Optimal dose of adrenaline auto-injector for children and young people at risk of anaphylaxis: A phase IV randomized controlled crossover study.
Optimal dose of adrenaline auto-injector for children and young people at risk of anaphylaxis: A phase IV randomized controlled crossover study.
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对于有过敏反应风险的儿童和青少年来说，肾上腺素自动注射器的最佳剂量：一项 IV 期随机对照交叉研究。
作者：
Patel N
背景：指南推荐肌肉注射500 μg肾上腺素（肾上腺素）治疗青少年和成人过敏反应；然而，大多数自动注射器的最大剂量为300 μg。我们评估了有过敏反应风险的青少年自我注射300 μg或500 μg肾上腺素后血浆肾上腺素水平和心血管参数（包括心输出量）。方法招募受试者进行随机、单盲、两期交叉试验。参与者在两次单独访问（随机分组设计）中接受所有3种注射（Emerade®500 μg, Emerade®300 μg, Epipen®0.3 mg），间隔至少28天。通过超声确认肌内注射，并通过连续监测评估心率/卒中量。该试验已在Clinicaltrials.gov注册（NCT03366298）。结果12例参与者（58%男性，中位年龄15.4岁）参与；所有人都完成了研究。与300 μg组相比，500 μg组血浆肾上腺素峰值浓度更高，峰值持续时间更长（p= 0.01），曲线下面积更大（p< 0.05），但不良事件无显著差异。肾上腺素引起心率显著增加，与剂量和装置无关。出乎意料的是，300 μg肾上腺素可显著增加Emerade®的脑卒中容量，而Epipen®则有负性肌力作用（p< 0.05）。结论支持500 μg剂量肾上腺素治疗社区中体重10 ~ 40 kg人群的过敏反应。尽管Epipen®和Emerade®的峰值血浆肾上腺素水平相似，但它们对脑卒中容量的影响却出乎意料。迫切需要更好地了解肾上腺素自动注射器给药后的药效学差异。同时，我们建议在医疗机构中，对初始治疗有过敏反应难治性的个体使用针/注射器注射肾上腺素。
BackgroundGuidelines recommend intramuscular injection of 500 μg adrenaline (epinephrine) for anaphylaxis in teenagers and adults; however, most autoinjectors deliver a maximum 300 μg dose. We evaluated plasma adrenaline levels and cardiovascular parameters (including cardiac output) following self‐injection with 300 μg or 500 μg adrenaline in teenagers at risk of anaphylaxis.MethodsSubjects were recruited to a randomized, single‐blind two period crossover trial. Participants received all 3 injections (Emerade® 500 μg, Emerade® 300 μg, Epipen® 0.3 mg) on 2 separate visits (allocated in a randomized block design), at least 28 days apart. Intramuscular injection was confirmed by ultrasound, and heart rate/stroke volume assessed using continuous monitoring. The trial was registered at Clinicaltrials.gov (NCT03366298).ResultsTwelve participants (58% male, median 15.4 years) participated; all completed the study. 500 μg injection resulted in a higher and more prolonged peak concentration (p= 0.01) and greater Area‐Under‐Curve for plasma adrenaline (p< 0.05) compared to 300 μg, with no difference in adverse events. Adrenaline caused a significant increase in heart rate irrespective of dose and device. Unexpectedly, 300 μg adrenaline resulted in a significant increase in stroke volume when delivered with Emerade®, but a negative inotropic effect with Epipen® (p< 0.05).ConclusionsThese data support a 500 μg dose of adrenaline to treat anaphylaxis in individuals >40 kg in the community. The contrasting effects on stroke volume between Epipen® and Emerade®, despite similar peak plasma adrenaline levels, are unexpected. There is an urgent need to better understand differences in pharmacodynamics following adrenaline administration by autoinjector. In the meantime, we recommend adrenaline injection by needle/syringe in the healthcare setting in individuals with anaphylaxis refractory to initial treatment.