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限时重症监护治疗癌症危重症患者的临床试验:多长时间才算足够长?

Time-Limited Trials of Intensive Care for Critically Ill Patients With Cancer: How Long Is Long Enough?

机构信息

Program in Global Surgery and Social Change, Harvard Medical School, Boston, Massachusetts 2Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.

Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands 4Department of Population Health Science and Policy, Institute for Healthcare Delivery Science, Icahn School of Medicine at Mount Sinai, New York, New York.

出版信息

JAMA Oncol. 2016 Jan;2(1):76-83. doi: 10.1001/jamaoncol.2015.3336.

Abstract

IMPORTANCE

Time-limited trials of intensive care are commonly used in patients perceived to have a poor prognosis. The optimal duration of such trials is unknown. Factors such as a cancer diagnosis are associated with clinician pessimism and may affect the decision to limit care independent of a patient's severity of illness.

OBJECTIVE

To identify the optimal duration of intensive care for short-term mortality in critically ill patients with cancer.

DESIGN, SETTING, AND PARTICIPANTS: Decision analysis using a state-transition microsimulation model was performed to simulate the hospital course of patients with poor-prognosis primary tumors, metastatic disease, or hematologic malignant neoplasms admitted to medical and surgical intensive care units. Transition probabilities were derived from 920 participants stratified by sequential organ failure assessment (SOFA) scores to identify severity of illness. The model was validated in 3 independent cohorts with 349, 158, and 117 participants from quaternary care academic hospitals. Monte Carlo microsimulation was performed, followed by probabilistic sensitivity analysis. Outcomes were assessed in the overall cohort and in solid tumors alone.

INTERVENTIONS

Time-unlimited vs time-limited trials of intensive care.

MAIN OUTCOMES AND MEASURES

30-day all-cause mortality and mean survival duration.

RESULTS

The SOFA scores at ICU admission were significantly associated with mortality. A 3-, 8-, or 15-day trial of intensive care resulted in decreased mean 30-day survival vs aggressive care in all but the sickest patients (SOFA score, 5-9: 48.4% [95% CI, 48.0%-48.8%], 60.6% [95% CI, 60.2%-61.1%], and 66.8% [95% CI, 66.4%-67.2%], respectively, vs 74.6% [95% CI, 74.3%-75.0%] with time-unlimited aggressive care; SOFA score, 10-14: 36.2% [95% CI, 35.8%-36.6%], 44.1% [95% CI, 43.6%-44.5%], and 46.1% [95% CI, 45.6%-46.5%], respectively, vs 48.4% [95% CI, 48.0%-48.8%] with aggressive care; SOFA score, ≥ 15: 5.8% [95% CI, 5.6%-6.0%], 8.1% [95% CI, 7.9%-8.3%], and 8.3% [95% CI, 8.1%-8.6%], respectively, vs 8.8% [95% CI, 8.5%-9.0%] with aggressive care). However, the clinical magnitude of these differences was variable. Trial durations of 8 days in the sickest patients offered mean survival duration that was no more than 1 day different from time-unlimited care, whereas trial durations of 10 to 12 days were required in healthier patients. For the subset of patients with solid tumors, trial durations of 1 to 4 days offered mean survival that was not statistically significantly different from time-unlimited care.

CONCLUSIONS AND RELEVANCE

Trials of ICU care lasting 1 to 4 days may be sufficient in patients with poor-prognosis solid tumors, whereas patients with hematologic malignant neoplasms or less severe illness seem to benefit from longer trials of intensive care.

摘要

重要性

在被认为预后不良的患者中,通常会进行限时重症监护试验。这种试验的最佳持续时间尚不清楚。癌症等诊断与临床医生的悲观情绪有关,并且可能会影响到独立于患者疾病严重程度而限制护理的决策。

目的

确定癌症危重病患者短期死亡率的最佳重症监护时间。

设计、地点和参与者:使用状态转换微模拟模型进行决策分析,以模拟预后不良的原发性肿瘤、转移性疾病或血液恶性肿瘤患者入住内科和外科重症监护病房的住院过程。转移概率来自于根据序贯器官衰竭评估(SOFA)评分分层的 920 名参与者,以确定疾病的严重程度。该模型在 3 家拥有 349、158 和 117 名来自四级护理学术医院参与者的独立队列中进行了验证。进行了蒙特卡罗微模拟,然后进行了概率敏感性分析。评估了整个队列和单纯实体瘤的结果。

干预措施

限时与不限时重症监护试验。

主要结果和测量指标

30 天全因死亡率和平均生存时间。

结果

重症监护病房入院时的 SOFA 评分与死亡率显著相关。与不限时积极治疗相比,3 天、8 天或 15 天的重症监护试验导致除最病重患者(SOFA 评分,5-9:48.4%[95%CI,48.0%-48.8%],60.6%[95%CI,60.2%-61.1%]和 66.8%[95%CI,66.4%-67.2%])外的所有患者的 30 天平均生存率降低;SOFA 评分,10-14:36.2%[95%CI,35.8%-36.6%],44.1%[95%CI,43.6%-44.5%]和 46.1%[95%CI,45.6%-46.5%]),与积极治疗相比,分别为 48.4%[95%CI,48.0%-48.8%];SOFA 评分,≥15:5.8%[95%CI,5.6%-6.0%],8.1%[95%CI,7.9%-8.3%]和 8.3%[95%CI,8.1%-8.6%]),与积极治疗相比,分别为 8.8%[95%CI,8.5%-9.0%]。然而,这些差异的临床幅度是不同的。在最病重的患者中,8 天的试验持续时间提供的平均生存时间与无限制治疗相差不超过 1 天,而在健康状况较好的患者中,需要 10-12 天的试验持续时间。对于实体瘤患者亚组,1 至 4 天的 ICU 护理试验持续时间与无限制治疗的平均生存时间无统计学显著差异。

结论和相关性

对于预后不良的实体瘤患者,1 至 4 天的 ICU 护理试验可能就足够了,而血液恶性肿瘤或病情较轻的患者似乎从更长时间的重症监护试验中受益。

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