Critical care clinics
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Sepsis is a global public health concern. Internationally it contributes to more than 5 million deaths annually. ⋯ Factors such as age, sex, socioeconomic status, comorbid disease, and type and site of infection impact the development of and outcomes from sepsis. Although advances have been made in treatment, its impact remains substantial.
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A biomarker is a characteristic by which a (patho)physiologic process can be identified. Biomarkers can be of diagnostic value (to discriminate infection from noninfectious conditions or to determine the causative pathogen), of prognostic value (assigning risk profiles and predict outcome), and in the future may be of theranostic value (aid in selection and monitoring of therapy). Systems biology provides a promising tool for the discovery of novel biomarkers. Biomarkers can be the key to personalized targeted treatment in the future clinical management of sepsis.
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Although acute survival from sepsis has improved in recent years, a large fraction of sepsis survivors experience poor long-term outcomes. In particular, sepsis survivors have high rates of weakness, cognitive impairment, hospital readmission, and late death. To improve long-term outcomes, in-hospital care should focus on early, effective treatment of sepsis; minimization of delirium, distress, and immobility; and preparing patients for hospital discharge. In the posthospital setting, medical care should focus on addressing new disability and preventing medical deterioration, providing a sustained period out of the hospital to allow for recovery.
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Fundamental features of septic shock are vasodilation, increased permeability, hypovolemia, and ventricular dysfunction. Vasodilation owing to increased nitric oxide and prostaglandins is treated with vasopressors (norepinephrine first). Increased permeability relates to several pathways (Slit/Robo4, vascular endothelial growth factor, angiopoietin 1 and 2/Tie2 pathway, sphingosine-1-phosphate, and heparin-binding protein), some of which are targets for therapies. ⋯ Cardiomyocyte-inflammatory interactions decrease contractility and dobutamine is recommended to increase cardiac output. There is benefit in decreasing heart rate in selected patients with esmolol. Ivabradine is a novel agent for heart rate reduction without decreasing contractility.
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Despite decades of sepsis research, no specific therapies for sepsis have emerged and current management still relies on source control, antibiotics, and organ support. With improved understanding of sepsis pathophysiology and the development of new techniques to enable better characterization of patients with sepsis, clinical trials are beginning to better target new interventions at those patients most likely to respond. This article discusses advances in sepsis therapeutics designed to improve endothelial cell function, purify the blood to help restore immune homeostasis, and provide immunostimulation for patients with immune exhaustion.