Simons F E, Gu X, Johnston L M, Simons K J
Section of Allergy and Clinical Immunology, Department of Pediatrics and Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Pediatrics. 2000 Nov;106(5):1040-4. doi: 10.1542/peds.106.5.1040.
For out-of-hospital treatment of anaphylaxis, inhalation of epinephrine from a pressurized metered-dose inhaler is sometimes recommended as a noninvasive, user-friendly alternative to an epinephrine injection.
To determine the feasibility of administering an adequate epinephrine dose from a metered-dose inhaler in children at risk for anaphylaxis by assessing the rate and extent of epinephrine absorption after inhalation.
We performed a prospective, randomized, observer-blind, placebo-controlled, parallel-group study in 19 asymptomatic children with a history of anaphylaxis. Based on the child's weight, 10, 15, or 20 carefully supervised epinephrine or placebo inhalations were attempted. Before dosing, and at intervals from 5 to 180 minutes after dosing, we monitored plasma epinephrine concentrations, blood glucose, heart rate, blood pressure, and adverse effects.
Eleven children (mean +/- standard error of the mean: 9 +/- 1 years and 33 +/- 3 kg) in the epinephrine group were able to inhale 11 +/- 2 (range: 3-20) puffs, equivalent to 74% +/- 7% of the precalculated dose or 0.078 +/- 0.009 mg/kg. They achieved a mean peak plasma epinephrine concentration of 1822 +/- 413 (range: 230-4518) pg/mL at 32.7 +/- 6.2 minutes. Eight children (10 +/- 1 years of age and 33 +/- 5 kg) in the placebo group were able to inhale 12 +/- 2 (range: 8-20) puffs, 89% +/- 3% of the precalculated dose, and had a peak endogenous plasma epinephrine concentration of 1316 +/- 247 (range: 522-2687) pg/mL at 44.4 +/- 16.7 minutes. In the children receiving epinephrine compared with those receiving placebo, mean plasma epinephrine concentrations were not significantly higher at any time, mean blood glucose concentrations were significantly higher from 10 to 30 minutes, mean heart rate was not significantly different at any time, and mean systolic and diastolic blood pressures were not significantly increased at most times. After the inhalations of epinephrine or placebo, the children complained of bad taste and many experienced cough or dizziness. After inhaling epinephrine, 1 child developed nausea, pallor, and muscle twitching.
Despite expert coaching, because of the number of epinephrine inhalations required and the bad taste of the inhalations, most children were unable to inhale sufficient epinephrine to increase their plasma epinephrine concentrations promptly and significantly. Therefore, we urge caution in recommending epinephrine inhalation as a substitute for epinephrine injection for out-of-hospital treatment of anaphylaxis symptoms in children.
对于院外过敏性反应的治疗，有时建议使用压力定量吸入器吸入肾上腺素，作为肾上腺素注射的一种无创、用户友好的替代方法。
通过评估吸入后肾上腺素的吸收速率和程度，确定在有过敏性反应风险的儿童中，使用定量吸入器给予足够剂量肾上腺素的可行性。
我们对19名有过敏性反应病史的无症状儿童进行了一项前瞻性、随机、观察者盲法、安慰剂对照、平行组研究。根据儿童体重，尝试进行10次、15次或20次在密切监督下的肾上腺素或安慰剂吸入。给药前以及给药后5至180分钟的间隔时间内，我们监测血浆肾上腺素浓度、血糖、心率、血压和不良反应。
肾上腺素组的11名儿童（平均±平均标准误：9±1岁，体重33±3千克）能够吸入11±2次（范围：3 - 20次）喷雾，相当于预先计算剂量的74%±7%或0.078±0.009毫克/千克。他们在32.7±6.2分钟时达到的血浆肾上腺素平均峰值浓度为1822±413（范围：230 - 4518）皮克/毫升。安慰剂组的8名儿童（10±1岁，体重33±5千克）能够吸入12±2次（范围：8 - 20次）喷雾，为预先计算剂量的89%±3%，在44.4±16.7分钟时内源性血浆肾上腺素峰值浓度为1316±247（范围：522 - 2687）皮克/毫升。与接受安慰剂的儿童相比，接受肾上腺素治疗的儿童在任何时候的平均血浆肾上腺素浓度均无显著升高，在10至30分钟时平均血糖浓度显著升高，在任何时候平均心率无显著差异，在大多数时间平均收缩压和舒张压无显著升高。吸入肾上腺素或安慰剂后，儿童抱怨味道不佳，并出现许多咳嗽或头晕症状。吸入肾上腺素后有1名儿童出现恶心、面色苍白和肌肉抽搐。
尽管有专家指导，但由于所需的肾上腺素吸入次数以及吸入剂味道不佳，大多数儿童无法吸入足够的肾上腺素以迅速且显著地提高其血浆肾上腺素浓度。因此，我们强烈建议谨慎推荐将肾上腺素吸入作为肾上腺素注射的替代方法，用于院外治疗儿童过敏性反应症状。
