Practice Essentials
Severe sepsis or septic shock is systemic inflammatory response syndrome (SIRS) secondary to a documented infection and arterial hypotension with some evidence of organ dysfunction. This response is a state of acute circulatory failure characterized by persistent arterial hypotension despite adequate fluid resuscitation or by tissue hypoperfusion (manifested by a lactate concentration >4 mg/dL) unexplained by other causes. See the image below.
Venn diagram showing the overlap of infection, bac
Venn diagram showing the overlap of infection, bacteremia, sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction.
Essential update: Study suggests lower hemoglobin transfusion threshold yields similar outcomes in septic shock
In a randomized clinical trial, adults with septic shock (N=998) in 32 intensive care units (ICUs) were randomized to a transfusion hemoglobin threshold of 7 g/dL or 9 g/dL.[1] Outcomes among patients receiving blood transfusion at the higher hemoglobin threshold were similar to those among patients receiving blood transfusion at the lower threshold but with fewer transfusions.
At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P =0.44).[1] The numbers of patients who had ischemic events, patients who had severe adverse reactions, and patients who required life support were similar in the two intervention groups.
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
Confusion
Anxiety
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
Skin infections – Petechiae, purpura, erythema, ulceration, bullous formation, fluctuance
See Clinical Presentation for more detail.
Diagnosis
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.
Laboratory tests
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
Imaging studies
The following radiologic studies, as indicated, may be used to evaluate patients with suspected severe sepsis and septic shock:
Chest, abdominal, or extremity radiography
Abdominal ultrasonography
Computed tomography of the abdomen or head
See Workup for more detail.
Management
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)
Pharmacotherapy
The following medications are 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)
Surgery
Patients with focal infections should be sent for definitive surgical treatment after initial resuscitation and administration of antibiotics.[2] 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.[2]
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.[2] However, any deep abscess or suspected necrotizing fasciitis should undergo drainage in the surgical suite.
See Treatment and Medication for more detail.
Background
Over many years, the terms sepsis and septicemia have referred to several ill-defined clinical conditions present in a patient with bacteremia. Definitions have not changed greatly since 1914, when Schottmueller wrote, “Septicemia is a state of microbial invasion from a portal of entry into the blood stream which causes sign of illness.”
In practice, these 2 terms have often been used interchangeably; however, only about half of patients with signs and symptoms of sepsis have positive results on blood culture.[3, 4, 5] Furthermore, not all patients with bacteremia have signs of sepsis. It follows, therefore, that sepsis and septicemia are not in fact identical.
In the past few decades, the discovery of endogenous mediators of the host response has led to the recognition that the clinical syndrome of sepsis is the result of excessive activation of host defense mechanisms rather than the direct effect of microorganisms. Sepsis and its sequelae represent a continuum of clinical and pathophysiologic severity.
Serious bacterial infections at any site in the body (see the image below), with or without bacteremia, are usually associated with important changes in the function of every organ system in the body. These changes are mediated mostly by elements of the host immune system against infection. Shock is deemed present when volume replacement fails to increase blood pressure to acceptable levels and when associated clinical evidence indicates inadequate perfusion of major organ systems, with progressive failure of organ system functions. Although hyperlactecemia is commonly seen in severe sepsis, its relationship to hypoperfusion is questionable and is more often due to the acute inflammatory state, impaired lactate clearance, and nonoxidative phosphorylation lactate production.
Strawberry tongue in a child with staphylococcal t
Strawberry tongue in a child with staphylococcal toxic shock syndrome. Reproduced with permission from Drage, LE. Life-threatening rashes: dermatologic signs of four infectious diseases. Mayo Clin P