Daily Sepsis Research Analysis
Analyzed 47 papers and selected 3 impactful papers.
Summary
Analyzed 47 papers and selected 3 impactful articles.
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 single-center randomized, sham-controlled pilot trial, daily taVNS for 7 days increased gastric antral motility and improved achievement of enteral nutrition targets in septic patients with acute gastrointestinal injury, without safety concerns. Clinical outcomes (ventilator-free days, LOS, 28-day mortality) were similar between groups, indicating the need for larger efficacy trials.
Impact: This is the first sham-controlled RCT to demonstrate physiologic augmentation of gastric motility by taVNS in septic AGI, opening a neuromodulatory avenue to address gut dysfunction in critical illness.
Clinical Implications: taVNS may serve as an adjunct to improve gastric emptying and facilitate enteral nutrition in sepsis-associated AGI, potentially reducing reliance on prokinetics and feeding interruptions. Implementation should await confirmatory multicenter trials powered for clinical endpoints and define target phenotypes and dosing parameters.
Key Findings
- Day-7 gastric antral motility index was higher with taVNS vs sham after baseline adjustment.
- A greater proportion of taVNS patients achieved prespecified enteral nutrition targets by day 7.
- Exploratory biomarker shifts (cytokines, GI hormones, barrier markers) were directionally favorable with taVNS.
- No serious stimulation-related adverse events; clinical outcomes (VFDs, LOS, 28-day mortality) were similar.
Methodological Strengths
- Randomized, sham-controlled design with blinded outcome assessment.
- Objective ultrasonographic measurement of gastric motility and predefined feasibility/safety endpoints.
Limitations
- Single-center pilot with modest sample size and short intervention period.
- Physiologic primary endpoint; study was not powered to detect differences in hard clinical outcomes.
Future Directions: Conduct multicenter, adequately powered RCTs to confirm efficacy on feeding intolerance, GI complications, infection risk, and mortality, and to refine patient selection and dosing parameters.
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. Coronary microvascular function in patients with sepsis and myocardial injury: an invasive coronary physiology study.
Invasive coronary physiology in sepsis with myocardial injury revealed common CMD (61%) with functional and structural phenotypes, reduced vasodilatory capacity versus matched CCS controls, and 22% previously unrecognized obstructive CAD. Troponin levels were not associated with microvascular indices, highlighting dissociation between injury biomarkers and coronary microvascular function.
Impact: This is among the first prospective invasive physiology studies in sepsis to phenotype CMD and quantify its heterogeneity, while uncovering a substantial burden of occult obstructive CAD with direct diagnostic implications.
Clinical Implications: In septic patients with myocardial injury, consideration of underlying CAD is warranted, and CMD assessment may inform mechanistic understanding of cardiac dysfunction. While routine invasive testing is not justified, selective coronary evaluation and echocardiographic assessment of ventriculo-arterial coupling and RV function may refine risk stratification.
Key Findings
- CMD was present in 61% (30/49) with distinct functional (MRR≤3, IMR≤25) and structural (MRR≤3, IMR>25) phenotypes.
- No association between hs-cTnT and IMR or MRR by restricted cubic spline analyses.
- Obstructive CAD was newly identified in 22% (12/55) of patients.
- Sepsis patients showed reduced MRR vs matched CCS controls, while IMR was similar.
- CMD associated with ventriculo-arterial uncoupling and RV systolic/pulmonary arterial coupling impairment.
Methodological Strengths
- Prospective enrollment with invasive thermodilution-based IMR/MRR and coronary angiography.
- Comparison with age-, sex-, and CAD-matched CCS controls; integrated echocardiography and regression modeling.
Limitations
- Modest sample size and single specialized setting; potential selection of clinically stable patients for invasive testing.
- Observational design limits causal inference; no longitudinal assessment of CMD prognostic impact.
Future Directions: Evaluate prognostic significance of CMD phenotypes and test targeted strategies (e.g., microvascular-directed therapies, CAD evaluation) in prospective outcome studies.
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.
3. Trajectories of Oxygenation Index and PEEP Levels Associated with 28-Day Mortality in Sepsis-Associated ARDS: A Multicenter Cohort Study.
Among 732 patients with sepsis-associated ARDS, dynamic 7-day oxygenation/PEEP trajectories yielded three phenotypes with marked 28-day mortality gradients (53.9%, 34.7%, 13.6%). Results were consistent across multivariable regression, propensity score matching, and inverse probability weighting. Phenotype-specific PEEP effects were observed, suggesting potential for trajectory-informed ventilatory strategies.
Impact: This large multicenter analysis links real-time oxygenation and PEEP trajectories to mortality in sepsis-associated ARDS and hints at phenotype-specific PEEP responses, paving the way for adaptive, trajectory-guided ventilation trials.
Clinical Implications: Early identification of trajectory phenotypes could inform ventilator settings, monitoring intensity, and escalation strategies. While specific PEEP targets require confirmation, a trajectory-aware approach may reduce mortality by avoiding one-size-fits-all ventilation.
Key Findings
- Three dynamic trajectory phenotypes were identified: Rebound Failure (26.4%), Gradual Recovery (57.5%), and Rapid Rebound (16.1%).
- A strong 28-day mortality gradient was observed across phenotypes: 53.9%, 34.7%, and 13.6% (P < 0.001).
- Mortality differences remained robust after multivariable regression, propensity score matching, and inverse probability weighting.
- Phenotype-specific PEEP effects emerged, supporting the concept of individualized ventilatory strategies.
Methodological Strengths
- Large multicenter cohort with 7-day high-frequency physiologic trajectories.
- Multiple analytic approaches (regression, PSM, IPW) confirming robustness of mortality associations.
Limitations
- Observational design precludes causal inference and is susceptible to residual confounding.
- Details of phenotype-specific PEEP thresholds are incomplete in the abstract and require full-text review and external validation.
Future Directions: Prospective trials should test trajectory- or phenotype-guided ventilation (including PEEP titration) to determine causal benefit on mortality and ventilator-related complications.
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