New South Wales Poisons Information Centre, Sydney Children's Hospitals Network, Westmead, Australia.
Emergency Department, Nepean Hospital, Sydney, Australia.
Clin Toxicol (Phila). 2024 Mar;62(3):168-173. doi: 10.1080/15563650.2024.2323678. Epub 2024 Mar 25.
Orphenadrine overdoses can cause antimuscarinic toxicity, respiratory failure, refractory seizures and cardiotoxicity. The dose-toxicity relationship is poorly defined. Orphenadrine is marketed as immediate and sustained release formulations, and it is not known how the formulation impacts on toxicity. We determined the clinical toxicity of orphenadrine in patients referred to a regional poisons centre.
Retrospective case series of patients in New South Wales with orphenadrine deliberate self-poisoning from January 2016 to April 2022 referred to the New South Wales Poisons Information Centre. Demographics, history of exposure, treatment and outcomes were extracted from clinical databases. Receiver-operating characteristic curves were constructed to determine thresholds predicting toxicity.
Forty-eight patients were identified, with information on clinical outcomes in 46 patients and doses in 41 patients. All patients were older than 12 years. The median orphenadrine dose was 770 mg (range 210-10,000 mg), 59 per cent as the immediate release formulation, and 67 per cent reported coingestants. Doses of sustained release formulations were significantly greater than immediate release formulations, median 2,750 mg versus 595 mg. Common clinical features were drowsiness (59 per cent), sinus tachycardia (37 per cent) and confusion (33 per cent). Three patients had mild hypotension, three were intubated for coma, and two had seizures; no patients suffered ventricular dysrhythmias. All patients survived, with 75 per cent being medically cleared within 24 hours of presentation. A dose-toxicity relationship was observed, but conclusions are limited by the small number of cases with moderate or severe toxicity.
All patients survived, and severe cardiac and neurological toxicity were not observed. This contrasts to published case reports noting severe poisoning at similar or lower doses. Formulation may have an impact on outcomes, with lesser toxicity from sustained release products.
Orphenadrine doses up to 10 g were associated with antimuscarinic toxicity and sedation, but not severe cardiotoxicity. More research exploring the effect of dose and formulation on outcomes is required.
奥芬那君过量可导致抗毒蕈碱毒性、呼吸衰竭、难治性癫痫发作和心脏毒性。剂量-毒性关系定义不佳。奥芬那君有速释和缓控释两种剂型上市，其剂型如何影响毒性尚不清楚。我们在新南威尔士毒物中心对因奥芬那君故意自我中毒而就诊的患者进行了奥芬那君临床毒性的研究。
这是一项回顾性病例系列研究，研究对象为 2016 年 1 月至 2022 年 4 月期间因奥芬那君故意自我中毒而被新南威尔士毒物信息中心收治的新南威尔士州患者。从临床数据库中提取人口统计学、暴露史、治疗和结局等信息。绘制受试者工作特征曲线以确定预测毒性的阈值。
共确定了 48 例患者，其中 46 例患者有临床结局信息，41 例患者有剂量信息。所有患者年龄均大于 12 岁。奥芬那君的中位剂量为 770mg（范围 210-10000mg），59%为速释制剂，67%报告为同时服用其他药物。缓控释制剂的剂量明显大于速释制剂，中位数为 2750mg 比 595mg。常见的临床特征是嗜睡（59%）、窦性心动过速（37%）和意识混乱（33%）。3 例患者有轻度低血压，3 例因昏迷行气管插管，2 例有癫痫发作；无患者发生室性心律失常。所有患者均存活，75%的患者在就诊后 24 小时内被医学治愈。观察到剂量-毒性关系，但由于有中度或重度毒性的病例数量较少，结论受到限制。
所有患者均存活，未观察到严重的心脏和神经毒性。这与发表的病例报告中提到的在类似或更低剂量下发生严重中毒的情况形成对比。剂型可能对结局有影响，缓控释产品的毒性较小。
奥芬那君剂量达 10g 时可引起抗毒蕈碱毒性和镇静作用，但不引起严重的心脏毒性。需要进一步研究探索剂量和剂型对结局的影响。
