Background: Although remifentanil provides effective analgesia for critically ill patients receiving invasive mechanical ventilation (IMV), its clinical utility is limited by opioid-related adverse events. Oliceridine, a G protein-biased μ-opioid receptor agonist, theoretically decouples analgesia from these adverse effects, yet robust evidence in this critically ill population is currently lacking. Methods: This multicenter, assessor- and patient-blinded, non-inferiority randomized controlled trial was conducted across 19 intensive care units (ICUs) in China. Adult patients receiving IMV were randomised 1:1 to receive oliceridine or remifentanil, with doses titrated to maintain Critical-Care Pain Observation Tool scores below 3. The primary endpoint was time in target analgesic range (TTR; non-inferiority margin, −10%). Findings: Of 307 randomized patients, 304 completed follow-up for analysis (151 oliceridine, 153 remifentanil), with comparable baseline characteristics. Median TTR was 96·0% versus 92·3% (absolute difference 3·7%, 95% CI −0·3% to 5·7%; one-sided P=0·008 for non-inferiority), meeting the predefined non-inferiority margin. Respiratory depression was 0% versus 4·6% during infusion (P=0·015) and 0% versus 7·9% post-extubation (P=0·005). Other adverse reactions, IMV and ICU duration, and mortality were comparable between groups, while oliceridine yielded significantly lower analgesic costs. Subgroup analyses showed superior analgesia in older patients (age > 60 years) and those on IMV for non-respiratory failure, with more prominent safety benefits in severely ill subjects (Acute Physiology and Chronic Health Evaluation II > 17). Interpretation: Oliceridine provides non-inferior analgesia to remifentanil with favorable respiratory safety in critically ill patients requiring IMV, supporting its use as a safer analgesic alternative in this major ICU population.

Introduction In the de-resuscitation phase of septic shock, resolving vasoplegia and fluid mobilisation can increase venous congestion in patients with sepsis-related myocardial dysfunction. This study will characterise the haemodynamic effects and safety of recombinant human brain natriuretic peptide (rh-BNP) in this population.Methods and analysis This single-centre, prospective, single-arm study will enrol 30 adults recovering from septic shock with improving infection/vasopressor trends, sinus rhythm, ongoing pulse-index continuous cardiac output (PiCCO) monitoring and measurable arm-equilibrium pressure (Parm). Eligibility will require cardiac dysfunction (left-ventricular ejection fraction ≤50% and/or ≥10% absolute decline when available) and volume overload (global end-diastolic volume index >800 mL/m² and extravascular lung water index >10 mL/kg). Participants will receive rh-BNP (2 µg/kg intravenous bolus over 15 min, then a 0.01 µg/kg/min infusion for up to 72 hours). Measurements will be obtained at baseline, acute response (30–60 min), 24, 48 and 72 hours. The primary outcome will be within-patient change in venous return pressure gradient (ΔPVR, Parm−central venous pressure) from baseline to acute response. Secondary outcomes will include indices of preload, cardiac function, tissue perfusion and venous congestion. Haemodynamic instability will be the safety endpoint. Paired tests and repeated-measures analyses will estimate within-patient changes over time.Ethics and dissemination Ethics approval has been obtained from the Ethics Committee of Sichuan Provincial People’s Hospital, Sichuan Academy of Medical Sciences (No. 2024-653-1). Written informed consent will be obtained. Findings will be disseminated via peer-reviewed publications and conferences.Trial registration number NCT06745206.

BACKGROUND:Remimazolam tosylate, a novel short-acting benzodiazepine, has shown effective and safe sedation in mechanically ventilated patients in intensive care units in a phase 2 trial. The authors conducted a multicenter, randomized, single-blind, actively controlled, phase 3 trial (NCT06222294) for further evaluation. METHODS:Mechanically ventilated patients, requiring sedation for 6 h or longer with a target Richmond Agitation-Sedation Scale (RASS) of -2 to +1, were randomized (1:1) to receive intravenous remimazolam tosylate (loading dose, 0.08 mg/kg; maintenance, 0 to 2.0 mg · kg -1 · h -1 ) or propofol (loading dose, 0.3 to 0.5 mg/kg; maintenance, 0.3 to 4.0 mg · kg -1 · h -1 ). Both allowed for adjusted infusion rates or additional doses to maintain target RASS. Maximum treatment duration was 24 h. The primary endpoint was the proportion of patients achieving sedation success, defined as maintaining target sedation range for 70% or more of drug administration time without rescue sedation. Noninferiority margin was -8%. RESULTS:Between March 12, 2024, and September 24, 2024, a total of 211 patients (mean age, 61.1 yr; 63.5% male; 99.1% postoperative) received remimazolam tosylate (n = 106) or propofol (n = 105). Mean ± SD treatment duration was 11.5 ± 3.6 h for remimazolam tosylate and 11.1 ± 3.1 h for propofol; mean ± SD total dose was 187.1 ± 134.4 mg and 593.7 ± 530.9 mg, respectively. Sedation success rate was 98.1% with remimazolam tosylate and 96.2% with propofol (difference, 1.9%; 95% CI, -3.3 to 7.8%); mean ± SD percentage of time in RASS target range was 95.1% ± 13.8% versus 95.0% ± 12.9%, and the proportion of patients receiving rescue sedation was 0.0% (0 of 106) versus 1.0% (1 of 105). Mean ± SD additional doses required totaled 0.03 ± 0.17 for remimazolam tosylate and 0.18 ± 0.77 for propofol. Adverse event occurred in 81 (76.4%) patients with remimazolam tosylate and 77 (73.3%) with propofol; all were mild-moderate, except one severe with propofol. Mean ± SD terminal half-life of remimazolam tosylate was 1.97 ± 1.62 h. CONCLUSIONS:Remimazolam tosylate demonstrated noninferior efficacy and good tolerability compared with propofol for short-term sedation in postoperative mechanically ventilated intensive care unit patients.

BACKGROUND:ARDS constitutes a major cause of mortality, with limited therapeutic options. RESEARCH QUESTION:Is STSA-1002 safe and clinically beneficial in ARDS caused by viral pneumonia? STUDY DESIGN AND METHODS:This was a phase 1b/2, multicenter, double-blind, placebo-controlled trial. Participants aged between 18 and 85 years with ARDS caused by viral pneumonia and Pao2/Fio2 ≤ 200 mm Hg were included. Patients were randomly assigned (1:1:1) to receive STSA-1002 1,350 mg, STSA-1002 750 mg, or placebo. The STSA-1002 or matched placebo was administered to participants on days 1, 3, and 7, with an optional additional dose on day 14 ± 1 at the physician's discretion. The primary end point was time to clinical improvement. Clinical improvement was defined as either blood oxygen saturation/Fio2 > 235 mm Hg or Pao2/Fio2 > 200 mm Hg, maintained for at least 48 hours, whichever occurred first, within 28 days. RESULTS:Between December 9, 2023, and March 20, 2025, a total of 49 patients were enrolled and randomized to treatment. Among the 47 patients who received study medication, 17 received STSA-1002 1,350 mg, 15 received STSA-1002 750 mg, and 15 received placebo. The time to clinical improvement was 6.0 days in the STSA 1002 1,350 mg group, 8.4 days in the STSA 1002 750 mg group, and 7.4 days in the control group. A subdistribution hazard ratio of 1.55 (95% CI, 0.68-3.55) was reported for the STSA-1002 1,350 mg group and 1.04 (95% CI, 0.46-2.38) for the STSA-1002 750 mg group according to a competing risk model, both compared with the control group. Following adjustment for baseline Pao2/Fio2, the subdistribution hazard ratio was 1.22 (95% CI, 0.52-2.86) and 1.13 (95% CI, 0.47-2.75), respectively. The 28-day all-cause mortality was 5.88% (1 of 17), 26.67% (4 of 15), and 40% (6 of 15). STSA-1002 was well tolerated. INTERPRETATION:STSA-1002 exhibited a favorable safety profile and potential efficacy. These findings warrant confirmation in a phase 3 trial. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT06038916; URL: www. CLINICALTRIALS:gov.

Extubation failure may occur despite a successful spontaneous breathing trial (SBT), suggesting that conventional SBT criteria may not fully capture respiratory reserve. The Flow index (FI), derived from inspiratory flow time waveform morphology, reflects inspiratory effort during pressure support ventilation. We investigated whether FI trajectories during SBT were associated with extubation failure. In this retrospective cohort study, FI values during the final 10 min of SBT were summarized within six prespecified 2 min windows using patient level medians. Latent class trajectory modeling was used to identify FI patterns, followed by clinically and statistically justified consolidation into three trajectory groups. Multivariable logistic regression evaluated the association between FI trajectory and extubation failure. Mean based trajectories and machine learning analyses were performed as exploratory supplementary analyses. Among 432 screened patients, 123 were included, and 27 (22.0%) experienced extubation failure. The consolidated groups were Traj1, stable/moderate reserve (n = 89; failures, 12.4%); Traj2, depleted/low effort (n = 18; failures, 50.0%); and Traj3, escalating/high effort (n = 16; failures, 43.8%). Compared with Traj1, Traj2 (adjusted odds ratio [OR], 8.23; 95% confidence interval [CI], 1.69-39.98; p = 0.009) and Traj3 (adjusted OR, 16.06; 95% CI, 3.02-85.40; p = 0.001) were associated with higher odds of extubation failure after adjustment for age, sex, SOFA score, and dynamic compliance. Median based FI trajectories during SBT identified distinct patterns associated with extubation failure and may provide complementary post SBT risk stratification information. Prospective external validation is required before clinical implementation.

Septic shock remains one of the most lethal emergency and critical care conditions, with underlying pathophysiology closely linked to uncontrolled vasodilation mediated by nitric oxide activation of the soluble guanylate cyclase pathway (NO–sGC–cGMP pathway). Methylene blue (MB), through its inhibition of this pathway, has demonstrated hemodynamic benefits and may serve as a targeted adjunctive therapy particularly in patients with septic shock requiring high-dose vasopressors, a severely vasoplegic subpopulation characterized by markedly elevated mortality. However, large-scale randomized controlled trials (RCTs) evaluating MB treatment for mortality benefit in high-dose vasopressor-dependent septic shock patients are currently lacking. This is an investigator-initiated, multicenter,open-label, blinded endpoint RCT that will recruit adult septic shock patients requiring norepinephrine equivalent doses > 0.3 μg/kg/min within 24 h of vasopressor initiation across multiple centers in China. A total of 566 patients will be randomized 1:1 to receive MB treatment (2 mg/kg loading dose followed by 0.25 mg/kg/h maintenance infusion for up to 48 h or 4 h after vasopressor discontinuation) or equal volume 5

RATIONALE:Physiological studies showed benefits for bedside setting of personalized positive end-expiratory pressure (PEEP) by electrical impedance tomography (EIT), balancing lung overdistension and collapse. OBJECTIVES:To evaluate whether EIT-guided PEEP improves the clinical outcomes of patients with acute respiratory distress syndrome (ARDS) compared to the lower PEEP/FiO2 table strategy. METHODS:This randomized trial enrolled adult patients with moderate to severe ARDS across five sites in China from February 2022 to June 2023. Participants were randomly assigned to EIT-guided PEEP (collapse-overdistension crossing point value by decremental PEEP trial) or the classical lower PEEP/FiO2 table. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS:The trial was terminated early for futility, based on a pre-planned interim analysis. A total of 190 patients were included and completed follow-up. PEEP levels didn't differ between groups during the first 7 days (difference in marginal means 0.2 [SE 0.1]; P = .187). At 28 days, mortality was 52 patients (55.9%) in the EIT-guided PEEP group and 51 patients (52.6%) in the lower PEEP/FiO2 table group (hazard ratio [HR] 0.96 [95% CI, 0.65-1.41]; P = .821). Ventilator-free days and other secondary clinical and safety outcomes did not differ, either. However, EIT-guided PEEP assigned higher PEEP and decreased mortality in patients with higher lung recruitability, as assessed by the recruitment-inflation ratio method (16 [35.6%] of 45 patients vs 27 [60.0%] of 45 patients; HR 0.49 [95% CI, 0.26-0.91]; P = .024). CONCLUSIONS:In patients with moderate to severe ARDS, EIT-guided PEEP did not significantly reduce 28-day mortality compared with the lower PEEP/FiO2 table strategy. Due to early termination, the study may have been underpowered to detect a clinically important difference. TRIAL REGISTRATION:clinicaltrials.gov NCT05207202.

Objectives We aimed to evaluate the effectiveness, safety, and pharmacokinetics of eravacycline in treating carbapenem-resistant organism (CRO) infections in immunocompromised hosts (ICHs). Methods A prospective study was conducted at five hospitals in China from January 2024 to July 2025. Patients with confirmed CRO infections who received intravenous eravacycline at a fixed, consecutive dose of 50 mg for at least 72 hours were included. Plasma concentrations were measured, and pharmacokinetic modeling was performed. Results Microbiological clearance rates differed by infection site: intra-abdominal infections showed the highest clearance (80.6%, 50/62) and pulmonary infections the lowest (32.4%, 23/71), compared with the overall cohort clearance rate of 51.4% (91/177) (P < 0.001). The 28-day mortality rate was 35.6%. PPK modeling (one-compartment), based on plasma concentration data from 80 patients (54 transplant and 26 non-transplant), revealed reduced clearance in non-transplant patients with cirrhosis, with 45.7% lower clearance in Child-Pugh B and 86.3% lower clearance in Child-Pugh C. In transplant recipients, body weight (BW) exhibited a significant linear association with clearance, while the C-reactive protein level was inversely correlated with distribution volume, while moderate CYP3A4/5 inhibitor use increased the volume by 38.9%. Adverse events occurred in 13.6% of patients. Multivariable analysis identified older age and fungal co-infection as factors associated with mortality. A treatment duration of ≥ 5 days was associated with improved survival. Conclusions Eravacycline monotherapy can achieve favorable outcomes in ICHs with CRO infections and help in managing future CRO infections.

Patient-ventilator asynchrony (PVA) is a common and critically import clinical problem in patients receiving mechanical ventilation. However, PVAs are often underrecognized, underestimated and delayed, and there has been minimal success in automating their detection. In this study, we develop an efficient and fast end-to-end model to recognize PVAs on ventilator waveforms: running the model costs 106.5ms on CPUs and 7.8ms on GPUs. We propose label striping and stripe-mask encoding for efficient multi-class multi-target detecting. The model innovatively integrates causal convolutional, depth-wise separable convolutional, and recurrent neural networks to memorize long short-term causal features. With 60s waveform segments, our model performs a cross-validation mean average precision (mAP) of 88.1% and a testing mAP of 65.7% for comprehensive PVA detection. Our approach might be implemented as a monitoring tool to automatically identify PVAs for improving bedside and remote care and prioritizing patient comfort.

As medical treatment advances, a growing proportion of sepsis patients survive from their initial critical illness. However, excessive treatment and diminished quality of life after discharge raise substantial concerns. Sarcopenia affects 40%–70% of sepsis survivors, manifesting as flaccid weakness in the extremities and diaphragm. This condition typically resolves within weeks or months, but in some cases, recovery does not occur and may last for 2 years after intensive care unit (ICU) discharge. Consequently, sepsis patients with sarcopenia face an unfavorable long-term influence, and they also consume considerable medical resources. The mechanisms and treatments of sepsis-associated sarcopenia (SASP) are increasingly recognized as research priorities. This review provides a comprehensive analysis of molecular mechanisms, measuring parameters, and therapeutic approaches for SASP.

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and fatal interstitial lung disease of unknown cause, characterized by severe dyspnea, restrictive lung function, impaired gas exchange, and progressive destruction of pulmonary tissue. While approved drugs can slow disease progression, improving patients’ quality of life remains a critical challenge. PolyPHb, a hemoglobin-based oxygen carrier (HBOC) derived from virally inactivated and purified human placental hemoglobin, efficiently transports and releases oxygen. In this study, we show that PolyPHb enhances exercise tolerance and mitigates inflammation and fibrosis in a bleomycin-induced pulmonary fibrosis mouse model. To elucidate the underlying mechanisms, we performed transcriptomic analysis of lung tissues following PolyPHb treatment, revealing potential regulatory networks involved in its protective effects. These results provide new insights into potential interventions of PolyPHb in IPF and suggest that it may contribute to improved functional outcomes, though further studies are needed to fully define its impact on exercise capacity and quality of life.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive scarring, alveolar destruction, and limited therapeutic options. Although the exact etiology of IPF remains unclear, emerging evidence suggests that ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation and oxidative stress, plays a significant role in its pathogenesis. Ferroptotic stress not only compromises alveolar epithelial cell integrity, but also triggers inflammatory responses and profibrotic signaling cascades that activate and sustain fibroblast dysfunction. This review delineates the core regulatory pathways of ferroptosis, iron metabolism, lipid peroxidation, antioxidant defenses, mitochondrial remodeling, and RNA editing, with an emphasis on their relevance in IPF. We explore how epithelial injury and macrophage-derived signals initiate ferroptosis, and how fibroblast subsets, shaped by scRNA-seq-defined heterogeneity and plasticity, respond to these cues by reinforcing ECM deposition and oxidative stress. Therapeutic avenues targeting ferroptosis, including antioxidant supplementation, iron chelation, and modulation of lipid metabolism, are discussed alongside cell-specific interventions and nanodelivery strategies. By integrating recent advances in molecular profiling and ferroptosis biology, this review provides a framework for leveraging ferroptosis as a tractable target in IPF and identifies novel directions for precision antifibrotic therapy.

ARDS (acute respiratory distress syndrome) and PF (pulmonary fibrosis) are severe pulmonary conditions with significant morbidity and mortality. This review focuses on the pyroptosis, a lytic, pro-inflammatory form of programmed cell death, as a central mechanism linking these two pathologies. We address how inflammasome activation stimulates the pyroptosis initiation and subsequently releases a cascade of inflammatory cytokines that drive the acute lung injury of ARDS. Subsequently, we elucidate how this sustained pyroptotic inflammation, combined with shifts in macrophage polarization, creates a pro-fibrotic microenvironment that promotes fibroblast activation and extracellular matrix deposition, thereby mechanistically driving the transition from ARDS to PF. The pathological landscape, from the early stage of ARDS to PF, is further shaped by a dynamic interaction between pyroptosis, necroptosis, and ferroptosis, with the temporal dominance of each pathway influencing the progression from acute inflammation to chronic fibrosis. Particularly, the clinical relevance of these mechanisms is also addressed in COVID-19-induced ARDS. Therefore, targeting key regulators of this axis, such as the NLRP3 inflammasome and the effector protein Gasdermin D, presents a promising therapeutic strategy to alleviate inflammatory responses upon tissue damage and halt fibrotic progression, offering new hope for these severe lung diseases.

Objective: To analyze the characteristics of pathogens and related risk factors of bloodstream infections (BSI) in patients undergoing ECMO support using mNGS technology. Methods: A retrospective analysis was conducted on 59 patients who received ECMO support in the Emergency Intensive Care Unit (EICU) of the Affiliated Hospital of Xuzhou Medical University from January 2021 to March 2024. The patients were divided into two groups based on the presence of BSI: the infection group (BSI group) and the noninfection group (N‐BSI group). The clinical data of the two groups were compared, and the characteristics of pathogens were analyzed using mNGS technology. Logistic regression was used to analyze the related risk factors for BSI associated with ECMO. Results: (1) The incidence of BSI in patients undergoing ECMO support was 20.34%. Compared to the N‐BSI group, the BSI group had significantly higher levels of procalcitonin (14.9 ± 7.2 vs. 9.4 ± 4.7), C‐reactive protein (140.58 ± 24.64 vs. 87.26 ± 11.06), blood lactate (8.55 ± 1.40 vs. 5.07 ± 0.55), and ECMO catheter indwelling time (12.00 ± 1.71 vs. 7.96 ± 0.76) ( p < 0.05). (2) mNGS detection indicated that the BSI group mainly identified viruses and Gram‐negative bacilli (G‐), with Acinetobacter baumannii being the most prevalent pathogen. The resistance genes were predominantly blaTEM, which confers resistance to penicillins and cephalosporins. (3) Logistic regression analysis revealed that diabetes, ECMO indwelling time, blood lactate levels, and G‐bacilli infection were risk factors for BSI during ECMO. Conclusion: Gram‐negative bacteria are the primary pathogens in BSI among patients undergoing ECMO support. Diabetes, ECMO catheter indwelling time, and elevated blood lactate are independent risk factors for these infections. Rational selection of antibiotics and strengthened management of related factors can effectively control the occurrence of BSI during ECMO support.

BACKGROUND:Mucormycosis is a life-threatening fungal infection with high mortality in critically ill patients. Clinical manifestations and outcomes of mucormycosis in intensive care units (ICUs) remain poorly investigated. METHODS:We conducted a multicenter retrospective study including 43 adult patients with confirmed mucormycosis admitted to 14 tertiary ICUs between January 2014 and May 2022. Clinical characteristics, diagnostic approaches, treatment strategies, and outcomes were analysed. RESULTS:The mean age was 56.8 ± 16.2 years, with 16/43 (37.2%) female patients. The 28-day survival rate was 46.5% (20/43). Lung involvement was predominant (29/43, 67.4%), and 29/43 (67.4%) patients received amphotericin B therapy. Survivors showed significantly better treatment response compared to non-survivors (16/20, 80% vs. 4/23, 17.4%, p < 0.001). Non-survivors demonstrated significantly higher levels of aspartate aminotransferase, C-reactive protein, and white blood cells, along with lower albumin levels. Metagenomic next-generation sequencing (mNGS) was associated with a shorter time to diagnosis. Multivariate analysis identified age, respiratory failure, time from symptom onset to diagnosis, and antifungal treatment response as independent predictors of 28-day mortality (AUC = 0.852). CONCLUSION:In critically ill patients with mucormycosis, early diagnosis and prompt targeted therapy are crucial determinants of survival, with our newly developed prediction model providing a practical tool for risk stratification, while mNGS shows promise in expediting diagnosis.

Acute Respiratory Distress Syndrome (ARDS) is a severe inflammatory lung condition often triggered by infections or sepsis, characterized by diffuse alveolar damage, pulmonary edema, and impaired gas exchange. Despite advances in supportive care, ARDS continues to have a high mortality rate. The pathogenesis of ARDS involves an exaggerated immune response leading to tissue damage and inflammation. Regulatory cell death pathways, particularly ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation and oxidative stress, play a critical role in ARDS progression. Ferroptosis is characterized by the accumulation of lipid peroxides and is regulated by enzymes such as glutathione peroxidase 4 (GPX4) and the system Xc- antiporter. Dysregulation of these pathways exacerbates oxidative stress and tissue damage in ARDS. In the context of ARDS, ferroptosis contributes to the destruction of alveolar and endothelial cells, leading to increased vascular permeability, pulmonary edema, and impaired gas exchange. Immune cells like macrophages and neutrophils, while essential for pathogen clearance, can also contribute to lung injury when overactivated, highlighting the need for therapeutic strategies to modulate ferroptosis. Therapeutic targeting of ferroptosis in ARDS includes the use of antioxidants, GPX4 activators, iron chelators, and inhibitors of lipid peroxidation. These approaches aim to reduce oxidative stress, restore antioxidant defenses, and prevent iron-driven cell death. Future research must address challenges in identifying reliable biomarkers, understanding subphenotype-specific mechanisms, and integrating ferroptosis inhibitors into existing therapeutic frameworks. By targeting ferroptosis, it may be possible to mitigate ARDS severity and improve patient outcomes, offering new hope for the management of this devastating condition.

ABSTRACT:Background : Although β-blockade for heart rate (HR) control in septic shock is conventionally initiated after 24 h of stabilization in most studies, we investigated whether esmolol could be safely and effectively administered immediately postinitial resuscitation in hyperkinetic septic shock patients with persistent tachycardia. Methods : In this randomized controlled pilot study, 24 hyperkinetic septic shock patients with sinus tachycardia (>95 bpm) after initial resuscitation were randomized to receive either esmolol (titrated for 10% HR reduction) as the treatment group or equal volume of normal saline as the control group. The primary endpoint was achievement of target HR reduction, with safety assessed through monitoring of tissue perfusion parameters and hemodynamic stability over 72 h. Results : Demographic and baseline characteristics were comparable between groups. The esmolol group achieved faster HR reduction (12/12 vs. 7/12 patients at 24 h, P = 0.037) with comparable hemodynamic stability. Despite initial decreases in cardiac index (4.5 ± 0.9 to 3.9 ± 0.6 L/min/m 2 , P = 0.009) and oxygen delivery index (585 ± 145 to 504 ± 132 mL, P = 0.040) at 1 h, tissue perfusion parameters remained stable. No significant between-group differences were observed in central venous oxygen saturation, CO 2 gap, microcirculation parameters, inflammatory markers, organ functions, or hospital mortality (42% vs. 42%, P = 1.000). Conclusion : This pilot study suggested that post-initial resuscitation early esmolol administration targeting modest HR reduction appears feasible and safe in hyperkinetic septic shock patients with persistent tachycardia, providing foundation for future large-scale investigations.

Acute Respiratory Distress Syndrome (ARDS) remains a critical challenge in intensive care, marked by high mortality and significant patient heterogeneity, which limits the effectiveness of conventional supportive therapies. This review highlights the transformative potential of Artificial Intelligence (AI) and Machine Learning (ML) in revolutionizing ARDS management. We explore diverse AI/ML applications, including early prediction and diagnosis using multi-modal data (electronic health records [EHR], imaging, ventilator waveforms), advanced prognostic assessment and risk stratification that outperform traditional scoring systems, and precise identification of ARDS subtypes to guide personalized treatment. Furthermore, we detail AI's role in optimizing mechanical ventilation (e.g., PEEP settings, patient-ventilator asynchrony detection, mechanical power-guided strategies), facilitating Extracorporeal Membrane Oxygenation (ECMO) support decisions, and advancing drug discovery. The review also delves into cutting-edge methodologies such as Graph Neural Networks, Causal Inference, Federated Learning, Self-Supervised Learning, and the emerging paradigm of Large Language Models (LLMs) and agent-based AI, which promise enhanced data integration, privacy-preserving research, and autonomous decision support. Despite challenges in data quality, model generalizability, interpretability, and clinical integration, AI-driven strategies offer unprecedented opportunities for precision medicine, real-time decision support, and ultimately, improved patient outcomes in ARDS.