Ebisawa Motohiro, Kaliner Michael A, Lowenthal Richard, Tanimoto Sarina
Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
Institute for Asthma and Allergy, Wheaton, Md.
J Allergy Clin Immunol Glob. 2023 May 23;2(3):100118. doi: 10.1016/j.jacig.2023.100118. eCollection 2023 Aug.
While epinephrine autoinjectors have been the standard of care for the out-of-hospital treatment of anaphylaxis, their use has been associated with potential cardiovascular risks including intravascular injection, resulting in rapid increases in blood pressure and pulse rate. ARS Pharmaceuticals, Inc conducted a clinical trial designed to assess the pharmacokinetics and pharmacodynamics of ARS-1, an intranasal epinephrine spray in development, compared to EpiPen in subjects with a documented history of seasonal allergies. During the conduct of this study, a presumed intrablood vessel injection following EpiPen administration by a medical professional was observed in a female subject. The subject reported palpitations within 1 minute of receiving EpiPen injection; at 4 minutes postinjection, blood pressure was 221/128 mmHg (baseline 118/79), and pulse rate was 71 (baseline 56). In contrast, across all subjects (N = 36) the mean maximum increases in systolic blood pressure, diastolic blood pressure, and pulse rate were 12.0 mmHg, 2.8 mmHg, and 16.3 bpm, respectively. When this subject was removed from the pharmacokinetic analysis, the mean epinephrine C of the remaining subjects was 801.1 pg/mL after administration of EpiPen; however, at 4 minutes postinjection this subject had a plasma epinephrine level of 4390 pg/mL, a >6.3-fold increase, illustrating the risks that may be associated with out-of-hospital epinephrine injections that are included as warnings in the product labeling. Despite the potential risks associated with accidental intravessel injection, it is important to note that intramuscular administration of epinephrine is currently the best currently available out-of-hospital treatment for severe allergic reactions and anaphylaxis.
虽然肾上腺素自动注射器一直是院外治疗过敏反应的标准护理手段，但其使用与潜在的心血管风险相关，包括血管内注射，可导致血压和脉搏率迅速升高。ARS制药公司进行了一项临床试验，旨在评估正在研发的鼻内肾上腺素喷雾剂ARS-1与EpiPen相比在有季节性过敏病史受试者中的药代动力学和药效学。在这项研究过程中，一名女性受试者在由医疗专业人员注射EpiPen后发生了疑似血管内注射。该受试者在接受EpiPen注射后1分钟内报告有心悸；注射后4分钟，血压为221/128 mmHg（基线为118/79），脉搏率为71（基线为56）。相比之下，在所有受试者（N = 36）中，收缩压、舒张压和脉搏率的平均最大增幅分别为12.0 mmHg、2.8 mmHg和16.3次/分钟。当将该受试者从药代动力学分析中排除后，其余受试者在注射EpiPen后的肾上腺素C平均水平为801.1 pg/mL；然而，在注射后4分钟，该受试者的血浆肾上腺素水平为4390 pg/mL，增加了6.3倍以上，这说明了产品标签中作为警告列出的院外肾上腺素注射可能存在的风险。尽管意外血管内注射存在潜在风险，但必须指出，目前肌肉注射肾上腺素是院外治疗严重过敏反应和过敏的最佳可用方法。
