Infectious Disease Compendium

Fever

Diagnosis

"Fever is a mighty engine which Nature brings into the world for conquest of her enemies." --Thomas Sydenham 1666.

What is fever, you ask? What is a normal temperature, I reply. And like every fool, you respond, "Why it's 98.6". Save me. I wish I had a nickel for every patient that said, "My normal temperature is 96, so 98.6 is a fever for me." No. Such. Thing.

ARRRGGHHHHHHHHHHHHHHHH. You know, my mind remains boggled by the number of medical people who do not know what normal temperature is, and therefore do not know what constitutes a fever. It is a so-called vital sigh, but it doesn't appear that knowing what is all that vital.

The worst thing (well, not really) that ever happened to doctors is the red line on the mercury thermometers at 98.6, although the line was important to my children when they were young as if the mercury went above the red line they got to miss school. And kids today will never know the fun of playing with mercury. Never hurt me.

98.6 is derived from 19th-century readings with miscalibrated foot long axillary thermometers and made famous by Carl Reinhold August Wunderlich in his wonderful book from 1871, On the Temperature in Diseases: A Manual of Medical Thermometry. He was the first to evaluate fever as a sign of disease, not a disease in and of itself. The book is a nice read but tests on with one of Wunderlich's thermometers showed that his instruments may have been calibrated by as much as 1.4 to 2.2°C (2.6 to 4.0°F) higher than today's instruments.

The overall mean is 36.59 from all studies. From a 2019 systematic review: "The calculated ranges (mean ± 2 standard deviations) were

37.04 (36.32–37.76) rectal,

36.64 (35.76–37.52) tympanic,

36.61 (35.61–37.6) urine,

36.57 (35.73–37.41) oral,

35.97 (35.01–36.93) axillary.

Older adults (age ≥ 60) had lower temperatures than younger adults (age <60) by 0.23°C, on average.

There was only an insignificant gender difference. Compared with the currently established reference point for normothermia of 36.8°C, our means are slightly lower but the difference likely has no physiological importance (PubMed)."

Recent studies with modern thermometers (and every health care provider should read Mackowiak et al JAMA, 1992:268 pg 1578) reveal the following:

The maximal temperature varies from a low of 37.2°C (98.9°F) at 6 AM to a high of 37.7°C (99.9°F) at 4 PM.

Please note the diurnal variation.

Ovulating women (but not ovulating men?) have the early morning relative hyperthermia. People use that as a form of natural birth control. We call those people parents. And have you ever noted that there is no such thing in Alternative Medicine as alternative birth control? Ovulation and sperm overpowers them all. And there are no meridians or acupoints on the genitals. Ironic how the life force of chi avoids the life-generating organs. Wonder why? But I digress.

Age does not significantly influence temperature. Maybe. See below.

Women have a slightly higher average oral temperature than men 36.9°C (98.4°F) versus 36.7°C (98.1°F). Or men are cooler than women? My wife would beg to differ.

Oral temperature of smokers does not differ nonsmokers.

No single temperature can be designated as the upper limit of normal. 37.2°C (98.9°F) was the maximal oral temperature (i.e., the 99th percentile) recorded at 6 AM, at 4 PM, the maximal oral temperature observed reached 37.7°C (99.9°F).

Fever is defined as an early-morning temperature of 37.2°C (99.0°F) or greater OR a temperature of 37.8°C (100°F) or greater at any time during the day. So there.

So anything above 100.4 is abnormal, but I usually start spending money at 101.

In an evaluation of 35,488 people the mean was temperature was 36.6° (97.88 in the real world) and we cool as we age (-0.021°C for every decade,) and heat up as we get fat (every 1 m/kg in BMI is associated with a 0.002°C temperature rise (PubMed). Since we get fat as we age, do the two cancel each other? And my kids would not agree with the idea that we get cooler as we get older.

We are also cooler in hot months and warmer in cold months.

One exception may be nursing home residents: "Mean population nonillness temperature was 97.7 ± 0.5 F. If “normal” were defined as less than 2 SDs above the mean, fever would be defined as any temperature above 98.7 F (PubMed)."

There is an idiopathic and rare "habitual fever" with malaise and low-grade fever in the evening that is treated with birth control pills (Pubmed).

The order is pyrogen, rigor, fever, sweat. But not all drenching sweats are due to fever.

FUO is discussed here.

Empiric Therapy

None. Fevers are good for you. Fevers augment all aspects of the immune response to infection and treating fevers either does nothing or lead to prolonged illness and worser (my 7-year-old's term) morbidity and mortality in virtually all animal and human studies. Not only that but most organisms simply cannot live at higher temperatures. Fevers exist for a purpose (my one nod to the naturalistic fallacy), mess with it at your peril.

• The resistance of animals to infection with increases in body temperature within the physiologic range.

• infection of the reptile Dipsosaurus dorsalis with Aeromonas hydrophila, Kluger and associates demonstrated a direct correlation between body temperature and survival.

• They also showed in their model that suppression of the febrile response with sodium salicylate is associated with a substantial increase in mortality. Covert and Reynolds corroborated these findings in an experimental model involving goldfish.

• In mammalian experimental models, increasing the body temperature by artificial means has been reported to enhance the resistance of mice to herpes simplex virus, poliovirus, coxsackie B virus, rabies virus, and Cryptococcus neoformans

• In a retrospective analysis of 218 patients with gram-negative bacteremia, Bryant and associates reported a positive correlation between the maximal temperature on the day bacteremia was diagnosed and survival.

• A similar relationship has been observed in patients with polymicrobial sepsis and mild (but not severe) underlying diseases.

• In an examination of factors influencing the prognosis of spontaneous bacterial peritonitis, Weinstein and coworkers identified a positive correlation between a temperature reading of greater than 38°C (100.4°F) and survival. 

• Children with chickenpox who are treated with acetaminophen have a longer time to total crusting of lesions than placebo-treated controls. 

• Adults infected with rhinovirus exhibit more nasal viral shedding when they receive aspirin than when given placebo. 

• The trend toward a longer duration of rhinovirus shedding in association with antipyretic therapy and have shown that the use of aspirin or acetaminophen is associated with suppression of the serum neutralizing antibody response and with increased nasal symptoms and signs.

• Increased resistance of rabbits to S. pneumoniae and C. neoformans, dogs to herpesvirus, piglets to gastroenteritis virus, and ferrets to influenza virus has also been observed when febrile.

And on and on. There is to my knowledge no benefit to be gained by treating a fever. Only harm.

With the caveats that if the patient does not have the cardiopulmonary reserve to tolerate a fever, has a stroke or MI or it is high enough to denature protein, then treat.

However, a meta-analysis suggests treating fevers does not prolong fevers in children (PubMed), although half the studies were in kids with malaria.

In my house, my children do not get antipyretics when they are febrile, and as a result, they are so quiet. Then I go to work and my wife, an NP, treats the fever. “Je vous renvoie à ce que disoit madame Cornuel, qu’il n’y avoit point de héros pour les valets de chambre, et point de pères de l’Église parmi ses contemporains.” N'est pas?

Treating sepsis fever in the ICU has no benefit (PubMed)(Pubmed). "Our study shows that there is no beneficial effect on reducing mortality risk with the use of antipyretic therapy in ICU patients with sepsis. External cooling may even be harmful in patients with sepsis (PubMed)." And if it does no good then it only can harm. Like all of alternative medicine.

Pearls

Antibiotics are NOT antipyretics; an obvious concept to my way of thinking. Many seem to act otherwise.

Many things can cause a fever, most of which are not treated with antibiotics. Except, probably, neutropenia and fever. And perhaps the elderly should receive antibiotics pending cultures as if the patient is > 55 and presenting to an ER with fever, the chance that the cause of the fever will be due to a serious, life-threatening infection is 66%. But get the cultures before the antibiotics are started.

An interesting article on the first-ever fever curve: (Pubmed)

Not only are fever important for the host immune system, but they also cause physicians to react: Present with sepsis and no fever: patients get less aggressive therapy, more delays in antibiotics and have a higher mortality rate (PubMed).

Rants

Cooling blankets do nothing except make the patient suffer and may increase mortality in septic patients (PubMed). They should be banned from the hospital.

Curious Cases

Relevant links to my Medscape blog

Hyperhydrosis, or Sweating with the ID doc

780.6

It Wasn't the Cigarettes

Rip, Tear, and Fever

Continuously sustained

It is what I do best.

More Rash Decisions

Persistently Continuous

Doing the Impossible

They say it is so, but I am skeptical

Ghost in the Machine

Flummoxed

Non falsifiable

Annoyed. Again.

Pyrogenic RBC

Aesthetic

A minor spleen vent

Doing Nothin'

An Old Cause of Fever

Cold

Last Update: 04/11/19.