Epidemiology

In the United States alone, more than 750,000 cases of sepsis occur, and approximately 215,000 deaths result from this disease annually.¹ Over the 25-year period between 1972 and 1997, little change occurred in the mortality rate (ranging from 40% to >60%) for patients with septic shock.² More recent advances in the early treatment of severe sepsis and septic shock have shown improvements in mortality and thus promise for patients and their treating physicians.^3–5

Pathophysiology

Sepsis is defined as a condition in which an identified or suspected source of infection leads to a systemic inflammatory process, known as the systemic inflammatory response syndrome (SIRS) (Box 172.1). Severe sepsis refers to sepsis that has progressed to cellular dysfunction and organ damage or evidence of hypoperfusion, whereas septic shock refers to sepsis with persistent hypotension despite adequate fluid resuscitation. SIRS can develop when an exaggerated response of the body’s immune system to infection results in the release of inflammatory cytokines (tumor necrosis factor-α, interleukin-1, and interleukin-6) as the immune cells encounter the organisms’ endotoxins.⁶ These cytokines can lead to activation of the coagulation cascade with subsequent thrombosis and disseminated intravascular coagulation, as well as the release and activation of nitric oxide, thought to be the key mediator in vasodilation and shock.^4,7 Progression of shock can lead to poor oxygen delivery and use at the tissue level, thereby creating an environment in which lactic acid is generated and mixed venous oxygenation is impaired.

Presenting Signs and Symptoms

The patient with classic severe sepsis or septic shock appears ill, with fever (less commonly hypothermia) and chills, an increased respiratory rate, and tachycardia. Patients may have cold skin showing outward signs of decreased perfusion (Fig. 172.1), and they may have mental status changes.

Fig. 172.1 A and B, Skin mottling.

This patient presented to the emergency department with septic shock and showed extreme signs of hypoperfusion. He underwent early goal-directed therapy and actually survived to discharge from the hospital.

The presentation may or may not direct the clinician to the potential source of infection. For example, dyspnea and crackles on a lung examination may point to a pneumonia source, or left lower quadrant tenderness on an abdominal examination may point to diverticulitis as the source. Determining the site of infection in the emergency department (ED) may be difficult, and even retrospectively, an initial source is not determined in up to 15% of patients (Box 172.2).⁸

More objective measures (SIRS criteria, lactate level, mixed venous oxygenation) are used to determine whether a patient has sepsis because patients can sometimes appear surprisingly well even when they have severe sepsis or septic shock. Their only complaint may be fever, even though other SIRS criteria and hypotension may be present, especially in relatively younger, healthier, immunocompetent patients (see Fig. 172.1).

Differential Diagnosis and Medical Decision Making

The differential diagnosis of sepsis includes many other life-threatening emergencies, including toxidromes (sympathomimetic, anticholinergic), thyrotoxicosis or myxedema coma, neuroleptic malignant syndrome, heat stroke, withdrawal (ethanol, sedative-hypnotics), pulmonary embolism, and other causes of shock (anaphylactic, cardiogenic, hypovolemic).

The diagnostic work-up may vary among patients, but most patients require standard testing to start. Serum lactate has become an important risk stratification tool because both the initial serum lactate level and lactate clearance have been shown to be important predictors of mortality.^9,10 Further work-up should be guided by the suspected source of infection. For example, concern about a possible abdominopelvic infection (e.g., diverticulitis, acute cholecystitis) may warrant a computed tomography scan of the abdomen or pelvis or a right upper quadrant ultrasound scan, whereas concern about a possible central nervous system infection (e.g., meningitis) may warrant lumbar puncture. A procalcitonin level determination may be helpful in guiding therapy and predicting outcomes, whereas future molecular assays may help in more rapid identification of pathogens.^11,