Nishiyama S, Uchino S, Saito T
… +4 more, Fukano K, Ono S, Kamio T, Katayama S
Crit Care Med
· 2026 Jun · PMID 42233727
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OBJECTIVES: To operationalize and temporally validate an electronic medical record (EMR)-integrated machine learning system (Big data-driven Evaluation of Survival and Treatment in Acute Illness [BEST-AI]) that generates...OBJECTIVES: To operationalize and temporally validate an electronic medical record (EMR)-integrated machine learning system (Big data-driven Evaluation of Survival and Treatment in Acute Illness [BEST-AI]) that generates hourly predictions for multiple ICU outcomes, with emphasis on discrimination, calibration, and workflow integration. DESIGN: Single-center hybrid study with stepwise clinical deployment and forward-in-time temporal validation. SETTING: Thirty-bed tertiary mixed medical-surgical ICU in Japan. PATIENTS: All ICU admissions from August 2017 to March 2025. Exclusions: age younger than 16 years or ICU stay less than 4 hours. Development cohort (n = 11,176; from August 2017 to July 2024) and temporal validation cohort (n = 1,127; from August 2024 to March 2025). INTERVENTIONS: EMR-integrated deployment of BEST-AI providing hourly probabilistic predictions to clinicians within the EMR; no protocolized clinical interventions were mandated. MEASUREMENTS AND MAIN RESULTS: Six prediction tasks (in-hospital mortality, ICU mortality, ICU discharge ≤ 72 hr, intubation ≤ 72 hr, extubation ≤ 72 hr, tracheostomy at ICU discharge) were evaluated. In temporal validation, the area under the receiver operating characteristic curves ranged from 0.856 to 0.960, and the area under the precision-recall curves from 0.302 to 0.786. Decile-based calibration showed overall good agreement; hospital mortality was slightly overestimated at higher predicted probabilities, whereas ICU mortality remained well aligned. The intubation task had comparatively lower discrimination and greater deviation from perfect calibration, consistent with low event counts and heterogeneous timing. A 24-hour landmark sensitivity analysis (one prediction per patient at 24 hr after ICU admission) preserved discrimination and calibration relative to the main analysis, supporting robustness beyond repeated-measures evaluation. The system was successfully maintained with automated hourly updates and EMR-embedded patient- and unit-level visualizations, without prescriptive alerts. CONCLUSIONS: A continuously deployed, EMR-integrated ICU prediction system achieved strong temporal discrimination and generally good calibration. Embedding real-time predictions into routine workflow was feasible, and the system was maintained with automated hourly updates. Prospective multicenter studies are warranted to assess transportability and clinical impact.
Suganuma S, Kanda N, Yoshida M
… +5 more, Takano H, Sakuramoto H, Kariya A, Ohbe H, Nakamura K
Crit Care Med
· 2026 Jun · PMID 42233714
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OBJECTIVES: To evaluate how heterogeneous diagnostic definitions of persistent inflammation, immunosuppression, and catabolism syndrome (PICS), identified through a systematic review, influence patient identification and...OBJECTIVES: To evaluate how heterogeneous diagnostic definitions of persistent inflammation, immunosuppression, and catabolism syndrome (PICS), identified through a systematic review, influence patient identification and associated clinical outcomes when applied to a nationwide Japanese ICU cohort. DESIGN: Systematic review and retrospective cohort study. SETTING: The multicenter inpatient administrative claims database with laboratory test values in Japan. PATIENTS: Critically ill adult patients admitted to ICUs in Japan between March 2010 and September 2021. A total of 215,474 ICU patients were analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A systematic review identified 23 clinical studies using varying diagnostic criteria for PICS. Definitions differed substantially in laboratory thresholds, assessment timing, and inclusion requirements. PICS definitions extracted from the review were applied to the Medical Data Vision cohort, and overlap among definitions was assessed using an UpSet plot. The number of patients meeting each definition varied widely (211-47,888 patients), demonstrating that even small differences in thresholds or timing markedly influence patient identification. The prevalence of PICS varied widely across definitions (range, 0.1-22.2%). In-hospital mortality also showed marked variability (range, 11.4-64.0%). Functional outcomes were consistently poor, with a high proportion of patients discharged with a Barthel Index less than 90 (range, 46.5-78.9%) and a prolonged hospital stay greater than 28 days (range, 54.9-94.7%). CONCLUSIONS: The present study revealed marked heterogeneity among existing PICS definitions, resulting in wide variations in prevalence and outcomes. Despite this variability, PICS consistently identified patients with prolonged hospitalization and physical impairment. These findings highlight the need for standardized diagnostic criteria to improve comparability across studies and support earlier identification and intervention for at-risk ICU survivors.
Kim D, Kim YJ, Ryoo SM
… +2 more, Kim WY, Korean Sepsis Alliance (KSA) Investigators
Crit Care Med
· 2026 Jun · PMID 42233709
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OBJECTIVE: Neutropenic sepsis is a high-risk form of sepsis associated with rapid deterioration and high mortality. Although early antibiotic administration is recommended, the benefit of shorter time to antibiotics (TTA...OBJECTIVE: Neutropenic sepsis is a high-risk form of sepsis associated with rapid deterioration and high mortality. Although early antibiotic administration is recommended, the benefit of shorter time to antibiotics (TTA) remains uncertain. This study aimed to determine the relationship between TTA and in-hospital mortality for patients with neutropenic sepsis and to identify specific phenotypes most vulnerable to TTA delays. DESIGN: Prospective, multicenter observational cohort study. SETTING: Twenty tertiary or university-affiliated hospitals in South Korea. PATIENTS: In this prospective multicenter cohort study, we analyzed 942 patients with sepsis and neutropenia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: TTA was categorized into three groups: less than 1 hour (early), 1-3 hours (intermediate), and greater than or equal to 3 hours (delayed). We used inverse probability of treatment weighting (IPTW) with logistic regression to evaluate the association between TTA and in-hospital mortality and a causal forest model to identify characteristics associated with the effect of longer TTA. Overall, 211, 531, and 200 patients belonged to the early, intermediate, and delayed groups, respectively. In IPTW-weighted logistic regression, odds ratio (OR) for in-hospital mortality was significantly higher in the delayed (OR: 1.50; 95% CI, 1.22-1.85; p < 0.001) and intermediate groups (OR: 1.26; 95% CI, 1.04-1.53; p = 0.021) than in the early group. The association between longer TTA and mortality was stronger among patients with septic shock and among those with hematologic malignancy in both models. The causal forest further identified elevated lactate as a potential effect modifier, indicating greater estimated benefit from earlier TTA; however, interaction tests in the weighted logistic model were not significant. CONCLUSIONS: Delayed antibiotic administration was associated with increased in-hospital mortality among patients with neutropenic sepsis. The impact on in-hospital mortality is heterogeneous, varying by patient characteristics, particularly septic shock and hematologic malignancy.
Nguyen CD, Panganiban HP, Karahalios A
… +11 more, Fazio T, Ankravs MJ, Fitzpatrick P, Richardson M, McAlister S, Tran-Duy A, MacIsaac CM, Ricciardone S, Rechnitzer T, Ali Abdelhamid Y, Deane AM
Crit Care Med
· 2026 Jun · PMID 42223327
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OBJECTIVES: Enteral magnesium replacement may be as effective as IV replacement while being a cheaper and more environmentally sustainable intervention. The primary objective was to evaluate whether enteral magnesium is...OBJECTIVES: Enteral magnesium replacement may be as effective as IV replacement while being a cheaper and more environmentally sustainable intervention. The primary objective was to evaluate whether enteral magnesium is noninferior to IV administration in correcting hypomagnesemia. DESIGN: Prospective, open-label, parallel-group, electronic medical record-embedded, randomized, noninferiority trial. SETTING: Single-center mixed medical-surgical-trauma ICU. PATIENTS: Patients with serum magnesium concentration between 0.35 and 0.7 mmol/L. INTERVENTIONS: Enteral or IV magnesium replacement. MEASUREMENTS AND MAIN RESULTS: The primary outcome was serum magnesium concentration at 24 hours after enrollment, with a noninferiority margin of 0.1 mmol/L. Secondary outcomes included dose of administered magnesium, urine magnesium excretion, costs of intervention delivery, waste, bloodstream infections, new atrial fibrillation, duration of admission, and mortality. Between June 2023 and May 2024, 360 patients were included. Baseline magnesium concentrations were comparable. At 24 hours, mean (sd) magnesium concentrations were 0.80 mmol/L (0.19 mmol/L) in the enteral arm and 0.92 mmol/L (0.23 mmol/L) in the IV arm, with a mean difference of -0.12 mmol/L (95% CI, -0.16 to -0.07 mmol/L) indicating inconclusive results about noninferiority. Enteral replacement substantially decreased urine magnesium concentrations compared with IV replacement (median difference of area under the curve, -46.2 mmol·hr/L), cost (median difference, -6.48 Australian dollars; 95% CI, -7.40 to -5.56 Australian dollars), waste (median difference, -55 grams; 95% CI, -58 to -51 grams), Co2 footprint (median difference, -946 grams; 95% CI, -996 to -896 grams), and additional IV fluid administration (median, -100 mL; interquartile range, -200 to -100 mL). There were no between group differences for other outcomes. CONCLUSIONS: Enteral magnesium replacement for mild-to-moderate hypomagnesemia did not establish noninferiority to IV replacement at a margin of 0.1 mmol/L but it reduced urinary concentration of magnesium, cost, environmental waste, carbon emissions, and IV fluid administration.
Li J, Liu S, Zhu X
… +8 more, Wang H, Pan M, Yan Y, Zhang R, Yan Y, Wang S, Pan Z, Zhan L
Crit Care Med
· 2026 Jun · PMID 42223319
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OBJECTIVES: To evaluate the clinical prognostic value of the core circadian transcription factor brain and muscle ARNT-like 1 (BMAL1) in sepsis-induced acute lung injury (SI-ALI) and explore its mechanistic role in orche...OBJECTIVES: To evaluate the clinical prognostic value of the core circadian transcription factor brain and muscle ARNT-like 1 (BMAL1) in sepsis-induced acute lung injury (SI-ALI) and explore its mechanistic role in orchestrating organellar homeostasis and macrophage resilience. DESIGN: Prospective clinical cohort study and randomized blinded preclinical laboratory investigation. SETTING: ICU and research laboratory of Renmin Hospital of Wuhan University. SUBJECTS: Thirty patients with SI-ALI and 12 healthy controls; adult male C57BL/6 mice and mouse alveolar macrophage cell line (MH-S) alveolar macrophages. INTERVENTIONS: Clinical monitoring of BMAL1, clock circadian regulator (CLOCK) genes, and hormones. Murine cecal ligation and puncture models, lipopolysaccharide treated MH-S cell treated with nobiletin, small interfering RNA-mediated knockdown of BMAL1, and pharmacological modulators of endoplasmic reticulum (ER)-phagy. MEASUREMENTS AND MAIN RESULTS: Patients with SI-ALI exhibited profound circadian arrhythmia with significantly reduced expression of BMAL1 and CLOCK. BMAL1 levels were significantly lower in nonsurvivors and served as a robust predictor of 28-day mortality (area under the curve = 0.8177), showing a significant negative correlation with Sequential Organ Failure Assessment scores. In preclinical models, pharmacological activation of BMAL1 via nobiletin significantly mitigated lung histopathological damage, improved 5-day survival, and enhanced macrophage phagocytic and bactericidal activity. Mechanistically, BMAL1 deficiency impaired family with sequence similarity 134, member B-mediated ER-phagy, leading to inositol-requiring enzyme 1 increased and NADH:ubiquinone oxidoreductase core subunit V1, ATP synthase F1 subunit alpha, and seahorse-derived respiration/adenosine triphosphate production decreased. Nobiletin rescued these organellar defects in a BMAL1-dependent manner. CONCLUSIONS: BMAL1 is a master regulator of cellular homeostasis in SI-ALI. It protects against lung injury by orchestrating a coordinated response between ER-phagy and mitochondrial metabolism. BMAL1 represents a clinically valuable prognostic biomarker and a potential therapeutic target for SI-ALI.
Crit Care Med
· 2026 Jun · PMID 42223318
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OBJECTIVES: Previous studies have shown that selective decontamination of the digestive tract can reduce the incidence and mortality of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. However,...OBJECTIVES: Previous studies have shown that selective decontamination of the digestive tract can reduce the incidence and mortality of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. However, the prophylactic role of IV antibacterials, one of its essential components, remains unclear. Therefore, this study aims to evaluate the efficacy and safety of systemic prophylactic use of antibacterials in mechanically ventilated patients. DATA SOURCES: We systematically searched PubMed, Embase, and The Cochrane Library from inception to November 30, 2025. STUDY SELECTION: Randomized controlled trials (RCTs) evaluating prophylactic use of systemic antibacterials in mechanically ventilated patients in the ICUs were included. DATA EXTRACTION: Two researchers independently conducted literature screening, data extraction, and quality assessment. Meta-analysis was performed using RevMan 5.4, and the quality of the evidence was evaluated using the recommended Grading of Recommendations, Assessment, Development, and Evaluation method. DATA SYNTHESIS: Eleven RCTs with 5562 patients were included. Meta-analysis results showed that the systemic prophylactic use of antibacterials probably reduces the incidence of VAP (relative risk [RR], 0.65; 95% CI, 0.55-0.77; moderate certainty) and the incidence of early VAP (RR, 0.52; 95% CI, 0.41-0.66; moderate certainty), but probably does not reduce in-hospital mortality (RR, 0.85; 95% CI, 0.68-1.06; moderate certainty) or duration of mechanical ventilation (mean difference [MD], -0.32; 95% CI, -0.79 to 0.16; moderate certainty), and may not reduce length of hospital stay (MD, -1.56; 95% CI, -5.15 to 2.02; low certainty). Subgroup analyses suggested that systemic prophylactic antibacterials probably reduces VAP in brain injury patients. No increased risk of drug resistance and adverse events was observed. CONCLUSIONS: The systemic prophylactic antibacterials probably reduces early VAP and overall VAP incidence in mechanically ventilated patients, but probably does not reduce in-hospital mortality. Subgroup analyses suggested potential benefits in brain injury patients. Given incomplete safety reporting, future research should include comprehensive resistance surveillance and cost-effectiveness analyses.
Xu S, Fang Z, Kong X
… +6 more, Shi J, Tang Y, Zhao B, Fang F, Huang J, Lu B
Crit Care Med
· 2026 Jun · PMID 42223312
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OBJECTIVES: Plant-based diets have been linked to favorable metabolic and immune regulation, suggesting their potential role in sepsis prevention. However, evidence supporting this association remains limited. This study...OBJECTIVES: Plant-based diets have been linked to favorable metabolic and immune regulation, suggesting their potential role in sepsis prevention. However, evidence supporting this association remains limited. This study aimed to examine the associations between adherence to plant-based dietary patterns and risk of sepsis. DESIGN: A large-scale cohort study. SETTING: This was a prospective cohort study including participants of the UK Biobank. PATIENTS: A total of 180,442 participants from the UK Biobank. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall, healthy, and unhealthy plant-based diet indices (PDI, hPDI, and uPDI, respectively) were constructed leveraging self-reported data on 17 major food groups. Multivariable-adjusted Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% CIs for the associations between PDIs and risk of sepsis. During a median follow-up of 13 years, 4031 incident cases of sepsis were identified. A greater adherence to PDI or hPDI was associated with a lower risk of sepsis (PDI: HR, 0.87; 95% CI, 0.79-0.96; p-trend = 0.003 and hPDI: HR, 0.84; 95% CI, 0.77-0.93; p-trend < 0.001) after multivariable adjustment. In contrast, a greater adherence to uPDI was associated with an increased sepsis risk (HR, 1.15; 95% CI, 1.05-1.27; p-trend < 0.001). These associations were generally consistent across stratified and sensitivity analyses. Mediation analysis revealed that 2.5-31.6% of the association between hPDI and sepsis and 1.7-13.7% of the association between uPDI and sepsis were mediated via metabolic and inflammatory biomarkers, including body mass index and C-reactive protein. CONCLUSIONS: Adherence to a healthy plant-based diet was associated with a lower risk of sepsis, whereas adherence to an unhealthy plant-based diet was associated with an increased risk, independently of other traditional risk factors. The associations may be partly mediated through metabolic and inflammatory pathways. These findings underscore the role of high-quality plant-based diet in sepsis prevention.
Bastos LSL, Burghi G, Brandão CE
… +22 more, de Almeida R, Alves A, Antunes ARS, de Carvalho AGR, de Castro JR, Chaiben VBO, Corrêa TD, Gottardo PC, Paulo Nassar A, Nunes NF, Oliveira LC, Pastore L, Pereira RC, Romano ER, Santos VM, Schettini DA, Veiga AMO, Vilela MC, Ramos GV, Kurtz P, Soares M, ORganizational CHaractEriSTics in cRitical cAre (ORCHESTRA) Study Investigators
Crit Care Med
· 2026 Jun · PMID 42223307
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OBJECTIVES: Frailty is frequently present in patients admitted to ICU and associated with worse outcomes. Standard severity-of-illness scores (SOISs) do not account for frailty. We investigated the impact of frailty burd...OBJECTIVES: Frailty is frequently present in patients admitted to ICU and associated with worse outcomes. Standard severity-of-illness scores (SOISs) do not account for frailty. We investigated the impact of frailty burden (proportion of frail patients per ICU) on performance indicators estimated by Simplified Acute Physiology Score (SAPS) 3 and Mortality Probability Model (MPM)0-III. DESIGN: Retrospective cohort study using prospectively collected data. SETTING: One hundred fifty-nine ICUs in Brazil and Uruguay. PATIENTS: Two hundred forty-two thousand one hundred forty-one patients admitted in 2022-2023. Frailty was defined as a Modified Frailty Index (MFI) of 3 or higher. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes were hospital mortality and ICU length of stay. Performance indicators were standardized mortality rate (SMR) and standardized resource use (SRU). SAPS 3 and MPM0-III were recalibrated, and SRU parameters reestimated. Associations between frailty burden and SMR or SRU were examined with scatter plots, Spearman correlations, and efficiency matrices. The median frailty burden was 23.0% (interquartile range [IQR], 16.8-31.7%); median hospital mortality was 14.8% (IQR, 9.1-25.2%). Although higher frailty burden ICUs showed greater mortality, no consistent trend emerged. Frailty burden was not significantly correlated with performance indicators: MPM0-III (SMR: r = -0.123 [95% CI, -0.262 to 0.035] and SRU: r = -0.091 [95% CI, -0.252 to 0.081]) and SAPS 3 (SMR: r = -0.105 [95% CI, -0.258 to 0.044] and SRU: r = -0.074 [95% CI, -0.236 to 0.096]). Recalibrating models with the addition of MFI did not improve estimates. These results were consistent in practically all sensitivity analyses. ICUs with varying frailty burdens were evenly distributed across efficiency matrix quadrants. CONCLUSIONS: Frailty burden had no significant impact on ICU benchmarking with SAPS 3 or MPM0-III, suggesting limited relevance for performance comparisons.
Parvizi J, Armenta Salas M, Aparicio MK
… +7 more, Zafar SF, Desai M, Karunakaran S, Gupta A, Kamousi B, Hirsch LJ, Struck AF
Crit Care Med
· 2026 Jul · PMID 42223304
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OBJECTIVES: Point-of-care (POC) electroencephalography (EEG) enabled with artificial intelligence (AI) algorithms hold the potential to address gaps in EEG access and interpretation. We assessed the clinical association...OBJECTIVES: Point-of-care (POC) electroencephalography (EEG) enabled with artificial intelligence (AI) algorithms hold the potential to address gaps in EEG access and interpretation. We assessed the clinical association of the patterns recognized by one of such systems. DESIGN: Secondary cohort analysis of the retrospective multicenter Seizure Assessment and Forecasting with Efficient Rapid-EEG (SAFER-EEG) study. SETTING: EEG and clinical data were gathered from three academic centers with access to POC EEG (Ceribell, Sunnyvale, CA) as part of their standard of care. We used a bedside seizure burden (SzB) monitor ("bedside" algorithm) and a more sensitive online algorithm ("portal" algorithm) to determine SzB. The modified Rankin Scale (mRS) score at discharge was selected as the outcome. PATIENTS: Four hundred enrolled adult patients, 359 with complete outcome and clinical data. INTERVENTIONS: Time in seizure and peak SzB assessed by AI. MEASUREMENTS AND MAIN RESULTS: Per the bedside algorithm, 39.8% of patients had peak 5-minute SzB greater than 0%. With every additional hour of seizure detected by the bedside algorithm, patients were more likely to have unfavorable outcome (mRS > 3) at discharge (adjusted odds ratio [aOR], 1.98; 95% CI, 1.11-4.29). Compared with 5-minute SzB = 0%, prolonged activity per the bedside algorithm (peak 5-min SzB ≥ 90%) was associated with a 3.4-fold increase in aOR of poor outcome. Every 30 seconds of activity in the maximum hourly SzB of the bedside algorithm was associated with increased odds of unfavorable outcome (aOR, 1.02; 95% CI, 1.00-1.03). Combining outputs from the algorithms increased the strength of associations with outcome, particularly in patients with peak 5-minute SzB greater than or equal to 90% (aOR, 4.4; 95% CI, 1.66-12.69). CONCLUSIONS: AI-estimated SzB is associated with functional outcomes at discharge in a dose-response fashion, even after controlling for clinical cofounds. This provides initial evidence of the clinical utility of AI algorithms for detecting clinically important EEG patterns.
Boulton AJ, Elfeky A, Court R
… +14 more, Grove A, Wilson A, Auguste P, Clayton D, Gallacher D, Goligher EC, MacLeod Hall C, McAuley DF, Perkins GD, Scholefield BR, Thompson M, Yeung J, Chen YF, Couper K
Crit Care Med
· 2026 Jul · PMID 42207935
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OBJECTIVES: To undertake a systematic review evaluating the clinical and cost-effectiveness of technology-enhanced positive end-expiratory pressure (PEEP) optimization strategies in adults and children receiving invasive...OBJECTIVES: To undertake a systematic review evaluating the clinical and cost-effectiveness of technology-enhanced positive end-expiratory pressure (PEEP) optimization strategies in adults and children receiving invasive mechanical ventilation on an ICU. DATA SOURCES: We searched key electronic databases (including MEDLINE and Embase) from inception to July 2024. STUDY SELECTION: We included randomized studies examining clinical or cost-effectiveness of technology-enhanced PEEP optimization strategies compared with standard care or an alternative PEEP optimization strategy in adults and children. The primary outcome was duration of mechanical ventilation and secondary outcomes were clinical effectiveness (e.g., mortality) and efficacy (e.g., PEEP). DATA EXTRACTION: Two reviewers independently assessed eligibility, extracted data, assessed risk of bias (Revised Cochrane tool) and performed Grading of Recommendations Assessment, Development and Evaluation evidence certainty assessments. DATA SYNTHESIS: Our database and trial register search retrieved 8845 results, of which 34 studies (2951 patients) were included. Eight studies were at low risk of bias. Across studies, 7 technologies were evaluated, most commonly esophageal balloon measurement of transpulmonary pressure (10 studies), electrical impedance tomography (7 studies), pressure-volume curve analysis (6 studies), and fully automated closed-loop ventilation (5 studies). Meta-analysis used random-effects models. Duration of mechanical ventilation was reported in only three studies (172 patients, two technologies) and there was no effect compared with standard care (mean difference -0.06 d; 95% CI, -0.20 to 0.09; very low-certainty evidence).For 28-day mortality (10 studies; 1,719 patients; six technologies), technology-enhanced PEEP optimization reduced 28-day mortality (risk ratio 0.69; 95% CI, 0.52-0.93; very low-certainty evidence). No significant differences were found for other clinical-effectiveness outcomes. We identified no evidence in children or on cost-effectiveness. CONCLUSIONS: Technology-enhanced PEEP optimization strategies did not reduce duration of mechanical ventilation, but these technologies may reduce mortality. Evidence certainty was low or very low, highlighting the urgent need for adequately powered randomized trials. REGISTRATION: PROSPERO (CRD42024555390).
Meerman M, Buijser M, Neto AS
… +9 more, van den Berg L, van den Heuvel AM, Hoohenkerk G, van Driel V, Munsterman L, de Vroege R, Bailey M, Bellomo R, Ludikhuize J
Crit Care Med
· 2026 Jul · PMID 42206948
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OBJECTIVES: To determine whether perioperative IV magnesium sulfate infusion, targeting serum magnesium concentrations of 1.5-2.0 mmol/L, reduces the incidence of postoperative atrial fibrillation (POAF) in patients unde...OBJECTIVES: To determine whether perioperative IV magnesium sulfate infusion, targeting serum magnesium concentrations of 1.5-2.0 mmol/L, reduces the incidence of postoperative atrial fibrillation (POAF) in patients undergoing cardiac surgery. DESIGN: Double-blind, randomized, placebo-controlled, single-center clinical trial with interim analysis for futility. SETTING: HagaZiekenhuis, The Hague, The Netherlands (February 2022-November 2023). PATIENTS: Adult patients undergoing coronary artery bypass grafting and/or valvular surgery without prior atrial arrhythmias or severe renal dysfunction. INTERVENTIONS: Continuous IV infusion of magnesium sulfate (3 mmol/hr, with bolus if [baseline] magnesium < 1.0 mmol/L) or placebo (Ringer's lactate), initiated after induction of anesthesia and continued until ICU discharge. MEASUREMENTS AND MAIN RESULTS: A total of 265 patients underwent randomization before the trial was stopped at interim analysis for futility. Magnesium supplementation achieved clear separation in serum magnesium concentrations between groups. POAF occurred in 50 of 132 patients (37.9%) in the magnesium group and 38 of 133 patients (28.6%) in the placebo group (relative risk, 1.29; 95% CI, 0.92-1.80). No subgroup demonstrated benefit. Time-to-event and day-by-day analyses showed no early reduction in POAF with magnesium. Vasopressor use was more frequent in the magnesium group, although differences were not statistically significant. No safety signal was identified. CONCLUSIONS: In this randomized trial, perioperative magnesium infusion targeting serum concentrations of 1.5-2.0 mmol/L did not reduce POAF after cardiac surgery. These findings do not support routine prophylactic magnesium supplementation for prevention of POAF.
Lamamri M, Werner M, Sigaut S
… +5 more, Dupont J, Rodrigues A, Gallet A, Weiss E, Jeantrelle C
Crit Care Med
· 2026 May · PMID 42206945
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OBJECTIVES: Recent studies have sought to define an optimal transfusion threshold in patients with traumatic brain injury (TBI). However, baseline hemoglobin levels differ by sex. Given the male predominance in TBI epide...OBJECTIVES: Recent studies have sought to define an optimal transfusion threshold in patients with traumatic brain injury (TBI). However, baseline hemoglobin levels differ by sex. Given the male predominance in TBI epidemiology, it is essential to determine if this sex-specific physiologic difference influences the prognosis. DESIGN: Bicentric, retrospective cohort study. SETTING: Two level 1 trauma centers in France from November 2010 to July 2025. PATIENTS: Adult critically ill patients with moderate-to-severe TBI. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 5513 TBI patients. After adjustment, every 1 g/dL increase in admission hemoglobin was associated with a 31% decrease in the odds of ICU mortality (odds ratio [OR], 0.69; 97.5% CI, 0.52-0.91; p = 0.0027). The sex × hemoglobin interaction effect was not significantly associated with ICU mortality (OR, 1.04; 97.5% CI, 0.91-1.19; p = 0.433). Predicted ICU mortality risk was lower in females across all hemoglobin levels (Wald tests, all p < 0.05 from 9.0 to 13.0 g/dL). However, causal inference methods found no evidence of a sex-specific difference in standardized ICU mortality risk at equivalent admission hemoglobin levels (adjusted OR, 1.01; 95% CI, 0.85-1.19; p = 0.936). CONCLUSIONS: No interaction between admission hemoglobin and sex was found regarding ICU mortality following TBI in this cohort. These results do not support the implementation of sex-differentiated hemoglobin transfusion thresholds based solely at admission hemoglobin levels in the initial management of TBI patients. Further prospective studies are needed to confirm these findings and to evaluate whether sex-related differences may emerge when considering longitudinal hemoglobin trajectories during the ICU stay and transfusion practices.
Bouquot M, Chelly J, Quenot JP
… +28 more, Lascarrou JB, Bernard C, Monchi M, Beuret P, Sigaud F, Sboui G, Bailly P, Chambon R, Fontaine C, Mongardon N, Cerf C, Bruel C, Pichon N, Argaud L, Kinane M, Desmeulles I, Kifouche F, Hassani ML, Boubekri A, Vieille T, Marzouk M, Ravaux H, Schnell D, Sedillot N, Brunel M, Jacq G, Lesieur O, Legriel S
Crit Care Med
· 2026 May · PMID 42206939
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OBJECTIVES: To report the prevalence of potentially surgical digestive complications in critically ill patients with status epilepticus (SE), identify the associated factors, and study the association between digestive c...OBJECTIVES: To report the prevalence of potentially surgical digestive complications in critically ill patients with status epilepticus (SE), identify the associated factors, and study the association between digestive complications and mortality at hospital discharge. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Twenty-three ICUs. PATIENTS: Adults prospectively included in the ICTAL Registry between February 2018 and July 2025. Inclusion criteria were age 18 years or older and ICU admission for SE. Digestive complications were defined by severe clinical and/or radiologic findings suggestive of a need for surgical intervention, including bowel ileus, colonic dilatation, and/or gut ischemia. A propensity score identified factors associated with digestive complications. Logistic multivariable regression assessed predictors of hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1007 patients, 16 patients (1.6%) developed digestive complications (median age, 58 yr; 37.5% male) at a median of 5 days (interquartile range, 3-9 d) after SE onset. Surgery was required in six patients (37.5%). Paralytic ileus or colonic dilatation occurred in 13 patients (81.3%), and bowel or colonic ischemia in 7 (43.8%). Refractory SE (RSE) and its treatment (propofol, midazolam, thiopental, and ketamine) were significantly associated with digestive complications. In-hospital mortality was higher in patients with digestive complications (50.0% vs. 18.4%; p = 0.005). Digestive complications independently predicted mortality (odds ratio, 3.43; 95% CI, 1.13-10.21; p = 0.03). CONCLUSIONS: Potentially surgical digestive complications in SE were rare but strongly associated with RSE and its treatment. These complications independently predicted hospital mortality.