Can empirical hypertonic saline or sodium bicarbonate treatment prevent the development of cardiotoxicity during serious amitriptyline poisoning? Experimental research: cardiovascular topic

Abstract

SummaryObjectiveThe aim of this experimental study was to investigate whether hypertonic saline or sodium bicarbonate administration prevented the development of cardiotoxicity in rats that received toxic doses of amitriptyline.MethodThirty-six Sprague Dawley rats were used in the study. The animals were divided into six groups. Group 1 received toxic doses of i.p. amitriptyline. Groups 2 and 3 toxic doses of i.p. amitriptyline, plus i.v. sodium bicarbonate and i.v. hypertonic saline, respectively. Group 4 received only i.v. sodium bicarbonate, group 5 received only i.v. hypertonic saline, and group 6 was the control. Electrocardiography was recorded in all rats for a maximum of 60 minutes. Blood samples were obtained to measure the serum levels of sodium and ionised calcium.ResultsThe survival time was shorter in group 1. In this group, the animals’ heart rates also decreased over time, and their QRS and QTc intervals were significantly prolonged. Groups 2 and 3 showed less severe changes in their ECGs and the rats survived for a longer period. The effects of sodium bicarbonate or hypertonic saline treatments on reducing the development of cardiotoxicity were similar. The serum sodium levels decreased in all the amitriptyline-applied groups. Reduction of serum sodium level was most pronounced in group 1.ConclusionEmpirical treatment with sodium bicarbonate or hypertonic saline can reduce the development of cardiotoxicity during amitriptyline intoxication. As hypertonic saline has no adverse effects on drug elimination, it should be considered as an alternative to sodium bicarbonate therapy.

Comparative Study of the Acute Toxicity of Fluoxetine Versus Amitriptyline and the Predictive Factors for Their Complications

“…The cardiovascular effects and toxicity of amitriptyline result from the combination of fast cardiac sodium (Na + ) channel blockade, alphaadrenergic blockade, anti-cholinergic effects, and direct myocardial depression (Gheshlaghi et al, 2012;Paksu et al, 2015).…”

“…Hyponatremia, on the other hand, is the most common electrolyte disturbance encountered in critically poisoned patients (Singhi, 2004). The condition is brought about by Na + loss due to vomiting during acute intoxication, gastric lavage with hypotonic fluids, the use of hypotonic fluids, impaired fluid excretion, but most importantly, is inappropriate secretion of anti-diuretic hormone due to critical illness (Paksu et al, 2015). Hyponatremia was detected in 26.9% and in 25% of TCAs poisoning cases in previous studies by Olgun et al (2009); Gheshlaghi et al (2012) respectively.…”

“…ricyclic antidepressants (TCAs), of which amitriptyline (Tryptizol ® ) is a prototype that is used widely to treat many neuro-psychiatric diseases, have remained one of the common causes of fatal drug poisoning and a leading cause of death among intentional overdoses world wild (Bek et al, 2008;Kiberd and Minor, 2012). Amitriptyline poisoning is often lethal in overdose because it induces cardiac conduction delays, ventricular dysrhythmias, hypotension, coma and seizure that may be refractory to even the most aggressive management (Reichert et al, 2014;Paksu et al, 2015). Previous studies have shown that these effects arise from the blockage of voltage-dependent sodium channels providing a fast flow of sodium (Na + ) into the cell in addition to antagonistic effects on many receptors (Paksu et al, 2015).…”

“…Amitriptyline poisoning is often lethal in overdose because it induces cardiac conduction delays, ventricular dysrhythmias, hypotension, coma and seizure that may be refractory to even the most aggressive management (Reichert et al, 2014;Paksu et al, 2015). Previous studies have shown that these effects arise from the blockage of voltage-dependent sodium channels providing a fast flow of sodium (Na + ) into the cell in addition to antagonistic effects on many receptors (Paksu et al, 2015).…”

Advanced Electrocardiogram Analysis in the Amitriptyline‐poisoned Pig Treated with Activated Charcoal Haemoperfusion

“…supratherapeutic doses achieving supratherapeutic concentrations. This has been observed and tested in human as well as in animal models [9,11,[23][24][25]. The treatment guidelines for AT-induced arrhythmias vary and are based on few laboratory trials and mostly case reports and case series as opposed to the recommendations of oral activated charcoal for early-phase poisonings [26][27][28].…”