Sepsis, a complex physiological and metabolic response to infection, is a common reason for admission to an intensive care unit. The first article in our Critical Care Medicine review series examines the basis, diagnosis, and current treatment of this disorder.
In 1992, an international consensus panel defined sepsis as a systemic inflammatory response to infection, noting that sepsis could arise in response to multiple infectious causes and that septicemia was neither a necessary condition nor a helpful term. Instead, the panel proposed the term “severe sepsis” to describe instances in which sepsis is complicated by acute organ dysfunction, and they codified “septic shock” as sepsis complicated by either hypotension that is refractory to fluid resuscitation or by hyperlactatemia.
• What is the most common cause of severe sepsis, and what organisms are most often implicated?
Severe sepsis occurs as a result of both community-acquired and health care-associated infections. Pneumonia is the most common cause, accounting for about half of all cases, followed by intraabdominal and urinary tract infections. Staphylococcus aureus and Streptococcus pneumoniae are the most common gram-positive isolates, whereas Escherichia coli, klebsiella species, and Pseudomonas aeruginosa predominate among gram-negative isolates. An epidemiologic study of sepsis showed that during the period from 1979 to 2000, gram-positive infections overtook gram-negative infections. However, in a more recent study involving 14,000 ICU patients in 75 countries, gram-negative bacteria were isolated in 62% of patients with severe sepsis who had positive cultures, gram-positive bacteria in 47%, and fungi in 19%.
• What are the risk factors for severe sepsis?
Risk factors for severe sepsis are related both to a patient’s predisposition for infection and to the likelihood of acute organ dysfunction if infection develops. There are many well-known risk factors for the infections that most commonly precipitate severe sepsis and septic shock, including chronic diseases (e.g., the acquired immunodeficiency syndrome, chronic obstructive pulmonary disease, and many cancers) and the use of immunosuppressive agents. Among patients with such infections, however, the risk factors for organ dysfunction are less well studied but probably include the causative organism and the patient’s genetic composition, underlying health status, and preexisting organ function, along with the timeliness of therapeutic intervention. Age, sex, and race or ethnic group all influence the incidence of severe sepsis, which is higher in infants and elderly persons than in other age groups, higher in males than in females, and higher in blacks than in whites.
Morning Report Questions
Q: What are common clinical manifestations of severe sepsis?
A: The signs of both infection and organ dysfunction may be subtle, and thus the most recent international consensus guidelines provide a long list of warning signs of incipient sepsis. Acute organ dysfunction most commonly affects the respiratory and cardiovascular systems. Respiratory compromise is classically manifested as the acute respiratory distress syndrome (ARDS), which is defined as hypoxemia with bilateral infiltrates of noncardiac origin. Cardiovascular compromise is manifested primarily as hypotension or an elevated serum lactate level. After adequate volume expansion, hypotension frequently persists, requiring the use of vasopressors, and myocardial dysfunction may occur. The brain and kidneys are also often affected. Central nervous system dysfunction is typically manifested as obtundation or delirium. Imaging studies generally show no focal lesions, and findings on electroencephalography are usually consistent with nonfocal encephalopathy. Critical illness polyneuropathy and myopathy are also common, especially in patients with a prolonged ICU stay. Acute kidney injury is manifested as decreasing urine output and an increasing serum creatinine level and frequently requires treatment with renal-replacement therapy. Paralytic ileus, elevated aminotransferase levels, altered glycemic control, thrombocytopenia and disseminated intravascular coagulation, adrenal dysfunction, and the euthyroid sick syndrome are all common in patients with severe sepsis.
Q: What are the principles of treatment of severe sepsis?
A: Intravenous antibiotic therapy should be started as early as possible and should cover all likely pathogens. It has not been determined whether combination antimicrobial therapy produces better outcomes than adequate single-agent antibiotic therapy in patients with severe sepsis. Current guidelines recommend combination antimicrobial therapy only for neutropenic sepsis and sepsis caused by pseudomonas species. Empirical antifungal therapy should be used only in patients at high risk for invasive candidiasis. After the first 6 hours, attention focuses on monitoring and support of organ function, avoidance of complications, and de-escalation of care when possible. De-escalation of initial broad-spectrum therapy may prevent the emergence of resistant organisms, minimize the risk of drug toxicity, and reduce costs, and evidence from observational studies indicates that such an approach is safe. The only immunomodulatory therapy that is currently advocated is a short course of hydrocortisone (200 to 300 mg per day for up to 7 days or until vasopressor support is no longer required) for patients with refractory septic shock. This recommendation is supported by a recent meta-analysis, but the two largest studies had conflicting results, and other clinical trials are ongoing.