INFECTIOUS SYNDROMES

Sepsis and Septic Shock

Classification: Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is sepsis requiring vasopressors to maintain a mean arterial pressure of at least 65 mm Hg with serum lactate greater than 2 mmol/L despite adequate volume resuscitation (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).

Key diagnostic discriminator: Suspected or confirmed infection plus acute organ dysfunction should trigger immediate evaluation and treatment. Fever alone does not define sepsis, and no single biomarker or screening score rules it in or out (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).

Clinical priority: Severe hypotension, mottling, altered mentation, oliguria, rising lactate, respiratory failure, or disseminated intravascular coagulation signals high mortality risk (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).

Etiology and risk factors

  • Any infection can cause sepsis. Risk rises with age extremes, immune compromise, chronic disease, pregnancy/postpartum state, invasive devices/procedures, recent healthcare exposure, delayed source control, and resistant organisms (Fiske & Bloch, 2019; Norris, 2020).
  • Common sources include lung, urinary tract, abdomen, skin/soft tissue, bloodstream/device, and central nervous system. Cultures may be negative (Fiske & Bloch, 2019; Norris, 2020).

Pathophysiology

  • Microbial products and injured host tissues activate innate immune and complement pathways. Cytokines, endothelial activation, and nitric oxide contribute to vasodilation, capillary leak, maldistributed blood flow, and myocardial depression (Fiske & Bloch, 2019; Norris, 2020).
  • Activation of coagulation and impaired anticoagulant and fibrinolytic pathways promote microvascular thrombosis. Cellular dysfunction and impaired perfusion compound organ failure (Fiske & Bloch, 2019; Norris, 2020).
  • Septic shock combines inadequate vascular tone, intravascular volume loss, and sometimes cardiac dysfunction (Fiske & Bloch, 2019; Norris, 2020).

Clinical manifestations

  • Possible fever or hypothermia, tachypnea, tachycardia, hypotension, altered mentation, mottling, delayed capillary refill, oliguria, hypoxemia, ileus, or bleeding/coagulopathy (Seller & Symons, 2018; Tess, 2012).
  • Organ dysfunction may appear as rising oxygen need, acute kidney injury, bilirubin elevation, thrombocytopenia/coagulopathy, encephalopathy, cardiovascular failure, or elevated lactate (Seller & Symons, 2018; Tess, 2012).
  • Older, immunocompromised, or medication-treated patients may lack fever or leukocytosis (Seller & Symons, 2018; Tess, 2012).

Findings that argue against or redirect

  • No single biomarker rules sepsis in or out. Normal lactate does not exclude sepsis; elevated lactate has nonseptic causes (Seller & Symons, 2018; Tess, 2012).
  • SIRS can occur without infection and is not synonymous with sepsis. Diagnosis requires infection-associated organ dysfunction and clinical assessment (Seller & Symons, 2018; Tess, 2012).
  • Consider hemorrhage, cardiogenic/obstructive shock, anaphylaxis, adrenal crisis, pancreatitis, medication/toxin, pulmonary embolism, and other noninfectious inflammatory states (Seller & Symons, 2018; Tess, 2012).

Diagnostic evaluation

  • Evaluate the likely source, organ dysfunction, perfusion, and competing diagnoses immediately. Obtain blood cultures as soon as possible and ideally before antimicrobials, plus source cultures, serum lactate, organ-function testing, and source-directed imaging (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).
  • Use serial clinical assessment of perfusion, mental status, urine output, lactate, and organ function. NEWS, NEWS2, MEWS, or SIRS may support screening; do not rely on qSOFA as the sole screening tool (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).
  • Reassess the diagnosis as data evolve. Culture-negative sepsis is possible, but empiric antimicrobials should be de-escalated or stopped when microbiology or a convincing alternative diagnosis supports that decision (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).

Expected diagnostic and laboratory findings

  • Supportive abnormalities may include elevated or rising lactate, leukocytosis/leukopenia, thrombocytopenia, creatinine/bilirubin increase, hypoxemia, coagulopathy, acidosis, and positive cultures. None is individually definitive (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).
  • Septic shock is supported by persistent circulatory failure after fluid resuscitation, vasopressor need, and accompanying organ dysfunction (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).
  • Microbiology and imaging may identify source, but culture-negative sepsis remains possible (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).

Differential diagnosis

  • Cardiogenic shock: ischemic/structural findings, congestion, and primary pump failure (Seller & Symons, 2018; Tess, 2012).
  • Hypovolemic/hemorrhagic shock: loss history, low filling state, bleeding evidence, and response/source evaluation (Seller & Symons, 2018; Tess, 2012).
  • Obstructive shock: pulmonary embolism, tamponade, or tension pneumothorax findings (Seller & Symons, 2018; Tess, 2012).
  • Anaphylaxis: abrupt exposure-associated skin/mucosal and airway findings; adrenal crisis and toxicologic syndromes require targeted laboratory/history clues (Seller & Symons, 2018; Tess, 2012).

Treatment and management

  • Treat sepsis and septic shock as medical emergencies. Administer antimicrobials immediately, ideally within one hour, for septic shock or probable or definite sepsis. When sepsis without shock is only possible, complete a rapid evaluation and give antimicrobials within three hours if concern persists (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).
  • For sepsis-induced hypoperfusion or septic shock, begin crystalloid resuscitation and consider at least 30 mL/kg during the first three hours, individualized to comorbidity and response. Balanced crystalloids are generally preferred, with frequent reassessment to avoid under- or over-resuscitation (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).
  • Use norepinephrine as the first-line vasopressor and target an initial mean arterial pressure of about 65 mm Hg. Peripheral initiation is reasonable when waiting for central access would delay treatment (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).
  • Pursue source control as soon as medically and logistically practical, ideally within six hours when required. Provide organ support and de-escalate therapy as clinical and microbiologic information becomes available (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).

Additional complications and red flags

  • Do not delay antimicrobials or source control while waiting for complete diagnostic certainty in shock (Fiske & Bloch, 2019; Society of Critical Care Medicine, 2026).

Content last reviewed:

References

Fiske, C. T., & Bloch, K. C. (2019). Infectious diseases. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed.). McGraw-Hill Education.

Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer.

Seller, R. H., & Symons, A. B. (2018). Differential diagnosis of common complaints (7th ed.). Elsevier.

Society of Critical Care Medicine. (2026). Surviving Sepsis Campaign adult guidelines. https://sccm.org/survivingsepsiscampaign/guidelines-and-resources/surviving-sepsis-campaign-adult-guidelines

Tess, A. V. (2012). Fever. In M. C. Henderson, L. M. Tierney, Jr., & G. W. Smetana (Eds.), The patient history: An evidence-based approach to differential diagnosis (2nd ed.). McGraw-Hill.