Fever

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Chapter 13 Fever

Jeffrey R. Avner, MD

1 What percentage of visits to the emergency department (ED) is for the evaluation of fever?

Fever is one of the most common presenting symptoms at the pediatric ED, representing 15–30% of all visits. During the first 2 years of life, a child typically has 4–6 episodes of febrile illness.

2 What temperature is considered normal?

There is no single value that represents a “normal” temperature. This is largely because normal body temperature varies with age, time of day, physical activity, and environmental conditions. This individual variability limits the application of mean body temperature values derived from population studies. Thus, no single temperature should be used as the upper limit of normal. Rather, normal temperature is best described as a range of values for each individual. Although only a rough guide, some consider abnormal temperature to be >38.0–38.2°C (rectally) in an infant and 37.2–37.7°C (orally) in an older child or adult.

3 Who is credited with the first systematic measurement of body temperature?

In the 1860s, German physician Carl Wunderlich used foot-long thermometers to record over 1 million axillary temperature readings from 25,000 patients. He identified 37.0°C (98.6°F) as the mean temperature of healthy adults.

4 Does body temperature vary during the day?

The variation of body temperature in typical circadian rhythm becomes established by 2 years of age. Peak temperature typically occurs in late afternoon (5:00–7:00 pm), and the trough occurs in early morning (2:00–6:00 am). Daily temperature variation ranges from 0.1°C–1.3°C.

5 How does the body produce fever?

During infection, exogenous pyrogens (microbial products such as endotoxins) produced by various infectious organisms act on host inflammatory cells (especially monocytes and macrophages) to produce numerous cytokines, including endogenous pyrogens (interleukin, tumor necrosis factor, interferon). These circulating pyrogens act on the preoptic area of the anterior hypothalamus, which produces prostaglandin E₂ and causes fever.

6 Where is the core body temperature set?

Core body temperature is set in the anterior hypothalamus. Variation in body temperature is detected by thermosensitive neurons in the preoptic nucleus, which then directs autonomic changes in sweat glands, blood vessels, somatic neurons, and skeletal muscles.

7 How does the body regulate temperature?

Thermoregulation is controlled by a variety of physiologic and behavioral mechanisms under the direction of the hypothalamus. Elevation of body temperature occurs primarily through metabolic activity associated with increased cell metabolism, increased muscle activity, and involuntary shivering. Body temperature is decreased primarily through vasodilatation, which thereby increases heat loss by conduction, convection, or radiation through the skin. In addition, sweating and cold preference behavior (e.g., removing clothes) help dissipate the heat.

8 Is fever beneficial or harmful?

Whether fever is friend or foe is a question for the ages. Fever has some physiologic benefits for the host, including an enhancement of both cellular and humoral immune responses as well as direct antimicrobial activity. On the other hand, fever makes the child uncomfortable and leads to a significant increase in metabolic activity (about 10% per degree Centigrade), which increases oxygen consumption, carbon dioxide production, and insensible water loss. Whether the benefits outweigh the metabolic costs is debatable. Regardless, the presence of fever alerts the parents and clinicians that the child is in the process of fighting disease and, as such, can serve as an invaluable diagnostic aid.

9 What is “fever phobia”?

Barton Schmitt coined the term in the early 1980s in reference to parents’ excessive concern about low-grade fever. Nowadays, the term fever phobia is often used to describe heightened anxiety about the presence of fever in the child that can lead to unnecessary ED visits, laboratory testing, or empiric antibiotic treatment. Of note, both parents and providers may have “fever phobia.”

Corneli HM. Beyond the fear of fever. Clin Ped Emerg Med 1:94–101, 2000.

Crocetti M, Moghbeli N, Serwint J: Fever phobia revisited: Have parental misconceptions about fever changed in 20 years? Pediatrics 107:1241–1246, 2001.

Poirer MP, Davis PH, Gonzalez-Del Rey JA, et al: Pediatric emergency department nurses’ perspectives on fever in children. Pediatr Emerg Care 16:9–12, 2000.

Schmitt BD: Fever phobia: Misconceptions of parents about fevers. Am J Dis Child 134:176–181, 1980.

10 What are the normal increases in heart rate and respiratory rate with each degree rise in body temperature?

Fever is associated with an increase in heart rate of about 10 to 15 beats per minute and an increase in respiratory rate of about 3 to 5 breaths per minute for each rise in degree Centigrade.

11 Does bundling cause fever in infants?

Overbundling of young infants, especially during the summer months, is known to increase measured temperatures. If an infant is heavily bundled or in a particularly hot environment, a 30- to 60-minute period of equilibration should be followed by a repeat temperature determination. This issue is particularly important in the evaluation of young febrile infants because the height of the fever by itself is often a determinant for proceeding with an evaluation for sepsis.

12 What are the differences in measurement among rectal, oral, and axillary temperature readings?

The core body temperature is best measured with an esophageal or nasopharyngeal probe, but this is difficult in the setting of an ED. Therefore, rectal temperature is used as the standard measurement to indirectly measure core body temperature. Oral measurement in the sublingual pocket is estimated to be 0.5–1°C lower than rectal temperature. Axillary temperatures are imprecise, inaccurate, and insensitive and therefore of limited value.

Craig JV, Lancaster GA, Williamson PR, et al: Temperature measured at the axilla compared with rectum in children and young people: Systemic review. BMJ 320:1174–1178, 2000.

13 Does otitis media increase tympanic membrane temperature?

Infrared tympanic thermometry is a popular method used in EDs, and recent studies show that, at least in older children and adults, the results are reasonably accurate. Otitis media has been shown to increase tympanic temperatures only slightly, by about 0.4°C. Interestingly, although nonobstructive cerumen does not affect tympanic thermometry, cerumen that completely obstructs the ear canal leads to underestimation of temperature.

Kelly B, Alexander D: Effect of otitis media on infrared tympanic thermometry. Clin Pediatr 30:46–48, 1991.

14 Can parents detect fever subjectively?

When parents say that their child is “burning up” with fever, they are usually correct. In general, parents are both moderately sensitive (75–85%) and specific (75–85%) in detecting the presence of fever subjectively in children. However, they may not be as accurate in estimating the height of fever. In young infants (less than 2 months old), when the height of the fever is crucial for determining management, always obtain a rectal temperature.

Hooker EA, Smith SW, Miles T, et al: Subjective assessment of fever by parents: Comparison with measurement by noncontact tympanic thermometer and calibrated rectal glass mercury thermometer. Ann Emerg Med 28:313–317, 1996.

15 When sponging a child for treatment of fever, what is the best temperature for the water?

The value of sponging to decrease temperature is controversial. Sponging uses evaporation to help cool the child. Sponging can be used in combination with an antipyretic and may take up to 20 minutes to be effective. Use tepid or lukewarm water so that the child remains comfortable and does not shiver. Never use cold water or isopropyl alcohol, as they cause excessive vasoconstriction and shivering. In addition, isopropyl alcohol can be toxic through skin absorption.

16 What did Hippocrates feel was the role of fever?

Hippocrates, the father of medicine, felt that fever helped balance the four humors (blood, yellow bile, black bile, and phlegm), which were believed to cause disease when out of balance. At the current time, this theory remains unproven!

17 Does high fever cause brain damage?

Although this concern is a cornerstone of “fever phobia” by parents, this fear is unfounded. Temperatures < 42°C have not, by themselves, been associated with any serious sequelae. Deleterious effects of temperatures > 42°C are based on in vitro effects on enzyme systems and not clinical studies. When brain damage does occur in association with fever, it is usually due to sequelae of the underlying disease (such as meningitis) rather than the fever itself.

18 Does fever trigger seizures?

Fever lowers the seizure threshold in children with an underlying seizure disorder and may precipitate a seizure in children (6 months to 5 years old) who are susceptible to simple febrile seizures. Fever, by itself, in the absence of predisposing factors, does not cause seizures.

19 Does teething cause fever?

Although some studies show a mild temperature elevation associated with teething, significant fever (temperature > 38.8°C) has never been shown to be associated with tooth emergence.

Macknin ML, Piedmonte M, Jacobs J, Skibinski C: Symptoms associated with infant teething: A prospective study. Pediatrics 105:747–752, 2000.

20 Why is the use of rubbing alcohol on children harmful?

Topical application of isopropyl alcohol can cause severe intoxication in children due to skin absorption or inhalation exposure. Furthermore, the resultant cooling effect on the skin causes peripheral vasoconstriction and limits the child’s ability to dissipate internal heat.

21 Does the response of fever to an antipyretic predict a more benign illness?

No. Fever response to antipyretics is not clinically useful in differentiating children with serious bacterial illness from those with a more benign etiology. Most children, regardless of the underlying etiology of their fever, experience some temperature decline with antipyretics, although rarely do they become afebrile. The decision to perform additional diagnostic tests, such as a complete blood count or lumbar puncture, should be determined on clinical grounds and not based on the degree of defervescence.

22 Is alternating acetaminophen and ibuprofen more effective for fever reduction?

Although a common practice among pediatricians, there is currently no scientific evidence that this combination of antipyretics has greater efficacy than either agent used alone and may, in fact, increase fever phobia and potential toxicity from incorrect dosing.

Mayoral CE, Marina RV, Rosenfeld W, Greensher J: Alternating antipyretics: Is this an alternative?. Pediatrics 105:1009–1012, 2000.

23 What are the risk factors to consider in evaluating a febrile child?

Children who have either immature or specific impairment of immunologic function are at higher risk of bacteremia and serious bacterial illness. Therefore, very young infants (less than 2 months), children with immune compromise (e.g., HIV infection, sickle cell disease), and children receiving immunosuppressive medication (such as chemotherapy and steroids) may require a blood culture and empiric antibiotic treatment as part of their management.

24 Why do we treat infants less than 2 months old with fever differently than the older child?

There are three main reasons: (1) the risk of serious bacterial illness in this age group is relatively high (approximately 10%), (2) young infants have immature immune responses that may not be able to contain infection, and (3) clinical appearance is difficult to interpret. At this age, the ability of a child to interact in an interpretable social manner is inconsistent. For example, a social smile is inconsistent, if not absent, in a 1-month-old. In a study by Baker et al, 66% of febrile infants 1–2 months of age with bacterial diseases were judged well-appearing by the ED attending physician.

Baker MD, Bell LM, Avner JR: Outpatient management without antibiotics of fever in selected infants. N Engl J Med 329:1437–1441, 1993.

25 What are the common pathogens that cause serious bacterial illness in febrile infants?

In infants less than 1 month old, maternal organisms, acquired perinatally, predominate: group B streptococcus, gram-negative enteric organisms, and Listeria. In infants older than 6 weeks, community-acquired organisms predominate: pneumococcus, meningococcus, and Haemophilus influenzae type B. Infants 4–6 weeks old are infected by pathogens from either age group. Immunizations have decreased the incidence of H. influenzae type B and pneumococcus.

26 What are low-risk criteria for the management of febrile infants?

In an attempt to avoid routine hospitalization of all febrile young infants, many investigators have sought to devise clinical and laboratory criteria that would identify a subset of febrile infants at “low risk” of having bacterial disease as a cause of their fever. Three major prospective studies have established somewhat different low-risk criteria (Table 13-1).

Table 13-1 Low-Risk Criteria for the Management of Febrile Infants

27 What is a “sepsis workup”?

A “sepsis workup” is typically considered an evaluation of certain body fluids for bacterial infection. It usually includes a complete blood count; urinalysis; lumbar puncture; and cultures of blood, urine, and spinal fluid. A “septic workup” is a test performed with a dirty needle.

28 Do all febrile infants need a sepsis workup and admission?

Although there is no absolute consensus, most agree that febrile infants less than 1 month of age require an evaluation for sepsis. Many also feel that the same evaluation applies to infants 1–2 months old. However, some clinicians withhold a lumbar puncture in well-appearing febrile infants. Infants younger than 1 month and those infants at high risk should be hospitalized pending culture results. Infants 1–2 months old who are at low risk (see Table 13-1) for serious bacterial illness may be managed as outpatients if follow-up is assured.

Avner JR, Baker MD: Management of fever in infants and children. Emerg Med Clin North Am 20:49–67, 2002.

Pantell RH, Newman TB, Bernzweig, et al: Management and outcomes of care of fever in early infancy. JAMA 291:1203–1212, 2004.

29 Do young febrile infants with respiratory syncytial virus (RSV) bronchiolitis need a sepsis workup?

A recent multicenter study of over 1200 infants (22% with RSV) found that febrile infants (< 60 days old) with RSV were at significantly lower risk of serious bacterial illness than RSV-negative infants; although the rate of certain infections, especially urinary tract infections, remained appreciable. However, in febrile infants less than 28 days old, the risk of serious bacterial illness remained “substantial” (about 13%) and was not altered by the presence of RSV infection.

Levine DA, Platt SL, Dayan PS, et al: Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections. Pediatrics 113:1728–1734, 2004.

KEY POINTS: THE FEBRILE INFANT

1 In febrile infants less than 28 days old, the risk of serious bacterial illness is substantial (about 10%) and is not altered by the presence of RSV infection.

2 Urinary tract infection is the most common bacterial infection in febrile infants less than 2 months old.

3 For well-appearing febrile infants 4–8 weeks old, a variety of testing and management strategies are available.

30 What is occult bacteremia?

Occult means “mysterious” or “hidden.” Bacteremia means bacteria in the blood. Simply put, occult bacteremia is unsuspected bacteria in the blood. This entity is used to describe a subset of febrile children (usually 3–36 months old) who are well-appearing and have no focus of infection but, nevertheless, have bacteremia. About 1–3% of such children in this age group have occult bacteremia. Note that the entity of occult bacteremia does not apply to a child who is ill-appearing or has an obvious focus of infection on physical examination.

31 What are the common pathogens for occult bacteremia?

The common pathogens are all encapsulated organisms. Streptococcus pneumoniae is responsible for 85–90% of cases, with the remainder shared among Neisseria meningitidis, group A streptococci, Salmonella sp., and Staphylococcus aureus. H. influenzae type B was a common pathogen prior to the widespread use of the HIB vaccine.

32 How will universal pneumococcal vaccine use affect the incidence of occult bacteremia?

The PCV-7 vaccine protects against seven of the most common serotypes involved in occult pneumococcal bacteremia. Since pneumococcal bacteremia is responsible for about 90% of cases of occult bacteremia, elimination of these serotypes will lead to a significant decline in the incidence of occult bacteremia. Some researchers suggest that the eventual occult bacteremia rate will drop to below 0.5% after vaccination.

Kaplan SL, Mason EO, Wald ER, et al: Decrease of invasive pneumococcal infections in children among 8 children’s hospitals in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine. Pediatrics 113;443–449, 2004.

Stoll ML, Rubin LG: Incidence of occult bacteremia among highly febrile young children in the era of the pneumococcal conjugate vaccine: A study from a Children’s Hospital Emergency Department and Urgent Care Center. Arch Pediatr Adolesc Med 158:671–675, 2004.

KEY POINTS: THE FEBRILE CHILD

1 Pneumococcal bacteria are responsible for about 90% of cases of occult bacteremia in children age 3–36 months.

2 The incidence of occult bacteremia is likely to decline to about 0.5% with the universal use of pneumococcal vaccination.

33 Does the height of the fever indicate serious bacterial illness?

A child with a very high fever (temperature > 41.1°C) is more likely to have occult bacteremia than a child with lower fever, but is not appreciably more likely to develop serious bacterial illness. In fact, most children with serious bacterial illness, such as meningitis, have a temperature below that range. Thus, it appears that the presence or absence of fever is what is most important. This does not mean that a thorough evaluation of a child with high fever is unnecessary; rather, any child with fever, regardless of the height of the temperature, should receive a complete evaluation.

34 What is the natural outcome of children with occult bacteremia?

Infection with S. pneumoniae, the most common cause of occult bacteremia, has the highest rate of spontaneous resolution. Most studies show that only a small number (4–7%) of untreated children with occult bacteremia caused by S. pneumoniae develop an invasive disease, such as meningitis. Invasion rates are higher for H. influenzae type B (7–20%) and N. meningitidis (25–35%). Whether empiric antibiotic therapy prevents the rare sequelae of occult bacteremia remains controversial. Clinicians should consider not only the probabilities of occult bacteremia and its progression to serious illness but also the cost of, and the value placed by parents on, the process of trying to detect these rare events.

35 Is the peripheral white blood cell count a helpful screen for bacteremia in otherwise healthy febrile children?

The risk of occult bacteremia increases as the white blood cell count increases; however, since the overall incidence of occult bacteremia is very low, the positive predictive value of the white blood cell count for occult bacteremia is also fairly low, thus limiting its utility as a screening test.

Bonsu BK, Harper MB: Identifying febrile young infants with bacteremia: Is the peripheral white blood cell count and accurate screen? Ann Emerg Med 42:216–225, 2003.

36 Should the decision on whether to perform a lumbar puncture on a febrile child be guided by the height of the fever or the peripheral white blood cell count?

No! Neither of these measures is sensitive enough at any threshold to predict meningitis. The criteria for lumbar puncture should be based on history and physical examination findings rather than nonspecific laboratory tests.

37 Why is the presence of a petechial rash in a febrile child of concern?

A petechial rash, especially if associated with fever, may be an early sign of infection with an invasive bacterial organism, especially N. meningitidis. Early identification of a child with meningococcemia is essential since the disease can progress rapidly and has high morbidity.

38 What is the incidence of invasive bacterial disease in children with fever and petechiae?

The most common bacterial causes of fever and petechiae are N. meningitidis, H. influenzae type B, S. pneumoniae, group A streptococcus, S. aureus, and Escherichia coli. The incidence of invasive bacterial disease has been estimated to be as high as 20% in children who are hospitalized. However, in a prospective study of 411 children with fever and petechiae who presented to a hospital ED, the incidence was only 1.9%. This study, performed in the post–H. influenzae type B vaccine era, included children who were managed as outpatients.

Mandl KD, Stack AM, Fleisher GR: Incidence of bacteremia in infants and children with fever and petechiae. J Pediatr 131:398–404, 1997.

39 What evaluation is necessary in managing the child with fever and petechiae?

If the child is ill-appearing or immunocompromised, a complete evaluation for sepsis is necessary. Hospitalization and empiric antibiotics are essential. Children who are well-appearing and have no clear cause for the petechiae should have a complete blood count and blood culture, as well as a rapid streptococcal antigen test if there is pharyngitis. Additional studies, such as coagulation tests and lumbar puncture hospitalization and need for empiric antibiotics are somewhat controversial. Management must be individualized. Most physicians admit and treat with parenteral antibiotics any child who is young (< 12 months) or has an elevated (or low) white blood cell count. For children who have normal laboratory tests, outpatient management with close follow-up is an option. The experience with outpatient antibiotic treatment in meningococcal disease is limited.

40 How long must fever be present to be considered fever of unknown origin (FUO)?

The definition of FUO has changed over recent years. FUO was applied to any febrile illness with unexplained, persistent temperature > 38.5°C for 3 or more weeks. In light of more sophisticated diagnostic techniques, many investigators have shortened the minimum duration of fever to 5–7 days.

41 What is the difference among intermittent fever, spiking fever, remittent fever, sustained fever, and relapsing fever?

Lorin and Feigin provide the following useful definitions: Intermittent fever refers to a pattern where the temperature returns to normal at least once a day. Hectic or spiking fever has a high peak and quick defervescence. In remittent fever, the temperature fluctuates, but always remains elevated. Sustained fevers remain persistent with little fluctuation. In relapsing fever, the temperature may return to normal for as much as a day or more before fever returns.

Lorin MI, Feigin RD: Fever of unknown origin. In McMillan JA (ed): Oski’s Pediatrics, 3rd ed. Philadelphia, Lippincott Williams & Wilkins, 1999, pp 844–848.

42 What is the leading cause of FUO?

In pediatrics, almost half of the cases of FUO are due to infectious diseases (usually respiratory tract infections, followed by infections of the urinary tract, skeleton, and central nervous systems).

43 How often does FUO have no diagnosis or resolve spontaneously?

Almost 25% of children with FUO are either undiagnosed or have spontaneous resolution.

44 What is the difference between fever and hyperthermia?

Fever is caused by a rise in the hypothalamic set point, which is usually the result of the triggering of several pyrogenic cytokines. Hyperthermia is often used to describe a condition in which the thermoregulatory system is either dysfunctional or simply overwhelmed by a variety of internal or external factors. Hyperthermia may result from disorders of excessive heat production (exertional heatstroke, thyrotoxicosis, cocaine intoxication), disorders of diminished heat dissipation (classic heatstroke, severe dehydration, autonomic dysfunction), or disorders of hypothalamic function (cerebrovascular accidents, trauma).

45 How do you decrease body temperature in children with heatstroke?

Management of heatstroke begins with aggressive attempts at cooling, such as ice packs, fanning, ice water immersions, and, occasionally, cool IV fluids, until the core temperature drops below 39°C. Avoid antipyretics and alcohol sponge baths (see question 15). Further management includes airway and cardiovascular support, IV rehydration, and pressor support if necessary.

46 What kind of fever is associated with bizarre movements in response to disco music?

Saturday Night Fever was first identified in the 1970s in a group of adolescents wearing unbuttoned silk shirts, flared pants, and platform shoes.

WEBSITES

1 eMedicine Health http://www.emedicinehealth.com/articles/10035-1.asp

2 eMedicine Health http://www.emedicine.com/emerg/topic377.htm

3 University of Chicago Priztker School of Medicine, Pediatrics Clerkship http://pedclerk.bsd.uchicago.edu/evaluationoffever.html

4 National Guideline Clearinghouse http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=4620&nbr=3401

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