Data Sheet 1_Is dexmedetomidine superior to non-dexmedetomidine sedatives (particularly propofol) for sedation in critically ill patients with septic shock? A systematic review and meta-analysis of randomized controlled trials.docx

BackgroundDexmedetomidine (DEX) and propofol (PROP) are both recommended as first-line short-acting sedative-analgesic agents for sepsis patients. However, existing studies have reported inconsistent clinical outcomes potentially attributable to their distinct hemodynamic profiles. The aim of our study was to systematically evaluate the comparative clinical efficacy and safety of DEX vs. non-Dexmedetomidine sedatives (particularly Propofol) in patients with septic shock.
MethodsThe study protocol was prospectively registered on PROSPERO (CRD42024626139). Randomized controlled trials (RCTs) meeting eligibility criteria were systematically searched up to December 2024. Statistical analyses were performed using RevMan 5.4, and trial sequential analysis (TSA) was employed to determine the required sample size.
Results17 RCTs were enrolled with 1,422 patients. Compared with non-DEX group, DEX group presented significantly reduced 28-day mortality (odds ratio [OR] 0.68, 95% CI 0.49–0.94, p = 0.02), lower IL-6 (mean difference [MD] −3.11 ng/L, 95% CI −5.32 to −0.90, p = 0.006) and TNF-α (MD −0.21 ng/L, 95% CI −0.30 to −0.12, p < 0.001). Importantly, the incidence of adverse effects did not increase compared to non-DEX groups, as evidenced by delirium (OR 0.82, 95% CI 0.34 to 1.97, p = 0.66), bradycardia (OR 1.36, 95% CI 0.66 to 2.78, p = 0.40), and hypotension (OR 1.38, 95% CI 0.59 to 3.19, p = 0.46). In the subgroup analysis, PROP showed no significant differences over DEX for key clinical outcomes, including: 28-day mortality and duration of invasive mechanical ventilation (IMV), length of stay in Intensive Care Unit (ICU LOS), etc. Regrettably, existing RCTs lacked sufficient data regarding inflammatory biomarkers and adverse event profiles above in direct comparisons between DEX and PROP. TSA on 28-day mortality between DEX and PROP indicated that a minimum of 1,269 additional participants would have required to achieve conclusive evidence (α = 0.10; β = 0.30; relative risk reduction [RRR] = 12.5%).
ConclusionDEX demonstrated superiority over non-DEX sedatives in critically ill patients with septic shock without increasing hemodynamic adverse events. However, current evidence showed no significant differences between DEX and PROP, warranting further high-quality RCTs for definitive conclusions.

背景：右美托咪定（Dexmedetomidine, DEX）与丙泊酚（propofol, PROP）均被推荐为脓毒症患者的一线短效镇静镇痛药物。然而现有研究报道的临床结局存在不一致，这可能与二者截然不同的血流动力学特征相关。本研究旨在系统评价右美托咪定对比非右美托咪定镇静药物（尤其是丙泊酚）在感染性休克患者中的临床疗效与安全性。
方法：本研究方案已在PROSPERO平台前瞻性注册（注册号：CRD42024626139）。系统检索截至2024年12月符合纳入标准的随机对照试验（randomized controlled trial, RCT）。采用RevMan 5.4软件开展统计学分析，并运用试验序贯分析（trial sequential analysis, TSA）确定所需样本量。
结果：本研究共纳入17项随机对照试验，涉及1422例患者。与非DEX组相比，DEX组28天死亡率显著降低（比值比[OR] 0.68，95%置信区间[CI] 0.49–0.94，P=0.02），白细胞介素-6（IL-6）水平显著下降（均数差[MD] −3.11 ng/L，95%CI −5.32至−0.90，P=0.006），肿瘤坏死因子-α（TNF-α）水平亦显著降低（均数差[MD] −0.21 ng/L，95%CI −0.30至−0.12，P<0.001）。值得注意的是，与非DEX组相比，DEX组不良事件发生率并未升高，具体体现为谵妄（OR 0.82，95%CI 0.34至1.97，P=0.66）、心动过缓（OR 1.36，95%CI 0.66至2.78，P=0.40）及低血压（OR 1.38，95%CI 0.59至3.19，P=0.46）。亚组分析显示，丙泊酚与DEX在关键临床结局方面无显著差异，包括28天死亡率、有创机械通气（invasive mechanical ventilation, IMV）时长、重症监护病房住院时长（Intensive Care Unit LOS, ICU LOS）等。遗憾的是，现有随机对照试验缺乏右美托咪定与丙泊酚直接对比的炎症生物标志物及不良事件特征相关的充足数据。针对DEX与丙泊酚28天死亡率的试验序贯分析显示，需至少额外纳入1269例受试者才能获得确定性证据（α=0.10；β=0.30；相对风险降低率[RRR]=12.5%）。
结论：右美托咪定在感染性休克重症患者中优于非右美托咪定镇静药物，且不会增加血流动力学不良事件风险。然而，现有证据显示右美托咪定与丙泊酚之间无显著差异，尚需开展更多高质量随机对照试验以得出确定性结论。