Alain Combes

The preferred method of renal-replacement therapy for acute kidney injury in critically ill patients remains uncertain. In this multicenter, open-label, noninferiority trial, we randomly assigned critically ill adults with acute kidney injury who had indications for renal-replacement therapy to undergo intermittent hemodialysis or continuous renal-replacement therapy as the initial treatment. The primary outcome was a major adverse kidney event - defined as death, dependence on renal-replacement therapy, or a serum creatinine concentration more than 25% above the baseline value - by day 90. The trial was stopped early after sequential interim analyses showed a sustained signal of higher mortality with intermittent hemodialysis than with continuous renal-replacement therapy. A total of 554 patients underwent randomization, with 272 patients assigned to undergo intermittent hemodialysis and 282 to undergo continuous renal-replacement therapy; 535 patients (260 in the intermittent group and 275 in the continuous group) were included in the intention-to-treat population. A major adverse kidney event occurred by day 90 in 203 patients (78.1%) in the intermittent group and in 197 patients (71.6%) in the continuous group (adjusted absolute risk difference, 6.28 percentage points; 95% confidence interval [CI], -1.22 to 13.79). Death by day 90 occurred in 164 patients (63.1%) and in 147 patients (53.5%), respectively. Kaplan-Meier mortality estimates at day 90 were 63.3% and 53.6% (hazard ratio, 1.30; 95% CI, 1.04 to 1.63). The most common complication potentially related to acute kidney injury or renal-replacement therapy was hypotension, which occurred in 179 patients (68.8%) in the intermittent group and in 183 patients (66.5%) in the continuous group. Among critically ill patients with acute kidney injury who had indications for renal-replacement therapy, intermittent hemodialysis as the initial treatment approach was not shown to be noninferior to continuous renal-replacement therapy with respect to major adverse kidney events by day 90 and was associated with higher mortality. (Funded by the French Ministry of Health; ICRAKI ClinicalTrials.gov number, NCT06032884.).

Purpose Obesity is increasingly encountered among patients requiring extracorporeal membrane oxygenation (ECMO) for severe respiratory or cardiac failure. It alters respiratory and cardiovascular physiology and drug pharmacokinetics and introduces technical and logistical challenges that may complicate patient selection, ECMO initiation, cannulation, anticoagulation, and monitoring. This review summarizes current evidence regarding the epidemiology, physiological implications, outcomes, and management of obesity in patients supported with veno-venous (VV) or veno-arterial (VA) ECMO. Results Available evidence, largely retrospective and based on body mass index classifications, suggests that obesity should not be considered a contraindication to VV-ECMO, with outcomes comparable to or potentially better than those of patients without obesity. However, obesity-related respiratory mechanics may exaggerate the apparent severity of lung injury, emphasizing the need for optimized conventional ARDS management, including appropriate ventilatory strategies and prone positioning, before ECMO initiation. In contrast, outcomes during VA-ECMO are more heterogeneous, particularly in extracorporeal cardiopulmonary resuscitation (ECPR), and may be influenced by patient selection, comorbidities, and timing of support. Obesity also creates important technical challenges requiring individualized cannulation, anticoagulation, and perfusion strategies. Conclusion Obesity alone should not preclude access to ECMO, particularly VV-ECMO. Successful management requires anticipation of obesity-related challenges, appropriate infrastructure, and structured multidisciplinary protocols. Further prospective studies are needed to clarify obesity-specific risks, optimize management strategies, and evaluate long-term outcomes. Graphic abstract

Extracorporeal life support (ECLS) is increasingly used to rescue patients with refractory respiratory failure, cardiogenic shock and/or cardiac arrest. Ac

BACKGROUND: The aim of the DESAC study (Devenir des Survivants d’Arrets Cardiaques) was to describe the survival rate and neurological status of out-of-hospital (out-of-hospital cardiac arrest) survivors, and to assess the influence of prehospital and intrahospital factors. METHODS: Between July 2015 and October 2018, consecutive nontraumatic out-of-hospital cardiac arrest patients aged over 18 years discharged alive from 33 intensive care units in Paris and the suburbs (France) were included. Their neurological status was assessed every 6 months using the Cerebral Performance Category (CPC) scale. Prognostic factors associated with a favorable neurological outcome at 24 months (CPC category of 1 or 2) were assessed by covariate-adjusted logistic regression. Trajectories of CPC level over time were derived using a linear mixed model in survivors with at least 3 repeated assessments. RESULTS: Out of 593 survivors, 525 were followed up for 24 months (mean age, 58.1±15.3 years, 79% males), and 449 of 525 (86%) had a favorable neurological outcome. Initial shockable rhythm (adjusted odds ratio, 3.33 [95% CI, 1.57–7.07]) and previous practice of sport (adjusted odds ratio, 3.13 [95% CI, 1.21–8.12]) were associated with favorable outcome, whereas factors with reduced odds ratio were older age (adjusted odds ratio per 10 years, 0.53 [95% CI, 0.41–0.69]) and prior percutaneous coronary intervention (adjusted odds ratio, 0.38 [95% CI, 0.17–0.85]). Therapeutic hypothermia or acute coronary interventions were not related to prognosis ( P >0.05). Overall, among the 514 patients with at least 3 repeated assessments, 5 distinct CPC trajectories (2 reflecting early death were combined) were derived: 64% remained in CPC1, 13.4% in CPC2, 11% improved from CPC2 to CPC1, and 11.6% died either early or lately (>3 months) during follow-up. CONCLUSIONS: This multicentric prospective study indicates that 86% of out-of-hospital cardiac arrest survivors had a favorable neurological outcome at 24 months. Pre-event and intraevent factors (including previous practice of sport and shockable rhythm), but not in-hospital management (therapeutic hypothermia or acute coronary interventions), were associated with a favorable outcome. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02494414.

Extracorporeal carbon dioxide removal (ECCO2R), when used as an adjunct to mechanical ventilation in patients with mild to moderate acute respiratory distr

Importance: Levosimendan may facilitate weaning from venoarterial extracorporeal membrane oxygenation (VA-ECMO) and improve survival, but supporting evidence remains limited. Objective: To assess whether early administration of levosimendan reduces the time to successful VA-ECMO weaning in patients with severe but potentially reversible cardiogenic shock. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial conducted across 11 intensive care units (ICUs) in France. Between August 27, 2021, and September 10, 2024, 205 adult patients with acute cardiogenic shock who had started VA-ECMO in the preceding 48 hours were enrolled. Final follow-up was completed on November 10, 2024. Interventions: Patients were randomized in a 1:1 ratio to receive levosimendan, 0.15 μg/kg per minute, to be increased to 0.20 μg/kg per minute after 2 hours (n = 101), or placebo (n = 104). Main Outcomes and Measures: The primary outcome was time to successful ECMO weaning within 30 days following randomization. Secondary outcomes included ECMO-, mechanical ventilation–, and organ failure–free days, ICU and hospital lengths of stay, serious adverse events, and all-cause 30- and 60-day mortality. Results: Among the 205 randomized patients (median age, 58 [IQR, 50-67] years; 149 [72.7%] male), main cardiogenic shock etiologies were postcardiotomy (79 [38.5%]), acute myocardial infarction (56 [27.3%]), and myocarditis (28 [13.7%]). Treatment dose was increased to 0.20 ± 0.01 μg/kg per minute in 93% of patients receiving levosimendan and in 96% of those receiving placebo. Within 30 days, 69 of 101 patients (68.3%) had a successful ECMO weaning in the levosimendan group compared with 71 of 104 (68.3%) in the placebo group (risk difference, 0.0% [95% CI, −12.8% to 12.7%]; subdistribution hazard ratio, 1.02 [95% CI, 0.74-1.39]; P = .92). In the levosimendan and placebo groups, respectively, median ECMO duration (5 [IQR, 4-7] days vs 6 [IQR, 4-11] days; P = .53), mean ICU length of stay (18 [SD, 15] days vs 19 [SD, 15] days; P = .42), and 60-day mortality (27.7% vs 25.0%; risk difference, 2.7% [95% CI, −9.0% to 15.3%]; P = .78) did not differ significantly. Ventricular arrhythmias occurred more frequently with levosimendan (18 [17.8%] vs 9 [8.7%]; absolute risk difference, 9.2% [95% CI, 0.4%-18.1%]). Conclusions and Relevance: Among patients with severe but potentially reversible cardiogenic shock supported by VA-ECMO, early levosimendan administration did not significantly reduce the time to successful weaning of ECMO compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04728932

Background: This study aimed to evaluate the safety and efficacy of inhaled pegylated adrenomedullin (PEG-ADM) for the management of acute respiratory distress syndrome in critically ill patients on mechanical ventilation. Methods: A Phase 2a/b randomised, double-blind, placebo-controlled multicentre trial was conducted. Patients with acute respiratory distress syndrome were assigned to receive PEG-ADM 960 μg or 1920 μg, or placebo. The primary endpoints were safety, efficacy, and ventilator-free survival at Day 28. Efficacy was assessed using ventilator-free survival and the clinical utility index, a composite endpoint that includes extravascular lung water index, oxygenation index, non-pulmonary Sequential Organ Failure Assessment score. Results: Ninety patients were randomised (PEG-ADM 960 μg: n = 29; PEG-ADM 1920 μg: n = 30; placebo: n = 31). Both dosages of PEG-ADM were well tolerated, with adverse event profiles similar to placebo. However, no significant efficacy was observed on the clinical utility index. Ventilator-free survival at Day 28 was lower in the PEG-ADM 960 μg group (52%) compared with the PEG-ADM 1920 μg (67%) and placebo (65%) groups. No significant differences were noted in overall mortality or the need for continued ventilation at Days 28 and 60. Conclusion: Inhaled PEG-ADM was well tolerated in patients with acute respiratory distress syndrome, but it did not improve clinical outcomes, which led to the early discontinuation after the first part of the trial for futility. Trial registration: ClinicalTrials.gov: NCT04417036 (date of registration: 4 June 2020).

Autoimmune hemolytic anemia (AIHA) is a rare but potentially life-threatening condition requiring intensive care unit (ICU) admission in severe cases. While corticosteroids and immunosuppressants are standard treatments, their delayed efficacy limits their utility in critical settings requiring rapid hemolysis control. Plasma exchange (PlEx) may offer a rapid intervention, but its effectiveness in severe AIHA remains uncertain. This study aims to assess the clinical characteristics, outcomes, and the potential benefit of PlEx in ICU cases with severe AIHA. We conducted a multicenter retrospective cohort study including patients with severe AIHA admitted to 15 ICUs within the Assistance Publique–Hôpitaux de Paris (AP-HP) network between 2017 and 2024. Clinical, biological, and therapeutic data were collected. A multivariate logistic regression model, an analysis adjusted on a propensity score (PS) and on inverse probability of treatment weighting (IPTW) were used to identify predictors of in-ICU mortality and evaluate the association between PlEx and in-ICU mortality. One hundred forty-eight ICU stays involving severe AIHA hemolytic crises were analyzed. The median age at ICU admission was 61 {48–71} years, with a balanced sex ratio (51% male). Admission median hemoglobin was 5.2 g/dL {4.2–7.2} and in-ICU mortality was 17.6%. Risk factors for in-ICU mortality included age > 60 years, renal replacement therapy, mechanical ventilation, and high-dose intravenous methylprednisolone (HDIM). Therefore, ICU mortality was mainly driven by organ dysfunction rather than anemia severity. Standard corticosteroid therapy (1–2 mg/kg) (OR:0.19 [0.03–0.94], P = 0.05) and PlEx (OR:0.04 [0.004–0.4], P = 0.008) were associated with improved survival. The association between PlEx and outcome persisted after PS (OR: 0.04 [0.001–0.39]; P = 0.012) and IPTW (OR: 0.13 [0.02–0.55]; P = 0.011) adjustment. In this large ICU cohort, severe AIHA was associated with high mortality, driven by organ failure rather than anemia severity. PlEx are associated with survival, suggesting its potential role as a bridge to immunosuppressive therapy in selected cases. Prospective studies are needed to confirm these findings.