Sepse

In acute respiratory distress syndrome (ARDS), increased pulmonary vascular permeability makes the lung vulnerable to edema. The use of conservative as compared to liberal fluid strategies may increase the number of ventilator-free days and survival, as well as reduce organ dysfunction. Monitoring the effects of fluid administration is of the utmost importance; dynamic indexes, such as stroke volume and pulse pressure variations, outperform static ones, such as the central venous pressure. The passive leg raise and end-expiratory occlusion tests are recommended for guiding fluid management decisions...

Sepsis is a life-threatening organ dysfunction that results from the body's response to infection. It requires prompt recognition, appropriate antibiotics, careful hemodynamic support, and control of the source of infection. With the trend in management moving away from protocolized care in favor of appropriate usual care, an understanding of sepsis physiology and best practice guidelines is critical.

BACKGROUND: Several studies were published to validate the quick Sepsis-related Organ Failure Assessment (qSOFA), namely in comparison with the systemic inflammatory response syndrome (SIRS) criteria. We performed a systematic review and meta-analysis with the aim of comparing the qSOFA and SIRS in patients outside the ICU. METHODS: We searched MEDLINE, CINAHL, and the Web of Science database from February 23, 2016 until June 30, 2017 to identify full-text English-language studies published after the Sepsis-3 publication comparing the qSOFA and SIRS and their sensitivity or specificity in diagnosing sepsis, as well as hospital and ICU length of stay and hospital mortality...

BACKGROUND: Whether hydrocortisone reduces mortality among patients with septic shock is unclear. METHODS: We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days. RESULTS: From March 2013 through April 2017, a total of 3800 patients underwent randomization...

The word, sepsis, dates back more than 2 millennia but has, over the past 2 centuries, come to be applied first to the clinical state evoked by invasive infection and, more recently, to describe the syndrome resulting from the host response to infection. Further refinements embodied in the recently published Sepsis-3 definition underline the concept of a dysregulated immune response resulting in potentially modifiable life-threatening organ dysfunction. This review summarizes the evolution and limitations of efforts to characterize a common and complex disorder...

Sepsis is characterized by early massive catabolism, lean body mass (LBM) loss, and escalating hypermetabolism persisting for months to years. Early enteral nutrition should attempt to correct micronutrient/vitamin deficiencies, deliver adequate protein and moderated nonprotein calories, as well-nourished patients can generate reasonable endogenous energy. After resuscitation, increasing protein/calories are needed to attenuate LBM loss and promote recovery. Malnutrition screening is essential, and parenteral nutrition can be safely added when enteral nutrition is failing based on preillness malnutrition...

Sepsis results in many deaths, prolonged suffering among survivors and relatives, and high use of resources both in developed and developing countries. The updated Surviving Sepsis Campaign guidelines should aid clinicians in improving the identification and management of these patients, but many uncertainties remain because most of the guidance is based on low-quality evidence. This article discusses how to use some of the specific items of the guidelines together with a common-sense approach to aid clinical management of patients with sepsis while trying to balance the potential benefit and harm of the items...

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...

Sepsis is a global public health concern. Internationally it contributes to more than 5 million deaths annually. Although rates are variable between countries, over the past 40 years reported incidence has continued to increase. Aside from potential differences in patient populations, the variation in reported rates also reflects differences in identification strategies, access to health care, and awareness of the diagnosis. Factors such as age, sex, socioeconomic status, comorbid disease, and type and site of infection impact the development of and outcomes from sepsis...

Sepsis describes a broad-based syndrome covering many infectious agents, affecting various sites in patients of differing age, gender, and comorbidity and resulting in varying degrees and combinations of organ dysfunction. Protocolized care with rigid goals may suit populations, assuming the evidence-lite recommendations are beneficial, but not necessarily individual patients. A personalized approach to management is rational and preferable. Other than clinical heterogeneity, a range of biological signatures exist in sepsis, and these fluctuate over the disease course...

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...

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...

It is now well established that profound immunosuppression develops within a few days after sepsis onset in patients. This should be considered additional organ failure because it is associated with increased rate of nosocomial infections, mortality, and long-term complications, thus constituting the rationale for immunomodulation in patients. Nevertheless, the demonstration of the efficacy of such therapeutic strategy in improving deleterious outcomes in sepsis remains to be made. Results from clinical trials based on interleukin 7 and granulocyte macrophage colony-stimulating factor immunoadjuvant therapies in septic shock patients are expected for 2018...

Sepsis induces profound neuroendocrine and metabolic alterations. During the acute phase, the neuroendocrine changes are directed toward restoration of homeostasis, and also limit unnecessary energy consumption in the setting of restricted nutrient availability. Such changes are probably adaptive. In patients not recovering quickly, a prolonged critically ill phase may ensue, with different neuroendocrine changes, which may represent a maladaptive response. Whether stress hyperglycemia should be aggressively treated or tolerated remains a matter of debate...

Sepsis-associated organ dysfunction involves multiple responses to inflammation, including endothelial and microvascular dysfunction, immune and autonomic dysregulation, and cellular metabolic reprogramming. The effect of targeting these mechanistic pathways on short- and long-term outcomes depends highly on the timing of therapeutic intervention. Furthermore, there is a need to understand the adaptive or maladaptive character of these mechanisms, to discover phase-specific biomarkers to guide therapy, and to conceptualize these mechanisms in terms of resistance and tolerance...

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. Hypovolemia is common and crystalloid is recommended for fluid resuscitation...

Sepsis is caused by a dysregulated host response to infection. Immune responses determine the characteristics of sepsis. The body's protection against infection involves danger signal surveillance and recognition from nonself, effector functions in response to sensing danger signals, homeostatic regulation, and generation of immunologic memory. During sepsis, the immune system is activated by pathogen-associated and host-derived molecular patterns. Detecting these molecular patterns generates multisystem responses...

Among the critically ill, infectious diseases can play a significant role in the etiology of neuropsychiatric disturbances. All critical care physicians are familiar with delirium as a secondary complication of systemic infection. This article focuses on key infectious diseases that commonly and directly produce neuropsychiatric symptoms, including direct infection of the central nervous system, human immunodeficiency virus infection, and AIDS.