Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Aug 2024
ReviewEarly Diagnosis of Sepsis: The Role of Biomarkers and Rapid Microbiological Tests.
Sepsis is a medical emergency resulting from a dysregulated response to an infection, causing preventable deaths and a high burden of morbidity. Protocolized and accurate interventions in sepsis are time-critical. Therefore, earlier recognition of cases allows for preventive interventions, early treatment, and improved outcomes. ⋯ There is a lack of a widely available tool enhancing preclinical diagnosis of sepsis. Sophisticated technologies for sepsis prediction have several limitations, including high costs. Novel technologies for fast molecular and microbiological diagnosis are focusing on bedside point-of-care combined testing to reach most settings where sepsis represents a challenge.
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Sepsis manifests as a dysregulated immune response to an infection, leading to tissue damage, organ failure, and potentially death or long-term health issues. Sepsis remains a major health challenge globally, causing approximately 50 million cases and 11 million deaths annually. Early management of sepsis focuses on source control, antimicrobial treatment, and supporting vital organ function. ⋯ Immune modulation is crucial due to the dual nature of sepsis-induced immune responses. Corticosteroids have shown benefits in shock and organ dysfunction reversal and in mortality reduction with current guidelines recommending them in vasopressor therapy-dependent patients. In conclusion, sepsis management beyond the initial hours requires a multifaceted approach, focusing on metabolic, nutritional, and immune system support tailored to individual patient needs to enhance survival and recovery.
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Semin Respir Crit Care Med · Aug 2024
ReviewEpigenetic Mechanisms in Sepsis-Associated Acute Kidney Injury.
Sepsis, the dysregulated immune response of the host to infections, leads to numerous complications, including multiple organ dysfunction with sepsis-associated acute kidney injury (SA-AKI) being a frequent complication associated with increased risk of mortality and the progression toward chronic kidney disease (CKD). Several mechanisms have been widely investigated in understanding the complex pathophysiology of SA-AKI, including hemodynamic alterations, inflammation, oxidative stress, and direct cellular injury driven by pathogens or cell-derived products (pathogen-associated molecular patterns and damage-associated molecular patterns). Despite advancements in the management of septic patients, the prognosis of SA-AKI patients remains significantly poor and is associated with high in-hospital mortality and adverse long-term outcomes. ⋯ At the same time, these modifications are dynamic and reversible processes that can alter gene expression in several pathways implicated in the context of SA-AKI, including inflammation, immune response, and tolerance status. In addition, specific epigenetic modifications may exacerbate renal damage by causing persistent inflammation or cellular metabolic reprogramming, leading to progression toward CKD. This review aims to provide a comprehensive understanding of the epigenetic characteristics that define SA-AKI, also exploring targeted therapies that can improve patient outcomes and limit the chronic progression of this syndrome.
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Semin Respir Crit Care Med · Aug 2024
ReviewManagement of Sepsis in the First 24 Hours: Bundles of Care and Individualized Approach.
Early diagnosis and prompt management are essential to enhance the outcomes of patients with sepsis and septic shock. Over the past two decades, evidence-based guidelines have guided appropriate treatment and recommended the implementation of a bundle strategy to deliver fundamental treatments within the initial hours of care. Shortly after its introduction, the implementation of a bundle strategy has led to a substantial decrease in mortality rates across various health care settings. ⋯ These innovative methodologies have the potential to improve the management of septic shock. However, their implementation in clinical practice should be guided by solid evidence. Therefore, it is imperative that future research evaluate the safety, efficacy, and cost-effectiveness of these strategies.
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Sepsis pathobiology is complex. Heterogeneity refers to the clinical and biological variation within sepsis cohorts. Sepsis subtypes refer to subpopulations within sepsis cohorts derived based on these observable variations and latent features. ⋯ The sepsis subtyping field is just starting to take shape. The current subtypes in the literature do not have a core set of shared features between studies. Thus, in this narrative review, we reason that there is a need to a priori state the purpose of sepsis subtyping and minimum set of features that would be required to achieve the goal of precision immunomodulation for future sepsis.