右美托咪定可缩短ICU机械通气患者拔管时间:一项回顾性队列研究OA
Dexmedetomidine shortens time to extubation in mechanically ventilated ICU patients:A retrospective cohort study
目的 探讨不同镇静策略对接受有创机械通气(invasive mechanical ventilation,IMV)的重症监护病房(ICU)患者短期预后的影响,同时评估在高龄、合并恶性肿瘤或肝功能受损等特殊人群中是否存在差异.方法 本研究为回顾性观察性队列研究,数据来源于MIMIC-IV(v2.2)与eICU-CRD(v2.0)两大重症数据库.纳入标准:年龄≥18岁;入ICU后48 h内接受气管插管并行有创机械通气;ICU住院时长≥48 h;气管插管前2 h至插管后48 h内启动单一镇静策略(右美托咪定、丙泊酚、苯二氮䓬类药物).排除联合镇静策略、再插管及单药样本量<100例者.主要结局为拔管时间;次要结局包括院内死亡率、ICU住院时间、谵妄发生率及心血管不良事件发生率.基于梯度提升机算法的倾向评分进行逆概率加权(IPTW)控制混杂偏倚,随后利用增强逆概率加权(AIPW)双重稳健模型估计平均处理效应(ATE)、OR及95%CI;预设亚组分析检验年龄、恶性肿瘤及肝病状态的交互作用.结果 本研究最终共纳入12 561名患者,其中右美托咪定组1 111例,丙泊酚组8 021例,苯二氮䓬类组3 429例.IPTW加权后,各基线变量总体达到平衡.在AIPW双重稳健模型中,与右美托咪定组相比,丙泊酚组拔管时间延长0.782 d(ATE=0.782 d,95%CI:0.769~0.796,P<0.001),苯二氮䓬类组延长 1.791 d(ATE=1.791 d,95%CI:1.779~1.804,P<0.001);与苯二氮䓬类相比,丙泊酚组拔管时间缩短1.009 d(ATE=-1.009 d,95%CI:-1.018~-1.000,P<0.001).次要结局:与右美托咪定相比,丙泊酚与苯二氮䓬类院内死亡风险升高(丙泊酚:OR=1.905,95%CI:1.647~2.201,P<0.001;苯二氮䓬类:OR=2.768,95%CI:2.262~3.388,P<0.001),谵妄风险亦升高(丙泊酚:OR=1.905,95%CI:1.428~2.541,P<0.001;苯二氮䓬类:OR=2.382,95%CI:1.681~3.376,P<0.001).此外,ICU住院时间在丙泊酚组与苯二氮䓬类组分别延长0.367 d与1.012 d(丙泊酚:ATE=0.367 d,95%CI:0.351~0.382,P<0.001;苯二氮䓬类:ATE=1.012 d,95%CI:0.996~1.029,P<0.001),总心血管不良事件次数分别增加6.527次与15.199次(丙泊酚:ATE=6.527次,95%CI:6.112~6.942,P<0.001;苯二氮䓬类:ATE=15.199次,95%CI:14.727~15.671,P<0.001).呼吸机相关肺炎(VAP)方面,丙泊酚相较右美托咪定风险更低(OR=0.722,95%CI:0.648~0.805,P<0.001),苯二氮䓬类与右美托咪定差异不显著(OR=1.082,95%CI:0.934~1.252,P=1.000).亚组与交互作用分析显示,镇静策略与恶性肿瘤(P-for-interaction=0.001)及中重度肝病(P-for-interaction=0.048)存在显著交互:在合并恶性肿瘤患者中,丙泊酚组较右美托咪定组拔管时间呈缩短趋势(ATE=-1.326 d,95%CI:-2.732~0.080,P=0.064);在中重度肝病患者中,丙泊酚组较右美托咪定组拔管时间亦呈缩短趋势(ATE=-1.232 d,95%CI:-2.939~0.475,P=0.157),提示上述特殊人群中右美托咪定的获益减弱甚至可能发生方向改变.结论 对于ICU有创机械通气患者,右美托咪定相较丙泊酚与苯二氮䓬类与更短拔管时间及更低院内死亡率、谵妄与心血管不良事件风险相关;但在合并恶性肿瘤或中重度肝病患者中,右美托咪定的优势减弱.
Objective To investigate the impact of different sedation strategies on short-term outcomes in intensive care unit(ICU)patients receiving invasive mechanical ventilation(IMV),and to assess whether these effects differ in special populations such as the elderly,those with malignancy,or hepatic impairment.Methods This retrospective observational cohort study utilized data from 2 large critical care databases,MIMIC-IV(v2.2)and eICU-CRD(v2.0).Inclusion criteria were:age≥18 years;endotracheal intubation and IMV within 48 h after ICU admission;ICU length of stay(LOS)≥48 h;initiation of a single-agent sedation strategy(dexmedetomidine,propofol,or benzodiazepines)from 2 h before to 48 h after intubation.Patients receiving combined sedatives,undergoing re-intubation,or with single-drug sample sizes<100 were excluded.The primary outcome was time to extubation;secondary outcomes included in-hospital mortality,ICU LOS,incidence of delirium,and major adverse cardiovascular events(MACEs).Inverse probability of treatment weighting(IPTW)based on gradient boosting machine algorithms was employed to control confounding bias,followed by augmented inverse probability weighting(AIPW)doubly robust models to estimate average treatment effects(ATE),odds ratios(ORs),and 95%confidence intervals(CIs).Prespecified subgroup analyses were applied to examine interactions with age,malignancy,and hepatic status.Results A total of 12 561 patients were enrolled,comprising 1 111 in the dexmedetomidine group,8 021 in the propofol group,and 3 429 in the benzodiazepine group.After IPTW weighting,baseline variables achieved overall balance across groups.In the AIPW doubly robust models,compared with the dexmedetomidine group,the propofol group demonstrated prolonged time to extubation by 0.782 d(ATE=0.782 d,95%CI:0.769 to 0.796,P<0.001),and the benzodiazepine group by 1.791 d(ATE=1.791 d,95%CI:1.779 to 1.804,P<0.001);compared with benzodiazepines,the propofol group showed shortened extubation time by 1.009 d(ATE=-1.009 d,95%CI:-1.018 to-1.000,P<0.001).For secondary outcomes,compared with dexmedetomidine,both propofol and benzodiazepines were associated with increased risk for in-hospital mortality(propofol:OR=1.905,95%CI:1.647 to 2.201,P<0.001;benzodiazepines:OR=2.768,95%CI:2.262 to 3.388,P<0.001)and for delirium(propofol:OR=1.905,95%CI:1.428 to 2.541,P<0.001;benzodiazepines:OR=2.382,95%CI:1.681 to 3.376,P<0.001).Additionally,ICU LOS was prolonged by 0.367 d and 1.012 d in the propofol and benzodiazepine groups,respectively(propofol:ATE=0.367 d,95%CI:0.351 to 0.382,P<0.001;benzodiazepines:ATE=1.012 d,95%CI:0.996 to 1.029,P<0.001),and the total incidence of MACEs increased by 6.527 and 15.199 events(propofol:ATE=6.527 events,95%CI:6.112 to 6.942,P<0.001;benzodiazepines:ATE=15.199 events,95%CI:14.727 to 15.671,P<0.001).Regarding ventilator-associated pneumonia(VAP),propofol was associated with a lower risk than dexmedetomidine(OR=0.722,95%CI:0.648 to 0.805,P<0.001),whereas no significant difference was observed between benzodiazepines and dexmedetomidine(OR=1.082,95%CI:0.934~1.252,P=1.000).Subgroup and interaction analyses revealed significant interactions between sedation strategy and malignancy(P-for-interaction=0.001)and moderate-to-severe liver disease(P-for-interaction=0.048).Among patients with malignancy,propofol showed a trend toward shorter time to extubation than dexmedetomidine(ATE=-1.326 d,95%CI:-2.732 to-0.080,P=0.064);similarly,in patients with moderate-to-severe liver disease,propofol also demonstrated a trend toward shorter extubation time than dexmedetomidine(ATE=-1.232 d,95%CI:-2.939 to-0.475,P=0.157),suggesting attenuated or even reversed benefits of dexmedetomidine in these special populations.Conclusion In ICU patients receiving invasive mechanical ventilation,dexmedetomidine,is associated with shorter time to extubation and lower risks of in-hospital mortality,delirium,and cardiovascular adverse events compared with propofol and benzodiazepines.However,these advantage of dexmedetomidine are diminished among patients with malignancy or moderate-to-severe liver disease.
孙静;李雨捷;刘祥;舒欣;朱易紫婷;易斌
陆军军医大学(第三军医大学)第一附属医院麻醉科,围手术期多器官保护与智慧麻醉重点实验室,重庆陆军军医大学(第三军医大学)第一附属医院麻醉科,围手术期多器官保护与智慧麻醉重点实验室,重庆陆军军医大学(第三军医大学)第一附属医院麻醉科,围手术期多器官保护与智慧麻醉重点实验室,重庆陆军军医大学(第三军医大学)第一附属医院麻醉科,围手术期多器官保护与智慧麻醉重点实验室,重庆陆军军医大学(第三军医大学)第一附属医院麻醉科,围手术期多器官保护与智慧麻醉重点实验室,重庆陆军军医大学(第三军医大学)第一附属医院麻醉科,围手术期多器官保护与智慧麻醉重点实验室,重庆
医药卫生
机械通气IPTW丙泊酚苯二氮䓬类右美托咪定
mechanical ventilationinverse probability of treatment weightingpropofolbenzodiazepinesdexmedetomidine
《陆军军医大学学报》 2026 (6)
768-782,15
重庆市卫生健康委青年拔尖人才(YXQN202434) Supported by the Top Young Medical Talent Project of Chongqing Health Commission(YXQN202434).
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