperature measurements are critical for diagnosis and management. For patients without these devices in place, oral or rectal temperatures over other temperature measurement methods that are less reliable such as axillary or tympanic membrane temperatures, noninvasive temporal artery thermometers, or chemical dot thermometers were recommended. Imaging studies including ultrasonography were recommended in addition to microbiological evaluation using rapid diagnostic testing strategies. Biomarkers were recommended to assist in guiding the discontinuation of antimicrobial therapy. All recommendations issued were weak based on the quality of data., Conclusions: The guidelines panel was able to formulate several recommendations for the evaluation of new fever in a critically ill adult patient, acknowledging that most recommendations were based on weak evidence. This highlights the need for the rapid advancement of research in all aspects of this issue-including better noninvasive methods to measure core body temperature, the use of diagnostic imaging, advances in microbiology including molecular testing, and the use of biomarkers., Competing Interests: Supported, in part, by the Intramural Research Program of the National Institutes of Health (NIH). Dr. Weber received funding from Pfizer, Merck, PDI, and Germitec. Dr. Pastores received funding from McGraw Hill; he disclosed that he is on the advisory board for AbbVie. Dr. Van Duin received funding from the National Institute of Allergy and Infectious Diseases (Antibiotic Resistance Leadership Group UM1AI104681), the NIH, and British Society for Antimicrobial Chemotherapy; he disclosed that he is a consultant for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, Karius, and Utility. Dr. Patel received funding from ContraFect, TenNor Therapeutics Limited, Hylomorph, BioFire, Shionogi, IDSA, NBME, UptoDate, and the Infectious Diseases Board Review Course; she disclosed that she is a consultant for Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences, Qvella, and Netflix; she disclosed that she has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. 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 Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: To describe the factors affecting critical care capacity and how critical care organizations (CCOs) within academic centers in the U.S. flow-size critical care resources under normal operations, strain, and surge conditions., Data Sources: PubMed, federal agency and American Hospital Association reports, and previous CCO survey results were reviewed., Study Selection: Studies and reports of critical care bed capacity and utilization within CCOs and in the United States were selected., Data Extraction: The Academic Leaders in the Critical Care Medicine Task Force established regular conference calls to reach a consensus on the approach of CCOs to "flow-sizing" critical care services., Data Synthesis: The approach of CCOs to "flow-sizing" critical care is outlined. The vertical (relation to institutional resources, e.g., space allocation, equipment, personnel redistribution) and horizontal (interdepartmental, e.g., emergency department, operating room, inpatient floors) integration of critical care delivery (ICUs, rapid response) for healthcare organizations and the methods by which CCOs flow-size critical care during normal operations, strain, and surge conditions are described. The advantages, barriers, and recommendations for the rapid and efficient scaling of critical care operations via a CCO structure are explained. Comprehensive guidance and resources for the development of "flow-sizing" capability by a CCO within a healthcare organization are provided., Conclusions: We identified and summarized the fundamental principles affecting critical care capacity. The taskforce highlighted the advantages of the CCO governance model to achieve rapid and cost-effective "flow-sizing" of critical care services and provide recommendations and resources to facilitate this capability. The relevance of a comprehensive approach to "flow-sizing" has become particularly relevant in the wake of the latest COVID-19 pandemic. In light of the growing risks of another extreme epidemic, planning for adequate capacity to confront the next critical care crisis is urgent., Competing Interests: Dr. Halpern received funding from Werfen and Airstrip Technologies. Dr. Jacobi received funding from La Jolla Pharmaceuticals, Pfizer Hospital Products Division, AcelRx, Society of Critical Care Medicine LEAD and Glycemic Guidelines Co-Chair, BD Voices of Vascular Educational Advisor, Visante, Infusion Nurses Society, and Postgraduate Healthcare Education. Dr. Pastores’ institution received funding from Biomerieux, RevImmune, and Eisai/Global Coalition for Adaptive Research; he received funding from McGraw Hill. 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 Wolters Kluwer Health, Inc. All Rights Reserved.)

In sepsis, dysregulation of the hypothalamic-pituitary-adrenal axis, alterations in cortisol metabolism, and tissue resistance to glucocorticoids can all result in relative adrenal insufficiency or critical illness-related corticosteroid insufficiency (CIRCI). The symptoms and signs of CIRCI during sepsis are nonspecific, generally including decreased mental status, unexplained fever, or hypotension refractory to fluids, and the requirement of vasopressor therapy to maintain adequate blood pressure. While we have been aware of this syndrome for over a decade, it remains a poorly understood condition, challenging to diagnose, and associated with significantly diverging practices among clinicians, particularly regarding the optimal dosing and duration of corticosteroid therapy. The existing literature on corticosteroid use in patients with sepsis and septic shock is vast with dozens of randomized controlled trials conducted across the past 4 decades. These studies have universally demonstrated reduced duration of shock, though the effects of corticosteroids on mortality have been inconsistent, and their use has been associated with adverse effects including hyperglycemia, neuromuscular weakness, and an increased risk of infection. In this article, we aim to provide a thorough, evidence-based, and practical review of the current recommendations for the diagnosis and management of patients with sepsis who develop CIRCI, explore the controversies surrounding this topic, and highlight what lies on the horizon as new evidence continues to shape our practice., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Dr. Weber received funding from Pfizer, Merck, PDI, and Germitec. Dr. Pastores received funding from McGraw Hill; he disclosed that he is on the advisory board for AbbVie. Dr. van Duin received funding from the National Institute of Allergy and Infectious Diseases (Antimicrobial Resistance Leadership Group UM1AI104681), the National Institutes of Health, and British Society for Antimicrobial Chemotherapy; he disclosed that he is a consultant for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, Karius, and Utility. Dr. Patel received funding from ContraFect, TenNor Therapeutics, Hylomorph, BioFire, Shionogi, Infectious Diseases Society of America, National Board of Medical Examiners, UptoDate, and the Infectious Diseases Board Review Course; she disclosed that she is a consultant for Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST Diagnostics, Torus Biosystems, Mammoth Biosciences, Qvella, and Netflix; she disclosed that she has a patent on Bordetella pertussis/parapertussis polymerase chain reaction issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Objectives: To determine the feasibility, safety, and efficacy of a biomarker-guided implementation of a kidney-sparing sepsis bundle (KSSB) of care in comparison with standard of care (SOC) on clinical outcomes in patients with sepsis., Design: Adaptive, multicenter, randomized clinical trial., Setting: Five University Hospitals in Europe and North America., Patients: Adult patients, admitted to the ICU with an indwelling urinary catheter and diagnosis of sepsis or septic shock, without acute kidney injury (acute kidney injury) stage 2 or 3 or chronic kidney disease., Interventions: A three-level KSSB based on Kidney Disease: Improving Global Outcomes (KDIGOs) recommendations guided by serial measurements of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 used as a combined biomarker [TIMP2]•[IGFBP7]., Measurements and Main Results: The trial was stopped for low enrollment related to the COVID-19 pandemic. Nineteen patients enrolled in five sites over 12 months were randomized to the SOC ( n = 8, 42.0%) or intervention ( n = 11, 58.0%). The primary outcome was feasibility, and key secondary outcomes were safety and efficacy. Adherence to protocol in patients assigned to the first two levels of KSSB was 15 of 19 (81.8%) and 19 of 19 (100%) but was 1 of 4 (25%) for level 3 KSSB. Serious adverse events were more frequent in the intervention arm (4/11, 36.4%) than in the control arm (1/8, 12.5%), but none were related to study interventions. The secondary efficacy outcome was a composite of death, dialysis, or progression of greater than or equal to 2 stages of acute kidney injury within 72 hours after enrollment and was reached by 3 of 8 (37.5%) patients in the control arm, and 0 of 11 (0%) patients in the intervention arm. In the control arm, two patients experienced progression of acute kidney injury, and one patient died., Conclusions: Although the COVID-19 pandemic impeded recruitment, the actual implementation of a therapeutic strategy that deploys a KDIGO-based KSSB of care guided by risk stratification using urinary [TIMP2]•[IGFBP7] seems feasible and appears to be safe in patients with sepsis., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

A diverse and inclusive critical care workforce is vital to the provision of culturally appropriate and effective care to critically ill patients of all backgrounds., Objectives: The purpose of this study is to determine the trends in gender, race, and ethnicity of U.S. critical care fellowships over the past 6 years (2016-2021)., Methods: Data on gender, race, and ethnicity of critical care fellows in five Accreditation Council on Graduate Medical Education-accredited training programs (internal medicine, pulmonary and critical care, anesthesiology, surgery, and pediatrics) from 2015 to 2016 to 2020-2021 were obtained from the joint reports of the American Medical Association (AMA) and Association of American Medical Colleges published annually in the Journal of the AMA., Results: From 2016 to 2021, the number of U.S. critical care fellows increased annually, up 23.8%, with the largest number of fellows in pulmonary critical care medicine (60.1%). The percentage of female critical care fellows slightly increased from 38.7% to 39.4% ( p = 0.57). White fellows significantly decreased from 57.4% to 49.3% ( p = 0.0001); similarly, Asian fellows significantly decreased from 30.8% to 27.5% ( p = 0.004). The percentage of Black or African American fellows was not statistically significantly different (4.9% vs 4.4%; p = 0.44). The number of fellows who self-identified as multiracial significantly increased from 52 (1.9%) to 91 (2.7%) ( p = 0.043). The percentage of fellows who identified as Hispanic was not significantly different (6.7% vs 7.5%; p = 0.23)., Conclusions: The percentage of women and racially and ethnically minoritized fellows (Black and Hispanic) remain underrepresented in critical care fellowship programs. Additional research is needed to better understand these demographic trends in our emerging critical care physician workforce and enhance diversity., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Pancreatic cancer is the fourth most common cause of cancer-related death in the United States. Despite advancements in surgery and chemoradiation therapies, pancreatic cancer has a 5-year survival rate of only 11% in the United States. Cryoablation is emerging as a new and effective therapy for locally advanced pancreatic cancer and symptom palliation in metastatic disease. To our knowledge, the occurrence of disseminated intravascular coagulation (DIC) after cryoablation is rare., Case Description: A 47-year-old woman with no significant past medical history was diagnosed with pancreatic cancer and underwent a Whipple procedure followed by chemotherapy with gemcitabine and paclitaxel. Due to the abdominal lymph nodes, peritoneum, right femur, and surrounding soft tissue metastases, she received systemic palliative chemotherapy with gemcitabine and paclitaxel and underwent right femur tumor excision, open reduction, and internal fixation, followed by radiation therapy. She continued to have persistent pain and underwent palliative percutaneous cryoablation of the metastatic tumor under computed tomography (CT) and ultrasound guidance. Immediately post procedure, she developed slow but continuous blood oozing at the ablation site, which was difficult to control despite compression dressings, reinforcement sutures, and local thrombin powder. The patient was transferred to the intensive care unit where she was noted to be hypotensive and tachycardic, with petechiae in both lower extremities. Laboratory studies were consistent with DIC and peripheral blood smear revealed multiple schistocytes. CT angiogram of the right lower extremity did not show any bleeding vessel amenable to embolization. She was transfused red blood cells, platelets, fresh frozen plasma, and cryoprecipitate. Despite multiple daily transfusions, she continued to have pain and remained persistently thrombocytopenic and coagulopathic. After discussion with the patient and her family, she chose to transition to comfort care measures and died., Conclusions: DIC is an unusual but life-threatening complication of advanced pancreatic cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-23-13/coif). The authors have no conflicts of interest to declare.

Background: Little is known regarding the career paths of adult multidisciplinary critical care medicine (CCM) fellowship graduates., Objective: The purpose of this study is to describe the demographic profiles and characteristics of the first jobs held by internal medicine-CCM fellowship graduates trained at a freestanding cancer center., Methods: An electronic survey was developed via Research Electronic Data Capture that addressed first employment parameters and was sent between May 1, 2019, and December 31, 2021, to 133 CCM fellows who completed CCM fellowship training from 2000 to 2020 at our institution., Results: A total of 93 fellows (70%) responded to the postfellowship job survey; 80 (60%) with complete responses were analyzed. Seventy-four percent of respondents were men, 41% were White, 81% were international medical graduates, and 31% were holders of J-1 exchange visitor ( n  = 8) or H-1B ( n  = 17) visas. The mean age at completion of CCM fellowship was 36 years. Twenty-seven respondents (34%) completed two years of fellowship training and 53 (66%) completed one year. Internal medicine was the primary residency training before CCM fellowship for 75 respondents (94%) and emergency medicine for 5 (6%). Of those who did one year of fellowship ( n  = 53), 45 (85%) had already completed two-year fellowships in pulmonary medicine. Thirty-two respondents (40%) completed training from 2000 to 2009 and 48 (60%) from 2010 to 2020. The first employment for the majority (>80%) of graduates was in community teaching hospitals. Of the graduates who spent ⩾50% of time clinically in CCM, 85% rounded in multiple intensive care units (ICU). Compensation sources were from hospitals for 81%, private billing for 15%, and through faculty practice plans for 4% of respondents. At the time of survey completion, 51 respondents (64%) were still at their first jobs; of these, slightly more than half (56%) had graduated from the fellowship program in the past 10 years., Conclusion: The majority of CCM fellowship graduates from our program practiced CCM at community teaching hospitals, rounded in multiple ICUs, and were compensated primarily by the hospital., (Copyright © 2023 by the American Thoracic Society.)

Purpose: To investigate the intent of, and reason for, administration of oncologic therapies in the intensive care unit (ICU)., Methods: Single center, retrospective, cohort study of patients with cancer who received oncologic therapies at a tertiary cancer center ICU between April 1, 2019 and March 31, 2020. Oncologic therapies included traditional cytotoxic chemotherapy, targeted therapy, immunotherapy, hormonal or biologic therapy directed at a malignancy and were characterized as initiation (initial administration) or continuation (part of an ongoing regimen)., Results: 84 unique patients (6.8% of total ICU admissions) received oncologic therapies in the ICU; 43 (51%) had hematologic malignancies and 41 (49%) had solid tumors. The intent of oncologic therapy was palliative in 63% and curative in 27%. Twenty-two (26%) patients received initiation and 62 (74%) received continuation oncologic therapies. The intent of oncologic therapy was significantly different by regimen type (initiation vs. continuation, p = <0.0001). Initiation therapy was more commonly prescribed with curative intent and continuation therapy was more commonly administered with palliative intent (p = <0.0001). Oncologic therapies were given in the ICU mainly for an oncologic emergency (56%) and because the patients happened to be in the ICU for a non-oncologic critical illness when their oncologic therapy was due (34.5%)., Conclusion: Our study provides intensivists with a better understanding of the context and intent of oncologic therapies and why these therapies are administered in the ICU.

Critical illness-related corticosteroid insufficiency (CIRCI) is a state of systemic inflammation involving dysregulation of the hypothalamic-pituitary-adrenal axis, altered cortisol metabolism, and tissue resistance to corticosteroids. Many conditions may be associated with CIRCI, including sepsis, septic shock, acute respiratory distress syndrome, and severe community-acquired pneumonia. Recommendations and practice for diagnosing and treating this condition have evolved as information has emerged. Here, the author reviews the current thinking., (Copyright © 2022 The Cleveland Clinic Foundation. All Rights Reserved.)

Purpose: To estimate the incidence of new prescription of enteral opioids on hospital discharge in opioid naïve, non-surgical, critically ill patients and evaluate the risk factors associated with such occurrence., Methods: Using hospital-wide and ICU databases, we retrospectively identified all patients (≥ 18 years old) who were admitted to the 20-bed adult ICU of Memorial Sloan Kettering Cancer Center (MSKCC) between July 1, 2015 and April 20, 2020. Patients' electronic medical records (EMR) were retrieved and patient demographics, peri-ICU admission data were captured and analyzed., Results: During the study period, a total of 3755 opioid naïve patients were admitted to the ICU and 848 patients met the inclusion criteria. Among these, 346 (40.8%) patients were discharged with a new opioid prescription. Age at ICU admission, preadmission use of benzodiazepine, and antidepressants, a diagnosis of sepsis, and use of mechanical ventilation, antidepressants or, opioid infusion for greater than 4 h during the ICU stay, hospital length of stay (LOS), and days between ICU discharge and hospital discharge were independently associated with increased odds of a new opioid prescription., Conclusions: A significant proportion of opioid naïve non-surgical ICU survivors receive a new opioid prescription on hospital discharge., Competing Interests: Declaration of competing interest LET is a grant recipient through Merck Investigator Studies Program (MISP) to fund clinical trial at MSKCC (NCT03808077). LET serves a consultancy and advisory role for Merck & Co. Pharmaceutical Company. LET serves a consultancy and advisory role for GE Healthcare., (Copyright © 2021. Published by Elsevier Inc.)

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., Competing Interests: This data was accepted to be presented as abstracts and an oral presentation at the Society of Critical Care Medicine Congress in Orlando, FL, 2020. Drs. Gutierrez, Brudno, and Athale received support for article research from the National Institutes of Health. Dr. Gutierrez disclosed the off-label product use of anakinra; she disclosed that she served, and will serve again, in the advisory board for Legend Biotech and Janssen in August 2020. Drs. Gutierrez, May, and McEvoy disclosed the off-label product use of Siltuximab. Dr. Brown received funding from La Jolla Pharmaceutical outside the submitted work. Dr. May disclosed the off-label product use of Corticosteroids. Dr. Beitinjaneh received funding from KITE pharmaceuticals on August 2018. Drs. Brudno and Kochenderfer disclosed government work. Dr. Kochenderfer’s institution received funding from KITE pharmaceuticals, Bristol Meyers Squibb, and Kyverna; he is the principal investigator of Cooperative Research and Development Agreements with Kite, a Gilead Company and Celgene. Dr. Lin as Principal Investigator Mayo Clinic receives compensation for research activities and clinical trials with Kite/Gilead, Janssen, Celgene, BlueBird Bio, Merck, Boston Scientific, Gamida, and Takeda; advisory board with Kite/Gilead, Novartis, Janssen, Legend BioTech, JUNO, Bristol-Myers-Squibb (BMS), Celgene, BlueBird Bio, and Ethos; Data and Safety Monitoring Board: Sorrento; and steering committee: Celgene, Janssen, and Legend BioTech. Dr. McEvoy received funding from United Therapeutics. Dr. Westin received funding from BMS, Novartis, Kite Gilead, Juno Celgene, Genentech, AstraZeneca, Morphosys, and ADC Therapeutics. 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.)

Objectives: The Society of Critical Care Medicine convened its Academic Leaders in Critical Care Medicine taskforce on February 22, 2016, during the 45th Critical Care Congress to develop a series of consensus papers with toolkits for advancing critical care organizations in North America. The goal of this article is to propose a framework based on the expert opinions of critical care organization leaders and their responses to a survey, for current and future critical care organizations, and their leadership in the health system to design and implement successful regionalization for critical care in their regions., Data Sources and Study Selection: Members of the workgroup convened monthly via teleconference with the following objectives: to 1) develop and analyze a regionalization survey tool for 23 identified critical care organizations in the United States, 2) assemble relevant medical literature accessed using Medline search, 3) use a consensus of expert opinions to propose the framework, and 4) create groups to write the subsections and assemble the final product., Data Extraction and Synthesis: The most prevalent challenges for regionalization in critical care organizations remain a lack of a strong central authority to regulate and manage the system as well as a lack of necessary infrastructure, as described more than a decade ago. We provide a framework and outline a nontechnical approach that the health system and their critical care medicine leadership can adopt after considering their own structure, complexity, business operations, culture, and the relationships among their individual hospitals. Transforming the current state of regionalization into a coordinated, accountable system requires a critical assessment of administrative and clinical challenges and barriers. Systems thinking, business planning and control, and essential infrastructure development are critical for assisting critical care organizations., Conclusions: Under the value-based paradigm, the goals are operational efficiency and patient outcomes. Health systems that can align strategy and operations to assist the referral hospitals with implementing regionalization will be better positioned to regionalize critical care effectively., Competing Interests: Dr. Galvagno’s institution received funding from the Department of Defense; he received funding from Northwest Anesthesia Seminars and from expert defense for medicolegal work. Dr. Jacobi received funding from Visante, Merck, Pfizer, American Society of Health System Pharmacists, and a Pharmacy Continuing Education group. 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.)

Purpose: Serious immune checkpoint inhibitor (ICI)-related neurotoxicity is rare. There is limited data on the specifics of care and outcomes of patients with severe neurological immune related adverse events (NirAEs) admitted to the Intensive Care Unit (ICU)., Materials and Methods: Retrospective study of patients with severe NirAEs admitted to the ICU at 3 academic centers between January 2016 and December 2018. Clinical data collected included ICI exposure, type of NirAE (central [CNS] or peripheral nervous system [PNS) disorders), and patient outcomes including neurological recovery and mortality., Results: Seventeen patients developed severe NirAEs. Eight patients presented with PNS disorders; 6 with myasthenia gravis (MG), 1 had a combination of MG and polyneuropathy and 1 had Guillain-Barre syndrome. Nine patients had CNS disorders (6 seizures and 5 had concomitant encephalopathy. During ICU admission, 65% of patients required mechanical ventilation, 35% vasopressors, and 18% renal replacement therapy. The median ICU and hospital length of stay were 7 (2-36) and 18 (4-80) days, respectively. Hospital mortality was 29%. At hospital discharge, 18% of patients made a full neurologic recovery, 41% partial recovery, and 12% did not recover., Conclusion: Severe NirAEs while uncommon, can be serious or even life-threatening if not diagnosed and treated early., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Adult patients with cancer have a greater likelihood of developing severe illness and death from coronavirus disease 2019 compared with patients without cancer. We sought to characterize the clinical characteristics and outcomes of cancer patients who tested positive for severe acute respiratory syndrome coronavirus 2 and were admitted to the ICU at the peak of the first wave of the pandemic in the United States., Design: A single-center retrospective cohort study., Setting: Two medical-surgical ICUs of a tertiary-care cancer center., Patients/subjects: All consecutive adult patients (≥ 18 yr) with current or past (< 2 yr) diagnosis of cancer who were admitted to the ICU with coronavirus disease 2019 between March 1, and June 30, 2020., Interventions: None., Measurements and Main Results: Demographic, clinical, and laboratory data of 89 critically ill cancer patients were extracted from electronic medical records. Median age was 65 years (interquartile range, 57-70 yr), 66% were White, and 58% male. Approximately a third of patients had three or more comorbidities. Fifty-one patients (57%) had solid tumors, and 38 (42%) had hematologic malignancies. Sixty-one patients (69%) received cancer-directed therapy within the previous 90 days. Sixty patients (67%) required mechanical ventilation, 56% required prone positioning, 28% underwent tracheostomy, and 71% required vasopressors. Hospital mortality was 45% (40/89). Among those who required mechanical ventilation, mortality was 53% (32/60). Hospital mortality was significantly higher among patients with hematologic malignancies, higher severity of illness and organ failure scores, need for invasive mechanical ventilation and vasopressor therapy, lower hemoglobin and platelet count, and higher d-dimer levels at ICU admission. ICU and hospital length of stay were 10 and 26 days, respectively. At 9-month follow-up, the mortality rate was 54% (48/89)., Conclusions: We report the largest case series and intermediate-term follow-up of cancer patients with coronavirus disease 2019 who were admitted to the ICU. Hospital mortality was 45%. Intermediate-term outcome after hospital discharge was favorable., Competing Interests: The 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.)

Corticosteroids, anti-CD20 agents, immunotherapies, and cytotoxic chemotherapy are commonly used in the treatment of patients with cancer. It is unclear how these agents affect patients with cancer who are infected with SARS-CoV-2. We retrospectively investigated associations between SARS-CoV-2-associated respiratory failure or death with receipt of the aforementioned medications and with pre-COVID-19 neutropenia. The study included all cancer patients diagnosed with SARS-CoV-2 at Memorial Sloan Kettering Cancer Center until June 2, 2020 (N = 820). We controlled for cancer-related characteristics known to predispose to worse COVID-19 as well as level of respiratory support during corticosteroid administration. Corticosteroid administration was associated with worse outcomes prior to use of supplemental oxygen; no statistically significant difference was observed in sicker cohorts. In patients with metastatic thoracic cancer, 9 of 25 (36%) and 10 of 31 (32%) had respiratory failure or death among those who did and did not receive immunotherapy, respectively. Seven of 23 (30%) and 52 of 187 (28%) patients with hematologic cancer had respiratory failure or death among those who did and did not receive anti-CD20 therapy, respectively. Chemotherapy itself was not associated with worse outcomes, but pre-COVID-19 neutropenia was associated with worse COVID-19 course. Relative prevalence of chemotherapy-associated neutropenia in previous studies may account for different conclusions regarding the risks of chemotherapy in patients with COVID-19. In the absence of prospective studies and evidence-based guidelines, our data may aid providers looking to assess the risks and benefits of these agents in caring for cancer patients in the COVID-19 era.

In recent years, major advances in oncology especially the advent of targeted agents and immunotherapies (immune checkpoint inhibitors [ICIs] and chimeric antigen receptor [CAR] T-cell therapy) have led to improved quality of life and survival rates in patients with cancer. This article focuses on the clinical features, and grading and management of toxicities associated with ICIs and CAR T-cell therapy. In addition, because cardiotoxicity is one of the most harmful effects of anticancer therapeutics, we describe the risk factors and mechanisms of cardiovascular injury associated with newer agents, screening technologies for at-risk patients, and preventive and treatment strategies., Competing Interests: Disclosure The authors have no commercial or financial conflicts of interest related to this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)