Daily Sepsis Research Analysis
Analyzed 47 papers and selected 3 impactful papers.
Summary
Top findings span neuromodulation, precision ventilation phenotypes, and coronary microvascular pathophysiology in sepsis. A sham-controlled pilot RCT shows transcutaneous auricular vagus nerve stimulation (taVNS) increases gastric motility in sepsis-associated acute gastrointestinal injury. A multicenter cohort delineates oxygenation/PEEP trajectory phenotypes with markedly different 28-day mortality, while an invasive physiology study reveals common and heterogeneous coronary microvascular dysfunction not reflected by troponin release.
Research Themes
- Noninvasive neuromodulation to restore gut function in sepsis
- Dynamic phenotyping of oxygenation/PEEP trajectories in sepsis-associated ARDS
- Coronary microvascular dysfunction in sepsis-related myocardial injury
Selected Articles
1. Transcutaneous Auricular Vagus Nerve Stimulation Is Associated With Higher Gastric Antral Motility in Septic Patients With Acute Gastrointestinal Injury: A Randomized, Sham-Controlled Pilot Trial with Blinded Outcome Assessment.
In a randomized, sham-controlled pilot trial with blinded outcome assessment (n=66), taVNS increased baseline-adjusted day-7 gastric antral motility and improved enteral nutrition target attainment in septic patients with AGI, without serious adverse events. Clinical outcomes (ventilator-free days, lengths of stay, 28-day mortality) did not differ, and exploratory biomarker shifts suggested physiological effects.
Impact: This is the first randomized, sham-controlled clinical signal that noninvasive neuromodulation can restore gastric motor function in septic AGI, a common barrier to nutrition delivery. It opens a mechanistically distinct therapeutic avenue beyond pharmacologic prokinetics.
Clinical Implications: taVNS could be considered as an adjunct to enhance gastric motility and feeding tolerance in septic AGI while awaiting confirmatory trials. It may reduce reliance on prokinetics and facilitate earlier achievement of nutrition goals without evident safety concerns.
Key Findings
- Baseline-adjusted day-7 gastric antral motility index was higher with taVNS versus sham.
- More patients receiving taVNS achieved predefined enteral nutrition targets by day 7.
- No differences in ventilator-free days, ICU/hospital length of stay, or 28-day mortality; no serious stimulation-related adverse events.
Methodological Strengths
- Randomized, sham-controlled design with blinded outcome assessment.
- Physiologically grounded primary endpoint (ultrasound-derived gastric motility index) with prespecified nutrition targets.
Limitations
- Single-center pilot with modest sample size; not powered for clinical outcomes.
- Primary endpoint is a surrogate physiological measure; biomarker analyses were exploratory.
Future Directions: Conduct multicenter, adequately powered RCTs to test clinical efficacy on feeding tolerance, time to nutrition targets, GI complications, and patient-centered outcomes; define optimal stimulation parameters and patient selection.
BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation approach engaging vagal afferent pathways involved in autonomic, gastrointestinal, and immune regulation; its effects on gastric motor function in critical illness remain uncertain. OBJECTIVE: To assess feasibility, safety, and preliminary physiological signals of taVNS on gastric motility in septic patients with acute gastrointestinal injury (AGI). METHODS: In this single-center, randomized, sham-controlled pilot trial with blinded outcome assessment, adult ICU patients with sepsis-associated AGI were randomized 1:1 to once-daily taVNS or sham stimulation for 7 days in addition to standard care. The primary outcome was gastric antral motility index (MI) measured by bedside ultrasonography on day 7. Secondary outcomes included enteral nutrition target attainment, inflammatory cytokines, gastrointestinal hormones, intestinal barrier injury markers, clinical outcomes, and adverse events; these were exploratory. RESULTS: Sixty-six patients were randomized (33 taVNS, 33 sham) with comparable baseline characteristics. Baseline-adjusted Day-7 MI was higher with taVNS than sham. More taVNS-treated patients achieved prespecified enteral nutrition targets by day 7. Exploratory changes in cytokines, gastrointestinal hormones, and intestinal barrier markers were directionally consistent with possible physiological effects of taVNS. Ventilator-free days, ICU and hospital length of stay, and 28-day mortality did not differ. No serious stimulation-related adverse events occurred. CONCLUSIONS: TaVNS was feasible and well tolerated and showed preliminary signals of higher gastric antral motility in sepsis-associated AGI, with exploratory changes in gut-related physiological markers. These findings are hypothesis-generating. Larger trials are needed to confirm these observations and determine clinical efficacy.
2. Trajectories of Oxygenation Index and PEEP Levels Associated with 28-Day Mortality in Sepsis-Associated ARDS: A Multicenter Cohort Study.
In 732 patients with sepsis-associated ARDS, 168-hour PaO2/FiO2 trajectories clustered into three phenotypes with distinct 28-day mortality (54%, 35%, 14%). Results were consistent across multivariable, propensity score–matched, and inverse-probability weighted analyses. Phenotype-specific PEEP effects were observed, suggesting heterogeneity of treatment effects.
Impact: This study operationalizes dynamic oxygenation/PEEP phenotyping with robust statistical validation and links it to mortality, informing precision ventilation strategies in sepsis-associated ARDS.
Clinical Implications: Continuous assessment of oxygenation trajectories may enable early identification of high-risk phenotypes and guide individualized PEEP strategies rather than one-size-fits-all protocols.
Key Findings
- Three 168-hour PaO2/FiO2 trajectory phenotypes were identified: Rebound Failure (26.4%), Gradual Recovery (57.5%), Rapid Rebound (16.1%).
- 28-day mortality showed a strong gradient across phenotypes: 53.9%, 34.7%, and 13.6% (P < 0.001).
- Findings persisted across multivariable regression, propensity score matching, and inverse-probability weighting; phenotype-specific PEEP effects emerged.
Methodological Strengths
- Multicenter cohort with large sample size and 168-hour high-resolution trajectories.
- Robust validation using multivariable adjustment, propensity score matching, and inverse-probability weighting.
Limitations
- Observational design precludes causal inference, including for PEEP effects.
- Details of PEEP thresholds and ventilatory co-interventions are truncated/unreported in the abstract; external generalizability requires full-text appraisal.
Future Directions: Prospective interventional trials testing phenotype-guided PEEP/ventilation strategies and external validation across diverse ICUs with integration of bedside decision support.
BACKGROUND: The prognostic value of dynamic PaO METHODS: This multicenter cohort study enrolled 732 SA-ARDS patients. K-means clustering identified phenotypes based on 168-hour PaO RESULTS: THREE PHENOTYPES WERE IDENTIFIED: 'Rebound Failure' (26.4%), 'Gradual Recovery' (57.5%), and 'Rapid Rebound' (16.1%). A significant mortality gradient was observed: 53.9%, 34.7%, and 13.6%, respectively (P < 0.001). Clusters 1 and 2 exhibited 3- to 8-fold higher 28-day mortality versus cluster 3, confirmed across multivariable regression, PSM, and IPW. Phenotype-specific PEEP effects emerged: early higher PEEP (≤ 10 cmH CONCLUSIONS: Dynamic PaO
3. Coronary microvascular function in patients with sepsis and myocardial injury: an invasive coronary physiology study.
Prospective invasive assessments showed coronary microvascular dysfunction in 61% of sepsis patients with myocardial injury, spanning functional and structural phenotypes, without association to hs-cTnT levels. Obstructive CAD was newly identified in 22%, and septic patients had reduced vasodilatory capacity versus matched chronic coronary syndrome controls.
Impact: Provides rare in vivo human evidence delineating coronary microvascular dysfunction phenotypes in sepsis and decoupling troponin elevations from microvascular indices, with direct implications for diagnostic workup.
Clinical Implications: Troponin elevations in sepsis should not be assumed to reflect microvascular dysfunction; consider evaluation for occult obstructive CAD. Microvascular phenotyping may guide targeted therapies and echocardiographic assessment of ventriculo-arterial and RV-PA coupling.
Key Findings
- CMD was present in 30/49 (61%) with distinct phenotypes: elevated IMR only (16%), functional CMD (18%), structural CMD (27%).
- No association between hs-cTnT and IMR or MRR by restricted cubic spline analyses.
- Previously unrecognised obstructive CAD identified in 22% of patients; septic patients had lower MRR than matched CCS controls.
Methodological Strengths
- Prospective enrollment with invasive thermodilution-based IMR/MRR assessment and coronary angiography.
- Matched comparator group (age/sex/CAD) and multivariable regression/mixed-effects analyses.
Limitations
- Modest sample size and assessments performed after clinical stabilization may introduce selection bias.
- Study was not designed to establish causality or link microvascular phenotypes to longitudinal outcomes.
Future Directions: Larger prospective studies to relate CMD phenotypes to outcomes and test targeted interventions; integrate microvascular assessment into sepsis cardiology pathways, including evaluation for occult CAD.
BACKGROUND: Myocardial injury is common in sepsis and associated with increased mortality, but its underlying mechanisms remain incompletely understood. Coronary microvascular dysfunction (CMD) has been proposed as a contributor, although in vivo evidence is limited. We characterised coronary microvascular function in patients with sepsis and myocardial injury and its relationship with cardiac troponin release. METHODS: Consecutive adults with sepsis (Sepsis-3 criteria) and myocardial injury (hs-cTnT ≥ 15 ng/L) were prospectively enrolled between June 2019 and December 2024. Patients underwent coronary angiography, invasive thermodilution-based assessment of coronary microvascular function, and transthoracic echocardiography after clinical stabilisation. CMD was defined as an index of microcirculatory resistance (IMR) > 25 and/or microvascular resistance reserve (MRR) ≤ 3. Associations between hs-cTnT concentrations and coronary microvascular indices, obstructive coronary artery disease (CAD), and echocardiographic variables were assessed using regression analyses. Coronary microvascular indices were compared with those of age-, sex-, and CAD-matched patients with chronic coronary syndrome (CCS) using mixed-effects models. RESULTS: Fifty-five patients underwent coronary angiography and 49 completed invasive coronary microvascular assessment. Obstructive CAD was identified in 12/55 (22%). CMD was present in 30/49 (61%). Among these, 8/49 (16%) had elevated IMR only, 9/49 (18%) had functional CMD (MRR ≤ 3 and IMR ≤ 25), and 13/49 (27%) had structural CMD (MRR ≤ 3 and IMR > 25). Restricted cubic spline analyses demonstrated no evidence of associations between hs-cTnT and IMR (overall P = 0.899; non-linearity P = 0.687) or MRR (overall P = 0.987; non-linearity P = 0.954). CMD was associated with a higher prevalence of ventriculo-arterial uncoupling, right ventricular systolic dysfunction, and impaired right ventricular-pulmonary arterial coupling. Patients with sepsis demonstrated reduced coronary microvascular vasodilatory capacity compared with matched CCS controls (MRR 3.2 [IQR 2.4-4.5] vs. 4.0 [2.7-6.2]). IMR was similar between groups. CONCLUSIONS: CMD was common and heterogeneous and exhibited distinct phenotypes in patients with sepsis and myocardial injury. Measures of coronary microvascular function were not associated with troponin release. Previously unrecognised obstructive CAD was identified in 22% of patients, supporting consideration of underlying CAD in patients with sepsis and myocardial injury. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06294730.