Importance: Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative.Objectives: To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies.Design, Settings, and Participants: The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis—114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023.Interventions: Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days.Main Outcomes and Measures: A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death).Results: Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, −14.7 [95% CI −6.2 to −23.2] and −14.7 [95% CI −6.2 to −23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, −13.5; 95% CI −2.6 to −24.3).Conclusions and Relevance: This randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis.Trial Registration: ClinicalTrials.gov Identifier: NCT04808882

Rationale: Psychological resilience (the ability to thrive in adversity) may protect against mental-health symptoms in healthcare professionals during coronavirus disease (COVID-19) waves. Objectives: To identify determinants of resilience in ICU staff members. Methods: In this cross-sectional survey in 21 French ICUs, staff members completed the 10-item Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Impact of Event Scale–Revised (for post-traumatic stress disorder [PTSD]). Factors independently associated with resilience were identified. Measurements and Main Results: The response rate was 73.1% (950 of 1,300). The median 10-item Connor-Davidson Resilience Scale score was 29 (interquartile range, 25–32). Symptoms of anxiety, depression, and PTSD were present in 61%, 39%, and 36% of staff members, respectively. Distress associated with the COVID-19 infodemic was correlated with symptoms of depression and PTSD. More resilient respondents less often had symptoms of anxiety, depression, and PTSD. Greater resilience was independently associated with male sex, having provided intensive care during the early waves, having managed more than 50 patients with COVID-19, and, compared with earlier waves, working longer hours, having greater motivation, and more often involving families in end-of-life decisions. Independent risk factors for lower resilience were having managed more than 10 patients who died of COVID-19, having felt frightened or isolated, and greater distress from the COVID-19 infodemic. Conclusions: This study identifies modifiable determinants of resilience among ICU staff members. Longitudinal studies are needed to determine whether prior resilience decreases the risk of mental ill health during subsequent challenges. Hospital and ICU managers, for whom preserving mental well-being among staff members is a key duty, should pay careful attention to resilience.

To evaluate the diagnostic performances of two training programs for residents with no prior ultrasound experience to reach competences in extended basic critical care transthoracic echocardiography (CCE) including Doppler capabilities. This is a prospective observational study in two intensive care units of teaching hospitals. Group I (five residents) completed a short training program (4-h theory; 3-h practical); group II (six residents) completed a longer training program (6-h theory; 12-h practical). The residents and an expert examined all patients who required a transthoracic echocardiography. Their agreement studied by Cohen’s κ coefficient, concordance coefficient correlation (CCC) and Bland–Altman plots was used as an indicator of program effectiveness. Group I performed 136 CCEs (mean/resident 27; range 22–32; 65 in ventilated patients) in 115 patients (62 men; 64 ± 18 years; Simplified Acute Physiologic Score [SAPS] II 37 ± 18). Group II performed 158 CCEs (mean/resident 26; range 21–31; 65 in ventilated patients) in 108 patients (64 men; 58 ± 17 years; SAPS II 42 ± 22). Both groups adequately assessed left ventricular (LV) systolic function (κ 0.75, 95 % confidence interval [CI] 0.64–0.86; κ 0.77, 95 % CI 0.66–0.88, respectively) and pericardial effusion (κ 0.83, 95 % CI 0.67–0.99; κ 0.76, 95 % CI 0.60–0.93, respectively). Group II appraised severe right ventricular dilatation and significant left-sided valve disease with good to very good agreement (κ 0.80, 95 % CI 0.56–0.96; κ 0.79, 95 % CI 0.66–0.93, respectively). Regarding left ventricular ejection fraction, E/A ratio, E/e′ ratio and aortic peak velocity assessed by group II, CCCs were all >0.70 and the bias (mean difference) ±SD on Bland–Altman analysis was 1.3 ± 8.8 %, 0 ± 0.3, 0.4 ± 2.2 and 0.1 ± 0.4 m/s, respectively. Detection of paradoxical septum (κ 0.65, 95 % CI 0.37–0.93), of heterogeneous LV contraction (κ 0.49, 95 % CI 0.33–0.65) and of respiratory variation of the inferior vena cava (κ 0.27, 95 % CI 0.09–0.45), as well as stroke volume measurement (CCC 0.65, 95 % CI 0.54–0.74; bias ± SD −1.4 ± 4.7 cm), was appraised by group II with moderate agreement requiring probably more comprehensive training. Although a training program blending 6-h theory and 12-h practical may be adapted to achieve some essential competences, it seems to be insufficiently to perform a complete extended basic critical care transthoracic echocardiography including Doppler capabilities.

Background: Septic shock remains a significant cause of death in critically ill patients. During septic shock, some patients will retain microcirculatory disorders despite optimal hemodynamic support (i.e., fluid resuscitation, vasopressors, inotropes). Alterations in the microcirculation are a key pathophysiological factor of organ dysfunction and death in septic shock patients. Ilomedin is a prostacyclin analog with vasodilatory effect and anti-thrombotic properties (i.e., inhibition of platelet aggregation) preferentially at the microcirculatory level. We hypothesize that early utilization of intravenous Ilomedin in septic shock patients with clinical persistence of microperfusion disorders would improve the recovery of organ dysfunction. Methods: The I-MICRO trial is a multicenter, prospective, randomized, double-blinded, placebo-controlled study. We plan to recruit 236 adult patients with septic shock and persistent microcirculatory disorders (i.e., skin mottling or increased capillary refill time) despite hemodynamic support. Participants will be randomized to receive a 48-h intravenous infusion of either Ilomedin or placebo starting at the earliest 6 h and later 24 h after septic shock. The primary outcome will be the change (delta) of sequential organ failure assessment (SOFA) score between randomization and day 7. Secondary outcomes will include mean SOFA score during the first 7 days after randomization, mortality at day 28 post-randomization, number of ventilation-free survival days in the 28 days post-randomization, number of renal replacement therapy-free survival days in the 28 days post-randomization, number of vasopressor-free survival days in the 28 days post-randomization, and mottling score at day 1 after randomization. Discussion: The trial aims to provide evidence on the efficacy and safety of Ilomedin in patients with septic shock and persistent microcirculatory disorders. Trial registration: NCT NCT03788837. Registered on 28 December 2018

Background: Echocardiographic parameters have been poorly investigated for estimating cardiovascular risk in patients with sepsis and new-onset atrial fibrillation. We aim to assess the prevalence of transesophageal echocardiographic abnormalities and their relationship with cardiovascular events in mechanically ventilated patients with sepsis and new-onset atrial fibrillation. Methods: In this prospective multicenter pilot study, left atrial/left atrial appendage (LA/LAA) dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were assessed using an initial transesophageal echocardiographic study, which was repeated after 48–72 h to detect LA/LAA thrombus formation. The study outcome was a composite of cardiovascular events at day 28, including arterial thromboembolic events (ischemic stroke, non-cerebrovascular arterial thromboembolism, LA/LAA thrombus), major bleeding, and all-cause death. Results: The study population comprised 94 patients (septic shock 63%; 35% women; median age 69 years). LA/LAA dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were detected in 17 (19%), 22 (24%), and 27 (29%) patients, respectively. At day 28, the incidence of cardiovascular events was 46% (95% confidence interval [CI]: 35 to 56). Arterial thromboembolic events and major bleeding occurred in 7 (7%) patients (5 ischemic strokes, 1 non-cerebrovascular arterial thromboembolism, 2 left atrial appendage thrombi) and 18 (19%) patients, respectively. At day 28, 27 patients (29%) died. Septic shock (hazard ratio [HR]: 2.36; 95% CI 1.06 to 5.29) and left ventricular systolic dysfunction (HR: 2.06; 95% CI 1.05 to 4.05) were independently associated with cardiovascular events. Conclusions: Transesophageal echocardiographic abnormalities are common in mechanically ventilated patients with sepsis and new-onset atrial fibrillation, but only left ventricular systolic dysfunction was associated with cardiovascular events at day 28.