Reply to: “Amitriptyline-induced Brugada pattern fails to respond to sodium bicarbonate”
To the Editor:
I thank Dr. Eken for his case report regarding our case of amitriptyline-induced Brugada pattern that failed to respond to intravenous sodium bicarbonate (Citation1). The use of hypertonic saline infusion for tricyclic antidepressant (TCA) toxicity is interesting and controversial. Some animal studies support it use. McCabe et al. demonstrated that hypertonic saline effectively increased blood pressure, narrowed QRS duration, and increased survival, but it was compared to normal saline (Citation2). In a followup study, he showed hypertonic saline was more effective than sodium bicarbonate; however, the dose used, 15 mEq Na+/kilogram, was much higher than the typical human dose of 1–2 mEq/kg (Citation3). An in vitro study supports the sodium loading benefit in addition to sodium bicarbonate (Citation4). One clinical example is the case report of temporal QRS narrowing after hypertonic infusion (Citation5). However, the patient's pH range was 7.49–7.54 and sodium bicarbonate bolus may have produced the same beneficial effect as it had earlier in the patient's course.
Other studies do not support the use of hypertonic saline in TCA toxicity (Citation6,Citation7). Pentel and Benowitz determined that it was just as effective as an equimolar amount of sodium bicarbonate (Citation8). In amitriptyline poisoned dogs, hypertonic saline showed no benefit over isotonic saline (Citation9). Finally, no published human studies have determined the appropriate dosing or efficacy. Because of the limited experimental data on hypertonic saline for TCA cardiovascular toxicity, it should used as a second line agent, after sodium bicarbonate. It may be used for cardiovascularly impaired patients whose pH is high or in those with refractory hypotension, wide complex dysrhythmias, and widened QRS despite sodium bicarbonate bolus.
In our report, the patient was in cardiac arrest. No cases have described hypertonic saline in TCA induced cardiac arrest. After 700 mEq of sodium bicarbonate, the patient's pH was 7.56; however, his sodium was also high at 150 mEq/L (150 mmol/L), which would have limited the use of intravenous sodium loading. Finally, his cardiovascular toxicity had responded to sodium bicarbonate, eliminating the need for alternate cardiovascular therapy.
Our patient's Brugada electrocardiographic pattern (BEP) did not resolve after sodium bicarbonate. An interesting question is whether large doses of hypertonic saline could reverse the BEP, since Brugada Syndrome is caused by slow inward myocardial sodium current. We have previously demonstrated that TCA overdoses with BEP were more likely to have complications of TCA; therefore, an effective, focused therapy would be important to characterize (Citation10). At this time no animal model exists to evaluate the role of hypertonic saline on TCA induced BEP, and no studies or cases have been published on its use.
References
- Bebarta VS, Waksman JC. Amitriptyline-induced Brugada pattern fails to respond to sodium bicarbonate. Clin Toxicol (Phila) 2007; 45(2)186–8
- McCabe JL, Menegazzi JJ, Cobaugh DJ, Auble TE. Recovery from severe cyclic antidepressant overdose with hypertonic saline/dextran in a swine model. Acad Emerg Med 1994; 1(2)111–5
- McCabe JL, Cobaugh DJ, Menegazzi JJ, Fata J. Experimental tricyclic antidepressant toxicity: A randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation. Ann Emerg Med 1998; 32(3 Pt 1)329–33
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- Pentel P, Benowitz N. Efficacy and mechanism of action of sodium bicarbonate in the treatment of desipramine toxicity in rats. J Pharmacol Exp Ther 1984; 230(1)12–9
- Nattel S, Mittleman M. Treatment of ventricular tachyarrhythmias resulting from amitriptyline toxicity in dogs. J Pharmacol Exp Ther 1984; 231(2)430–5
- Bebarta VS, Phillips S, Eberhardt A, Calihan KJ, Heard K, Waksman J. Incidence and outcomes of patients with the Brugada pattern in a large case series of tricyclic overdoses. J Toxicol Clin Toxicol 2004; 42(5)714