Heat Stroke in A Case Of Schizophrenia During The Treatment Of Olanzapine, Trihexyphenidyl,and Trazodone1Chin-Pang Lee, 1,2Chia-Ming Chang1Department of Psychiatry, Chang Gung Memorial Hospital, Linkou branch, Taoyuan2School of Medicine, Chang Gung University, TaoyuanNovember 2, 2013

Introduction

Heat stroke is a medical emergency with cardinal features of hyperthermia and centralnervous system dysfunction. Mentally ill patients are found to be susceptible to heatstroke, particularly under antipsychotic and anticholinergic medication. Awareness of heatstroke would reduce the risk or even prevent the development of the fatal consequencesin mentally ill patients.

Case presentation

Mr. A is a 47-year-old Taiwanese man. He only received 9 years of compulsory educationdue to his poor academic performance. At age 16, he had a blunt head trauma in a trafficaccident. There was no loss of conscious or specific sequel. He could complete mandatorymilitary service at age 20. After military service, he had been a factory worker for only afew months. He got fired due to his poor attention and performance. He had few friendsand never married. He had a loose life at home. At age 29, he suffered from the firstpsychotic episode with commentary auditory hallucination, dysphoric mood, insomnia,and poor attention. He had history of one suicide attempt by ingestion of sulfuric acid,and then he underwent tracheostomy. The tracheostomy was closed after his physicalcondition. Thereafter, He had regular followed-ups at our psychiatric clinics and receivedmaintenance treatment of chlorpromazine 150mg, trifluoperazine 10mg, and adjunctivebenzodiazepines. His medication adherence was supervised by his family. Despite therewas no overt psychotic symptoms, he still suffered insomnia, anxiety, dysphoria, markednegative symptoms as well as impaired socio-occupational function. He developed lingualtardive dyskinesia at his age 30s. At age 45, he had acute exacerbation of psychosis, man-ifesting with agitation, dysphoric mood, insomnia, and irrelevant speech. He had a suicideattempt by swallowing thumbtacks and needles, and was admitted to our psychiatric inpa-tient ward. His physical condition was stable with no complication under supportive care.His mental condition stabilized after switching to olanzapine 20 mg/d. After 1-monthtreatment, he was transferred to our chronic ward and received rehabilitative treatmentfor 8 months. However, 2 months after discharge, he had aggravated anxiety, irritability,self-talking, commanding auditory hallucination, wandering, and delusion of guilt. Hismental symptoms improved with combined olanzapine 20mg and sulpiride400mg. Due tohis prominent negative symptoms and loosening lifestyle, he was admitted to our chronicpsychiatric ward for rehabilitation at age 46. During the 2 years of repeated hospitaliza-tions, he easily got choking, and had several episodes of aspiration pneumonia. Sulpiridewas discontinued concerning possible extrapyramidal side effects (EPS). Nevertheless, hewas fair after Apr 2012. Besides olanzapine 20mg, the adjunctive medication included tri-hexyphenidyl 4mg and trazodone 50mg before bedtime. The electrocardiogram (ECG) inJune 2012 showed normal sinus rhythm. He did not have other systemic illness. He smoked2 packs of cigarettes per day, and rarely had a drink. He did not have any history of illicitdrug use. During the hospitalization of our chronic ward, Mr. A regularly had adaptivetreatment in community that he had leaves to his home in frequency of twice monthly,each lasting from 2 to 4 days. His medication adherence was supervised by his family. Mr.A had a leave on 9th, July with his family, and was scheduled to return to the ward on 10,July. At home, his mother mistakenly gave one additional dose of trihexyphenidyl 2mg atnight of 9 July. He was fair in the next morning. Heat wave hit Taiwan in July 2012. Thetemperature reached 38.3°C in Taipei on 10 July, and was the second of the all-time recordin Taipei. At 13:15, his family found him lying on the sofa and feeling uncomfortable.They had him rest and went out. However, when his family went back home at 14:00,he presented with drowsy consciousness, general flaccidity, and slurred speech. Therewas no muscle spasm, tremor, twitching, or other involuntary movement. His family didnot noticed any fever, cough, diarrhea, headache, head trauma, or other medication uselately. He was brought back to our ward immediately at 17:50. He had an ear temperatureof 40.9°C, blood pressure 116/70mmHg, pulse rate 145beats/min, and respiratory rate32breaths/min. He was confused [Glascow Coma Scale (GCS) E4V4M6] and agitated.He was immediately transferred to our emergency department (ED). At the triage hehad an ear temperature of 43.0°C, blood pressure 98/32mmHg, pulse rate 142beats/min,

respiratory rate 32breaths/min, and GCS E3V2M4. Under impression of acute respira-tory failure, he underwent endotracheal intubation and mechanical ventilation. Exceptgeneral weakness, physical examination was otherwise without abnormalities. Neurolog-ical examination by consultant neurologist showed coarse hand tremors, oral dyskinesia,equivocal limb rigidity, and absence of deep tendon reflexes; there was no lateralizing sign.All psychotropic medication was discontinued concerning possible neuroleptic malignantsyndrome (NMS). Laboratory workup was shown in Table 1. There were acute kidneyinjury, hypokalemia, and elevated muscle enzymes. The ECG showed sinus tachycardia(164beats/min), non-specific ST-T changes, and QTc prolongation (QTc= 495ms). Thechest x-ray showed hazy infiltration at the both lungs, normal heart size and configu-ration, clear costophrenic angles of the both sides, midline position of the trachea, andno evidence of pneumothorax. The non-contrast computed tomography (CT) of brainshowed infarcts in the left caudate lobe and cerebellum, in which most features fit withchronic insult. Pyuria was noted but urine culture could not be obtained due to failureof urinary catheterization. He was admitted to the neurology intensive care unit. Hisconsciousness became clear, and hyperthermia, acute kidney injury and hypokalemia im-proved with supportive care. Electroencephalography (EEG) on 11 July, did not showevidence of cortical dysfunction. His breathing was smooth under pressure support mode,and he got extubated on 12th July. His respiration was fair in the daytime. However, 15hours after extubation, he presented with tachycardia, dyspnea, and desaturation downto 90% under 70% of inspiration oxygen. Stridor was noticed over the upper airway.His condition stabilized after intravenous dexamethasone and inhalation therapy of epi-nephrine was administered. The muscle enzymes peaked on 12 July and then graduallyreturned normal. He was transferred to the neurology ward on 16 July. Gram stain of thesputum and sputum culture were obtained due to increased sputum. Empiric antibiotic,oral levofloxacin 500mg, was prescribed. Amisulpride 400mg/d was prescribed on 18 Julyfor residual psychotic symptoms. His physical condition kept stable except intermittenttachycardia. The follow-up EEG on 20 July did not show evidence of cortical dysfunction.Antibiotic was discontinued on 23 July. His blood and sputum cultures had no growth.He was transferred back to our chronic psychiatric ward on 24 July. Mr. A returned tohis baseline mental status (lack of positive symptoms but significant negative symptoms).The follow-up ECG showed sinus rhythm with occasional premature ventricular complexesor short run of ventricular rhythm. He kept well after one year follow-up except prominentnegative symptoms under amisulpride 400mg/d. He no longer had pneumonia episode.Interestingly, he had significant weight gain (from 68 to 77kg; 11.8%) in one year.

Discussion

Psychotropic agents are listed as risk factors for heat-related illness, particularly antipsy-chotics and agents with anticholinergic property. Most cases reports were associatedwith first-generation antipsychotics. Among second-generation antipsychotic, there wasone case report of heat stroke under polypharmacy of zuclopenthixol, quetiapine, andbenztropine. The `pine’ antipsychotics have anticholinergic property, and in theory mayimpair heat dissipisation. Schizophrenia is also a risk factor of heat-related illness. Theimpaired thermoregulation in hypothalamus is thought to be a key pathophysiological fac-tor in schizophrenic patients. In addition, Patients may have inadequate water intake andinactivity related to their cognitive and negative symptoms, further heightening risk ofheat-related illness.

Conclusion

Awareness of heat stroke would reduce the risk or even prevent the development of thefatal consequences in mentally ill patients. Preventive measures such as patient and familyeducation should be implemented for mentally ill patients receiving psychotropic agentsparticularly during a heat wave. Clinicians should also avoid polypharmacy as possible andinform patients and their family of risk of heat stroke under psychotropic agents.

Date 7/10 7/11 7/12 7/13 7/16 7/19

Cr 0.86 0.60 0.49ALT 29 22 40

K 3.5 3.0 3.6 4.0 4.6CRP 18.40 38.82 95.57 27.92CK 151.0 723.0 1076.0 705.0 457.0 144.0

Myoglobin 188.2 284.4 50.2 29.9Troponin-I 0.300 0.022

CK-MB 1.0WBC 8100 11300 10300 9700Hb 13.7 13.7 13.6 14.4

Platelet 207 135 248 291

Table 1 Laboratory data