Article, Toxicology

Tricyclic antidepressant toxicity treated with massive sodium bicarbonate

Case Report

tricyclic antidepressant toxicity treated with massive sodium bicarbonate

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 ug/min, dopamine at 18 ug/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

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Fig. 1 Initial recordings show a widened QRS interval and peaked T waves.

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 ug/ min and dopamine at 20 ug/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 normal- ized. As her metabolic derangements improved, her neurologic status improved. Ten hours after intensive care unit admission, the patient’s Glasgow coma

Fig. 2 ECG revealing normal sinus rhythm with flattened P waves 1 hour after ED presentation.

Table 1

ECG figure

PR interval (ms)

QRS Interval (ms)

QTC (ms)

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

Fig. 2

220

177

527

7.50 to 7.55 if the QRS complex is 111 milliseconds or

Fig. 3

162

136

591

greater, or the terminal right-axis deviation is more than 120?

Fig. 4

150

102

425

[3]. Sodium bicarbonate also narrows the QRS complex and

decreases dysrhythmias. Previous reports have not provided

a minimum or maximum dose for sodium bicarbonate

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

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 atrioventri- cular 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 ?-adrenergic blockade. The clinical result is hypotension and dysrhythmias.

The sodium bicarbonate infusion was initiated to counter- act 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

Fig. 3 ECG showing sinus tachycardia at 101.

Time

Na

K

HCO3

Cl

BUN

Cr

Ca

Phos

Mg

3

148

3.8

35.9

102

3.213

61.88

1.525

5

155

3.2

44.4

97

2.499

70.72

1.475

0.3876

0.5754

8

159

3.4

37.6

107

2.142

97.24

2.25

13

158

3.5

42.2

107

0.714

70.72

1.725

0.2261

0.7809

24

145

5.1

34.8

106

0.357

53.04

1.875

1.6796

0.7398

37

135

4.2

28.7

103

1.428

61.88

2.05

0.6576

91

138

4.0

28.3

106

3.213

70.72

2.1

0.969

0.8631

140

140

3.5

27.6

104

2.499

53.04

2.225

0.822

Reference range

137-147

3.3-5.1

20-30

97-108

1.785-9.282

70.72-150.28

2.225-2.575

0.7429-1.4535

0.7398-1.0275

SI unit

mmol/L

mmol/L

mmol/L

mmol/L

mmol/L

umol/L

mmol/L

mmol/L

mmol/L

Time on far left is time from arrival to toxicology ICU expressed in hours. All units are expressed in SI units.

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.

Table 2 Chemistry values

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.

Jessica E. Pierog DO Kathleen E. Kane MD Bryan G. Kane MD Lehigh Valley Hospital Bethlehem, PA 18107, USA

E-mail address: [email protected]

J. Ward Donovan MD PinnacleHealth Toxicology Center Pennsylvania State University

Harrisburg Hospital, Harrisburg, PA, USA

Tracey Helmick RN

Harrisburg Hospital, Harrisburg, PA, USA

doi:10.1016/j.ajem.2008.11.026

Fig. 4. After 48 hours of ICU care, patient’s ECG showed sinus tachycardia at 113.

References

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