Daily Sepsis Research Analysis
Three sepsis-related studies stand out today: a prospective ICU physiology study shows that 10-second end-expiratory occlusion-induced pulse pressure changes reliably detect preload responsiveness; a re-analysis of the PREMILOC trial finds prophylactic hydrocortisone does not significantly increase late-onset sepsis in extremely preterm neonates and is associated with reduced mortality; and a double-blind RCT reports curcumin–piperine supplementation improves inflammatory and laboratory indices
Summary
Three sepsis-related studies stand out today: a prospective ICU physiology study shows that 10-second end-expiratory occlusion-induced pulse pressure changes reliably detect preload responsiveness; a re-analysis of the PREMILOC trial finds prophylactic hydrocortisone does not significantly increase late-onset sepsis in extremely preterm neonates and is associated with reduced mortality; and a double-blind RCT reports curcumin–piperine supplementation improves inflammatory and laboratory indices without mortality benefit.
Research Themes
- Bedside hemodynamic assessment in critical care
- Safety of prophylactic steroids in extremely preterm neonates
- Adjunct anti-inflammatory therapies in sepsis
Selected Articles
1. Real-time changes in pulse pressure during a 10-second end-expiratory occlusion test reliably detect preload responsiveness.
In 143 ventilated patients with sinus rhythm, real-time pulse pressure changes during a 10-second end-expiratory occlusion reliably identified preload responsiveness using fluid bolus or passive leg-raising cardiac index thresholds. This approach offers a simple bedside surrogate to cardiac index monitoring for fluid responsiveness testing.
Impact: Provides a practical, time-efficient physiologic test to guide fluid therapy, potentially reducing unnecessary fluid loading in septic and other critically ill patients.
Clinical Implications: A 10-second EEO-induced pulse pressure change can be adopted at the bedside to screen for fluid responsiveness without advanced cardiac output monitors, aiding fluid stewardship in mechanically ventilated ICU patients.
Key Findings
- Real-time ∆PP during a 10-second EEO reliably detected preload responsiveness.
- Preload responsiveness was defined using reference standards: fluid bolus-induced ΔCI ≥15% or passive leg raising-induced ΔCI ≥10%.
- Among 143 ventilated patients with sinus rhythm, 61 (43%) were preload responders.
Methodological Strengths
- Prospective physiologic evaluation in mechanically ventilated patients with predefined reference standards (fluid bolus or passive leg raising).
- Direct arterial waveform analysis enabling real-time bedside assessment.
- Study registration reported (IDRCB 2010A0095942).
Limitations
- Results truncated in abstract; full diagnostic metrics (AUC, thresholds) are not provided here.
- Applicability to patients with arrhythmias or spontaneous breathing was not addressed.
- Single physiologic test; not a randomized comparison of strategies.
Future Directions: Quantify diagnostic performance (AUC, optimal ∆PP thresholds), validate in broader populations (including arrhythmias/spontaneous breathing), and test EEO-guided fluid strategies in outcome trials.
BACKGROUND: The end-expiratory occlusion (EEO) test detects preload responsiveness through changes in cardiac index (ΔCI) during a 15-second respiratory hold at end-expiration. We investigated the diagnostic accuracy of EEO-induced changes in arterial pulse pressure (∆PP), especially when the duration of EEO is reduced to 10'' and 5'', and whether adding an end-inspiratory occlusion (EIO) improves this diagnostic accuracy. METHODS: In 143 mechanically ventilated patients with sinus rhythm, EEO and EIO were performed while recording ΔCI and ∆PP values. Either a fluid bolus-induced ΔCI ≥ 15% or a passive leg raising-induced ΔCI ≥ 10% defined preload responsiveness. The effects of the EEO and EIO tests on PP and CI were evaluated as the percentage difference between values averaged either over the last five seconds of the 15-sec respiratory holds (ΔPP RESULTS: Sixty-one (43%) patients were preload responders. Both ∆CI CONCLUSION: In ventilated patients with sinus rhythm, real-time changes in PP during a 10-second EEO reliably detect preload responsiveness. TRIAL REGISTRATION: No. IDRCB 2010A0095942. Registered 04 January 2010.
2. Prophylactic hydrocortisone and the risk of sepsis in neonates born extremely preterm.
Secondary analyses of the PREMILOC RCT show no significant increase in late-onset sepsis with prophylactic hydrocortisone after adjustment (RR ~1.04) while competing risk analyses suggest reduced mortality (HR ~0.43). Higher gestational age, vaginal delivery, and supplemental corticosteroids after day 10 were associated with lower LOS risk.
Impact: Clarifies the safety profile of prophylactic hydrocortisone regarding late-onset sepsis while highlighting mortality benefits, informing neonatal steroid protocols.
Clinical Implications: Prophylactic low-dose hydrocortisone to prevent BPD in extremely preterm neonates appears not to increase LOS risk after adjustment and may reduce mortality; clinicians can consider its use while monitoring infection risk and individual perinatal factors.
Key Findings
- Late-onset sepsis occurred in 24% (placebo) vs 30% (hydrocortisone), P=0.12.
- Adjusted association between hydrocortisone and LOS was non-significant (RR 1.041, 95% CI 0.738–1.471; P=0.817); competing risks confirmed no significant effect (HR 1.105, 95% CI 0.787–1.552; P=0.560).
- Hydrocortisone was associated with reduced competing death (HR 0.427, 95% CI 0.259–0.707; P<0.001).
Methodological Strengths
- Re-analysis of randomized trial data with multiple models (Poisson, Cox, Fine–Gray competing risks).
- Adjustment for perinatal covariates and exploration of interactions.
- Prospectively collected RCT dataset with trial registration (NCT00623740).
Limitations
- Post hoc secondary analyses may be subject to residual confounding and multiple testing.
- Generalizability limited to extremely preterm populations similar to PREMILOC.
- LOS follow-up window beyond day 3 is not precisely defined in the abstract.
Future Directions: Prospective confirmation of infection risk under standardized hydrocortisone protocols and exploration of mechanisms underlying mortality reduction.
UNLABELLED: Bronchopulmonary dysplasia (BPD) is a serious complication of extreme prematurity and has few treatment options. The postnatal use of steroids to prevent BPD remains controversial, but prophylactic low-dose hydrocortisone (HC) has been shown to improve survival without BPD. However, an increased risk of late-onset sepsis (LOS) was also reported in extremely preterm neonates exposed to prophylactic HC treatment. Because its causal link remains unclear, our objective was to assess the effect of prophylactic HC exposure on LOS risk, adjusted for perinatal risk factors of LOS. We re-analyzed the PREMILOC trial to investigate the postnatal factors influencing the incidence of LOS occurring after day 3 from baseline conditions and to evaluate the potential interaction produced by prophylactic HC exposure. We used three different statistical models (poisson, Cox regression, competing risks) to test the effect of HC on LOS occurrence. LOS was reported in 64/264 (24%) and 77/255 (30%) in the placebo and HC groups, respectively (P = 0.12). A decreasing risk of LOS was observed with increasing gestational age (P < 0.001), vaginal delivery (P = 0.005), and supplemental corticosteroids given after a 10-day treatment with prophylactic HC but before the LOS (P < 0.001). A trend of higher risk of LOS was noted in infants exposed to perinatal asphyxia (P = 0.065). Adjusted for these covariates, we found a non-significant association between HC exposure and risk of LOS (relative risk, 1.041 (95% CI, 0.738 to 1.471]), P = 0.817). Using a survival competing risk analysis, we confirmed the lack of significant effect of HC on LOS (hazard risk ratio, 1.105 [95% CI, 0.787 to 1.552], P = 0.560), while competing death was significantly reduced by the treatment (hazard risk ratio, 0.427 [95% CI, 0.259 to 0.707], P < 0.001). CONCLUSION: The effect of prophylactic HC compared with placebo on LOS is summarized by a risk ratio varying within the interval [0.90-1.10] and this effect was never significant. TRIAL REGISTRATION: EudraCT number 2007-002041-20, ClinicalTrials.gov number NCT00623740. WHAT IS KNOWN: • Prophylactic hydrocortisone improves survival without bronchopulmonary dysplasia in extremely preterm neonates. • It increases the risk of late-onset sepsis in the most immature infants. • Causality remains unclear. WHAT IS NEW: • A lower risk of late-onset sepsis was observed with higher gestational age at birth, vaginal delivery, and, more surprisingly, with supplemental corticosteroids administration after day 10. • Competing survival by Fine and Gray analysis suggests that death was reduced by prophylactic hydrocortisone, without a significant effect of treatment on the risk of late-onset sepsis.
3. Therapeutic effects of curcumin and piperine combination in critically ill patients with sepsis: a randomized double-blind controlled trial.
In a double-blind RCT of 66 ICU patients with sepsis, 7-day curcumin–piperine supplementation improved inflammatory and laboratory markers (e.g., lower CRP, ESR, bilirubin; altered hematologic indices) without a mortality difference. Analyses were intention-to-treat.
Impact: Provides randomized evidence for a low-cost, widely available adjunct that modulates inflammatory markers in sepsis, motivating larger trials focused on clinical outcomes.
Clinical Implications: Curcumin–piperine may be considered as an adjunct in research settings to modulate inflammation, but current evidence does not justify routine use to improve survival or organ failure outcomes.
Key Findings
- Double-blind RCT (n=66) in ICU sepsis: mortality 10/33 vs 12/33 (no significant difference).
- Significant reductions vs placebo in total/direct bilirubin (P=0.02), CRP (P=0.04), ESR (P<0.001), pH (P<0.001), and platelet count (P=0.01).
- Smaller declines in RBC, hemoglobin, and hematocrit; higher MCH and MCHC in the intervention group.
Methodological Strengths
- Double-blind randomized controlled design with intention-to-treat analysis.
- Pre-specified 7-day supplementation and standardized dosing with enteral feeding.
- Registered clinical trial (IRCT20150613022681N4).
Limitations
- Small single-trial sample with limited power for mortality and clinical endpoints.
- Short intervention period (7 days) and surrogate outcomes predominate.
- No detailed adverse event profile beyond laboratory indices in the abstract.
Future Directions: Larger multicenter RCTs powered for mortality/organ failure, with pharmacokinetic–pharmacodynamic assessments and safety profiling.
BACKGROUND: Sepsis, an organ dysfunction caused by deregulated host response to infection, is a major health problem worldwide. Sepsis is associated with high rates of mortality, especially in critically ill patients. Curcumin may improve sepsis through its anti-inflammatory and antioxidant effects. This study aimed to investigate the effects of curcumin-piperine administration in critically ill septic patients. METHOD: This double-blind randomized controlled trial (RCT) conducted on 66 patients with sepsis hospitalized in the intensive care unit (ICU). Patients were randomized to either the intervention group receiving two tablets of curcumin-piperine (each containing 500 mg curcuminoids and 5 mg piperine) (n = 33), or the placebo group receiving two matched tablets of placebo (n = 33) daily for 7 consecutive days along with enteral feeding. Clinical, laboratory, and biochemical indices were evaluated before and after the intervention. Statistical analyses were performed based on an intention-to-treat method. RESULT: Mortality was observed in 10 patients in the curcumin-piperine group, and 12 patients in the control group. Curcumin-piperine significantly reduced bilirubin-total (P = 0.02), bilirubin-direct (P = 0.02), pH (P < 0.001), C-reactive protein (P = 0.04), erythrocyte sedimentation rate (P < 0.001), and platelet count (P = 0.01) compared with the placebo. A significantly lower reduction was found in red blood cell (P = 0.003), hemoglobin (P = 0.001), and hematocrit (P = 0.002) levels in the intervention vs. placebo group. In addition, mean corpuscular hemoglobin (P < 0.001) and mean corpuscular hemoglobin concentration (P = 0.001) were significantly higher in the intervention vs. placebo group. CONCLUSION: Curcumin-piperine supplementation over a short period had beneficial effects on some inflammatory and laboratory indices in critically ill patients with sepsis. TRIAL REGISTRATION: IRCT20150613022681N4; available on: https://en.irct.ir/trial/52661 . Registration date: 2021-01-02, 1399/10/13.