Ms. B.: Schizophrenia, dementia, and eventually accidental hypothermia
Over the course of several months, Ms. B., a woman in her mid-70s, manifested features of accidental hypothermia, which went undiagnosed amid a backdrop of a long history of schizophrenia and a more recent history of dementia.
In 1996, almost 5 years before developing accidental hypothermia, Ms. B. sought care for paranoia, nervousness, and dysphoria. The records showed a history of cigarette abuse, diet-controlled type 2 diabetes mellitus of more than 20 years duration, and kidney surgery. She was cognitively intact and had received doses of up to 3 mg/bid of risperidone and desipramine. A few months later, temazepam was added for insomnia. Still later, following the death of her husband, lorazepam was added.
Until late 1999, Ms. B. remained psychiatrically stable. Then she became more anxious and her lorazepam dosage was increased. But in June 2000, she was admitted to a local hospital following a month of confusion, weakness, and slurred speech. The precipitating event was a fall. A head CT scan showed brain atrophy and white-matter disease. Extensive condylomata led to a partial vulvectomy. Her lowest recorded oral temperature was 95.6°F.
Ms. B. returned to a residential home briefly but was readmitted when she was found unresponsive; hypotension and bradycardia were detected. Cardiac catheterization showed normal left ventricular function and severe 3-vessel coronary artery disease with a 50% obstruction of the left main coronary artery. This procedure was complicated by severe agitation, confusion, and a large post-catheterization hematoma requiring blood transfusions.
Following discussions with the cardiac surgeons, the family considered Ms. B. too ill to undergo coronary artery bypass surgery. The lowest recorded oral temperature was 94°F.
Ms. B. returned to the residential home—but not for long. In August 2000, she was again taken to the hospital. She was confused, threatening to harm herself with a knife, and eating “hair grease.” Her medications now included temazepam, lorazepam, risperidone, paroxetine, and desipramine—plus aspirin, verapamil, lisinopril, metoprolol, amlodipine, and isosorbide dinitrate for coronary heart disease and hypertension. The admission database included a temperature of 96.2°F. She received a Global Assessment of Functioning score of 20 contrasted with a high score of 70 the preceding year.
Ms. B.’s hospital stay lasted 2 months. Confusion and disorientation persisted one month after admission while still undergoing psychiatric care. Midway during her hospitalization, she underwent a cholecystectomy.
When she was discharged to an assisted living facility, Ms. B. required assistance with self-care and restraint with a posey vest. Dementia was considered the major psychiatric problem. Medications now included amlodipine, aspirin, famotidine, isosorbide dinitrate, lisinopril, metoprolol, oxybutynin, metoclopramide, lorazepam 0.5 mg 3 times a day, and risperidone 1 mg twice daily.
Two weeks later, Ms. B. was still confused and disoriented. Risperidone was increased to 1 mg 3 times daily and lorazepam was increased to 0.5 mg 4 times daily. A week later, the nursing staff noted further deterioration. She would wander, on occasion even into the street. Subsequently, she began disrobing for no apparent reason, 3 to 4 times a week.
In early December 2000, nurses called an ambulance because Ms. B. was “lethargic, unresponsive to name call.” The ambulance crew noted she was “foaming at the mouth,” lying "naked" in bed, and very “cold” to the touch. At the hospital, hypothermia was documented with a body temperature of 84°F rectally. (Of note, the patient’s roommate manifested a normal body temperature, was cognitively intact, and did not complain that their room was cold.) Medications at the time of admission included lisinopril 10 mg/d, aspirin 325 mg/d, amlodipine 10 mg/d, oxybutynin 5 mg twice daily, lorazepam 0.5 mg 3 times daily, metoprolol 50 mg twice daily, famotidine 20 mg twice daily, isosorbide dinitrate 10 mg 3 times daily, metoclopramide 10 mg 4 times daily, and risperidone 1 mg twice daily.
Initially, Ms. B. manifested bradycardia requiring temporary pacing, and hemoconcentration without explanation for the low body temperature. Despite return to normal body temperature within 24 hours, vasomotor instability, body temperatures ranging between 95.9°F and 100.1°F, encephalopathy, and general organ failure persisted. Ms. B. was pronounced dead on the 18th hospital day. An autopsy was not performed.
Amlodipine, a calcium channel blocker, enhances vasodilatation and may also have limited Ms. B.’s capacity to vasoconstrict. Calcium channel blockers may have variable effects on intraoperative core body temperature in humans.10
Phenothiazines, particularly the low-potency agents in this class, are the antipsychotic drugs most commonly associated with drug-induced hypothermia.6,9,11 Phenothiazines seem to have a direct effect on hypothalamic thermoregulation. About a month before developing moderate hypothermia, Ms. B. received an increase in her risperidone dosage from 1 mg twice daily to 1 mg 3 times daily because of agitation. The package insert for risperidone states: