Smithburger Pamela L, Buckley Mitchell S, Culver Mark A, Sokol Sarah, Lat Ishaq, Handler Steven M, Kirisci Levent, Kane-Gill Sandra L
1Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA. 2Department of Pharmacy, Banner Good Samaritan Medical Center, Phoenix, AZ. 3Department of Pharmaceutical Services, University of Chicago Medical Center, Chicago, IL. 4Department of Pharmacy, Rush University Medical Center, Chicago, IL. 5Department of Geriatric Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA. 6Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA. 7Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA.
Crit Care Med. 2015 Aug;43(8):1612-21. doi: 10.1097/CCM.0000000000001022.
Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult ICU population.
Multicenter, observational study
: Medical ICUs at three academic medical centers.
Adult patients (age ≥ 18 yr old) receiving medication therapy.
All administered medications were evaluated for Food and Drug Administration-approved or off-label use. Patients were assessed daily for the development of an adverse drug reaction through active surveillance. Three adverse drug reaction assessment instruments were used to determine the probability of an adverse drug reaction resulting from drug therapy. Severity and harm of the adverse drug reaction were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of adverse drug reactions.
Overall, 1,654 patient-days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen adverse drug reactions were categorized dichotomously (Food and Drug Administration or off-label), with 56% and 44% being associated with Food and Drug Administration-approved and off-label use, respectively. The number of adverse drug reactions for medications administered and the number of harmful and severe adverse drug reactions did not differ for medications used for Food and Drug Administration-approved or off-label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of adverse drug reactions increases by 8% for every one additional off-label medication (hazard ratio = 1.08; 95% CI, 1.018-1.154).
Although adverse drug reactions do not occur more frequently with off-label use, adverse drug reaction risk increases with each additional off-label medication used.
先前的研究表明，在重症监护病房（ICU）中，药品的非标签使用很常见；然而，非标签使用的安全性尚未得到评估。本研究的目的是确定与非标签使用相关的药物不良反应的发生率，并评估非标签使用作为成年ICU患者发生药物不良反应的一个风险因素。
多中心观察性研究
三家学术医疗中心的内科重症监护病房
接受药物治疗的成年患者（年龄≥18岁）
对所有使用的药物进行评估，确定其是否为美国食品药品监督管理局（FDA）批准使用或非标签使用。通过主动监测，每天对患者进行评估，以确定是否发生药物不良反应。使用三种药物不良反应评估工具来确定药物治疗导致药物不良反应的可能性。还对药物不良反应的严重程度和危害进行了评估。采用Cox比例风险回归分析来确定一组影响药物不良反应发生率的协变量。
总体而言，共评估了1654个患者日（327例患者）和16391种药物，其中43%的药物为非标签使用。116例药物不良反应被分为两类（FDA批准使用或非标签使用），分别有56%和44%与FDA批准使用和非标签使用相关。FDA批准使用或非标签使用的药物的药物不良反应数量、有害及严重药物不良反应数量并无差异（0.74%对0.67%；p = 0.336；33例对31例，p = 0.567；24例对24例，p = 0.276）。Cox比例风险回归分析纳入了年龄、性别、高风险药物数量、非标签药物数量和疾病严重程度评分。结果发现，每增加一种非标签药物，药物不良反应发生率增加8%（风险比=1.08；95%置信区间，1.018 - 1.154）。
虽然非标签使用药物不良反应的发生频率并不更高，但每增加一种非标签使用的药物，药物不良反应风险就会增加。
