Fever

Definitions

  • Fever: increased body temperature due to a change in temperature setpoint at the level of the hypothalamus
    • Elevated levels of prostaglandin E2 (PGE2) in the hypothalamus appear to be the trigger for raising the set-point
    • Response to Antipyretics
      • Antipyretics (Adequate Doses of either Aspirin or Acetaminophen) Can Reduce the Body Temperature in Fever
  • Hyperpyrexia: fever >41.5°C
    • Examples
      • Central Nervous System (CNS) Hemorrhage (see xxxx)
      • Severe Infection
    • Response to Antipyretics
      • Antipyretics (Adequate Doses of either Aspirin or Acetaminophen) Can Reduce the Body Temperature in Hyperpyrexia
      • Although antipyretics reduce the body temperature in hyperpyrexic fever, cooling blankets and cool water sponging are recommended to accelerate peripheral heat losses
        • However, peripheral cooling with cooling blankets can be counterproductive in the absence of antipyretics since cold receptors in the skin trigger reactive vasoconstriction, thus reducing heat loss mechanisms
  • Hyperthermia: elevated body temperature NOT due to a change in temperature setpoint at the level of the hypothalamus (i.e. body temperature exceeds the ability to dissipate heat)
    • Examples
      • Atropine: due to interference with thermoregulation by blocking sweating or vasodilation
      • Ecstasy (3,4-Methylenedioxymethamphetamine) (see Ecstasy): due to a loss in heat dissipation (vasoconstriction) and heat production via uncoupling protein 3
      • Heat Stroke (see Heat Stroke)
      • Hyperthyroidism (see Hyperthyroidism): may cause mild elevation of the core temperature
      • Malignant Hyperthermia (see Malignant Hyperthermia)
      • Neuroleptic Malignant Syndrome (NMS) (see Neuroleptic Malignant Syndrome)
      • Serotonin Syndrome (seeSerotonin Syndrome)
    • Lack of Response to Antipyretics
      • In Contrast to Fever/Hyperpyrexia, Antipyretics Do Not Decrease the Elevated Body Temperature in Hyperthermia

Etiology

Infection

Cardiovascular

Dermatologic

Endocrinologic

Gastrointestinal

Neurologic

Ophthalmologic

  • Tularemia (see Tularemia)
    • Oculoglandular Tularemia

Otolaryngologic

Pulmonary

Renal/Urologic

Reproductive/Pregnancy-Associated

Other

Hematologic/Immunologic

Neoplasm

Neurologic

  • Intracerebral Hemorrhage (Hemorrhagic Cerebrovascular Accident) (see Intracerebral Hemorrhage)
    • Epidemiology
      • Fever is a Common After Brain Injury (Due to Traumatic Brain Injury, Ischemic CVA, and/or Intracerebral Hemorrhage) (J Intensive Care Med, 2015) [MEDLINE]
    • Prognosis
      • Fever is a Risk Factor for In-Hospital Mortality (J Intensive Care Med, 2015) [MEDLINE]
  • Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident)
    • Epidemiology
      • Fever is a Common After Brain Injury (Due to Traumatic Brain Injury, Ischemic CVA, and/or Intracerebral Hemorrhage) (J Intensive Care Med, 2015) [MEDLINE]
    • Prognosis
      • Fever is a Risk Factor for In-Hospital Mortality (J Intensive Care Med, 2015) [MEDLINE]
      • In Patients with Patients with Ischemic CVA/TBI, Fever (with Peak Temperature Below 37 Degrees C or Above 39 Degrees C) Increased In-Hospital Mortality, as Compared to Normothermia (Intensive Care Med, 2015) [MEDLINE]
        • However, for Patients with Central Nervous System Infection, Elevated Peak Temperature was Not Associated with Increased Mortality, as Compared to Normothermia (37-37.4 Degrees C) (Intensive Care Med, 2015) [MEDLINE]
  • Subarachnoid Hemorrhage (SAH) (see Subarachnoid Hemorrhage)
    • Epidemiology: fever occurs in 41-72% of cases
    • Risk Factors for Fever
      • Intraventricular Hemorrhage
      • Poor Hunt–Hess Grade SAH
    • Physiology: due to a non-infectious, systemic inflammatory reaction
    • Prognosis
      • Fever is Associated with Increased Incidence of Cerebral Infarction
      • Fever is Associated with Worse Outcome
  • Traumatic Brain Injury (TBI) (see Traumatic Brain Injury)
    • Epidemiology
      • Fever is a Common After Brain Injury (Due to Traumatic Brain Injury, Ischemic CVA, and/or Intracerebral Hemorrhage) (J Intensive Care Med, 2015) [MEDLINE]
    • Prognosis
      • Fever is a Risk Factor for In-Hospital Mortality (J Intensive Care Med, 2015) [MEDLINE]
      • In Patients with Patients with Ischemic CVA/TBI, Fever (with Peak Temperature Below 37 Degrees C or Above 39 Degrees C) Increased In-Hospital Mortality, as Compared to Normothermia (Intensive Care Med, 2015) [MEDLINE]
        • However, for Patients with Central Nervous System Infection, Elevated Peak Temperature was Not Associated with Increased Mortality, as Compared to Normothermia (37-37.4 Degrees C) (Intensive Care Med, 2015) [MEDLINE]

Otolaryngologic

Pulmonary

Renal

Rheumatologic

Drugs

Intoxication

Withdrawal

Other


Physiology

Defintion of Fever

  • Fever is Defined as Morning Temperature >37.2°C (98.9°F) or Afternoon Temperature of >37.7°C (99.9°F)
    • VA Study of Normal Body Temperature (JAMA, 1992) [MEDLINE]: n = 148 healthy men and women (age 18-40 y/o), 700 measurements
      • Oral temperatures in the cohort ranged from 35.6°C (96.0°F) to 38.2°C (100.8°F) with a mean of 36.8 ± 0.4°C (98.2 ± 0.7°F)
      • Low levels occurred at 6 AM and higher levels at 4 to 6 PM
      • The maximum normal oral temperature at 6 AM was 37.2°C (98.9°F), and the maximum level at 4 PM was 37.7°C (99.9°F), both values defining the 99th percentile for healthy subjects
  • Site of Temperature Measurement
    • Rectal temperatures are generally 0.6°C (1.0°F) higher than oral readings
    • Oral readings are lower probably because of mouth breathing, which is particularly important in patients with respiratory infections and rapid breathing
    • Tympanic membrane temperature readings are close to core temperature
  • Sex Differences in Body Temperature
    • Although it is well established that women in the luteal (post-ovulatory) phase have higher body temperature, the amplitude of the circadian rhythm for body temperature is the same as in men (Respir Physiol Neurobiol, 2017) [MEDLINE]

Physiologic Implications of Fever

  • Fever May Potentiate Neurologic Injury

Clinical Manifestations

Neurologic Manifestations

  • Increased Intracranial Pressure (see Increased Intracranial Pressure)
    • Physiology: fever causes cerebral vasodilation
    • Clinical: potentiation of neurologic injury in traumatic brain injury (TBI), etc

Pulmonary Manifestations

Delayed Weaning from Mechanical Ventilation and Worsened Outcome in Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

  • Study of the Effect of Sepsis on Weaning Outcomes in Patients Recovering from Respiratory Failure (Chest, 1997) [MEDLINE]
    • Patients with Respiratory Failure and Sepsis Breathe with a Higher Respiratory Rate/Tidal Volume Ratio, Have a Lower Maximal Inspiratory Pressure, and Tend to More Likely Encounter First Day Ventilator Weaning Failure, as Compared to Patients with respiratory Failure without Sepsis
      • Severity of Illness on ICU Admission Could Explain Some of These Differences
  • Analysis of Prospective Cohort Study Evaluating the Impact of Fever on Ventilator Weaning in Patients with Acute Respiratory Distress Syndrome (Ann Am Thorac Soc, 2013) [MEDLINE]: n = 450 (from 13 ICU’s at 4 hospitals in Baltimore, Maryland)
    • Only 12% of Patients were Normothermic During the First 3 Days After Onset of Acute Respiratory Distress Syndrome
    • Fever was Associated with Delayed Liberation from Mechanical Ventilation
      • During the First Week Post-Acute Respiratory Distress Syndrome, Each Additional Day of Fever Resulted in a 33% Reduction in the Likelihood of Successful Ventilator Liberation (95% Confidence Interval for Adjusted Hazard Ratio, 0.57-0.78; P<0.001
    • Hypothermia was Associated with Delayed Liberation from Mechanical Ventilation and Increased Mortality Rate
      • Hypothermia was Independently Associated with Decreased Ventilator-Free Days (Hypothermia During Each of the First 3 Days: Reduction of 5.58 Days, 95% CI: -9.04 to -2.13; P = 0.002)
      • Hypothermia was Independently Associated with Increased Mortality (Hypothermia During Each of the First 3 Days: Relative Risk, 1.68; 95% CI: 1.06-2.66; P = 0.03)

Other Manifestations

  • Fever

Special Clinical Circumstances-Fever in the Returning Traveler


Treatment

Anti-Pyretics

Acetaminophen (Tylenol) (see Acetaminophen)

  • Clinical Efficacy
    • Australian/New Zealand Randomized HEAT Trial of Early Administration of Acetaminophen for Fever Due to Suspected Infection in the ICU (NEJM, 2015) [MEDLINE]
      • Early Acetaminophen Administration to Treat Fever Due to Probable Infection Did Not Impact the Number of ICU-Free Days (Through Day 28)

Ibuprofen (Motrin) (see Ibuprofen)

  • Clinical Efficacy
    • xxxx

Surface Cooling

  • Indications: may be indicated in those who do not respond to anti-pyretics

Intravascular Cooling

  • Indications: may be indicated in those who do not respond to anti-pyretics

References

General

  • Hyperthermia and fever control in brain injury. Crit Care Med 2009;37(7):S250-57 [MEDLINE]
  • HEAT Trial. Acetaminophen for Fever in Critically Ill Patients with Suspected Infection. NEJM 2015 vol. 373(23) pp. 2215-24 [MEDLINE]
  • Brain injury as a risk factor for fever upon admission to the intensive care unit and association with in-hospital case fatality: a matched cohort study. J Intensive Care Med. 2015 Feb;30(2):107-14. doi: 10.1177/0885066613508266. Epub 2013 Oct 16 [MEDLINE]
  • Early temperature and mortality in critically ill patients with acute neurological diseases: trauma and stroke differ from infection. Intensive Care Med. 2015 May;41(5):823-32. doi: 10.1007/s00134-015-3676-6. Epub 2015 Feb 3 [MEDLINE]

Clinical Manifestations

  • A critical appraisal of 98.6 degrees F, the upper limit of the normal body temperature, and other legacies of Carl Reinhold August Wunderlich. JAMA. 1992;268(12):1578 [MEDLINE]
  • The effect of sepsis on breathing pattern and weaning outcomes in patients recovering from respiratory failure. Chest. 1997;112(2):472 [MEDLINE]
  • Fever is associated with delayed ventilator liberation in acute lung injury. Ann Am Thorac Soc. 2013;10(6):608 [MEDLINE]
  • Gender and the circadian pattern of body temperature in normoxia and hypoxia. Respir Physiol Neurobiol. 2017 Nov;245:4-12 [MEDLINE]