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IntroductionStatus epilepticus (SE) in adults is a serious neurological emergency that can lead to high morbidity and mortality rates. Although functional outcomes are often assessed using general scoring systems, limited data on health-related quality of life (HRQoL) in patients admitted to intensive care units (ICUs) are still limited. Furthermore, comprehensive evaluations of patient-reported physical, cognitive, mental health and psychological outcomes are lacking in this population. POSEIDON 2 aims to assess HRQoL and cognitive, physical and psychological impairments at 3 and 12 months after ICU discharge following SE and quantify caregiver burden.Methods and analysisPOSEIDON 2 is a prospective, multicentre, longitudinal study conducted in 19 French ICUs. The study combines data from the SE ICTAL Registry with data from patients who survived admission to the ICU for SE, who will be recruited for the study. The study also includes patient-reported outcome (PRO) data collected 3 (M3) and 12 (M12) months after discharge from the ICU using validated instruments. The Zarit scale will be used to measure the burden on caregivers at M3 and M12. The primary endpoint is the prevalence of overall HRQOL impairment at M3 and M12, as defined by dichotomous scores on the physical and mental components of the 36-Item Short Form Health Survey compared with those of the general population. Secondary endpoints include domain-specific impairments, such as cognitive function, dependence, mental health and patient experiences. The sample size has been calculated based on an estimated prevalence of 75% for HRQoL impairment, with a planned sample size of 140 patients.Ethics and disseminationThe POSEIDON 2 study protocol received ethical approval from the ethics committee ‘Comité de Protection des Personnes Ouest VI’ on 5 October 2023 (#2023-A01223-42). The study is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice and the regulatory requirements of France. Written informed consent is obtained from participants, who are able to decline participation or withdraw from the study at any time. Findings will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences.Trial registration numberNCT06100978.

ObjectiveTargeted temperature management (TTM), through its physiological effects on intracranial pressure, may impede the progression to brain death (BD) in severe anoxic brain injury post-cardiac arrest (CA). We examined the potential association between the use of TTM and the occurrence of BD after CA.DesignMonocentric, retrospective study.SettingIntensive care unit, Versailles Hospital, France.ParticipantsComatose survivors of CA who died from BD or postanoxic encephalopathy (PAE) after 24 hours.Main outcome measuresPAE deaths corresponded to withdrawal of life-sustaining therapy (WLST) due to irreversible postanoxic coma or vegetative state according to prognostication guidelines. BD corresponded to the cessation of cerebral vascularisation secondary to intracranial hypertension. The diagnosis of BD was definite by clinical diagnosis of deep coma according to the Glasgow Coma Scale 3, loss of all brainstem reflexes and the demonstration of apnoea during a hypercapnia test. A cerebral omputed tomography (CT) scan or two isoelectric and unreactive electroencephalograms were used to confirm BD. To identify the independent association between TTM and BD, we conducted a multivariable logistic regression analysis.ResultsOut of 256 patients included between 2005 and 2021, 54.3% received TTM for at least 24 hours, and 56 patients (21.9%) died from BD. In the multivariable analysis, TTM for 24 hours or more was not associated with a decrease in BD (Odds Ratio 1.08, 95% CI 0.51 to 2.32). Factors associated with BD included a total duration of no-flow plus low-flow exceeding 30 min, CA due to neurological causes or hanging and a high arterial partial pressure of carbon dioxide between days 1 and 2 after admission.ConclusionsThis exploratory analysis of post-CA patients with severe anoxic brain injury did not find an association between TTM ≥24 hours and a reduction in BD. Further studies are needed to identify specific subgroups of post-CA patients for whom TTM may be especially futile or even harmful.

Ascitic fluid infection (AFI) is a life-threatening complication of cirrhosis. We aimed to identify early indicators of secondary peritonitis (SP), which requires emergency surgery, and to describe the outcomes of SP and spontaneous bacterial/fungal peritonitis (SBFP). Adults with cirrhosis and AFI admitted to 16 university or university-affiliated ICUs in France between 2002 and 2017 were studied retrospectively. Cases were identified by searching the hospital databases for relevant ICD-10 codes and hospital charts for AFI. Logistic multivariate regression was performed to identify factors associated with SP. Secondary outcomes were short- and long-term mortality and survivors’ functional outcomes. Of 178 included patients (137 men and 41 women; mean age, 58 ± 11 years), 21 (11.8%) had SP, confirmed by surgery in 16 cases and by abdominal computed tomography in 5 cases. Time to diagnosis exceeded 24 h in 7/21 patients with SP. By multivariate analysis, factors independently associated with SP were ascitic leukocyte count > 10,000/mm 3 (OR 3.70; 95%CI 1.38–9.85; P  = 0.009) and absence of laboratory signs of decompensated cirrhosis (OR 4.53; 95%CI 1.30–15.68; P  = 0.017). The 1-year mortality rates in patients with SBFP and SP were 81.0% and 77.5%, respectively (Log-rank test, P  = 0.92). Patients with SP vs. SBFP had no differences in 1-year functional outcomes. This multicenter retrospective study identified two indicators of SP as opposed to SBFP in patients with cirrhosis. Using these indicators may help to provide early surgical treatment.

Natraemia is often abnormal in critically ill patients and may change rapidly during renal replacement therapy (RRT). This database study in a single intensive care unit (ICU) evaluated natraemia before and after the first RRT session for acute kidney injury. Of 252 patients who required RRT in 2018–2020, 215 were included. Prevalences were 53.9% for hyponatraemia (≤ 135 mmol/L) and 3.7% for hypernatraemia (> 145 mmol/L). Dialysate sodium was ≥ 145 mmol/L in 83% of patients. Median dialysis sodium gradient was 12 mmol/L, with a value above 16 mmol/L in 25% of patients. Median natraemia increased from 135 before to 140 mmol/L after RRT, the median hourly increase being faster than recommended, at 1.0 mmol/L [0.2–1.7]. By multivariate analysis, the only variable significantly associated with the RRT-induced natraemia change was the dialysis sodium gradient [odds ratio, 1.66; 95% confidence interval 1.39–2.10]. Pearson’s correlation coefficient between the gradient and the natraemia change was 0.57. When performing RRT in ICU patients, in addition to the haemodynamic considerations put forward in recommendations, the dialysis sodium gradient deserves careful attention in order to control natraemia variations. Studies to devise a formula for predicting natraemia variations might prove helpful to confirm our results.

Pain is a universal issue and is of particular concern in mechanically ventilated patients, as they require intensive nursing care and multiple invasive procedures, while being unable to communicate verbally. The aim of this study was to assess the effect of music on pain experienced by mechanically ventilated patients during morning bed bathing. Of the 60 mechanically ventilated patients enrolled in this single-center pilot study between March 2013 and October 2015, the first 30 received no music and the next 30 the music intervention, during the morning bed bath. The Behavioral Pain Scale (BPS) score was determined during and at the end of the bath then 30, 60, and 120 minutes after the bath. BPS score changes over time were assessed and the proportions of bath times spent with a BPS score ≥5 and with the maximal BPS score were determined. At baseline, no patient had pain (defined as a BPS score <5) and the median BPS score was 3 [IQR, 3;3] in both groups (P = 0.43). After bed bath initiation, 88% of patients experienced pain. The maximum BPS value during the bath was lower in the music group (5 [5;6.7] vs. 7 [5;7]). Proportions of total bath time spent with BPS≥5 and with the maximum BPS were significantly lower in the music group than in the control group (2.0 [0.3;4.0] vs. 10 [4.3;18.0]; P < .0001 and 1.5 [0;3.0] vs. 3.5 [2.0;6.0]; P = .005; respectively). Two hours after the end of the bath, the BPS values had returned to baseline in both groups. In our population, music significantly decreased pain intensity and duration during the morning bed bath in mechanically ventilated patients. These results warrant further assessment in a large multicenter randomized controlled trial. ClinicalTrials.gov NCT02883959.

Patients discharged from intensive care units (ICUs) are at high risk of adverse long-term outcomes including cardiovascular and/or renal events and a 1-year mortality of approximately 22%. Plasma biomarkers measured at ICU discharge have demonstrated strong prognostic value, with elevated cardiac or renal biomarkers identifying patients at particularly high risk of poor outcomes. Sodium-glucose cotransporter 2 inhibitors are now widely recognised for their cardioprotective and nephroprotective effects in chronic conditions such as type 2 diabetes, heart failure or chronic kidney disease. These agents improve both morbidity and mortality across a range of high-risk populations. We hypothesise that a therapeutic strategy aimed at preventing the progression of cardiovascular and/or renal injury following ICU discharge may improve long-term outcomes in ICU survivors. This is a multicentre, double-blind, randomised, placebo-controlled clinical trial conducted across 16 teaching and non-teaching ICUs in France. We will enrol 600 adult patients (18 years of age or older) who have received mechanical ventilation and/or vasopressors for at least 24 hours during their ICU stay, and who meet at least one of the following criteria at ICU discharge: N-terminal pro-B-type natriuretic peptide (NT-proBNP) >800 pg/mL or BNP >90 ng/L, an estimated glomerular filtration rate between 25 and 90 mL/min/m². Eligible patients will be randomised in a 1:1 ratio to receive either dapagliflozin (10 mg once daily) or a matching placebo for a duration of 1 year. The primary outcome is a composite endpoint assessed at 1 year after randomisation, comprising: all-cause mortality, unscheduled hospitalisation for acute heart failure and decrease in renal function. Feasibility will be assessed based on patient and clinical acceptability and recruitment performance, including enrolment rates across participating centres. This study has been approved by the Institutional Review Board (CPP Ile-de-France 5). Written informed consent will be obtained from all participants prior to enrolment and the initiation of any study-related procedures. Dapagliflozin is a widely available medication with an established safety profile. If proven effective, it would represent a readily deployable strategy to improve long-term outcomes in ICU survivors. The study is described in accordance with the Standard Protocol Items: Recommendations for Interventional Trials framework, and key design features and methodological decisions are outlined accordingly. DAPA-ICU aims to evaluate the efficacy of dapagliflozin in cardiorenal protection among critically ill patients following ICU discharge. The main trial results will be submitted for publication in a peer-reviewed journal as soon as they become available after final analysis. NCT07025629.

To demonstrate the feasibility and safety of weekly high-dose liposomal amphotericin B (L-AmB) (as a pre-emptive antifungal treatment) for 2 weeks in patients with septic shock and Candida colonization. Pilot, multicentre, open-label, prospective study conducted in seven French ICUs. Non-immunocompromised patients, receiving mechanical ventilation were eligible if they presented ICU-acquired severe sepsis requiring newly administered antibacterial agents and Candida colonization in at least two sites. Exclusion criteria included the need for antifungal therapy and creatinine > 220 μmol/L. All patients were to receive a high-dose L-AmB (10 mg/kg/week) for two weeks. A follow-up period of 21 days following the second administration of L-AmB was conducted. Treated patients were compared to 69 matched untreated controls admitted in the same ICUs before the study period. Twenty-one patients were included in the study, of which 20 received at least one infusion of high-dose L-AmB. A total of 24 adverse events were identified in 13(61%) patients. Fourteen adverse events were categorized as serious in 8(38%) patients. In four cases the adverse events were considered as potentially related to study drug administration and resulted in L-AmB discontinuation in one patient. Few patients experienced severe renal toxicity since no patient presented with severe hypokalemia. No patients required renal replacement therapy. Compared to matched controls, no significant increase in serum creatinine levels in patients receiving high-dose L-AmB was reported. Weekly administration of high-dose L-AmB has a manageable safety profile and is feasible in patients with ICU-acquired sepsis and multiple Candida colonization. Trials of L-AmB versus other antifungal agents used as pre-emptive antifungal therapy are warranted. ClinicalTrials.gov NCT00697944.