Annals of Long Term Care

Introduction

Hypothermia is defined as a core temperature below 35 degrees C (95 degrees F), and can be further classified by severity1 (Table I). Fever is the most commonly encountered disorder of thermoregulation; however, hypothermia was the reported cause of death of 16,655 persons in the United States between 1979 and 2002 (average, 689 persons/yr). Nearly one-half of these deaths involved patients older than age 65 years, with an overall male-to-female ratio of 2.5:1.2,3 In addition, researchers have speculated that hypothermia could explain some of the unexpected sudden deaths that have been observed in patients treated with neuroleptic drugs.4,5

Important risk factors that predispose the body to poor temperature regulation include very young or advanced age, the presence of comorbid conditions such as infections, and hypothyroidism.2 Additional comorbid conditions, which often occur in the psychiatric population, increase the risk of hypothermia. These include nocturnal enuresis, seizure disorder, debilitating physical illness, and mental retardation. The risk of hypothermia in this population is further increased by the use of several classes of medications used to treat psychiatric disorders, such as typical and atypical antipsychotics, beta-adrenergic antagonists, benzodiazepines, and other sedatives.4,6

Multiple potential etiologies of hypothermia include environmental exposure, hypothyroidism, adrenal insufficiency, sepsis, neuromuscular disease, malnutrition, and hypoglycemia. Certain medications such as beta-blockers, clonidine, meperidine, and general anesthetic agents can impair a patient’s ability to compensate for a low ambient temperature and increase the risk of accidental hypothermia.1 Hypothermia has been described previously as an adverse reaction to neuroleptic drugs, particularly to phenothiazines, but also to haloperidol and olanzapine.5

Differential diagnosis of hypothermia in psychiatric patients should include primary accidental hypothermia, central nervous system (CNS) disorders, metabolic disorders, infections, and medications7 (Table II).

This article presents a case of a geriatric patient with multiple comorbidities, who was presumed to have experienced clozapine-induced hypothermia.

Discussion

The body temperature regulation center is located in the hypothalamus. Dopamine, noradrenaline, and serotonin systems are considered to be involved in temperature regulation. Blockade of alpha-receptors involved in peripheral vasodilation is also important.5 Medications can alter the body temperature by acting on any component of the thermoregulatory system, including heat production, heat conservation, heat loss, and thermosensors.8

Dopaminergic mechanisms are involved in both the genesis and the dissipation of body heat. This can explain why neuroleptic medications can cause temperature dysregulation and produce either hypothermia or hyperthermia.6,9 In animals, and possibly in humans, ambient temperature may be a factor in determining whether hypothermia or hyperthermia is produced. The most dramatic and devastating syndrome of temperature dysregulation due to antipsychotics is neuroleptic malignant syndrome, a life-threatening emergency typically presenting as hyperthermia, muscle rigidity, delirium, and autonomic instability. Neuroleptic malignant syndrome has been described in patients treated with typical antipsychotic agents, as well as in patients treated with the newer atypical antipsychotics.6

In addition, antipsychotic blockade of skin alpha-1 receptors may reduce the shivering capability and cause peripheral vasodilatation.10,11 Some researchers have attempted to antagonize the hypothermia in animals produced by peripheral administration of two neuroleptics with phenylephrine, an alpha-adrenoceptor agonist that does not cross the blood-brain barrier.