Summary:
This comprehensive review discusses the multifaceted nature of sepsis, emphasizing its high mortality and complex management, spanning early recognition, acute intervention, and long-term rehabilitation. Post-sepsis syndrome (PSS) represents a critical challenge with sustained immune dysregulation, chronic inflammation, and metabolic dysfunction leading to recurrent infections, cardiovascular disease, and neurocognitive impairment. The review underscores mitochondrial dysfunction, immunological changes, organ-specific impacts, and the necessity of precision medicine, artificial intelligence, and integrated care strategies to enhance patient outcomes.
Key Points
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Sepsis Pathophysiology and Management: Sepsis is characterized by dysregulated host responses to infection, involving inflammation, immune dysfunction, and metabolic reprogramming, necessitating timely antimicrobial therapy, hemodynamic support, and structured rehabilitation.
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Post-Sepsis Syndrome (PSS): PSS includes long-term immune dysregulation, chronic inflammation, and metabolic dysfunction, significantly impacting survivors through heightened vulnerability to recurrent infections, cardiovascular complications, and neurocognitive decline.
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Immune Dysfunction in PSS: Persistent immunosuppression post-sepsis arises from alterations in leukocyte function, cytokine production, and antigen presentation, significantly reducing resistance to subsequent infections and contributing to chronic inflammation.
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Mitochondrial and Metabolic Dysfunction: Mitochondrial impairment during sepsis exacerbates metabolic disturbances, leading to reduced cellular energy availability, amplifying organ damage and perpetuating immune incompetence.
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Cardiovascular Complications: Sepsis survivors face increased cardiovascular risks, including myocardial dysfunction mediated by inflammatory cytokines (e.g., TNF-α, IL-6) and accelerated vascular aging, elevating the likelihood of long-term adverse cardiovascular events.
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Neurological Impact: Sepsis-induced brain dysfunction involves neuroinflammation, blood-brain barrier (BBB) disruption, oxidative stress, and accumulation of neurotoxic proteins (amyloid β and tau), resulting in long-term cognitive deficits and increased dementia risk.
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Renal Dysfunction (SA-AKI): Sepsis-associated acute kidney injury (SA-AKI) frequently progresses to chronic kidney disease, driven by persistent microvascular damage, chronic inflammation, and maladaptive repair mechanisms involving podocyte dysfunction.
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Innovations in Diagnostic and Therapeutic Approaches: Recent advances, including transcriptomic profiling, immune stratification (SRS1 and IDS endotypes), machine learning applications, and precision biomarkers (e.g., pentraxin-3, MR-proADM), enhance sepsis diagnosis, prognosis, and personalized treatment strategies.
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Rehabilitation in Sepsis Survivors: Structured rehabilitation focusing on physical therapy and nutritional support can potentially improve quality of life, although evidence for reducing mortality and enhancing physical recovery remains limited, necessitating further research.
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Guideline Adherence Challenges: Despite well-defined international guidelines, adherence is limited by healthcare provider variability, resource constraints, and infrastructural challenges, especially in low-resource settings, highlighting the need for enhanced training, protocol standardization, and integrated care networks.
Conclusion
Addressing sepsis comprehensively requires a coordinated, multidisciplinary approach spanning early detection, targeted acute interventions, structured rehabilitation, and continuous long-term care. Emphasis on improving adherence to guidelines, harnessing advanced diagnostic technologies, and developing personalized therapeutic strategies is critical to reducing mortality and enhancing quality of life for sepsis survivors.
Watch the following video on “World Sepsis Day 2024” by Intensive Care Society
Copyright © 2025 Torres, Tamayo-Giraldo, Bejarano-Zuleta, Nati-Castillo, Quintero, Ospina-Mejía, Salazar-Santoliva, Suárez-Sangucho, Ortiz-Prado and Izquierdo-Condoy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
