Abstract
Within patients with sepsis, there exists significant heterogeneity, and while all patients should receive conventional therapy, there are subgroups of patients who may benefit from specific therapies, often referred to as rescue therapies. Therefore, the identification of these specific patient subgroups is crucial and lays the groundwork for the application of precision medicine based on the development of targeted interventions. Over the years, efforts have been made to categorize sepsis into different subtypes based on clinical characteristics, biomarkers, or underlying mechanisms. For example, sepsis can be stratified into different phenotypes based on the predominant dysregulated host response. These phenotypes can range from hyperinflammatory states to immunosuppressive states and even mixed phenotypes. Each phenotype may require different therapeutic approaches to improve patient outcomes. Rescue strategies for septic shock may encompass various interventions, such as immunomodulatory therapies, extracorporeal support (e.g., ECMO), or therapies targeted at specific molecular or cellular pathways involved in the pathophysiology of sepsis. In recent years, there has been growing interest in precision medicine approaches to sepsis and phenotype identification. Precision medicine aims to tailor treatments to each individual patient based on their unique characteristics and disease mechanisms.
Key Points
- Sepsis Heterogeneity and Precision Medicine: Sepsis encompasses diverse clinical presentations, requiring precision medicine approaches that stratify patients based on biomarkers, immune response, and organ dysfunction to optimize treatment strategies.
- Sepsis Phenotypes and Targeted Therapies: Sepsis is increasingly categorized into hyperinflammatory and hypoinflammatory phenotypes, guiding the use of immunomodulatory therapies, such as cytokine adsorption, interferon-gamma, or IL-1 inhibitors, tailored to patient-specific immune dysfunction.
- Rescue Therapies in Septic Shock: Patients with refractory septic shock may benefit from advanced interventions like extracorporeal membrane oxygenation (ECMO), hemoadsorption, or endothelial-stabilizing therapies, depending on their hemodynamic profile and inflammatory state.
- Hemoadsorption and Cytokine Removal: Technologies like polymyxin-B hemoperfusion and CytoSorb aim to mitigate excessive inflammation by filtering endotoxins and cytokines from circulation, though their efficacy remains debated in clinical trials.
- Vasopressor Strategies and Catecholamine Resistance: Personalized vasopressor management is essential, with alternatives like vasopressin and angiotensin-II offering benefits in patients resistant to norepinephrine, particularly those with persistent hypotension and high renin levels.
- Immunoparalysis and Immune Restoration: Immunoparalysis, characterized by monocyte dysfunction and low HLA-DR expression, increases the risk of secondary infections and mortality. Recombinant interferon-gamma and immune checkpoint inhibitors are being explored as potential interventions.
- Endothelial Dysfunction and Microvascular Injury: Sepsis-induced endothelial damage leads to capillary leak, organ failure, and disseminated intravascular coagulation (DIC). Biomarkers such as adrenomedullin and soluble TREM-1 are emerging as potential therapeutic targets.
- Thrombocytopenia-Associated Multiple Organ Failure (TAMOF): TAMOF, characterized by microvascular thromboses and platelet consumption, requires early recognition and may respond to therapeutic plasma exchange (TPE) in severe cases.
- Corticosteroid and Metabolic Resuscitation: Hydrocortisone remains a debated adjunct in septic shock, with potential benefits in catecholamine-resistant hypotension. Vitamin C, often combined with thiamine and corticosteroids, has shown mixed results in recent trials.
- Future Directions in Sepsis Management: Ongoing research focuses on refining sepsis phenotyping, identifying novel biomarkers, and developing personalized treatment algorithms to improve survival and reduce organ failure in septic patients.
