Critical Care Medicine最新文献

Objectives: COVID-19 treatment guidelines recommend baricitinib or tocilizumab for the management of hospitalized patients with COVID-19. We compared the effectiveness of baricitinib vs. tocilizumab on mortality and clinical outcomes among hospitalized patients with COVID-19.

Design: Multicenter, retrospective, propensity-weighted cohort study using a target trial emulation approach.

Setting: The National COVID Cohort Collaborative (N3C), which is the largest electronic health records data on COVID-19 in the United States. The setting included 75 hospitals.

Patients: Adults who were hospitalized for COVID-19.

Interventions: Newly initiated on baricitinib or tocilizumab.

Measurements and main results: Our primary outcome was 28-day mortality. We used propensity scores with inverse probability of treatment weights (IPTWs) to control bias and confounding while comparing treatments. Among 10,661 individuals included in the study, 6,229 (58.4%) received baricitinib and 4,432 (41.6%) tocilizumab. Overall, the mean age of the cohort was 60.0 ± 15.1 years, 6429 (60.3%) were male, and 19.2% received invasive mechanical ventilation. After IPTW adjustment, baricitinib use was associated with lower 28-day mortality (odds ratio [OR], 0.91; 95% CI, 0.85-0.98) and hospital (OR, 0.88; 95% CI, 0.82-0.94) mortality compared with tocilizumab. Baricitinib was also associated with shorter hospital length of stay (incident rate ratio, 0.92; 95% CI, 0.90-0.94) and lower rates of hospital-acquired infections (OR, 0.86; 95% CI, 0.75-0.99), although no difference in ICU length of stay was noted between the two groups.

Conclusions: In this large, diverse cohort of U.S. hospitalized adults with COVID-19, baricitinib was associated with significantly lower 28-day mortality, hospital mortality, shorter hospital length of stay, and less hospital-acquired infections compared with tocilizumab.

Objectives: The benefits of early rehabilitation for patients with acute heart failure (HF) requiring IV inotropic drugs have yet to be determined. We investigated the association between early rehabilitation and short-term clinical outcomes in patients with acute HF requiring IV inotropic drugs.

Design: Retrospective cohort study.

Setting: This study used data including more than 90% of patients at a tertiary emergency hospital in Japan.

Patients: This study included patients with acute HF who required IV inotropic drugs within 2 days of admission.

Interventions: We compared patients who commenced rehabilitation within 2 days of admission (the early rehabilitation group) and those who did not (the control group).

Measurements and main results: Propensity score matching was used to compare in-hospital mortality, 30-day all-cause and HF readmissions, length of stay, and Barthel Index (BI) at discharge between patients who received early rehabilitation and those who did not. Totally, 38,302 patients were eligible for inclusion; of these, 5,127 received early rehabilitation and 5,126 pairs were generated by propensity score matching. After propensity score matching, the patients who received early rehabilitation had a lower in-hospital mortality rate than those who did not (9.9% vs. 13.2%; p < 0.001). The relative risk (95% CI) of early rehabilitation for in-hospital mortality was 0.75 (0.67-0.83). Patients undergoing early rehabilitation exhibited a shorter mean length of stay (25.5 vs. 27.1; p < 0.001), lower 30-day all-cause (14.1% vs. 16.4%; p = 0.001) and HF (8.6% vs. 10.4%; p = 0.002) readmissions, and higher BI scores at discharge (68 vs. 67; p = 0.096). Consistent findings were observed across subgroups, including in patients 80 years old or older, those with a body mass index less than 18.5 kg/m 2 , and those with BI scores less than 60.

Conclusions: The early prescription of rehabilitation was associated with favorable short-term outcomes even for patients with acute HF requiring IV inotropic drugs.

Objectives: Pulmonary ventilation/perfusion (V/Q) mismatch measured by electrical impedance tomography (EIT) is associated with the outcome of patients with the acute respiratory distress syndrome (ARDS), but the underlying pathophysiological mechanisms have not been fully elucidated. The present study aimed to verify the correlation between relevant pathophysiological markers of ARDS severity and V/Q mismatch.

Design: Prospective observational study.

Setting: General ICU of a university-affiliated hospital.

Patients: Deeply sedated intubated adult patients with ARDS under controlled mechanical ventilation.

Interventions: Measures of V/Q mismatch by EIT, respiratory mechanics, gas exchange, lung imaging, and plasma biomarkers.

Measurements and main results: Unmatched V/Q units were assessed by EIT as the fraction of ventilated nonperfused plus perfused nonventilated lung units. At the same time, plasma biomarkers with proven prognostic and mechanistic significance for ARDS (carbonic anhydrase 9 [CA9], hypoxia-inducible factor 1 [HIF1], receptor for advanced glycation endproducts [RAGE], angiopoietin 2 [ANG2], gas exchange, respiratory mechanics, and quantitative chest CT scans were measured. Twenty-five intubated ARDS patients were included with median unmatched V/Q units of 37.1% (29.2-49.2%). Unmatched V/Q units were correlated with plasma levels of CA9 (rho = 0.47; p = 0.01), HIF1 (rho = 0.40; p = 0.05), RAGE (rho = 0.46; p = 0.02), and ANG2 (rho = 0.42; p = 0.03). Additionally, unmatched V/Q units correlated with plateau pressure ( r = 0.38; p = 0.05) and with the number of quadrants involved on chest radiograph ( r = 0.73; p < 0.01). Regional unmatched V/Q units were correlated with the corresponding fraction of poorly aerated lung tissue ( r = 0.62; p = 0.01) and of lung tissue weight (rho: 0.51; p = 0.04) measured by CT scan.

Conclusions: In ARDS patients, unmatched V/Q units are correlated with pathophysiological markers of lung epithelial and endothelial dysfunction, increased lung stress, and lung edema. Unmatched V/Q units could represent a comprehensive marker of ARDS severity, reflecting the complex organ pathophysiology and reinforcing their prognostic significance.

Objectives: Vascular complications after venoarterial extracorporeal membrane oxygenation (ECMO) remains poorly studied, although they may highly impact patient management after ECMO removal. Our aim was to assess their frequency, predictors, and management.

Design: Retrospective, observational cohort study.

Setting: Two ICUs from a tertiary referral academic hospital.

Patients: Adult patients who were successfully weaned from venoarterial ECMO between January 2021 and January 2022.

Interventions: None.

Primary outcome: Vascular complications frequency related to ECMO cannula.

Measurements and main results: A total of 288 patients were implanted with venoarterial ECMO during the inclusion period. One hundred ninety-four patients were successfully weaned, and 109 underwent a CT examination to assess for vascular complications until 4 days after the weaning procedure. The median age of the cohort was 58 years (interquartile range [IQR], 46-64 yr), with a median duration of ECMO support of 7 days (IQR, 5-12 d). Vascular complications were observed in 88 patients (81%). The most frequent complication was thrombosis, either cannula-associated deep vein thrombosis (CaDVT) ( n = 63, 58%) or arterial thrombosis ( n = 36, 33%). Nonthrombotic arterial complications were observed in 48 patients (44%), with 35 (31%) presenting with bleeding. The most common site of CaDVT was the inferior vena cava, occurring in 33 (50%) of cases, with 20% of patients presenting with pulmonary embolism. There was no association between thrombotic complications and ECMO duration, anticoagulation level, or ECMO rotation flow. CT scans influenced management in 83% of patients. In-hospital mortality was 17% regardless of vascular complications.

Conclusions: Vascular complications related to venoarterial ECMO cannula are common after ECMO implantation. CT allows early detection of complications after weaning and impacts patient management. Patients should be routinely screened for vascular complications by CT after decannulation.

Objectives: The optimal approach for resuscitation in septic shock remains unclear despite multiple randomized controlled trials (RCTs). Our objective was to investigate whether previously uncharacterized variation across individuals in their response to resuscitation strategies may contribute to conflicting average treatment effects in prior RCTs.

Design: We randomly split study sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation cohorts. We trained machine learning models to predict individual absolute risk differences (iARDs) in 90-day mortality in derivation cohorts and tested for heterogeneity of treatment effect (HTE) in validation cohorts and swapped these cohorts in sensitivity analyses. We fit the best-performing model in a combined dataset to explore roles of patient characteristics and individual components of early goal-directed therapy (EGDT) to determine treatment responses.

Setting: Eighty-one sites in Australia, New Zealand, Hong Kong, Finland, Republic of Ireland, and the United States.

Patients: Adult patients presenting to the emergency department with severe sepsis or septic shock.

Interventions: EGDT vs. usual care.

Measurements and main results: A local-linear random forest model performed best in predicting iARDs. In the validation cohort, HTE was confirmed, evidenced by an interaction between iARD prediction and treatment ( p < 0.001). When patients were grouped based on predicted iARDs, treatment response increased from the lowest to the highest quintiles (absolute risk difference [95% CI], -8% [-19% to 4%] and relative risk reduction, 1.34 [0.89-2.01] in quintile 1 suggesting harm from EGDT, and 12% [1-23%] and 0.64 [0.42-0.96] in quintile 5 suggesting benefit). Sensitivity analyses showed similar findings. Pre-intervention albumin contributed the most to HTE. Analyses of individual EGDT components were inconclusive.

Conclusions: Treatment response to EGDT varied across patients in two multicenter RCTs with large benefits for some patients while others were harmed. Patient characteristics, including albumin, were most important in identifying HTE.