Delayed Cardiotoxicity From a Massive Nortriptyline Overdose Requiring Prolonged Treatment

PURPOSE: A case of a nortriptyline overdose complicated by delayed ventricular arrhythmias necessitating prolonged sodium bicarbonate infusion is presented, along with a review of tricyclic antidepressant (TCA) toxicology and key concepts for massive overdose management. SUMMARY: A 61-year-old man presented after an intentional nortriptyline overdose with a possible consumption of up to 2500 mg of nortriptyline. Electrocardiogram on presentation demonstrated QRS widening to 240 milliseconds. Despite treatment with a sodium bicarbonate infusion and further narrowing of his QRS interval, his course was complicated by repeated episodes of wide complex tachycardia. Given these episodes, an elevated quantitative serum nortriptyline level of 468 μg/L on hospital day 6 and persistently positive TCA urine screens, the patient was continued on a sodium bicarbonate infusion until hospital day 14. Based on our patient's quantitative serum nortriptyline levels, we calculated an elimination half-life of 184 hours, 6 days post ingestion as compared to the reported half-life of nortriptyline of 14 to 51 hours. CONCLUSION: This case demonstrates that at toxic levels of ingestion, routine TCA pharmacokinetics may be unreliable due to delayed absorption, enterohepatic recirculation, large volume of distribution, and saturable kinetics. Therefore, in these cases, pharmacokinetic values derived from routine dosing should not be used to make clinical decisions (such as timing of discontinuation of sodium bicarbonate infusion). We found that urine TCA screens provided similar information to quantitative nortriptyline levels and can be used to guide therapy along the QRS duration.