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Septic shock

Septic shock is a potentially fatal medical condition that occurs when sepsis, which is defined as an abnormal immune response to infection that leads to life-threatening organ dysfunction, leads to dangerously low blood pressure and abnormalities in cellular and metabolic dysfunction. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defines septic shock as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock are cared for in the emergency department and intensive care units.

Causes
Septic shock is a result of a systemic response to infection or multiple infectious causes. Interestingly, pneumonia is the most common cause of sepsis. Indwelling devices, such as pacemakers or knee replacements can also lead to sepsis. Severe infections, such as meningitis, encephalitis, and endocarditis are also causes of sepsis. All together indwelling devices and severe infections make up 1 percent of sepsis cases. Bacteria are the microorganisms responsible for a majority of cases of sepsis. ==Pathophysiology==
Pathophysiology
The pathophysiology of septic shock is not entirely understood, but it is known that a key role in the development of severe sepsis is played by an immune and coagulation response to an infection. Both pro-inflammatory and anti-inflammatory responses play a role in septic shock. Septic shock involves a widespread inflammatory response that produces a hypermetabolic effect. This is manifested by increased cellular respiration, protein catabolism, and metabolic acidosis with a compensatory respiratory response. Both gram positive and gram negative bacteria are the most common causes of septic shock. Gram-positive In gram-positive bacteria, these are exotoxins or enterotoxins, which may vary depending on the species of bacteria. These are divided into three types. Gram-negative In gram-negative sepsis, a free LPS attaches to a circulating LPS-binding protein, and the complex then binds to the CD14 receptor on monocytes, macrophages, and neutrophils. Engagement of CD14 (even at doses as minute as 10 pg/mL) results in intracellular signaling via an associated "Toll-like receptor" protein 4 (TLR-4). This results in significant activation of mononuclear cells and synthesis of effector cytokines such as IL-1, IL-6, and TNF-α. TLR-mediated activation helps to trigger the innate immune system to efficiently eradicate invading microbes, but the cytokines they produce also act on endothelial cells. The effects of the cytokines may be amplified by TLR-4 engagement on endothelial cells. This is called compensatory anti-inflammatory response syndrome (CARS). Both the inflammatory and anti-inflammatory reactions are responsible for the course of sepsis and are described as MARS (Mixed Antagonist Response Syndrome). The ability of TLR4 to respond to a distinct LPS species is clinically important. Pathogenic bacteria may employ LPS with low biological activity to evade proper recognition by the TLR4/MD-2 system, dampening the host immune response and increasing the risk of bacterial dissemination. ==Diagnosis==
Diagnosis
Definitions Sepsis is the precipitating condition to septic shock, hence the diagnostic criteria for sepsis are pertinent to the diagnosis of septic shock. There are three different systems to diagnosis sepsis. The most recent gathering of professionals to discuss the topic of sepsis was called "sepsis-3" and set forth the latest guidelines for the diagnosis and management of sepsis. SIRS The SIRS criteria were recently excluded from sepsis-3, but are still the most used diagnostic tool for identifying sepsis. A patient that meets SIRS criteria has a possible, or documented, source of infection plus at least two or more of the criteria listed below. • Tachypnea (fast rate of breathing), which is defined as more than 20 breaths per minute, or when testing blood gas, a PaCO2| less than 32 mm Hg, which signifies hyperventilation • White blood cell count either significantly low (3), or elevated (> 12000 cells/mm3) • Tachycardia (rapid heart rate), which in sepsis is defined as a rate greater than 90 beats per minute • Altered body temperature: Fever > or hypothermia < Documented evidence of infection may include positive blood culture, signs of pneumonia on chest x-ray, or other radiologic or laboratory evidence of infection. Signs of end-organ dysfunction are present in septic shock, including kidney failure, liver dysfunction, changes in mental status, or elevated serum lactate. One limitation of the SIRS criteria is that it can be present in many non-infectious conditions, such as autoimmune conditions, pancreatitis, recent surgery, or vasculitis. qSOFA and SOFA qSOFA is another set of criteria used to diagnose sepsis and help clinicians identify sepsis in settings other than the ICU. SOFA criteria is used in critically ill patients and assesses the severity of dysfunction in the 6 organ systems. At the time of ICU admission the score is calculated as the baseline. After this the score is calculated every 48 hours. Septic shock refers specifically to distributive shock due to sepsis as a result of infection. However, in recent years, it has been found that hypotension is a later manifestation of septic shock. Specifically, lack of blood flow to the tissue (tissue hypoperfusion) has been found to occur well before hypotension in cases of septic shock. Therefore, a lactate measurement has become an integral part to the diagnosis of septic shock. A lactate level of 18 mg/dL (or 2 mmol per L) is diagnostic for septic shock according to sepsis-3. In particular, fever can be absent in immunocompromised patients, older patients, and patients with chronic alcohol abuse. Musculoskeletal Joint pains, mylagias, edema, weakness, and crepitus. Genitourinary Dysuria, hematuria, frequency, costovertebral angle tenderness, pyuria, vaginal bleeding, and vaginal discharge. Dermatologic Petechiae, bullous lesions, erythema, rash, splinter hemorrhages, bruising, and purulent lesions. Diagnostic tools Imaging Chest X-rays are typically indicated for every case of sepsis as pneumonia is the most common cause of sepsis. CT scans of the chest can also be used when empyema or infectious effusions are suspected. CT scans of other areas of the body can be used if abscesses are suspected. Laboratory testing A large amount of laboratory tests are indicated when sepsis is suspected. In terms of cultures, typically clinicians order two sets of peripheral blood cultures, urine cultures, stool cultures, sputum, and skin cultures. Sepsis biomarkers The two main biomarkers used for sepsis and septic shock are lactate and procalcitonin. A procalcitonin level of 0.05 ng/mL is considered normal and patients with procalcitonin levels less than 0.25 ng/mL have low likelihood of sepsis. Several studies have shown that the severity of sepsis and the procalcitonin levels have a statistically significant relationship. ==Treatment==
Treatment
Treatment primarily consists of the following: • Giving intravenous fluids • Early antibiotic administration Fluid balance can be assessed in many ways such as, dynamic blood pressure response, urine output (should be greater than 0.5 mL per hour), lactate clearance, ultrasound of the inferior vena cava, passive leg raise, and pulse pressure variation. At 72 hours patients should ideally have a fluid balance of zero. De-escalation of antibiotic therapy is controversial and no consensus has been reached in the literature. Typically most patients can be effectively treated with 7–10 days of antibiotic therapy. If the patient has an allergy to beta-lactams, one can administer vancomycin, moxifloxacin, and trimethoprim/sulfamethoxazole (TMP-SMX). For community-acquired pneumonia with risk for drug resistance or hospital-acquired pneumonia, a fluoroquinolone can be given, or zoysn, or cefepime, or carbapenem. If a necrotizing infection is suspected then a carbapenem with vancomycin and clindamycin is recommended and surgery should also be consulted. Intrabdominal infections Can administer zoysn, or carbapenem, or primaxin, or flagyl. If the patient has a beta lactam allergy then vancomycin with aztreonam and metronidazole can be given. Surgery should also be consulted in cases of intrabdominal infection. If the patient is neutropenic with septic shock, pneumonia, has an infected venous catheter, skin and soft-tissue infection, gram-positive bacteremia, or mucositis then vancomycin should be added. It has also been shown that the mortality of patients with septic shock increases by 5% per hour that the vasopressor is not given. If the placement of a central venous catheter is delayed then norepinephrine can be given through a peripheral IV. In more recent years it has been shown, however, that giving vasopressors through a peripheral IV is safe for short-term use and offers practical advantages. The most common regimen of corticosteroids for patients with septic shock is 200–300 mg/ day of hydrocortisone for 5–7 days. However, it has also been shown that β-blockers can increase the duration that patients would need to be on vasopressors. There are multiple meta-analyses that suggest that methylene blue could reduce mortality in cases of septic shock. Methylene blue has also been shown to reduce time to vasopressor discontinuation, length of ICU stay, and mechanical ventilation duration. ==Epidemiology==
Epidemiology
Sepsis has a worldwide incidence of more than 49 million cases a year, with 11 million sepsis-related deaths per year. Septic shock has a mortality rate of 40 percent despite advances in care. The in-hospital mortality for septic shock specifically has been shown to increase 1.8% for each additional hour that antibiotics are not administered after the patient has arrived in the emergency department. ==References==
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