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Article(id=1320441130949394707, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1320441010094715145, articleNumber=null, orderNo=null, doi=10.16016/j.2097-0927.202512139, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1766505600000, receivedDateStr=2025-12-24, revisedDate=1769011200000, revisedDateStr=2026-01-22, acceptedDate=null, acceptedDateStr=null, onlineDate=1792747298227, onlineDateStr=2026-10-23, pubDate=1774800000000, pubDateStr=2026-03-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792747298227, onlineIssueDateStr=2026-10-23, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792747298227, creator=13701087609, updateTime=1792747298227, updator=13701087609, issue=Issue{id=1320441010094715145, tenantId=1146029695717560320, journalId=1319373162502258839, year='2026', volume='48', issue='6', pageStart='663', pageEnd='830', issueExtLink='null', onlineDate='null', pubDate='1774800000000', pubDateStr='2026-03-30', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1792747269413, creator='13701087609', updateTime=1792749761919, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1320451464481321472, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1320441010094715145, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1320451464481321473, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1320441010094715145, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=768, endPage=782, ext={EN=ArticleExt(id=1320441132652282132, articleId=1320441130949394707, tenantId=1146029695717560320, journalId=1319373162502258839, language=EN, title=Dexmedetomidine shortens time to extubation in mechanically ventilated ICU patients: A retrospective cohort study, columnId=1320435174995772212, journalTitle=Journal of Army Medical University, columnName=Clinical Medicine, runingTitle=null, highlight=null, articleAbstract=
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.

, authors=Jing SUN, Yujie LI, Xiang LIU, Xin SHU, Yiziting ZHU, Bin YI, authorsList=Jing SUN, Yujie LI, Xiang LIU, Xin SHU, Yiziting ZHU, Bin YI, authorCompany=null, correspAuthors=Bin YI, authorNote=null, correspAuthorsNote=null, copyrightStatement=© 2026 Journal of Army Medical University, copyrightOwner=Editorial Office of Journal of Army Medical University, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1320441137274405155, articleId=1320441130949394707, tenantId=1146029695717560320, journalId=1319373162502258839, language=CN, title=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, columnId=1320435175822050102, journalTitle=陆军军医大学学报, columnName=论著·临床医学, runingTitle=null, highlight=null, articleAbstract=
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。

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易斌，Email：
YI Bin, E-mail：
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Sci Data， 2018， 5： 180178., articleTitle=The eICU Collaborative Research Database， a freely available multi-center database for critical care research, refAbstract=null), Reference(id=1320441177044795813, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, doi=10.1093/aje/kwq439, pmid=null, pmcid=null, year=2011, volume=173, issue=7, pageStart=761, pageEnd=767, url=null, language=null, rfNumber=49, rfOrder=48, authorNames=FUNK M J, WESTREICH D, WIESEN C, journalName=Am J Epidemiol, refType=null, unstructuredReference=FUNK M J， WESTREICH D， WIESEN C， et al. Doubly robust estimation of causal effects［J］. Am J Epidemiol， 2011， 173（7）： 761-767., articleTitle=Doubly robust estimation of causal effects, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1320441138473976100, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, xref=1, ext=[AuthorCompanyExt(id=1320441138528502053, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, companyId=1320441138473976100, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Anesthesiology， Key Laboratory of Perioperative Multi-organ Protection and Intelligent Anesthesia， First Affiliated Hospital， Army Medical University （Third Military Medical University）， Chongqing， China), AuthorCompanyExt(id=1320441138553667878, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, companyId=1320441138473976100, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1陆军军医大学（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)])], figs=[ArticleFig(id=1320441150314496337, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=EN, label=Figure 1, caption=Flowchart of study population selection based on inclusion and exclusion criteria, figureFileSmall=zyvSyL2ww9EVTmBXkdQw2Q==, figureFileBig=8XfEd8djldDd7WDlNcSaYA==, tableContent=null), ArticleFig(id=1320441151119802706, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=CN, label=图1, caption=研究人群纳入排除流程图, figureFileSmall=zyvSyL2ww9EVTmBXkdQw2Q==, figureFileBig=8XfEd8djldDd7WDlNcSaYA==, tableContent=null), ArticleFig(id=1320441152399065427, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=EN, label=Figure 2, caption=Standardized differences of covariates before and after IPTW adjustment, figureFileSmall=c6JoFUKxmA3zo+0ktMBECg==, figureFileBig=Ee+g8rS0MZIi8AIe5Re7cg==, tableContent=null), ArticleFig(id=1320441152768164180, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=CN, label=图2, caption=IPTW前后协变量间的标准化偏差

sedation failures： number of times target sedation level was not achieved

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Baseline characteristics of the study cohort ［M（P25，P75），n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
ItemBefore IPTWAfter IPTW
Dexmedetomidine
（n=1 111）		Propofol
（n=8 021）		Benzodiazepines
（n=3 429）		Pp_dex vs. prop_dex vs.benp_ pro vs.benDexmedetomidine
（n=10 393）		Propofol
（n=12 418）		Benzodiazepines
（n=11 788）		smd_ dex vs.prosmd_ dex vs.bensmd_ pro vs.ben
Age/years66 （56， 75）66 （56， 76）66 （55， 76）<0.0010.2410.7320.02466 （55，75）66 （55，76）66 （55，76）0.0060.0220.016
APS III43 （32， 59）49 （34， 68）60 （44， 80）<0.001<0.001<0.001<0.00150 （35，69）51 （36，71）52 （37，72）-0.040-0.077-0.037
BMI/（kg/m²）29.5
（25.1， 34.0）		28.4
（24.5， 33.44）		28.3
（24.0， 33.6）		<0.0010.002<0.0010.15028.7
（24.6，33.7）		28.4
（24.5，33.5）		28.4
（24.4，33.5）		-0.007-0.0000.006
CCI4 （3， 6）4 （3， 6）5 （3， 7）<0.0010.001<0.0010.0014 （3，6）5 （3，6）5 （3，7）-0.061-0.070-0.009
GCS score15 （10， 15）15 （11， 15）15 （10， 15）<0.0010.1920.8450.02115 （10，15）15 （11，15）15 （10，15）-0.043-0.0230.020
Sedation Failures1 （0， 3）0 （0， 2）0 （0， 4）<0.001<0.001<0.0010.0620 （0，2）0 （0，2）0 （0，2）-0.032-0.049-0.017
Gender<0.001<0.001<0.0010.0390.0330.0630.030
Female381 （34.3）3 401 （42.4）1 526 （44.5）4 225 （40.7）5 249 （42.3）5 156 （43.8）
Male730 （65.7）4 620 （57.6）1 903 （55.5）6 169 （59.3）7 169 （57.7）6 631 （56.2）
Malnutrition82 （7.4）684 （8.5）400 （11.7）<0.0010.204<0.001<0.001877 （8.4）1 144 （9.2）1 136 （9.6）-0.027-0.042-0.014
Surgery259 （23.3）2 919 （36.4）1 541 （44.9）<0.001<0.001<0.001<0.0013 336 （32.1）4 646 （37.4）4 448 （37.7）-0.112-0.119-0.007
), ArticleFig(id=1320441156614340961, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=CN, label=表1, caption=

研究人群的基线特征 ［M（P25，P75），例（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
ItemBefore IPTWAfter IPTW
Dexmedetomidine
（n=1 111）		Propofol
（n=8 021）		Benzodiazepines
（n=3 429）		Pp_dex vs. prop_dex vs.benp_ pro vs.benDexmedetomidine
（n=10 393）		Propofol
（n=12 418）		Benzodiazepines
（n=11 788）		smd_ dex vs.prosmd_ dex vs.bensmd_ pro vs.ben
Age/years66 （56， 75）66 （56， 76）66 （55， 76）<0.0010.2410.7320.02466 （55，75）66 （55，76）66 （55，76）0.0060.0220.016
APS III43 （32， 59）49 （34， 68）60 （44， 80）<0.001<0.001<0.001<0.00150 （35，69）51 （36，71）52 （37，72）-0.040-0.077-0.037
BMI/（kg/m²）29.5
（25.1， 34.0）		28.4
（24.5， 33.44）		28.3
（24.0， 33.6）		<0.0010.002<0.0010.15028.7
（24.6，33.7）		28.4
（24.5，33.5）		28.4
（24.4，33.5）		-0.007-0.0000.006
CCI4 （3， 6）4 （3， 6）5 （3， 7）<0.0010.001<0.0010.0014 （3，6）5 （3，6）5 （3，7）-0.061-0.070-0.009
GCS score15 （10， 15）15 （11， 15）15 （10， 15）<0.0010.1920.8450.02115 （10，15）15 （11，15）15 （10，15）-0.043-0.0230.020
Sedation Failures1 （0， 3）0 （0， 2）0 （0， 4）<0.001<0.001<0.0010.0620 （0，2）0 （0，2）0 （0，2）-0.032-0.049-0.017
Gender<0.001<0.001<0.0010.0390.0330.0630.030
Female381 （34.3）3 401 （42.4）1 526 （44.5）4 225 （40.7）5 249 （42.3）5 156 （43.8）
Male730 （65.7）4 620 （57.6）1 903 （55.5）6 169 （59.3）7 169 （57.7）6 631 （56.2）
Malnutrition82 （7.4）684 （8.5）400 （11.7）<0.0010.204<0.001<0.001877 （8.4）1 144 （9.2）1 136 （9.6）-0.027-0.042-0.014
Surgery259 （23.3）2 919 （36.4）1 541 （44.9）<0.001<0.001<0.001<0.0013 336 （32.1）4 646 （37.4）4 448 （37.7）-0.112-0.119-0.007
), ArticleFig(id=1320441156903747938, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=EN, label=Table 2, caption=

Primary outcome in the study cohort ［M（P25，P75）

, figureFileSmall=null, figureFileBig=null, tableContent=
Primary outcomeDexmedetomidine
（n=1 111）		Propofol
（n=8 021）		Benzodiazepines
（n=3 429）		Pp_dex vs prop_dex vs benp_ pro vs ben
Extubation time/d0.82 （0.31， 2.15）1.44 （0.58， 3.53）2.87 （1.41， 5.62）<0.001<0.001<0.001<0.001
), ArticleFig(id=1320441156970856803, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=CN, label=表2, caption=

研究人群的主要结局 ［M（P25，P75）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Primary outcomeDexmedetomidine
（n=1 111）		Propofol
（n=8 021）		Benzodiazepines
（n=3 429）		Pp_dex vs prop_dex vs benp_ pro vs ben
Extubation time/d0.82 （0.31， 2.15）1.44 （0.58， 3.53）2.87 （1.41， 5.62）<0.001<0.001<0.001<0.001
), ArticleFig(id=1320441157037965668, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=EN, label=Table 3, caption=

Primary outcome after IPTW adjustment ［M（P25，P75）

, figureFileSmall=null, figureFileBig=null, tableContent=
Primary outcomeDexmedetomidine
（n=10 393）		Propofol
（n=12 418）		Benzodiazepines
（n=11 788）		Pp_dex vs prop_dex vs benp_ pro vs ben
Extubation time/d0.9 （0.34 ，2.41）1.61 （0.63 ， 3.76）2.45 （1.13 ， 4.99）<0.001<0.001<0.001<0.001
), ArticleFig(id=1320441159005094246, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=CN, label=表3, caption=

IPTW后的主要结局 ［M（P25，P75）

, figureFileSmall=null, figureFileBig=null, tableContent=
Primary outcomeDexmedetomidine
（n=10 393）		Propofol
（n=12 418）		Benzodiazepines
（n=11 788）		Pp_dex vs prop_dex vs benp_ pro vs ben
Extubation time/d0.9 （0.34 ，2.41）1.61 （0.63 ， 3.76）2.45 （1.13 ， 4.99）<0.001<0.001<0.001<0.001
), ArticleFig(id=1320441159101563239, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=EN, label=Table 4, caption=

Secondary outcomes in the study cohort ［M（P25，P75），n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Secondary outcomesDexmedetomidine
（n=1 111）		Propofol
（n=8 021）		Benzodiazepines
（n=3 429）		Pp_dex vs prop_dex vs benp_ pro vs ben
LOS/d9.79 （6.82， 15.90）10.30 （6.75， 16.84）10.42 （6.59， 17.12）0.6850.3050.4960.639
ICU-LOS/d3.83 （2.71， 5.96）4.07 （2.83， 6.79）5.04 （3.21， 8.29）<0.001<0.001<0.001<0.001
Major adverse cardiovascular events6 （1， 17）7 （1， 25）17 （4， 48）<0.001<0.001<0.001<0.001
Bradycardia0 （0， 0）0 （0， 0）0 （0， 0）<0.0010.015<0.001<0.001
Tachycardia0 （0， 0）0 （0， 1）0 （0， 6）<0.001<0.001<0.001<0.001
Hypertension0 （0， 0）0 （0， 1）0 （0， 2）<0.001<0.001<0.001<0.001
Hypotension4 （1， 14）4 （0， 17）9 （1， 34）<0.0010.181<0.001<0.001
Delirium18 （1.6）318 （4.0）167 （4.9）<0.001<0.001<0.0010.029
In-hospital mortality81 （7.3）1262 （15.7）907 （26.5）<0.001<0.001<0.001<0.001
VAP35 （3.2）190 （2.4）136 （4.0）<0.0010.1210.239<0.001
), ArticleFig(id=1320441159172866408, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=CN, label=表4, caption=

研究人群的次要结局 ［M（P25，P75），例（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Secondary outcomesDexmedetomidine
（n=1 111）		Propofol
（n=8 021）		Benzodiazepines
（n=3 429）		Pp_dex vs prop_dex vs benp_ pro vs ben
LOS/d9.79 （6.82， 15.90）10.30 （6.75， 16.84）10.42 （6.59， 17.12）0.6850.3050.4960.639
ICU-LOS/d3.83 （2.71， 5.96）4.07 （2.83， 6.79）5.04 （3.21， 8.29）<0.001<0.001<0.001<0.001
Major adverse cardiovascular events6 （1， 17）7 （1， 25）17 （4， 48）<0.001<0.001<0.001<0.001
Bradycardia0 （0， 0）0 （0， 0）0 （0， 0）<0.0010.015<0.001<0.001
Tachycardia0 （0， 0）0 （0， 1）0 （0， 6）<0.001<0.001<0.001<0.001
Hypertension0 （0， 0）0 （0， 1）0 （0， 2）<0.001<0.001<0.001<0.001
Hypotension4 （1， 14）4 （0， 17）9 （1， 34）<0.0010.181<0.001<0.001
Delirium18 （1.6）318 （4.0）167 （4.9）<0.001<0.001<0.0010.029
In-hospital mortality81 （7.3）1262 （15.7）907 （26.5）<0.001<0.001<0.001<0.001
VAP35 （3.2）190 （2.4）136 （4.0）<0.0010.1210.239<0.001
), ArticleFig(id=1320441159491633513, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=EN, label=Table 5, caption=

Secondary outcomes after IPTW adjustment ［M（P25，P75），n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Secondary outcomesDexmedetomidine
（n=10 393）		Propofol
（n=12 418）		Benzodiazepines
（n=11 788）		Pp_dex vs prop_dex vs benp_ pro vs ben
LOS/d10.45 （6.94，16.5）10.56 （6.81，17.32）9.97 （6.47，16.38）0.0020.8930.041<0.001
ICU-LOS/d3.88 （2.83，6.12）4.17 （2.88，7.00）4.76 （3.05，7.76）<0.001<0.001<0.001<0.001
Major adverse cardiovascular events7 （1，20）8 （2，28）12 （2，39）<0.0010.001<0.001<0.001
Bradycardia0 （0， 0）0 （0，0）0 （0，0）0.0310.1870.0170.047
Tachycardia0 （0，0）0 （0，1）0 （0，3）<0.001<0.001<0.001<0.001
Hypertension0 （0，1）0 （0，1）0 （0，1）<0.001<0.001<0.001<0.001
Hypotension5 （1，15）5 （0，19）6 （1，26）<0.0010.704<0.001<0.001
Delirium236 （2.3）504 （4.1）574 （4.9）<0.001<0.001<0.0010.003
In-hospital mortality1025 （9.9）2167 （17.4）2532 （21.5）<0.001<0.001<0.001<0.001
VAP318 （3.1）333 （2.7）381 （3.2）0.0360.0820.4770.012
), ArticleFig(id=1320441159873315178, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1320441130949394707, language=CN, label=表5, caption=

IPTW后的次要结局 ［M（P25，P75），例（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
Secondary outcomesDexmedetomidine
（n=10 393）		Propofol
（n=12 418）		Benzodiazepines
（n=11 788）		Pp_dex vs prop_dex vs benp_ pro vs ben
LOS/d10.45 （6.94，16.5）10.56 （6.81，17.32）9.97 （6.47，16.38）0.0020.8930.041<0.001
ICU-LOS/d3.88 （2.83，6.12）4.17 （2.88，7.00）4.76 （3.05，7.76）<0.001<0.001<0.001<0.001
Major adverse cardiovascular events7 （1，20）8 （2，28）12 （2，39）<0.0010.001<0.001<0.001
Bradycardia0 （0， 0）0 （0，0）0 （0，0）0.0310.1870.0170.047
Tachycardia0 （0，0）0 （0，1）0 （0，3）<0.001<0.001<0.001<0.001
Hypertension0 （0，1）0 （0，1）0 （0，1）<0.001<0.001<0.001<0.001
Hypotension5 （1，15）5 （0，19）6 （1，26）<0.0010.704<0.001<0.001
Delirium236 （2.3）504 （4.1）574 （4.9）<0.001<0.001<0.0010.003
In-hospital mortality1025 （9.9）2167 （17.4）2532 （21.5）<0.001<0.001<0.001<0.001
VAP318 （3.1）333 （2.7）381 （3.2）0.0360.0820.4770.012
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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
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孙静 , 李雨捷 , 刘祥 , 舒欣 , 朱易紫婷 , 易斌
陆军军医大学学报 | 论著·临床医学 2026,48(6): 768-782
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陆军军医大学学报 |论著·临床医学 2026 , 48 (6) : 768 -782
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
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孙静, 李雨捷, 刘祥, 舒欣, 朱易紫婷, 易斌
作者信息
  • 1陆军军医大学（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
通讯作者:
易斌，Email：
YI Bin, E-mail：
Dexmedetomidine shortens time to extubation in mechanically ventilated ICU patients: A retrospective cohort study
Jing SUN, Yujie LI, Xiang LIU, Xin SHU, Yiziting ZHU, Bin YI
Affiliations
  • 1Department of Anesthesiology， Key Laboratory of Perioperative Multi-organ Protection and Intelligent Anesthesia， First Affiliated Hospital， Army Medical University （Third Military Medical University）， Chongqing， China
出版时间: 2026-03-30 doi: 10.16016/j.2097-0927.202512139
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摘要
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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。

机械通气  /  IPTW  /  丙泊酚  /  苯二氮䓬类  /  右美托咪定
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.

mechanical ventilation  /  inverse probability of treatment weighting  /  propofol  /  benzodiazepines  /  dexmedetomidine
孙静, 李雨捷, 刘祥, 舒欣, 朱易紫婷, 易斌. 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. 陆军军医大学学报, 2026 , 48 (6) : 768 -782 . DOI: 10.16016/j.2097-0927.202512139
Jing SUN, Yujie LI, Xiang LIU, Xin SHU, Yiziting ZHU, Bin YI. Dexmedetomidine shortens time to extubation in mechanically ventilated ICU patients: A retrospective cohort study[J]. Journal of Army Medical University, 2026 , 48 (6) : 768 -782 . DOI: 10.16016/j.2097-0927.202512139
正文
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有创机械通气是重症监护病房（intensive care unit， ICU）中挽救生命的关键支持技术［1］，但也可能增加死亡、谵妄、呼吸机相关性肺炎、心血管不良事件等并发症风险［2］。合理有效的镇静治疗对保障患者安全、促进及早脱机至关重要。目前，临床上用于ICU机械通气患者的镇静药物主要包括右美托咪定、丙泊酚、苯二氮䓬类药物［3］。丙泊酚起效快、代谢迅速，便于调控镇静深度［4］；而苯二氮䓬类药物则存在蓄积风险和谵妄发生可能；右美托咪定具有独特的“清醒镇静”特性，呼吸抑制轻微，有利于早期脱机和谵妄管理［5］。
然而，对于这三种镇静药物在拔管时间这一重要结局指标上的影响，目前已有的研究得出的结论并不统一。有部分研究指出，当患者需要保持浅镇静状态、尽早脱离呼吸机以及降低发生谵妄的风险时，右美托咪定相较于丙泊酚或者咪达唑仑，可能更具优势［6-8］；然而，近期的A2B试验（alpha 2 agonists for sedation to produce better outcomes from critical illness）结果显示，和以丙泊酚为主要镇静药物的方案相比，右美托咪定在缩短患者成功拔管时间方面，并没有体现出优势［9］。在像肝功能受损患者、恶性肿瘤患者以及超高龄（年龄≥80岁）患者这类特殊人群中，目前还缺乏高质量的证据来指导镇静药物的选择［10-11］。而且，多数研究在开展时，有选择性地没有将这些特殊人群纳入研究范围［12］，这就使得临床决策缺乏具有针对性的指导依据［13］。
本研究拟比较右美托咪定、丙泊酚及苯二氮䓬类药物三种镇静策略对ICU有创机械通气患者拔管时间的影响，并评估其在降低院内死亡率、减少谵妄发生率及预防心血管不良事件方面的差异。
1　方法
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1.1　数据来源
本研究为回顾性观察性队列研究，使用的两个数据库分别是重症监护医疗信息市场（MIMIC）-IV（版本2.2）［14-15］与eICU合作研究数据库（eICU-CRD，版本2.0）［16］。MIMIC-IV数据库记录了2008年至2019年间美国马萨诸塞州波士顿贝斯以色列女执事医疗中心所有住院患者的完整临床资料［17］。eICU-CRD则包含了2014至2015年间来自美国本土208家医院共139 367名患者的200 859次ICU住院记录［18］。这两个数据库均已对患者身份标识符去识别化，用匿名编码替代，因此本研究无需额外申请伦理审查。研究团队已获得使用授权（认证编号：刘祥-62584102）。
1.2　研究队列
本研究明确界定了研究人群，具体纳入标准如下：年龄≥18岁；入ICU后的48 h内接受气管插管并进行有创机械通气；ICU 住院时长不少于48 h；插管前2 h至插管后48 h内，开始使用镇静药物。研究对象需满足仅采用单一镇静策略：右美托咪定策略、丙泊酚策略或苯二氮䓬类策略，苯二氮䓬类策略包括咪达唑仑、地西泮、劳拉西泮。
排除标准设定为：拔管后再次进行气管插管的患者；使用两类及以上镇静药物的患者；单一种类镇静药物使用总人数少于100例的患者。观察终止点为拔管、出ICU或出院/死亡；本研究不涉及出院后随访。
符合基本入组条件的高龄、肿瘤或肝功能受损患者并未被排除，而是保留在队列中。由于这些人群的镇静风险收益比可能异于常人，我们在分析阶段预先设定了亚组比较和交互效应验证。
1.3　镇静策略暴露定义与分组
本研究比较了三种镇静策略（右美托咪定策略、丙泊酚策略及苯二氮䓬类药物策略）对ICU有创机械通气患者短期预后的影响。其中，右美托咪定与丙泊酚组均为单一药物暴露，而苯二氮䓬类组包含了咪达唑仑、地西泮和劳拉西泮三种药物。将这三者合并分析，主要是考虑到这些药物同属苯二氮䓬类，均通过作用于GABA-A受体发挥镇静效应，作用机制相近；此外，在临床实践及既往研究中，按药物类别进行比较也较为常见［19］。
根据镇静药物的使用情况，将接受气管插管并进行有创机械通气的患者划分为右美托咪定组、丙泊酚组以及苯二氮䓬类组。
1.4　数据提取和数据处理
本研究采集患者基线特征：人口学资料包括年龄、性别及体重指数（body mass index， BMI）；疾病严重程度评分包括急性生理评分Ⅲ（acute physiology score Ⅲ， APSⅢ）、格拉斯哥昏迷量表（glasgow coma scale， GCS）评分；基线健康状况包括营养不良状况、查尔森合并症指数（Charlson comorbidity index， CCI）；治疗相关情况包括未达到目标镇静的次数和入ICU前外科手术史。采集治疗相关信息：机械通气参数（包括设定潮气量、呼气末正压及呼吸频率）及其启用时间；镇静药物（右美托咪定、丙泊酚、咪达唑仑、地西泮、劳拉西泮）的使用情况、给药起始时间。采集研究结局指标：插管时间、拔管时间、入ICU、出ICU时间，以及呼吸机相关性肺炎、谵妄和心血管不良事件（涵盖心动过速、心动过缓、高血压和低血压）的发生情况。
营养不良状态判定：①诊断；②BMI<18.5。本研究中，手术特指传统外科手术如开放性手术和腔镜手术。目标镇静范围设定为里士满镇静躁动量表（Richmond agitation sedation scale， RASS）评分在<+1且>-2之间，超出此范围则视为未达目标镇静。
数据清洗整理过程中，设定身高（90~230 cm）、体质量（30~200 kg）的合理区间，超出此范围的值视为异常并赋值为缺失。本研究数据集所有变量的缺失率均未超过30%，采用R语言中的“MICE”包进行多重插补［20］，插补次数（m=5），连续变量采用预测均值匹配方法，二分类变量采用逻辑回归方法，多分类变量采用多项逻辑回归方法。
1.5　主要研究终点
主要结局是拔管时间。针对MIMIC-IV数据库，拔管时间定义为拔管操作时间，若患者出ICU后仍未拔管，则以ICU出院时间作为拔管时间。在eICU-CRD队列中，插管时间定义为呼吸机参数的最早起始时间，拔管时间则为最后一个呼吸机参数记录时间。结局收集范围为ICU住院期间及住院期间（院内结局），不包含出院后随访。
1.6　次要研究终点
次要结局指标包括院内死亡率、ICU停留时间、住院时间、呼吸机相关肺炎发生率、谵妄发生率以及心血管不良事件（包括心动过速、心动过缓、高血压、低血压等）的发生情况。呼吸机相关性肺炎在MIMIC-IV数据库中依据ICD诊断代码筛选，而在eICU-CRD队列中则选取诊断名称符合呼吸机相关肺炎的患者。谵妄状态采用CAM-ICU量表（The Confusion Assessment Method for the Intensive Care Unit）评估：在MIMIC-IV中，需同时满足特征1（急性起病或波动）与特征2（注意力障碍）阳性，且特征3（思维混乱）或特征4（意识水平改变）至少一项阳性；在eICU-CRD中，则直接采纳临床记录中标记为“谵妄”的状态。机械通气期间符合上述任一标准即判定为发生谵妄事件。心血管不良事件定义如下：心率<40次/min判定为心动过缓，心率>120次/min判定为心动过速；收缩压>180 mmHg或舒张压>100 mmHg判定为高血压；收缩压<80 mmHg或舒张压<50 mmHg判定为低血压。
1.7　亚组分析
为评估不同镇静策略在特殊人群中的潜在效应差异，我们按以下变量进行预设亚组分析：年龄分层（<65岁、65~79岁、≥80岁）、是否合并恶性肿瘤、是否合并慢性肺部疾病、是否存在肝脏疾病以及手术状态。合并恶性肿瘤与肝脏疾病的判定采用数据库中CCI进行识别。肝脏疾病进一步区分为轻度与中重度肝病。超高龄定义为≥80岁，并据此进行分层分析。在各亚组内，采用IPTW加权线性回归模型估计三种镇静药物两两比较的回归系数及其95%CI；同时在加权模型中纳入“治疗×亚组变量”的交互项以检验效应修饰，并报告P-for-interaction，用于评估人群异质性。
1.8　偏倚
作为观察性研究，本研究可能存在指征混杂、流程差异、暴露分类错误（推注与持续输注记录差异、滴定频率/中断信息不全）及结局测量差异等偏倚。为降低混杂偏倚，我们在患者层面纳入人口学、疾病严重程度、合并症与治疗相关变量估计倾向评分并实施IPTW加权，同时采用AIPW进行双重稳健估计；中心流程差异与部分过程指标由于缺乏统一结构化变量，无法完全控制，已在讨论中说明其对结果的潜在影响。
1.9　统计学分析
本研究未事先进行效能分析，样本量来自两个数据库在预设纳入与排除标准下能够获取到的所有符合条件的样本。为确保组间比较的稳定性和估计的可行性，我们预先剔除单一用药总数不足100例的暴露类别。
为了有效控制混杂偏倚对研究结果的影响，运用梯度提升机（gradient boosting machine， GBM）来估计倾向性评分，并依据这一评分计算逆概率处理权重（inverse probability of treatment weighting， IPTW）［21］。为增强权重稳定性减少极端值的干扰，对权重进行1%~99%分位数截断。采用标准化均数差（standardized mean difference ，SMD）评估加权前后的基线特征的平衡性（SMD<0.2 视为平衡良好）［22］。
镇静策略对各项结局的平均处理效应（average treatment effect， ATE）及其95%CI，通过增强逆概率加权（augmented inverse probability weighting， AIPW）这一双重稳健模型进行估计。该方法结合倾向评分加权与结局回归模型，只要任一模型设定正确即可获得处理效应的一致估计量，从而提供更稳健的结果。最终通过Rubin法则合并多重插补数据集的结果［23］。
符合正态分布的连续变量表示为均值±标准差（standard deviation， SD），采用方差分析（analysis of variance， ANOVA）进行3组整体比较，两两比较采用独立样本t检验进行比较，而非正态分布变量报告为中位数（四分位数），采用Kruskal-Wallis 检验进行3组整体比较，两两比较采用Mann-Whitney U 检验进行分析。分类变量以频率（百分比）表示，并使用χ2检验或Fisher精确检验进行评估。所有组间比较结果均通过 Rubin 法则合并。所有数据分析均采用R 4.5.1版完成，统计显著性设定为双侧P值<0.05。
本研究未开展额外敏感性分析，相关稳健性验证将在后续研究中补充。
2　结果
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2.1　研究人群
本研究最终共纳入12 561名患者，其中右美托咪定组1 111例（8.8%），丙泊酚组8 021例（63.9%），苯二氮䓬类组3 429例（27.3%），详见图1。各组患者年龄中位数均为66岁。右美托咪定组中男性730例（65.7%）、女性381例（34.3%）；丙泊酚组男性4 620例（57.6%）、女性3 401例（42.4%）；苯二氮䓬类组男性1 903例（55.5%）、女性1 526例（44.5%），详见表1。
2.2　基线特征
IPTW加权前，3组患者的基线特征存在显著差异，苯二氮䓬类药物组的疾病严重程度最高，其APSIII评分中位数为60分，CCI评分中位数为5分，且接受手术的比例最高（44.9%），均显著高于右美托咪定组和丙泊酚组（P）。经IPTW调整后，所有SMD绝对值<0.2，组间基线特征分布均衡，有效降低了潜在混杂偏倚（图2、表1）。
2.3　主要结局
与丙泊酚组相比，右美托咪定组患者的中位拔管时间显著缩短（0.82 d vs 1.44 d，P<0.001）；与苯二氮䓬类组相比，右美托咪定组的中位拔管时间亦显著缩短（0.82 d vs 2.87 d，P<0.001）；丙泊酚组的中位拔管时间也显著短于苯二氮䓬类组（1.44 d vs 2.87 d， P<0.001），详见表2。经逆概率加权调整后，右美托咪定组患者的中位拔管时间仍显著低于丙泊酚组和苯二氮䓬类组，且差异均有统计学意义（均P<0.001），见表3。
基于AIPW模型计算的平均处理效应显示，与右美托咪定组相比，丙泊酚组和苯二氮䓬类组的拔管时间分别显著延长0.782 d（95%CI： 0.769~0.796）和1.791 d（95%CI： 1.779~1.804）。此外，丙泊酚组的拔管时间也显著短于苯二氮䓬类组（ATE=-1.009 d，95%CI：-1.018~ -1.000）。详见图3。
2.4　次要结局
在次要结局方面，未加权与IPTW后结果总体一致（表4、5）：右美托咪定组在ICU-LOS更短、院内死亡率与谵妄发生率更低，且总心血管不良事件水平更低；苯二氮䓬类组整体最差。IPTW后，右美托咪定组ICU-LOS最短［3.88（2.83，6.12）d］，低于丙泊酚组［4.17（2.88，7.00）d］与苯二氮䓬类组［4.76（3.05，7.76）d］（均P<0.001）；谵妄（2.3% vs 4.1% vs 4.9%）与院内死亡率（9.9% vs 17.4% vs 21.5%）呈阶梯式差异（均P<0.001）。心血管结局方面，右美托咪定组心血管不良事件更低［7（1，20）］，低于丙泊酚［8（2，28）］与苯二氮䓬类［12（2，39）］（P=0.001；P<0.001）。VAP在IPTW后右美托咪定与另外两组差异均不显著，仅丙泊酚低于苯二氮䓬类（表5）。
AIPW双重稳健估计进一步量化了上述差异（图3、4）：与右美托咪定相比，丙泊酚与苯二氮䓬类分别使院内死亡风险升高（OR=1.904；OR=2.768）及谵妄风险升高（OR=1.905；OR=2.382），并分别延长ICU住院时间0.367 d与1.012 d。心血管安全性方面，丙泊酚与苯二氮䓬类分别增加心血管不良事件次数6.527次与15.199次，主要由心动过速（ATE=2.277次与5.287次）及低血压（ATE=3.246次与8.990次）事件增加所驱动。相比之下，丙泊酚在多项次要结局上优于苯二氮䓬类（如院内死亡OR=0.688、谵妄OR=0.800、ICU天数减少0.646 d、心血管不良事件减少8.672次）。VAP方面，丙泊酚相较右美托咪定风险更低（OR=0.722），而苯二氮䓬类与右美托咪定差异不显著（OR=1.082）。
2.5　亚组分析
亚组分析结果提示（图5~7），镇静策略与患者是否合并恶性肿瘤（P-for-interaction=0.001）及是否存在中重度肝病（P-for-interaction=0.048）存在显著交互，但与超高龄患者不存在交互作用。超高龄患者中，丙泊酚组相较右美托咪定组拔管时间呈延长（平均延长0.457 d，P=0.094），但差异没有统计学意义；苯二氮䓬类组相较右美托咪定组拔管时间呈显著延长（平均延长1.123 d，P<0.001）；苯二氮䓬类组相较丙泊酚组拔管时间呈显著延长（平均延长0.665 d，P<0.001），但三组比较的交互作用P值均>0.05。在合并恶性肿瘤的患者中，丙泊酚组相较右美托咪定组拔管时间缩短（平均缩短1.326 d，P=0.064，P-for-interaction=0.001），效应方向与总体主效应不同；苯二氮䓬类药物相较右美托咪定的拔管时间缩短（平均缩短0.162 d，P=0.828，P-for-interaction=0.012）。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（平均缩短1.232 d，P=0.157），且苯二氮䓬类药物与右美托咪定的差异同样不显著（P-for-interaction=0.002）。以上结果提示：在合并恶性肿瘤或中重度肝病等特殊人群中，镇静策略的获益-风险平衡可能不同于总体人群，需在外部队列或前瞻性研究中进一步验证。
3　讨论
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本研究基于MIMIC-IV与eICU-CRD两大数据库构建多中心回顾性队列，比较三种单一镇静策略在接受持续有创机械通气ICU患者中的短期结局。主要发现为：与丙泊酚及苯二氮䓬类相比，右美托咪定与更短拔管时间相关，并在院内死亡率、谵妄及总体心血管不良事件方面呈一致获益；但在合并恶性肿瘤或中重度肝功能障碍人群中，该优势明显减弱甚至出现方向逆转，提示镇静策略需强调“总体获益”与“人群差异”的并重。
3.1　右美托咪定显著缩短拔管时间
机械通气患者的预后与脱机效率密切相关，拔管时间常被视为反映撤机效率的重要指标，且与院内死亡率、ICU住院时间及并发症（如谵妄）存在关联［24-25］。本研究中，右美托咪定组的中位拔管时间比丙泊酚组和苯二氮䓬类组都要短。该发现与既往研究中“右美托咪定更利于浅镇静与早期撤机”的观点整体一致［6-8， 26］。此外，我们的结论与2025年《Clinical Practice Guidelines for the Prevention and Management of Pain， Agitation/Sedation， Delirium， Immobility， and Sleep Disruption in Adult Patients in the ICU》（简称PADIS指南）的最新推荐高度契合［27］，该指南明确建议，对机械通气的成人ICU患者应该优先选择右美托咪定而不是丙泊酚来进行镇静。从药理机制看，右美托咪定是高选择性α2肾上腺素能受体激动剂，通过激活蓝斑核α2A受体诱导“可唤醒镇静”，且对呼吸驱动影响极小。因此，右美托咪定在理论上更适配“轻镇静-早苏醒-早脱机”的路径［28-30］。
3.2　右美托咪定不仅缩短拔管时间，院内死亡率与谵妄同步改善
除拔管时间外，本研究对多项次要结局的分析进一步提示，右美托咪定的获益并非仅体现在“更早脱机”，而是可能同时反映在ICU阶段恢复速度、神经精神并发症及短期生存结局等多个维度。右美托咪定组ICU住院时间更短，谵妄发生率与院内死亡率更低［31］，该结果提示，右美托咪定“可唤醒镇静”的特性可能减少过度镇静与苏醒延迟，从而降低谵妄风险；谵妄减少又可能通过改善治疗依从性、减少非计划拔管或再插管风险等间接影响整体恢复过程［32］。相对而言，苯二氮䓬类在谵妄、死亡率及ICU住院时间等结局中表现欠佳，而丙泊酚整体介于两者之间，这与苯二氮䓬类易蓄积、苏醒延迟及谵妄风险更高的临床认识相符［4， 33-34］，也提示临床实践中应尽量避免将苯二氮䓬类作为主要镇静策略［35］。需要强调的是，本研究将咪达唑仑、地西泮与劳拉西泮合并为“苯二氮䓬类策略”，尽管同属苯二氮䓬类，但在起效速度、半衰期、脂溶性与组织蓄积、代谢途径及活性代谢产物等方面存在差异［36］，理论上可能影响镇静深度调控、苏醒速度与拔管时机，并对谵妄及血流动力学相关不良事件产生不同影响。因此，将苯二氮䓬类合并后的处理效应解读为“苯二氮䓬类镇静策略”的总体平均效应，可能在一定程度上掩盖特定单药之间的差异。与此同时，VAP与住院总天数等结局未呈现与死亡、谵妄完全一致的方向，可能与其更易受感染防控、诊断记录差异及出院路径等多因素影响有关［37］，因此更适合作为补充观察指标而非单一决策依据。
3.3　右美托咪定策略在心血管不良事件中存在优势，但仍需个体化调整给药
心血管不良事件结果显示，右美托咪定组总体不良事件水平更低，主要是心动过速和低血压的发生率低，这表明不同镇静策略可能会对患者的血流动力学事件产生不同的影响［38］。临床上仍需结合患者循环状态进行个体化镇静与动态监测［35，39］。
3.4　特殊人群差异：恶性肿瘤与中重度肝病中右美托咪定优势减弱
高龄、慢性器官功能不全等因素，是致使机械通气时间延长以及脱机失败的独立预测因素［4， 40］。既往研究常排除高龄、肝功能障碍或恶性肿瘤患者，导致相关证据缺失。为弥补这一空白，我们在研究设计阶段预设亚组分析，并通过交互作用检验来评估不同镇静策略在特定人群中的效果是否存在差异。结果显示，在多数亚组中，右美托咪定仍能有效缩短拔管时间。然而，在合并恶性肿瘤或中重度肝功能障碍的患者群体中，右美托咪定的优势显著减弱，甚至出现结果方向逆转的情况，这提示这两类人群可能有着不同的获益-风险平衡模式。
在恶性肿瘤患者中，丙泊酚可能更有优势，这可能与丙泊酚潜在的抗肿瘤相关通路作用，以及肿瘤状态下其药代动力学的差异有关［41］。部分临床研究也表明右美托咪定在肿瘤相关人群中可能会增加低血压、心动过缓的发生率，或者提高血管活性药物的使用需求，进而影响患者的整体恢复进程［42-43］。在中重度肝功能障碍患者中，右美托咪定的优势并不突出，这主要与其药代动力学特性相关。右美托咪定几乎全部经肝脏代谢，具体通过葡萄糖醛酸化以及CYP2A6途径进行。肝硬化时，其清除率降低、半衰期延长，这可能增加药物蓄积与过度镇静的风险［44］。而丙泊酚具有肝外代谢等特性，在肝功能受损时，其药代动力学参数相对稳定，血液中的药物浓度和镇静深度更易预测，从而降低了苏醒延迟和呼吸抑制的风险。综上所述，对于无恶性肿瘤或中重度肝病等合并症的患者，右美托咪定仍可作为优先选择的镇静策略；但对于合并恶性肿瘤或中重度肝病的患者，应更注重个体化选择，丙泊酚可能是更为合理的策略选项。
3.5　多中心流程差异下，镇静策略应用需个体化权衡
不同ICU之间，镇静管理策略和撤机流程往往存在一定差异［35-45］，比如是以镇痛为先还是镇静为先、设定的镇静目标范围及实际达标情况、是否常规开展每日唤醒或镇静中断、谵妄筛查和处理的规范程度，以及呼吸治疗资源和撤机流程的配置等。这些流程上的差异，不仅可能影响镇静药物与临床结局之间的关联［46］，也是导致同类研究结论不一致的重要原因。因此，对本研究结果的解读也需要更加审慎，应理解为在真实世界多中心、异质性临床实践背景下，基于“镇静策略”层面观察到的总体平均效应，反映的是某一类镇静药物在实际使用过程中的综合表现，而非对某种固定剂量或标准化方案的直接推断。在将该结果应用于某一具体机构时，仍需结合本地的临床流程和患者结构进行综合判断［38］。
3.6　研究优势与局限性
本研究基于大型真实世界数据库开展观察性队列研究，本身面临多方面方法学挑战。首先，临床镇静管理过程复杂，存在大量潜在混杂和信息缺失。其次，数据库中对部分关键合并用药（如镇痛药、抗精神病药、神经肌肉阻滞剂、糖皮质激素等）的记录不够完整，难以标准化控制［47］。此外，eICU-CRD缺乏统一、完善的随访信息［47-48］，也限制了对30/90 d死亡率、再入院率等长期结局的评估。
针对上述问题，我们在设计和分析阶段尽可能采取了多种手段来降低偏倚。例如，在人群筛选上，严格统一两大数据库的纳入排除标准及暴露与结局定义，以提高组间可比性；在混杂控制上，纳入了人口学特征、疾病严重程度、合并症负担以及治疗相关变量等多维协变量，采用基于GBM的倾向评分估计并实施IPTW加权，同时结合AIPW双重稳健模型进行效应估计。该因果推断框架在理论上只要倾向评分模型或结局模型中至少有一个设定正确，即可获得一致估计，从而在一定程度上降低已测量混杂对效应估计的影响［49］。三是在缺失数据处理方面，我们使用了R语言“MICE”包进行多重插补，并通过Rubin法则合并估计值［20］，从而尽可能保留样本量、减少因简单删失导致的选择偏倚和估计不稳定性，尤其是在关键协变量存在中低程度缺失的情况下，提高了模型拟合与效应估计的精度和稳健性。
尽管如此，受数据库结构和记录详尽度所限，本研究仍不可避免存在残余混杂和信息不足。一方面，两个数据库在镇静深度动态变化、每日唤醒执行情况、累计用药剂量和暴露时长以及给药滴定细节等方面，信息尚不够完整或统一，这可能导致一定程度的暴露分类误差，以及不同ICU之间操作差异性的影响无法完全消除。另一方面，部分合并用药信息的不完善，也使得我们无法全面纳入模型进行控制，可能对效应估计带来一定干扰。此外，本研究主要关注ICU期间短期结局，尚缺乏统一的长期预后数据。后续研究如果要进一步回答不同镇静策略对患者远期结局的影响，仍需在更精细的用药与过程信息基础上，将关键合并用药、剂量和暴露时长等变量系统纳入因果推断模型，并结合外部队列或前瞻性研究设计加以验证。
对于接受有创机械通气的ICU患者，使用右美托咪定相较于苯二氮䓬类药物或丙泊酚，可能与更短的拔管时间及更低的院内死亡率、谵妄和心血管不良事件风险相关；然而在合并恶性肿瘤或中重度肝病的特定人群中，丙泊酚可能是更合理的镇静选择。

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doi: 10.16016/j.2097-0927.202512139
  • 接收时间：2025-12-24
  • 首发时间：2026-10-23
  • 出版时间：2026-03-30
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  • 收稿日期：2025-12-24
  • 修回日期：2026-01-22
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    1陆军军医大学（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

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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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