II. Pathophysiology

  1. See Fever
  2. Fever is a sign of systemic inflammation, and is NOT synonymous with infection

III. Exam

  1. Temperature measurement in the ICU in order of accuracy
    1. Pulmonary artery, esophagus or Bladder catheters with thermistors (preferred)
    2. Rectal Temperature (avoid in Neutropenia)
    3. Oral Temperature
    4. Tympanic MembraneTemperature
    5. Avoid axillary and temporal artery Temperatures (too low accuracy)
  2. Fever thresholds
    1. Body Temperature >38.0 C (100.4 F) in immunocompromised (esp. Neutropenia)
    2. Body Temperature >38.3 C (101.0 F) in other patients

IV. Causes: Noninfectious Fever Causes (50% of cases)

  1. Common
    1. Systemic Inflammatory Response (SIRS)
      1. Tissue injury (major injury, tissue ischemia or infarction)
      2. Gastrointestinal release of inflammatory Cytokines and endotoxin
      3. Acute Respiratory Distress Syndrome (ARDS)
    2. Early Postoperative Fever
      1. Major surgery
        1. Results in fever in 15-40% on postoperative day 1 (most without infection)
        2. Major surgery related early fever resolves in first 24-48 hours (if not infectious)
      2. Malignant Hyperthermia (Anesthetic induced)
      3. Atelectasis is NOT a cause of fever
        1. Atelectasis is coincidental with Post-operative Fever and resolves in the same timeline
    3. Venous Thromboembolism
    4. Red Blood Cell Transfusion
      1. Occurs in 0.5% of RBC Transfusions, typically within first 6 hours
    5. Platelet Transfusion
      1. Occurs in 30% of Platelet Transfusions, related to antibodies to donor Leukocytes
  2. Uncommon
    1. Drug-Induced Fever
      1. Hypersensitivity Reaction (associated with Eosinophilia, rash)
      2. Idiosyncratic Reaction
      3. Drug-Induced Hyperthemia Syndromes (muscle rigidity and fever >40 C)
        1. Malignant Hyperthermia
        2. Neuroleptic Malignant Syndrome
        3. Serotonin Syndrome
    2. Acalculous Cholecystitis (1.5% of ICU patients)
    3. Thyrotoxicosis
    4. Acute Addisonian Crisis (Adrenal Hemorrhage)
    5. Iatrogenic fever
      1. Malfunctioning Temperature regulator on water mattress or Ventilator humidifier

V. Causes: Nosocomial Infectious Fever Causes (50% of cases)

  1. Common (76-78% of nosocomial infections)
    1. Pneumonia
      1. Intubated patients account for 83% of Nosocomial Pneumonia cases in ICU
    2. Urinary Tract Infection
      1. Indwelling Foley Catheters account for 97% of nosocomial Urinary Tract Infections in ICU (CAUTI)
    3. Bloodstream infections
      1. Central Line-Associated Bloodstream Infections account for 87% of bloodstream infections
    4. Surgical Site Infections
      1. Occurs at day 5-7 after surgery, with fever typically suggesting deep space infection
      2. Necrotizing Soft Tissue Infection have onset within days of surgery and rapidly progress
  2. Uncommon
    1. Intubation Associated Sinusitis
      1. Associated with Nasotracheal tubes and Nasogastric Tubes
    2. Clostridium difficile Infection
    3. Consider patient specific predispositions for infection (e.g. Cirrhosis related Spontaneous Bacterial Peritonitis)

VI. Labs

  1. Laboratory testing should be directed at most likely causes (50% of cases are non-infectious)
  2. Blood Cultures
    1. Obtain in all cases in which infectious cause is thought to be most likely
    2. Obtain at least 2 sets of Blood Cultures (each with 20-30 ml split over aerobic and anaerobic bottles)

VII. Management: General

  1. Temperature lowering
    1. Fever is not typically harmful, but is uncomfortable
    2. Acetaminophen 650 mg every 4-6 hours oral or rectal as needed
  2. Measures to avoid in Temperature lowering
    1. Avoid cooling blankets (outside of hyperthermia syndromes)
    2. Avoid NSAIDs in the Intensive Care unit
      1. Nephrotoxicity due to NSAIDs
      2. NSAID Gastrointestinal Adverse Effects

VIII. Management: Empiric Antibiotics

  1. Indications
    1. Infectious cause is thought most likely (50% of cases)
    2. Neutropenic patients (Absolute Neutrophil Count <500/mm3)
      1. Do not delay empiric therapy
  2. Empiric antibiotic selection in the Intensive Care unit
    1. Broad spectrum antibiotics that also cover Aerobic Gram Negative Rods
      1. Piperacillin/Tazobactam (Zosyn)
      2. Carbapenem (Imipenem or Meropenem)
      3. Cefepime
    2. Staphylococcus Coverage Indicated in suspected Central Line-Associated Bloodstream Infection
      1. Vancomycin (avoid in cases where MRSA in unlikely)
      2. Linezolid (may be preferred in decreased Renal Function)
    3. Disseminated Candidiasis coverage indicated in Prolonged Fever (>3 days), immunocompromised, recent antibiotics
      1. Fluconazole (first-line)
      2. Caspofungin (Neutropenia)
  3. Antibiotics to avoid
    1. Fluoroquinolones
      1. Increased Antibiotic Resistance, Clostridium difficile, Neuropathy, Tendinopathy and Delirium
    2. Aminoglycosides
      1. Increased nephrotoxicity, without significant benefit from double coverage of Gram Negative Bacteria

IX. Resources

  1. Internet Book of Critical Care (EMCRIT.org)
    1. https://emcrit.org/ibcc/guide/

X. References

  1. Marino (2014) The ICU Book, p. 777-95

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