Sepsis - to Reduce Mortality in the Intensive Care Unit

Sepsis is a severe, life-threatening condition caused by an abnormal host response to infection, which includes systemic inflammation, oxidative stress, and increasing organ dysfunction. It is frequently associated with bacterial, viral, fungal, or parasite infections, as well as non-infectious illnesses like trauma and pancreatitis. It remains a primary cause of mortality in hospitals, with rates nearing 40% in severely ill patients. pathophysiological, excessive cytokine release (e.g., TNFα, IL-6, IL-1β) and reactive oxygen/nitrogen species lead to mitochondrial injury, immunosuppression, and multiple organ failure. Sepsis diagnosis is guided byNEWS2 \& a SOFA score ≥2, hypotension, and elevated lactate, while worsening SOFA scores predict poor outcomes. Standard management focusses on early antibiotic therapy, fluid resuscitation, and vasoactive support. Standard anti-inflammatory methods using steroidal or non-steroidal medicines may show little efficacy to improve the patient's clinical outcomes. Adjunctive antioxidant therapies, including vitamins C and E, NAC, and melatonin, have demonstrated reductions in oxidative stress and organ dysfunction. Nicotinamide (NAM) (vitamin B3), a precursor of NAD+/NADP+ critical for energy metabolism and cellular repair, has emerged as a potential therapeutic candidate due to its ability to attenuate cytokine production, modulate immune responses, and mitigate oxidative damage. Usual dose of NAM (500mg-1500mg per day) is generally safe. A dose of 1000 mg was found to be safe and effective in reducing the circulating inflammatory cytokines showing a good profile as an anti-inflammatory adjunct therapy. Higher than usual NAM dose can increase the likelihood of adverse effects, such as diarrhea, increased liver enzymes (rarely occurring at doses exceeding 3 grams per day), symptoms of thrombocytopenia (including increased bruising and bleeding), and stomach upset. Since the role of NAM as adjunct therapy in sepsis management is not yet established, further large-scale clinical studies are recommended to establish its efficacy and safety in sepsis management. The aim of our study is to evaluate the efficacy and safety of the addition of Nicotinamide (1000mg oral tablet) as an adjunct therapy to improve the outcome of septic patients.

Sepsis is a dysregulated host response to infection that leads to life-threatening organ dysfunction and represents a major healthcare problem. Septic shock is the most severe form, characterized by increased capillary permeability and vasodilation, resulting in hypotension and tissue hypoxia. Early identification and treatment of tissue hypoperfusion are pivotal components of initial resuscitation to limit progression to multiple organ dysfunction and death. The 2021 Surviving Sepsis Guidelines recommend guiding initial resuscitation by targeting decreases in serum lactate levels in patients with elevated lactate. However, although elevated lactate levels may reflect tissue hypoxia, serum lactate is not a direct marker of tissue perfusion. Hyperlactatemia may be attributable to mechanisms other than tissue hypoperfusion, such as accelerated aerobic glycolysis driven by excessive β-adrenergic stimulation or impaired clearance (e.g., in liver failure). The venous-to-arterial carbon dioxide partial pressure difference (CO₂ gap), which is inversely related to cardiac output, has been shown to reflect the adequacy of venous blood flow to remove CO₂ from tissues. The CO₂ gap is closely linked to microcirculatory blood flow during the early resuscitation phase of septic shock and may effectively identify persistent tissue hypoperfusion in shock states. A persistently high CO₂ gap during early resuscitation has been associated with significantly higher 28-day mortality and increased Sequential Organ Failure Assessment (SOFA) scores. Moreover, the CO₂ gap has been shown to respond to changes in cardiac output during inotrope infusion in patients with low blood flow, suggesting that its assessment could be useful for therapeutic adjustments. Therefore, there are compelling arguments to evaluate the usefulness of the CO₂ gap in guiding early resuscitation in patients with septic shock. The investigators postulated that CO₂ gap-guided early resuscitation may be more effective in improving outcomes than lactate-guided resuscitation.

Sepsis is a life-threatening condition caused by the body's dysregulated response to an infection. While corticosteroids are known to help stabilize blood pressure in septic shock, their ability to reduce mortality is still debated. Recent analyses suggest that combining fludrocortisone with hydrocortisone may be more effective at saving lives than hydrocortisone alone. To test this hypothesis, a large, definitive international trial is needed. However, this research proposal is for a smaller pilot study (Phase II) involving 32 critically ill patients. The primary goal of this pilot is to determine the feasibility of conducting the subsequent large-scale trial that would compare hydrocortisone alone against the combination therapy and potentially change medical practice.

This prospective diagnostic accuracy study evaluates the performance of presepsin and C-reactive protein (CRP) as early biomarkers for suspected sepsis in adult burn patients. From January 2021 to December 2022, 370 patients with ≥20% total body surface area burns admitted to the Burn Intensive Care Unit at Hallym University Hangang Sacred Heart Hospital were screened; 221 met inclusion criteria. At each clinical suspicion of sepsis (≥2 SIRS criteria), venous blood was drawn for simultaneous measurement of presepsin (via chemiluminescent immunoassay) and CRP (via immunoturbidimetric assay). Diagnostic accuracy will be quantified by sensitivity, specificity, positive/negative predictive values, and area under the ROC curve. The goal is to determine whether presepsin outperforms CRP for early sepsis detection in severe burn patients.

This prospective observational study aims to investigate the ability of advanced ROTEM analysis using Principal Component Analysis (PCA) to detect early signs of disseminated intravascular coagulation (DIC) and trauma-induced coagulopathy (TIC) in hospitalized patients with sepsis or trauma. Standard coagulation tests and ROTEM measurements will be collected and analyzed in relation to clinical outcomes.

The aim of this study is to investigate if an initial short double dose of beta-lactam antibiotics will reduce mortality in critically ill patients with sepsis.