Fever: Definition, Classification, Evaluation, and Management
Definition of Fever
Fever is a regulated elevation in body temperature resulting from an upward shift in the thermoregulatory set-point, mediated by pyrogenic cytokines released in response to infection or trauma. 1, 2 This distinguishes fever from other forms of hyperthermia, where temperature rises despite normal thermoregulatory mechanisms attempting to maintain homeostasis. 2, 3
Population-Specific Temperature Thresholds
The definition of fever varies by patient population and clinical context:
Adult ICU patients: A single temperature ≥38.3°C (101°F) defines fever and should trigger diagnostic evaluation. 4, 5
Pediatric patients (age 1 day to 3 years): Rectal temperature >38.0°C (100.4°F). 6, 5 This is the most reliable measurement method in young children. 5
Elderly patients in long-term care facilities: 4, 5
- Single oral temperature >37.8°C (100°F) (70% sensitive, 90% specific for infection)
- Repeated oral temperatures >37.2°C (99°F) or rectal >37.5°C (99.5°F)
- Increase >1.1°C from individual baseline
Neutropenic/immunocompromised patients: Single oral temperature ≥38.3°C (101°F) or sustained temperature ≥38.0°C (100.4°F) for ≥1 hour. 4, 5 This lower threshold reflects the higher mortality risk in this population.
CAR T-cell therapy patients (Cytokine Release Syndrome): Fever ≥38°C defines Grade 1 CRS. 6, 4 After antipyretic or anticytokine therapy, fever is no longer required for grading—hypotension or hypoxia alone determine severity. 6, 4
Temperature Measurement Methods
Hierarchy of Accuracy
Use central temperature monitoring whenever precise measurement is essential for diagnosis or management. 4 The accuracy hierarchy is:
- Pulmonary artery catheter thermistors (gold standard) 4, 5
- Bladder catheter thermistors (continuous core-temperature readings, less invasive, stable regardless of urine flow) 4
- Esophageal balloon thermistors (comparable accuracy but may be uncomfortable; requires careful placement verification) 4
- Rectal thermometers (reads 0.2-0.3°C higher than true core temperature; acceptable when central devices unavailable) 4
- Oral thermometers (safe for alert, cooperative patients; distorted by mouth-breathing, recent hot/cold fluid intake, or endotracheal intubation) 4
Methods to Avoid
Never rely on axillary, tympanic/infrared ear, temporal-artery scanners, or chemical-dot thermometers for critical decision-making. 4, 5 These methods are unreliable in critically ill patients.
Practical Algorithm for Temperature Measurement
| Clinical Situation | Recommended Method |
|---|---|
| Central monitoring devices already in place (PA catheter, bladder probe, esophageal probe) | Use the existing central device [4] |
| No central device; patient alert and cooperative | Oral thermometry (avoid within 15-30 min after hot/cold fluid intake) [4] |
| Patient uncooperative, intubated, or mouth-breathing | Rectal thermometry if not contraindicated (avoid in neutropenic, coagulopathic, or recent rectal surgery patients) [4] |
Always document the measurement site with every temperature reading to ensure consistency and avoid misinterpretation. 4
Classification and Physiologic Context
Normal Temperature Variability
- The classic "normal" body temperature of 37.0°C (98.6°F) can fluctuate by 0.5-1.0°C due to circadian rhythm, menstrual cycle, age, gender, and individual factors. 4, 5, 7
- Average normal body temperature has declined by approximately 0.03°C per birth decade over the past 157 years. 4, 5
- Heavy physical activity can raise core temperature by 2-3°C in healthy individuals. 4
Fever vs. Hyperthermia
Fever is fundamentally different from other forms of hyperthermia. 2, 3
- Fever: Regulated rise with upward displacement of the thermoregulatory set-point; defended by fully functional thermoregulatory mechanisms; responds to aspirin-like drugs. 2
- Hyperthermia: Forced temperature elevation that exceeds the body's capacity to thermoregulate without affecting the set-point; does not respond to antipyretics; requires whole-body cooling. 2, 3
Adaptive Value
Fever represents a normal physiologic response and part of an integrated host defense system. 6, 1 Failure to generate fever in response to infection is generally associated with poorer prognosis. 1
Common Causes
While the provided evidence focuses on definitions and measurement rather than comprehensive etiology, fever in clinical settings results from:
- Infectious pathogens (bacterial, viral, fungal) triggering pyrogenic cytokine release 6, 1
- Serious bacterial infections (particularly concerning in young children and immunocompromised patients) 6
- Immune-mediated processes (e.g., CAR T-cell therapy-induced cytokine release syndrome) 6
Evaluation: Critical Pitfalls and Alternative Indicators
The Absence of Fever Does Not Exclude Serious Infection
A substantial proportion of infected patients remain euthermic or become hypothermic, and lack of fever is linked to worse outcomes. 4, 5 This is a critical pitfall that can lead to delayed diagnosis and treatment.
Populations with Blunted Fever Response
High-risk groups include: 4
- Elderly patients
- Patients with large burns or open abdominal wounds
- Those receiving ECMO or continuous renal replacement therapy
- Individuals with congestive heart failure, end-stage liver disease, or chronic renal failure
- Patients taking anti-inflammatory drugs, corticosteroids, or antipyretics
Alternative Infection Indicators When Fever Is Absent
Initiate comprehensive infection work-up if any of the following are present: 4, 5
- Unexplained hypotension, tachycardia, or tachypnea
- New confusion or altered mental status
- Rigors or new skin lesions
- Oliguria or rising lactate levels
- Leukocytosis, leukopenia, or ≥10% immature neutrophils (bands)
- Thrombocytopenia
In older adults, suspect infection with functional decline: new or increasing confusion, incontinence, falls, deteriorating mobility, reduced food intake, or failure to cooperate with staff—even in the absence of fever. 4, 5
First-Line Management
General Approach by Fever Grade
For fever ≥38.3°C in critically ill adults or neutropenic patients, initiate sepsis work-up immediately: 6, 4
- Obtain blood cultures before antibiotics
- Perform imaging as clinically indicated
- Consider empirical broad-spectrum antibiotics, especially in neutropenic or critically ill patients 6
CAR T-Cell Therapy-Specific Management
Grade 1 CRS (fever ≥38°C only, no hypotension or hypoxia): 6
- For prolonged CRS (>3 days) or patients with significant symptoms, comorbidities, or elderly: consider tocilizumab 8 mg/kg IV over 1 hour (max 800 mg)
- For axicabtagene ciloleucel or brexucabtagene autoleucel: consider tocilizumab if symptoms persist >24 hours
- Supportive care: sepsis screen, empirical broad-spectrum antibiotics (especially if neutropenic), judicious IV fluids, electrolyte repletion, management of specific organ toxicities
Grade 2 CRS (fever with hypotension not requiring vasopressors and/or hypoxia requiring low-flow nasal cannula): 6
- Tocilizumab 8 mg/kg IV over 1 hour (max 800 mg/dose) is recommended
- Consider corticosteroids if no improvement after tocilizumab
Pediatric Considerations
Infants <3 months with fever require hospitalization for IV antibiotics due to decreased immune function and increased risk of serious bacterial infection. 8 Children aged 3-36 months can be managed with closer observation if well-appearing, but serious bacterial infection remains a concern requiring treatment. 8
Environmental and Iatrogenic Factors
Consider non-infectious causes in the ICU setting: specialized mattresses, hot lights, air-conditioning, cardiopulmonary bypass, and dialysis can alter measured temperature independent of infection. 4 Distinguish these from true fever to avoid unnecessary antibiotic exposure.