Sepsis is defined as life-threatening organ dysfunction due to dysregulated host response to infection, and organ dysfunction is defined as an acute change in total Sequential Organ Failure Assessment (SOFA) score greater than 2 points secondary to the infection cause.  Septic shock occurs in a subset of patients with sepsis and comprises of an underlying circulatory and cellular/metabolic abnormality that is associated with increased mortality. Septic shock is defined by persisting hypotension requiring vasopressors to maintain a mean arterial pressure of 65 mm Hg or higher and a serum lactate level greater than 2 mmol/L (18 mg/dL) despite adequate volume resuscitation.  This new 2016 definition, also called Sepsis-3, eliminates the requirement for the presence of systemic inflammatory response syndrome (SIRS) to define sepsis, and it removed the severe sepsis definition. What was previously called severe sepsis is now the new definition of sepsis.
Signs and symptoms
Detrimental host responses to infection occupy a continuum that ranges from sepsis to severe sepsis to septic shock and multiple organ dysfunction syndrome (MODS). The specific clinical features depend on where the patient falls on that continuum.
Signs and symptoms of sepsis are often nonspecific and include the following:
- Fever, chills, or rigors
- Difficulty breathing
- Fatigue, malaise
- Nausea and vomiting
Alternatively, typical symptoms of systemic inflammation may be absent in severe sepsis, especially in elderly individuals.
It is important to identify any potential source of infection. Localizing signs and symptoms referable to organ systems may provide useful clues to the etiology of sepsis and are as follows:
- Head and neck infections – Severe headache, neck stiffness, altered mental status, earache, sore throat, sinus pain/tenderness, cervical/submandibular lymphadenopathy
- Chest and pulmonary infections – Cough (especially if productive), pleuritic chest pain, dyspnea, dullness on percussion, bronchial breath sounds, localized rales, any evidence of consolidation
- Cardiac infections – Any new murmur, especially in patients with a history of injection or IV drug use
- Abdominal and gastrointestinal (GI) infections – Diarrhea, abdominal pain, abdominal distention, guarding or rebound tenderness, rectal tenderness or swelling
- Pelvic and genitourinary (GU) infections – Pelvic or flank pain, adnexal tenderness or masses, vaginal or urethral discharge, dysuria, frequency, urgency
- Bone and soft-tissue infections – Localized limb pain or tenderness, focal erythema, edema, swollen joint, crepitus in necrotizing infections, joint effusions
- Chest, abdominal, or extremity radiography
- Abdominal ultrasonography
- Computed tomography of the abdomen or headSkin infections – Petechiae, purpura, erythema, ulceration, bullous formation, fluctuance
Patients with sepsis may present in a myriad of ways, and a high index of clinical suspicion is necessary to identify subtle presentations. The hallmarks of severe sepsis and septic shock are changes that occur at the microvascular and cellular level and may not be clearly manifested in the vital signs or clinical examination. This process includes diffuse activation of inflammatory and coagulation cascades, vasodilation and vascular maldistribution, capillary endothelial leakage, and dysfunctional utilization of oxygen and nutrients at the cellular level.
Cardiac monitoring, noninvasive blood pressure monitoring, and pulse oximetry are indicated in patients with septic shock.
The following are investigative studies to detect a clinically suspected focal infection, the presence of a clinically occult focal infection, and complications of sepsis and septic shock:
- Complete blood count with differential
- Coagulation studies (eg, prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen levels)
- Blood chemistry (eg, sodium, chloride, magnesium, calcium, phosphate, glucose, lactate)
- Renal and hepatic function tests (eg, creatinine, blood urea nitrogen, bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, albumin, lipase)
- Blood cultures
- Urinalysis and urine cultures
- Gram stain and culture of secretions and tissue
Patients with sepsis, severe sepsis, and septic shock require admission to the hospital. Initial treatment includes support of respiratory and circulatory function, supplemental oxygen, mechanical ventilation, and volume infusion.
Treatment of patients with septic shock has the following major goals:
- Start adequate antibiotics (proper spectrum and dose) as early as possible
- Resuscitate the patient from septic shock by using supportive measures to correct hypoxia, hypotension, and impaired tissue oxygenation (hypoperfusion)
- Identify the source of infection and treat with antimicrobial therapy, surgery, or both (source control)
- Maintain adequate organ system function, guided by cardiovascular monitoring, and interrupt the progression of MODS
Management principles for septic shock include the following:
- Early recognition
- Early and adequate antibiotic therapy
- Source control
- Early hemodynamic resuscitation and continued support
- Proper ventilator management with low tidal volume in patients with acute respiratory distress syndrome (ARDS)
The following medications may be used in the management of septic shock:
- Alpha-/beta-adrenergic agonists (eg, norepinephrine, dopamine, dobutamine, epinephrine, vasopressin, phenylephrine)
- Isotonic crystalloids (eg, normal saline, lactated Ringer solution)
- Volume expanders (eg, albumin)
- Antibiotics (eg, cefotaxime, ticarcillin-clavulanate, piperacillin-tazobactam, imipenem-cilastatin, meropenem, clindamycin, metronidazole, ceftriaxone, ciprofloxacin, cefepime, levofloxacin, vancomycin)
- Corticosteroids (eg, hydrocortisone, dexamethasone)
Patients with focal infections should be sent for definitive surgical treatment after initial resuscitation and administration of antibiotics.  However, although urgent management is indicated for hemodynamically stable patients without evidence of acute organ failure, delay of invasive procedures for as long as 24 hours may be possible if the patient receives very close clinical monitoring and appropriate antimicrobial therapy. 
Certain conditions will not respond to standard treatment for septic shock until the source of infection is surgically removed (eg, intra-abdominal sepsis [perforation, abscesses], empyema, mediastinitis, cholangitis, pancreatic abscesses, pyelonephritis or renal abscess from ureteric obstruction, infective endocarditis, septic arthritis, infected prosthetic devices, deep cutaneous or perirectal abscess, and necrotizing fasciitis).
When possible, percutaneous drainage of abscesses and other well-localized fluid collections is preferred to surgical drainage.  However, any deep abscess or suspected necrotizing fasciitis should undergo drainage in the surgical suit