Daily Sepsis Research Analysis
Three studies advance sepsis care across distinct fronts: a double-blind RCT in postoperative ventilated neonates shows vitamin C infusion improves respiratory mechanics and shortens ventilation and inotrope use; an economic evaluation suggests procalcitonin-guided antibiotic duration can be cost-effective for adult sepsis stewardship; and a cohort analysis indicates early nutrition may benefit viral sepsis but not bacterial sepsis. Together, these works refine supportive therapy, precision stew
Summary
Three studies advance sepsis care across distinct fronts: a double-blind RCT in postoperative ventilated neonates shows vitamin C infusion improves respiratory mechanics and shortens ventilation and inotrope use; an economic evaluation suggests procalcitonin-guided antibiotic duration can be cost-effective for adult sepsis stewardship; and a cohort analysis indicates early nutrition may benefit viral sepsis but not bacterial sepsis. Together, these works refine supportive therapy, precision stewardship, and pathogen-specific nutrition timing.
Research Themes
- Adjunctive antioxidant therapy in neonatal sepsis
- Procalcitonin-guided antibiotic stewardship and health economics
- Pathogen-specific effects of early nutrition in sepsis
Selected Articles
1. Role of vitamin C infusion in postoperative mechanically ventilated neonates with sepsis: a randomized controlled trial.
In a double-blind RCT of 50 post-surgical, mechanically ventilated neonates with confirmed sepsis, vitamin C infusion improved respiratory mechanics and reduced ventilation and inotrope duration. No differences were observed in NICU/hospital length of stay or mortality.
Impact: Provides randomized evidence for an inexpensive adjunctive therapy that improves short-term respiratory outcomes in a high-risk neonatal sepsis population.
Clinical Implications: Consider vitamin C infusion as an adjunct to standard care to improve respiratory parameters and potentially shorten ventilator and inotrope use in septic neonates after surgery, while recognizing no proven mortality benefit.
Key Findings
- Vitamin C group had significantly lower respiratory rate and peak inspiratory pressure at 24, 72, and 120 hours versus placebo.
- FiO2 requirements were reduced at 72 and 120 hours with vitamin C infusion.
- Duration of mechanical ventilation and inotropic support was reduced in the vitamin C group.
- No significant differences in NICU/hospital length of stay or mortality.
Methodological Strengths
- Double-blind randomized controlled design with trial registration (NCT06780345).
- Standardized dosing regimen and serial assessment of objective respiratory parameters.
Limitations
- Single-center, small sample size limits power for mortality and length-of-stay endpoints.
- Mechanistic biomarkers (e.g., oxidative stress) were not reported to explain observed effects.
Future Directions: Larger multicenter RCTs should evaluate optimal dosing, timing, safety, and patient-centered outcomes (including neurodevelopment) and assess mechanistic biomarkers.
2. Cost-effectiveness of procalcitonin-guided antibiotic duration for hospitalized patients with sepsis.
Economic modeling using ADAPT-Sepsis and meta-analyzed data suggests that daily PCT-guided antibiotic duration can be cost-effective, with an ICER of €2384/QALY under meta-analyzed assumptions, though trial-based analysis showed dominance against PCT due to uncertain mortality effects. Stewardship gains may be achievable at modest per-patient costs when only antibiotic use and test costs differ.
Impact: Directly informs system-level decisions on implementing PCT-guided protocols for sepsis, balancing stewardship, outcomes, and costs using large RCT data and synthesized evidence.
Clinical Implications: Hospitals may consider PCT-guided antibiotic discontinuation protocols to enhance stewardship, recognizing cost-effectiveness depends on assumed mortality effects; focusing on reduced antibiotic days and test costs yields modest incremental spending.
Key Findings
- ADAPT-Sepsis-based analysis showed PCT-guided protocol cost €427 more per patient with a marginal QALY loss (0.001), indicating dominance against PCT.
- Meta-analyzed assumptions yielded €330 higher costs and 0.139 more QALYs, with an ICER of €2384 per QALY gained.
- If only antibiotic days and PCT testing differ, incremental per-patient costs are estimated at ≤€110 with equivalent QALYs.
Methodological Strengths
- Uses both trial-based and meta-analyzed evidence with lifetime horizon modeling.
- Explores scenario analyses separating antibiotic use differences from mortality assumptions.
Limitations
- Cost-effectiveness hinges on uncertain mortality effects; confidence/credible intervals include no effect.
- Generalizability may vary across healthcare systems and cost structures.
Future Directions: Prospective implementation trials with embedded economic evaluations should quantify real-world antibiotic reduction, resistance impacts, and patient outcomes across diverse health systems.
3. The impact of early nutritional support on in-hospital mortality in patients with sepsis caused by bacterial or viral infections: a retrospective cohort study.
In a retrospective ICU cohort (n=2,278), early nutrition within 48 hours was associated with lower in-hospital mortality in viral sepsis but not in bacterial sepsis; early support in bacterial sepsis correlated with longer ICU and ventilation duration among survivors.
Impact: Introduces pathogen-specific heterogeneity in the benefits of early nutritional support, challenging one-size-fits-all protocols and informing individualized nutrition strategies in sepsis.
Clinical Implications: Consider tailoring early nutrition based on suspected pathogen class; prioritize cautious application and monitoring in bacterial sepsis while exploring potential benefit in viral sepsis pending RCT confirmation.
Key Findings
- Early nutrition (≤48 h) associated with lower in-hospital mortality in viral sepsis (aOR 0.79; 95% CI 0.63–0.99; p=0.046).
- No mortality benefit observed with early nutrition in bacterial sepsis (aOR 1.02; 95% CI 0.98–1.06; p=0.328).
- In bacterial sepsis survivors, early nutrition correlated with longer ICU length of stay and duration of mechanical ventilation.
Methodological Strengths
- Large ICU cohort with pathogen stratification and robust confounding control (PSM and IPW).
- Clear exposure definition (≤48 h from sepsis diagnosis) and clinically relevant outcomes.
Limitations
- Retrospective single-center design with potential residual confounding and selection bias.
- Small viral sepsis subgroup (n=119) with borderline significance limits certainty.
Future Directions: Prospective, pathogen-stratified RCTs should test timing, route, and composition of nutrition in sepsis, with mechanistic endpoints (e.g., immunometabolism) to explain differential effects.