Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

Contains fulltext : 218568.pdf (publisher's version ) (Open Access)BACKGROUND: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. METHODS: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 >/= 0.60 during hyperoxemia). RESULTS: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). CONCLUSIONS: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. TRIAL REGISTRATION: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073

Apport du FDG-PET et de la biologie moléculaire dans les fièvres prolongées inexpliquées (à propos d'une série rétrospective de 103 cas)

La prise en charge des fièvres prolongées inexpliquées demeure un défi malgré l'apport des nouveaux outils paracliniques. Des séries récentes suggèrent l'intérêt du PET-scan dans la stratégie diagnostique mais aucune n'a étudié l'apport de' la biologie moléculaire pour le diagnostic des pathologies infectieuses. Nous avons réalisé une étude rétrospective à partir de 1 03 patients afin de préciser l'apport diagnostique de ces outils ainsi que l'évolution clinique et la mortalité de ces patients. Etude rétrospective au sein de 2 services de médecine interne d'un centre hospitalo-universitaire entre 2002 et 2012. Le diagnostic de fièvres prolongées inexpliquées repose sur les critères actualisés par Durack et Street en 1991. Le diagnostic final n'a pas été établi dans 50% des cas (n=52). Les étiologies étaient d'origine infectieuse dans 12% des cas (n=12}, inflammatoires dans 29% des cas (n=30}, tumorale dans 3% des cas (n=3) et diverses dans 6% des cas (n=6). Le taux de mortalité est de 10,5% (n=11) et indépendant de l'existence d'un diagnostic. Le décès est imputable dans 5 cas au tableau clinique et dans 2 cas chez des patients sans diagnostic final. Un PET-scan a été réalisé chez 47% des patients (n=48) et était contributif dans 21% des cas (n=10).Parmi ces 48 patients, 6 résultats de TDM étaient contributifs (12,5%) dont 2 associés à un PET-scan négatif. Aucun facteur prédictif de Pet-scan contributif n'a été identifié .Vingt-huit patients ont bénéficié de techniques de biologie moléculaire dont une seule était contributive au diagnostic (PCR CMV). Comme cela a été observé dans les études récentes, le groupe des patients sans diagnostic rend compte de la majorité des fièvres prolongées inexpliquées et la part de maladies infectieuses diminue. Le rendement du PET -scan est de l'ordre de 20%. L'intérêt de la biologie moléculaire semble mineur. Le taux de mortalité globale observée dans l'étude (10%) et le taux de mortalité dans les groupe avec ou sans diagnostic, respectivement 6% et 4% est conforme aux données de la littérature.LYON1-BU Santé (693882101) / SudocSudocFranceF

Fever of unknown origin in the 2000s: Evaluation of 103 cases over eleven years

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Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis (RECORDS): study protocol for a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial

International audienceIntroduction: Corticosteroids affect variably survival in sepsis trials, suggesting heterogeneity in patients’ response to corticosteroids. The RECORDS (Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis) trial aimed at defining endotypes associated with adults with sepsis responsiveness to corticosteroids.Methods and analysis: RECORDS, a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial, will randomly assign to a biomarker stratum 1800 adults with community-acquired pneumonia, vasopressor-dependent sepsis, septic shock or acute respiratory distress syndrome. In each stratum, patients will be randomly assigned to receive a 7-day course of hydrocortisone and fludrocortisone or their placebos. Patients with COVID-19 will be treated with a 10-day standard course of dexamethasone and randomised to fludrocortisone or its placebo. Primary outcome will be 90-day death or persistent organ dysfunction. Large simulation study will be performed across a range of plausible scenarios to foresee power to detect a 5%–10% absolute difference with corticosteroids. We will assess subset-by-treatment interaction by estimating in a Bayesian framework two quantities: (1) measure of influence, relying on the value of the estimation of corticosteroids’ effect in each subset, and (2) measure of interaction.Ethics and dissemination: The protocol was approved by the Ethics Committee ( Comité de Protection des Personnes, Dijon, France), on 6 April 2020. Trial results will be disseminated at scientific conferences and results will be published in peer-reviewed journals.Trial registration number ClinicalTrials.gov Registry ( NCT04280497 )

Study protocol and statistical plan for the ICRAKI trial: Intermittent haemodialysis versus continuous renal replacement therapy for severe acute kidney injury in critically ill patients

International audienceBackground: The effect of intermittent haemodialysis (IHD) vs continuous renal replacement therapy (CRRT) on mortality and/or renal function recovery in adults with acute kidney injury (AKI) and a recognised indication for renal replacement therapy (RRT) remains controversial.Objective: To summarise the protocol and statistical analysis plan for the ICRAKI trial.Design, settings and participantsICRAKI is a non-inferiority multicentre randomised controlled trial comparing IHD and CRRT. We will include 1000 patients with AKI receiving (or who have received) invasive mechanical ventilation and/or catecholamine infusion and who have at least one recognised criterion for initiating RRT.Intervention: The study compares IHD with CRRT.Main outcomes measures: The primary endpoint is the proportion of patients who will meet one or more criteria for a major adverse kidney event (composite of death, RRT dependence and/or more than a 25 % increase in serum creatinine from baseline value) 90 days after randomisation. Secondary endpoints are time to death; mortality at day (D)28, D60 and D90; number of patients with RRT dependency at D28, D60 and D90; number of patients with more than a 25 % increase in serum creatinine from baseline value at D28, D60 and D90; intensive care unit (ICU) and hospital length of stay; time until cessation of RRT; catecholamine-free days, ventilator-free days and RRT-free days through day 28; estimated glomerular filtration rate at hospital discharge; the number of episodes of adverse events.Conclusion: The ICRAKI trial will inform the choice of RRT modalities in critically ill patients with severe AKI. More than 300 patients were already included

Applying positive end-expiratory pressure before and during endotracheal tube removal versus extubation with concomitant aspiration: protocol for the randomised controlled multicentre EXSUPEEP trial

International audienceIntroduction The optimal method for removing the endotracheal tube (ETT) during extubation in the intensive care unit (ICU) remains uncertain. Two methods are described for removing the ETT in ICU, namely the ‘Traditional technique’ with continuous aspiration during cuff deflation and ETT removal; and the ‘PEEP’ method, which consists in applying positive end-expiratory pressure (PEEP) before and during cuff deflation and ETT removal. Our hypothesis is that applying PEEP during extubation in the ICU would improve clinical outcome. Methods and analysis This is a prospective, multicentre, randomised, open-label, controlled, superiority trial, analysed by intention-to-treat, comparing ETT removal with concomitant suction vs application of PEEP before and during ETT removal. In total, 424 patients will be recruited and randomly assigned in a 1:1 ratio to one of two groups, according to the strategy of ETT removal. The primary outcome is the number of days free from any mechanical ventilation within 28 days following extubation. Secondary outcomes include the reintubation rate up to 7 days after ETT removal, the cumulative duration of non-invasive ventilation up to 7 days following extubation, the rate of acute respiratory failure, the rate of acquired pneumonia during the first 7 days following ETT removal, the length of stay in ICU and in hospital and all-cause mortality at 28 days following ETT removal. Ethics and dissemination The study was approved by the Ethics Committee ‘CPP Ile de France II’. Patients will be included after providing written informed consent. The results will be submitted for publication in peer-reviewed journals, and in national and international congresses. Trial registration number NCT05147636

A Bundle of Interventions to Prevent Pressure Ulcers During Prone Position in Adult Patients With Acute Respiratory Distress Syndrome: Results of a French Stepped‐Wedge Randomized Controlled Trial

International audienceABSTRACT Background In patients with moderate‐to‐severe acute respiratory distress syndrome, the frequency of pressure ulcers is higher in the prone position than in the supine position. Aim To assess the effect of a bundle of interventions to prevent pressure ulcers in patients with acute respiratory distress syndrome prone. Study Design ESCARD is a stepped‐wedge prospective multicentre trial conducted in France that included patients with moderate‐to‐severe acute respiratory distress syndrome, intubated and with an indication for pronation. In the control period, patients received the routine means of each centre. In the experimental period, the bundle of specific standardized means included: eye protection with methylcellulose; strapped lower eyelids; 15° body inclination; specific cushions inserted between the mattress and head/thorax and knees/feet; head rotation every 4 h. The primary end‐point was the occurrence of a new pressure ulcer at any location and stage in the anterior part of the body 7 days after inclusion. It was assessed from pictures taken in the supine position and independently analysed by two experts blinded to the allocated period. Results From 16 April 2018 to 3 December 2020 (with an interruption between 12 March and 15 July 2020 because of COVID pandemic), a total of 160 patients were included in 9 centres; 156 were analysed. At the first proning session, all 6 specific preventive means were implemented in 1.2% of the patients in the control period and 91.8% in the experimental period. At Day 7, 53 patients (63.9%) in the control versus 40 (54.8%) in the experimental period had a new pressure ulcer at any location and of any stage (odds ratio = 0.92; 95% confidence interval [0.39; 2.18]). There was a 42.8% discrepancy between the two experts. Conclusions In this prospective multicentre stepped‐wedge trial, the bundle of interventions did not lead to a significant reduction in the frequency of new pressure ulcers in moderate‐to‐severe acute respiratory distress syndrome patients treated by prone position. Relevance to Clinical Practice The critical care nurses were able to manage patients enrolled in a complex trial up to its planned end. Even though negative, the study should encourage intensive care unit (ICU) nurses to better define the bundle of interventions including introducing other methods not used in the present study. ICU nurses should also assess the stage of pressure ulcers consistently over time. ICU nurses should consider further studies because pressure ulcer is a relevant issue of concern during the pronation in acute respiratory distress syndrome patients. If so, the new trial should include a larger number of ICUs. Trial Registration: The protocol was approved by an ethics committee (number 2017‐A01449‐44 on 7 October 2017) and was recorded in clinicaltrials.gov (NCT03125421

The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2): study protocol for a randomized controlled trial

Abstract Background The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration &gt; 40 mmol/l and oliguria/anuria &gt; 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed “standard”) with another in which RRT is further delayed for a longer period (termed “delayed strategy”). Methods/design This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration &gt; 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects. Discussion The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019. Trial registration ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018. </jats:sec

The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2): study protocol for a randomized controlled trial

International audienceBackground: The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed “standard”) with another in which RRT is further delayed for a longer period (termed “delayed strategy”).Methods/design: This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation.Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l).The primary outcome will be the number of RRT-free days at day 28.One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects.Discussion: The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019