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Emergency and Acute Medicine - Sepsis
Sepsis is defined as the presence of an infection accompanied by a systemic inflammatory response. This response is classically described by systemic inflammatory response syndrome (SIRS), which includes abnormalities in temperature (>38°C or <36°C), heart rate (>90 bpm), respiratory rate (>20/min or PaCO₂ <32 mm Hg), and white blood cell count (>12,000/mm³, <4,000/mm³, or >10% band forms). Sepsis occurs when infection is associated with at least two of these criteria. The condition results from the release of inflammatory mediators, leading to macrocirculatory failure (reduced cardiac output or perfusion pressure), microcirculatory dysfunction with impaired oxygen delivery, and cellular metabolic failure due to mitochondrial dysfunction.
Hemodynamic changes in sepsis initially include increased cardiac output due to vasodilation, followed later by myocardial depression. As the disease progresses, patients may develop multiple organ dysfunction syndrome (MODS), which can involve acute respiratory distress syndrome, acute kidney injury, hepatic failure, and disseminated intravascular coagulation. Sepsis exists on a continuum: severe sepsis involves sepsis with organ dysfunction such as acidosis, renal impairment, altered mental status, pulmonary dysfunction, hypotension, thrombocytopenia, or liver dysfunction, while septic shock is defined as persistent hypotension despite adequate fluid resuscitation. Sepsis remains a major cause of mortality, with septic shock carrying an in-hospital mortality of about 30%.
The most common causes of sepsis are bacterial infections. Gram-negative organisms such as Escherichia coli, Pseudomonas aeruginosa, Rickettsiae, and Legionella species are frequent causes, while gram-positive organisms include Enterococcus species, Staphylococcus aureus, and Streptococcus pneumoniae. Fungal infections, particularly Candida species, and viral infections may also contribute. In pediatric patients, important pathogens include Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, although children with minor infections may still meet SIRS criteria.
Patients commonly present with nonspecific symptoms such as fever, dyspnea, nausea, vomiting, and altered mental status including confusion or delirium. Identifying the source of infection is essential and may involve respiratory symptoms (cough, shortness of breath), gastrointestinal complaints (abdominal pain, diarrhea), or urinary symptoms (dysuria, frequency). Risk factors include immunosuppression, malignancy, recent chemotherapy, HIV, diabetes, splenectomy, and residence in nursing facilities. On examination, tachypnea is often an early sign, while blood pressure may initially remain normal before progressing to hypotension in septic shock. Patients may appear warm and flushed due to vasodilation. Physical examination should focus on identifying infection sources, including lungs, abdomen, skin, indwelling catheters, and central nervous system signs such as neck stiffness or coma.
Early diagnostic evaluation is critical. Serum lactate should be measured promptly, as levels >4 mmol/L indicate severe sepsis, although normal levels do not exclude shock. Blood cultures should be obtained prior to antibiotic administration. Laboratory investigations include complete blood count, electrolytes, renal and liver function tests, coagulation studies, and blood gas analysis, often revealing mixed acid–base disorders such as respiratory alkalosis with metabolic acidosis. Imaging studies such as chest radiography, abdominal CT, or ultrasound help identify the infection source. Lumbar puncture is indicated if meningitis is suspected, and central venous access may be required for monitoring and therapy.
Management begins with rapid stabilization of airway, breathing, and circulation. Supplemental oxygen should be provided to maintain adequate oxygenation, and mechanical ventilation may be required in cases of respiratory failure. Aggressive fluid resuscitation with isotonic crystalloids is essential, typically using repeated boluses. Early goal-directed therapy includes targeting adequate central venous pressure, mean arterial pressure, and central venous oxygen saturation.
If hypotension persists despite adequate fluid resuscitation, vasopressors should be initiated. Norepinephrine is the preferred first-line agent, especially in patients with tachyarrhythmias, while dopamine may be used in selected cases. Epinephrine may be considered in refractory shock. If oxygen delivery remains inadequate, blood transfusion and inotropic support such as dobutamine may be required. Broad-spectrum antibiotics must be administered as early as possible and tailored to the suspected source of infection, with coverage for resistant organisms such as MRSA, VRE, and Pseudomonas when indicated. Source control, such as drainage of abscesses or removal of infected devices, is crucial. Corticosteroids like hydrocortisone may be considered in refractory shock or suspected adrenal insufficiency.
Most patients with sepsis require hospital admission, often to an intensive care unit, particularly if there is evidence of organ dysfunction or shock. Only patients with mild infections and stable vital signs may be considered for discharge. Early recognition, prompt antibiotic administration, and aggressive fluid resuscitation are essential to improving outcomes. Failure to recognize multiorgan dysfunction or delays in treatment remain major pitfalls in the management of sepsis.
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