Li Yan, Ma Jun, Jin Yinghui, Li Nan, Zheng Rui, Mu Wei, Wang Jiaying, Si Jin Hua, Chen Jing, Shang Hong Cai
Beijing Anzhen Hospital, Capital Medical University, Center for Anesthesiology, No.2 Anzhen Road, Chaoyang District, Beijing, Beijing, China, 100029.
Tianjin University of Traditional Chinese Medicine, Nursing, #312 West Anshan Road, Tianjin, China.
Cochrane Database Syst Rev. 2020 Feb 28;2(2):CD012670. doi: 10.1002/14651858.CD012670.pub2.
Delirium is a very common condition associated with significant morbidity, mortality, and costs. Current critical care guidelines recommend first and foremost the use of nonpharmacological strategies in both the prevention and treatment of delirium. Pharmacological interventions may augment these approaches and they are currently used widely in clinical practice to manage the symptoms of delirium. Benzodiazepines are currently used in clinical practice to treat behavioural disturbances associated with delirium but current guidelines do not recommend their use for this indication. The use of these medicines is controversial because there is uncertainty about whether they are effective for patients or have the potential to harm them.
To assess the effectiveness and safety of benzodiazepines in the treatment of delirium (excluding delirium related to withdrawal from alcohol or benzodiazepines) in any healthcare settings other than intensive care units (ICU).
We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialized Register up to 10 April 2019. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (including MEDLINE, Embase, PsycINFO, CINAHL, LILACS), numerous trial registries (including national, international and pharmaceutical registries), and grey literature sources.
We included randomised controlled trials (RCTs) conducted in healthcare settings that ranged from nursing homes and long-term care facilities to any hospital setting except for ICUs, involving adult patients with delirium excluding those with delirium related to alcohol or benzodiazepine withdrawal. Included RCTs had to assess the effect of benzodiazepines, at any dose and given by any route, compared with placebo or another drug intended to treat delirium.
Two review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of included studies. We decided whether or not to pool data on the basis of clinical heterogeneity between studies. We used GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods to assess the quality of evidence.
We identified only two trials that satisfied the selection criteria. We did not pool the data because of the substantial clinical differences between the trials. In one trial, participants (n = 58) were patients in an acute palliative care unit with advanced cancer who had a mean age of 64 years. All of the participants had delirium, were treated with haloperidol, and were randomised to receive either lorazepam or placebo in combination with it. Due to very serious imprecision, all evidence was of low certainty. We were unable to determine whether there were clinically important differences in the severity of delirium (mean difference (MD) 2.10, 95% CI -0.96 to 5.16; n = 50), length of hospital admission (MD 0.00, 95% CI -3.45 to 3.45; n = 58), mortality from all causes (risk ratio (RR) 0.33, 95% CI 0.04 to 3.02; participants = 58) or any of a number of adverse events. Important effects could not be confirmed or excluded. The study authors did not report the length of the delirium episode. In the other trial, participants (n = 30) were patients in general medical wards with acquired immune deficiency syndrome (AIDS) who had a mean age of 39.2 years. Investigators compared three drug treatments: all participants had delirium, and were randomised to receive lorazepam, chlorpromazine, or haloperidol. Very low-certainty evidence was identified, and we could not determine whether lorazepam differed from either of the other treatments in the effect on severity of delirium, any adverse event, or mortality from all causes. The study authors did not report the length of the delirium episode or the length of hospital admission.
AUTHORS' CONCLUSIONS: There is no enough evidence to determine whether benzodiazepines are effective when used to treat patients with delirium who are cared for in non-ICU settings. The available evidence does not support their routine use for this indication. Because of the scarcity of data from randomised controlled trials, further research is required to determine whether or not there is a role for benzodiazepines in the treatment of delirium in non-ICU settings.
谵妄是一种非常常见的病症，与显著的发病率、死亡率及费用相关。当前的重症监护指南首先推荐在谵妄的预防和治疗中使用非药物策略。药物干预可辅助这些方法，目前在临床实践中广泛用于管理谵妄症状。苯二氮䓬类药物目前在临床实践中用于治疗与谵妄相关的行为障碍，但当前指南不推荐将其用于这一适应症。这些药物的使用存在争议，因为它们对患者是否有效或是否有潜在危害尚不确定。
评估苯二氮䓬类药物在除重症监护病房（ICU）之外的任何医疗环境中治疗谵妄（不包括与酒精或苯二氮䓬类药物戒断相关的谵妄）的有效性和安全性。
我们检索了ALOIS：Cochrane痴呆与认知改善小组的专业注册库，检索截至2019年4月10日的数据。ALOIS包含从多个主要医疗保健数据库（包括MEDLINE、Embase、PsycINFO、CINAHL、LILACS）的月度检索、众多试验注册库（包括国家、国际和制药注册库）以及灰色文献来源中识别出的临床试验记录。
我们纳入了在从疗养院和长期护理机构到除ICU之外的任何医院环境等医疗环境中开展的随机对照试验（RCT），涉及患有谵妄的成年患者，但不包括与酒精或苯二氮䓬类药物戒断相关的谵妄患者。纳入的RCT必须评估任何剂量、通过任何途径给予的苯二氮䓬类药物与安慰剂或另一种用于治疗谵妄的药物相比的效果。
两位综述作者独立评估研究的合格性、提取数据并评估纳入研究的偏倚风险。我们根据研究之间的临床异质性决定是否合并数据。我们使用GRADE（推荐分级、评估、制定与评价）方法评估证据质量。
我们仅识别出两项符合入选标准的试验。由于试验之间存在实质性临床差异，我们未合并数据。在一项试验中，参与者（n = 58）为急性姑息治疗病房中患有晚期癌症的患者，平均年龄64岁。所有参与者均患有谵妄，接受氟哌啶醇治疗，并随机分组接受劳拉西泮或安慰剂联合氟哌啶醇治疗。由于非常严重的不精确性，所有证据的确定性都很低。我们无法确定谵妄严重程度（平均差（MD）2.ll，95%CI -0.96至5.16；n = 50）､住院时间（MD 0.00，95%CI -3.45至3.45；n = 58）､全因死亡率（风险比（RR）0.33，95%CI 0.04至3.02；参与者 = 58）或任何不良事件是否存在临床上的重要差异。无法确认或排除重要影响。研究作者未报告谵妄发作的时长。在另一项试验中，参与者（n = 30）为普通内科病房中患有获得性免疫缺陷综合征（AIDS）的患者，平均年龄39.2岁。研究者比较了三种药物治疗：所有参与者均患有谵妄，并随机分组接受劳拉西泮、氯丙嗪或氟哌啶醇治疗。识别出的证据确定性非常低，我们无法确定劳拉西泮在谵妄严重程度､任何不良事件或全因死亡率方面的效果是否与其他两种治疗方法中的任何一种存在差异。研究作者未报告谵妄发作的时长或住院时间。
没有足够的证据来确定苯二氮䓬类药物用于治疗非ICU环境中谵妄患者时是否有效。现有证据不支持将其常规用于这一适应症。由于随机对照试验的数据稀缺，需要进一步研究以确定苯二氮䓬类药物在非ICU环境中治疗谵妄时是否有作用。
