Fever_facts Fictions Physiology

8/2/2019 Fever_facts Fictions Physiology

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Elevated body temperature in crit-ically ill patients is a long-stand-ing concern for nurses. Studies

have shown that 29% to 36% of all hos-pitalized patients have fever listed asone of their signs and symptoms.1

Several questions usually arise. Are alllevations in temperature a fever? Ifhis is a fever, when is it severe enougho become a concern? If this is not aever, what is it? What signs and symp-oms give clues to differentiate the pos-ible causes of body temperature eleva-ion?

Temperature homeostasis is con-rolled by the hypothalamus, which acts

as a thermostat that sets the bodys tar-get temperature. In fever, this tempera-ure set point is elevated and the bodyesponds by implementing internal heatonservation methods to reach this newemperature. This heat conservationesults in an elevation in core body tem-

perature, a process that is metabolicallyxpensive. However, although fever is

often given a negative connotation, thisesponse must provide some benefit forhe host or it would not have been pre-erved throughout human evolution.2

Many different syndromes can leado elevation of body temperature. Fever

s one cause and is most frequently trig-gered by infection or inflammation.Other causes of temperature elevationare heat stroke, neuroleptic malignantyndrome, and malignant hyperther-

mia. These causes differ from feverbecause the temperature elevation seenwith these syndromes is the result of anmbalance between heat productionand heat loss rather than a change inhypothalamic set point.

Physiology of Temperature Regulation

Body temperature is controlled byhe hypothalamus, which sets the targetemperature, or set point, for the body.

This set point has diurnal fluctuationswith a nadir occurring at 6 AM and aenith at 6 PM. Although 37C is con-idered normal, each person has his or

her own baseline temperature, usuallybetween 36.4C and 37.7C. Overall,xcluding illness and exercise-induced

hyperthermia, a persons body temper-ature varies less than 1C during a life-ime.3

The hypothalamus receives feedback

through 2 different pathways.Peripheral nerves provide 1 pathway bydirecting cool/warmth sensations backto the brain. The hypothalamus pro-vides another feedback pathway bysensing heat from the surroundingbrain tissues. If either of these 2 path-ways senses a heat level above the setpoint, the hypothalamus responds tolower the body temperature by increas-ing heat loss. This increased heat lossoccurs through vasodilatation of cuta-neous circulation and increased sweat-ing from sweat glands. If the heatsensed in the periphery and around the

hypothalamus is below the set point,the hypothalamus triggers heat conser-vation through sympathetic activityleading to decreased heat dissipation.Through these mechanisms, the hypo-thalamus regulates the balance betweenheat loss and heat production.4

Pathophysiology of Fever

The thermoregulatory center islocated in the anterior portion of thehypothalamus. When the vascular bedsurrounding the hypothalamus is

exposed to certain exogenous pyrogens(bacterial) or endogenous pyrogens(interleukin-1, interleukin-6, tumornecrosis factor), arachidonic acidmetabolites are released from theendothelial cells of this vascular net-work. These metabolites, such asprostaglandin E2, cross the blood-brainbarrier and diffuse into the thermoregu-latory area of the hypothalamus, trig-gering the cascade of events that ulti-mately increases the set point. With thehigher set point established, the hypo-

thalamus sends sympathetic signals to

peripheral blood vessels, causing vaso-constriction and decreased heat lossthrough the skin. Increased sympathet-ic activity also initiates piloerection,which thickens the bodys insulatingshell. If these adjustments do not sal-

vage enough heat to match the new setpoint, shivering is triggered through thespinal and supraspinal motor system tocause an increase in heat production.The goal of the body is to reach the newset point.3

The initiation phase is the periodwhen the bodys temperature is increas-ing but has not reached the set point.Chills, cold skin, and shivering are theprimary symptoms indicating thebodys attempt to conserve heat. Theplateau phase occurs when the actualbody temperature matches the set pointtemperature. At that time, the chills andshivering cease. When the hypothala-mus is no longer stimulated by pyro-gens, the set point returns to normal.This final phase, called defervescence,is characterized by flushing, diaphore-sis, and feeling warm as the body triesto dissipate heat. In some severe statesof sepsis, these 3 phases do not occur.In this case, the toxins released by theinfection overwhelm the body, causing

early vasodilatation, loss of the abilityto conserve heat, and initiation of theshock syndrome.1 The elderly also maylose the ability to generate a fever, pos-sibly because of malnutrition, loss ofsubcutaneous fat, decreased compensa-tory peripheral vascular tone,decreased thermal feedback, orimpaired shivering.5

When fever occurs, many physiolog-ical stresses take place. Some of theseinclude increased oxygen consumptionas a response to increased cell metabo-

lism, increased heart rate, increasedcardiac output, increased leukocytecount, and an increased level of C-reac-tive protein. Oxygen consumptionincreases by 13% for every 1C increasein body temperature, provided no shiv-ering occurs. If shivering is present,oxygen consumption may increase by100% to 200%.1 Some cytokinesreleased during fever states also inducephysiological stress. These cytokinescan trigger accelerated muscle catabo-lism by causing weight loss, loss of

strength, and negative nitrogen bal-

Fever: Facts, Fiction, PhysiologyBy Ellen M. Prewitt, RN, MSN, ACNP, CCRN, Summa Health System, Akron, Ohio

FEVER:Facts, Fiction, Physiology

Learning objectives:

Differentiate 3 physiological

causes that will lead to temperatureelevation.

Describe 2 symptoms that assistin differentiating the cause oftemperature elevation.

Discuss appropriate actions forvarious cases involving temperatureelevation.


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ance. Physiological stress can be mani-ested by decreased mental acuity,

delirium, and seizures, which are morerequent in children.4

Results of studies with various ani-mal models suggest that fever has somebeneficial effects on the bodysesponse to infection. Heat shock pro-eins are one of the more recently stud-ed fever-responsive proteins. These

proteins are produced during fevertates and are critical for cellular sur-

vival during stress. Studies suggest thathese proteins may have anti-inflamma-ory effects by decreasing the levels of

proinflammatory cytokines.6 Fever alsoriggers other beneficial effects, includ-ng an increase in the phagocytic andbacteriocidal activity of neutrophils andenhanced cytotoxic effects of lympho-cytes. Some bacteria become less viru-ent and grow slower at the higher tem-peratures associated with fever.ncreased levels of C-reactive protein

promote phagocytic adherence tonvading organisms, modulate inflam-mations, and encourage tissue repair.2

Differential Diagnosis

When heat production overruns heatdissipation, an elevated temperatureesults. If this is the result of an adjustedet point in the hypothalamus, fever ishe outcome. In contrast, hyperthermia

may result from either an increase in

he bodys heat production or thebodys loss of the ability to dissipateheat efficiently. Hyperthermia can pres-ent as a symptom of various physiolog-cal conditions such as malignant

hyperthermia, neuroleptic malignantyndrome, and heat stroke.

Malignant hyperthermia is a rareautosomal dominant disorder affectinghe sarcoplasmic reticulum. In unaffect-

ed persons, the sarcoplasmic reticulumtores the calcium for the myocyte ands also responsible for the reuptake of

calcium to terminate muscle contrac-ion. In persons affected by this geneticdefect, signs and symptoms are usuallyriggered by exposure to inhalational

anesthetics or succinylcholine. Thesemedications appear to cause a rapidnflux of calcium into the sarcomere ofhe muscle cell due to the abnormalityn the sarcoplasmic reticulum. Thencrease in intracellular calcium triggersmultiple events that lead to productionof large quantities of heat. The body isunable to dissipate that amount of heat,

and hyperthermia develops. Signs and

symptoms appear suddenly, usuallystarting with ventricular ectopy, rapidrespirations, and labile blood pressure.Hyperthermia develops quickly withtemperatures increasing 1C every 5minutes and peaking at temperatures of42C to 46C. Muscle rigidity usuallyfollows, resulting from the failure ofreuptake of calcium by the sarcoplas-mic reticulum. Laboratory studies

demonstrate severe mixed acidosis,hyperglycemia, hyperkalemia, hyper-magnesemia, hyperphosphatemia, andhypercalcemia as early findings. As thesyndrome progresses, serum calciumlevels decrease and muscle enzyme lev-els increase. Elevation in creatinekinase level is frequently observed andserves as an indicator of the develop-ment of rhabdomyolysis.7

Treatment begins by immediate ces-sation of anesthesia and administrationof dantrolene sodium, which is thoughtto lower the cellular calcium concentra-tion and thus decrease heat production.Supportive care involves intravenousfluids, electrolyte monitoring and man-agement, oxygenation with possibleventilatory support, and physical cool-ing. Cooling may involve both externalcooling, by means of cooling blankets,fans, and sponge baths, and also inter-nal cooling by iced gastric or peritoneallavages. Antipyretics are ineffective inthis situation because the problem

resides in the function of the sarcoplas-mic reticulum rather than the hypothal-amic set point.4

Neuroleptic malignant syndrome isanother pharmacologically inducedhyperthermia. This syndrome is associ-ated most frequently with the use ofphenothiazines, tricyclic antidepres-sants, metoclopramide, fluoxetine, andbutyrophenones such as haloperidol.Abnormal inhibition of the centraldopamine receptors in the hypothala-mus by these drugs appears to lead to

autonomic dysregulation. This dysregu-lation leads to muscle rigidity and heatproduction. Because these dopaminereceptors normally stimulate heat loss,dysfunction then causes vasoconstric-tion and decreased ability to dissipateheat. The patient usually exhibitschange in sensorium, rigidity and invol-untary muscle movements, hyperther-mia, unstable blood pressures, tachy-cardia, tachypnea, pallor, diaphoresis,and pulmonary congestion.Dehydration, rhabdomyolysis, and

exhaustion are the possible conse-

quences.7

Treatment for neuroleptic malignantsyndrome is similar to malignant hyper-thermia. Determination and cessationof the use of the offending pharmaco-logical agent is imperative. Supportivecare is essential in order to decrease thenegative consequences. Dantrolenesodium is the drug of choice to decreasemuscular heat production by decreas-

ing intracellular calcium in themyocytes. Other medications such asbromocriptine and amantadine mayalso have some benefit.7

Heat stroke can be classified aseither classic or exertional. Classic heatstroke usually involves the very youngand very old, particularly during heatwaves. Many times, these groups areunable to satisfy thirst signals independ-ently or control their environmentaltemperature. The elderly may be takingdiuretics, anticholenergic agents, orantiparkinsonian medications that putthem at risk for dehydration and hyper-thermia. As their environmental tem-perature increases, it becomes more dif-ficult for their normal physical mecha-nisms to balance normal heat produc-tion with heat loss. Sweating is usuallyabsent because of dehydration orresults of medications. On the otherhand, exertional heat stroke usuallyresults from strenuous activity, whereheat production overwhelms the bodys

ability to dissipate it. Sweating is a com-mon finding. Athletes and those in themilitary are more prone to heat strokebecause of activity level, but forunknown reasons, this tendency is lesscommon in women. Unlike the classicform, exertional heat stroke is morelikely to manifest as lactic acidosis,rhabdomyolysis, hypoglycemia, andacute renal failure. With this youngadult age group, if pharmacologicalagents are involved, they are more like-ly to be amphetamines or cocaine.

Mental status changes, from confusionto coma, are common in both types ofheat stroke. Complications for bothtypes include renal failure, hyper-kalemia, and shock. Shock usuallydevelops because of peripheral vasodi-latation and usually responds to thecooling process. To prevent fluid over-load, fluid resuscitation with isotonicsodium chloride solution should beattempted only after cooling is initiat-ed.7

Treatment for heat stroke is first to

remove the patient from the environ-


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ment or cease activity. Supportive cares again essential, with the goal being toower the body temperature.4 Mistinghe body with tepid water is just as

effective as ice water baths but decreas-es risk of shivering. Avoiding shiverings important because shivering increas-es heat production and may lead toeizures. Ice water lavages are not rec-

ommended because they may lead to

arge fluid shifts causing water intoxica-ion and electrolyte abnormalities. Thisesult does not occur in neuroleptic

malignant syndrome and malignanthyperthermia because in those casesdehydration is not as large a compo-nent as in heat stroke. Even with aggres-ive treatment, permanent damage tohe central nervous system may occur,ncluding dystonia, thermoregulatorydysfunction, and dementia.7

Other potential causes of hyperther-mia are drug reactions, especially toantineoplastics and antibiotics, bloodeactions, and endocrine problems such

as thyroid storm and pheochromocy-oma.

Myths and History of Fever

One of the first known written refer-ences to fever was found in Akkadiannscriptions from about the sixth centu-y BC. These appear to have been inter-

pretations of ancient Sumerian hiero-glyphics depicting fever. In the fifth

centuryBC

, written works ofHippocrates presented thoughts on thepathogenesis of fever. Health, duringhat time, was described as the delicate

balance among the 4 corporeal humors:blood, phlegm, black bile, and yellowbile. An excess of yellow bile washought to cause fever. The goal was toestore balance among these humors sohat health would be restored. Willow

bark, a precursor to aspirin, was alsomentioned in his writings as a remedyor fever, along with various aches and

pains. During the Middle Ages, feverswere thought to be the sign of demonicpossession, to be dealt with on the spir-tual and ritualistic level. By the 1700s,new information on blood circulationand microbiology brought otherhypotheses that fever was caused byermentation occurring in the blood.2

One of the well-known fables ofever, which can be traced back to 1574,s Feed a cold, starve a fever. JohnWithals, a lexicographer, printed one ofhe wives tales on fever, fasting is a

great remedie for fever in one of his

books, A Short Dictionary Most Profitablefor Young Beginners. The exact statementwas first noted in Mark Twains TheCelebrated Jumping Frog of CalaverasCounty in 1865. The original thoughtto the statement was If you stuff a coldnow, you will have to later starve afever. The idea was that if an ill personwas fed, then more fuel was availablefor the body to rally a higher fever.8

Recently, several studies looked at just that idea, the bodys immuneresponse to feeding and starvation. G.R van den Brink9 spearheaded a smallstudy in the Netherlands and found thatfood intake resulted in increased cell-mediated immunity with elevated levelsof a cytokine, -interferon. This specificcytokine is thought to increase thebodys defense against chronic illnesses.When the participants received onlyliquids, higher concentrations of acytokine, interleukin-4, were found.This cytokine indicates a strongerhumoral immune response, which isassociated with antibody production,the front-line defense against acuteinfections.9 Further studies are neededon a larger scale to determine the accu-racy of these findings.

Medical Management

When elevation of body temperatureoccurs, the first priority is to determineif the elevation is due to a fever or to

hyperthermia. Evaluating signs andsymptoms, severity and onset of thetemperature elevation, absence of aprodromal period, and the clinical situ-ation in which the patient is found willhelp in differentiating fever from hyper-thermia. If the elevation in temperatureis hyperthermia, then prompt actionshould be taken, as mentioned earlier.

Fever is a sign of an underlying prob-lem. Therefore, the focus must be ondetermining the original clinical prob-lem so as to relieve that problem. Fever

is thought to be a protective response ofthe body to a clinical problem.Allowing the fever to take its course canhelp determine the cause. Fever pat-terns and timing of the fevers develop-ment can assist in including or exclud-ing certain clinical problems. Althoughantipyretics can relieve constitutionalsymptoms of malaise, headache, andmyalgias, these medications canobscure clinical information and maskinflammatory features helpful in deter-mining the cause of the clinical situa-

tion. Only if the increase in body tem-

perature is severe (to 41C) shouldfever reduction be considered.Exceptions are children with history offebrile seizures, pregnant women, anddebilitated patients with impaired car-diac, pulmonary, or cerebral function,owing to their inability to compensatefor the increased metabolic demands.4

Physiological cooling, through coolingblankets or misting, should accompany

pharmacological management. Avoid-ance of bundling the patient in blanketsis crucial because this discourages heatdissipation. Awareness of patients fluidstatus and the prevention of dehydra-tion are essential. The following is ashort summary of the more frequentlyused antipyretics. Although most ofthese are over-the-counter medications,nurses should become familiar with theuse and the consequences of misuse ofthese commonly used drugs.

Aspirin blocks the production ofprostaglandins and the brains responseto interleukin-1, which is released bymacrophages. Blocking the brainsresponse to interleukin-1 decreases thestimulation of the thermoregulatorycenter of the hypothalamus and allowsdown-regulation of the temperature setpoint. As the set point decreases, thebody then triggers vasodilatation tooccur. Recommended dosage is 325 to650 mg every 4 hours with maximum4.0 g a day for an adult. Children less

than 16 years old should not takeaspirin because of the risk of Reye syn-drome, especially after viral infections.10

Reye syndrome results in brain swellingand massive fatty deposits in the liver.

Ibuprofen also inhibits the synthesisof prostaglandin, causing less stimula-tion of the set point of temperature inthe hypothalamus. A dose of 2.4 g ofibuprofen daily is equivalent to 4.0 g ofaspirin daily. The usual dosage ofibuprofen is 200 to 400 mg every 4 to 6hours, with a maximum daily dose of

1.2 g. Because ibuprofen is metabolizedin the liver, caution is needed withpatients with liver disease.Hemorrhage, acute renal failure, hepat-ic dysfunction, and angioedema are allpossible adverse effects of both ibupro-fen and aspirin.

In the cerebral cortex, acetamino-phen is converted into an active form ofcyclooxygenase inhibitor, which has anantipyretic effect. Cyclooxygenase isthought to be responsible for stimulat-ing prostaglandin production. There-

fore, inhibiting cyclooxygenase results


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n a reduction in hypothalamic temper-ature set point, leading to vasodilatationand sweating.4 Usual dosage is 325 to650 mg every 4 to 6 hours or 1000 mg3 to 4 times a day with a maximum 4.0g a day for an adult. For infants andchildren, a reduced dose of 10 to 15mg/kg every 6 hours is recommended.Hepatotoxicity is a concern, especiallyat higher doses. Use caution with peo-

ple with liver disease, alcoholism, andmpaired renal function.10

Glucocorticoids can also be used toreat fever, functioning by inhibiting

prostaglandin synthesis. They havetrong immunosuppressive and

antiphagocytic properties, however,which limits their use during infectioustates. Meperidine, morphine, and

chlorpromazine are effective in reduc-ng severe rigors that may accompanyevers.4

An elevated body temperature maynot always be a fever. Because manyyndromes can lead to an elevated

body temperature, understanding thepathophysiology of each will provide aramework to guide the diagnosis. With

appropriate assessment, accurate differ-entiation of fever from hyperthermia ispossible. Appropriate therapy must betarted quickly to address the physical

cause of the temperature elevation.Fever is the bodys response to infec-ion. Awareness of both the beneficial

and injurious effects of fever helps toguide clinicians in the care of patients.

References

. Henker R, Kramer D, Rogers S. Fever. AACN Clin

Issues. 1997;3:351-367.

. Mackowiak PA. Concepts of fever. Arch Intern

Med. 1998;158:1870-1881.

. Boulant JA. Thermoregulation. In Mackowiak,

PA, ed. Fever: Basic Mechanisms and

Management. 2nd ed. New York, NY: Lippincott-

Raven Publishers; 1997:35-58.

. Gelfand JA, Dinarello CA. Fever and hyperther-

mia. In Fauci AS, Braunwald E, Isselbacher KJ,et al, eds. Harrisons Principles of Internal

Medicine. 14th ed. New York, NY: McGraw-Hill;

1998:84-89.

. Bender BS, Scarpace PJ. Fever in the elderly. In

Mackowiak PA, ed. Fever: Basic Mechanisms

and Management. 2nd ed. New York, NY:

Lippincott-Raven Publishers; 1997:363-381.

. Ryan M Levy MM. Clinical review: fever in the

intensive care patients. Crit Care. 2003;7:221-

225.

. Knochel JP, Goodman EL. Heat stroke and other

forms of hyperthermia. In Mackowiak PA, ed.

Fever: Basic Mechanisms and Management. 2nd

ed. New York, NY: Lippincott-Raven Publishers;

1997:437-457.

8. Flexner S, Flexner D. Wise Word and Wives

Tales: The Origins, Meanings and Time-Honored

Wisdom of Proverbs and Folk Sayings Olde and

New. New York, NY: Avon Books; 1993.

9. van den Brink GR, van den Boogardt DEM, van

Deventer SJH, Peppelenbosch MP. Feed a cold,

starve a fever? Clin Diagnostic Lab Immunol.

2002;9:182-183.

10. Turkoski BB, Lance BR, Bonfiglio MF. Drug

Information Handbook for Advanced Practice

Nursing. 3rd ed. Hudson, Ohio: Lexi-Comp Inc;

2001.

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Fever_facts Fictions Physiology