Impact of daily cyclic enteral nutrition versus standard continuous enteral nutrition in critically ill patients: a study protocol for a randomised controlled trial in three intensive care units in France (DC-SCENIC).

INTRODUCTION: Current guidelines on clinical nutrition of ventilated patients in the intensive care unit (ICU) recommend initiating continuous enteral nutrition within 48 hours of ICU admission when feasible. However, discontinuous feeding regimens, alternating feeding and fasting intervals, may have an impact on clinical and patient centred outcomes. The ongoing "Impact of daily cyclic enteral nutrition versus standard continuous enteral nutrition in critically ill patients" (DC-SCENIC) trial aims to compare standard continuous enteral feeding with daily cyclic enteral feeding over 10 hours to evaluate if implementing a fasting-mimicking diet can decrease organ failure in ventilated patients during the acute phase of ICU management. METHODS AND ANALYSIS: DC-SCENIC is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients 18 years of age or older receiving invasive mechanical ventilation and having an indication for enteral nutrition through a gastric tube. Enteral feeding is continuous in the control group and administered over 10 hours daily in the intervention group. Both groups receive isocaloric nutrition with 4 g of protein per 100 mL, and have the same 20 kcal/kg/day caloric target. The primary endpoint is the change in the Sequential Organ Failure Assessment score at 7 days compared with the day of inclusion in the study. Secondary outcomes include daily caloric and protein delivery, digestive, respiratory and metabolic tolerance as well as 28-day mortality, duration of mechanical ventilation and ventilator-free days. Outcomes will be analysed on an intention-to-treat basis. Recruitment started in June 2023 in 3 French ICU's and a sample size of 318 patients is expected by February 2026. ETHICS AND DISSEMINATION: This study received approval from the national ethics review board on 8 November 2022 (Comité de Protection des Personnes Sud-Est VI, registration number 2022-A00827-36). Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05627167.

Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME).

INTRODUCTION: Expanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF. METHODS AND ANALYSIS: HYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C-35°C) and normothermia (36.5°C-37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients. ETHICS AND DISSEMINATION: The trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings. TRIAL REGISTRATION NUMBER: NCT03098706.

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.

"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.

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome.

BACKGROUND: The efficacy of venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) remains controversial. METHODS: In an international clinical trial, we randomly assigned patients with very severe ARDS, as indicated by one of three criteria - a ratio of partial pressure of arterial oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 50 mm Hg for more than 3 hours; a Pao2:Fio2 of less than 80 mm Hg for more than 6 hours; or an arterial blood pH of less than 7.25 with a partial pressure of arterial carbon dioxide of at least 60 mm Hg for more than 6 hours - to receive immediate venovenous ECMO (ECMO group) or continued conventional treatment (control group). Crossover to ECMO was possible for patients in the control group who had refractory hypoxemia. The primary end point was mortality at 60 days. RESULTS: At 60 days, 44 of 124 patients (35%) in the ECMO group and 57 of 125 (46%) in the control group had died (relative risk, 0.76; 95% confidence interval [CI], 0.55 to 1.04; P=0.09). Crossover to ECMO occurred a mean (±SD) of 6.5±9.7 days after randomization in 35 patients (28%) in the control group, with 20 of these patients (57%) dying. The frequency of complications did not differ significantly between groups, except that there were more bleeding events leading to transfusion in the ECMO group than in the control group (in 46% vs. 28% of patients; absolute risk difference, 18 percentage points; 95% CI, 6 to 30) as well as more cases of severe thrombocytopenia (in 27% vs. 16%; absolute risk difference, 11 percentage points; 95% CI, 0 to 21) and fewer cases of ischemic stroke (in no patients vs. 5%; absolute risk difference, -5 percentage points; 95% CI, -10 to -2). CONCLUSIONS: Among patients with very severe ARDS, 60-day mortality was not significantly lower with ECMO than with a strategy of conventional mechanical ventilation that included ECMO as rescue therapy. (Funded by the Direction de la Recherche Clinique et du Développement and the French Ministry of Health; EOLIA ClinicalTrials.gov number, NCT01470703 .).

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.

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.

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.