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
Cytomegalovirus-Associated Infectious Mononucleosis (see Cytomegalovirus)
Epidemiology
Cytomegalovirus May Cause a Syndrome Which is Clinically Similar, But Typically Milder, than Epstein-Barr Virus-Associated Infectious Mononucleosis (see Epstein-Barr Virus) (Br Med J, 1965) [MEDLINE] (Ann Intern Med, 1973) [MEDLINE]
All Patients Received Glucocorticoid with At Least Partial Response, But Relapses were Common (Requiring Other Immunosuppressives) (Resp Med, 2023) [MEDLINE]
Pulmonary Involvement Appeared to Improve with Tocilizumab and JAK Inhibitors (Resp Med, 2023) [MEDLINE]
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]
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]
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]
Study of Data from the RIETE Registry of Symptomatic Deep Venous Thrombosis Cases (J Thromb Thrombolysis, 2011) [MEDLINE]: n = 14,480
Fever was Present (at Presentation) in 4.9% of Symptomatic Deep Venous Thrombosis Cases
Patients Initially Presenting with Fever Had a Higher Mortality Rate, as Compared to Those without Fever (5.8% vs 2.9%; Odds Ratio 2.6; 95% CI: 1.9-3.5)
Among the Causes of Death, Pulmonary Embolism (0.7% vs 0.1%) and Infection (1.1% vs 0.3%) were Significantly More Common in Symptomatic Deep Venous Thrombosis Patients Presenting with Fever
Multivariate Analysis Confirmed that Deep Venous Thrombosis Patients with Fever Had an Increased Mortality (Hazard Ratio 2.00; 95% CI: 1.44-2.77), Irrespective of the Patient Age, Body Weight, and Risk Factors for Venous Thromboembolism
Noninfectious Etiologies of Fever in the ICU (Crit Care Med, 2023) [MEDLINE]
Acalculous Cholecystitis
Acute myocardial infarction
Adrenal insufficiency
Atelectasis
Blood product transfusion
Cytokine release syndrome
Dressler syndrome (pericardial injury syndrome)
Drug fever
Fat emboli
Fibroproliferative phase of acute respiratory distress syndrome
Gout
Heterotopic ossification
Immune reconstitution inflammatory syndrome
Intracranial bleed
Jarisch-Herxheimer reaction
Malignant hyperthermia
Neuroleptic malignant syndrome
Nonconvulsive status epilepticus
Pancreatitis
Pulmonary infarction
Pneumonitis without infection
Serotonin syndrome
Stroke
Thyroid storm
Transplant rejection
Tumor lysis syndrome
Venous thrombosis
Withdrawal from certain substances including alcohol, opiates, barbiturates, benzodiazepines
Physiology
Definition 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]
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)
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)
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]
