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Oxygen therapy can be delivered using low-flow, intermediate-flow (air entrainment mask), or high-flow devices. Low/intermediate-flow oxygen devices have several drawbacks that cause critically ill patients discomfort and translate into suboptimal clinical results. These include limitation of the FiO 2 (due to the high inspiratory flow often observed in patients with respiratory failure), and insufficient humidification and warming of the inspired gas. High-flow nasal cannula oxygenation (HFNCO) delivers oxygen flow rates of up to 60 L/min and over the last decade its effect on clinical outcomes has widely been evaluated, such as in the improvement of respiratory distress, the need for intubation, and mortality. Mechanisms of action of HFNCO are complex and not limited to the increased oxygen flow rate. The main aim of this review is to guide clinicians towards evidence-based clinical practice guidelines. It summarizes current knowledge about HFNCO use in ICU patients and the potential areas of uncertainties. For instance, it has been recently suggested that HFNCO could improve the outcome of patients with hypoxemic acute respiratory failure. In other settings, research is ongoing and additional evidence is needed. For instance, if intubation is required, studies suggest that HFNCO may help to improve preoxygenation and can be used after extubation. Likewise, HFNCO might be used in obese patients, or to prevent respiratory deterioration in hypoxemic patients requiring bronchoscopy, or for the delivery of aerosol therapy. However, areas for which conclusive data exist are limited and interventions using standardized HFNCO protocols, comparators, and relevant clinical outcomes are warranted.

Patients treated with targeted temperature management (32 to 34°C) after cardiac arrest are at increased risk for early ventilator-associated pneumonia. In this multicenter trial, intravenous amoxicillin–clavulanate for 48 hours after cardiac arrest resulted in a lower incidence of early ventilator-associated pneumonia than placebo but did not affect ventilator-free days or mortality at day 28.

To the Editor: In the BOX trial, Kjaergaard et al. (Oct. 20 issue) 1 found no significant difference in the percentages of patients who died or had severe disability between those who were treated with a high (77 mm Hg) or a low (63 mm Hg) mean arterial blood-pressure target. As discussed by the authors, the clinical significance of the mean difference in mean arterial blood pressure between the two groups, at only 10.7 mm Hg, is unclear. In addition, it is possible that the targeted mean arterial pressure was insufficient in patients with impaired cerebral autoregulation. Ameloot et al. reported . . .

Purpose Preoxygenation with high-flow therapy by nasal cannulae (HFNC) is now widespread in the intensive care unit (ICU). However, no large randomized study has assessed its relevance in non-severely hypoxemic patients. In a randomized controlled trial (PROTRACH study), we aimed to evaluate preoxygenation with HFNC vs. standard bag-valve mask oxygenation (SMO) in non-severely hypoxemic patients during rapid sequence intubation (RSI) in the ICU. Methods Randomized controlled trial including non-severely hypoxemic patients requiring intubation in the ICU. Patients received preoxygenation by HFNC or SMO during RSI. HFNC was maintained throughout the intubation procedure whereas SMO was removed to perform laryngoscopy. The primary outcome was the lowest pulse oximetry (SpO 2 ) throughout the intubation procedure. Secondary outcomes included drop in SpO 2 , adverse events related to intubation, and outcome in the ICU. Results A total of 192 patients were randomized. In the intent-to-treat analysis, 184 patients (HFNC n  = 95; SMO n  = 89), the median [IQR] lowest SpO 2 was 100% [97; 100] for HFNC and 99% [95; 100] for the SMO group ( P  = 0.30). Mild desaturation below 95% was more frequent with SMO (23%) than with HFNC (12%) (RR 0.51, 95% CI 0.26–0.99, P  = 0.045). There were fewer adverse events in the HFNC group (6%) than in the SMO group (19%) (RR 0.31, 95% CI 0.13–0.76, P  = 0.007), including fewer severe adverse events, respectively 6 (6%) and 14 (16%) with HFNC and SMO (RR 0.38, 95% CI 0.15–0.95, P  = 0.03). Conclusions Compared with SMO, preoxygenation with HFNC in the ICU did not improve the lowest SpO 2 during intubation in the non-severely hypoxemic patients but led to a reduction in intubation-related adverse events. Trial registration Clinical trial Submission: 7 March 2016. Registry name: Benefits of high-flow nasal cannulae oxygen for preoxygenation during intubation in non-severely hypoxemic patients: the PROTRACH study. Clinicaltrials.gov identifier: NCT02700321. Eudra CT: 2015-A00145-44. CPP: 15/13-975 (Comité de protection des personnes de Rennes). URL registry: https://clinicaltrials.gov/ct2/show/record/NCT02700321 .

IntroductionPatients in intensive care units (ICUs) frequently require mechanical ventilation, with approximately half needing invasive ventilation through an orotracheal tube. For these patients, gastric tube (GT) insertion is routinely performed to administer nutrition and medications or to drain gastric contents. The insertion route (oral or nasal) may affect the incidence of ventilator-associated pneumonia (VAP), a significant ICU care complication. This study aims to compare the impact of oral versus nasal GT insertion on the incidence of VAP in intubated ICU patients.Methods and analysisThe SONG trial (NCT 05915663) is a multicentre, open-label, two-period, two-intervention, cluster randomised crossover superiority trial. 16 French ICUs will participate. ICUs will be randomised to periods of nasogastric or orogastric tube placement. The trial includes a practice standardisation period, followed by two 12-month inclusion periods separated by a monitoring and washout period. The primary endpoint is the incidence rate of VAP at day 28, confirmed by three independent physicians. Secondary endpoints include the ease of GT insertion, measured by the number of attempts.Ethics and disseminationThis study received approval from a central ethical review board on 12 April 2024 (CPP Sud-est VI, registration number 23.00943.000175). Patients are included after informed consent or, when not possible, from next of kin. If none are available, the investigator will proceed with emergency inclusion, following French law. When consent is initially obtained from the next of kin or through emergency inclusion, the investigator will seek consent from the patient as soon as possible. Data will be anonymised and patient confidentiality maintained. Results will be published in peer-reviewed journals and presented at scientific meetings.Trial registration numberNCT05915663.

Treatment of respiratory diphtheria requires prompt administration of equine diphtheria antitoxin (DAT) to neutralize circulating toxin. We conducted surveys of key procurement agencies and manufacturers currently engaged in DAT manufacturing or procurement, along with key informant interviews with developers of monoclonal antibodies. Our findings indicate that prices and availability of DAT vary and that prediction of demand is challenging for both manufacturers and procurement agencies. Substantial concerns were raised over the inability to obtain enough DAT to respond to increasing global outbreaks. Monoclonal antibody developers noted financial challenges in advancing their clinical and manufacturing progress.

Background The early recognition and management of sepsis improves outcomes. Biomarkers may help in identifying earlier sub-clinical signs of sepsis. We explored the potential of serial measurements of C-reactive protein (CRP), procalcitonin (PCT) and pancreatic stone protein (PSP) for the early recognition of sepsis in patients hospitalized in the intensive care unit (ICU). Methods This was a multicentric international prospective observational clinical study conducted in 14 ICUs in France, Switzerland, Italy, and the United Kingdom. Adult ICU patients at risk of nosocomial sepsis were included. A biomarker-blinded adjudication committee identified sepsis events and the days on which they began. The association of clinical sepsis diagnoses with the trajectories of PSP, CRP, and PCT in the 3 days preceding these diagnoses of sepsis were tested for markers of early sepsis detection. The performance of the biomarkers in sepsis diagnosis was assessed by receiver operating characteristic (ROC) analysis. Results Of the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3–8 days). Clinical sepsis diagnosis was associated with an increase in biomarkers value over the 3 days preceding this diagnosis [PSP ( p  = 0.003), PCT ( p  = 0.025) and CRP ( p  = 0.009)]. PSP started to increase 5 days before the clinical diagnosis of sepsis, PCT 3 and CRP 2 days, respectively. The area under the ROC curve at the time of clinical sepsis was similar for all markers (PSP, 0.75; CRP, 0.77; PCT, 0.75). Conclusions While the diagnostic accuracy of PSP, CRP and PCT for sepsis were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary to clinical diagnose sepsis. This observation justifies further evaluation of the potential clinical benefit of serial PSP measurement in the management of critically ill patients developing nosocomial sepsis. Trial registration The study has been registered at ClinicalTrials.gov (no. NCT03474809), on March 16, 2018. https://www.clinicaltrials.gov/ct2/show/NCT03474809?term=NCT03474809&draw=2&rank=1 .

High-flow oxygen therapy (HFOT) has become the most common oxygen-supplementation modality in patients with acute respiratory failure, based chiefly on data from tightly selected patients included in randomized trials. Our objective was to obtain real-life data on HFOT failure. This prospective observational multicenter French study done in 13 intensive care units in 2019–2020 was designed to determine the proportion of patients with failed HFOT, defined as intubation, noninvasive ventilation, standard oxygen therapy with an estimated FiO 2 >50%. We included 257 patients before prematurely ending the study due to the COVID-19 pandemic. HFOT failed in 79 patients (32%), including 42 (17%) who required intubation. Mean HFOT duration was 2.4 ± 2.2 days. By multivariate analysis, a low ROX index (ratio of pulse-oximeter saturation (SpO 2 ) over FiO 2 , over the respiratory rate (RR) was associated with HFOT failure (adjusted hazard ratio [aHR], 0.83; 95%CI, 0.77–0.90, P  < 0.0001), as were elevated mean arterial pressure (aHR, 1.03; 95%CI, 1.02–1.05), vasopressor therapy (aHR, 3.35; 95%CI, 1.44–7.79), and worse Glasgow Coma Scale score (aHR, 0.69; 95%CI, 0.57–0.80, P  < 0.001). The identification of factors independently associated with HFOT failure should help to determine which patients are most likely to benefit from HFOT, thereby preventing delayed intubation. Additional studies are needed to further assess these risk factors and to determine the optimal HFOT weaning modalities. Trial registration : The study was registered on the ClinicalTrials.gov registry on February 11, 2019 (NCT04141956).

IntroductionFirst-line oxygenation strategy in patients with acute hypoxaemic respiratory failure consists in standard oxygen or high-flow nasal oxygen therapy. Clinical practice guidelines suggest the use of high-flow nasal oxygen rather than standard oxygen. However, findings remain contradictory with a low level of certainty. We hypothesise that compared with standard oxygen, high-flow nasal oxygen may reduce mortality in patients with acute hypoxaemic respiratory failure.Method and analysisThe Standard Oxygen versus High-flow nasal Oxygen-trial is an investigator-initiated, multicentre, open-label, randomised controlled trial comparing high-flow nasal oxygen versus standard oxygen in patients admitted to an intensive care unit (ICU) for acute respiratory failure with moderate-to-severe hypoxaemia. 1110 patients will be randomly assigned to one of the two groups with a ratio of 1:1. The primary outcome is the number of patients who died 28 days after randomisation. Secondary outcomes include comfort, dyspnoea and oxygenation 1 hour after treatment initiation, the number of patients intubated at day 28, mortality in ICU, in hospital and until day 90, and complications during ICU stay.Ethics and disseminationThe study has been approved by the central Ethics Committee ‘Sud Méditerranée III’ (2020-07-05) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04468126.

Background This study investigated changes in plasma level of soluble endothelial protein C receptor (sEPCR) in association with outcome in patients with septic shock. We explored sEPCR for early sepsis prognosis assessment and constructed a scoring system based on clinical and biological data, in order to discriminate between surviving at hospital discharge and non-surviving patients. Methods Clinical data and samples were extracted from the prospective “STREPTOGENE” cohort. We enrolled 278 patients, from 50 intensive care units (ICUs), with septic shock caused by pneumococcal pneumonia. Patients were divided into survivors ( n  = 194) and non-survivors ( n  = 84) based on in-hospital mortality. Soluble EPCR plasma levels were quantified at day 1 (D1) and day 2 (D2) by ELISA. The EPCR gene A 3 haplotype was determined. Patients were followed up until hospital discharge. Univariate and multivariate analyses were performed. A scoring system was constructed using least absolute shrinkage and selection operator (lasso) logistic regression for selecting predictive variables. Results In-hospital mortality was 30.2% ( n  = 84). Plasma sEPCR level was significantly higher at D1 and D2 in non-surviving patients compared to patients surviving to hospital discharge ( p  = 0.0447 and 0.0047, respectively). Early increase in sEPCR at D2 was found in non-survivors while a decrease was observed in the survival group ( p  = 0.0268). EPCR A3 polymorphism was not associated with mortality. Baseline sEPCR level and its variation from D1 to D2 were independent predictors of in-hospital mortality. The scoring system including sEPCR predicted mortality with an AUC of 0.75. Conclusions Our findings confirm that high plasma sEPCR and its increase at D2 are associated with poor outcome in sepsis and thus we propose sEPCR as a key player in the pathogenesis of sepsis and as a potential biomarker of sepsis outcome.