1. 
   

   What is the difference between hyperthermia and fever?

   
   
2. 
   

   What are the underlying mechanisms of hyperthermia and fever?

   
   
3. 
   

   What are the implications of treatment for hyperthermia and fever?

   
   
4. 
   

   Who is at greatest risk of developing hyperthermia?

   
   
5. 
   

   What are the lasting effects of prolonged hyperthermia?

Vital signs are routinely measured for all hospitalized patients on admission, during nursing shifts, and when infusions are being administered. Clinicians should be able to recognize when abnormal temperatures require immediate action to avoid adverse consequences that may be potentially life threatening.

The 99th percentile for healthy individuals defines the maximum oral temperature as 37.2°C (98.9°F) at 6 am and 37.7°C (99.9°F) at 4 pm. The normal daily temperature typically varies no more than 0.5°C (0.9°F). The hypothalamus thermoregulatory center maintains a normal temperature despite variations in environment causing heat dissipation from the skin and lungs balanced by metabolic activity from muscle and liver. The postprandial state, pregnancy, and endocrine disorders may affect body temperature. The morning temperature tends to be lower in the 2 weeks prior to ovulation in menstruating women and then rises by 0.6°C (1.6°F) with ovulation until the next period (Table 90-1).

Hyperthermia

Hyperthermia is defined as an elevation in the body’s temperature due to excess generation of heat, or the inability to eliminate heat. A fever is defined as a morning temperature >37.2°C (98.9°F) and an evening temperature >37.7°C (99.9°F). Fever is a subset of hyperthermia, and the two should be distinguished from each other because hyperthermia can rapidly cause death and does not respond to antipyretics.

Hyperthermiais the elevation of the body temperature due to imbalances in metabolic heat production and heat loss, or exposure to extreme environmental heat. This is not mediated by inflammatory cytokines. Body temperatures may rise to levels greater than 41.1°C. An infectious etiology rarely results in a fever this high unless the hypothalamic regulatory center has been damaged by the infection, as might occur with a brain abscess or severe meningitis. Other causes of hyperthermia include malignant hyperthermia, neuroleptic malignant syndrome, serotonin syndrome, anticholinergic drugs, sympathomimetic drugs, thyrotoxicosis, and heat stroke (Table 90-2).

The clinical presentation of the causes of hyperthermia is varied, but the most common presentation of anyone with hyperthermia is mental status changes or confusion. Hyperthermia can be difficult to distinguish from fever, but it should be considered in the presence of a high temperature and significant mental status changes, especially when infection has been excluded. Key historical clues such as exposure to extremely high ambient temperatures or to certain medications, anesthetics, or recreational drugs should guide the clinician’s evaluation. Common offending agents include halothane, isoflurane, succinylcholine, and the recreational drugs cocaine, ecstasy, and amphetamines. An alteration in mental status is one of the earliest signs in 80% of patients with severe hyperthermia. Heat stroke is often preceded by symptoms of heat exhaustion such as fatigue, malaise, nausea, muscle cramping, and headache. The progression to mental status changes such as confusion or coma is consistent with heat stroke and the inability to dissipate excessive heat. The core temperature usually exceeds 40.0°C.

Certain populations are at greater risk for hyperthermia. The very young, very old, bedridden, and those confined to poorly ventilated areas without air conditioning are at significant risk for nonexertional heat stroke. Young men tend to be at greatest risk for exertional heat stroke, but anyone engaging in strenuous activity, especially in high ambient temperatures, is at risk. Outdoor athletes, especially football players, and military recruits have a higher incidence. Dehydration, medications with anticholinergic effects, and recreational drugs, may accelerate the time to heat stroke in susceptible populations.

Prolonged hyperthermia may result in irreversible neurologic damage. Severe morbidity and even death may result from disseminated intravascular coagulation, rhabdomyolysis, electrolyte disorders, and severe acid–base disturbances, often due to buildup of lactic acid, in the setting of sustained hyperthermia.

Fever

Fever is the most common temperature disturbance in the hospital setting. Fever is the body’s upregulation of the thermal set point, and it is mediated by the hypothalamus in response to cytokine activation. These cytokines include interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF-α). Fever is defined as a core body temperature greater than 38.0°C. Because most microbial organisms have a defined thermal range for survival, it is theorized that fever is a teleological advantage in overcoming infection. However, there is no clinical evidence that fever hastens recovery from infection or that use of antipyretics delays recovery. While noninfectious causes of fever exist, the presumption should be that an infection is the cause of fever until excluded.

Many patients may be asymptomatic and have fever as the only sign of illness. In others, fever is one marker among a constellation of signs and symptoms. Symptoms that commonly accompany fever include diaphoresis, flushing, rigors, and chills. Rigors and chills are due to the quick alteration in the body’s thermal set point, causing the sensation that the body’s current temperature (under the newly elevated set point) is too low, thus inducing a sensation of chills. The rigors, isometric contraction of muscles, are an effort to elevate the body’s core temperature to meet the new thermal set point.

In the elderly and residents of long-term-care facilities, a decline in functional status, confusion, incontinence, falling, deteriorating mobility, reduced food intake, or failure to cooperate with staff should prompt a temperature measurement and evaluation for potential infectious causes. Fever is less common in hemodialysis patients, as the core body temperature is lost with each dialysis episode; over time, the baseline thermal set point is adjusted to a value lower than normal. Elevations in temperate between 0.5°C and 1.0°C in dialysis patients should prompt evaluation for infection.

Infections are the most common cause of fever, but many noninfectious inflammatory conditions cause the release of proinflammatory cytokines with a febrile response. Noninfectious disorders rarely cause a fever greater than 38.9°C, although notable exceptions include adult Still disease, lymphoma, transfusion reactions, biologic cytokine therapy, as well as agents implicated in hyperthermia. Any temperature above this threshold should prompt an evaluation for infection, as well as consideration of hyperthermia (hyperpyrexia) not mediated by inflammatory cytokines, but by disrupted thermoregulation.

Hyperthermia

Hyperthermia is the result of a mismatch between heat production and heat loss, in the same way that overheating a home is due to a mismatch between heat production and heat loss from the home’s fireplace. The resultant problems usually stem from one of three components: there is too much firewood being burned (too much fuel), too much fire (metabolism), or too much insulation (heat retention).

The fuel (firewood) for basal metabolism must be adequate in order to generate heat. This includes normoglycemia, adequate nutrition, and adequate muscle mass. Increased muscle mass is a risk factor for malignant hyperthermia, due to increased metabolic demands. The extra available fuel allows the body to reach the higher temperatures much more rapidly because the main source of increasing basal metabolism is through skeletal muscle.

Rarely, excessive fuel supplies the cause of hyperthermia; instead, the body’s metabolism (fire) should be considered as a potential cause. Acute hyperthyroidism, malignant hyperthermia, neuroleptic malignant syndrome, and the serotonin syndrome are the common causes of acute elevations in metabolic rate. In these scenarios, the catalyst is endogenous (acute thyroid hormone elevations), or iatrogenic: anesthesia (in patients with a genetic predisposition), neuroleptics, or a combination of drugs that work on the serotonin receptors. The metabolism reaches levels far too great for the normal compensatory mechanisms of heat loss to handle.

Once fuel supplies and metabolism have been excluded, causes of heat elimination/conservation (insulation) should be considered. The vasoconstriction associated with cocaine, sympathomimetics, and anticholinergic drugs may result in hyperthermia due to the inability to expel heat. Although mortality from cocaine overdose increases substantially in hot weather due to the inability to dissipate heat, cocaine has not been shown to affect core temperature in the absence of external heat stress. Anticholinergics competitively antagonize muscarinic receptors in sweat glands, decreasing the body’s ability to sweat, a phenomenon dependent on cholinergic nerve fibers.

If the foregoing categories have been excluded, the mechanism for regulating the thermal set point (uncontrollable fire) should be considered. Core body temperature is maintained through balancing the intrinsic mechanisms of heat production and heat loss. This equilibrium is rigorously managed by the hypothalamus, brain stem, and cervical spinal cord. While damage to any of these components may result in hyperthermia or hypothermia, the most common etiology is the administration of antipsychotic drugs. Barbiturates, opioids, tricyclic antidepressants, and benzodiazepines can cause central thermoregulatory failure resulting in either hypothermia or hyperthermia. Phenothiazines impair central thermoregulation and inhibit peripheral vasoconstriction.

Although usually obvious from the history, prolonged exposure to heat may cause hyperthermia. The history or manner in which the patient is brought into the hospital should provide the clinical clues.

Fever