Maalouf Roger, Mosley Mark, James Kallail K, Kramer Karen M, Kumar Gaurav
Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS, USA.
Acad Emerg Med. 2009 Feb;16(2):157-61. doi: 10.1111/j.1553-2712.2008.00318.x. Epub 2008 Dec 6.
The common practice is to use 162 mg of aspirin orally in the emergency department (ED) for patients presenting with myocardial infarction. If the patient cannot take aspirin orally in the authors' facility, then 600 mg of aspirin is given rectally. However, no strong evidence exists as to whether the oral and rectal doses provide equivalent risk protection. The authors hypothesized that the salicylic acid levels for orally and rectally administered aspirin will not be similar, because of the different dosages used and the different routes of administration.
The study sample consisted of healthy, nonpregnant, adult volunteers without active illness, who did not take any medication regularly. Each subject served as his or her own control to account for any confounding factors. The study was conducted on 2 days, separated by a 1-week washout period. On the first day, 162 mg of oral aspirin was chewed and swallowed. Salicylic acid levels were obtained at baseline (i.e., before taking the aspirin) and then 30, 60, and 90 minutes after dosing. The 600-mg aspirin suppository was self-administered 1 week later with a sample for laboratory measures again drawn at baseline and then 30, 60, and 90 minutes after dosing.
Twenty-four subjects completed the study. The rectal suppository provided significantly more salicylic acid into the blood than the oral tablets over 90 minutes (p < 0.001). No statistical difference was noted between oral and rectal administration from baseline to 30 minutes (p > 0.05). However, mean salicylic acid levels from the rectal suppository were statistically higher than from the oral tablets from 30 to 60 minutes (p < 0.001) and from 60 to 90 minutes (p = 0.002). More than 60% of the subjects had an increasing salicylic acid level response over time to the rectal suppository. The salicylic acid level response to the oral administration was more evenly divided between those subjects whose salicylic acid levels peaked quickly and then fell or held steady (33%), those whose salicylic acid levels increased over time (29%), and those whose salicylic acid levels were measureable only after 60 minutes (25%). Although not statistically significant, these differences in group distributions for the type of salicylic acid level response between oral and rectal doses suggested the possibility of a rectal advantage.
Whether the higher salicylic acid levels and faster absorption of the rectal aspirin translate into better clinical outcomes is unknown and cannot be concluded from our study. Previous evidence, however, has shown that 162 mg of aspirin chewed and swallowed provided lower mortality in patients presenting with myocardial infarction. Our results suggested the rectal administration of a 600-mg suppository provides sufficient levels of salicylic acid within 90 minutes to meet or exceed that of oral aspirin.
对于急诊科出现心肌梗死的患者,常规做法是口服162毫克阿司匹林。如果在作者所在机构患者无法口服阿司匹林,则直肠给予600毫克阿司匹林。然而,关于口服和直肠给药剂量是否提供同等风险保护,尚无有力证据。作者推测,由于所用剂量不同和给药途径不同,口服和直肠给予阿司匹林后的水杨酸水平不会相似。
研究样本包括健康、非妊娠、无活动性疾病且未定期服用任何药物的成年志愿者。每个受试者作为自身对照,以排除任何混杂因素。研究分两天进行,中间间隔1周的洗脱期。第一天,咀嚼并吞服162毫克口服阿司匹林。在基线时(即服用阿司匹林前)以及给药后30、60和90分钟获取水杨酸水平。1周后自行给予600毫克阿司匹林栓剂,并在基线时以及给药后30、60和90分钟再次采集实验室检测样本。
24名受试者完成了研究。在90分钟内,直肠栓剂进入血液的水杨酸明显多于口服片剂(p < 0.001)。从基线到30分钟,口服和直肠给药之间未观察到统计学差异(p > 0.05)。然而,从30到60分钟(p < 0.001)以及从60到90分钟(p = 0.002),直肠栓剂的平均水杨酸水平在统计学上高于口服片剂。超过60%的受试者对直肠栓剂的水杨酸水平随时间呈上升反应。对口服给药的水杨酸水平反应在以下受试者中分布更为均匀:水杨酸水平迅速达到峰值然后下降或保持稳定的受试者(33%)、水杨酸水平随时间增加的受试者(29%)以及仅在60分钟后水杨酸水平可测量的受试者(25%)。尽管无统计学意义,但口服和直肠剂量之间水杨酸水平反应类型的这些组间分布差异提示直肠给药可能具有优势。
直肠给予阿司匹林后较高的水杨酸水平和更快的吸收是否能转化为更好的临床结果尚不清楚,且无法从我们的研究中得出结论。然而,先前的证据表明,咀嚼并吞服162毫克阿司匹林可降低心肌梗死患者的死亡率。我们的结果表明,直肠给予600毫克栓剂在90分钟内可提供足够的水杨酸水平,以达到或超过口服阿司匹林的水平。