A narrative review of advances in emergency and critical care medicine in 2025: from bundle-based care to precision phenotyping and pragmatic implementation

Introduction

Background

Emergency and critical care medicine accounts for a substantial share of global mortality and disability. In 2019, the Global Burden of Disease study estimated that acute conditions requiring emergency care and/or surgical intervention contributed to approximately 37.85 million deaths and more than 1.3 billion disability-adjusted life-years (1). Sepsis and septic shock are implicated in an estimated 48 million cases annually and more than 11 million deaths worldwide, representing approximately one-fifth of all global deaths (2). Acute respiratory distress syndrome (ARDS) occurs in about 10% of intensive care unit (ICU) patients, and in-hospital mortality remains substantial despite evolving management strategies (3). Trauma also remains a major cause of preventable death, particularly in settings without mature trauma systems, where reported preventable mortality rates range from approximately 15% to 30% and outcomes continue to depend heavily on system organization and timely access to definitive care (4). Together, sepsis, acute respiratory failure, trauma, and cardiac arrest define a group of time-sensitive syndromes that continue to shape priorities in emergency and critical care. Cardiac arrest, addressed in the resuscitation section, remains an archetypal time-sensitive condition requiring coordinated system-wide integration across prehospital response, emergency care, and intensive care.

Over the past decade, efforts to improve outcomes have emphasized protocolized care, bundle-based management, and system-level quality infrastructure. In sepsis, bundled care and performance programs have been widely implemented, and higher bundle adherence has been associated with lower hospital and ICU mortality (2,5,6). In acute respiratory failure, lung-protective ventilation, prone positioning, and related strategies have supported a more standardized approach to ventilatory support across selected patient groups (7-13). In trauma, regional trauma systems, graded trauma centers, and team-based care have been associated with approximately 10% to 20% lower mortality, particularly among severely injured patients (14,15). These approaches have improved reliability in high-risk care, but important outcome gaps remain.

Rationale and knowledge gap

The limits of uniform strategies are increasingly apparent. Even well-supported protocols may yield variable benefit across heterogeneous patients and settings, and a single approach is unlikely to fit all patients (3,16). In sepsis, phenotype and endotype research highlights biologic heterogeneity that is not captured by syndrome-level labels. Across multiple domains, randomized trials conducted in high-resource settings with high protocol adherence have often demonstrated modest average treatment effects, emphasizing the need to identify which patients benefit, which do not, and where harms may occur when interventions are applied broadly (17-19).

At the same time, evidence emerging in late 2024 and becoming more prominent in 2025 has pointed to several interrelated shifts across emergency and critical care medicine. Collectively, these developments reflect a reorientation from fixed protocols to adaptive, person-centered strategies; from isolated episodes to integrated, whole-course care; and from proof-of-concept innovation to accountable implementation. Although prior reviews have summarized selected advances in sepsis, ARDS, resuscitation, trauma, or critical care artificial intelligence (AI), these topics have largely been addressed in isolation or within disease-specific frameworks. Fewer reviews have integrated these developments within a single framework that links bedside supportive care, care-continuum redesign, personalized supportive care, and pragmatic implementation across emergency and critical care medicine. This gap is important because the emergency department (ED) is no longer merely a site of triage or transfer, but an increasingly important therapeutic decision-making node within the broader continuum of critical illness care.

Objective

In this narrative review, we synthesize clinically relevant advances reported from November 2024 through December 15, 2025, with selective inclusion of foundational studies when needed for context. Our objective is not to provide an exhaustive catalog of all publications, but to identify the major conceptual and practice shifts most likely to influence adult emergency and critical care medicine. We focus on supportive care, systems redesign, personalized supportive therapy, precision phenotyping, and pragmatic implementation, with emphasis on patient-important outcomes, feasibility, and implications for bedside decision-making and future research. Key randomized trials and major guideline updates discussed in this review are summarized in Table 1. An overview of the major domains and cross-cutting themes discussed in this review is shown in Figure 1. We present this article in accordance with the Narrative Review reporting checklist (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2026-1-0004/rc).

Figure 1 Key advances in emergency and critical care medicine in 2025. AI, confidence interval; ARDS, acute respiratory distress syndrome; ECPR, extracorporeal cardiopulmonary resuscitation; EHR, electronic health record; ICU, intensive care unit.

Methods

This article is a structured, narrative review of recent advances most relevant to adult emergency and critical care practice. Rather than aiming to provide a full-year summary of 2024, we focused on literature published from November 2024 through December 15, 2025, because late-2024 publications provided the immediate evidentiary context for several major developments that became more visible, clinically influential, or operationalized in 2025. We searched PubMed, Embase, and the Cochrane Library, supplemented by targeted screening of major professional society and guideline websites, to identify randomized clinical trials, high-quality observational studies, consensus statements, and practice guidelines relevant to sepsis, ARDS, resuscitation and extracorporeal life support, trauma, precision phenotyping, and clinical AI in emergency and critical care medicine. The search was restricted to English-language publications involving adult populations, with selective inclusion of foundational studies from 2015 onward when they established current standards of supportive care.

We prioritized studies most likely to inform current practice, including major randomized trials, influential implementation studies, updated definitions or scoring systems, and guideline documents from internationally recognized professional societies. Additional relevant articles were identified through manual review of reference lists when they provided important clinical or conceptual context. Literature selection was targeted and interpretive rather than fully systematic; no formal meta-analysis was performed, and the review was not prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO). Accordingly, this review should be interpreted as a clinically oriented synthesis of recent, practice-relevant evidence rather than as a formal systematic review. A summary of the search strategy is provided in Table 2.

Sepsis and septic shock

From early resuscitation to the sepsis chain of survival: a continuum-of-care framework

Evidence in 2025 reframed sepsis care from an early resuscitation event to a continuum-of-care pathway, described as the “Sepsis Chain of Survival” (20). The conceptual framework of this care continuum is illustrated in Figure 2. Hidalgo and colleagues proposed that sepsis management should extend from prevention and risk reduction through prehospital recognition and transport, ED and ICU resuscitation, ongoing organ support, and post-acute recovery, with each link supported by defined processes and measurable quality indicators (20). The framework places greater emphasis on prevention in high-risk populations, including vaccination strategies and infection prevention programs intended to reduce incident sepsis (21). It also prioritizes earlier recognition in prehospital and ED settings through standardized screening and emergency medical services (EMS) alert pathways aimed at reducing delays to treatment. In the acute phase, it frames ED-ICU care as a coordinated workflow anchored to the time of sepsis recognition, integrating timely antimicrobials, fluid resuscitation, hemodynamic assessment, vasoactive support, and organ support rather than treating them as isolated tasks. Finally, it extends accountability beyond discharge; for example, the 2025 German S3 sepsis guideline update highlights health-related quality of life, cognitive impairment, and psychological sequelae as follow-up targets and recommends structured post-ICU follow-up, including multidisciplinary rehabilitation and dedicated post–intensive care clinics. Overall, this shift expands quality improvement targets beyond early antibiotics and fluids to include prevention, prehospital coordination, and post-sepsis outcomes. Unlike traditional bundle-based approaches centered on early resuscitation, the “Sepsis Chain of Survival” conceptualizes sepsis care as a continuous and accountable system extending across prevention, prehospital recognition, emergency and ICU care, and post-acute recovery.

Figure 2 Sepsis chain of survival. The figure illustrates a continuum of sepsis care from awareness and prevention, early recognition and call for help, continuous source control, appropriate fluids, oxygen, and antibiotics, critical care without walls, to post-sepsis care and return to community.

Timing of antimicrobial initiation: from a universal 1-hour target to risk-stratified windows

In 2025, antimicrobial timing in suspected sepsis continued to shift from a universal 1-hour mandate toward risk-stratified initiation with explicit reassessment. The 2021 Surviving Sepsis Campaign guideline recommends antibiotics as soon as possible (ideally within 1 hour) for adults with possible septic shock or a high likelihood of sepsis, while allowing up to 3 hours for rapid evaluation and treatment initiation when sepsis is suspected without shock (22). Subsequent guidance, including the 2024 Korean Society of Critical Care Medicine guideline and a 2025 evidence synthesis, aligns with this approach: the most time-dependent benefit appears concentrated in septic shock, whereas in hemodynamically stable patients the priority is avoiding delays beyond 3 hours rather than enforcing a universal 1-hour deadline (23,24). In parallel, 2025 trials shifted emphasis from initiation alone to stewardship after initiation. In ADAPT-Sepsis, daily procalcitonin–guided decisions reduced antibiotic exposure without an observed increase in mortality (25). In INHALE WP3, rapid ICU-based syndromic polymerase chain reaction (PCR) improved appropriate and proportionate prescribing at 24 hours (absolute difference, 21%) but did not demonstrate noninferiority for 14-day clinical cure (26). Although BALANCE enrolled patients with bloodstream infection rather than sepsis per se, its findings support shorter-course antibiotic strategies in selected critically ill populations with favorable clinical response and controlled sources, but do not directly establish practice for all sepsis syndromes. Consistent with a “start promptly, then reassess” strategy, the BALANCE noninferiority trial in bloodstream infection (n=3,608; 55% ICU) found 7 days of antibiotics noninferior to 14 days for 90-day mortality (14.5% vs. 16.1%) (27). Taken together, the 2025 evidence supports treating septic shock as time-critical while preserving a short diagnostic window for stable presentations and prioritizing early reassessment, de-escalation, and shorter evidence-based courses once infection probability and clinical trajectory are clarified.

Fluid resuscitation and de-resuscitation: from fixed doses to individualized targets

Guideline updates and randomized trials in 2025 further moved sepsis fluid management away from fixed-volume dosing toward phase-based strategies that emphasize repeated reassessment and earlier de-resuscitation when appropriate. The 2025 European Society of Intensive Care Medicine (ESICM) guideline suggests administering up to 30 mL/kg of intravenous crystalloids during initial resuscitation for sepsis or septic shock, with dosing tailored to clinical context and repeated reassessment, and it does not endorse a uniform restrictive or liberal strategy during the optimization phase (28). Beyond volume, the clinical impact of crystalloid choice at the system level may be modest: in a pragmatic, hospital-wide, cluster-randomized crossover trial, a policy favoring lactated Ringer’s solution rather than normal saline did not significantly reduce the incidence of death or hospital readmission within 90 days (29). Randomized trials targeting perfusion and hemodynamics have yielded mixed results. In ANDROMEDA-SHOCK-2, a personalized hemodynamic protocol centered on capillary refill time normalization improved a hierarchical composite outcome that incorporated mortality, duration of life support, and length of stay {win ratio, 1.16 [95% confidence interval (CI): 1.02–1.33]}; the signal was driven primarily by shorter duration of life support, without a clear reduction in 28-day mortality (30). By contrast, in TARTARE-2S, a tissue perfusion–targeted protocol incorporating capillary refill time, peripheral temperature, lactate, and a lower mean arterial pressure (MAP) target (50–65 mmHg) did not improve the primary outcome of days alive with lactate normalization and freedom from vasoactive support at 30 days, and no new safety concerns emerged (31). After initial resuscitation, the REDUCE feasibility trial tested early de-resuscitation aimed at near-zero fluid balance within 3 days using fluid restriction with diuretics or mechanical removal when needed; the intervention achieved a lower cumulative fluid balance by day 3 (−2,353 vs. 793 mL; P<0.001) and shorter ICU and hospital stays (7 vs. 10 days; 16 vs. 22 days), whereas mortality effects remained exploratory and require confirmation in larger trials (32). In sum, these results support reassessment-driven fluids and selective targets, while highlighting that physiologic personalization has not reliably reduced mortality and that early de-resuscitation remains promising but unconfirmed for patient-important outcomes.

Precision use of corticosteroids in sepsis: from average effects to phenotype-stratified treatment

Recent analyses published in 2025 emphasized treatment-effect heterogeneity for corticosteroids in infection-associated sepsis and septic shock, shifting the focus from average effects to identifying subgroups more likely to benefit or be harmed. In a transcriptomic secondary analysis of the ADRENAL trial (n=540), patients were classified using a prespecified gene-expression signature into immune adaptive-prevalent (IA-P) (267/540) and immune innate-prevalent (IN-P) (273/540) endotypes; hydrocortisone was not associated with lower 28-day mortality in either group, and no clear endotype-by-treatment interaction was observed overall (33). In a pulmonary sepsis subgroup (232/540), however, IA-P patients who received hydrocortisone had higher 28-day mortality {odds ratio (OR), 5.55 [95% credible interval (CrI): 1.81–21.2]}, suggesting that infection source and immune state may jointly modify risk (34). A post hoc analysis of HYPRESS (n=317) similarly did not support biomarker-guided steroid targeting: baseline bio-adrenomedullin (bio-ADM) was prognostic for progression to septic shock and for 90-day mortality, but hydrocortisone did not reduce shock or mortality and showed no meaningful interaction across bio-ADM strata (shock interaction P=0.58) (35). In parallel, a multicenter target-trial emulation using eICU and MIMIC data (propensity-matched n=13,704) found a modestly higher hazard of 28-day mortality associated with corticosteroid exposure overall [hazard ratio (HR), 1.10 (95% CI: 1.04–1.16)], with heterogeneous associations across predicted organ-dysfunction trajectory subtypes (34). Collectively, current evidence supports continued pragmatic use of corticosteroids for vasopressor-dependent septic shock while treating immune endotypes, biomarkers, and trajectory phenotypes as hypothesis-generating rather than decision-ready stratifiers; a priority is prospective, stratified randomized trials using patient-centered outcomes (e.g., 90-day mortality or persistent organ dysfunction) (36).

Modernizing sepsis-related organ dysfunction assessment with Sequential Organ Failure Assessment (SOFA) 2.0

In 2025, sepsis-related organ dysfunction assessment was updated with SOFA 2.0 to better align grading thresholds with contemporary ICU therapeutics and organ support. SOFA 2.0 (published online October 29, 2025) was developed through a consensus-led, data-validated process intended to update the original score for contemporary ICU practice (37,38). Investigators analyzed 10 international multicenter cohorts from 2014 to 2023 (1,319 ICUs across 9 countries; 3,339,470 adult ICU admissions; ICU mortality, 8.1%). Overall, SOFA 2.0 preserves the familiarity of the original framework while updating operational definitions for modern ICU care. Its key contribution lies less in substantially improved discrimination than in enhanced face validity and usability in contemporary ICU practice, with potential advantages for more consistent bedside application and cross-study comparability.

Sepsis immunomodulation: from nonstratified therapy to phenotype-guided trials

The 2025 immunomodulation literature continued to move from nonstratified immune enhancement toward phenotype-guided enrollment and targeted therapy. In ImmunoSep, patients were classified at enrollment using ferritin and monocyte human leukocyte antigen (HLA)-DR as either a macrophage activation syndrome-like phenotype (MALS-like) or sepsis-induced immunoparalysis and were assigned to anakinra or recombinant interferon-γ, respectively; the stratified approach improved organ dysfunction by day 9 (35.1% vs. 17.9% with placebo), although 28-day mortality did not show a clear difference (39). In contrast, the phase 3 TESTS trial (n=1,106) evaluated thymosin α1 without phenotype-based selection and did not reduce 28-day mortality (23.4% vs. 24.1%; OR, 0.96) (40). Similarly, biomarker-enriched targeting has not consistently translated into better outcomes: in AdrenOSS-2, adrecizumab was well tolerated in septic shock but did not improve clinical outcomes or 90-day mortality (41). The dissociation between improvement in organ dysfunction and the absence of a clear mortality signal in ImmunoSep highlights the challenge of selecting appropriate endpoints in precision trials, particularly when biological enrichment and treatment-response heterogeneity may affect intermediate and definitive outcomes differently. Taken together, immunomodulation is increasingly being tested as a precision strategy, but phenotype definitions and outcome selection remain the rate-limiting steps for demonstrating durable, patient-important benefit.

For reference, ongoing and planned randomized clinical trials in sepsis and septic shock with key milestones expected in 2026 are summarized in Table 3.

What this means for clinicians

In sepsis, bedside decisions should move beyond uniform protocol compliance toward reassessment-driven care that accounts for shock status, physiologic trajectory, and evolving treatment response. Clinicians should treat septic shock as time-critical while integrating prehospital recognition, ED decision-making, and post-sepsis follow-up into a continuous care pathway.

ARDS

Global ARDS: implementation and evolving evidence in emergency and resource-limited settings

In 2025, adoption of the Global ARDS definition increasingly shifted ARDS identification upstream—toward earlier recognition outside the ICU, including EDs and general wards. Building on the Berlin framework, the consensus accepts high-flow nasal cannula (HFNC; ≥30 L/min) as qualifying support, allows an peripheral oxygen saturation (SpO₂)/fraction of inspired oxygen (FiO₂) ratio ≤315 (when SpO₂ ≤97%) as an alternative to arterial blood gases, and recognizes lung ultrasound as an imaging option; importantly for resource-limited settings, it avoids requiring specific devices, oxygen-flow thresholds, or positive end-expiratory pressure (PEEP) levels, thereby improving feasibility for non-intubated hypoxemic respiratory failure (42). This “front-loaded” approach aligns with trials of ward-deliverable noninvasive support: in NAVIGATE, scheduled early noninvasive ventilation (NIV) (2-hour cycles every 8 hours) reduced progression to severe acute respiratory failure compared with usual care [18.5% vs. 28.3%; relative risk (RR), 0.65 (95% CI: 0.48–0.90)] (43). Low-cost adjuncts such as awake prone positioning remain appealing but have not consistently produced definitive outcome benefits when used alone; in PROVID [coronavirus disease 2019 (COVID-19)-related hypoxemic respiratory failure; n=445], the posterior probability favored benefit for the composite of intubation and/or death by 28 days, but the CrI crossed the null [mean OR, 0.74 (95% CrI: 0.48–1.09)] (44). Definitive effectiveness trials in resource-constrained environments are now positioned to clarify net benefit across strategies: ARISE-AFRICA (Uganda) is a stepped-wedge trial comparing continuous positive airway pressure (CPAP), HFNC, and standard oxygen with 28-day mortality as the primary outcome (enrollment reported as complete), and the BREATHE implementation-effectiveness trial (Kenya, Malawi, Rwanda) is evaluating high-flow vs. standard-flow oxygen and remains ongoing (45-47). Overall, 2025 evidence supports earlier, pragmatic ARDS identification beyond the ICU while shifting the research agenda toward scalable noninvasive bundles and context-specific trials that reflect constraints in oxygen supply, staffing, and escalation capacity.

2025 ARDS ventilation and liberation trials: from physiologic optimization to patient-important outcomes

Randomized trials published in 2025 increasingly tested whether more individualized ventilation and liberation strategies improve patient-important outcomes rather than physiologic targets alone. In STAMINA, a driving pressure-limiting strategy that titrated PEEP to best respiratory-system compliance and adjusted tidal volume did not increase ventilator-free days at 28 days compared with a conventional low-PEEP strategy [mean, 6 vs. 7 days; proportional OR, 0.72 (95% CI: 0.39–1.32)] (48). Similarly, physiologic “tools” improved intermediate measures without definitive clinical benefit: in a randomized trial of electrical impedance tomography (EIT)-guided PEEP (n=108), EIT titration improved day-1 oxygenation [arterial oxygen partial pressure (PaO₂)/FiO₂, 180 vs. 159 mmHg] and mechanics and was associated with greater early improvement in organ dysfunction, but the lower 28-day mortality (29% vs. 44%) was not statistically significant (49). Liberation outcomes were also shaped by nonventilatory choices; in SESAR, inhaled sevoflurane sedation (vs. propofol) was associated with fewer ventilator-free days and lower 90-day survival [HR, 1.31 (95% CI: 1.05–1.62)] (50). Pragmatic trials further questioned routine escalation of oxygen and postextubation support: in UK-ROX (97 ICUs; 16,500 randomized), a conservative oxygen strategy reduced oxygen exposure by 29% but did not lower 90-day mortality [35.4% vs. 34.9%; adjusted risk difference, 0.7 percentage points (95% CI: −0.7 to 2.0)] (51), and after extubation, HFNC at 60 vs. 40 L/min did not reduce reintubation or NIV within 48 hours [16.9% vs. 22.1%; risk difference, 5.2% (95% CI: −6.7% to 17.1%)] (52). Taken together, 2025 trials suggest that imaging-guided and physiologic optimization strategies do not currently warrant routine adoption as outcome-improving defaults, but remain promising candidates for phenotype-stratified or context-specific trials that prespecify responsive subgroups (e.g., recruitability or physiologic responsiveness) and prioritize end points such as mortality, liberation success, and longer-term function.

Corticosteroids for adult ARDS: from routine use to dose- and phenotype-targeted therapy

Guideline updates and trial evidence in 2025 shifted attention in adult ARDS from routine corticosteroid use toward regimen selection—agent, dose, duration, and patient selection. A 2025 JAMA Clinical Guidelines Synopsis, informed by the Society of Critical Care Medicine’s 2024 focused update, issued a conditional recommendation (moderate certainty of evidence) to use systemic corticosteroids in critically ill adults with ARDS, while noting insufficient evidence to specify the optimal agent, dose, or duration (53,54). Consistent with this uncertainty, the RECOVERY platform trial compared higher-dose dexamethasone (20 mg daily for 5 days, then 10 mg daily for 5 days) with usual care (most commonly dexamethasone 6 mg daily) in hospitalized patients with COVID-19 requiring ventilatory support and did not reduce 28-day mortality [n=477; 35% vs. 37%; rate ratio, 0.87 (95% CI: 0.64–1.33); P=0.37] (55). These findings caution against empiric dose escalation beyond established low-dose regimens as a default strategy and reinforce the need to weigh potential complications, including secondary infection, hyperglycemia, and ICU-acquired weakness or myopathy. In sum, 2025 evidence supports systemic corticosteroids as a guideline-concordant option for moderate to severe ARDS but does not justify higher-dose regimens as routine escalation; priority research gaps include non-COVID-19 trials that prespecify agent-dose-duration and test phenotype- or biomarker-guided targeting using patient-important outcomes (e.g., mortality, liberation success, and long-term functional recovery).

Randomized evidence for novel ARDS imaging and physiologic monitoring tools and the shift toward precision stratification

Randomized trials in 2025 of novel ARDS imaging and physiologic monitoring tools reinforced a recurring theme: bedside visualization and transpulmonary pressure-guided approaches can improve physiologic measures, but evidence for patient-important benefit remains insufficient. In a randomized trial of EIT-guided PEEP (n=108), EIT-based decremental titration improved oxygenation on days 1–2 (day-1 PaO₂/FiO₂, 180 vs. 159 mmHg), increased respiratory-system compliance, reduced driving pressure, and was associated with greater early improvement in organ dysfunction, yet the reduction in 28-day mortality was not statistically significant (29% vs. 44%; P=0.09) (51). A single-center randomized trial comparing airway pressure release ventilation (APRV) with low-tidal volume ventilation (n=40) used EIT to assess regional ventilation and perfusion and found improved dorsal ventilation, enhanced ventilation-perfusion matching, and higher oxygenation with APRV, but it was designed around short-term physiologic end points rather than clinical outcomes (56). Implementation heterogeneity also limited generalizability: in a randomized crossover study (n=20), different esophageal pressure-based calculation algorithms produced clinically meaningful differences in recommended PEEP (≥3 cmH₂O in 70% of patients) with weak agreement between methods, and short-term oxygenation and hemodynamic end points did not consistently favor either approach (57). Collectively, these data support these tools as physiologic adjuncts but not as outcome-improving defaults; priority next steps include multicenter trials that standardize measurement and algorithms, prespecify phenotype-based stratification (e.g., recruitability and chest wall load), formally test treatment interaction, and are powered for patient-important outcomes (mortality, liberation success, and long-term functional recovery).

What this means for clinicians

In ARDS, physiologic optimization alone should not be assumed to improve patient-important outcomes. Clinicians should prioritize evidence-based supportive care, avoid routine escalation without clear indication, and interpret imaging-, ventilation-, or phenotype-guided strategies as selective rather than default approaches.

Resuscitation and extracorporeal life support

2025 advances in cardiopulmonary resuscitation (CPR)

In 2025, advances in CPR emphasized a system-based Chain of Survival—extending from prevention and preparedness to early recognition, resuscitation, post-cardiac arrest care, and recovery across in-hospital and out-of-hospital settings. The 2025 American Heart Association (AHA) Guidelines for CPR and Emergency Cardiovascular Care (ECC) represent the first comprehensive revision since 2020 and are explicitly organized around this unified chain for adults and children (58). For lay rescuers and dispatch-supported prehospital care, the most operational updates prioritize actions that can be executed immediately: for severe foreign-body airway obstruction in adults, the guideline recommends repeating cycles of 5 back blows followed by 5 abdominal thrusts until the obstruction is relieved or the patient becomes unresponsive, and it incorporates this sequence into the adult basic life support algorithm. In parallel, suspected opioid overdose is addressed as a system strategy by integrating a structured response algorithm and expanding public-access naloxone, with attention to policy enablement and Good Samaritan protections to reduce delays in reversal before respiratory arrest progresses to cardiac arrest (59,60). Pragmatic prehospital randomized trials published in 2025 highlight the distinction between process gains and patient outcomes: in IVIO (1,506 randomized; 1,479 analyzed), an intraosseous-first strategy increased successful access within 2 attempts (92% vs. 80%) but did not improve sustained return of spontaneous circulation (ROSC) [30% vs. 29%; RR, 1.06 (95% CI: 0.90–1.24)] or 30-day survival [12% vs. 10%; RR, 1.16 (95% CI: 0.87–1.56)] (61), and PARAMEDIC-3 (6,082 randomized) found no improvement in 30-day survival [4.5% vs. 5.1%; adjusted OR (aOR), 0.94 (95% CI: 0.68–1.32)] with slightly lower ROSC at any time [36.0% vs. 39.1%; aOR, 0.86 (95% CI: 0.76–0.97)] (62). Taken together, 2025 evidence suggests that while faster vascular access improves operational performance, gains in survival are more likely to depend on coordinated chain-wide delivery—early recognition, bystander action, timely defibrillation, high-quality CPR, and integrated post–cardiac arrest care—rather than routine escalation of a single technical approach.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO)/extracorporeal cardiopulmonary resuscitation (ECPR) in 2025: from feasibility to selection and systems of care

Randomized trials published in 2025 reinforced that the central challenge for VA-ECMO and ECPR is less technical feasibility than patient selection and reproducible systems of care. In LEVOECMO (11 ICUs in France; n=205), early levosimendan did not shorten time to successful VA-ECMO weaning within 30 days or increase weaning success [68.3% vs. 68.3%; subdistribution HR, 1.02 (95% CI: 0.74–1.39); P=0.92], and 60-day mortality was similar, while ventricular arrhythmias were more frequent with levosimendan (17.8% vs. 8.7%) (63). In EVIDENCE (n=197), an accelerated pathway prioritizing transport under mechanical CPR with immediate catheterization-laboratory evaluation for coronary intervention and/or ECPR did not improve survival with favorable neurologic status at hospital discharge [cerebral performance category (CPC) 1–2] [15% vs. 16%; risk difference, −1.1% (95% CI: −12.2% to 10.0%); adjusted RR, 0.95 (95% CI: 0.50–1.80)] (64). In cardiogenic shock supported with VA-ECMO, 1-year follow-up of EARLY-UNLOAD showed no benefit of routine early left ventricular unloading [all-cause mortality, 56.9% vs. 57.1%; HR, 0.97 (95% CI: 0.60–1.58)] (65). Overall, these trials do not support default escalation to more intensive pharmacologic augmentation, accelerated ECPR pathways, or routine early unloading; instead, resource-intensive strategies should be targeted to prespecified eligibility criteria (e.g., reversible etiology, low-flow duration, and cardiopulmonary phenotype) and delivered within standardized, measurable workflows, with pragmatic trials needed to define net benefit using patient-centered outcomes (survival with favorable neurologic function, long-term recovery, and meaningful weaning and rehabilitation end points).

What this means for clinicians

In resuscitation and extracorporeal support, speed and technical capability remain important, but implementation should be guided by patient selection, system readiness, and downstream functional outcomes rather than procedural intensity alone. Clinicians should view ECPR and related pathways as system-level interventions requiring coordinated protocols, training, and outcome surveillance.

Trauma

Factor concentrates vs. plasma for early hemostatic resuscitation in severe trauma

Randomized evidence published in 2025 in severe traumatic hemorrhage tested whether early hemostatic resuscitation can be improved by substituting factor concentrates for plasma within contemporary massive hemorrhage protocols. In FiiRST-2, adults (≥16 years) with severe trauma who triggered a massive hemorrhage protocol on arrival at 6 Canadian level I trauma centers were randomized to receive fibrinogen concentrate (4 g) plus prothrombin complex concentrate (PCC; 2,000 IU) within the first 2 protocol packs or 4 units of fresh frozen plasma, with subsequent component-based resuscitation delivered per protocol (66). Among 217 randomized patients (107 vs. 110), 137 were included in the primary analysis (66 vs. 71). Total allogeneic blood product use within 24 hours was similar between groups [20.8 units (95% CI: 16.7–25.9) vs. 23.8 units (95% CI: 19.2–29.4)], and thromboembolic events and 24-hour and 28-day mortality did not differ; the trial stopped early after interim analysis suggested low conditional power. Overall, these findings do not support routine empiric substitution of fibrinogen concentrate plus PCC for plasma on top of component-based resuscitation and instead support future trials that target therapy to measurable coagulopathy phenotypes using bedside thresholds (e.g., viscoelastic testing) with prespecified interaction analyses.

Trauma pain management in 2025

Randomized evidence in 2025 suggests that simply “adding a stronger analgesic or sedative” is not equivalent to delivering high-quality multimodal analgesia in critically injured patients. In the prehospital PACKMaN double-blind trial (n=449), titrated ketamine vs. morphine for severe acute traumatic pain did not improve the primary outcome (prearrival pain difference score), with an adjusted between-group difference near zero (67). In ICU patients with rib fractures, a small double-blind randomized trial published in JAMA Surgery (n=41) found that adding dexmedetomidine to an existing multimodal regimen did not improve 48-hour pain control or reduce opioid use, and treatment discontinuations were common (68). Emerging data also support early regional anesthesia, including fascial plane blocks, in patients with rib fractures, although large pragmatic comparative trials remain limited. These findings shift the emphasis from medication escalation to execution: standardized pathways that begin with structured pain assessment and repeated reassessment, prioritize nonopioid and regional techniques, and use the minimum effective opioid strategy while aligning analgesia goals with respiratory support, delirium prevention, and liberation plans. Taken together, 2025 trials do not support routine “add-on” escalation of single agents as a default approach and instead support protocolized, injury- and risk-stratified multimodal analgesia strategies evaluated using patient-centered outcomes (e.g., pulmonary complications, duration of ventilation, delirium, long-term function, and persistent opioid use) (67,68).

What this means for clinicians

In trauma, better outcomes depend not only on faster interventions but also on structured systems of triage, analgesia, imaging, and definitive care. Clinicians should favor protocolized, injury-stratified management and use multimodal pain strategies that align analgesia goals with respiratory support, delirium prevention, and recovery.

Precision multi-omics phenotyping

Multi-omics studies in 2025 increasingly moved beyond subtype description by tying molecular strata to candidate treatment strategies. The CMAISE consortium assembled a prospective longitudinal cohort across 43 hospitals (1,327 ICU patients; sampling on ICU days 1, 3, and 5) integrating high-granularity clinical phenotyping with transcriptomic (n=2,776), proteomic (n=468), and metabolomic (n=457) profiles, and proposed a goal-directed subgroup identification framework designed to maximize differential treatment effects (e.g., restrictive vs. more liberal fluid strategies; ulinastatin exposure), yielding cross-omics-concordant subgroups (Light’s κ≈0.63) and simplified classifiers evaluated in external ICU datasets (MIMIC-IV, eICU-CRD, AmsterdamUMCdb) (17). A related 2024 septic shock analysis applied a similar treatment-linked approach, deriving a transcriptome-informed fluid benefit score associated with improved survival when management was concordant (HR, 0.82) and distilling the signal into a 6-protein panel (area under the curve, 0.802), supporting a potential path toward deployable testing (19). In parallel, standardization efforts advanced: Scicluna and colleagues harmonized ICU admission-day transcriptomes from MARS and GAinS (n=1,122) into 3 consensus subtypes supported by an 18-gene classifier (out-of-bag error, 2.2%) (69), and the SUBSPACE consortium compared endotyping frameworks across 37 cohorts (>7,074 samples) to derive cell-type-specific signatures quantifying myeloid and lymphoid dysregulation, enabling prespecified tests of treatment interaction (70); in ARDS, time-aware integration of ROSE metabolomic and transcriptomic data using MEFISTO identified mortality-associated molecular signatures persisting from day 0 to day 2 and replicating externally (71). In sum, the 2025 trajectory suggests that the most clinically useful multi-omics work will pair parsimonious assays with prospectively testable, treatment-linked hypotheses (including formal interaction testing) and incorporate time-aware modeling to connect biological mechanisms to patient-important outcomes.

What this means for clinicians

Multi-omics phenotyping is beginning to clarify clinically meaningful heterogeneity in sepsis and other critical illnesses, but most approaches are not yet ready for routine bedside decision-making. For now, clinicians should view these tools primarily as a framework for trial enrichment and future treatment stratification rather than as stand-alone guides for current care.

Clinical AI

Across 2025, clinical AI in emergency and critical care moved from retrospective model development toward implementation, governance, and measurable clinical impact. A systematic review of 1,263 ICU AI studies found that 74% remained in early development and only 25 (2%) reached clinical integration; reporting was frequently incomplete and more than half of studies were rated at high risk of bias, underscoring the persistent gap between retrospective modeling and implementable, outcome-focused evidence (72). A 2025 consensus statement in Critical Care similarly treated AI as a high-risk intervention and emphasized governance requirements for patient safety, transparency, and interdisciplinary oversight (73). Against this backdrop, three strands of evidence pointed toward more clinically relevant directions. Large-scale electronic health record (EHR) foundation models (e.g., ETHOS, pretrained on 285,622 patient trajectories) were developed for multitask prediction, supporting a shift from single-purpose tools to more transferable clinical representations (74). In parallel, dynamic decision models began to face broader external validation: in septic shock, a vasopressin-timing model validated across 227 hospitals showed lower in-hospital mortality with concordant treatment [aOR, 0.81 (95% CI: 0.68–0.97)] and higher mortality with discordant treatment [OR, 1.20 (95% CI: 1.04–1.39)], strengthening the case for prospective testing of policy recommendations (75). Pragmatic trials of electronic screening also yielded outcome signals, although not without trade-offs. In the stepped-wedge SCREEN trial (5 hospitals; 45 wards; n=60,055), quick Sequential Organ Failure Assessment (qSOFA) based electronic screening increased lactate testing within 12 hours [adjusted RR, 1.30 (95% CI: 1.16–1.45)] and orders for intravenous fluids [adjusted RR, 2.17 (95% CI: 1.92–2.46)] and was associated with lower 90-day in-hospital mortality [adjusted RR, 0.85 (95% CI: 0.77–0.93); P<0.001], while higher rates of code blue events, renal replacement therapy, and Clostridioides difficile events were also observed during implementation. These findings should be interpreted as associations observed within the study context rather than as direct evidence that the early detection intervention itself caused these events, but they underscore the need for careful calibration and safety surveillance when earlier detection tools are embedded into clinical workflows (76). Collectively, these developments suggest a transition from benchmarking model accuracy to building transferable representations, testing decision policies, and evaluating real-world deployment with explicit safety monitoring. The next evidence step is larger pragmatic randomized trials with prespecified calibration and fairness assessments across sites, coupled with routine postdeployment monitoring (“algorithmovigilance”) integrated into hospital quality and safety programs and supported by dedicated informatics oversight, standardized reporting pathways, and institutional resources for ongoing surveillance.

What this means for clinicians

Clinical AI should be judged not only by model performance but also by how safely and reliably it functions in real-world care. Clinicians and health systems should treat deployment as an ongoing clinical implementation process requiring calibration checks, governance, and postdeployment monitoring rather than as a one-time technical success.

Strengths and limitations of this review

This review has several strengths. It synthesizes recent clinically relevant advances across emergency and critical care medicine within a single framework, with emphasis on supportive care, systems redesign, personalized supportive care, precision phenotyping, and pragmatic implementation. It also prioritizes randomized trials, major observational studies, consensus statements, and guideline documents most likely to influence current practice.

This review also has limitations. It was designed as a structured, narrative review with targeted literature selection rather than a formal systematic review. Accordingly, no protocol was prospectively registered, no dual-reviewer screening was performed, no formal risk-of-bias assessment was undertaken, and no meta-analysis was conducted. The search was restricted to English-language publications and focused on studies judged most relevant to adult emergency and critical care practice, which may have introduced selection bias and limited comprehensiveness. In addition, some findings discussed in this review were derived from specific health systems, trial settings, or highly selected patient populations, which may limit generalizability across settings and regions.

Conclusions

Much of the progress in emergency and critical care has come from standardizing what can be standardized. The 2025 evidence, however, underscores a familiar problem: improvements in intermediate physiology do not consistently become durable, patient-important benefit, and effects differ by patient and by phase of illness. What is needed now are phase-based strategies that update goals as shock evolves, rather than fixed volumes or single cutoffs, with prespecified, clinically credible subgroups (for example, cardiac dysfunction, persistent hyperlactatemia, or early congestion). Fluid and vasopressor trials will be more informative if they define exposure by dose, timing, and trajectory; measure harm as carefully as benefit; and emphasize recovery outcomes such as organ support–free days, functional status, and discharge disposition. In ARDS, ventilation and liberation studies should connect changes in mechanics to longer-term cognition and quality of life. Study designs should extend beyond hospital discharge, with 90-day and 1-year follow-up. Systems interventions—ECPR pathways, trauma networks, and care beyond the ICU—are better tested with cluster or stepped-wedge designs that also address equity and cost. Finally, if clinical AI and Tele-ICU are to influence outcomes, they need prospective evaluations with external validation and ongoing monitoring, reporting calibration, drift, workflow effects, and safety alongside governance.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2026-1-0004/rc

Peer Review File: Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2026-1-0004/prf

Funding: This study was supported by the Prevention and control of Emerging and Major Infectious Diseases-National Science and Technology Major Project (No. 2025ZD01902500, No. 2025ZD01902501), the China National Key Research and Development Program (No. 2023YFC3603104), the National Natural Science Foundation of China (No. 82472243 and 82272180), the Fundamental Research Funds for the Central Universities (No. 226-2025-00024), the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China (No. LHDMD24H150001), the Key Research & Development Project of Zhejiang Province (No. 2024C03240), a collaborative scientific project co-established by the Science and Technology Department of the National Administration of Traditional Chinese Medicine and the Zhejiang Provincial Administration of Traditional Chinese Medicine (No. GZY-ZJ-KJ-24082), the General Health Science and Technology Program of Zhejiang Province (No. 2024KY1099), the Project of Zhejiang University Longquan Innovation Center (No. ZJDXLQCXZCJBGS2024016), Beijing Natural Science Foundation (No. 7252298), Wu Jieping Medical Foundation Special Research Grant (No. 320.6750.2024-23-07), and Zhejiang Provincial Science and Technology Program for Disease Control and Prevention (No. 2026JKZ042).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-2026-1-0004/coif). Y.Y. serves as an Editor-in-Chief of Journal of Emergency and Critical Care Medicine from September 2024 to August 2026. Z.Z. serves as an unpaid Executive Editor of Journal of Emergency and Critical Care Medicine from March 2023 to December 2026. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Wimmer S, Sarabu S, Calvello Hynes E, et al. Global burden of emergency and operative conditions: an analysis of Global Burden of Disease data, 2011-2019. Bull World Health Organ 2025;103:194-203. [Crossref] [PubMed]
2. Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet 2020;395:200-11. [Crossref] [PubMed]
3. Bellani G, Laffey JG, Pham T, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA 2016;315:788-800. [Crossref] [PubMed]
4. Shammassian BH, Wooster L, Wright JM, et al. Systematic review of trauma system regionalization and implementation on outcomes in traumatic brain injury patients. Neurol Res 2021;43:87-96. [Crossref] [PubMed]
5. Meyer NJ, Prescott HC. Sepsis and Septic Shock. N Engl J Med 2024;391:2133-46. [Crossref] [PubMed]
6. Luethi N, Niemi T, Endrich O, et al. Incidence, mortality, and economic burden of sepsis in Switzerland, 2019-2023: A nationwide population-based analysis. Int J Infect Dis 2026;163:108262. [Crossref] [PubMed]
7. Sud S, Friedrich JO, Adhikari NKJ, et al. Comparative Effectiveness of Protective Ventilation Strategies for Moderate and Severe Acute Respiratory Distress Syndrome. A Network Meta-Analysis. Am J Respir Crit Care Med 2021;203:1366-77.
8. Chiumello D, Carlesso E, Brioni M, et al. Airway driving pressure and lung stress in ARDS patients. Crit Care 2016;20:276. [Crossref] [PubMed]
9. Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA 2012;308:1651-9. [Crossref] [PubMed]
10. Cornejo RA, Díaz JC, Tobar EA, et al. Effects of prone positioning on lung protection in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2013;188:440-8. [Crossref] [PubMed]
11. Boesing C, Rocco PRM, Luecke T, et al. Positive end-expiratory pressure management in patients with severe ARDS: implications of prone positioning and extracorporeal membrane oxygenation. Crit Care 2024;28:277. [Crossref] [PubMed]
12. Boesing C, Graf PT, Schmitt F, et al. Effects of different positive end-expiratory pressure titration strategies during prone positioning in patients with acute respiratory distress syndrome: a prospective interventional study. Crit Care 2022;26:82. [Crossref] [PubMed]
13. Rezoagli E, Bastia L, Brochard L, et al. Physical manoeuvres in patients with ARDS and low compliance: bedside approaches to detect lung hyperinflation and optimise mechanical ventilation. Eur Respir J 2023;61:2202169. [Crossref] [PubMed]
14. Moore L, Evans D, Hameed SM, et al. Mortality in Canadian Trauma Systems: A Multicenter Cohort Study. Ann Surg 2017;265:212-7. [Crossref] [PubMed]
15. MacKenzie EJ, Rivara FP, Jurkovich GJ, et al. A national evaluation of the effect of trauma-center care on mortality. N Engl J Med 2006;354:366-78. [Crossref] [PubMed]
16. Ma W, Tang S, Yao P, et al. Advances in acute respiratory distress syndrome: focusing on heterogeneity, pathophysiology, and therapeutic strategies. Signal Transduct Target Ther 2025;10:75. [Crossref] [PubMed]
17. Zhang Z, Chen L, Shen H, et al. Deriving consensus sepsis clusters via goal-directed subgroup identification in multi-omics study. Nat Commun 2025;16:10328. [Crossref] [PubMed]
18. Zhang Z, Zhang G, Goyal H, et al. Identification of subclasses of sepsis that showed different clinical outcomes and responses to amount of fluid resuscitation: a latent profile analysis. Crit Care 2018;22:347. [Crossref] [PubMed]
19. Zhang Z, Chen L, Sun B, et al. Identifying septic shock subgroups to tailor fluid strategies through multi-omics integration. Nat Commun 2024;15:9028. [Crossref] [PubMed]
20. Hidalgo JL, Kumar VK, Akech SO, et al. The Sepsis Chain of Survival: A Comprehensive Framework for Improving Sepsis Outcomes. Crit Care Med 2025;53:e1886-92. [Crossref] [PubMed]
21. Deinhardt-Emmer S, Chousterman BG, Schefold JC, et al. Sepsis in patients who are immunocompromised: diagnostic challenges and future therapies. Lancet Respir Med 2025;13:623-37. [Crossref] [PubMed]
22. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021;47:1181-247. [Crossref] [PubMed]
23. Park C, Ku NS, Park DW, et al. Early management of adult sepsis and septic shock: Korean clinical practice guidelines. Acute Crit Care 2024;39:445-72. [Crossref] [PubMed]
24. Ku NS, Lee Y, Park DW. Appropriate timing of antibiotic initiation in patients with sepsis or septic shock: a systematic review and meta-analysis. Korean J Intern Med 2025;40:725-33. [Crossref] [PubMed]
25. Dark P, Hossain A, McAuley DF, et al. Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial. JAMA 2025;333:682-93. [Crossref] [PubMed]
26. Enne VI, Stirling S, Barber JA, et al. INHALE WP3, a multicentre, open-label, pragmatic randomised controlled trial assessing the impact of rapid, ICU-based, syndromic PCR, versus standard-of-care on antibiotic stewardship and clinical outcomes in hospital-acquired and ventilator-associated pneumonia. Intensive Care Med 2025;51:272-86. [Crossref] [PubMed]
27. BALANCE Investigators. Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections. N Engl J Med 2025;392:1065-78.
28. Mekontso Dessap A, AlShamsi F, Belletti A, et al. European Society of Intensive Care Medicine (ESICM) 2025 clinical practice guideline on fluid therapy in adult critically ill patients: part 2-the volume of resuscitation fluids. Intensive Care Med 2025;51:461-77. [Crossref] [PubMed]
29. McIntyre L, Fergusson D, McArdle T, et al. A Crossover Trial of Hospital-Wide Lactated Ringer’s Solution versus Normal Saline. N Engl J Med 2025;393:660-70. [Crossref] [PubMed]
30. ANDROMEDA-SHOCK-2 Investigators for the ANDROMEDA Research Network. Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial. JAMA 2025;334:1988-99.
31. Pettilä V, Pfortmüller CA, Perner A, et al. Targeted Tissue Perfusion Versus Macrocirculatory-Guided Standard Care in Patients With Septic Shock: A Randomized Clinical Trial-The TARTARE-2S Trial. Crit Care Med 2026;54:24-34. [Crossref] [PubMed]
32. Naorungroj T, Prajantasen U, Sanla-Ead T, et al. Restrictive fluid management with early de-escalation versus usual care in critically ill patients (reduce trial): a feasibility randomized controlled trial. Crit Care 2025;29:405. [Crossref] [PubMed]
33. Venkatesh B, Rey DA, Evans DM, et al. A gene expression-based approach for the precision use of hydrocortisone in septic shock patients; a secondary analysis of the ADRENAL trial. Crit Care Resusc 2025;27:100109. [Crossref] [PubMed]
34. Rajendran S, Xu Z, Pan W, et al. Multicenter target trial emulation to evaluate corticosteroids for sepsis stratified by predicted organ dysfunction trajectory. Nat Commun 2025;16:4450. [Crossref] [PubMed]
35. Neumann C, Leitner M, Bloos F, et al. Clinical value of circulating bioactive adrenomedullin for prediction of outcome and hydrocortisone response in sepsis patients-a post-hoc analysis of the HYPRESS trial. Infection 2025;53:2383-95. [Crossref] [PubMed]
36. Fleuriet J, Heming N, Meziani F, et al. Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis (RECORDS): study protocol for a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial. BMJ Open 2023;13:e066496. [Crossref] [PubMed]
37. Ranzani OT, Singer M, Salluh JIF, et al. Development and Validation of the Sequential Organ Failure Assessment (SOFA)-2 Score. JAMA 2025;334:2090-103. [Crossref] [PubMed]
38. Moreno R, Rhodes A, Ranzani O, et al. Rationale and Methodological Approach Underlying the Development of the Sequential Organ Failure Assessment (SOFA)-2 Score: A Consensus Statement. JAMA Netw Open 2025;8:e2545040. [Crossref] [PubMed]
39. Giamarellos-Bourboulis EJ, Kotsaki A, Kotsamidi I, et al. Precision Immunotherapy to Improve Sepsis Outcomes: The ImmunoSep Randomized Clinical Trial. JAMA 2026;335:775-86. [Crossref] [PubMed]
40. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ 2025;389:r1098.
41. Laterre PF, Pickkers P, Marx G, et al. Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial. Intensive Care Med 2021;47:1284-94. [Crossref] [PubMed]
42. RENOVATE Investigators and the BRICNet Authors. High-Flow Nasal Oxygen vs. Noninvasive Ventilation in Patients With Acute Respiratory Failure: The RENOVATE Randomized Clinical Trial. JAMA 2025;333:875-90.
43. Monti G, Cabrini L, Kotani Y, et al. Early noninvasive ventilation in general wards for acute respiratory failure: an international, multicentre, open-label, randomised trial. Br J Anaesth 2025;134:382-91. [Crossref] [PubMed]
44. Harrois A, Jouffroy R, Ayed S, et al. Awake Prone Positioning in Patients With COVID-19 Respiratory Failure: A Randomized Clinical Trial. JAMA Netw Open 2025;8:e2548201. [Crossref] [PubMed]
45. Twagirumugabe T, Gashame DF, Uwamahoro DL, et al. Advanced non-invasive respiratory support in resource-constrained settings: a narrative review. Crit Care 2025;29:492. [Crossref] [PubMed]
46. Kwizera A, Kabatoro D, Owachi D, et al. Respiratory support with standard low-flow oxygen therapy, high-flow oxygen therapy or continuous positive airway pressure in adults with acute hypoxaemic respiratory failure in a resource-limited setting: protocol for a randomised, open-label, clinical trial - the Acute Respiratory Intervention StudiEs in Africa (ARISE-AFRICA) study. BMJ Open 2024;14:e082223. [Crossref] [PubMed]
47. Calhoun T, Onofrey L, Limbani F, et al. Evaluating the process while testing the intervention: a process evaluation protocol for the breathe oxygen therapy randomized controlled trial in Kenya, Malawi, and Rwanda. Chest 2024;166:A1897-8.
48. Maia IS, Cavalcanti AB, Tramujas L, et al. Effect of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome secondary to community-acquired pneumonia: the STAMINA randomised clinical trial. Br J Anaesth 2025;134:693-702. [Crossref] [PubMed]
49. Van Trung D, Giang BTH, Tuan DQ, et al. The impact of PEEP-guided electrical impedance tomography on oxygenation and respiratory mechanics in moderate-to-severe ARDS: a randomized controlled trial. Sci Rep 2025;16:391. [Crossref] [PubMed]
50. Jabaudon M, Quenot JP, Badie J, et al. Inhaled Sedation in Acute Respiratory Distress Syndrome: The SESAR Randomized Clinical Trial. JAMA 2025;333:1608-17. [Crossref] [PubMed]
51. Martin DS, Gould DW, Shahid T, et al. Conservative Oxygen Therapy in Mechanically Ventilated Critically Ill Adult Patients: The UK-ROX Randomized Clinical Trial. JAMA 2025;334:398-408. [Crossref] [PubMed]
52. Ruan SY, Kuo YW, Huang CT, et al. Effect of Flow Rates of High-Flow Nasal Cannula on Extubation Outcomes: A Randomized Controlled Trial. Chest 2025;167:1388-96. [Crossref] [PubMed]
53. Leung PB, Davis AM, Davis J. Corticosteroids for Sepsis, Acute Respiratory Distress Syndrome, or Community-Acquired Pneumonia. JAMA 2025;333:421-2. [Crossref] [PubMed]
54. Chaudhuri D, Nei AM, Rochwerg B, et al. 2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia. Crit Care Med 2024;52:e219-33. [Crossref] [PubMed]
55. Higher dose corticosteroids in hospitalised COVID-19 patients requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial. EClinicalMedicine 2025;81:103080.
56. Zou X, Zhang H, Wu Y, et al. Physiologic Comparison of Airway Pressure Release Ventilation and Low Tidal Volume Ventilation in ARDS: A Randomized Controlled Trial. Chest 2025;167:453-65. [Crossref] [PubMed]
57. Chean D, Courtais A, Pavlovsky B, et al. Comparison of two transpulmonary pressure-based positive end-expiratory pressure titration strategies in acute respiratory distress syndrome: a randomized crossover study. Crit Care 2025;29:409. [Crossref] [PubMed]
58. Del Rios M, Bartos JA, Panchal AR, et al. Part 1: Executive Summary: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2025;152:S284-S312. [Crossref] [PubMed]
59. Dezfulian C, Cabañas JG, Buckley JR, et al. Part 4: Systems of Care: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2025;152:S353-84. [Crossref] [PubMed]
60. Kleinman ME, Buick JE, Huber N, et al. Part 7: Adult Basic Life Support: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2025;152:S448-78. [Crossref] [PubMed]
61. Vallentin MF, Granfeldt A, Klitgaard TL, et al. Intraosseous or Intravenous Vascular Access for Out-of-Hospital Cardiac Arrest. N Engl J Med 2025;392:349-60. [Crossref] [PubMed]
62. Couper K, Ji C, Deakin CD, et al. A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest. N Engl J Med 2025;392:336-48. [Crossref] [PubMed]
63. Combes A, Saura O, Nesseler N, et al. Levosimendan to Facilitate Weaning From ECMO in Patients With Severe Cardiogenic Shock: The LEVOECMO Randomized Clinical Trial. JAMA 2026;335:60-9. [Crossref] [PubMed]
64. Burns B, Marschner IC, Buscher H, et al. Expedited transfer from the scene for refractory out-of-hospital cardiac arrest in Australia: a prospective, multicentre, parallel, open label, randomised clinical trial. Lancet Respir Med 2025;13:921-32. [Crossref] [PubMed]
65. Lim Y, Kim MC, Lee SH, et al. Early left ventricular unloading after venoarterial extracorporeal membrane oxygenation: 1-year outcomes of the EARLY-UNLOAD randomized clinical trial. Eur Heart J Acute Cardiovasc Care 2025;14:203-11. [Crossref] [PubMed]
66. da Luz LT, Karkouti K, Carroll J, et al. Factors in the Initial Resuscitation of Patients With Severe Trauma: The FiiRST-2 Randomized Clinical Trial. JAMA Netw Open 2025;8:e2532702. [Crossref] [PubMed]
67. Smyth MA, Noordali H, Starr K, et al. Paramedic analgesia comparing ketamine and morphine in trauma (PACKMaN): a randomised, double-blind, phase 3 trial. Lancet Reg Health Eur 2025;53:101265. [Crossref] [PubMed]
68. Nahmias J, Stopenski S, Jebbia M, et al. Dexmedetomidine for Analgesia in Nonintubated Patients With Traumatic Rib Fractures: A Randomized Clinical Trial. JAMA Surg 2025;160:1047-56. [Crossref] [PubMed]
69. Scicluna BP, Cano-Gamez K, Burnham KL, et al. A consensus blood transcriptomic framework for sepsis. Nat Med 2025;31:4119-30. [Crossref] [PubMed]
70. Moore AR, Zheng H, Ganesan A, et al. A consensus immune dysregulation framework for sepsis and critical illnesses. Nat Med 2025;31:4084-96. [Crossref] [PubMed]
71. Alipanah-Lechner N, Neyton L, Sinha P, et al. Longitudinal multiomic signatures of ARDS and sepsis inflammatory phenotypes identify pathways associated with mortality. J Clin Invest 2025;136:e196290.
72. Berkhout WEM, van Wijngaarden JJ, Workum JD, et al. Operationalization of Artificial Intelligence Applications in the Intensive Care Unit: A Systematic Review. JAMA Netw Open 2025;8:e2522866. [Crossref] [PubMed]
73. Cecconi M, Greco M, Shickel B, et al. Implementing Artificial Intelligence in Critical Care Medicine: a consensus of 22. Crit Care 2025;29:290. [Crossref] [PubMed]
74. Renc P, Grzeszczyk MK, Oufattole N, et al. Foundation model of electronic medical records for adaptive risk estimation. Gigascience 2025;14:giaf107. [Crossref] [PubMed]
75. Kalimouttou A, Kennedy JN, Feng J, et al. Optimal Vasopressin Initiation in Septic Shock: The OVISS Reinforcement Learning Study. JAMA 2025;333:1688-98. [Crossref] [PubMed]
76. Arabi YM, Alsaawi A, Alzahrani M, et al. Electronic Sepsis Screening Among Patients Admitted to Hospital Wards: A Stepped-Wedge Cluster Randomized Trial. JAMA 2025;333:763-73. [Crossref] [PubMed]