Citation

Pierog JE, Kane KE, Kane BG, Donovan JW, Helmick T. Am. J. Emerg. Med. 2009; 27(9): 1168.e3-1168.e7.

Copyright

(Copyright © 2009, Elsevier Publishing)

DOI

10.1016/j.ajem.2008.11.026

PMID

unavailable

Abstract

Tricyclic antidepressant (TCA) morbitity is primarily due to cardiac arrhythmias and hypotension, which become more refractory to treatment as acidosis progresses (Ann Emerg Med. 1985;14:1-9; Clin Toxicol. 2007;45:203-233; Flomenbaum N, Goldfrank L, Hoffman R, et al. Goldfrank's toxicologic emergencies. 8th ed. McGraw-Hill Companies, Inc, 2006). Early recognition and aggressive treatment are necessary for patient survival. The study aimed to discuss the treatment of TCA toxicity with the administration of sodium bicarbonate as dictated by electrocardiogram, vital signs, and clinical course. We describe the case of a 53-year-old woman with severe TCA toxicity manifested by altered mental status, hypotension, and cardiac conduction abnormalities. Seventy-five 50-mL ampules of 7.5% sodium bicarbonate were required over a 10-hour period as boluses and part of a continuous infusion. Criteria for administration of boluses included hypotension, conduction abnormalities, or deviation from goal pH on arterial blood gas. No previous publications describe this quantity of sodium bicarbonate administration, given within this short amount of time, with a successful patient outcome. Successful treatment of severe TCA poisoning requires clinical recognition of the ingestion; it may also require massive serum alkalinization and electrolyte replacement. Sodium bicarbonate can be given as frequently as needed with dosages based on clinical findings, including blood pressure, degree of conduction delay, arterial blood gas, and electrolytes. Based on this case, massive amounts of sodium bicarbonate can be given with both successful case outcome and without negative sequelae. Tricyclic antidepressant (TCA) toxicity can be a severe and life-threatening condition [1-3]. The lethality of TCA overdose is primarily due to cardiac arrhythmias [1,2,4]. We describe the case of a 53-year-old woman whose treatment included seventy-five 50-mL ampules of 7.5% sodium bicarbonate (NaHCO3) administered over a 10-hour period based on the patient's clinical course. No previous publications describe this quantity of sodium bicarbonate, given within this short amount of time, with a successful patient outcome. A 53-year-old woman was found by emergency medical services at home, unresponsive with agonal respirations, surrounded by empty pill bottles. The patient's medical history is remarkable for depression with a previous suicide attempt. Her medications include amitriptyline, venlafaxine, and desipramine. In addition, she had access to her late husband's medications including hydrocodone/APAP. The patient later admitted to taking 20 hydrocodone/APAP (7.5 mg/325 mg) tablets, 10 desipramine (100 mg) tablets, and 10 venlafaxine (150 mg) tablets 4 to 7 hours before being discovered. The patient arrived in a local emergency department (ED) with a Glasgow coma score of 3 and was intubated without medications. On exam, pupils were 4 mm, equal, round and sluggishly reactive to light. Initial telemetry recordings showed a widened QRS interval and peaked T waves (Fig. 1). The patient's blood pressure cuff measurements of 50-70/24-35 were confirmed with an arterial line. Initial treatment included 2 L of normal saline, 2 mg of naloxone IV bolus, and sodium bicarbonate 100 mEq IV bolus followed by a sodium bicarbonate drip composed of 150 mEq in 1 L of D5W (concentration used throughout) at a rate of 250 mL/h. There was no change in mental status after these medications. One hour after the patient's arrival to the ED, the electrocardiogram (ECG) revealed a normal sinus rhythm with flattened P waves (Fig. 2, Table 1). At this point, the patient was transferred to the regional toxicology center. En route, medevac administered sodium bicarbonate 100 mEq IV, 4 mg IV lorazepam for sedation, and drips of norepinephrine at 9 μg/min, dopamine at 18 μg/kg per minute, and sodium bicarbonate at 500 mL/h. On arrival to the toxicology center, the patient had no gag reflex, minimal corneal reflexes, and exhibited no spontaneous movement. Initial vital signs were as follows: blood pressure 70/40, P 100, core body temperature 34°C, saturated oxygen 100% ventilated, weight 70.45 kg. Pupils remained 4 mm, equal, round, and sluggishly reactive. Despite a lack of paralysis, extremities were flaccid and no deep tendon reflexes were noted. An ECG showed a sinus tachycardia at 101 (Fig. 3, Table 1). Infusions of norepinephrine at 30 μg/min and dopamine at 20 μg/kg per minute were followed with a central venous pressure monitor; goal established as 10 cm H2O. The sodium bicarbonate drip was continued at 500 mL/h, and an ideal arterial pH was set at 7.5 to 7.55, with the ultimate goal being persistent narrowing of the QRS interval [5]. During treatment, the patient's blood pressure quickly responded to sodium bicarbonate boluses. The QRS duration also shortened and central venous pressure improved. The bolus dosages ranged from 2 to 4 ampules of 7.5% sodium bicarbonate based on the clinical response. Arterial blood gases were drawn frequently; results were used to titrate her bicarbonate drip. Within the first 10 hours, the patient had received 1500 mEq of sodium bicarbonate IV bolus and 1000 mEq via continuous IV infusion. In addition to the bicarbonate described above, the patient received 86.4 mEq of calcium chloride (6 ampules), 6 g of magnesium sulfate, 120 mEq potassium chloride, 63 mmol of potassium phosphate, and 17 L of fluid. The patient's serial chemistries are presented in detail in Table 2. The bicarbonate drip was slowly weaned over 24 hours as her hemodynamic and acid/base status normalized. As her metabolic derangements improved, her neurologic status improved. Ten hours after intensive care unit (ICU) admission, the patient's Glasgow coma score had improved to 10T. After 48 hours of ICU care, her ECG showed sinus tachycardia at 113 (Fig. 4, Table 1). At the time of discharge from the toxicology center to the inpatient psychiatric facility, she was back to her baseline and able to perform all activities of daily living. Tricyclic antidepressant toxicity can occur with ingestion of 10 mg/kg body weight, although doses of less than 20 mg/kg are unlikely to result in severe complications or fatalities [4,6,7]. Symptoms correlate poorly with quantity ingested because of individual variation in absorption, metabolism, and protein binding, thereby limiting clinical prediction [6,7]. Measured serum drug levels have the same limitations. Therefore, the dose ingested, even if reliably confirmed, is a poor predictor of the subsequent clinical outcome [1]. Tricyclic antidepressants are variably bound to albumin in a pH-sensitive fashion [8,9]. As serum pH increases, cyclic antidepressants become increasingly albumin bound with less free drug available to impair the myocardial cells [8,9]. Alkalinizing the serum minimizes drug distribution and enhances the elimination [10,11]. Dialysis is not an option for drug removal because of the combination of the high volume of distribution and high protein binding. Thus, treatment focuses on serum alkalinization with pH goal of 7.50 to 7.55 if the QRS complex is 111 milliseconds or greater, or the terminal right-axis deviation is more than 120° [3]. Sodium bicarbonate also narrows the QRS complex and decreases dysrhythmias. Previous reports have not provided a minimum or maximum dose for sodium bicarbonate therapy. The suggested bicarbonate dose is 1 to 2 mEq/kg [5-7,12]. In the myocardium, TCAs decrease influx of sodium through gated fast channels. This blockade leads to a widened QRS complex, prolongation of PR and QT intervals, and decreases in phase 0 of the cardiac cell cycle. The blockade of the sodium channels prolongs the cardiac action potential, refractory period, and atrioventricular conduction. In vitro studies have shown that TCAs directly decrease myocardial contractility in a dose-dependent manner [1,2,7]. In addition, TCAs prevent norepinephrine and serotonin uptake and cause peripheral α-adrenergic blockade. The clinical result is hypotension and dysrhythmias. The sodium bicarbonate infusion was initiated to counteract the effects of the TCA and acidosis; however, doses considered standard did not result in improvement in the patient's condition. As a result, additional dosages were administered in bolus form. In this case study, we report 2500 mEq of sodium bicarbonate given in the initial 10 hours and a total of 3750 mEq sodium bicarbonate given over a 48-hour ICU stay. Total bicarbonate administered was in excess of 50 mEq/kg. Concomitant electrolyte therapy was also necessary. It is difficult to draw definitive conclusions from a single case, notably one with multiple ingestions. This case study illustrates the survivability of a severe TCA overdose when sodium bicarbonate administration is dictated by abnormal ECG and vital signs. The current recommended dose of sodium bicarbonate administration may be inadequate both for initial and subsequent sodium bicarbonate dosages. Based on our experience, sodium bicarbonate should be given as frequently as needed when prompted by changes in vital signs, continuous cardiac monitoring, electrolyte assessment, and arterial blood gas samples, exceeding the current recommendations. © 2009 Elsevier Inc. All rights reserved.; Indications:1 patient with depression.; Patients:One 53-year-old female outpatient.; Results:The patient was found at home, unresponsive with agonal respirations. She admitted to taking 20 tablets of hydrocodone/acetaminophen, 10 tablets of Pertofran, and 10 tablets of venlafaxine, 4 to 7 hours before being discovered. She had a Glasgow coma score of 3 and was intubated without medications. On examination, pupils were 4 mm, equal, round and sluggishly reactive to light. Initial telemetry recordings showed a widened QRS interval and peaked T waves. She received normal saline, naloxone, and sodium bicarbonate bolus followed by drip. One hour after arrival at the emergency department, ECG showed a normal sinus rhythm with flattened P waves. On arrival to the toxicology center, the patient had no gag reflex, minimal corneal reflexes, and showed no spontaneous movement. Initial vital signs were as follows: blood pressure 70/40, P 100, core body temperature 34°C, and saturated oxygen 100% ventilated. An ECG showed a sinus tachycardia. Infusions of norepinephrine and dopamine were given. The sodium bicarbonate drip was continued and an ideal arterial pH was set at 7.5 to 7.55. The patient's blood pressure quickly responded to sodium bicarbonate boluses. The QRS duration also shortened and central venous pressure improved. The patient also received calcium chloride, magnesium sulfate, potassium chloride, potassium phosphate, and fluids. At the time of discharge from the toxicology center, she was back to her baseline and able to perform all activities of daily living.; AdverseEffects:1 patient had drug intoxication characterized by agonal respiration, ECG abnormalities (widened QRS interval and peaked T waves, flattened P waves, sinus tachycardia), hypothermia and hypotension.; TypeofStudy:A case report describing tricyclic antidepressant (TCA; including Pertofran) toxicity treated with massive sodium bicarbonate in a patient with depression.; DosageDuration:10 tablets of 100 mg (=1000 mg) during intoxication. Duration: single dose.; AuthorsConclusions:This case study illustrates the survivability of a severe TCA overdose when sodium bicarbonate administration is dictated by abnormal ECG and vital signs. The current recommended dose of sodium bicarbonate administration may be inadequate both for initial and subsequent sodium bicarbonate dosages. Based on our experience, sodium bicarbonate should be given as frequently as needed when prompted by changes in vital signs, continuous cardiac monitoring, electrolyte assessment, and arterial blood gas samples, exceeding the current recommendations.; FreeText:The patient's history included a previous suicide attempt. Her medications include amitriptyline, venlafaxine, and Pertofran. Tests: electrocardiography (ECG), vital signs (blood pressure, core body temperature, saturated oxygen, weight), and Glasgow coma score. Concomitant drugs: amitriptyline, venlafaxine (10 tablets of 150 mg), hydrocodone/acetaminophen (20 tablets of 7.5 mg/325 mg).

Language: en

Keywords

adult; human; mental health; naloxone; female; survival; case report; depression; suicide attempt; morbidity; article; drug intoxication; amitriptyline; desipramine; venlafaxine; priority journal; disease course; paracetamol; potassium chloride; heart muscle conduction disturbance; hypotension; heart arrhythmia; bicarbonate; electrocardiogram; magnesium sulfate; sinus tachycardia; add on therapy; hydrocodone; potassium dihydrogen phosphate; drug dose titration; continuous infusion; vital sign; calcium chloride; acidosis