原创 毛毛弟 一起学科研 2022-05-07 17:00
In this issue of Critical Care Medicine, Tian Wang et al (1) present the results of a meta-analysis designed to investigate whether physical rehabilitation during ICU stay improves patient outcomes. They also assessed the effect of dosage and of modality of training. The investigators conclude that physical rehabilitation reduces ICU and hospital length of stay and slightly improves physical function at hospital discharge. Physical rehabilitation, however, has no impact on muscle strength, duration of mechanical ventilation, mortality, and health-related quality of life. Rehabilitation delivered less than 5 days per week is less effective than higher dosages of physical rehabilitation.
在本期Critical Care Medicine杂志中，Tian Wang等人提出了一项Meta分析的结果，旨在研究ICU住院期间的身体康复是否能改善患者的预后。他们还评估了剂量和训练方式的影响。研究者的结论是，身体康复可以减少ICU和医院的住院时间，并略微改善出院时的身体功能。然而，身体康复对肌肉力量、机械通气时间、死亡率和健康相关的生活质量没有影响。每周提供少于5天的康复服务不如较高剂量的身体康复有效。
Should we concern ourselves with physical rehabilitation in the ICU? Yes. Most critically ill patients experience profound muscle weakness; force of knee flexion objectively assessed using femoral nerve stimulation can be reduced to less than one-tenth of expected (2). Patients who successfully wean from prolonged ventilation still require over 50% assistance in performing basic tasks such as rolling in bed and toileting at the time of hospital discharge (3). Finally, indirect arguments to provide physical rehabilitation in the ICU include the association between clinical weakness and poor patient outcomes and increased duration of hospitalization (1, 4).
我们应该关注ICU的身体康复吗？是的。大多数危重患者都有严重的肌肉无力；使用股神经刺激客观评估的屈膝力可以减少到预期的十分之一以下。成功脱离长期通气的患者在出院时仍然需要50%以上的协助来完成基本任务，如在床上翻滚和上厕所。最后，在ICU提供身体康复的间接论据包括临床虚弱与患者预后不佳和住院时间延长之间的联系。
Tian Wang et al (1) report that rehabilitation in the ICU results in a small improvement in physical function at hospital discharge. Subgroup analysis, however, found that compared with controls, physical function improved in the group of studies involving what the authors classified as nonfunctional exercises such as neuromuscular electrical stimulation (see Physical Function, Subgroup Analysis e-Appendix 2 of Tian Wang et al [1]). In contrast, in the group of studies focused on what the authors classified as functional exercises such as turning in bed, sitting up, and walking, the exercises resulted in no difference in physical function compared with controls. Does this mean that physical rehabilitation in the ICU should abandon functional exercise programs and focus only on nonfunctional exercise programs? No. The group of studies focused on nonfunctional exercises contained two investigations; in both investigations, patients received neuromuscular electrical stimulation as an adjunct to conventional (functional) physical rehabilitation (5, 6). One of these two investigations was not powered to assess changes in physical function (6). The other was prematurely stopped due to slow accrual and end of research funding (5). As a result, only 12 patients in the neuromuscular electrical stimulation group and 17 in the standard of care group were available for analysis (5). The sample size, although adequate for statistical significance, is not optimal for generalization.
Tian Wang等人报告说，在ICU的康复治疗导致出院时身体功能的小幅改善。然而，亚组分析发现，与对照组相比，在涉及作者归类为非功能锻炼（如神经肌肉电刺激）的研究组中，身体功能得到了改善（见亚组分析）。相反，在专注于作者归类为功能性锻炼的一组研究中，如在床上翻身、坐起和行走，锻炼的结果与对照组相比，身体功能没有差异。这是否意味着ICU的身体康复应该放弃功能锻炼项目而只关注非功能锻炼项目？不是的。专注于非功能锻炼的研究组包含两项调查；在这两项调查中，患者接受神经肌肉电刺激作为常规（功能）身体康复的辅助手段。这两项调查中的一项没有能力评估身体功能的变化。另一项由于招募缓慢和研究经费的结束而提前停止。因此，只有神经肌肉电刺激组的12名患者和标准护理组的17名患者可用于分析。该样本量虽然对统计学意义来说是足够的，但对普及来说并不是最佳的。
The finding that functional exercises did not result in an improvement in physical function compared with controls is intriguing. Several overlapping mechanisms may explain this finding (7). Muscle necrosis or neurotransmission defects, which can occur in critical illness, can lead to reduced excitability of the muscle (4). Anabolic resistance is enhanced by patient characteristics such as older age and chronic comorbidities. Delivery of physical rehabilitation may itself be insufficient. This possibility is supported by the novel observations of Supinski et al (7) who recorded leg electromyograms during exercise in patients requiring prolonged mechanical ventilation. During exercise, electromyogram signals indicated that patients failed to sustain high levels of muscle activation necessary for muscle training, resulting in the waste of large portions of the training sessions. The failure of functional exercises may also stem from a need to combine exercises with yet to be identified pharmacological compounds that safely and effectively augment muscle regrowth. It is unknown whether a potential target of interest could be the optimization of proteostasis—a collection of cellular processes handling protein folding, misfolding, unfolding, and degradation (8).
与对照组相比，功能锻炼并没有导致身体功能的改善，这一发现耐人寻味。有几种重叠的机制可以解释这一发现。肌肉坏死或神经传导缺陷，在危重病中可能发生，可导致肌肉的兴奋性降低。同化阻力会因患者的特点而增强，如年龄大和慢性合并症。提供身体康复服务本身可能是不够的。Supinski等人的新观察支持了这种可能性，他们在需要长期机械通气的患者运动时记录了腿部肌电图。在运动过程中，肌电图信号表明，患者未能维持肌肉训练所需的高水平肌肉激活，导致训练课程的大部分时间被浪费。功能性锻炼的失败也可能是由于需要将锻炼与尚未确定的安全和有效增强肌肉再生的药理学化合物结合起来。目前还不知道一个潜在的兴趣目标是否可以是蛋白质稳定的优化--处理蛋白质折叠、错误折叠、展开和降解的细胞过程的集合。
Physical rehabilitation was associated with an overall reduction in ICU and hospital length of stay. On subgroup analysis, these benefits were observed only in the group of studies where patients in the intervention group received task-specific, functional exercises and in the group of studies where patients in the control group received low-dose physical therapy (low-dose physical therapy was defined as a situation in which patients received or were assessed for rehabilitation < 5 d per wk.) Several mechanisms likely contributed to these reductions in length of stay. First, as pointed out by the investigators, to participate in functional exercises patients must be alert. For patients to be alert, physicians must decrease or pause administration of sedatives. Sedation holidays, which are known to decrease ICU length of stay (9), may be an upstream factor conferring the benefits associated with physical rehabilitation. A second factor that coexists with the sedation effect is the reported positive impact of physical rehabilitation on delirium (10), a well-known independent determinant of length of stay (11). Finally, Tian Wang et al (1) speculate that length of stay can be influenced by improvements in patients’ physical function, particularly if they are to be discharged home. This thought-provoking consideration deserves careful examination in future investigations.
身体康复与ICU和住院时间的总体减少有关。在亚组分析中，只有在干预组患者接受特定任务、功能锻炼的研究组和对照组患者接受低剂量身体治疗的研究组中观察到这些益处（低剂量身体治疗被定义为患者每星期接受或被评估的康复时间少于5天）。有几个机制可能促成了这些住院时间的减少。首先，正如研究者所指出的，为了参与功能锻炼，患者必须保持警惕。为了使患者保持警觉，医生必须减少或暂停使用镇静剂。已知镇静剂假期可减少ICU住院时间，可能是赋予身体康复相关益处的上游因素。与镇静效果并存的第二个因素是有报道称身体康复对谵妄的积极影响，这是一个众所周知的决定住院时间的独立因素。最后，Tian Wang等人推测，住院时间可以受到患者身体功能改善的影响，特别是在他们要出院回家的时候。这一发人深省的考虑值得在未来的调查中仔细研究。
In their meta-analysis of pooled data, Tian Wang et al (1) reported that rehabilitation in the ICU does not reduce duration of mechanical ventilation. This result is not surprising considering that there is a limited association between diaphragm dysfunction and limb muscle weakness in critically ill, mechanically ventilated patients (12, 13). On subgroup analysis, the investigators report that duration of mechanical ventilation was reduced in the intervention group when the control group received low-dose physical rehabilitation (< 5 d per wk) but not when the control groupreceived high-dose physical rehabilitation (at least 5 d per wk). Similarly, duration of mechanical ventilation was reduced when the intervention group received functional experimental interventions. In contrast, nonfunctional experimental interventions increased duration of mechanical ventilation. These results must be interpreted with caution considering the lack of standardization of ventilator and weaning strategies among the various studies. Nevertheless, they raise the possibility that the more frequent sedation holidays associated with more frequent rehabilitation interventions requiring patients’ cooperation contribute to a decrease in the duration of mechanical ventilation (10).
Tian Wang等人在他们的集合数据的Meta分析中报告，ICU中的康复治疗并不能减少机械通气的时间。考虑到危重患者、机械通气患者的膈肌功能障碍和肢体肌肉无力之间存在着有限的关联，这一结果并不令人惊讶。在亚组分析中，研究者报告说，当对照组接受低剂量的身体康复治疗（每星期<5天）时，干预组的机械通气时间减少，但当对照组接受高剂量的身体康复治疗（每星期至少5天）时，则没有减少。同样，当干预组接受功能性锻炼干预时，机械通气的时间也减少了。相反，非功能性锻炼干预措施增加了机械通气的时间。考虑到不同的研究中缺乏标准化的呼吸机和撤机策略，必须谨慎地解释这些结果。然而，它们提出了一种可能性，即更频繁的镇静期与更频繁的需要患者合作的康复干预措施有关，有助于减少机械通气的时间。
Tian Wang et al (1) reported no effect of physical rehabilitation on short-term and long-term mortality. These results, together with the lack of effect of rehabilitation on duration of mechanical ventilation and health-related quality of life at 6 months, raise the possibility that peripheral muscle weakness in the ICU is a marker of disease severity rather than the proximate mechanism contributing to poor clinical outcomes.
Tian Wang等人报告了身体康复对短期和长期死亡率没有影响。这些结果，再加上康复治疗对机械通气时间和6个月的健康相关生活质量没有影响，提出了一种可能性，即ICU中的周围肌肉无力是疾病严重程度的标志，而不是导致不良临床结果的近似机制。
In spite of the thought-provoking and novel insights of the meta-analysis of Tian Wang et al (1), some points require mentioning. The risk of bias (assessed using the Cochrane Risk-of-Bias tool [14] and the Risk of Bias in Nonrandomized Studies of Interventions tool [15]) was considered high in 54% of the randomized controlled trials included in the meta-analysis. The authors acknowledge this limitation and recommend caution in the application of the results to clinical practice. The diversity of physical rehabilitation interventions in the studies included in the meta-analysis make interpretation of the pooled analysis challenging. The authors attempt to address the heterogeneity of rehabilitation strategies by performing a subgroup analysis of functional versus nonfunctional exercise interventions. The group of nonfunctional studies encompassed a vast array of therapeutic interventions including passive and active-assisted range of motion exercises, neuromuscular electrical stimulation of locomotor and nonlocomotor muscles, and active and passive cycle ergometry. By combining these rehabilitation strategies into one group, any potential benefit of one modality over another would be obscured. The investigators present strong arguments supporting delivery of rehabilitation at least 5 days a week (16, 17). Whether patients may benefit from extending rehabilitation sessions from 5 days a week to 6 or even 7 days a week is unknown because such comparisons were not available to the investigators.
尽管Tian Wang等人的Meta分析有发人深省的新见解，但仍有几点需要提及。Meta分析中包括的54%的随机对照试验的偏倚风险（使用Cochrane偏倚风险工具和干预措施的非随机研究偏倚风险工具评估）被认为很高。作者承认这一局限性，并建议在将结果应用于临床实践时要谨慎。Meta分析所包括的研究中，身体康复干预措施的多样性使得对集合分析的解释具有挑战性。作者试图通过对功能性与非功能性锻炼干预进行亚组分析来解决康复策略的异质性。非功能研究组包含了大量的治疗干预措施，包括被动和主动辅助运动范围练习、运动肌和非运动肌的神经肌肉电刺激，以及主动和被动踏车。将这些康复策略合并到一组，一种模式对另一种模式的潜在好处就会被掩盖。研究者提出了强有力的论据，支持每周至少提供5天的康复治疗。患者是否会从每周5天的康复训练中受益，因为研究者没有进行这样的比较，所以不知道。
In conclusion, the results of the rigorous meta-analysis of Tian Wang et al (1) suggest that physical rehabilitation that includes functional exercises delivered 5 days a week during ICU stay is indeed worth the effort. Yet, challenges remain. What is the confounding effect of sedation on physical rehabilitation, and how does this affect clinical outcomes? Is there a role for implementing early interventions requiring no patient cooperation such as neuromuscular electrical stimulation when patients are still sedated? Does the psychological response to physical rehabilitation impact patients’ outcomes? Could improvements in physical function be amplified by monitoring muscle activation using electromyogram recordings during training (7)? These challenges are formidable, but now is the time to tackle them. Our patients deserve no less
总之，Tian Wang等人的严格的Meta分析结果表明，在ICU住院期间每周5天进行包括功能锻炼在内的身体康复确实值得努力。然而，挑战依然存在。镇静对身体康复的混杂影响是什么，这对临床结果有什么影响？在患者仍处于镇静状态时，实施不需要患者合作的早期干预措施，如神经肌肉电刺激，是否有作用？对身体康复的心理反应是否会影响患者的结果？在训练过程中使用肌电图记录监测肌肉的激活，是否可以扩大身体功能的改善？这些挑战是艰巨的，但现在是解决它们的时候了。我们的患者应该得到更多。
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