Department of Palliative Care, Cologne University Hospital, Cologne, Germany.
Drug Saf. 2012 Sep 1;35(9):745-58. doi: 10.1007/BF03261971.
Patients at the end of life often receive numerous medications for symptom management. In contrast to all other clinical situations, the aim of pharmacotherapy is strictly focused on quality of life.
The primary aims of this study were to assess the potential for drug-drug interactions (DDIs) in patients at the very end of life by identifying drug combinations and risk factors associated with a high risk of DDIs; and evaluate the clinical relevance of the potential DDIs in this unique patient population. Secondary objectives were to increase prescriber awareness and to derive a comprehensive framework for physicians to minimize DDIs in this specific setting of end-of-life care.
Charts of 364 imminently dying inpatients of two hospices were reviewed retrospectively. Drugs prescribed during the last 2 weeks of life were screened for DDIs by the electronic database of the Federal Union of German Associations of Pharmacists, which classifies DDIs by therapeutic measures required to reduce possible adverse events according to the ORCA system (OpeRational ClAssification of Drug Interactions).
Potential DDIs were detected in 223 patients (61%). In a multivariate analysis, polypharmacy was the major predictor for DDIs (odds ratio 1.5, 95% CI 1.4, 1.6). The drugs most commonly involved in therapeutically relevant potential DDIs were antipsychotics, antiemetics (e.g. metoclopramide, antihistamines), antidepressants, insulin, glucocorticoids, cardiovascular drugs and, in particular, NSAIDs. The most prevalent potential adverse effects were pharmacodynamically additive anticholinergic, antidopaminergic, cardiac (QT interval prolongation) and NSAID-associated toxicity (e.g. gastrointestinal, renal).
In the context of end-of-life care, the clinical relevance of DDIs differs from other clinical settings. Most DDIs can be prevented if the prescribing physician considers a few therapeutic principles. Specifically, this concerns the awareness of futile and high-risk medications, as well as rational alternatives.
生命末期的患者通常会接受多种药物来缓解症状。与所有其他临床情况不同，药物治疗的目的严格集中在提高生活质量上。
本研究的主要目的是通过识别与高药物-药物相互作用（DDI）风险相关的药物组合和风险因素，评估生命末期患者发生 DDI 的可能性，并评估该独特患者群体中潜在 DDI 的临床相关性。次要目的是提高开处方者的认识，并为医生提供一个综合框架，以最大限度地减少生命末期护理中的 DDI。
回顾性审查了两家临终关怀机构的 364 名即将死亡的住院患者的病历。通过德国药剂师联邦联盟的电子数据库筛选生命最后 2 周内开具的药物，以确定潜在的 DDI。该数据库根据 ORCA 系统（操作药物相互作用分类）按需要采取治疗措施对可能的不良反应进行分类，将 DDI 分类为具有临床相关性和不具有临床相关性。
在 223 名患者（61%）中检测到潜在的 DDI。在多变量分析中，联合用药是 DDI 的主要预测因素（优势比 1.5，95%置信区间 1.4，1.6）。最常涉及具有治疗相关性的潜在 DDI 的药物是抗精神病药、止吐药（如甲氧氯普胺、抗组胺药）、抗抑郁药、胰岛素、糖皮质激素、心血管药物，尤其是 NSAIDs。最常见的潜在不良影响是药效学上相加的抗胆碱能、抗多巴胺能、心脏（QT 间期延长）和 NSAID 相关毒性（如胃肠道、肾脏）。
在生命末期护理中，DDI 的临床相关性与其他临床情况不同。如果开处方的医生考虑一些治疗原则，大多数 DDI 是可以预防的。具体而言，这涉及到对无效和高风险药物的认识，以及合理的替代药物。
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