BackgroundThe α2 agonists, dexmedetomidine and clonidine, are used as sedative drugs during critical illness. These drugs may have anti-inflammatory effects, which might be relevant to critical illness, but a systematic review of published literature has not been published. We reviewed animal and human studies relevant to critical illness to summarise the evidence for an anti-inflammatory effect from α2 agonists.MethodsWe searched PubMed, the Cochrane library, and Medline. Animal and human studies published in English were included. Broad search terms were used: dexmedetomidine or clonidine, sepsis, and inflammation. Reference lists were screened for additional publications. Titles and abstracts were screened independently by two reviewers and full-text articles obtained for potentially eligible studies. Data extraction used a bespoke template given study diversity, and quality assessment was qualitative.ResultsStudy diversity meant meta-analysis was not feasible so descriptive synthesis was undertaken. We identified 30 animal studies (caecal ligation/puncture (9), lipopolysaccharide (14), acute lung injury (5), and ischaemia-reperfusion syndrome (5)), and 9 human studies. Most animal (26 dexmedetomidine, 4 clonidine) and all human studies used dexmedetomidine. In animal studies, α2 agonists reduced serum and/or tissue TNFα (20 studies), IL-6 (17 studies), IL-1β (7 studies), NFκB (6 studies), TLR4 (6 studies), and a range of other mediators. Timing and doses varied widely, but in many cases were not directly relevant to human sedation use. In human studies, dexmedetomidine reduced CRP (4 studies), TNFα (5 studies), IL-6 (6 studies), IL-1β (3 studies), and altered several other mediators. Most studies were small and low quality. No studies related effects to clinical outcomes.ConclusionEvidence supports potential anti-inflammatory effects from α2 agonists, but the relevance to clinically important outcomes is uncertain. Further work should explore whether dose relationships with inflammation and clinical outcomes are present which might be separate from sedation-mediated effects.

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右美托咪定和可乐定对危重疾病炎症反应的影响：动物和人类研究的系统评价

背景α2激动剂右美托咪定和可乐定在危重症期间用作镇静药物。这些药物可能具有抗炎作用，这可能与危重疾病有关，但尚未发表对已发表文献的系统评价。我们回顾了与危重疾病相关的动物和人类研究，以总结 α2 激动剂具有抗炎作用的证据。方法我们搜索了 PubMed、Cochrane 图书馆和 Medline。包括以英文发表的动物和人类研究。使用了广泛的搜索词：右美托咪定或可乐定、败血症和炎症。筛选参考列表以查找其他出版物。标题和摘要由两名审稿人独立筛选，并为可能符合条件的研究获得全文文章。鉴于研究多样性，数据提取使用定制模板，质量评估是定性的。结果研究多样性意味着荟萃分析不可行，因此进行了描述性综合。我们确定了 30 项动物研究（盲肠结扎/穿刺 (9)、脂多糖 (14)、急性肺损伤 (5) 和缺血再灌注综合征 (5)）和 9 项人体研究。大多数动物（26 个右美托咪定，4 个可乐定）和所有人类研究都使用右美托咪定。在动物研究中，α2 激动剂降低了血清和/或组织 TNFα（20 项研究）、IL-6（17 项研究）、IL-1β（7 项研究）、NFκB（6 项研究）、TLR4（6 项研究）和一系列其他调解员。时间和剂量差异很大，但在许多情况下与人类镇静剂的使用没有直接关系。在人体研究中，右美托咪定降低 CRP（4 项研究）、TNFα（5 项研究）、IL-6（6 项研究）、IL-1β（3 项研究），并改变了其他几种介质。大多数研究规模小且质量低。没有研究与临床结果的影响相关。结论证据支持 α2 激动剂的潜在抗炎作用，但与临床重要结果的相关性尚不确定。进一步的工作应该探索是否存在与炎症和临床结果的剂量关系，这可能与镇静介导的作用不同。