Intensive Care Unit, Watford General Hospital, Watford, UK; Faculty of Medicine, Imperial College London, South Kensington Campus, London, UK.
Health Research Building, University of Hertfordshire, Hatfield, UK.
Lancet Respir Med. 2017 Sep;5(9):727-737. doi: 10.1016/S2213-2600(17)30234-5. Epub 2017 Jul 19.
Delirium in critically ill patients is associated with poor clinical outcomes. Neuroinflammation might be an important mechanism in the pathogenesis of delirium, and since simvastatin has anti-inflammatory properties it might reduce delirium. We aimed to establish whether early treatment with simvastatin would decrease the time that survivors of critical illness spent in delirium or coma.
We undertook this randomised, double-blind, placebo-controlled trial in a general adult intensive care unit (ICU) in Watford General Hospital (Watford, UK). We enrolled critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission. We randomly assigned patients (1:1 ratio) to receive either simvastatin 80 mg or placebo daily for up to a maximum of 28 days, irrespective of coma or delirium status. We assessed delirium using the Confusion Assessment Method for the ICU (CAM-ICU). The primary outcome was number of days alive and was assessed as delirium-free and coma-free in the first 14 days after being randomly allocated to receive treatment or placebo. ICU clinical and research staff and patients were masked to treatment. We did intention-to-treat analyses with no extrapolation. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN89079989.
Between Feb 1, 2013, and July 29, 2016, 142 patients were randomly assigned to receive simvastatin (n=71) or placebo (n=71), and were included in the final analysis. The mean number of days alive without delirium and without coma at day 14 did not differ significantly between the two groups (5·7 days [SD 5·1] with simvastatin and 6·1 days [5·2] with placebo; mean difference 0·4 days, 95% CI -1·3 to 2·1; p=0·66). The most common adverse event was an elevated creatine kinase concentration to more than ten times the upper limit of normal (eight [11%] in the simvastatin group vs three [4%] in the placebo group p=0·208). No patient had a serious adverse event related to the study drug.
These results do not support the hypothesis that simvastatin modifies duration of delirium and coma in critically ill patients.
National Institute for Health Research.
危重症患者的谵妄与不良临床结局相关。神经炎症可能是谵妄发病机制中的一个重要机制，而辛伐他汀具有抗炎作用，因此可能会减少谵妄。我们旨在确定早期使用辛伐他汀是否会减少重症患者幸存者处于谵妄或昏迷状态的时间。
我们在英国沃特福德综合医院（沃特福德）的普通成人重症监护病房（ICU）进行了这项随机、双盲、安慰剂对照试验。我们招募了需要在入院后 72 小时内接受机械通气的危重症患者（≥18 岁）。我们将患者（1:1 比例）随机分配接受辛伐他汀 80mg 或安慰剂，每天一次，最多 28 天，无论昏迷或谵妄状态如何。我们使用 ICU 意识模糊评估法（CAM-ICU）评估谵妄。主要结局是存活天数，并在随机分配接受治疗或安慰剂后的前 14 天内评估为无谵妄和无昏迷。重症监护病房的临床和研究人员及患者对治疗均不知情。我们进行了意向治疗分析，没有外推。该试验在国际标准随机对照试验注册中心注册，编号为 ISRCTN89079989。
2013 年 2 月 1 日至 2016 年 7 月 29 日，共有 142 名患者被随机分配接受辛伐他汀（n=71）或安慰剂（n=71），并纳入最终分析。两组第 14 天无谵妄和无昏迷的平均存活天数无显著差异（辛伐他汀组 5.7 天[SD 5.1]，安慰剂组 6.1 天[5.2]；平均差异 0.4 天，95%CI-1.3 至 2.1；p=0.66）。最常见的不良事件是肌酸激酶浓度升高至正常值上限的 10 倍以上（辛伐他汀组 8[11%]例，安慰剂组 3[4%]例；p=0.208）。没有患者发生与研究药物相关的严重不良事件。
这些结果不支持辛伐他汀可改变重症患者谵妄和昏迷持续时间的假设。
英国国家健康研究所。
