Strom B L, Berlin J A, Kinman J L, Spitz P W, Hennessy S, Feldman H, Kimmel S, Carson J L
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA.
JAMA. 1996 Feb 7;275(5):376-82.
To evaluate the risk of gastrointestinal and operative site bleeding associated with the use of parenteral ketorolac tromethamine.
Postmarketing surveillance inception cohort study.
A total of 35 hospitals throughout the Philadelphia, Pa, region, 1991 to 1993.
Patients administered 10,272 courses of parenteral ketorolac therapy were compared with patients administered 10,247 courses of a parenteral opiate who were matched to the ketorolac patients by hospital, admitting service, and date of initiation of study drug.
Medical records were reviewed for demographics, medical history, doses and duration of study drug, various aspects of the hospital course including surgery and concomitant medications, and adverse events.
The multivariate adjusted odds ratio (OR) comparing ketorolac with opiates for gastrointestinal bleeding was 1.30 (95% confidence interval [CI], 1.11 to 1.52); for operative site bleeding, the OR was 1.02 (95% CI, 0.95 to 1.10). The OR was elevated further in subjects 75 years of age or older for both gastrointestinal bleeding (OR = 1.66; 95% CI, 1.23 to 2.25) and operative site bleeding (OR = 1.12; 95% CI, 0.94 to 1.35). A dose-response relationship was evident between average daily ketorolac dose and both gastrointestinal bleeding and operative site bleeding (trend test P < .001 for both). When analgesic therapy lasted 5 or fewer days, ketorolac was associated with only a small increased risk of gastrointestinal bleeding (OR = 1.17; 95% CI, 0.99 to 1.30); when therapy was prolonged beyond 5 days, the OR was 2.20 (95% CI, 1.36 to 3.57). The association of ketorolac with operative site bleeding was not affected by duration of therapy.
The overall associations between ketorolac use and both gastrointestinal bleeding and operative site bleeding are small. However, the risk associated with the drug is larger and clinically important when ketorolac is used in higher doses, in older subjects, and for more than 5 days. Improving physicians' prescribing practices by limiting the dose and duration of ketorolac use, especially in the elderly, should enhance its overall risk-benefit balance.
评估胃肠外注射酮咯酸氨丁三醇所致胃肠及手术部位出血的风险。
上市后监测起始队列研究。
1991年至1993年期间，宾夕法尼亚州费城地区的35家医院。
将接受10272疗程胃肠外注射酮咯酸治疗的患者与接受10247疗程胃肠外注射阿片类药物治疗的患者进行比较，后者在医院、收治科室及研究药物起始日期方面与酮咯酸治疗患者相匹配。
查阅病历以获取人口统计学资料、病史、研究药物的剂量和疗程、包括手术及合并用药在内的住院过程的各个方面以及不良事件。
在多变量调整后，酮咯酸与阿片类药物相比，发生胃肠出血的比值比（OR）为1.30（95%置信区间[CI]，1.11至1.52）；手术部位出血的OR为1.02（95%CI，0.95至1.10）。在75岁及以上的受试者中，胃肠出血（OR = 1.66；95%CI，1.23至2.25）和手术部位出血（OR = 1.12；95%CI，0.94至1.35）的OR进一步升高。平均每日酮咯酸剂量与胃肠出血和手术部位出血之间存在明显的剂量-反应关系（两者趋势检验P <.001）。当镇痛治疗持续5天或更短时间时，酮咯酸仅使胃肠出血风险略有增加（OR = 1.17；95%CI，0.99至1.30）；当治疗延长超过5天时，OR为2.20（95%CI，1.36至3.57）。酮咯酸与手术部位出血的关联不受治疗持续时间的影响。
使用酮咯酸与胃肠出血和手术部位出血之间的总体关联较小。然而，当高剂量使用酮咯酸、用于老年患者以及使用超过5天时，该药物相关风险更大且具有临床意义。通过限制酮咯酸的使用剂量和疗程，尤其是在老年人中，改善医生的处方习惯，应能提高其总体风险效益平衡。
