Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Department of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA.
J Pharm Pract. 2020 Aug;33(4):543-547. doi: 10.1177/0897190019838700. Epub 2019 Apr 14.
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.
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.
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.
报告了一例因多虑平过量导致延迟性室性心律失常而需要长时间输注碳酸氢钠的病例，并回顾了三环类抗抑郁药（TCA）毒理学和大量药物过量管理的关键概念。
一名 61 岁男性因故意服用多虑平过量，可能摄入多达 2500 毫克多虑平而就诊。就诊时的心电图显示 QRS 波增宽至 240 毫秒。尽管给予了碳酸氢钠输注治疗，并进一步缩小了 QRS 间隔，但他的病情仍因反复出现宽复合性心动过速而复杂化。鉴于这些发作，第 6 天血清定量多虑平水平为 468μg/L，且 TCA 尿液筛查持续阳性，患者继续接受碳酸氢钠输注，直至第 14 天。根据我们患者的血清定量多虑平水平，我们计算出摄入后 6 天的消除半衰期为 184 小时，而多虑平的报告半衰期为 14 至 51 小时。
本例表明，在摄入毒性水平时，由于延迟吸收、肠肝循环、大体积分布和饱和动力学，常规 TCA 药代动力学可能不可靠。因此，在这些情况下，不应根据常规剂量得出的药代动力学值来做出临床决策（例如停止输注碳酸氢钠的时间）。我们发现，尿液 TCA 筛查提供了与定量多虑平水平相似的信息，并可用于指导治疗，以 QRS 持续时间为依据。
