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.

Late-onset argininosuccinic aciduria in a 72-year-old man presenting with fatal hyperammonemia.

Argininosuccinate lyase deficiency (ASLD, MIM #207900) is an inherited urea cycle disorder. There are mainly two clinical forms, an acute neonatal form which manifests as life-threatening hyperammonemia, and a late-onset form characterised by polymorphic neuro-cognitive or psychiatric presentation with transient hyperammonemia episodes. Here, we report a late-onset case of ASLD in a 72-year-old man carrying a homozygous pathogenic variant in the exon 16 of the ASL gene, presenting for the first time with fatal hyperammonemic coma. This case report shows the need to systematically carry out an ammonia assay when faced with an unexplained coma.

Attributable mortality of ICU acquired bloodstream infections: a propensity-score matched analysis.

The mortality attributable to ICU-acquired bloodstream infection (BSI) differs between studies due to statistical methods used for cohort matching. Propensity-score matching has never been used to avoid eventual bias when studying BSI attributable mortality in the ICU. We conducted an observational prospective study over a 4-year period, on patients admitted for at least 48 h in 2 intensive care units. Based on risk factors for death in the ICU and for BSI, each patient with BSI was matched with 3 patients without BSI using propensity-score matching. We performed a competitive risk analysis to study BSI mortality attributable fraction. Of 2464 included patients, 71 (2.9%) had a BSI. Propensity-score matching was highly effective and group characteristics were fully balanced. Crude mortality was 36.6% in patients with BSI and 21.6% in propensity-score matched patients (p=0.018). Attributable mortality of BSI was 2.3% [1.2-4.0] and number needed to harm was 6.7. With Fine and Gray model, a higher risk for death was observed in patients with BSI than in propensity-score matched patients (sub distribution Hazard Ratio (sdHR) = 2.11; 95% CI [1.32-3.37] p = 0.002). Patients with BSI had a higher risk for death and BSI attributable mortality fraction was 2.3%.

Incidence and risk factors for acquired colonization and infection due to extended-spectrum beta-lactamase-producing Gram-negative bacilli: a retrospective analysis in three ICUs with low multidrug resistance rate.

The purpose of this study is to assess risk factors for the acquisition of extended-spectrum ß-lactamase-producing Gram-negative bacilli (ESBL-GNB) colonization and infection (AI) in ICUs with low ESBL-GNB prevalence rate. We conducted a retrospective observational study in three ICUs in Bretagne, France. All patients admitted from January 2016 to September 2017 with a length of stay of 2 days or more were included. Universal screening for ESBL-GNB colonization was performed in all participating ICUs. Of the 3250 included patients, 131 (4.0%) were colonized at admission, 59 acquired colonization while hospitalized (1.9%; 95% CI [1.5-2.5%]), and 15 (0.5%; 95% CI [0.3-0.8%]) acquired ESBL-GNB infections. In the case of infection, the specificity and the negative predictive values of preexistent colonization for the ESBL-GNB etiology were 93.2% [91.5-95.1%] and 95.2% [93.5-97.1%], respectively. Colonization was the main risk factor for ESBL-GNB AI (OR = 9.61; 95% CI [2.86-32.29]; p < 0.001). Antimicrobial susceptibility of non-ESBL-GNB isolates responsible for AI was similar for any non-carbapenem ß-lactam (95%) and imipenem (94%). ESBL-GNB AIs were rare in ICUs with low ESBL-GNB prevalence rate. Prior colonization was the main risk factor for subsequent infection. Empirical carbapenem therapy could be avoided in non ESBL-GNB colonized patients with suspected AI.