Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury. METHODS: In this multicentre, double-blind, placebo-controlled trial, done at 43 centres in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating centre and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and >24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimise the risk of adverse events, the IVIG administration was divided into four perfusions of 0·5 g/kg each administered over at least 8 hours. Patients in the placebo group received an equivalent volume of sodium chloride 0·9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on ClinicalTrials.gov, NCT04350580. FINDINGS: Between April 3, and October 20, 2020, 146 patients (43 [29%] women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0·0 [IQR 0·0-8·0]) and the placebo group (0·0 [0·0-6·0]; difference estimate 0·0 [0·0-0·0]; p=0·21). Serious adverse events were more frequent in the IVIG group (78 events in 22 [32%] patients) than in the placebo group (47 events in 15 [20%] patients; p=0·089). INTERPRETATION: In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials. FUNDING: Programme Hospitalier de Recherche Clinique.

Use of BRASS in sedated critically-ill patients as a predictable mortality factor: BRASS-ICU.

Objectives: To demonstrate that a BRASS score≥ 3 at admission of intubated, ventilated and sedated patients is predictive of mortalityMethods: we have realized an Observational prospective multicenter study.All Major patients without neurological history, admitted to ICU for a non-neurological cause, sedated and admitted under mechanical ventilation were included.Results: One hundred and ten patients were included, the BRASS score as well as the FOUR and RASS scores were collected.At day 28, patients with a BRASS score ≥ 3 had an excess mortality (OR 3.29 - CI 95% [1.42-7.63], p = 0.005) as well as day 90 (OR 2.65 - CI 95% [1.19-5.88], p = 0.02), without impact on the delirium measured by CAM-ICU (OR 1.8 - CI 95% [0.68-4.77], p = 0.023). After adjustment with SAPS II, FOUR and RASS, difference in mortality was not any more different.It is also noted that patients with BRASS ≥ 3 are more sedated (RASS: -5 [-5 - -5] vs -4 [-5 - -3], p < 0.0001) and more comatose (FOUR: 2 [1-4] vs 6 [4-9], p < 0.0001), and have higher doses of midazolam (10 mg/h [5-15] vs 7.5 mg/h [5-10], p = 0.02) and sufentanil (20 µg/h [15-22.5] vs 10 [10-12.5], p = 0.01).Conclusions: The early alteration of brainstem reflexes measured by the BRASS score was not independently predictable in terms of mortality in the non-neurological ICU patients, admitted under sedation and mechanical ventilation.Trial registration: ClinicalTrials.gov Identifier: NCT03835091,Registered 8 February 2019 - prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03835091.

Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic.

BACKGROUND: We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. METHODS: This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. RESULTS: In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p < 0.001), and higher levels of overall perceived stress (p < 0.001), compared to low-intensity zones. Factors associated with higher overall perceived stress were female sex (B = 0.13; 95% confidence interval [CI] = 0.08-0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09-0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02-0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = - 0.32, 95% CI = - 0.54, - 0.11. CONCLUSION: COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).

"You helped me keep my head above water"-experience of bereavement research after loss of a loved one in the ICU: insights from the ARREVE study.

PURPOSE: Bereavement research has helped to improve end-of-life practices in the ICU. However, few studies have explored bereaved relatives experience of research participation in this context. We aimed to explore the experience of bereaved relatives' participation in the ARREVE study which included three telephone follow-up calls to complete several quantitative tools. METHODS: Volunteer relatives who participated in the 12-month follow-up call completed a questionnaire about research participation that included ten open-ended questions so that respondents could use their own words and thoughts. These open-ended questions were analyzed using qualitative analysis that examines themes within the data. RESULTS: 175/311 relatives completed the questionnaire. Three themes were derived from the thematic analysis: (1) struggling: reactivation of emotional distress associated with the ICU experience and the loss is frequent, specifically during the 1st follow-up call. (2) Resilience: as time goes by, research participation becomes increasingly positive. The calls are a help both in giving meaning to the relatives' experience and in accepting the loss. (3) Recognition: research calls can compensate for the absence of support during bereavement. CONCLUSION: Although some emotional difficulties must be acknowledged, bereavement research is overall associated with benefits, by facilitating emotional adjustments, meaning-making and resilience. Lack of support and social isolation during bereavement are frequent experiences, revealing that support strategies for bereaved relatives should be developed after the loss of a loved one in the ICU.

A comparison between intravascular and traditional cooling for inducing and maintaining temperature control in patients following cardiac arrest.

Therapeutic temperature control has been widely used during the last decade to improve clinical outcomes. We conducted this retrospective observational study to compare traditional cooling with endovascular cooling in post-cardiac arrest comatose survivors and to compare results with current guidelines. PATIENTS AND METHODS: All patients admitted to our ICU for cardiac arrest and for whom temperature control was performed were included. Traditional cooling included cold infusions, ice packs and cooling blankets. Endovascular cooling consisted in the insertion of a catheter in which cold fluid circulates in a closed circuit provided by a heat exchanger. Temperature control was started at a target temperature of 32°C to 34°C. Rewarming was performed passively in the traditional group and via computer-assistance in endovascular group. We evaluated the delay prior to and speed of cooling, thermic stability during the maintenance phase and the speed of rewarming. RESULTS: Thirty-four patients were included. The speed of cooling was faster with the endovascular (-0.66±0.35°C/h) compared to the traditional (-0.35±0.38°C/h, P=0.006) technique, with target temperatures reached in 4.0 and 6.0h, respectively (P=0.14). Temperatures were more stable with the endovascular technique (0.03±0.05°C2) than with the traditional technique (0.26±0.16°C2, P<10-4). There were more deviations from the guideline target range in the traditional group (64.7% versus 17.6%, P=0.008). Rewarming was faster in the traditional group (+0.64±0.33°C/h, versus +0.36±0.12°C/h, P=0.01). No significant difference was found concerning mortality or length of stay in the ICU. CONCLUSION: Temperature control with a cooling catheter was associated with faster cooling, improved thermic stability in the target range, less overcooling or overheating and slower rewarming in comparison with traditional techniques.

Terminal weaning or immediate extubation for withdrawing mechanical ventilation in critically ill patients (the ARREVE observational study).

PURPOSE: The relative merits of immediate extubation versus terminal weaning for mechanical ventilation withdrawal are controversial, particularly regarding the experience of patients and relatives. METHODS: This prospective observational multicentre study (ARREVE) was done in 43 French ICUs to compare terminal weaning and immediate extubation, as chosen by the ICU team. Terminal weaning was a gradual decrease in the amount of ventilatory assistance and immediate extubation was extubation without any previous decrease in ventilatory assistance. The primary outcome was posttraumatic stress symptoms (Impact of Event Scale Revised, IES-R) in relatives 3 months after the death. Secondary outcomes were complicated grief, anxiety, and depression symptoms in relatives; comfort of patients during the dying process; and job strain in staff. RESULTS: We enrolled 212 (85.5%) relatives of 248 patients with terminal weaning and 190 relatives (90.5%) of 210 patients with immediate extubation. Immediate extubation was associated with airway obstruction and a higher mean Behavioural Pain Scale score compared to terminal weaning. In relatives, IES-R scores after 3 months were not significantly different between groups (31.9 ± 18.1 versus 30.5 ± 16.2, respectively; adjusted difference, -1.9; 95% confidence interval, -5.9 to 2.1; p = 0.36); neither were there any differences in complicated grief, anxiety, or depression scores. Assistant nurses had lower job strain scores in the immediate extubation group. CONCLUSIONS: Compared to terminal weaning, immediate extubation was not associated with differences in psychological welfare of relatives when each method constituted standard practice in the ICU where it was applied. Patients had more airway obstruction and gasps with immediate extubation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01818895.

Correction to: Terminal weaning or immediate extubation for withdrawing mechanical ventilation in critically ill patients (the ARREVE observational study).

Correction to: Intensive Care Med (2017) DOI 10.1007/s00134-017-4891-0.

ICU physicians' and nurses' perceptions of terminal extubation and terminal weaning: a self-questionnaire study.

PURPOSE: Terminal extubation (TE) and terminal weaning (TW) are the methods available for withdrawing mechanical ventilation. Perceptions of TE and TW by intensive care unit (ICU) staff may influence bedside practices and the feasibility of studies comparing these methods. METHODS: From January to June 2013, 5 nurses and 5 physicians in each of 46 (out of 70, 65.7 %) French ICUs completed an anonymous self-questionnaire. Clusters of staff members defined by perceptions of TE and TW were identified by exploratory analysis. Denominators for computing percentages were total numbers of responses to each item; cases with missing data were excluded for the relevant item. RESULTS: Of the 451 (98 %) participants (225 nurses and 226 physicians), 37 (8.4 %) had never or almost never performed TW and 138 (31.3 %) had never or almost never performed TE. A moral difference between TW and TE was perceived by 205 (45.8 %) participants. The exploratory analysis identified three clusters defined by personal beliefs about TW and TE: 21.2 % of participants preferred TW, 18.1 % preferred TE, and 60.7 % had no preference. A preference for TW seemed chiefly related to unfavorable perceptions or insufficient knowledge of TE. Staff members who preferred TE and those with no preference perceived TE as providing a more natural dying process with less ambiguity. CONCLUSION: Nearly two-fifths of ICU nurses and physicians in participating ICUs preferred TW or TE. This finding suggests both a need for shared decision-making and training before performing TE or TW and a high risk of poor compliance with randomly allocated TW or TE.