IMPORTANCE The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. OBJECTIVES To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. EXPOSURES Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. MAIN OUTCOMES AND MEASURES The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. RESULTS A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (Ն80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (Ն40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (PaO 2 :FIO 2 <100 vs Ն300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs Ն100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. CONCLUSIONS AND RELEVANCE This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.

IMPORTANCE Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. OBJECTIVE To test whether tocilizumab decreases mortality in this population. DESIGN, SETTING, AND PARTICIPANTS The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. EXPOSURES Treatment with tocilizumab in the first 2 days of ICU admission. MAIN OUTCOMES AND MEASURES Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. RESULTS Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). CONCLUSIONS AND RELEVANCE Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.

ARDS seems to be a common and fatal syndrome in a hospital in Rwanda, with few patients admitted to an ICU. The Berlin definition is likely to underestimate the impact of ARDS in low-income countries, where resources to meet the definition requirements are lacking. Although the Kigali modification requires validation before widespread use, we hope this study stimulates further work in refining an ARDS definition that can be consistently used in all settings.

IMPORTANCEPostoperative delirium is common following cardiac surgery and may be affected by choice of analgesic and sedative.OBJECTIVE To evaluate the effect of postoperative intravenous (IV) acetaminophen (paracetamol) vs placebo combined with IV propofol vs dexmedetomidine on postoperative delirium among older patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS Randomized, placebo-controlled, factorial clinical trial among 120 patients aged 60 years or older undergoing on-pump coronary artery bypass graft (CABG) surgery or combined CABG/valve surgeries at a US center. Enrollment was September 2015 to April 2018, with follow-up ending in April 2019.INTERVENTIONS Patients were randomized to 1 of 4 groups receiving postoperative analgesia with IV acetaminophen or placebo every 6 hours for 48 hours and postoperative sedation with dexmedetomidine or propofol starting at chest closure and continued for up to 6 hours (acetaminophen and dexmedetomidine: n = 29; placebo and dexmedetomidine: n = 30; acetaminophen and propofol: n = 31; placebo and propofol: n = 30). MAIN OUTCOMES AND MEASURESThe primary outcome was incidence of postoperative in-hospital delirium by the Confusion Assessment Method. Secondary outcomes included delirium duration, cognitive decline, breakthrough analgesia within the first 48 hours, and ICU and hospital length of stay. RESULTS Among 121 patients randomized (median age, 69 years; 19 women [15.8%]), 120 completed the trial. Patients treated with IV acetaminophen had a significant reduction in delirium (10% vs 28% placebo; difference, −18% [95% CI, −32% to −5%]; P = .01; HR, 2.8 [95% CI, 1.1-7.8]). Patients receiving dexmedetomidine vs propofol had no significant difference in delirium (17% vs 21%; difference, −4% [95% CI, −18% to 10%]; P = .54; HR, 0.8 [95% CI, 0.4-1.9]). There were significant differences favoring acetaminophen vs placebo for 3 prespecified secondary outcomes: delirium duration (median, 1 vs 2 days; difference, −1 [95% CI, −2 to 0]), ICU length of stay (median, 29.5 vs 46.7 hours; difference, −16.7 [95% CI, −20.3 to −0.8]), and breakthrough analgesia (median, 322.5 vs 405.3 μg morphine equivalents; difference, −83 [95% CI, −154 to −14]). For dexmedetomidine vs propofol, only breakthrough analgesia was significantly different (median, 328.8 vs 397.5 μg; difference, −69 [95% CI, −155 to −4]; P = .04). Fourteen patients in both the placebo-dexmedetomidine and acetaminophen-propofol groups (46% and 45%) and 7 in the acetaminophendexmedetomidine and placebo-propofol groups (24% and 23%) had hypotension.CONCLUSIONS AND RELEVANCE Among older patients undergoing cardiac surgery, postoperative scheduled IV acetaminophen, combined with IV propofol or dexmedetomidine, reduced in-hospital delirium vs placebo. Additional research, including comparison of IV vs oral acetaminophen and other potentially opioid-sparing analgesics, on the incidence of postoperative delirium is warranted.

Purpose Limited data are available on venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure from coronavirus disease 2019 (COVID-19). Methods We examined the clinical features and outcomes of 190 patients treated with ECMO within 14 days of ICU admission, using data from a multicenter cohort study of 5122 critically ill adults with COVID-19 admitted to 68 hospitals across the United States. To estimate the effect of ECMO on mortality, we emulated a target trial of ECMO receipt versus no ECMO receipt within 7 days of ICU admission among mechanically ventilated patients with severe hypoxemia (PaO 2 /FiO 2 < 100). Patients were followed until hospital discharge, death, or a minimum of 60 days. We adjusted for confounding using a multivariable Cox model. Results Among the 190 patients treated with ECMO, the median age was 49 years (IQR 41–58), 137 (72.1%) were men, and the median PaO 2 /FiO 2 prior to ECMO initiation was 72 (IQR 61–90). At 60 days, 63 patients (33.2%) had died, 94 (49.5%) were discharged, and 33 (17.4%) remained hospitalized. Among the 1297 patients eligible for the target trial emulation, 45 of the 130 (34.6%) who received ECMO died, and 553 of the 1167 (47.4%) who did not receive ECMO died. In the primary analysis, patients who received ECMO had lower mortality than those who did not (HR 0.55; 95% CI 0.41–0.74). Results were similar in a secondary analysis limited to patients with PaO 2 /FiO 2 < 80 (HR 0.55; 95% CI 0.40–0.77). Conclusion In select patients with severe respiratory failure from COVID-19, ECMO may reduce mortality. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-020-06331-9.

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Objective The mechanisms leading to worse outcomes in African-American (AA) women with preeclampsia/eclampsia remain unclear. Our objective was to identify racial differences in maternal comorbidities, peripartum characteristics, and maternal and fetal outcomes. Methods/Results When compared to white women with preeclampsia/eclampsia, AA women had an increased unadjusted risk of inpatient maternal mortality (OR 3.70, 95% CI: 2.19-6.24). After adjustment for covariates, in-hospital mortality for AA women remained higher than that for white women (OR 2.85, 95% CI: 1.38-5.53), while, the adjusted risk of death among Hispanic women did not differ from that for white women. We also found an increased risk of intrauterine fetal death (IUFD) among AA women. When compared to white women with preeclampsia, AA women had an increased unadjusted odds of IUFD (OR 2.78, 95% CI: 2.49-3.11), which remained significant after adjustment for covariates (adjusted OR 2.45, 95% CI: 2.14-2.82). In contrast, IUFD among Hispanic women did not differ from that for white women after adjusting for covariates. Conclusions and Relevance Our data suggest that African American women are more likely to have risk factors for preeclampsia and more likely to suffer an adverse outcome during peripartum care. Future research should examine whether controlling co-morbidities and other risk factors will help to alleviate racial disparities in outcomes in this cohort of women.

BackgroundCardiogenic shock (CS) is associated with significant morbidity, and mortality rates approach 40% to 60%. Treatment for CS requires an aggressive, sophisticated, complex, goal‐oriented, therapeutic regimen focused on early revascularization and adjunctive supportive therapies, suggesting that hospitals with greater CS volume may provide better care. The association between CS hospital volume and inpatient mortality for CS is unclear.Methods and ResultsWe used the Nationwide Inpatient Sample to examine 533 179 weighted patient discharges from 2675 hospitals with CS from 2004 to 2011 and divided them into quartiles of mean annual hospital CS case volume. The primary outcome was in‐hospital mortality. Multivariate adjustments were performed to account for severity of illness, relevant comorbidities, hospital characteristics, and differences in treatment. Compared with the highest volume quartile, the adjusted odds ratio for inpatient mortality for persons admitted to hospitals in the lowest‐volume quartile (≤27 weighted cases per year) was 1.27 (95% CI 1.15 to 1.40), whereas for admission to hospitals in the low‐volume and medium‐volume quartiles, the odds ratios were 1.20 (95% CI 1.08 to 1.32) and 1.12 (95% CI 1.01 to 1.24), respectively. Similarly, improved survival was observed across quartiles, with an adjusted inpatient mortality incidence of 41.97% (95% CI 40.87 to 43.08) for hospitals with the lowest volume of CS cases and a drop to 37.01% (95% CI 35.11 to 38.96) for hospitals with the highest volume of CS cases. Analysis of treatments offered between hospital quartiles revealed that the centers with volumes in the highest quartile demonstrated significantly higher numbers of patients undergoing coronary artery bypass grafting, percutaneous coronary intervention, or intra‐aortic balloon pump counterpulsation. A similar relationship was demonstrated with the use of mechanical circulatory support (ventricular assist devices and extracorporeal membrane oxygenation), for which there was significantly higher use in the higher volume quartiles.ConclusionsWe demonstrated an association between lower CS case volume and higher mortality. There is more frequent use of both standard supportive and revascularization techniques at the higher volume centers. Future directions may include examining whether early stabilization and transfer improve outcomes of patients with CS who are admitted to lower volume centers.