Definition

T > 38.5°C (101.3°F) and in neutropenic, transplant, and dialysis patients, T > 38.0°C (100.4°F).

Differential Diagnosis

• Infection (lung, urine, sinuses, skin, catheters, heart, brain, prostate, abdomen, foreign bodies)
  • Nosocomial infection: After day 3 of hospitalization, nosocomial infection incidence increases and drug-induced fever goes up substantially.  Note that nosocomial meningitis is exceedingly rare in the absence of head injury or neurosurgery. 
  • Common nosocomial infections: UTI (especially in patients with Foley catheters), pneumonia, vascular catheter related infections, wound infections, antibiotic-associated colitis.
  • Less common: decubitus ulcers, acalculous cholecystitis, nosocomial sinusitis.
• Inflammation (collagen vascular disease, neoplastic disease, mucositis).
• Drug fever: Common in hospitalized patients.  Clues include relative bradycardia, presence of a rash, eosinophilia, and the patient being subjectively unaware of fever despite high temperatures.  Always look at the medication record! (Diagnosis of exclusion; beta-lactam antibiotics, amphotericin, and chemotherapy are frequent offenders)
• Pulmonary embolism or deep venous thrombosis.
• Neurologic (spinal cord injury, hypothalamic injury, intracranial hemorrhage, seizures).
• Endocrine (adrenal insufficiency, thyrotoxicosis).
• Post-op: consider common etiologies of post-operative fever in patients who have recently had surgery (e.g., atelectasis, PNA, UTI, PE, wound infection, drug fever)
• Toxidromes such as neuroleptic malignant syndrome, serotonin syndrome, anticholinergic toxicity, and sympathomimetic toxicity (e.g. cocaine or amphetamine overdose). Note that hyperthermia due to a drug/toxin will not respond to antipyretics.
• Miscellaneous aspiration, blood product reaction, atelectasis, hematoma, pancreatitis, MI, CVA

Evaluation

• Is the patient stable? Look at vital signs and examine the patient. If unstable (e.g., altered mental status, respiratory distress), call for backup and arrange for transfer to ICU. Remember, tachycardia/tachypnea may be the first signs of sepsis. (See Critical Care: Protocol for Septic Shock)
• Take a focused H&P.  Remember drug allergies. 
• Determine whether additional studies to rule out the above diagnoses are indicated (e.g., CXR and urinalysis are often indicated)
• Determine whether blood cultures have been drawn within the previous 48 hours. If so, there is generally no need to draw additional cultures unless specific instructions from primary team indicate otherwise.

Management

• In most cases, it is prudent to withhold empiric antibiotics unless obvious signs of infection (e.g., new infiltrate on CXR). An exception to this rule is for patients with hemodynamic instability or neutropenia. See Hematology/Oncology: Neutropenic Fever.
• Antipyretics: Tylenol 650-1000 mg PO, ibuprofen 600 mg, or for suspected neoplastic fevers, naproxen 375 mg PO q12h.NSAIDS not recommended in patients with renal, cardiovascular, GI, or bleeding disorders (many hospitalized patients).
• Ice packs and other cooling measures
• Fever can augment the host defense system, and routine antipyretics can mask the disease process and delay diagnostic evaluation. Therefore, unless the patient has discomfort, altered mental status due to fever (common in the elderly), or cardiac disease vulnerable to the hypermetabolic state, consider resisting the temptation to lower the temperature.

Key points

• Always ask for a full set of vital signs when called for fever; if any concern for hemodynamic instability, go evaluate the patient right away.
• If a patient is stable and there is no clear source of infection, avoid giving empiric antibiotics.