Daily Sepsis Research Analysis
Three impactful sepsis studies span resuscitation strategy, point-of-care hemodynamic assessment, and mortality risk stratification. A large RCT protocol (ARISE FLUIDS) will directly compare restricted fluids with early vasopressors, a clinical ultrasonography study identifies high-performing indices for fluid responsiveness in septic shock, and a 13,717-patient nomogram achieves practical 28-day ICU mortality prediction with temporal validation.
Summary
Three impactful sepsis studies span resuscitation strategy, point-of-care hemodynamic assessment, and mortality risk stratification. A large RCT protocol (ARISE FLUIDS) will directly compare restricted fluids with early vasopressors, a clinical ultrasonography study identifies high-performing indices for fluid responsiveness in septic shock, and a 13,717-patient nomogram achieves practical 28-day ICU mortality prediction with temporal validation.
Research Themes
- Early sepsis resuscitation: fluids versus vasopressors
- Point-of-care ultrasonography for fluid responsiveness
- Risk stratification of ICU mortality in sepsis
Selected Articles
1. Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In emergency Department Sepsis (ARISE FLUIDS) trial: study protocol.
This multicenter RCT will randomize 1000 ED patients with septic shock to restricted fluids with early vasopressors versus larger initial fluids with later vasopressors. The primary outcome is days alive and out of hospital at day 90, with comprehensive secondary outcomes and long-term follow-up to 12 months.
Impact: The trial directly tests two widely used but debated resuscitation strategies and uses a patient-centered primary outcome, positioning it to influence sepsis resuscitation guidelines.
Clinical Implications: If early vasopressor with restricted fluids improves patient-centered outcomes, initial ED management of septic shock could shift toward earlier vasopressors and judicious fluids.
Key Findings
- Design: 1000-participant, multicenter, randomized, open-label, parallel-group RCT in ED septic shock across Australia, New Zealand, and Ireland.
- Intervention arms: restricted fluids with early vasopressors versus larger initial fluids with later vasopressors.
- Primary outcome: days alive and out of hospital at day 90; extensive secondary outcomes include mortality, organ support–free days, disability, and quality of life up to 12 months.
Methodological Strengths
- Large, multicenter randomized design with pragmatic ED enrollment
- Patient-centered primary outcome and prespecified long-term follow-up
Limitations
- Open-label design may introduce performance bias
- Protocol report; no clinical outcomes available yet
Future Directions: Completion of enrollment, reporting of primary and subgroup analyses (e.g., source of infection, baseline hypotension), and integration with prior fluid/vasopressor trials for meta-analyses.
INTRODUCTION: International consensus guidelines support the initial administration of 30 mL/kg of intravenous fluids for haemodynamic resuscitation of newly diagnosed septic shock. Practice variation exists between the volume of fluids administered and timing of vasopressor commencement. The optimal approach in patients with septic shock is uncertain. METHODS AND ANALYSIS: Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In emergency Department Sepsis is a 1000-participant multicentre, randomised, open-label, parallel group clinical trial conducted in patients with septic shock presenting to the emergency department in participating sites in Australia, New Zealand and Ireland. Participants are randomised (1:1) to either restricted fluids and early vasopressors or a larger initial intravenous fluid volume and later vasopressors. The primary outcome is days alive and out of hospital at day 90 postrandomisation. Secondary outcomes are all-cause mortality at day 90, time from randomisation until death (to day 90), days alive and at home at day 90 and ventilator-free, vasopressor-free and renal replacement-free days to day 28 postrandomisation and death or disability at 6-month and 12-month postrandomisation. Health-related quality of life will be assessed at day 180 and 12 months following randomisation. ETHICS AND DISSEMINATION: The study was approved by Northern Sydney Local Health District Human Research Ethics Committee (HREC2020/ETH02874) on 21 January 2021. Patients will be enrolled under a waiver of prior consent. The patient or next-of-kin (or equivalent according to local jurisdiction) is approached at the first available opportunity and given a trial information sheet. According to local approvals, the patient or next-of-kin chooses to either continue in the trial or opt-out/decline continued participation. Results will be disseminated in peer-reviewed journals and presented at academic conferences. TRIAL REGISTRATION NUMBER: NCT04569942.
2. Evaluating the Role of Critical Care Ultrasonography in Predicting Volume Responsiveness Among Septic Shock Patients Undergoing Fluid Resuscitation: A Clinical Study.
In 90 septic shock patients, ultrasonographic indices (ΔVTI, ΔFTc, ΔVpeakCA, RVI) strongly correlated with stroke volume variation and accurately discriminated fluid responders (AUC up to 0.944 for ΔVTI). Responders had improved ScvO2, higher PaO2, and lower lactate after resuscitation.
Impact: Provides practical, noninvasive bedside metrics with strong discriminative performance to individualize fluid therapy in septic shock.
Clinical Implications: Clinicians can incorporate ΔVTI, ΔFTc, ΔVpeakCA, and RVI to guide fluid challenges and avoid unnecessary fluids, potentially reducing fluid overload and improving oxygenation/lactate clearance.
Key Findings
- Nonresponders had significantly lower ΔVTI, ΔFTc, ΔVpeakCA, RVI, and SVV than responders (P < 0.05).
- Strong positive correlations between ultrasound indices and SVV (r ≈ 0.74 for all indices).
- Discrimination of responders: ΔVTI AUC 0.944; ΔFTc 0.867; ΔVpeakCA 0.874; combined indices 0.935.
- Responders showed higher ScvO2 and PaO2 and lower lactate after resuscitation.
Methodological Strengths
- Pre/post fluid challenge assessment with multiple ultrasound indices
- Receiver operating characteristic analysis with high AUCs and correlation with SVV
Limitations
- Single-center observational design with modest sample size (n=90)
- Potential selection bias and lack of external validation across settings
Future Directions: Prospective multicenter validation and integration into decision-support algorithms to standardize ultrasound-guided fluid management.
This study aimed to evaluate the predictive efficacy of critical care ultrasonography for volume responsiveness in septic shock patients undergoing fluid resuscitation. Ninety septic shock patients admitted between January 2021 and December 2023 were divided into responsive and nonresponsive groups based on fluid responsiveness. Ultrasonic indices, including velocity time integration (ΔVTI), corrected flow time (ΔFTc), peak velocity of the carotid artery (ΔVpeakCA), and Respiratory Variation Index (RVI), as well as oxygen metabolism parameters, were measured before and after the fluid resuscitation trial. The correlation between ultrasonic indices and stroke volume variation (SVV) was assessed, and the predictive efficacy of these indices was analyzed using receiver operating characteristic curves. Results showed that ΔVTI, ΔFTc, ΔVpeakCA, RVI, and SVV were significantly lower in the nonresponsive group compared with the responsive group (P < 0.05). Pearson correlation analysis indicated a strong positive correlation between ΔVTI, ΔFTc, ΔVpeakCA, RVI, and SVV (r = 0.737, 0.741, 0.743, 0.739). Receiver operating characteristic analysis revealed that the areas under the curve for ΔVTI, ΔFTc, ΔVpeakCA, RVI and the combined indices were 0.944, 0.867, 0.874, and 0.935, respectively. Postresuscitation, the responsive group demonstrated significantly higher central venous oxygen saturation levelselevated partial pressure of oxygen and markedly reduced lactate levels compared with the nonresponsive group. These findings suggest that ΔVTI, ΔFTc, ΔVpeakCA, and RVI are effective for assessing volume responsiveness in mechanically ventilated septic shock patients, with the responsive group showing improved resuscitation outcomes.
3. Development and temporal validation of a nomogram for predicting ICU 28-day mortality in middle-aged and elderly sepsis patients: An eICU database study.
Using 13,717 sepsis patients aged ≥45 years from eICU, the authors built a nomogram based on 11 variables and temporally validated it (AUC 0.805 training; 0.756 validation) with good calibration. Predictors included SOFA, lactate, RDW, pH, urine output, platelets, total protein, temperature, heart rate, GCS, and WBC.
Impact: Provides an interpretable, validated risk tool tailored to older sepsis patients, enabling practical bedside stratification beyond generic ICU scores.
Clinical Implications: The nomogram can support triage, goals-of-care discussions, and resource allocation by identifying high-risk patients early in ICU stay.
Key Findings
- Large retrospective cohort (n=13,717) of sepsis patients aged ≥45 years from eICU (2014–2015).
- Final nomogram used 11 independent predictors spanning organ dysfunction, metabolic status, and basic labs/vitals.
- Temporal validation showed good discrimination (AUC 0.805 training; 0.756 validation) and good calibration.
Methodological Strengths
- Large sample with temporal split for validation
- Robust variable selection (random forest importance, LASSO) and multivariable modeling with calibration assessment
Limitations
- Retrospective design and reliance on database variables
- External validation beyond temporal split not reported
Future Directions: Prospective external validation, impact analyses on clinical decision-making, and integration into EHR decision support.
BACKGROUND AND OBJECTIVE: Despite advances in intensive care, sepsis remains a leading cause of mortality in intensive care unit (ICU) patients, especially middle-aged and elderly individuals. Given the limitations of conventional scoring systems and the interpretability challenges of machine learning models, this study aims to develop and temporally validate a nomogram for predicting 28-day ICU mortality in middle-aged and elderly sepsis patients via the eICU database (2014--2015), providing a clinically practical prediction tool. METHODS: This retrospective study included 13,717 sepsis patients aged ≥45 years. The cohort was temporally divided into training (n = 6,397, 2014) and validation (n = 7,320, 2015) sets. Variable selection was performed via random forest importance ranking and LASSO regression. A nomogram was developed on the basis of multivariable logistic regression analysis. RESULTS: The 28-day ICU mortality rates were 9.08% and 9.49% in the training and validation cohorts, respectively. The final nomogram incorporated 11 independent predictors: red cell distribution width (RDW), SOFA score, lactate, pH, 24-hour urine output, platelet count, total protein, temperature, heart rate, GCS score, and white blood cell (WBC) count. The model showed good discrimination in both the training (AUC: 0.805) and validation (AUC: 0.756) cohorts. The calibration curves demonstrated good agreement between the predicted and observed probabilities. CONCLUSIONS: We developed and temporally validated a nomogram with good predictive performance for 28-day ICU mortality in middle-aged and elderly sepsis patients, providing a practical tool for risk stratification and clinical decision-making.