美国芝加哥大学Kevin G. Buell团队研究了机械通气危重症成人个体化氧合目标的治疗效果。这一研究成果于2024年3月19日发表在《美国医学会杂志》上。

在危重成年患者中，随机试验尚未发现氧合目标会影响总体预后。氧合目标的作用是否因个体特征而异尚不清楚。为了确定个体的特征是否改变了较低和较高外周氧合饱和度（SpO₂）目标对死亡率的影响，研究组在最佳氧气目标的实用研究（PILOT）试验中推导了一个机器学习模型，用于预测较低与较高SpO₂目标治疗对个体患者死亡率的影响，并在重症监护室比较两种氧气治疗方法的随机试验（ICU-ROX）中进行了外部验证。

2018年7月至2021年8月，美国重症监护室（ICU）有1682名危重成年人接受了有创机械通气，进行了PILOT；2015年9月至2018年5月期间，965名患者在澳大利亚和新西兰的21个ICU中进行了ICU-ROX。将这些患者随机分组到较低与较高的SpO₂目标组。主要结局为28天死亡率。

在ICU-ROX验证队列中，对个体患者使用较低与较高SpO₂目标治疗的预测效果，28天死亡率从27.2%的绝对降低到34.4%的绝对增加不等。例如，预测受益于较低SpO₂目标的患者急性脑损伤的发生率较高，而预测受益于较高SpO₂目标的患者败血症和生命体征异常升高的发生率更高。预测受益于较低SpO₂目标的患者在随机分配到较低SpO₂目标组时死亡率较低，而预测受益于较高SpO₂目标的患者在随机化到较高SpO₂目标组时死亡较低（效应修正的似然比检验P = .02）。使用预测对每位患者最有利的SpO₂目标，而不是随机的SpO₂目标，将使绝对总死亡率降低6.4%（95%CI，1.9%-10.9%）。

研究结果表明，使用随机试验的机器学习分析进行个性化的氧合目标可以降低危重成年人的死亡率。但仍需要进行一项前瞻性试验，以评估个体化氧合目标的使用情况。

附：英文原文

Title: Individualized Treatment Effects of Oxygen Targets in Mechanically Ventilated Critically Ill Adults

Author: Kevin G. Buell, Alexandra B. Spicer, Jonathan D. Casey, Kevin P. Seitz, Edward T. Qian, Emma J. Graham Linck, Wesley H. Self, Todd W. Rice, Pratik Sinha, Paul J. Young, Matthew W. Semler, Matthew M. Churpek

Issue&Volume: 2024-03-19

Abstract:

Importance  Among critically ill adults, randomized trials have not found oxygenation targets to affect outcomes overall. Whether the effects of oxygenation targets differ based on an individual’s characteristics is unknown.

Objective  To determine whether an individual’s characteristics modify the effect of lower vs higher peripheral oxygenation-saturation (Spo2) targets on mortality.

Design, Setting, and Participants  A machine learning model to predict the effect of treatment with a lower vs higher Spo2 target on mortality for individual patients was derived in the Pragmatic Investigation of Optimal Oxygen Targets (PILOT) trial and externally validated in the Intensive Care Unit Randomized Trial Comparing Two Approaches to Oxygen Therapy (ICU-ROX) trial. Critically ill adults received invasive mechanical ventilation in an intensive care unit (ICU) in the United States between July 2018 and August 2021 for PILOT (n=1682) and in 21 ICUs in Australia and New Zealand between September 2015 and May 2018 for ICU-ROX (n=965).

Exposures  Randomization to a lower vs higher Spo2 target group.

Main Outcome and Measure  28-Day mortality.

Results  In the ICU-ROX validation cohort, the predicted effect of treatment with a lower vs higher Spo2 target for individual patients ranged from a 27.2% absolute reduction to a 34.4% absolute increase in 28-day mortality. For example, patients predicted to benefit from a lower Spo2 target had a higher prevalence of acute brain injury, whereas patients predicted to benefit from a higher Spo2 target had a higher prevalence of sepsis and abnormally elevated vital signs. Patients predicted to benefit from a lower Spo2 target experienced lower mortality when randomized to the lower Spo2 group, whereas patients predicted to benefit from a higher Spo2 target experienced lower mortality when randomized to the higher Spo2 group (likelihood ratio test for effect modification P=.02). The use of a Spo2 target predicted to be best for each patient, instead of the randomized Spo2 target, would have reduced the absolute overall mortality by 6.4% (95% CI, 1.9%-10.9%).

Conclusion and relevance  Oxygenation targets that are individualized using machine learning analyses of randomized trials may reduce mortality for critically ill adults. A prospective trial evaluating the use of individualized oxygenation targets is needed.

DOI: 10.1001/jama.2024.2933

Source: https://jamanetwork.com/journals/jama/fullarticle/2816677