What is the first line of treatment for a patient with a fever?

First-Line Treatment for Fever

Paracetamol (acetaminophen) 1000 mg orally every 4-6 hours (maximum 4 g/day) is the first-line treatment for fever in adults, prioritizing patient comfort rather than temperature reduction alone. 1, 2

Core Treatment Principles

Antipyretics should be used primarily for symptomatic relief and patient comfort, not routinely to reduce temperature itself, as fever reduction does not improve mortality or clinical outcomes. 1, 2 The American College of Critical Care Medicine emphasizes that antipyretic medications should not be administered solely to reduce temperature, as this approach has not demonstrated survival benefit in multiple randomized trials. 1

Pharmacologic Management

First-Line Agent: Paracetamol

• Paracetamol up to 4 g/day is the oral analgesic of first choice due to its excellent safety profile, superior cardiovascular safety compared to NSAIDs, and no increased gastrointestinal complications. 2

• For patients capable of oral intake, administer paracetamol 1000 mg every 4-6 hours (maximum 4 g/day). 2

• Paracetamol represents the first choice for fever treatment in emergency settings, with 90.5% of patients achieving symptom control within 2 hours. 3

Alternative: Combination Therapy

• The combination of paracetamol 500 mg/ibuprofen 150 mg may be more effective than paracetamol alone for bacterial fever at 1 hour (48.6% vs 33.6% response rate), though both achieve similar efficacy by 2 hours. 3

Route of Administration

• All patients capable of oral intake should receive oral paracetamol; parenteral routes are reserved for those unable to take oral medications due to persistent vomiting, altered mental status, or NPO status. 2

• Intramuscular administration should be avoided due to injection site pain, tissue trauma, and risk of hematoma, especially in anticoagulated patients. 2

What NOT to Do

Physical Cooling Methods

• Physical cooling methods (tepid sponging, fanning, cold bathing) cause discomfort without improving outcomes and are not recommended. 4, 2

• Cooling devices should only be considered for refractory fevers that do not respond to antipyretics. 2

Temperature Targets

• Do not treat fever solely to normalize temperature—focus on identifying and treating the underlying cause while using antipyretics selectively for comfort. 1

Diagnostic Approach (Before or Concurrent with Treatment)

Essential Workup

• Obtain blood cultures before starting antibiotics, especially in seriously ill or deteriorating patients. 1

• Perform chest radiography for all hospitalized patients with new fever, as pneumonia is the most common infection causing fever in critically ill patients. 1

• Consider both infectious causes (pulmonary infections, urinary tract infections, sepsis, endocarditis) and non-infectious causes (pulmonary embolism, drug fever, inflammatory conditions). 1

Temperature Measurement

• Use oral or rectal temperatures when central monitoring (pulmonary artery catheters, bladder catheters, esophageal thermistors) is unavailable; avoid axillary or tympanic measurements. 1

Special Populations and Contexts

Suspected Infection

• When infection is suspected, initiate empiric antimicrobial therapy within 1 hour, as delayed effective therapy increases mortality. 1

• Tailor therapy based on suspected source, patient risk for multidrug-resistant organisms, and local susceptibility patterns. 1

Neutropenic Patients

• For neutropenic patients, initiate immediate hospitalization and empiric antibacterial therapy with vancomycin plus antipseudomonal antibiotics. 1

Neurologic Patients

• For acute ischemic stroke patients, fever should be promptly treated with antipyretic medications as first-line therapy, as fever is associated with worse outcomes. 1

• For post-cardiac arrest patients, prevent and treat fever after completion of targeted temperature management (32-36°C). 1

Pediatric Considerations

• In children with febrile seizures, antipyretics (including paracetamol) do not prevent seizure recurrence. 2

• Ensure adequate fluid intake to prevent dehydration; physical cooling methods cause discomfort and should be avoided. 4

Dosing Precautions

• Reduce paracetamol dosage in patients with hepatic insufficiency or history of alcohol abuse. 2

• Avoid paracetamol in acute liver failure. 2

Clinical Pitfalls to Avoid

• Do not withhold antipyretics based on the misconception that fever should "run its course"—while fever has evolved as a defense mechanism, symptomatic treatment for comfort is appropriate and does not worsen outcomes. 1, 2

• Do not use empiric antimicrobial therapy for fever of unknown origin except in neutropenic, immunocompromised, or critically ill patients. 5

• Do not rely on antipyretics alone—always investigate the underlying cause, as up to 75% of fever of unknown origin cases resolve spontaneously but require diagnostic evaluation. 5