The purpose of this module is to provide the professional nurse with information from the current medical literature about:
After completing this module the learner will be able to:
Fever is a common alteration of the vital signs, and fever is a very common complication of infectious diseases. Fever can also be caused by non-infectious diseases, inflammation, injury, and by drugs. Many hospitalized patients will present with a fever; many patients develop a fever at some point during their hospital stay (Chiumello et al., 2016; Doyle et al., 2016; Nakajima, 2016; Dai et al., 2012). Fever is also one of the most common signs of illness in children (Peetom et al., 2016), and the care and treatment of patients with fever occupy a considerable amount of time for many nurses.
But despite this extensive experience, there are important questions about fever that are unanswered, and even healthcare professionals have misconceptions about the adverse effects of a fever and disagree about when and how a fever should be treated (Brick et al., 2017; Lava et al., 2016; Schortgen et al., 2012). In most cases, a fever will not cause harm, and it may be helpful. In addition, fever reduction is often not needed and may be harmful. In certain clinical situations, fever reduction can be beneficial, and nurses need to know when and how fever reduction should be done. For very young children who are febrile and the elderly patient who has a fever, the evaluation process must consider specific information about risks of fever and signs and symptoms that are specific to those groups.
Fever and hyperthermia are not interchangeable terms: they are different and distinct processes. Hyperthermia and other clinical conditions characterized by an elevated body temperature will be briefly discussed later in the module.
A 56-year-old male comes to the emergency room, and he reports that he has had abdominal pain, anorexia, diaphoresis, fever, and vomiting for five days prior to arrival. He has a past medical history of alcohol abuse and hypertension. The patient’s temperature is 39.8°C (measured rectally), his pulse is 116, his blood pressure is 78/40 mm Hg, and his respiratory rate is 28. He is pale, diaphoretic, and his extremities are cool to the touch. The results of the laboratory tests are normal except for a white blood cell count of 19, 000/μL. Because of the fever, hypotension, tachypnea, and the leukocytosis, a diagnosis of septic shock is made. Blood and urine cultures are obtained, an IV infusion of Ringer’s lactate is started, therapy with several broad-spectrum antibiotics is started, and the patient is assigned a bed in the intensive care unit (ICU). At this point (three hours after arrival at the hospital) the source of the infection is not known; the physician suspects necrotizing pancreatitis, but more diagnostic tests need to be done. The physician asks the nurse to give the patient an acetaminophen suppository, 650 mg. She also orders a cooling blanket to be applied and the patient’s temperature be monitored by a rectal probe. The physician makes a point of telling the nurse that the acetaminophen should be given before external cooling is started. The physician also informs the nurse that the current research does not provide strong evidence of a beneficial or a detrimental effect of fever control in all critical patients. However, she says that there is a lot of strong evidence that suggests that lowering body temperature in cases of septic shock may decrease mortality rate, decrease the need for vasopressors, and improve outcome. She advises the nurse to watch the patient closely for signs that cooling is proceeding too fast. Cooling techniques, she says, can lower body temperature very quickly, but temperature probes “lag” behind in the reading.
Body temperature is lowest in the early morning and highest in the early evening; the normal range is considered to be 37.2°C at 6 am and 37.9°C at 4 pm. Children normally have a body temperature that is higher than that of adults, and women who are menstruating have a greater variation in the range of body temperature than do other adults, especially in the two weeks prior to ovulation and during ovulation. Elderly people typically have a lower body temperature than adults and children. During strenuous exercise, the body temperature can be as high as 40°C, and strenuous exercise can increase heat production up to 20 times the normal level.
When we measure body temperature, we are attempting to determine the coretemperature. Core temperature is the temperature of the organs and structures deep within the body, and it is the temperature at which the body functions best. Body temperature can be measured invasively or non-invasively. These methods of measuring body temperature are all accurate and consistent if done correctly but they are all, even the sophisticated invasive methods, subject to operator error.
Oral: Measuring body temperature orally is usually an accurate and reliable method of determining body temperature, and it is convenient. Oral temperature readings are lower than the core temperature, and there are many variables that can affect the reliability and accuracy of this method. Oral temperatures are usually lower than rectal temperatures (Wang, 2011).
Rectal: Measuring body temperature rectally is the commonly used method that most accurately and consistently reflects core temperature (Batra et al., 2012; Wang, 2011).
Tympanic: Tympanic temperatures measure the heat of the tympanic membrane and the ear canal, and they are typically lower than the rectal temperature. (Wang, 2011). In children < three months old, the tympanic thermometer has been found to be less accurate if it is not placed properly in the ear canal or if there is excessive cerumen (Treitz et al., 2016).
Axillary: The axillary temperature is typically lower than an oral or a rectal temperature (Wang, 2011).
Temperature strips: Temperature strips (Tempa•Dot™ is a commonly used brand) are small plastic strips that are placed in the mouth, on the forehead, or in the axilla and measure body temperature.
Skin temperature over the carotid artery: A sensor placed on the skin over the carotid artery can accurately measure core temperature; when compared to rectal temperature measurement, this method provides readings that are accurate and consistent albeit slightly lower than rectal measurement (Imani et al., 2016; Jay et al., 2013).
Temporal artery thermometer: Temporal artery thermometers measure heat emitted from the temporal artery. The temporal artery is highly perfused, this method of obtaining a temperature has been shown to be an accurate way of estimating core temperature, and it compares well with other methods (Batra et al., 2013).
Bladder temperature sensor: A urinary bladder sensor can provide an accurate measurement of body temperature. A small study (22 patients) found that a urinary bladder sensor was more accurate than rectal or axillary measurements of body temperature (Lefrant et al., 2003).
Esophageal temperature probe:An esophageal temperature probe has been shown to provide an accurate measurement of core temperature (Snoek et al.,2016), but the accuracy is very dependent on proper positioning of the probe (Snoek et al., 2016; Makic et al., 2012).
Invasive cardiovascular catheter sensor: Most often via a pulmonary artery catheter. The temperature measured by a sensor in a pulmonary artery catheter is considered to most closely reflect core temperature (Batra et al., 2012).
The method that should be used will depend on the clinical situation. When done correctly, all methods will consistently provide a measurement of the body temperature that accurately reflects the core temperature - within their limits. The cardiovascular catheters, the bladder temperature sensors, and the esophageal temperature probes provide the closest approximation of core temperature (Stelfox et al., 2010). However, in almost all clinical situations in which a patient’s temperature must be measured, or when a patient who has a fever needs constant temperature monitoring, using the axillary, oral, or rectal methods is appropriate, accurate, and consistent (Batra et al., 2013; Jefferies et al., 2011; Rubia-Rubia et al., 2011).
A fever is an elevated body temperature. However, a body temperature that is 0.1 degree above the upper limit of normal is elevated, but this would not be a fever.
Fever then is an elevation of body temperature at or above a specific point. The definition of fever varies depending on the source; the age of the patient; the time of day when body temperature was measured, and; where and how body temperature was measured. Several definitions of fever are provided in Table 1.
Neonates and children up to three months of age: Rectal temperature ≥38.0ºC (100.4ºF) (Smitherman et al., 2017; Ward, 2016).
Children aged three months to 36 months: Rectal temperature from ≥38.0 to 39.0ºC (100.4 to 102.2ºF) (Ward, 2016).
Older children and adults: An oral temperature ≥37.8 to 39.4ºC (100.0 to 103.0ºF) (Ward, 2016).
Body temperature ≥ 38.3°C (O’Grady, the American College of Critical Care Medicine, the International Statistical Classification of Diseases and the Infectious Diseases Society of America, 2008).
Normal body temperature ranges from >37.2°C/98.9°F in the morning and >37.7°C/99.9°F in the evening, in conjunction with an increase in the hypothalamic set point (Kasper et al., 2016).
The last definition contains an important point. Fever is an elevated body temperature with a specific cause that is distinct from other mechanisms that increase body temperature. In addition, in certain clinical situations, a body temperature that is < 38°C should be considered a fever. This point will be discussed later in the module.
The letter C indicates that the temperature was measured using the Celsius scale; the letter F indicates that the temperature was measured using the Fahrenheit scale. Either scale can be used, but the Celsius scale is more commonly used by medical personnel than the Fahrenheit. Celsius will be used in this module when referring to body temperature.
To convert Fahrenheit to Celsius:
1. Subtract 32 from the temperature in degrees Fahrenheit;
2. multiply the result from step 1 by 5;
3. divide the result from step 2 by 9.
Example: 100°F - 1) 100 – 32 = 68; 2) 68 x 5 = 340; 3) 340 ÷ 9 = 37.7°C.
To convert Celsius to Fahrenheit:
1. Multiply the temperature in degrees Celsius by 9;
2. Divide the result from step 1 by 5;
3. Add 32 to the result from step 2.
Example: 36°C – 1) 36 x 9 = 324; 2) 324/5 = 64.8; 3) 64.8 + 32 = 96.8°F
A three-year-old boy is brought to the emergency room by his parents. The parents report that for the past two days the child has had a fever - the temperature has been as high as 102°F - and he has been listless, and his oral intake has been well below normal. The child has no prior medical history and does not take any prescription medications. The parents have been giving the child acetaminophen whenever his temperature was above 99°F because they had read on the internet that a high fever can cause permanent brain damage and seizures, and that “the normal temperature shouldn’t be higher than 98.6°F”. Neither parent can remember how much acetaminophen they give the child with each dose or how often they have given it and the mother says “you can buy acetaminophen at any drug store, and they wouldn’t sell it over-the-counter if it weren't safe.” They have also been giving the child ibuprofen “every once in a while” because again, they had read on the internet that using acetaminophen and ibuprofen was a better way to lower a fever than using either one alone.
After reviewing the history of the current illness and examining the child, the physician makes the diagnosis of otitis media and prescribes an antibiotic. The physician informs the parents that a temperature of 102°F is not unusual in cases of otitis media, higher fevers are not uncommon, and except for cases of hyperthermia, the seriousness of the illness does not correlate with the degree of fever. She also tells the parents:
A fever can be treated, she notes, if it is > 100.4°, but this is an arbitrary number and lowering the fever itself is not the goal; the goal is to lower the fever to make the child comfortable and help increase oral intake. Finally, she advises the parents that there is no evidence that alternating antipyretics is more effective than using one alone and that overusing over-the-counter antipyretics, especially acetaminophen and especially in the context of giving this drug to a child who has a fever, can be dangerous and cause liver damage.
Body temperature represents the balance between heat production and heat loss. Body heat is produced by the metabolic activity of organs such as the brain, heart, and liver, and by involuntary and voluntary muscular activity. These processes generate as a byproduct of their functions. Body heat is lost by radiation, conduction, convection, and evaporation. Small amounts of body heat are also lost by defecation, respiration, and urination.
Radiation is defined as the movement of heat from one object to another colder one, in this case, the body to the environment.
Conductionis defined as the transfer of heat between objects that are in contact with each other and are at different temperatures.
Evaporation is defined as is heat loss caused by vaporization of water: in humans, evaporation happens when we sweat and breathe and by insensible water loss.
Convection causes heat loss by cold air moving past and over the body. The surface temperature is lowered, blood vessels dilate to bring more heat to the skin, and heat is lost from the circulating blood.
Humans can maintain body temperature at an optimal point, increasing or decreasing heat production and increasing or decreasing heat loss. This process is called thermoregulation and thermoregulation is activated and maintained through a structure in the brain called the hypothalamus. The hypothalamus contains a group of heat-sensitive neurons collectively called the temperature regulating center. The heat sensitive neurons in the hypothalamus receive input from the temperature of the blood as it passes through the hypothalamus. The heat sensitive neurons also receive afferent messages from peripheral temperature receptors in the skin that monitor external temperature, and afferent messages about body temperature from deep tissues and the spinal cord. The thermoregulatory center of the hypothalamus can be usefully thought of as a thermostat, and it has a “set point” of body temperature that it tries to maintain in response to the conditions of the internal and external environment.
If the body temperature as sensed by the hypothalamus is too high these heat sensitive neurons in the thermoregulatory center initiate cooling mechanisms:
If the body temperature is too low, heat conservation mechanisms are initiated:
|Increased body temperature||Decreased body temperature|
|Increased sweating||Decreased sweating|
|Decreased metabolism||Increased metabolism|
|Decreased muscular activity||Increased muscular activity|
These mechanisms for heat loss and heat conservation are usually coordinated and balanced, and despite changes in the internal and external environment, a normal body temperature is maintained.
Fever is usually caused by an infection with a micro-organism, and the bacteria or the virus or other pathogen act as pyrogens and stimulate monocytes, macrophages, and Kuppfer cells to produce and release cytokines (Doyle et al., 2016; Ward, 2016). Cytokines are small proteins produced by cells of the immune system. Cytokines perform many complex activities, but they typically are involved in generating an immune response to illness or infection. These cytokines - interferon, interleukin-1, interlukin-6, tumor necrosis factor, and others - act as endogenous pyrogens, and they stimulate the hypothalamus to produce an elevated level of prostaglandin E2 (PGE2) (Doyle et al., 2016). An elevated level of PGE2 causes the “set point” of the temperature regulation center in the hypothalamus to be elevated, and this is the basic mechanism that causes fever.
When this set point is changed upwards, the thermoregulatory center senses incorrectly that body temperature is too low. Heat production and heat conservation mechanisms are activated, and the patient develops a fever (Kasper et al., 2016; Barrett et al., 2012). Elevated levels of PGE2 are also produced in the peripheral tissues, and it also accounts for the arthralgias and myalgias, aka the aches and pains, which are often part of a febrile illness.
Fever: Helpful or Harmful?
Is fever helpful or harmful? Should it be treated and if so, when, how, and in whom? Fever is one of the most common signs of illness, but even with years of experience and research, the answers to these questions are not clear (Doyle et al., 2016).
Fever has long been considered by lay people to be dangerous (Kelly et al., 2016; Bunik et al., 2012), and health care professionals are at times apprehensive and misinformed about the consequences and implications of fever (Ward, 2016; Rafaelli et al., 2016; Chiappinni et al., 2012; Sherman et al., 2012).
But fever is a self-limiting phenomenon, and in many situations, it is not harmful and is probably helpful (Doyle et al., 2016; Dai, et al., 2012; Gardner, 2012; Sherman et al., 2012). A fever can be directly toxic to the bacteria, viruses, and other pathogens that are the cause of fever, and fever can also inhibit their growth (Kiekkas, et al., 2012). Fever also increases the expression and activity of heat shock proteins (HSPs), proteins that protect the host’s cells and tissues against heat stress (Singh et al., 2013). Fever reduces the expression and activity of intracellular proteins that are produced in response to heat stress, and these proteins can be damaging to the host (Ryan, et al., 2003). Unless the elevated body temperature is caused by hyperthermia, neuroleptic malignant syndrome, or malignant hyperthermia (processes distinct from a fever that will be discussed later), feedback mechanisms prevent body temperature from rising to dangerous levels that cause systemic damage (Carey, 2010). Fever can also be used as a diagnostic and prognostic tool (Section on Clinical Pharmacology and Therapeutics et al., 2011).
However, the basic enzymatic processes of the cells and organs do not function optimally if the body temperature is abnormally elevated. Generating a fever requires the body to increase its metabolic rate six times beyond baseline (Singh et al., 2013). Increasing body temperature from 37°C to 39°C increases the metabolic rate by approximately 25%, increasing cardiac output, heart rate, and oxygen demand (Kiekkas et al., 2012).
For most people who have a fever caused by a self-limiting infectious process, the body temperature will not be that high. The fever will be unpleasant but of no consequence. But fever can be a significant stressor if a febrile patient has a chronic illness such as cardiovascular disease, diabetes, or pulmonary disease and in some clinical situations, e.g., cerebral hemorrhage or septic shock, lowering a fever can decrease mortality rate.
Infection is the most likely source of a fever, but auto-immune disorders, drugs, endocrine disorders, inflammatory reactions, malignancies, and vascular disorders can also cause fever (Bond, 2017; Miller et al., 2012; Sherman et al., 2012). Examples of non-infectious causes of fever include:
Certain drugs, because of their basic pharmacologic effects, can increase body temperature when they are taken in excess amounts. These medications increase body temperature by:
Non-steroidal anti-inflammatory drugs such as ibuprofen and corticosteroids such as prednisone can decrease the fever response to an infection.
The following are examples of commonly used drugs that can increase body temperature in these ways (Hoffman et al., 2015; Hayes et al., 2013; Olson, 2012):
|Anticholinergics, e.g., antihistamines, benztropine, tricyclic anti-depressants|
|Hallucinogenic amphetamines, e.g., MDMA (a.k.a. ecstasy)|
|Monoamine oxidase inhibitors (MAOIs)|
|Selective serotonin re-uptake inhibitors (SSRIs), e.g., fluoxetine, paroxetine can cause the serotonin syndrome, which increases body temperature.|
|Sympathomimetics, e.g., amphetamine, cocaine, phencyclidine (PCP)|
|Thyroid medications, e.g., levothyroxine|
Another non-infectious source of fever is drug fever. Drug fever is a febrile response that is caused by administration of a therapeutic dose of a medication. The elevated temperature coincides with drug administration, and the body temperature returns to normal when the drug is discontinued (Patel, 2010). Antimicrobials, anticonvulsants, and antiarrhythmics are the drugs that are the most likely to cause drug fever, but the list of medications implicated as a cause of this phenomenon is extensive (Mackowiak, 1987).
Drug fever can happen at any time, and it is not uncommon for drug fever to begin weeks, months, or even years after a medication has been first prescribed (Bor, April 27, 2016), but 7-10 days after starting medication therapy is the median time of onset (Patel, 2010). There are at least five mechanisms that can cause drug fever: a hypersensitivity reaction is the most common (Johnson et al., 1996; Hanson, 1991). Drugs that have been commonly associated with drug fever are listed in Table 4 (Bor, April 27, 2016).
Antiarrhythmic drugs (quinidine, procainamide)
Antiepileptic drugs (barbiturates and phenytoin)
|Antimicrobials (sulfonamides, penicillin, nitrofurantoin, vancomycin, anti-malarial drugs)|
Contaminants such as quinine that accompany injected cocaine or heroin
H1- and H2-blocking antihistamines
Nonsteroidal anti-inflammatory drugs (including salicylates)
Metal fume fever is a febrile illness that is caused by the inhalation of fumes that contain metal particles. Metal fume fever can happen when galvanized metal is being burned or welded, and the person or persons doing the work is not wearing a respirator.
Persons with metal fume fever typically have a fever, and they complain of a headache, malaise, and muscle aches. Metal fume fever is self-limiting; there should be no sequelae, and the illness resolves with time and supportive care, although severe cases may take several weeks to resolve (Greenberg et al., 2015; Wong et al., 2012). The pathogenesis of metal fume fever is not completely understood, but the disorder is probably caused by an inflammatory reaction and the release of cytokines and neutrophil activation (Greenberg et al., 2015; Wong et al., 2012). Treatment is symptomatic and supportive.
Polymer fume fever is caused by inhalation of fumes that are produced when polymer-containing compounds such as Teflon® are heated. The pathogenesis of polymer fume fever is incompletely understood, but it is thought to be the same as that of metal fume fever (Greenberg et al., 2015).
There is essentially no difference in the clinical presentation between metal fume fever and polymer fume fever. It is a self-limiting illness, but with repeated exposures, long-term pulmonary sequelae are possible (Greenberg et al., 2015). The treatment is symptomatic and supportive.
The typical signs of fever are chills, diaphoresis, flushing, shivering, and tachycardia. Arthralgias, malaise, and myalgias are also common. Most people who have a simple febrile illness such as influenza will be uncomfortable, and they may not feel well enough to work, but they will be able to perform basic activities of daily living.
Someone who has a fever will have noticeable signs and symptoms. She/he looks sick and feels sick, that person can tell you about the symptoms, and there is objective data - the body temperature is > 38°C - that this person is ill. However, the presentation of a febrile illness can be very different and less obvious in two populations: the elderly and the very young. There is also a complication of febrile illnesses, febrile seizures, which happens only to children; this will be discussed separately.
Infection is a very common source of illness and fever in the elderly (Mody, 2017), but advancing age increases the possibility of a medical condition, anon-infectious source, or a drug as the cause of the fever. The second consideration is that the elderly who have a febrile illness may present differently and the presence of a fever is more likely to indicate a serious illness (Mody et al., 2013; High et al., 2009; Norman, 2007).
Another important point is that the febrile response in elderly persons can be absent: approximately 20-50% of elderly patients who have a serious infection such bacteremia or meningitis may not have a fever (Loby, 2017; Cassel et al., 2003). The fever response of an elderly person can also be blunted meaning the temperature may not reach 38°C or the fever response may be essentially normal, but the patient’s baseline core temperature is lower than average, therefore, the temperature elevation does not meet the standard definition of fever (Loby, 2017; Loby et al., 2013; Cassel et al., 2003). Obviously, some part or parts of the febrile response is not normal; perhaps the sensitivity of the hypothalamus may be decreased, the quantity and activity of the endogenous pyrogens may be diminished, or the level of prostaglandin E2 produced is not sufficient. But although this phenomenon of an altered febrile response in the elderly is well known and well described, it is still not clear why it happens.
Finally, the elderly patient with a febrile illness may not have the typical signs of a fever such as chills, diaphoresis, flushing, etc.: he/she may be confused, have shortness of breath, or the patient’s activity level or mobility may be noticeably decreased (Mody et al., 2013). The safest and most sensible approach is to keep in mind the possibility of an infectious process if an elderly patient has a sudden change in his/her mental or physical functioning.
The Infectious Disease Society of America recommends a clinical evaluation if the resident of a long-term care facility has a fever, and their definition of fever in this situation is provided below (High et al., 2009). Loby (2017) concurs with this definition and adds parameters for tympanic temperature.
Evaluation of a febrile neonates or infant is far more important than fever reduction (Smitherman et al., 2017; Ward, 2016; Sherman et al., 2012) but it is also challenging. Because of their age and level of development, the physical exam is a somewhat limited tool, and there are fewer behavioral clues that can be used to determine the severity of the illness or determine what illness the child has. This patient population is more difficult to evaluate than older children. In addition, a fever in these age groups is more likely to indicate the presence of a serious bacterial infection (SBI), and an infection in the first week of life is likely to be from vertical transmission from the mother (Bunik et al., 2012). Febrile neonates and infants are at risk for a specific complication, febrile seizures.
Febrile seizures are a complication of common febrile illnesses occurring in children, and febrile seizures are the most common cause of seizures in the pediatric population. According to Ganzales (2016), the definition of a febrile seizure is:
“Seizures occurring in a child aged 6-60 months with a temperature ≥ 38 degrees C (100.4 degrees F) and no central nervous system infection, metabolic disturbance, or history of a febrile seizure.”
Febrile seizures are the most common cause of seizures in children (Feng et al., 2016). The exact incidence of febrile seizures is not known, but it has been estimated to be 2%-5% (Feng et al., 2016; Gonzales, 2016; Nilsson et al., 2016). Febrile seizures are most often associated with common infectious illnesses such as otitis media and upper respiratory infections. The most powerful risk factor for febrile seizure is age (Whelan et al., 2017). Other factors that may contribute to an increased risk for febrile seizures include: antenatal complications, day care attendance, developmental delay, family history of febrile seizure, male gender, a high peak body temperature, hypocalcemia, hypoglycemia, iron, selenium, and zinc deficiency, and microcytic hypochromic anemia (Gonzales, 2016; Sharawat et al., 2016; Graves et al., 2012). Childhood vaccinations have been associated with an increased risk for febrile seizures (Francis et al., 2016; Gonzales, 2016; Sun et al., 2012), but the risk is very small (Gonzales, 2016).
Most febrile seizures are what are called simple febrile seizures: the seizure is generalized; the duration of the seizure is < 15 minutes; there is only one seizure in 24 hours; there are no post-seizure complications or sequelae (Whelan et al., 2017; Graves et al., 2012), and; the child has no history of neurological disease. Serious neurological sequelae can occur, albeit rarely, after a simple febrile seizure, especially if the seizure was particularly long or severe, the child had a very high fever, or the seizure was caused by infection with measles or salmonella (Whelan et al., 2017).
Febrile seizures may occur once, or they may be recurrent. The risk of recurrent febrile seizures is approximately 30%-35% (Millchap et al., 2016). The risk for recurrent varies considerably, and febrile seizures appear to be clustered in children who are very young; have a first-degree relative who had febrile seizures, or; had a brief period between the onset of fever and the first febrile seizure (Millchap et al., 2016).
There are also complex febrile seizures and febrile status epilepticus (Whelan et al., 2017).
Complex febrile seizures are seizures that “. . . focal or localized to a specific part of the body, duration longer than 15 minutes but less than 30 minutes, or involves recurrence of seizures in a 24-hour period; 20–25% of febrile seizures are complex.” (Whelan et al., 2017)
Approximately one-third of febrile seizures are complex febrile seizures (Feng et al., 2016), and this type of febrile seizure is associated with a risk of developing epilepsy (Feng et al., 2016). This risk has been estimated at 6%-7% (Whelan et al., 2017), but varies widely and some research has not found an association between complex febrile seizures and epilepsy (Whelan et al., 2017).
Febrile status epilepticus is a seizure that is prolonged, lasting longer than 30 minutes or longer (Whelan et al., 2017; Millchap et al., 2016). Children who have febrile status epilepticus appear to have the same basic risk factors for the febrile seizures as children who have simple febrile seizures (Millchap et al., 2017).
Febrile seizures are treated on an individual basis. Simple febrile seizures do not require specific care, and they usually resolve spontaneously; complex febrile seizures may be treated with anti-epileptic medications (Millchap et al., 2016). Antipyretics can make the child more comfortable, but they will not prevent a recurrence (Millchap et al., 2016).
There are three clinical conditions that can cause a very elevated body temperature and that are distinct from the infectious processes and non-infectious medical conditions that were previously discussed, including hyperthermia, malignant hyperthermia, and neuroleptic malignant syndrome.
These conditions differ from the typical febrile illness in four ways:
Hyperthermia is defined as a body temperature > 40.1°C/104°F (Olson, 2012). Hyperthermia is caused by:
Heatstroke and drugs are common causes of hyperthermia. Hyperthermia is very dangerous. Body temperatures this high can denature proteins in the central nervous system and can cause irreversible brain damage. Hyperthermia can also cause acid-base-disturbances, coagulation disorders, liver damage, rhabdomyolysis, seizures, and other systemic effects. A fever caused by an excess of drugs (see Table 3) is relatively common, but hyperthermia caused by these drugs would be unusual. Antipyretics are not useful for treating hyperthermia because the elevated body temperature is not caused by an alteration of the hypothalamic set point.
Malignant hyperthermia is a life-threatening condition caused by volatile inhalational anesthetics such as halothane and by the non-depolarizing muscle relaxer succinylcholine (Prasad, 2016). It is an inherited metabolic disorder, and when people who have this disorder receive a volatile inhalational anesthetic or succinylcholine, massive amounts of calcium are released from the sarcoplasmic reticulum. This causes a very complex systemic hypermetabolic state, and the patient’s body temperature can rapidly rise as high as 45°C. Malignant hyperthermia can also be an idiosyncratic event (Prasad, 2016). Patients who have malignant hyperthermia should be given dantrolene and treated with symptomatic, supportive care (Lexicomp®, 2017; Prasad, 2016; Kearney, 2012).
Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially dangerous reaction to typical or atypical antipsychotics such as haloperidol and risperidone. These drugs are (in part) dopamine receptor antagonists, and NMS is thought to be initiated by a drastic blockade of dopamine activity in the central nervous system (Oruch et al., 2017; Rae-Grant, 2016). The decrease in dopamine activity causes intense muscular contraction, it affects the thermoregulatory center of the hypothalamus, and hyperthermia is possible. There also appears to be a genetic component to NMS (Oruch et al., 2017).
Neuroleptic malignant syndrome is very uncommon; the incidence of NMS has been estimated to be 0.02%-0.3% (Widjicks, 2014). The onset of NMS is usually within the first two weeks after starting therapy with a neuroleptic, but it can happen after one dose and after many years of taking the same drug (Widjicks, 2014).
The classic signs of NMS are autonomic dysfunction, delirium, hyperthermia, metabolic changes, muscular rigidity; a body temperature of 40°C is not unusual during NMS (Widjicks, 2014). A patient who has NMS must be treated with aggressive supportive care, including cooling methods. Amantadine, bromocriptine, and dantrolene have been prescribed as antidotes for NMS, but there is limited evidence for or against their use that they are effective (Oruch et al., 2017; Widjicks, 2014).
Children 90 days old and younger:
A child who has a fever and is three months old or younger is more likely to have a serious bacterial infection (SBI) than an older child; the incidence of SBI neonates has been estimated to be 12% (Starr, 2016). The most common source of SBI in children aged 90 days and younger is a urinary tract infection, but sepsis, meningitis, cellulitis, sinusitis, and pneumonia are possible, as well (Smitherman et al., 2017; Starr, 2016; Wang, 2011). These illnesses are very serious and especially so in this age group because children who are three months old or younger have a relatively weak immune response to infection and fewer barriers against pathogens.
Risk factors for an SBI is this population include: (Smitherman et al., 2017)
Evaluation for the presence of an SBI in these patients is complicated. Criteria that can be used to distinguish febrile children 90 days old and younger who have an SBI from those who simply have a self-limiting viral illness have been developed, e.g., the Boston, Milwaukee, Philadelphia, and Rochester criteria (Nield et al., 2011). However, these criteria do not have good specificity, and they require extensive laboratory testing (Smitherman et al., 2017; Agency for Healthcare Research and Quality, 2012). Smitherman et al. (2017) recommend that instead of using these tools, the following approach should be applied:
A well-appearing febrile infant 29-60 days old who does not have a focal bacterial infection; does not have risk factors for, or findings of a herpes simplex virus infection, and; has a rectal temperature of <38.6°C (101.5°F) – the following tests should be done.
Adults: Fever of unknown origin (FUO):
Febrile illnesses in adults are often self-limiting viral illnesses, or there is a clear cause for the fever, or the cause can be quickly determined. If the febrile illness persists and despite a complete evaluation no cause is found, this is called fever of unknown origin.
The criteria for fever of unknown origin were developed in 1961 and are listed below. Slight revisions have been suggested; they are still in use (Kasper et al., 2016; Petersdorf et al., 1961). Kasper et al. (2016) include a documented absence of an immunocompromised state in the criteria and Bor (2017) notes that neutropenic states and healthcare associated infections should be considered as well.
Fever of unknown origin is usually caused by a common disease or disorder, but the presentation is atypical (Kasper et al., 2016). The most common causes of FUO are infections such as abscesses, diverticulitis, osteomyelitis, and tuberculosis; malignancies such as malignant lymphoma, and; non-infectious inflammatory diseases such a sarcoidosis (Kasper et al., 2016). Bor lists another category for FUO, connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus (Bor, 2016). Infections, malignancies, and non-infectious inflammatory diseases/connective tissue disease are approximately equal regarding incidence as a cause of FUO (Bor, April 25, 2016). An FUO for which no cause can be found is very unusual (Bor, April 27, 2016). Drug fever should also be considered as a cause of FUO.
Assessment of a patient who has FUO should begin with history taking and a physical examination. This point seems obvious, but as noted in Kasper et al. (2016), the “. . . most important step in the diagnostic workup is the search for potentially diagnostic clues (PDCs) through complete and repeated history taking and physical examination.” Be sure to ask the patient about exposure to animals, travel experiences, and recent or past use of drugs, prescription, illicit, or over-the-counter, use of supplements or alternative medicines.
If no cause can be found after the history and physical examination or from the results of basic laboratory/diagnostic tests (e.g., blood cultures, complete blood count, chest radiography, urinalysis), then the following tests should be done (Bor, April 27, 2016):
If there is a strong suspicion that the patient has an illness such as tuberculosis, then empiric treatment can be started. Antipyretics should be used cautiously as they may make finding the cause of a FUO more difficult (Bor, April 27, 2016).
When and how should a fever be treated? The only reasonable answer is: it depends. Fever reduction should not be routinely done, and fever reduction should be subject to the same considerations as any therapy. There should be an indication for fever reduction, the patient should be considered individually to determine if she/he will benefit - or suffer - from fever reduction, and the advantages and potential adverse effects of fever reduction should be factored into the decision to use or not use cooling techniques.
Most patients who have a fever, either adults or children, have an infectious illness that is quickly diagnosed and treated or they have a non-serious, self-limiting illness such as influenza. In the first case, specific therapies are more important than fever reduction and in the second case, the illness and the fever last at most a few days and neither the illness nor the fever require specific therapies. There is no evidence that treating a fever in either of these situations will decrease the length of the illness, and there is some evidence that suggests that antipyretics and cooling techniques may prolong the course of illness (Carey, 2010). So for these patients, treating a fever would be a comfort measure and not a vital part of therapy.
But there can be times when reducing a fever can be beneficial. Treating a fever can increase patient comfort, and that can be very helpful. If the patient has a fever and has chronic cardiac or pulmonary disease, fever reduction should be considered. These patients have limited physical reserves, and the increased metabolic demand and oxygen consumption caused by a fever could be harmful. The use of fever reduction in specific clinical situations is described below.
Neonates and infants: A fever in these age groups is more likely to indicate the presence of a serious bacterial infection (SBI), and an infection in the first week of life is likely to be from vertical transmission from the mother (Bunik et al., 2012). In addition, because of their age, these children are more difficult to evaluate than older children; the physical exam is a somewhat limited tool, and there are fewer behavioral clues that can be used to determine the severity of the illness or what illness the child has.
Fever evaluation in these patients is more important than fever reduction.
The American Academy of Pediatrics recommends that acetaminophen and ibuprofen should not be used in febrile children < three months of age and six months of age, respectively (Section on Clinical Pharmacology and Therapeutics et al., 2011). Ward (2016) writes “Fever may be the only sign of serious infection in a young infant, and such infections should be excluded before symptomatic treatment of fever is initiated.
Children: In most febrile children, fever is caused by a self-limiting viral illness so lowering body temperature is not necessary. However, fever reduction can make the child more comfortable, help her/him maintain an adequate state of hydration, and antipyretics have an analgesic effect, as well (Ward, 2016).
Carefully evaluate each febrile child on a case-by-case basis. Fever can be one of the signs of a serious illness in a child (Ward, 2016; Hague, 2015) or if the febrile child has a pre-existing condition like a cardiac abnormality, reducing a fever may be wise.
Acute brain injury: fever reduction is recommended for patients who have had an acute brain injury (Chiumello et al., 2016; Doyle et al., 2016).
Sepsis: Fever increases the inflammatory response of sepsis, but it helps decrease the pathogen load (Doyle et al., 2016). Current literature reviews indicate that fever reduction in a septic patient may be beneficial; it is unlikely to be harmful, and; it not be routinely done, only considered on a case-by-case basis and with recognition of the benefits and risks (Chiumello et al., 2016; Doyle et al., 2016).
Status epilepticus: Fever decreases seizure threshold and fever reduction is commonly recommended for patients having status epilepticus reduction (Doyle et al., 2106; Ehrlich, 2017)
Stroke: Fever has been identified as a risk factor for poor outcome in patients who have had a stroke (Chiumello et al., 2016). Fever reduction is recommended by the American Heart Association/American Stroke Association guidelines (Jauch et al., 2013), and it is commonly recommended by other authoritative sources, but there is no definitive evidence that for adult or pediatric stroke patients fever reduction is beneficial (Chiumello et al., 2016; Doyle et al., 2016; Grelli et al., 2016).
Reducing fever in critically ill patients who have a neurological injury has many positive effects. It can decrease cerebral edema, decrease the metabolic rate and oxygen demand of the brain, enhance cellular function, decrease the risk of seizures, and reduce intracranial pressure (Polderman, 2008). However, the line between benefits and risks of fever reduction in this situation appears to be small, and it is not well defined.
Fever reduction can be done using antipyretics drugs to reset the temperature-regulating center of the hypothalamus, by using physical cooling techniques that encourage heat loss, or by using both. Both methods are effective: the physical cooling techniques work faster, but they are more complex and time consuming to initiate and monitor than using antipyretics.
The drugs that are used as antipyretics are non-steroidal anti-inflammatories (NSAIDs) such as aspirin and ibuprofen, or acetaminophen. Aspirin is very seldom used and the reason for this will be discussed later.
The NSAIDs inhibit the activity of cyclooxygenase-1 and cyclooxygenase-2 enzymes. Decreased activity of these enzymes decreases the amount of prostaglandin that is formed and the set point of the temperature regulating center is re-adjusted to the normal level. The antipyretic mechanism of acetaminophen is not completely understood, but it probably works through the temperature regulating center of the hypothalamus.
Either drug can be used for fever reduction, but ibuprofen is slightly more effective (Jayawardena et al., 2016; Wong et al., 2014). The safety profile of each drug is comparable, but ibuprofen is more likely to cause GI distress, and it should be used cautiously in people who are dehydrated or who have renal impairment. Acetaminophen therapeutic overdoses are a leading cause of liver failure.
Alternating acetaminophen and ibuprofen have often been recommended as a useful technique for lowering fever in children. There is no conclusive evidence that this technique is more effective than using a single drug (Wong et al., 2014; Pereira et al., 2012)
Physical cooling can be done by using simple, traditional methods such as fans, cool bathing, and ice packs; air-circulating blankets, water circulating blankets and hydrogel-coated water circulating pads; endovascular cooling devices, cold peritoneal lavage, rectal or nasal lavage, or infusion of cold IV fluids, and; extracorporeal access and infusion of cold fluids (Doyle et al., 2016; Salgado et al., 2016; Tunali et al., 2016; Hammond et al., 2011; Polderman et al., 2009).
Some of these methods no longer appear to be in favor because they are ineffective (fans) unpleasant and/or have a short duration of action (cool bathing), or they are labor and time intensive (rectal or nasal lavage). There are few reviews of head to head comparisons of physical cooling methods. The two found by this author suggest that endovascular cooling devices are superior to external, surface cooling devices (Doyle et al., 2016; Hammond, et al., 2011). The one review this author found that compared pharmacologic cooling to physical cooling found physical cooling to be superior (Hammond et al., 2011), an opinion shared by Doyle et al. (2016).
Side effects associated with or caused by cooling methods include (Doyle et al., 2016, Polderman et al., 2009):
Of these five, the first four are obviously concerning but shivering, by common definition, sounds relatively benign. However, Shah et al. (2012) found that shivering caused by cooling blankets and ice packs increased VO2 by almost 60% and increased blood pressure by 15%. Doyle et al. (2016) noted that shivering “. . . promotes the cardiovascular and respiratory stress response and increases cerebral metabolic stress.”
Many lay persons have misconceptions about fever. They believe a fever is dangerous; the higher the temperature, the greater the danger; fever can cause brain damage, and; a fever will almost always cause febrile seizures (Elkon-Tamier et al., 2017; Purssell et al., 2016). Misconceptions about fever and how to treat it are not uncommon in healthcare professionals, as well (Martins et al., 2016; Greensmith et al., 2013).
These beliefs can be very upsetting at the least and at the worst can cause behaviors that are non-productive and occasionally, harmful (Peetoom et al., 2016). Emergency rooms see many, many patients who have a simple viral syndrome and the patient or the patient’s parents specifically because of concern about a high fever. Patients and parents may overuse antipyretics and over-the-counter cough and cold preparations. Therapeutic overuse of acetaminophen can cause liver damage, and the excessive dosing of a cough and cold preparations that are used to treat febrile illness can, and has caused serious harm (Acheampong et al., 2016; Bertille et al., 2016; Lancaster et al., 2015). Patient education about fever can do much to avoid this emotional distress and encourage sensible treatment of a fever.
The following points about fever and febrile illnesses should be discussed with parents (UpToDate; Ward, 2015):
Aspirin should not be given to a child who has a fever or to anyone 19 years of age or younger (Ward, 2015). Aspirin is an effective antipyretic, but its use in febrile children has been associated with an encephalopathic disease called Reye’s syndrome. Reye’s syndrome is quite rare, and the link between aspirin and Reye’s syndrome is still somewhat controversial: some authorities do not believe aspirin can cause Reye’s. But Reye’s syndrome is a very serious disease, acetaminophen and ibuprofen are as effective as aspirin, and if they are used correctly, they are much safer, as well.
Other medications such as antibiotics, vitamin supplements, mineral supplements, and antihistamines will not be effective treatments for children who have a fever from a simple illness (Fashner, et al., 2012), and parents should never treat a febrile child with any medication unless the pediatrician has been consulted and approved its use.
Some children who have a fever do have a serious illness, and some children are susceptible to SBIs. If a child has a fever, parents should be instructed to bring the child to the pediatrician as soon as possible in these situations (UpToDate):
Much of the same information for parents applies to adults. Adults who have a fever should be instructed to rest and stay well hydrated. An over-the-counter cough and cold medications offer minimal benefit, and some of the ingredients they have can cause harmful interactions with many commonly used prescription medications. For example, dextromethorphan is an anti-tussive, and it can cause serotonin syndrome if it is used in combination with anti-depressants such as fluoxetine or paroxetine. Phenylephrine is a decongestant that is a sympathomimetic, and it should not be used, or only used cautiously by people who have cardiovascular disease. Acetaminophen or ibuprofen can be used for fever control. But adults, especially older adults, should check with a physician before using these medications. Acetaminophen may not be safe for someone who has liver disease, and ibuprofen should be used cautiously by people who have gastric ulcers. Aspirin is an effective antipyretic, but even for adults, it is not the drug of choice. Acetaminophen and ibuprofen are safer alternatives, especially for elderly adults.
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