Factors Associated with Fatigue in COVID-19 ICU Survivors.

PURPOSE: Approximately 30% of people infected with COVID-19 require hospitalization and 20% of them are admitted to an intensive care unit (ICU). Most of these patients experience symptoms of fatigue weeks post-ICU, so understanding the factors associated with fatigue in this population is crucial. METHODS: Fifty-nine patients [38-78 yr] hospitalized in ICU for COVID-19 infection for 32 [6-80] days including 23 [3-57] days of mechanical ventilation, visited the laboratory on two separate occasions. The first visit occurred 52 ± 15 days after discharge and was dedicated to questionnaires, blood sampling and cardiopulmonary exercise testing, while measurements of the knee extensors neuromuscular function and performance fatigability were performed in the second visit 7 ± 2 days later. RESULTS: Using the FACIT-F questionnaire, 56% of patients were classified as fatigued. Fatigued patients had worse lung function score than non- fatigued (i.e. 2.9 ± 0.8 L vs 3.6 ± 0.8 L; 2.4 ± 0.7 l vs 3.0 ± 0.7 L for forced vital capacity and forced expiratory volume in one second, respectively) and forced vital capacity was identified as a predictor of being fatigued. Maximal voluntary activation was lower in fatigued patients than non-fatigued patients (82 ± 14% vs 91 ± 3%) and was the only neuromuscular variable that discriminated between fatigued and non-fatigued patients. Patient-reported outcomes also showed differences between fatigued and non-fatigued patients for sleep, physical activity, depression and quality of life (p < 0.05). CONCLUSIONS: COVID-19 survivors showed altered respiratory function 4 to 8 weeks after discharge, that was further deteriorated in fatigued patients. Fatigue was also associated with lower voluntary activation and patient-reported impairments (i.e. sleep satisfaction, quality of life or depressive state). The present study reinforces the importance of exercise intervention and rehabilitation to counteract cardiorespiratory and neuromuscular impairments of COVID-19 patients admitted in ICU, especially individuals experiencing fatigue.

Dosing Regimen for Cefotaxime Should Be Adapted to the Stage of Renal Dysfunction in Critically Ill Adult Patients-A Retrospective Study.

Cefotaxime administration is recommended in doses of 3-12 g/day in adults with a Glomerular Filtration Rate (GFR) > 5 mL/min. This study aimed to assess the impact of renal function and obesity on cefotaxime concentrations in intensive care unit (ICU) patients. A retrospective cohort study was conducted on consecutive ICU patients receiving continuous cefotaxime infusion between 2020 and 2022 [IRBN992021/CHUSTE]. Doses were not constant; consequently, a concentration-to-dose ratio (C/D) was considered. Statistical analysis was performed to assess the relationship between cefotaxime concentrations, renal function, and obesity. A total of 70 patients, median age 61 years, were included, with no significant difference in cefotaxime concentrations between obese and non-obese patients. However, concentrations varied significantly by GFR, with underdosing prevalent in patients with normal to increased renal function and overdosing in those with severely impaired renal function. Adjustment of cefotaxime dosing according to GFR was associated with improved target attainment. Cefotaxime dosing in critically ill patients should consider renal function, with higher initial doses required in patients with normal to increased GFR and lower doses in those with severely impaired renal function. Therapeutic drug monitoring may aid in optimising dosing regimens. Prospective studies are warranted to validate these findings and inform clinical practice.

Renal replacement therapy initiation strategies in comatose patients with severe acute kidney injury: a secondary analysis of a multicenter randomized controlled trial.

PURPOSE: The effect of renal replacement therapy (RRT) in comatose patients with acute kidney injury (AKI) remains unclear. We compared two RRT initiation strategies on the probability of awakening in comatose patients with severe AKI. METHODS: We conducted a post hoc analysis of a trial comparing two delayed RRT initiation strategies in patients with severe AKI. Patients were monitored until they had oliguria for more than 72 h and/or blood urea nitrogen higher than 112 mg/dL and then randomized to a delayed strategy (RRT initiated after randomization) or a more-delayed one (RRT initiated if complication occurred or when blood urea nitrogen exceeded 140 mg/dL). We included only comatose patients (Richmond Agitation-Sedation scale [RASS] < - 3), irrespective of sedation, at randomization. A multi-state model was built, defining five mutually exclusive states: death, coma (RASS < - 3), incomplete awakening (RASS [- 3; - 2]), awakening (RASS [- 1; + 1] two consecutive days), and agitation (RASS > + 1). Primary outcome was the transition from coma to awakening during 28 days after randomization. RESULTS: A total of 168 comatose patients (90 delayed and 78 more-delayed) underwent randomization. The transition intensity from coma to awakening was lower in the more-delayed group (hazard ratio [HR] = 0.36 [0.17-0.78]; p = 0.010). Time spent awake was 10.11 days [8.11-12.15] and 7.63 days [5.57-9.64] in the delayed and the more-delayed groups, respectively. Two sensitivity analyses were performed based on sedation status and sedation practices across centers, yielding comparable results. CONCLUSION: In comatose patients with severe AKI, a more-delayed RRT initiation strategy resulted in a lower chance of transitioning from coma to awakening.

Cefoxitin versus carbapenems as definitive treatment for extended-spectrum ß-lactamase-producing Klebsiella pneumoniae bacteremia in intensive care unit: a propensity-matched retrospective analysis.

BACKGROUND: Despite cefoxitin's in vitro resistance to hydrolysis by extended-spectrum beta-lactamases (ESBL), treatment of ESBL-producing Klebsiella pneumoniae (KP) infections with cefoxitin remains controversial. The aim of our study was to compare the clinical efficacy of cefoxitin as definitive antibiotic therapy for patients with ESBL-KP bacteremia in intensive care unit, versus carbapenem therapy. METHODS: This retrospective study included all patients with monomicrobial bacteremia hospitalized in intensive care unit between January 2013 and January 2023 at the University Hospital of Guadeloupe. The primary outcome was the 30-day clinical success defined as a composite endpoint: 30-day survival, absence of relapse and no change of antibiotic therapy. Cox regression including a propensity score (PS) and PS-based matched analysis were performed for endpoint analysis. RESULTS: A total of 110 patients with bloodstream infections were enrolled. Sixty-three patients (57%) received definitive antibiotic therapy with cefoxitin, while forty-seven (43%) were treated with carbapenems. 30-day clinical success was not significantly different between patients treated with cefoxitin (57%) and carbapenems (53%, p = 0.823). PS-adjusted and PS-matched analysis confirmed these findings. Change of definitive antibiotic therapy was more frequent in the cefoxitin group (17% vs. 0%, p = 0.002). No significant differences were observed for the other secondary endpoints. The acquisition of carbapenem-resistant Pseudomonas aeruginosa was significantly higher in patients receiving carbapenem therapy (5% vs. 23%, p = 0.007). CONCLUSIONS: Our results suggest that cefoxitin as definitive antibiotic therapy could be a therapeutic option for some ESBL-KP bacteremia, sparing carbapenems and reducing the selection of carbapenem-resistant Pseudomonas aeruginosa strains.

Towards optimization of ceftazidime dosing in obese ICU patients: the end of the 'one-size-fits-all' approach?

BACKGROUND: Ceftazidime is commonly used as a key antibiotic against Pseudomonas aeruginosa in critically ill patients. ICU patients have severely altered and variable antibiotic pharmacokinetics, resulting in lower antimicrobial concentrations and potentially poor outcome. Several factors, including obesity and renal function, may influence pharmacokinetics. Thus, the objective of the study was to evaluate the impact of obesity and renal function on ceftazidime plasma concentrations and dosing regimen in ICU patients. METHODS: All consecutive adult patients from six ICUs, treated with continuous ceftazidime infusion and under therapeutic drug monitoring evaluation, were included. Obesity was defined as BMI ≥30 kg/m². Glomerular filtration rate (GFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboration formula. The ceftazidime recommended target for plasma concentrations was between 35 and 80 mg/L. RESULTS: A total of 98 patients (45 obese), with an average weight of 90 (±25) kg, were included. Mean GFR was 84.1 (±40.4) mL/min/1.73 m2. Recommended ceftazidime plasma concentrations were achieved for only 48.0% of patients, with median dosing regimen of 6 g/day. Obese patients had lower ceftazidime plasma concentrations compared with non-obese patients (37.8 versus 56.3 mg/L; P = 0.0042) despite similar dosing regimens (5.83 g/day versus 5.52 g/day, P = 0.2529). Almost all augmented renal clearance patients were underdosed despite ceftazidime dosing of 6.6 (±0.8) g/day. Weight-based ceftazidime dosing seemed to attenuate such obesity-related discrepancies, regardless of GFR. CONCLUSIONS: Obese ICU patients required significantly greater ceftazidime doses to achieve the target range. A tailored dosing regimen may be considered based on weight and GFR. Future prospective studies should be performed to confirm this individualized dosing approach.

Epidemiology and outcome predictors in 450 patients with hanging-induced cardiac arrest: a retrospective study.

Background: Cardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors. Methods: This retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period. Results: Of 450 patients (350 men, median age, 43 [34-52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0-5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10-30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02-10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60-15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71-21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02-0.37; p = 0.0009). Conclusion: In patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality.

Long-term outcomes of COVID-19 intensive care unit survivors and their family members: a one year follow-up prospective study.

Purpose: To describe the long-term physical, functional and mental status of COVID-19 intensive care unit (ICU) patients and their family members 1 year after ICU discharge. Methods: We performed a prospective observational cohort study among patients admitted to the ICU for COVID-19-associated respiratory failure and their family members. Patients attended a one-year follow-up consultation with family members. Physical, functional and respiratory outcomes were collected. In addition, participants completed the Hospital Anxiety and Depression Scale and the Revised Impact of Event Scale. Qualitative components were collected during a 2-h face-to-face interview. Results: Fifty-four patients and 42 family members were included. Thirty-four (63%) patients reported chronic fatigue and 37 (68.5%) dyspnea. Computed tomography scans were abnormal in 34 patients (72.3%). Anxiety symptoms were present in 23 (48%) patients and 26 (66%) family members, depression in 11 (23%) and 13 (33%), and post-traumatic stress disorder in 12 (25%) and 23 (55%), respectively. Visit limitation was reported as the most painful experience for family members. Numerous patients recalled nightmares that contributed to the anxiety. Long-term reconstruction was difficult for both patients and family members. Conclusion: The vast majority of patients and their relatives reported long-term consequences on various physical and mental components, leading to a profound impact on their well-being.

Ultra-low tidal volume ventilation for COVID-19-related ARDS in France (VT4COVID): a multicentre, open-label, parallel-group, randomised trial.

BACKGROUND: COVID-19-related acute respiratory distress syndrome (ARDS) is associated with a high mortality rate and longer mechanical ventilation. We aimed to assess the effectiveness of ventilation with ultra-low tidal volume (ULTV) compared with low tidal volume (LTV) in patients with COVID-19-related ARDS. METHODS: This study was a multicentre, open-label, parallel-group, randomised trial conducted in ten intensive care units in France. Eligible participants were aged 18 years or older, received invasive mechanical ventilation for COVID-19 (confirmed by RT-PCR), had ARDS according to the Berlin definition, a partial pressure of arterial oxygen to inspiratory oxygen fraction (PaO2/FiO2) ratio of 150 mm Hg or less, a tidal volume (VT) of 6·0 mL/kg predicted bodyweight or less, and received continuous intravenous sedation. Patients were randomly assigned (1:1) using randomisation blocks to receive ULTV (intervention group) aiming for VT of 4·0 mL/kg predicted bodyweight or LTV (control group) aiming for VT 6·0 mL/kg predicted bodyweight. Participants, investigators, and outcome assessors were not masked to group assignment. The primary outcome was a ranked composite score based on all-cause mortality at day 90 as the first criterion and ventilator-free days among patients alive at day 60 as the second criterion. Effect size was computed with the unmatched win ratio, on the basis of pairwise prioritised comparison of primary outcome components between every patient in the ULTV group and every patient in the LTV group. The unmatched win ratio was calculated as the ratio of the number of pairs with more favourable outcome in the ULTV group over the number of pairs with less favourable outcome in the ULTV group. Primary analysis was done in the modified intention-to-treat population, which included all participants who were randomly assigned and not lost to follow-up. This trial is registered with ClinicalTrials.gov, NCT04349618. FINDINGS: Between April 15, 2020, and April 13, 2021, 220 patients were included and five (2%) were excluded. 215 patients were randomly assigned (106 [49%] to the ULTV group and 109 [51%] to the LTV group). 58 (27%) patients were female and 157 (73%) were male. The median age was 68 years (IQR 60-74). 214 patients completed follow-up (one lost to follow-up in the ULTV group) and were included in the modified intention-to-treat analysis. The primary outcome was not significantly different between groups (unmatched win ratio in the ULTV group 0·85 [95% CI 0·60 to 1·19]; p=0·38). 46 (44%) of 105 patients in the ULTV group and 43 (39%) of 109 in the LTV group died by day 90 (absolute difference 4% [-9 to 18]; p=0·52). The rate of severe respiratory acidosis in the first 28 days was higher in the ULTV group than in the LTV group (35 [33%] vs 14 [13%]; absolute difference 20% [95% CI 9 to 31]; p=0·0004). INTERPRETATION: In patients with moderate-to-severe COVID-19-related ARDS, there was no significant difference with ULTV compared with LTV in the composite score based on mortality and ventilator-free days among patients alive at day 60. These findings do not support the systematic use of ULTV in patients with COVID-19-related ARDS. FUNDING: French Ministry of Solidarity and Health and Hospices Civils de Lyon.

Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial.

Background: Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients. Methods: In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2. Eligible patients were randomly assigned (1:1 ratio) to receive an intermediate weight-adjusted prophylactic dose or a fixed-dose of subcutaneous low-molecular-weight heparin during the hospital stay. The primary outcome corresponded to symptomatic deep-vein thrombosis (fatal) pulmonary embolism during hospitalization (COVI-DOSE ClinicalTrials.gov number: NCT04373707). Findings: Between May 2020, and April 2021, 1000 patients underwent randomisation in medical wards (noncritically ill) (80.1%) and intensive care units (critically ill) (19.9%); 502 patients were assigned to receive a weight-adjusted intermediate dose, and 498 received fixed-dose thromboprophylaxis. Symptomatic venous thromboembolism occurred in 6 of 502 patients (1.2%) in the weight-adjusted dose group and in 10 of 498 patients (2.1%) in the fixed-dose group (subdistribution hazard ratio, 0.59; 95% CI, 0.22-1.63; P = 0.31). There was a twofold increased risk of major or clinically relevant nonmajor bleeding: 5.9% in the weight-adjusted dose group and 3.1% in the fixed-dose group (P = 0.034). Interpretation: In the COVI-DOSE trial, the observed rate of thromboembolic events was lower than expected in patients hospitalized for COVID-19 infection, and the study was unable to show a significant difference in the risk of venous thromboembolism between the two low-molecular-weight-heparin regimens. Funding: French Ministry of Health, CAPNET, Grand-Est Region, Grand-Nancy Métropole.

ICU health care workers opinion on physician-assisted-suicide and euthanasia: a French survey.

BACKGROUND: In France, physician-assisted suicide or euthanasia are not legal but are still debated. French intensive care unit (ICU) health care workers (HCWs) have an insider's perspective on the global quality of the patient's end-of-life, whether it occurs in ICU or not. However, their opinion about euthanasia/physician-assisted suicide remains unknown. The aim of this study is to investigate the opinion of French ICU HCWs about physician-assisted suicide/euthanasia. RESULTS: A total of 1149 ICU HCWs participated to a self-administered anonymous questionnaire: 411 (35.8%) physicians and 738 (64.2%) non-physicians. Among them, 76.5% indicated they were in favor of legalizing euthanasia/physician-assisted suicide. Non-physicians HCWs were significantly more in favor of the legalization of euthanasia/physician assisted suicide than physicians (87% vs 57.8% p < 0.001). Euthanasia/physician-assisted suicide of an ICU patient raised the most important difference in positive judgment between physicians and non-physicians HCWs (80.3% vs 42.2%; p < 0.001 of non-physicians and physicians, respectively). The questionnaire included three case vignettes of concrete examples which participated to the increase in the rate of response in favor of euthanasia/physician-assisted suicide legalization (76.5-82.9%; p < 0.001). CONCLUSIONS: Keeping in mind the unknown representation of our sample, ICU HCWs, particularly non physicians, would be in favor of a law legalizing euthanasia/physician-assisted suicide.

Long-term outcomes after severe acute kidney injury in critically ill patients: the SALTO study.

BACKGROUND: The extent of the consequences of an episode of severe acute kidney injury (AKI) on long-term outcome of critically ill patients remain debated. We conducted a prospective follow-up of patients included in a large multicenter clinical trial of renal replacement therapy (RRT) initiation strategy during severe AKI (the Artificial Kidney Initiation in Kidney Injury, AKIKI) to investigate long-term survival, renal outcome and health related quality of life (HRQOL). We also assessed the influence of RRT initiation strategy on these outcomes. RESULTS: Follow-up of patients extended from 60 days to a median of 3.35 years [interquartile range (IQR), 1.89 to 4.09] after the end of initial study. Of the 619 patients included in the AKIKI trial, 316 survived after 60 days. The overall survival rate at 3 years from inclusion was 39.4% (95% CI 35.4 to 43.4). A total of 46 patients (on the 175 with available data on long-term kidney function) experienced worsening of renal function (WRF) at the time of follow-up [overall incidence of 26%, cumulative incidence at 4 years: 20.6% (CI 95% 13.0 to 28.3)]. Fifteen patients required chronic dialysis (5% of patients who survived after day 90). Among the 226 long-term survivors, 80 (35%) answered the EQ-5D questionnaire. The median index value reported was 0.67 (IQR 0.40 to 1.00) indicating a noticeable alteration of quality of life. Initiation strategy for RRT had no effect on any long-term outcome. CONCLUSION: Severe AKI in critically ill patients was associated with a high proportion of death within the first 2 months but less so during long-term follow-up. A quarter of long-term survivors experienced a WRF and suffered from a noticeable impairment of quality of life. Renal replacement therapy initiation strategy was not associated with mortality outcome.

Cardiorespiratory Fitness and Neuromuscular Function of Mechanically Ventilated ICU COVID-19 Patients.

OBJECTIVES: The aim of the current study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration. DESIGN: Prospective nonrandomized study. SETTING: Patients hospitalized in ICU for COVID-19 infection. PATIENTS: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status. CONCLUSIONS: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.

Factors associated with acute mesenteric ischemia among critically ill ventilated patients with shock: a post hoc analysis of the NUTRIREA2 trial.

PURPOSE: Acute mesenteric ischemia (AMI) is a rare, but life-threatening condition occurring among critically ill patients. Several factors have been associated with AMI, but the causal link is debated, most studies being retrospective. Among these factors, enteral nutrition (EN) could be associated with AMI, in particular among patients with shock. We aimed to study the factors independently associated with AMI in a post hoc analysis of the NUTRIREA-2 trial including 2410 critically ill ventilated patients with shock, randomly assigned to receive EN or parenteral nutrition (PN). METHODS: Post hoc analysis of the NUTRIREA-2 trial was conducted. Ventilated adults with shock were randomly assigned to receive EN or PN. AMI was assessed by computed tomography, endoscopy, or laparotomy. Factors associated with AMI were studied by univariate and multivariate analysis. RESULTS: 2410 patients from 44 French intensive care units (ICUs) were included in the study: 1202 patients in the enteral group and 1208 patients in the parenteral group. The median age was 67 [58-76] years, with 67% men, a SAPS II score of 59 [46-74], and a medical cause for ICU admission in 92.7%. AMI was diagnosed among 24 (1%) patients, mainly by computed tomography (79%) or endoscopy (38%). The mechanism of AMI was non-occlusive mesenteric ischemia (n = 12), occlusive (n = 4), and indeterminate (n = 8). The median duration between inclusion in the trial and AMI diagnosis was 4 [1-11] days. Patients with AMI were older, had a higher SAPS II score at ICU admission, had higher plasma lactate, creatinine, and ASAT concentrations and lower hemoglobin concentration, had more frequently EN, dobutamine, and CVVHDF at inclusion, developed more frequently bacteremia during ICU stay, and had higher 28-day and 90-day mortality rates compared with patients without AMI. By multivariate analysis, AMI was independently associated with EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin concentration ≤ 10.9 g/dL. CONCLUSION: Among critically ill ventilated patients with shock, EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin ≤ 10.9 g/dL were independently associated with AMI. Among critically ill ventilated patients requiring vasopressors, EN should be delayed or introduced cautiously in case of low cardiac output requiring dobutamine and/or in case of multiple organ failure with high SAPS II score.

Association of COVID-19 Acute Respiratory Distress Syndrome With Symptoms of Posttraumatic Stress Disorder in Family Members After ICU Discharge.

IMPORTANCE: Persistent physical and mental disorders are frequent in survivors of COVID-19-related acute respiratory distress syndrome (ARDS). However, data on these disorders among family members are scarce. OBJECTIVE: To determine the association between patient hospitalization for COVID-19 ARDS vs ARDS from other causes and the risk of posttraumatic stress disorder (PTSD)-related symptoms in family members. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study in 23 intensive care units (ICUs) in France (January 2020 to June 2020 with final follow-up ending in October 2020). ARDS survivors and family members (1 family member per patient) were enrolled. EXPOSURES: Family members of patients hospitalized for ARDS due to COVID-19 vs ARDS due to other causes. MAIN OUTCOMES AND MEASURES: The primary outcome was family member symptoms of PTSD at 90 days after ICU discharge, measured by the Impact of Events Scale-Revised (score range, 0 [best] to 88 [worst]; presence of PTSD symptoms defined by score >22). Secondary outcomes were family member symptoms of anxiety and depression at 90 days assessed by the Hospital Anxiety and Depression Scale (score range, 0 [best] to 42 [worst]; presence of anxiety or depression symptoms defined by subscale scores ≥7). Multivariable logistic regression models were used to determine the association between COVID-19 status and outcomes. RESULTS: Among 602 family members and 307 patients prospectively enrolled, 517 (86%) family members (median [IQR] age, 51 [40-63] years; 72% women; 48% spouses; 26% bereaved because of the study patient's death; 303 [50%] family members of COVID-19 patients) and 273 (89%) patients (median [IQR] age, 61 [50-69] years; 34% women; 181 [59%] with COVID-19) completed the day-90 assessment. Compared with non-COVID-19 ARDS, family members of patients with COVID-19 ARDS had a significantly higher prevalence of symptoms of PTSD (35% [103/293] vs 19% [40/211]; difference, 16% [95% CI, 8%-24%]; P < .001), symptoms of anxiety (41% [121/294] vs 34% [70/207]; difference, 8% [95% CI, 0%-16%]; P= .05), and symptoms of depression (31% [91/291] vs 18% [37/209]; difference, 13% [95% CI, 6%-21%]; P< .001). In multivariable models adjusting for age, sex, and level of social support, COVID-19 ARDS was significantly associated with increased risk of PTSD-related symptoms in family members (odds ratio, 2.05 [95% CI, 1.30 to 3.23]). CONCLUSIONS AND RELEVANCE: Among family members of patients hospitalized in the ICU with ARDS, COVID-19 disease, as compared with other causes of ARDS, was significantly associated with increased risk of symptoms of PTSD at 90 days after ICU discharge. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04341519.

Open-label randomized controlled trial of ultra-low tidal ventilation without extracorporeal circulation in patients with COVID-19 pneumonia and moderate to severe ARDS: study protocol for the VT4COVID trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19 pneumonia, with a mortality rate amounting to 34-50% in moderate and severe ARDS, and is associated with prolonged duration of invasive mechanical ventilation. Such as in non-COVID ARDS, harmful mechanical ventilation settings might be associated with worse outcomes. Reducing the tidal volume down to 4 mL kg-1 of predicted body weight (PBW) to provide ultra-low tidal volume ventilation (ULTV) is an appealing technique to minimize ventilator-inducted lung injury. Furthermore, in the context of a worldwide pandemic, it does not require any additional material and consumables and may be applied in low- to middle-income countries. We hypothesized that ULTV without extracorporeal circulation is a credible option to reduce COVID-19-related ARDS mortality and duration of mechanical ventilation. METHODS: The VT4COVID study is a randomized, multi-centric prospective open-labeled, controlled superiority trial. Adult patients admitted in the intensive care unit with COVID-19-related mild to severe ARDS defined by a PaO2/FiO2 ratio ≤ 150 mmHg under invasive mechanical ventilation for less than 48 h, and consent to participate to the study will be eligible. Patients will be randomized into two balanced parallels groups, at a 1:1 ratio. The control group will be ventilated with protective ventilation settings (tidal volume 6 mL kg-1 PBW), and the intervention group will be ventilated with ULTV (tidal volume 4 mL kg-1 PBW). The primary outcome is a composite score based on 90-day all-cause mortality as a prioritized criterion and the number of ventilator-free days at day 60 after inclusion. The randomization list will be stratified by site of recruitment and generated using random blocks of sizes 4 and 6. Data will be analyzed using intention-to-treat principles. DISCUSSION: The purpose of this manuscript is to provide primary publication of study protocol to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Enrollment of patients in the study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04349618 . Registered on April 16, 2020.