Shoulders Bethany R, Smithburger Pamela L, Tchen Stephanie, Buckley Mitchell, Lat Ishaq, Kane-Gill Sandra L
1 UPMC Presbyterian Shadyside, Pittsburgh, PA, USA.
2 University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.
Ann Pharmacother. 2017 Jul;51(7):529-542. doi: 10.1177/1060028017699635. Epub 2017 Mar 15.
Non-Food and Drug Administration (FDA) or off-label medication prescribing occurs commonly in the intensive care unit (ICU). Off-label medication use creates a concern for untoward adverse effects; however, this worry may be alleviated by supportive literature.
To evaluate the evidence behind off-label medication use by determining the presence of guideline support and compare graded recommendations to an online tertiary resource, DRUGDEX.
Off-label medication use was identified prospectively over 3 months in medical ICUs in 3 academic medical centers. Literature searches were conducted in PubMed and the national guideline clearinghouse website to determine the presence of guideline support. DRUGDEX was also searched for strength-of-evidence ratings to serve as a comparator.
A total of 287 off-label medication indication searches resulted in 44% (126/287) without identified evidence; 253 guidelines were identified for 56% (161/287) of indications. Of the published guidelines, 89% (226/253) supported the off-label indication. In the DRUGDEX comparison, 67% (97/144) of guideline gradings disagree with DRUGDEX, whereas 33% (47/144) of the gradings matched the online database.
Because more than half of off-label medication use has the benefit of supportive guidelines recommendations and a majority of gradings are inconsistent with DRUGDEX, clinicians should consider utilizing guidelines to inform off-label medication use in the ICU. Still, there is a considerable amount of off-label medication use in the ICU that lacks supporting evidence, and use remains concerning because it may lead to inappropriate treatment and adverse events.
非美国食品药品监督管理局（FDA）批准的用药或标签外用药在重症监护病房（ICU）中很常见。标签外用药引发了对不良副作用的担忧；然而，相关支持性文献可能会减轻这种担忧。
通过确定指南支持情况来评估标签外用药背后的证据，并将分级推荐与在线三级资源DRUGDEX进行比较。
在3个学术医疗中心的内科ICU中对标签外用药进行了为期3个月的前瞻性识别。在PubMed和国家指南交换中心网站上进行文献检索，以确定是否存在指南支持。还在DRUGDEX中搜索证据强度评级作为比较对象。
总共287次标签外用药适应症检索中，44%（126/287）未找到证据；56%（161/287）的适应症找到了253条指南。在已发表的指南中，89%（226/253）支持标签外适应症。在与DRUGDEX的比较中，67%（97/144）的指南分级与DRUGDEX不一致，而33%（47/144）的分级与在线数据库匹配。
由于超过一半的标签外用药有支持性指南推荐，且大多数分级与DRUGDEX不一致，临床医生应考虑利用指南为ICU中的标签外用药提供依据。不过，ICU中仍有相当数量的标签外用药缺乏支持证据，其使用仍令人担忧，因为可能导致不恰当的治疗和不良事件。
