Advances and Challenges in Sepsis Management: Modern Tools and Future Directions

Abstract

Sepsis, a critical condition marked by systemic inflammation, profoundly impacts both innate and adaptive immunity, often resulting in lymphopenia. This immune alteration can spare regulatory T cells (Tregs) but significantly affects other lymphocyte subsets, leading to diminished effector functions, altered cytokine profiles, and metabolic changes. The complexity of sepsis stems not only from its pathophysiology but also from the heterogeneity of patient responses, posing significant challenges in developing universally effective therapies. This review emphasizes the importance of phenotyping in sepsis to enhance patient-specific diagnostic and therapeutic strategies. Phenotyping immune cells, which categorizes patients based on clinical and immunological characteristics, is pivotal for tailoring treatment approaches. Flow cytometry emerges as a crucial tool in this endeavor, offering rapid, low cost and detailed analysis of immune cell populations and their functional states. Indeed, this technology facilitates the understanding of immune dysfunctions in sepsis and contributes to the identification of novel biomarkers. Our review underscores the potential of integrating flow cytometry with omics data, machine learning and clinical observations to refine sepsis management, highlighting the shift towards personalized medicine in critical care. This approach could lead to more precise interventions, improving outcomes in this heterogeneously affected patient population.

Inflammaging in Multidrug-Resistant Sepsis of Geriatric ICU Patients and Healthcare Challenges

“…Moreover, tailoring treatment for geriatric ICU patients requires a nuanced approach, focusing on individualized therapy guided by clinical management strategies. Consideration of patient-specific conditions is paramount, especially in cases of MDR sepsis where comorbidities play a crucial role in treatment outcomes [89]. For instance, conditions such as diabetes can compromise immune function, while renal or hepatic dysfunction may affect drug metabolism, and immunosuppression heightens susceptibility to infections [90].…”

Revolution in sepsis: a symptoms-based to a systems-based approach?

“…To highlight the lethality of MODS during sepsis, the 2023 guidelines redefined sepsis as “life-threatening organ dysfunction resulting from a dysregulated host response to infection” [ 143 ]. In 1975, Arthur Bauer introduced the term MODS as multiple physiological derangements [ 8 ].…”

“…Notwithstanding the ongoing challenges in treating sepsis, great strides are being made in personalized care based on blood biomarkers [ 143 ]. Individualized treatments have also progressed in the chronic, immunosuppressive stage of sepsis responsible for later-stage morbidity and mortality [ 143 ].…”

“…Of those who die, most are from multiple organ failure which is a still poorly understood consequence rather than the immediate effect of infection. Coccolini and colleagues (2023) [27] To highlight the lethality of MODS during sepsis, the 2023 guidelines redefined sepsis as "life-threatening organ dysfunction resulting from a dysregulated host response to infection" [143]. In 1975, Arthur Bauer introduced the term MODS as multiple physiological derangements [8].…”

“…Clinical study of antiinflammation strategies to treat sepsis has been characterized by a predictable cycle of abundant clinical failures punctuated by an intermittent positive result. Shapiro and colleagues (2023) [149,150] Notwithstanding the ongoing challenges in treating sepsis, great strides are being made in personalized care based on blood biomarkers [143]. Individualized treatments have also progressed in the chronic, immunosuppressive stage of sepsis responsible for later-stage morbidity and mortality [143].…”