Section of Emergency Medicine, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, CO, USA.
Departments of Emergency Medicine and Medical Toxicology, St. Luke's University Health Network, Bethlehem, PA, USA.
Clin Toxicol (Phila). 2021 Aug;59(8):698-704. doi: 10.1080/15563650.2020.1854281. Epub 2020 Dec 9.
Toxicity from antimuscarinic agents precipitates a constellation of signs and symptoms; two of the most significant are agitation and delirium. Benzodiazepines are commonly used for treatment; physostigmine is also effective but is underutilized due to concerns for safety and short duration of action. The objective of this study was to compare lorazepam to physostigmine for the treatment of antimuscarinic delirium and agitation.
This was a blinded, randomized clinical trial in patients presenting for antimuscarinic toxidrome. Inclusion criteria were: ≥10-<18 years old, at least one central and two peripheral antimuscarinic symptoms, delirium and moderate agitation. Subjects were randomized to either (1) lorazepam bolus (0.05 mg/kg) followed by a 4-h normal saline infusion, or (2) physostigmine 0.02 mg/kg bolus followed by a 4-h physostigmine infusion (0.02 mg/kg/h). Primary outcomes were the control of delirium and agitation after bolus and during the infusion.
Ten (53%) subjects were enrolled in the lorazepam arm, 9 (47%) in the physostigmine arm. Diphenhydramine was the most common agent ingested (16, 84%). Fewer patients receiving physostigmine had delirium after the initial bolus (44% vs 100%, = 0.01) and at the 4th hour of infusion (22% vs 100%, < 0.001) compared to patients who received lorazepam. There was a significant decrease in agitation scores in the physostigmine arm compared to the lorazepam arm after the initial bolus (89% vs 30%, = 0.02), but no difference at the 4th hour of infusion ( > 0.99). There were no seizures, bradycardia, bronchorrhea, bronchospasm, intubation, or cardiac dysrhythmias.
Physostigmine was superior to lorazepam in controlling antimuscarinic delirium and agitation after bolus dosing, and control of delirium after a 4-h infusion. There were no serious adverse events in either treatment arm. Physostigmine bolus and infusion should be considered in adolescent patients with significant delirium and agitation from antimuscarinic agents.
抗毒蕈碱药物的毒性会引发一系列症状和体征；其中两个最显著的症状是激越和意识混乱。苯二氮䓬类药物通常用于治疗；毒扁豆碱也很有效，但由于安全性和作用持续时间短的问题，使用较少。本研究的目的是比较劳拉西泮和毒扁豆碱治疗抗毒蕈碱性谵妄和激越。
这是一项在出现抗毒蕈碱中毒症状的患者中进行的盲法、随机临床试验。纳入标准为：年龄≥10-<18 岁，至少有一个中枢和两个外周抗毒蕈碱症状，有谵妄和中度激越。患者随机分为（1）劳拉西泮推注（0.05mg/kg），随后进行 4 小时生理盐水输注，或（2）毒扁豆碱 0.02mg/kg 推注，随后进行 4 小时毒扁豆碱输注（0.02mg/kg/h）。主要结局是推注后和输注期间对谵妄和激越的控制。
10 名（53%）患者被纳入劳拉西泮组，9 名（47%）患者被纳入毒扁豆碱组。苯海拉明是最常见的摄入药物（16 例，84%）。接受毒扁豆碱治疗的患者初始推注后（44% 与 100%， = 0.01）和输注第 4 小时（22% 与 100%， < 0.001）出现谵妄的患者较少。与接受劳拉西泮治疗的患者相比，接受毒扁豆碱治疗的患者激越评分在初始推注后（89% 与 30%， = 0.02）和第 4 小时输注后（ > 0.99）显著下降。没有发生癫痫、心动过缓、鼻溢、支气管痉挛、插管或心律失常。
与劳拉西泮相比，毒扁豆碱在控制抗毒蕈碱谵妄和激越方面具有优势，在 4 小时输注后也能控制谵妄。在两种治疗组中均未发生严重不良事件。在出现明显抗毒蕈碱药物所致谵妄和激越的青少年患者中，应考虑使用毒扁豆碱推注和输注。
