Scheiman J M, Patel P M, Henson E K, Nostrant T T
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Am J Gastroenterol. 1995 May;90(5):754-7.
Gastrointestinal symptoms, particularly pyrosis, complicate nonsteroidal anti-inflammatory drug (NSAID) use. NSAIDs cause esophageal injury, and H2 blockers are often prescribed for, and successfully control, NSAID-related symptoms. To determine whether NSAIDs can induce gastroesophageal reflux, we studied the effect of a commonly used NSAID, naproxen, on reflux parameters and esophageal function.
Nine healthy volunteers (five males, four females, age 23-34 yr) were studied. After basal measurements were taken, the subjects randomly received naproxen 500 mg p.o. b.i.d. or placebo for 1 wk. On day 6, the subjects underwent esophageal manometry with a water-perfused system and Dent sleeve. Body pressures, contraction velocity, and duration of contraction were recorded in the distal 7 cm of the esophagus. The lower esophageal sphincter pressure (LESP) and number of transient relaxations (TLESRs) were monitored. This was followed by 24-h pH monitoring. The subjects then crossed over to the other drug after a minimum 14-day wash-out period.
No subject experienced any GI symptoms during the study. One subject developed reflux-induced symptoms a few months after completing the study and was excluded from the analysis. The total fraction of time (pH < 4) was 4.9 +/- 1.0% in the basal state, 5.5 +/- 1.4% on placebo, and 5.4 +/- 1.5% on naproxen. These differences were not significant. The number of reflux episodes and the esophageal clearance time were not affected by naproxen. The LESP in the basal state was 32.1 +/- 5.6 mm Hg, 32.3 +/- 4.2 mm Hg on placebo, and 29.9 +/- 3.3 mm Hg on naproxen (p = NS). The number of TLESRs per 30 minutes in the basal state was 3.5 +/- 0.9, 4.6 +/- 1.2 on placebo, and 5.8 +/- 1.0 on naproxen (p = NS). The speed and duration of contractions were not affected by naproxen. The excluded subject had marked basal reflux (total fraction of time pH < 4 = 10.7%), low LESP (8 mm Hg), and a marked increase in reflux on naproxen (total fraction of time pH < 4 = 53%).
Naproxen did not induce reflux in normal subjects, although reflux did increase in some subjects. Naproxen had no significant effect on motility parameters. Our data suggest that NSAIDs do not impair the anti-reflux barrier or induce reflux. Pyrosis experienced during NSAID use may not arise from the esophagus or may reflect altered esophageal sensitivity. A single subject with decreased LESP and asymptomatic increased acid exposure in the basal state had a marked increase in reflux on naproxen. This person subsequently developed symptomatic gastroesophageal reflux. The effect of NSAIDs on individuals with a propensity to reflux deserves further study.
胃肠道症状，尤其是烧心，使非甾体抗炎药（NSAID）的使用变得复杂。NSAIDs会导致食管损伤，H2阻滞剂常被用于治疗并成功控制与NSAID相关的症状。为了确定NSAIDs是否能诱发胃食管反流，我们研究了常用的NSAID萘普生对反流参数和食管功能的影响。
研究了9名健康志愿者（5名男性，4名女性，年龄23 - 34岁）。在进行基础测量后，受试者随机口服萘普生500 mg，每日两次，或服用安慰剂，为期1周。在第6天，受试者使用水灌注系统和Dent套囊进行食管测压。记录食管远端7 cm处的体压、收缩速度和收缩持续时间。监测食管下括约肌压力（LESP）和一过性下食管括约肌松弛（TLESRs）的次数。随后进行24小时pH监测。在至少14天的洗脱期后，受试者交叉使用另一种药物。
在研究期间，没有受试者出现任何胃肠道症状。一名受试者在完成研究几个月后出现反流诱发的症状，并被排除在分析之外。基础状态下pH < 4的总时间百分比为4.9 ± 1.0%，服用安慰剂时为5.5 ± 1.4%，服用萘普生时为5.4 ± 1.5%。这些差异无统计学意义。反流发作次数和食管清除时间不受萘普生影响。基础状态下LESP为32.1 ± 5.6 mmHg，服用安慰剂时为32.3 ± 4.2 mmHg，服用萘普生时为29.9 ± 3.3 mmHg（p = 无统计学意义）。基础状态下每30分钟的TLESRs次数为3.5 ± 0.9，服用安慰剂时为4.6 ± 1.2，服用萘普生时为5.8 ± 1.0（p = 无统计学意义）。收缩速度和持续时间不受萘普生影响。被排除的受试者基础反流明显（pH < 4的总时间百分比 = 10.7%），LESP较低（8 mmHg），服用萘普生时反流显著增加（pH < 4的总时间百分比 = 53%）。
萘普生在正常受试者中未诱发反流，尽管在一些受试者中反流确实增加。萘普生对动力参数无显著影响。我们的数据表明，NSAIDs不会损害抗反流屏障或诱发反流。使用NSAIDs期间出现的烧心可能并非源于食管，或可能反映食管敏感性改变。一名基础状态下LESP降低且无症状性酸暴露增加的受试者，服用萘普生后反流显著增加。该患者随后出现有症状的胃食管反流。NSAIDs对有反流倾向个体的影响值得进一步研究。
