Treatment of amitriptyline intoxications by extended high cut-off dialysis

Abstract

Antidepressants, especially amitriptyline, are among the most frequent drug classes involved in intoxications. Despite its small molecular weight, amitriptyline is not considered to be eliminated by extracorporeal treatment methods due to its high protein binding and large volume of distribution. New high cut-off dialysers have so far not been used for removal of amitriptyline. We report two cases of amitriptyline poisoning in which we measured the amitriptyline elimination using extended high cut-off (HCO) dialysis. Despite dialyser clearances of 33 and 58 mL/min, resulting in the reduction of initial serum concentrations by ∼30%, only 211 and 920 µg of amitryptilin, respectively, (<3% of the ingested amount) could be recovered in the total collected dialysate. Hence, due to the high volume of distribution of amitriptyline, even HCO dialysis does not contribute substantially to the extracorporeal removal of amitryptilin.

A Case of Severe Amitriptyline Intoxication: Electrocardiography Signs Suggesting Ventricular Tachycardia

“…In patients with life threatening amitriptyline intoxication successful results had been reported with plasma exchange had been (7,(18)(19)(20)(21). Recently one study reported successful result with extended high cut-off dialysis (9). In our case, we performed selective plasma exchange due to the persisting life threatening clinical condition despite all other treatment options.…”

“…Amitriptylin is one of the most common used antidepressants. Also the tricyclic antidepressants, especially the amitryptiline, are the most common used drugs in drug intoxication worldwide (8,9). Acute results of amitriptyline intoxication had been well defined both in children and adults (1, 3, 4, 10).…”

“…First-line treatment focuses on general measures as well as correction of electrolyte disorders and arrhythmia (6,9). If the patient admits during the first 12 hours, gastric lavage should be performed and active charcoal should be administered.…”

Why are we Still Dialyzing Overdoses to Tricyclic Antidepressants? A subanalysis of the NPDS database

“…ECTR is unlikely to be useful for such toxins because of their large volume of distribution, which limits their extracorporeal removal, and availability of alternative treatments. However, some clinicians still consider that ECTR may be indicated for some nonclassic toxins like tricyclic antidepressants (17)(18)(19).…”

Physiologically based pharmacokinetic-quantitative systems toxicology and safety (PBPK-QSTS) modeling approach applied to predict the variability of amitriptyline pharmacokinetics and cardiac safety in populations and in individuals

“…The found cases were divided into three groups with corresponding methodology: Cases without ingested dose reported [ 35 , 43 ]: the free cardiac AT and NT concentrations were estimated based on observed plasma AT and NT concentrations according to the (Eq. 5 ): where C free,cardiac is drug free cardiac concentration, Kp ht is heart tissue to plasma partition coefficient, and fu ht is drug unbound fraction in heart tissue.…”