1. In febrile infants 0-3 months old:
    1. Recognize the risk of occult bacteremia.
    2. Investigate thoroughly (e.g., blood cultures, urine, lumbar puncture +/- chest X-ray).
  2. In a febrile patient with a viral infection, do NOT prescribe antibiotics.
  3. In a febrile patient requiring antibiotic therapy, prescribe the appropriate antibiotic(s) according to likely causative organism(s) and local resistance patterns.
  4. Investigate patients with fever of unknown origin appropriately (e.g., with blood cultures, echocardiography, bone scans).
  5. In febrile patients, consider life-threatening infectious causes (e.g., endocarditis, meningitis).
  6. Aggressively and immediately treat patients who have fever resulting from serious causes before confirming the diagnosis, whether these are infectious (e.g., febrile neutropenia, septic shock, meningitis) or non-infectious (e.g., heat stroke, drug reaction, malignant neuroleptic syndrome).
  7. In the febrile patient, consider causes of hyperthermia other than infection (e.g., heat stroke, drug reaction, malignant neuroleptic syndrome).
  8. In an elderly patient, be aware that no good correlation exists between the presence or absence of fever and the presence or absence of serious pathology.

See Pediatric Fever, Fever in Returning Traveller.

General Overview

  • Fever (usually >38°C) is an elevation in core body temperature seen in infections, autoimmune, autoinflammatory diseases
    • Hyperpyrexia (>41.5° C) is seen in severe infection or CNS hemorrhage
  • Older adults and patients being treated with biologic agents may have a low-grade fever in serious infection
  • Aspirin (NSAIDs) and Acetaminophen are potent antipyretics
    • If fever does not change with aspirin/acetaminophen, consider hyperthermia (see below)

Fever Unknown Origin

  • T>38.3 C for >3w without etiology


  • Infectious (Endocarditis, TB, osteomyelitis, intraabdominal abscess, dental abscess)
  • Malignancies (Hematologic, metastatic, renal cell carcinoma)
  • Connective tissue diseases (Giant cell arteritis, PMR, RA, IBD)
  • Drug (antibiotics, methyldopa, phenytoin)
  • DVT


  • Exposures
  • Travel, endemic diseases
  • Family history
  • Medical history, malignancy
  • Surgical history, prosthesis (osteomyelitis)
  • Risky behaviours (IVDU, STI exposure)


  • Rash
  • Conjunctivitis, uveitis (autoimmune)
  • Hepato-splenomegaly
  • Joint swelling
  • Lymphadenopathy

Labs to consider

  • Blood cultures r/o endocarditis
  • CBC
  • LDH
  • HIV Ab and Viral load
  • RF
  • Heterophile antibody test
  • CPK
  • ANA
  • TB skin test (or interferon-gamma release assay)
  • Serum protein electrophoresis


  • CT abdo/chest (r/o abscess, malignancy)
  • Consider
    • Echocardiography (r/o endocarditis)
    • PET-CT (r/o malignancy/inflammation)
    • Referral to ID, rheumatology, oncology


  • Distinction between Hyperthermia and Fever important
    • Hyperthermia (fatal): Thermoregulatory center unchanged despite increasing temperature
      • Suspect based on history
      • Suspect if skin hot and dry (heat stroke or atropine), or if antipyretics do not decrease body temperature
    • Fever: Thermoregulatory center compensates for increasing temperature


  • Hyperthermia must be treated by RAPID reduction of body temperature by PHYSICAL means → find underlying cause
    • Ice packs, cool damp sponges/towels/water, fan
      • Avoid cooling blankets (vasoconstriction → less heat loss)
    • IV fluids for dehydration

Nonexertional/Exertional heat stroke

  • Consider heat stroke in T>40C, CNS dysfunction (altered mental status), exposure to heat, and absence of other explanation
  • ABC, may need intubation and ventilation
  • Rapid cooling and rehydration
  • Continuous rectal probe temperature monitoring
  • Labs (CBC, lytes, UA, CK, LFT, Coags)

Pharmacology/drug-induced (atropine, ecstasy)

  • Charcoal if <1-2h ingestion
  • Benzodiazepines for agitation/seizure (eg. lorazepam 1-2mg IV push until hypertension controlled or patient sedated)
  • Consult Poison Control Center
    • Atropine - consider physostigmine (antidote)
    • Ecstasy - only correct hyponatremia if severe/symptomatic

Metabolic disease (hyperthyroid)

  • Thyroid storm (suspect in tachycardia, hyperpyerxia, CNS dysfunction, GI symptoms, goiter, hyperthyroidism on labs)
    • B-Blockers (Propranolol 60-80mg PO q4-6h)
    • PTU 200mg PO q4h
    • Iodine solution (delayed 1h after PTU)
    • Iodinated radiocontrast
    • High-dose IV hydrocortisone 100mg IV q8h

Anesthetics (malignant hyperthermia)

  • Discontinue anethestic, add charcoal fibers to anesthesia breathing circuit
  • Hyperventilate with 100% O2
  • Dantrolene

Neuroleptic (neuroleptic malignant syndrome)

  • Discontinue neuroleptic
  • Supportive
  • Consider dantrolene, bromocriptine, amantadine if do not respond after 1-2 days

Serotonin syndrome

  • Diagnose clinically if on serotonergic agent and one of the following:
    • Spontaneous clonus
    • Inducible clonus PLUS agitation or diaphoresis
    • Ocular clonus PLUS agitation or diaphoresis
    • Tremor PLUS hyperreflexia
    • Hypertonia PLUS temperature above 38°C PLUS ocular clonus or inducible clonus
  • Discontinue serotonergic agent
  • Supportive care aimed to normalize vital signs
  • Benzodiazepine sedation
  • Serotonin antagonist
  • Consider sedation, paralysis, intubation
  • Consider Cyproheptadine (antidote)