Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.
Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.
JAMA Netw Open. 2023 Mar 1;6(3):e233265. doi: 10.1001/jamanetworkopen.2023.3265.
Many conventional end points in randomized clinical trials of interventions for critically ill patients do not account for patient-centered concerns such as time at home, physical function, and quality of life after critical illness.
To establish whether days alive and at home at day 90 (DAAH90) is associated with long-term survival and functional outcomes in mechanically ventilated patients.
DESIGN, SETTING, AND PARTICIPANTS: The RECOVER prospective cohort study was conducted from February 2007 to March 2014, using data from 10 intensive care units (ICUs) in Canada. Patients were included in the baseline cohort if they were aged 16 years or older and underwent invasive mechanical ventilation for 7 or more days. The follow-up cohort analyzed here comprised RECOVER patients who were alive and had functional outcomes ascertained at 3, 6, and 12 months. Secondary data analysis occurred from July 2021 to August 2022.
Composite of survival and days alive and at home at day 90 after ICU admission (DAAH90).
Functional outcomes at 3, 6, and 12 months were evaluated with the Functional Independence Measure (FIM), the 6-Minute Walk Test (6MWT), the Medical Research Council (MRC) Scale for Muscle Strength, and the 36-Item Short Form Health Survey physical component summary (SF-36 PCS). Mortality was evaluated at 1 year from ICU admission. Ordinal logistic regression was used to describe the association between DAAH90 tertiles and outcomes. Cox proportional hazards regression models were used to examine the independent association of DAAH90 tertiles with mortality.
The baseline cohort comprised 463 patients. Their median age was 58 years (IQR, 47-68 years), and 278 patients (60.0%) were men. In these patients, Charlson Comorbidity Index score, Acute Physiology and Chronic Health Evaluation II score, ICU intervention (eg, kidney replacement therapy or tracheostomy), and ICU length of stay were independently associated with lower DAAH90. The follow-up cohort comprised 292 patients. Their median age was 57 years (IQR, 46-65 years), and 169 patients (57.9%) were men. Among patients who survived to day 90, lower DAAH90 was associated with higher mortality at 1 year after ICU admission (tertile 1 vs tertile 3: adjusted hazard ratio [HR], 0.18 [95% CI, 0.07-0.43]; P < .001). At 3 months of follow-up, lower DAAH90 was independently associated with lower median scores on the FIM (tertile 1 vs tertile 3, 76 [IQR, 46.2-101] vs 121 [IQR, 112-124.2]; P = .04), 6MWT (tertile 1 vs tertile 3, 98 [IQR, 0-239] vs 402 [IQR, 300-494]; P < .001), MRC (tertile 1 vs tertile 3, 48 [IQR, 32-54] vs 58 [IQR, 51-60]; P < .001), and SF-36 PCS (tertile 1 vs tertile 3, 30 [IQR, 22-38] vs 37 [IQR, 31-47]; P = .001) measures. Among patients who survived to 12 months, being in tertile 3 vs tertile 1 for DAAH90 was associated with higher FIM score at 12 months (estimate, 22.4 [95% CI, 14.8-30.0]; P < .001), but this association was not present for ventilator-free days (estimate, 6.0 [95% CI, -2.2 to 14.1]; P = .15) or ICU-free days (estimate, 5.9 [95% CI, -2.1 to 13.8]; P = .15) at day 28.
In this study, lower DAAH90 was associated with greater long-term mortality risk and worse functional outcomes among patients who survived to day 90. These findings suggest that the DAAH90 end point reflects long-term functional status better than standard clinical end points in ICU studies and may serve as a patient-centered end point in future clinical trials.
许多针对危重症患者干预措施的随机临床试验中的常规终点并未考虑到患者关注的问题,例如在家的时间、身体功能和重症后生活质量。
确定第 90 天存活且在家的天数(DAAH90)与机械通气患者的长期生存和功能结局是否相关。
设计、地点和参与者:RECOVER 前瞻性队列研究于 2007 年 2 月至 2014 年 3 月进行,使用了来自加拿大 10 个重症监护病房(ICU)的数据。如果患者年龄在 16 岁或以上且接受了 7 天或更长时间的有创机械通气,则将其纳入基线队列。这里分析的随访队列包括在第 3、6 和 12 个月时存活且功能结局可评估的 RECOVER 患者。二次数据分析于 2021 年 7 月至 2022 年 8 月进行。
ICU 入住后第 90 天存活且在家的天数(DAAH90)的复合指标。
使用功能独立性测量(FIM)、6 分钟步行试验(6MWT)、肌肉力量医学研究理事会(MRC)量表和 36 项简短健康调查问卷身体成分总分(SF-36 PCS)评估 3、6 和 12 个月的功能结局。ICU 入住后 1 年评估死亡率。有序逻辑回归用于描述 DAAH90 三分位与结局之间的关系。Cox 比例风险回归模型用于检查 DAAH90 三分位与死亡率的独立关联。
基线队列包括 463 名患者。他们的中位年龄为 58 岁(四分位距,47-68 岁),278 名患者(60.0%)为男性。在这些患者中,Charlson 合并症指数评分、急性生理学和慢性健康评估 II 评分、ICU 干预(如肾脏替代治疗或气管切开术)和 ICU 住院时间与较低的 DAAH90 独立相关。随访队列包括 292 名患者。他们的中位年龄为 57 岁(四分位距,46-65 岁),169 名患者(57.9%)为男性。在存活至第 90 天的患者中,较低的 DAAH90 与 ICU 入住后 1 年的死亡率较高相关(三分位 1 与三分位 3:调整后的危险比[HR],0.18[95%CI,0.07-0.43];P<0.001)。在 3 个月的随访中,较低的 DAAH90 与 FIM 的中位数评分独立相关(三分位 1 与三分位 3,76[四分位距,46.2-101]与 121[四分位距,112-124.2];P=0.04)、6MWT(三分位 1 与三分位 3,98[四分位距,0-239]与 402[四分位距,300-494];P<0.001)、MRC(三分位 1 与三分位 3,48[四分位距,32-54]与 58[四分位距,51-60];P<0.001)和 SF-36 PCS(三分位 1 与三分位 3,30[四分位距,22-38]与 37[四分位距,31-47];P=0.001)。在存活至 12 个月的患者中,DAAH90 处于三分位 3 与三分位 1 相比,FIM 评分在 12 个月时更高(估计值,22.4[95%CI,14.8-30.0];P<0.001),但在无呼吸机天数(估计值,6.0[95%CI,-2.2 至 14.1];P=0.15)或 ICU 无天数(估计值,5.9[95%CI,-2.1 至 13.8];P=0.15)方面无差异。
在这项研究中,DAAH90 较低与第 90 天存活的患者的长期死亡风险增加和功能结局较差相关。这些发现表明,DAAH90 终点比 ICU 研究中的标准临床终点更好地反映了长期功能状态,可能成为未来临床试验中的患者为中心的终点。