Daily Sepsis Research Analysis
A multicenter RCT (C-EASIE) found that early high-dose intravenous vitamin C did not reduce organ dysfunction in sepsis, tempering enthusiasm for routine use. A 371,061-catheter cohort showed peripheral IV catheter bloodstream infection risk rises sharply after day 3, supporting earlier review/replacement. A UK nationwide EHR study linked new-onset atrial fibrillation during sepsis to higher stroke and mortality risks, underscoring the need for monitoring and post-discharge prevention.
Summary
A multicenter RCT (C-EASIE) found that early high-dose intravenous vitamin C did not reduce organ dysfunction in sepsis, tempering enthusiasm for routine use. A 371,061-catheter cohort showed peripheral IV catheter bloodstream infection risk rises sharply after day 3, supporting earlier review/replacement. A UK nationwide EHR study linked new-onset atrial fibrillation during sepsis to higher stroke and mortality risks, underscoring the need for monitoring and post-discharge prevention.
Research Themes
- Adjunctive therapy in sepsis resuscitation
- Device-related infection prevention and vascular access management
- Cardiovascular complications and long-term outcomes after sepsis
Selected Articles
1. Early administration of vitamin C in patients with sepsis or septic shock in emergency departments: a multicenter, double-blind, randomized controlled trial: the C-EASIE trial.
In 292 randomized ED patients with sepsis/septic shock, early high-dose IV vitamin C did not significantly reduce the average post-baseline SOFA score (ratio 0.91, 95% CI 0.77–1.08; P=0.30) versus placebo. A prespecified subgroup with baseline SOFA ≥6 showed lower SOFA (ratio 0.76, 95% CI 0.86–0.99; P=0.042), and per-protocol analyses suggested lower renal replacement therapy use, but overall secondary outcomes and adverse events were similar.
Impact: This rigorous multicenter, double-blind RCT addresses a high-profile, controversial adjunct in sepsis care and provides definitive negative evidence for routine early vitamin C use.
Clinical Implications: Do not routinely administer high-dose IV vitamin C early in sepsis/septic shock. Consider that any potential benefit may be limited to severe subgroups and is not practice-changing; prioritize evidence-based bundles and organ support.
Key Findings
- No significant reduction in average post-baseline SOFA scores with vitamin C versus placebo (ratio 0.91, 95% CI 0.77–1.08; P=0.30).
- In patients with baseline SOFA ≥6, vitamin C reduced average post-baseline SOFA (ratio 0.76, 95% CI 0.86–0.99; P=0.042; prespecified subgroup).
- Per-protocol analysis showed a lower probability of renal replacement therapy with vitamin C (ratio 0.28, 95% CI 0.078–1.0; P=0.05).
- No differences in maximum SOFA, 28-day mortality, ICU or hospital length of stay, or adverse events between groups.
Methodological Strengths
- Prospective, multicenter, double-blind, randomized, placebo-controlled design with trial registration.
- Early intervention window (≤6 hours) and standardized dosing schedule (1.5 g q6h for 4 days).
Limitations
- Not powered to detect mortality differences; primary endpoint was organ dysfunction (SOFA).
- Subgroup findings are exploratory and require confirmation; conducted in Belgian EDs which may limit generalizability.
Future Directions: Pursue biomarker- or severity-stratified trials and combination strategies (e.g., with corticosteroids/thiamine) with patient-centered endpoints and pharmacokinetic-pharmacodynamic profiling.
BACKGROUND: Sepsis and septic shock are associated with high mortality and morbidity despite adequate standard care. Vitamin C deficiency is a common, potentially reversible, contributor to morbidity and mortality in sepsis. Previous studies have shown mixed and conflicting results. Our study aimed to determine the potential benefit of early administration (within 6 h after admission) of vitamin C in patients with sepsis or septic shock. METHODS: This was a phase 3b prospective, multicenter, double-blinded, randomized placebo-controlled trial. Participants were enro
2. Dwell Time and Risk of Bloodstream Infection With Peripheral Intravenous Catheters.
Among 371,061 upper-extremity PIVCs, instantaneous BSI risk was low during the first 2 days and rose rapidly thereafter; dwell time >3 days was associated with markedly increased BSI risk (AOR 13.55, 95% CI 5.44–34.00). Elevated risk persisted beyond 4–6 days (AORs 5.38–8.53), supporting review of indication and potential replacement after day 3.
Impact: The largest contemporary evaluation of PIVC dwell time shows a clear inflection in BSI risk after day 3, providing actionable guidance for line maintenance policies to prevent hospital-onset bacteremia and downstream sepsis.
Clinical Implications: Implement daily PIVC necessity reviews and consider replacement after day 3 if ongoing IV access is required. Optimize alternative access (e.g., midline) and aseptic maintenance to mitigate BSI risk.
Key Findings
- Instantaneous BSI risk was low during the first 2 days of dwell time and increased rapidly thereafter.
- Dwell time >3 days was associated with a markedly increased BSI risk (adjusted OR 13.55, 95% CI 5.44–34.00).
- Risk remained elevated beyond 4, 5, and 6 days (>4 days AOR 8.53; >5 days AOR 5.38; >6 days AOR 7.63).
Methodological Strengths
- Extremely large cohort with prospective BSI surveillance and multivariable modeling.
- Hazard rate function and kernel-based methods to assess day-by-day risk.
Limitations
- Single health system; observational design limits causal inference and residual confounding is possible.
- Upper-extremity PIVCs only; may not generalize to other sites or catheter types.
Future Directions: Test dwell-time–based replacement policies in pragmatic trials and evaluate outcomes, costs, and patient comfort; compare strategies using midlines and ultrasound-guided cannulation.
IMPORTANCE: Bloodstream infections (BSIs) associated with peripheral intravenous catheters (PIVCs) are rare but preventable adverse events. The association of dwell time with the risk of BSIs with PIVCs remains controversial. OBJECTIVE: To analyze the risk of BSIs during PIVC maintenance therapy. DESIGN, SETTING, AND PARTICIPANTS: In this observational cohort study, all patients hospitalized at Geneva University Hospitals with at least 1 PIVC insertion on the upper extremity (N = 371 061) between January 1, 2016, and February 29, 20
3. Risk Factors and Prognosis of New-Onset Atrial Fibrillation in Sepsis: A Nationwide Electronic Health Record Study.
In linked UK EHRs, sepsis patients developing new-onset AF had longer hospital stays, higher septic shock and in-hospital mortality, and increased postdischarge risks of stroke (adjusted HR 1.18, 95% CI 1.08–1.30), heart failure, myocardial infarction, and mortality (adjusted HR 1.07, 95% CI 1.03–1.12) versus sepsis without AF. Demographic, behavioral, and cardiovascular comorbidities were associated with AF occurrence.
Impact: This nationwide study quantifies both inpatient and long-term risks associated with sepsis-related new-onset AF, informing monitoring and secondary prevention strategies, including stroke prevention after discharge.
Clinical Implications: Actively monitor for AF during sepsis, especially in older patients with cardiopulmonary comorbidities; plan post-discharge cardiovascular follow-up and consider individualized stroke prevention when AF persists or recurs.
Key Findings
- Identified demographic, behavioral, and cardiovascular comorbidities as risk factors for new-onset AF during sepsis.
- Sepsis with new-onset AF had longer hospitalization, higher septic shock rates, and higher in-hospital mortality than sepsis without AF.
- Postdischarge stroke risk increased (adjusted HR 1.18, 95% CI 1.08–1.30) and all-cause mortality increased (adjusted HR 1.07, 95% CI 1.03–1.12).
Methodological Strengths
- Large linked nationwide EHR dataset with multivariable adjustment and competing risk methods (Fine-Gray).
- Comprehensive assessment of both inpatient and long-term outcomes.
Limitations
- Observational design with potential residual confounding; AF identification may rely on coding and clinical detection.
- Study period (1998–2016) may not fully reflect contemporary sepsis and AF management.
Future Directions: Prospective studies to evaluate rhythm monitoring strategies and anticoagulation decision pathways after sepsis-related AF, with stroke and bleeding endpoints.
BACKGROUND: Atrial fibrillation (AF) may occur in patients with sepsis and is associated with a worse prognosis. To date, no UK nationwide studies have investigated the risks and impact of AF and sepsis. OBJECTIVES: The authors aimed to: 1) identify risk factors contributing to the development of new-onset AF in patients with sepsis; and 2) assess the impact of new-onset AF on in-hospital and long-term outcomes. METHODS: Utilizing linked UK-electronic health records of 5.6 million people between 1998 and 2016, we analyzed risk factors for new-o