Harvard Medical Toxicology Fellowship, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, MA 02215, USA.
National Capital Poison Center, 3201 New Mexico Avenue, Suite 310, Washington, DC 20016, USA; Department of Emergency Medicine, The George Washington University School of Medicine, 230 Eye Street, NW, Washington, DC 20037, USA.
Am J Emerg Med. 2023 May;67:163-167. doi: 10.1016/j.ajem.2023.02.036. Epub 2023 Mar 1.
Antimuscarinic delirium (AD), a potentially life-threatening condition frequently encountered by emergency physicians, results from poisoning with antimuscarinic agents. Treatment with physostigmine and benzodiazepines is the mainstay of pharmacotherapy, and use of dexmedetomidine and non-physostigmine centrally-acting acetylcholinesterase inhibitors (cAChEi) such as rivastigmine has also been described. Unfortunately, these medications are subject to drug shortages which negatively impact the ability to provide appropriate pharmacologic treatment of patients with AD.
Drug shortage data were retrieved from the University of Utah Drug Information Service (UUDIS) database from January 2001 through December 2021. Shortages of first-line agents used to treat AD (physostigmine and parenteral benzodiazepines) and second-line agents (dexmedetomidine and non-physostigmine cAChEi) were examined. Drug class, formulation, route of administration, reason for shortage, shortage duration, generic status, and whether the drug was a single-source product (made by only one manufacturer) were extracted. Shortage overlap and median shortage durations were calculated.
Twenty-six shortages impacting drugs used to treat AD were reported to UUDIS from January 1, 2001 to December 31, 2021. Median shortage duration for all medication classes was 6.0 months. Four shortages were unresolved at the end of the study period. The single medication most often on shortage was dexmedetomidine, however benzodiazepines were the most common medication class on shortage. Twenty-five shortages involved parenteral formulations, and one shortage involved the transdermal patch formulation of rivastigmine. The majority (88.5%) of shortages involved generic medications, and 50% of products on shortage were single-source. The most common reported reason for shortage was a manufacturing issue (27%). Shortages were often prolonged and, in 92% of cases, overlapped temporally with other shortages. Shortage frequency and duration increased during the second half of the study period.
Shortages of agents used in the treatment of AD were common during the study period and affected all agent classes. Shortages were often prolonged and multiple shortages were ongoing at study period end. Multiple concurrent shortages involving different agents occurred, which could hamper substitution as a means of mitigating shortage. Healthcare stakeholders must develop innovative patient- and institution-specific solutions in times of shortage and work to build resilience into the medical product supply chain to minimize future shortages of drugs used for treatment of AD.
抗毒蕈碱谵妄（AD）是一种潜在的危及生命的疾病，经常被急诊医生遇到，它是由抗毒蕈碱药物中毒引起的。毒扁豆碱和苯二氮䓬类药物的治疗是药物治疗的主要方法，使用右美托咪定和非毒扁豆碱中枢乙酰胆碱酯酶抑制剂（cAChEI）如利伐斯的明也有描述。不幸的是，这些药物都面临短缺，这对提供 AD 患者的适当药物治疗的能力产生负面影响。
药物短缺数据从 2001 年 1 月至 2021 年 12 月从犹他大学药物信息服务（UUDIS）数据库中检索。检查了用于治疗 AD 的一线药物（毒扁豆碱和肠外苯二氮䓬类药物）和二线药物（右美托咪定和非毒扁豆碱 cAChEI）的短缺情况。提取了药物类别、制剂、给药途径、短缺原因、短缺持续时间、通用状态以及药物是否为单一来源产品（仅由一家制造商生产）。计算了短缺重叠和中位短缺持续时间。
从 2001 年 1 月 1 日至 2021 年 12 月 31 日，UUDIS 报告了 26 例影响 AD 治疗药物的短缺情况。所有药物类别的中位短缺持续时间为 6.0 个月。研究结束时，仍有 4 个短缺未解决。最常短缺的单一药物是右美托咪定，然而，苯二氮䓬类药物是最常见的短缺药物类别。25 例短缺涉及肠外制剂，1 例短缺涉及利伐斯的明的透皮贴剂制剂。大多数（88.5%）短缺涉及仿制药，50%的短缺药物为单一来源。短缺的主要原因是生产问题（27%）。短缺时间往往很长，在 92%的情况下，与其他短缺时间重叠。在研究期间，短缺的频率和持续时间增加。
在研究期间，AD 治疗药物的短缺情况很常见，影响了所有药物类别。短缺时间往往很长，在研究结束时仍有多个短缺。同时发生多个涉及不同药物的短缺，这可能会阻碍替代作为缓解短缺的手段。在短缺期间，医疗保健利益相关者必须为患者和机构制定创新的解决方案，并努力建立医疗产品供应链的弹性，以尽量减少 AD 治疗药物的未来短缺。
