Hypothermic overdose, not all bad?

A 51-year-old woman was brought into the Emergency Department (ED) following an intentional overdose of alcohol and her medication. Along with two bottles of wine it was estimated that she had taken 5800 mg of Quetiapine and 240 mg of Citalopram along with the wine. The ambient temperature in her flat was thought to be 10°C. On arrival to the ED her GCS was 8. She had agonal respirations with a pulse of 56/min, hypotensive 55/35 mmHg and a temperature 24°C. The patient was intubated and was given sodium bicarbonate, magnesium sulphate, calcium gluconate and an adrenaline infusion. She received active and passive rewarming measures. She had significant ECG findings related to her hypothermia and polypharmacy overdose which seemed to have been cumulative. The patient recovered and the only neurological deficit was numbness in her left leg which was thought to be related to prolonged immobility. Hypothermia may have contributed to her good outcome as hypothermia has been shown to improve both cardiac and neurological outcome.

INTRODUCTION

The case presented is a polypharmacy overdose of quetiapine, citalopram and a large amount of alcohol in an intentional overdose. The ingestion combined with environmental factors caused significant hemodynamic compromise requiring intubation, pressors, calcium, magnesium, bicarbonate and active rewarming measures. The effect of the overdose and environmental factors produced an interesting ECG and led to management decisions which are discussed in the manuscript. In this case the hypothermia that contributed to the presentation may have contributed to the patient's favorable outcome.

CASE REPORT

A 51-year-old woman presented to the emergency department (ED) in the evening following an intentional overdose of alcohol and her psychiatric medication and was not seen for the previous 24 h. She was found unresponsive at home on the kitchen floor by her parents who had been trying to contact her who then called the ambulance service to her flat. She was lying with her face down and had blood on her face and it was presumed by the paramedics that she had fallen and may have rolled on the floor as there was blood smears on the floor. She was supine on the floor and surrounded by empty packets of medication and two empty wine bottles. It was estimated from the dates on the packets and missing pills that she had taken 5800 mg of quetiapine and 240 mg of citalopram. Paramedics reported that they read the thermostat in her flat read 10°C.

Paramedics brought the patient to the ED and her Glascow Coma Scale as eight with agonal respirations, pulse of 56/min, blood pressure of 55/35 mmHg, and a core temperature of 24°C. Her ears, nose, and mouth were covered with blood from her nose. There were no other external injuries and the remainder of the exam was unremarkable.

Arterial blood gas demonstrated a pH-7.05, pCO2-55 mmHg, pO2-107 mmHg, Bicarb - 15 mmol/L, and Lactate - 11 mmol/L. Full blood count and electrolytes were unremarkable. Cardiac enzymes were not performed. The electrocardiogram (ECG) demonstrated multiple axis changes with increased QRS, prolonged QTc, ventricular ectopic beats, and Osborne (J) waves [Figure 1]. Chest X-ray demonstrated right lower lobe infiltrate suggesting aspiration. Toxicology showed an ethanol concentration of 21 mmol/L and paracetamol of < 30 μmol/L. computed tomography (CT) scans of her head and c-spine were normal.

Figure 1

Presentation ECG

In the ED, the patient was intubated and ventilated with warmed humidified oxygen. An orogastric tube was inserted and 200 ml of blood was aspirated, likely from swallowed blood as there was no other evidence of gastrointestinal bleeding or internal injury found during her hospital course. She was given 200 mmols of sodium bicarbonate, 2 g of magnesium sulfate, 4.4 mmols of calcium gluconate, and a low-dose adrenaline infusion of 0.5 mg/h. Management of hypothermia included removal of clothing, warming blanket, active warming with warmed intravenous normal saline and warmed bladder, and gastric lavage. An indwelling rectal thermometer was placed and her core temperature rose approximately 0.5°C an hour until it reached 38°C.

A Her body temperature returned to normal over the next day and her vital signs returned to normal. She was extubated 24 h later and was treated for aspiration pneumonia. She recovered completely except for numbness in her left leg. She was transferred to the psychiatric ward after 72 h of medical admission as she had admitted to this being a suicide attempt.

DISCUSSION

Alcohol is a well-known central nervous system (CNS) depressant and can contribute to hypothermia.[1] The patient presumably ingested a significant amount of alcohol (1.5 L of wine) which would have caused decreased mental status and significantly contributed to her presentation. The hypothermia may have given her some cerebral-protective effects. Therapeutic hypothermia has been shown to improve both cardiac and neurological outcomes.[2] This may have attributed to her overall recovery.

There were multiple reasons for this patient's ECG and clinical findings. Hypothermia slows impulse conduction through potassium channels in myocardial pacemaker cells, which decreases spontaneous depolarization, prolongs action potential, and generates a slowed myocardial impulse.[34] Characteristic findings include T-wave inversions, prolonged intervals (PR, QRS, and QT), muscle tremor artifact, Osborn waves, bradycardia, atrial fibrillation or flutter, atrioventricular block, premature ventricular contractions, and ventricular fibrillation.[5]

The most common ECG finding of profound hypothermia is the Osborn wave (or J-wave), which is seen in approximately 80% of hypothermic patients.[4] It is depicted as a positive deflection at the QRS-ST junction and is most prominent in precordial leads.[34] The height of the Osborn wave is roughly proportional to the degree of hypothermia.[67] Osborn waves are not pathognomonic and can be seen in hypercalcemia and cardiac arrest.[4] The physiological compensatory mechanism of shivering can cause a rhythmic irregularity of the ECG baseline, which represents a muscle tremor artifact that can resemble atrial flutter.[38]

Long QT syndrome is characterized by a prolonged QT interval and results from a disorder of myocardial repolarization.[9] Long QT syndrome may result from genetic or acquired phenomena including: Hypocalcemia, hypokalemia, hypomagnesemia, bradycardia, increased age, female sex, and congestive heart failure.[10] Drug-induced long QT is commonly caused by psychotropic medications. Antipsychotics including haloperidol, thioridazine, risperidone, quetiapine, and olanzapine were found to prolong the QT interval.[1011] Quetiapine was found to prolong the QTc interval in overdose and clinical approval studies.[1213] Another study examined the combined effect of antipsychotic medications (either haloperidol, olanzapine, risperidone, or quetiapine) with an antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine, or clomipramine) and identified “significantly increased” mean QTc intervals.[14] Citalopram has also been associated with ECG changes. At doses greater than 600 mg/day of citalopram, QT prolongation, QRS widening, and bundle branch block are produced.[15] In a case report, ingestion of only 400 mg of citalopram produced QTc interval prolongation.[15] When the corrected QT (QTc) interval exceeds a value of 450 ms, it may be associated with a risk of life-threatening arrhythmias like torsades de pointes and sudden death.[1014]

Hypothermia is not uncommon in patients with atypical antipsychotic overdose. Gibbons describes a case of hypothermia in a patient with overdose from the atypical antipsychotic ziprasidone.[16] It was thought that the hypothermia was driven by antagonism of the dopamine (D1-4) and 5-hydroxytryptamine-2 (5-HT-2) receptors.[6] Another theory was that antagonism of alpha-1 receptors caused vasodilatation and shunting of blood to the skin causing profound heat loss.[16] Quetiapine is also an antagonist to these same receptors.[17]

CONCLUSION

This patient presented in extremis and was profoundly hypothermic. The ECG is interesting in this case with its multiple findings. Overdose of psychiatric medication and alcohol may have contributed to this patient's presentation. Hypothermia likely contributed to her clinical presentation as well but also may have contributed to her favorable outcome. It is important for the emergency physician to consider the multiple possible causes when making therapeutic decisions in complex polypharmacy and environmental exposures.