How do you identify and manage sepsis mimics in clinical practice?

Identifying and Managing Sepsis Mimics in Clinical Practice

A thorough understanding of sepsis mimics is essential for accurate diagnosis and appropriate management, as approximately 25% of patients presumed to have sepsis actually have non-infectious conditions that require different treatments. 1

Common Sepsis Mimics

Several conditions can present with clinical features similar to sepsis due to shared pathophysiologic responses:

• Cardiovascular conditions:

  • Acute heart failure
  • Cardiogenic shock
  • Pulmonary embolism

• Respiratory conditions:

  • Acute respiratory distress syndrome (ARDS) of non-infectious origin
  • Unspecific respiratory failure

• Immunologic/Inflammatory conditions:

  • Anaphylaxis
  • Vasculitis
  • Autoimmune flares

• Metabolic/Toxic conditions:

  • Adrenal insufficiency
  • Thyroid storm
  • Toxin ingestion/withdrawal
  • Severe electrolyte abnormalities

• Other conditions:

  • Gastrointestinal emergencies
  • Spinal cord injury
  • Malignancy-related complications 2, 3

Diagnostic Approach to Differentiate Sepsis from Mimics

1. Initial Assessment

• Apply qSOFA (quick Sequential Organ Failure Assessment) for rapid bedside assessment:

  • Altered mental status (GCS <15)
  • Respiratory rate ≥22 breaths/min
  • Systolic blood pressure ≤100 mmHg 4

• For patients with positive qSOFA, perform full SOFA score assessment to characterize organ dysfunction 4, 5

2. Detailed History and Examination

Focus on:

• Recent procedures or indwelling devices
• Nursing home residence (higher likelihood of infection) 6
• Immune status and medications
• Travel history
• Exposure to toxins
• Pre-existing conditions that could mimic sepsis

3. Laboratory and Imaging Studies

• Essential laboratory tests:

  • Complete blood count
  • Comprehensive metabolic panel
  • Lactate level
  • C-reactive protein (modest discriminatory power with AUROC 0.71) 1
  • Procalcitonin when available
  • Blood cultures (before antibiotics when possible) 5

• Targeted imaging based on suspected source:

  • Chest X-ray
  • Ultrasound
  • CT scan as indicated 4

• Specialized tests when sepsis mimics are suspected:

  • Cardiac biomarkers (troponin, BNP)
  • Thyroid function tests
  • Cortisol levels
  • Toxicology screens

4. Source Identification

• Sample fluid or tissue from suspected infection sites before antimicrobial therapy when possible 4
• Examine samples by Gram stain, culture, and antibiotic susceptibility testing 4
• Consider specialized tests for endemic parasitic infections (e.g., thick smear for malaria) 4

Management Algorithm

1. Initial Stabilization (regardless of whether sepsis or mimic):

   • Secure airway, breathing, circulation
   • Administer oxygen targeting SpO2 92-96%
   • Provide fluid resuscitation (30 mL/kg IV crystalloid) for hypotension or hypoperfusion 5

2. Empiric Treatment while differentiating:

   • Administer broad-spectrum antibiotics within 1 hour of recognition if sepsis remains in differential 5
   • Initiate vasopressors if fluid-refractory shock (target MAP ≥65 mmHg) 5

3. Targeted Management once diagnosis clarified:

   • For confirmed sepsis:

     • Continue antimicrobial therapy
     • Perform source control when applicable 4, 5
     • Provide supportive care

   • For sepsis mimics:

     • Discontinue unnecessary antibiotics
     • Initiate specific therapy for the identified condition:
       • Acute heart failure: Diuretics, vasodilators
       • Anaphylaxis: Epinephrine, antihistamines, steroids
       • Adrenal crisis: Hydrocortisone
       • Thyroid storm: Anti-thyroid medications, beta-blockers

Critical Pitfalls to Avoid

1. Confirmation bias: Assuming sepsis in all patients with SIRS criteria without considering mimics 3

2. Delayed diagnosis: Failing to reassess the diagnosis when patients don't respond to standard sepsis therapy

3. Premature closure: Stopping the diagnostic workup once sepsis is presumed

4. Overreliance on biomarkers: Using CRP or procalcitonin in isolation rather than as part of a comprehensive assessment 1

5. Culture-negative sepsis confusion: Remember that 44% of culture-negative presumed sepsis cases still have clinical infections, while 32% have non-infectious mimics 6

By maintaining a high index of suspicion for sepsis mimics, particularly in patients who don't respond to standard sepsis therapy, clinicians can ensure appropriate treatment and improve outcomes for this challenging patient population.