Continued enteral nutrition until extubation compared with fasting before extubation in patients in the intensive care unit: an open-label, cluster-randomised, parallel-group, non-inferiority trial.

BACKGROUND: Fasting is frequently imposed before extubation in patients in intensive care units, with the aim to reduce risk of aspiration. This unevaluated practice might delay extubation, increase workload, and reduce caloric intake. We aimed to compare continued enteral nutrition until extubation with fasting before extubation in patients in the intensive care unit. METHODS: We conducted an open-label, cluster-randomised, parallel-group, non-inferiority trial in 22 intensive care units in France. Patients aged 18 years or older were eligible for enrolment if they had received invasive mechanical ventilation for at least 48 h in the intensive care unit and received prepyloric enteral nutrition for at least 24 h at the time of extubation decision. Centres were randomly assigned (1:1) to continued enteral nutrition until extubation or 6-h fasting with concomitant gastric suctioning before extubation, to be applied for all patients within the unit. Masking was not possible because of the nature of the trial. The primary outcome was extubation failure (composite criteria of reintubation or death) within 7 days after extubation, assessed in both the intention-to-treat and per-protocol populations. The non-inferiority margin was set at 10%. Pneumonia within 14 days of extubation was a key secondary endpoint. This trial is now complete and is registered with ClinicalTrials.gov, NCT03335345. FINDINGS: Between April 1, 2018, and Oct 31, 2019, 7056 patients receiving enteral nutrition and mechanical ventilation were admitted to the intensive care units and 4198 were assessed for eligibility. 1130 patients were enrolled and included in the intention-to-treat population and 1008 were included in the per-protocol population. In the intention-to-treat population, extubation failure occurred in 106 (17·2%) of 617 patients assigned to receive continued enteral nutrition until extubation versus 90 (17·5%) of 513 assigned to fasting, meeting the a priori defined non-inferiority criterion (absolute difference -0·4%, 95% CI -5·2 to 4·5). In the per-protocol population, extubation failure occurred in 101 (17·0%) of 595 patients assigned to receive continued enteral nutrition versus 74 (17·9%) of 413 assigned to fasting (absolute difference -0·9%, 95% CI -5·6 to 3·7). Pneumonia within 14 days of extubation occurred in ten (1·6%) patients assigned to receive continued enteral nutrition and 13 (2·5%) assigned to fasting (rate ratio 0·77, 95% CI 0·22 to 2·69). INTERPRETATION: Continued enteral nutrition until extubation in critically ill patients in the intensive care unit was non-inferior to a 6-h fasting maximum gastric vacuity strategy comprising continuous gastric tube suctioning, in terms of extubation failure within 7 days (a patient-centred outcome), and thus represents a potential alternative in this population. FUNDING: French Ministry of Health. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

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.

Determinants of hospital and one-year mortality among older patients admitted to intensive care units: results from the multicentric SENIOREA cohort.

BACKGROUND: Improving outcomes of older patients admitted into intensive care units (ICU) is a raising concern. This study aimed at determining which geriatric and ICU parameters were associated with in-hospital and long-term mortality in this population. METHODS: We conducted a prospective multicentric observational cohort study, including patients aged 75 years and older requiring mechanical ventilation, admitted between September 2012 and December 2013 into ICU of 13 French hospitals. Comprehensive geriatric assessment at ICU admission and ICU usual parameters were registered in a standardized manner. Survival was recorded and comprehensive geriatric assessment was updated after 1 year during a dedicated home visit. RESULTS: 501 patients were analyzed. 108 patients (21.6%) died during the hospital stay. One-year survival rate was 53.8% (IC 95% [49.2%; 58.2%]). Factors associated with increased in-hospital mortality were higher acute illness severity score, resuscitated cardiac arrest as primary ICU diagnosis, perception of anxiety and low quality of life by the proxy, and living in a chronic care facility before ICU admission. Among patients alive at hospital discharge, factors associated with increased 1-year mortality in multivariate analysis were longer duration of mechanical ventilation, all primary ICU diagnoses other than septic shock, a Katz-activities of daily living (ADL) score below 5 and living in a chronic care facility before ICU admission. Among the 163 survivors at 1 year who received a second comprehensive geriatric assessment, the ADL score (functional abilities) showed a significant but moderate decline over time, whereas the Mini-Zarit score (family burden) improved. No significant change in patients' place of life was observed after 1 year, and quality of life was reported as happy-to-very-happy in 88% of survivors. CONCLUSIONS: The mortality rate remains high among older ICU patients requiring mechanical ventilation. Factors associated with short- and long-term mortality combined geriatric and ICU criteria, which should be jointly evaluated in routine care. Clinical trial registration NCT01679171.

Admission of tetanus patients to the ICU: a retrospective multicentre study.

BACKGROUND: An extended course of tetanus (up to 6 weeks) requiring ICU admission and protracted mechanical ventilation (MV) may have a significant impact on short- and long-term survival. The subject is noteworthy and deserves to be discussed. METHODS: Twenty-two ICUs in France performed tetanus screenings on patients admitted between January 2000 and December 2014. Retrospective data were collected from hospital databases and through the registers of the town hall of the patients. RESULTS: Seventy patients were included in 15 different ICUs. Sixty-three patients suffered from severe or very severe tetanus according to the Ablett classification. The median age was 80 years [interquartile range 73-84], and 86% of patients were women. Ninety per cent of patients (n = 63) required MV for a median of 36 days [26-46], and 66% required administration of a neuromuscular-blocking agent for 23 days [14-29]. A nosocomial infection occurred in 43 patients (61%). ICU and 1-year mortality rates were 14% (n = 10) and 16% (n = 11), respectively. Forty-five per cent of deaths occurred during the first week. Advanced age, a higher SAPS II, any infection, and the use of vasopressors were significantly associated with a lower number of days alive without ventilator support by day 90. Age was the only factor that significantly differed between deceased and survivors at 1 year (83 [81-85] vs. 79 [73-84] years, respectively; p = 0.03). Sixty-one per cent of survivors suffered no impairment to their functional status. CONCLUSION: In a high-income country, tetanus mainly occurs in healthy elderly women. Despite prolonged MV and extended ICU length of stay, we observed a low 1-year mortality rate and good long-term functional status.

Acute respiratory distress syndrome (ARDS)-associated acute cor pulmonale and patent foramen ovale: a multicenter noninvasive hemodynamic study.

INTRODUCTION: Acute cor pulmonale (ACP) and patent foramen ovale (PFO) remain common in patients under protective ventilation for acute respiratory distress syndrome (ARDS). We sought to describe the hemodynamic profile associated with either ACP or PFO, or both, during the early course of moderate-to-severe ARDS using echocardiography. METHODS: In this 32-month prospective multicenter study, 195 patients with moderate-to-severe ARDS were assessed using echocardiography during the first 48 h of admission (age: 56 (SD: 15) years; Simplified Acute Physiology Score: 46 (17); PaO2/FiO2: 115 (39); VT: 6.5 (1.7) mL/kg; PEEP: 11 (3) cmH2O; driving pressure: 15 (5) cmH2O). ACP was defined by the association of right ventricular (RV) dilatation and systolic paradoxical ventricular septal motion. PFO was detected during a contrast study using agitated saline in the transesophageal bicaval view. RESULTS: ACP was present in 36 patients, PFO in 21 patients, both PFO and ACP in 8 patients and the 130 remaining patients had neither PFO nor ACP. Patients with ACP exhibited a restricted left ventricle (LV) secondary to RV dilatation and had concomitant RV dysfunction, irrespective of associated PFO, but preserved LV systolic function. Despite elevated systolic pulmonary artery pressure (sPAP), patients with isolated PFO had a normal RV systolic function. sPAP and PaCO2 levels were significantly correlated. CONCLUSIONS: In patients under protective mechanical ventilation with moderate-to-severe ARDS, ACP was associated with LV restriction and RV failure, whether PFO was present or not. Despite elevated sPAP, PFO shunting was associated with preserved RV systolic function.

Prevalence and prognostic value of acute cor pulmonale and patent foramen ovale in ventilated patients with early acute respiratory distress syndrome: a multicenter study.

PURPOSE: We sought to determine the prevalence of and factors associated with acute cor pulmonale (ACP) and patent foramen ovale (PFO) at the early phase of acute respiratory distress syndrome (ARDS), and to assess their relation with mortality. METHODS: In this prospective multicenter study, 200 patients submitted to protective ventilation for early moderate to severe ARDS [PaO2/F(I)O2: 115 ± 39 with F(I)O2: 1; positive end-expiratory pressure (PEEP): 10.6 ± 3.1 cmH2O] underwent transthoracic (TTE) and transesophageal echocardiography (TEE) <48 h after admission. Echocardiograms were independently interpreted by two experts. Factors associated with ACP, PFO, and 28-day mortality were identified using multivariate regression analysis. RESULTS: TEE depicted ACP in 45/200 patients [22.5%; 95% confidence interval (CI) 16.9-28.9%], PFO in 31 patients (15.5%; 95% CI 10.8-21.3%), and both ACP and PFO in 9 patients (4.5%; 95% CI 2.1-8.4%). PFO shunting was small and intermittent in 27 patients, moderate and consistent in 4 patients, and large or extensive in no instances. PaCO2 >60 mmHg was strongly associated with ACP [odds ratio (OR) 3.70; 95% CI 1.32-10.38; p = 0.01]. No factor was independently associated with PFO, with only a trend for age (OR 2.07; 95% CI 0.91-4.72; p = 0.08). Twenty-eight-day mortality was 23%. Plateau pressure (OR 1.15; 95% CI 1.05-1.26; p < 0.01) and air leaks (OR 5.48; 95% CI 1.30-22.99; p = 0.02), but neither ACP nor PFO, were independently associated with outcome. CONCLUSIONS: TEE screening allowed identification of ACP in one-fourth of patients submitted to protective ventilation for early moderate to severe ARDS. PFO shunting was less frequent and never large or extensive. ACP and PFO were not related to outcome.