Daily Respiratory Research Analysis
Analyzed 201 papers and selected 3 impactful papers.
Summary
A large multicenter randomized trial (PRONTO) found that adding rapid procalcitonin testing to NEWS2-based emergency department care for suspected sepsis reduced 28-day mortality without changing early antibiotic initiation. A target trial emulation across ICU cohorts supported administering antibiotics and fluids within 1 hour but found no survival benefit to very-early vasopressors. A systematic review/meta-analysis showed point-of-care ultrasound reliably aids diagnosis in acute dyspnea, though operator variability remains a key limitation.
Research Themes
- Sepsis management in acute and critical care
- Rapid diagnostics and decision support
- Point-of-care imaging in respiratory emergencies
Selected Articles
1. Procalcitonin testing combined with NEWS2 evaluation compared with usual care based on NEWS2 for identification of sepsis and antibiotic initiation in the emergency department in England and Wales (PRONTO): a multicentre, randomised, controlled, open-label, phase 3 trial.
In 5453 analyzed patients, procalcitonin-guided care did not change 3-hour IV antibiotic initiation versus usual care (~48% in both) but significantly reduced 28-day mortality (13.6% vs 16.6%; adjusted risk difference −3.12 percentage points), meeting both non-inferiority and superiority criteria. Adverse events were similar and clinicians considered the procalcitonin result in about two-thirds of cases.
Impact: This large, pragmatic phase 3 RCT provides robust evidence that adding rapid procalcitonin testing to NEWS2-driven ED care improves survival in suspected sepsis without increasing early antibiotic use.
Clinical Implications: Emergency departments should consider integrating rapid procalcitonin testing into sepsis pathways alongside NEWS2. Implementation should focus on workflow integration and clinician adherence to guidance while monitoring antibiotic stewardship and mortality outcomes.
Key Findings
- 3-hour IV antibiotic initiation was similar between groups (48.4% procalcitonin-guided vs 48.2% usual care).
- 28-day mortality was lower with procalcitonin-guided care (13.6% vs 16.6%; adjusted risk difference −3.12 percentage points, meeting non-inferiority and superiority).
- Adverse events were comparable, and the procalcitonin result was considered in 64.7% of guided-care decisions.
Methodological Strengths
- Large multicenter, individually randomized, phase 3 trial with prespecified co-primary endpoints
- Pragmatic design reflecting real-world ED workflows across 20 hospitals
Limitations
- Open-label design with potential performance bias and variable adherence to the guidance algorithm
- No reduction in early antibiotic initiation; mechanisms for mortality benefit require further study
Future Directions: Identify mechanisms underpinning mortality reduction, define subgroups that benefit most, and evaluate implementation strategies and cost-effectiveness across diverse ED settings.
BACKGROUND: Sepsis is a common and serious condition, defined as a dysregulated host response to infection, that leads to life-threatening organ dysfunction. In emergency department settings, accurate diagnosis can be challenging, as many non-infectious conditions have similar presenting features and there is no gold standard diagnostic test, which can lead to misdirected use of antibiotics. Procalcitonin is a well characterised biomarker that responds rapidly and with high specificity to the presence of bacterial infection. We aimed to investigate whether supplementing current practice with rapid procalcitonin testing would improve recognition of sepsis and allow reduced antibiotic prescribing with at least no change in overall mortality. METHODS: A parallel, two-arm, open-label, individually randomised controlled trial was done in 20 hospital emergency departments within 17 National Health Service (NHS) Trusts or Health Boards across England and Wales. Patients aged 16 years and older with suspected sepsis were randomly assigned to either usual care or procalcitonin-guided care in a 1:1 ratio via a centrally controlled web-based randomisation programme. Participants, research staff, those assessing outcomes, and statisticians analysing the data were not masked to group assignment. Participants in the usual care group were assessed according to standard clinical management based on National Early Warning Score 2 (NEWS2). In the procalcitonin-guided care group, rapid procalcitonin testing was used in combination with NEWS2 assessment by use of a guidance-only algorithm for clinicians. This algorithm for clinical management was used for both usual care and procalcitonin-guided care groups and clinicians were free to use, ignore, or deviate from the algorithm. The co-primary endpoints were intravenous antibiotic initiation at 3 h (superiority) and 28-day mortality (non-inferiority) from triage assessment, assessed in all randomly assigned consenting participants with data for both co-primary outcomes available.
2. Timing of Core Sepsis Bundle Elements Initiation in Critically Ill Patients: A Multicenter Target Trial Emulation Study.
Across ICU cohorts, initiating antibiotics within 1 hour and fluids within 1 hour (with ≥30 mL/kg within 3 hours) was associated with lower 28-day mortality and earlier ICU discharge. Early vasopressor initiation (≤1 hour) did not confer survival benefit.
Impact: This rigorous target trial emulation informs time-sensitive priorities in ICU sepsis resuscitation, reinforcing early antibiotics and fluids while questioning very-early vasopressors.
Clinical Implications: Prioritize timely antibiotic administration and early fluid resuscitation in ICU sepsis resuscitation, while individualizing vasopressor timing based on hemodynamics rather than strict clock targets.
Key Findings
- Antibiotics within 1 hour vs 1–3 hours: HR 0.65 for 28-day mortality; earlier ICU discharge (SHR 1.20).
- Fluids within 1 hour with ≥30 mL/kg by 3 hours: HR 0.72 for 28-day mortality; earlier discharge (SHR 1.17).
- Vasopressors within 1 hour: no survival benefit (HR 1.07) and no earlier ICU discharge.
Methodological Strengths
- Target trial emulation with inverse probability weighting across multiple cohorts
- Robust sensitivity and subgroup analyses including expanded time windows
Limitations
- Observational design with residual confounding risk despite adjustment
- Generalizability may vary across healthcare systems and ICU practices
Future Directions: Prospective trials to test optimized sequencing of antibiotics, fluids, and vasopressors, and to validate timing thresholds across diverse ICU settings.
PURPOSE: One-hour sepsis bundle was developed in 2018. However, the optimal timing for antibiotic, fluid resuscitation, and vasopressor initiation in intensive care units (ICUs) remains debated. High-quality randomized evidence is limited, particularly for ICU patients. Therefore, we emulated three target trials using observational data. PATIENTS AND METHODS: We conducted a retrospective, multicenter cohort study using data from the Medical Information Mart for Intensive Care-IV database (primary dataset), and two ICU cohorts from China (Zhujiang and Xiangya hospitals). Within a target trial emulation framework with inverse probability of treatment weighting, we constructed three two-arm trials comparing initiation of (1) antibiotics, (2) fluid resuscitation, and (3) vasopressors within 0-1 hour versus 1-3 hours after a prespecified time zero. RESULTS: In the target trial emulations, antibiotic initiation within 1 hour was associated with lower 28-day mortality (HR 0.65; 95% CI 0.54-0.79) and earlier ICU discharge (competing-risk analysis; SHR 1.20; 95% CI 1.12-1.27) compared with initiation at 1-3 hours. For fluid resuscitation, initiating within 1 hour and delivering ≥30 mL/kg crystalloid within 3 hours resulted in lower mortality (HR 0.72; 95% CI 0.53-0.97) and earlier discharge (SHR 1.17; 95% CI 1.02-1.33). However, vasopressor initiation within 1 hour showed no survival benefit (HR 1.07; 95% CI 0.89-1.29) or reduction in time to ICU discharge (SHR 1.02; 95% CI 0.95-1.08). These findings remained consistent across sensitivity and subgroup analyses, including comparisons using a 1-6 hour window.
3. Point-of-care ultrasound for evaluating acute dyspnoea in emergency departments: Systematic review and meta-analysis.
In adult ED patients with acute dyspnea, POCUS demonstrated pooled sensitivity of 85.6% and specificity of 80.8%, with a negative likelihood ratio of 0.14, supporting its utility to rule out serious pathology. Considerable heterogeneity was driven by operator variability and differing protocols.
Impact: This synthesis reinforces POCUS as a high-yield diagnostic adjunct for acute dyspnea in EDs and quantifies performance across studies, guiding training and implementation.
Clinical Implications: Adopt standardized POCUS protocols and invest in operator training to leverage high rule-out performance for dyspnea while minimizing variability. Integrate POCUS with clinical assessment to expedite diagnosis and disposition.
Key Findings
- Pooled sensitivity 85.6% and specificity 80.8% for POCUS in acute ED dyspnea.
- Negative likelihood ratio 0.14 and DOR 68.09 indicate strong rule-out capability.
- Substantial heterogeneity due to operator variability, study designs, and protocols.
Methodological Strengths
- PRISMA 2020準拠とPROSPERO登録、QUADAS-2による質評価
- 統合感度・特異度、尤度比、DORを用いた包括的診断性能評価
Limitations
- High heterogeneity and operator dependence limit generalizability of pooled estimates
- Limited data on downstream clinical outcomes and standardized training effects
Future Directions: Prospective multicenter studies using standardized POCUS protocols to quantify impact on time-to-diagnosis, disposition, and patient outcomes; competency-based training evaluations.
BACKGROUND: Acute dyspnoea is a common yet diagnostically complex presentation in emergency departments (EDs), representing approximately 2.4% of all visits. Traditional diagnostic tools-clinical assessment, chest radiography, and laboratory tests-may lack the precision required for timely and accurate diagnosis. Point-of-care ultrasound (POCUS) offers real-time, bedside imaging and has emerged as a promising tool to address these limitations. AIM: To evaluate the diagnostic accuracy and clinical effectiveness of POCUS METHODS: A comprehensive literature search was conducted across PubMed, EBSCO Host, MAG Online Library, Elsevier, and ProQuest without date restrictions. Studies were included if they involved adult ED patients undergoing POCUS for dyspnoea evaluation. Following PRISMA 2020 guidelines and PROSPERO registration (CRD42025649145), eligible studies were assessed using QUADAS-2, and diagnostic performance was analysed using MetaDisc software. Pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), and receiver operating characteristic curves were calculated. RESULTS: Out of 581 identified records, 44 studies met the inclusion criteria, with 19 included in the meta-analysis. The pooled sensitivity of POCUS was 85.6% (95%CI: 84.0%-87.2%) and specificity was 80.8% (95%CI: 79.0%-82.5%). The DOR was 68.09 (95%CI: 27.07-171.28), and the negative likelihood ratio was 0.14 (95%CI: 0.085-0.231), indicating strong potential to rule out serious pathology. Substantial heterogeneity was noted, mainly due to operator variability, study design, and diagnostic protocols.