Hypothermia Associated With Antipsychotic Medication: A Clinical Surveillance Study

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To the Editors
Hypothermia as a basic clinical parameter may frequently be observed in the presence of trauma, accidental undercooling in mountaineering and diving activities, severe infection, (alcoholic) intoxication, hypothyroidism, and a variety of other clinical conditions.1–5 The descriptive term hypothermia refers to the lowering of the human body core temperature to levels lower than 35.0°C.1,6,7 In mammals, the hypothalamus serves as a superordinate thermoregulatory controlling and regulating center.8 Dopaminergic neurotransmission seems to be critically involved in these complex regulatory processes,9 providing an explanation for alterations of body temperature associated with antipsychotic medication. In contrast to the well-known syndrome of malignant hyperthermia as an adverse reaction to antipsychotic medication,10 also a reduction of body temperature associated with antipsychotic drug intake has been reported previously.11–13 According to the World Health Organization database, 480 reports of hypothermia were registered in patients under antipsychotic medication in 2007.14 With the lack of systematically assessed population-based data, current estimations of the incidence of drug-associated hypothermia in clinical health care situations remain largely speculative. Thus, we consulted emergency department data of a primary health care hospital in Germany to systematically investigate the frequency of hypothermia and particularly drug-associated hypothermia.
The “Asklepios Klinik Burglengenfeld“ is a hospital located in a rural region of Bavaria (Southern Germany) with 130 beds in total and specific sections for anesthesia, surgery, and internal medicine. All patients treated in the emergency unit are classified according to the Manchester triage system,15 and the vital parameters are registered in the clinical database program as a matter of routine. Data from all internal medicine patients who were treated in 2014 with a body temperature of 35.5°C (95.9°F) or less were extracted from this clinical database. In a second step, the whole set of clinical records of each hypothermic patient was retrospectively searched for further information by hand. Thus, the following data were integrated in the study database: (a) age and sex, (b) laboratory results, (c) additional symptoms and comorbidities, (d) specific circumstances leading to hospital treatment, (e) the diagnosis at dismissal, and (f) medication at the time of (initial) presentation. In the next step, cases were screened for the following potential etiologic factors: (1) severe hypoglycemia (glucose <40 mg/dL), (2) hypothyroidism (thyroid-stimulating hormone >4.2 μIU/mL), (3) alcohol/drug intoxication, (4) infection (leukocytes >11.000/μL or C-reactive protein >5 mg/dL), and (5) antipsychotic drug intake. For descriptive statistics, mean values and SDs were calculated.
Of 1945 patients with internal ailments admitted to the emergency unit between January 1, and December 31, 2014, 53 patients (29 male/24 female) had a body temperature of 35.5°C (95.9°F) or less, corresponding to 2.72% of all patients. Overall mean (SD) age was 63.4 (20.4) years (median age, 68.3 years), and the average (SD) age of all hypothermic patients was 67.7 (21.15) years (median age, 74.6 years). One patient had moderate hypothermia (29.5°C), and all others showed mild hypothermia, with values between 34.0°C and 35.5°C (mean [SD] value, 35.1°C [0.9°C]). The percentage fractions of clinical states possibly leading to hypothermia are listed in order of their frequency: signs of infection (20.8%; 11 patients), alcohol/drug intoxication (17.0%; 9), hypothyroidism (13.2%; 7), antipsychotic drug intake (9.4%; 5), and severe hypoglycemia (5.7%; 3). In 26 patients (49.1%), no potential etiologic factor could be detected. Some patients could be allocated to 2 or more groups, but elevated leukocytes in intoxicated patients did not lead to grouping as infection.
Following our descriptive analysis, Supplementary Table 1, Supplemental Digital Content 1, http://links.lww.com/JCP/A484, shows the full set of medication lists, diagnoses, and clinical parameters of all 53 hypothermic patients. In 5 patients, antipsychotic drug intake was recorded (patients 3, 5, 18, 36, and 40).
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