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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JHHR</journal-id>
      <journal-title-group>
        <journal-title>Journal of Human Health Research</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2576-9383</issn>
      <publisher>
        <publisher-name>Open Access Pub</publisher-name>
        <publisher-loc>United States</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">JHHR-22-4146</article-id>
      <article-id pub-id-type="doi">10.14302/issn.2576-9383.jhhr-22-4146</article-id>
      <article-categories>
        <subj-group>
          <subject>review-article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Progress in Rehabilitation Treatments for Sepsis Patients in ICU</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Ling</surname>
            <given-names>Wang</given-names>
          </name>
          <xref ref-type="aff" rid="idm1843132516">1</xref>
          <xref ref-type="aff" rid="idm1843132876">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Zhen</surname>
            <given-names>Zhang</given-names>
          </name>
          <xref ref-type="aff" rid="idm1843132516">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1843132516">
        <label>1</label>
        <addr-line>Research PA-C/Research Coordinator, University of Texas MD Anderson Cancer Center</addr-line>
      </aff>
      <aff id="idm1843132876">
        <label>*</label>
        <addr-line>Corresponding author</addr-line>
      </aff>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Neslihan</surname>
            <given-names>Lok</given-names>
          </name>
          <xref ref-type="aff" rid="idm1843272868">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1843272868">
        <label>1</label>
        <addr-line>Selcuk University, Faculty of Health Sciences</addr-line>
      </aff>
      <author-notes>
        <corresp>
    
    Ling Wang, <addr-line>Department of Intensive Care Unit, People’s Hospital of </addr-line><addr-line>Qiandongnan</addr-line><addr-line> Miao and Dong Autonomous Prefecture, </addr-line><addr-line>Kaili</addr-line><addr-line>, Guizhou 556000, China</addr-line><email>463082910@qq.com</email></corresp>
        <fn fn-type="conflict" id="idm1842524212">
          <p>The authors have declared that no competing interests exist.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub" iso-8601-date="2022-05-02">
        <day>02</day>
        <month>05</month>
        <year>2022</year>
      </pub-date>
      <volume>1</volume>
      <issue>4</issue>
      <fpage>1</fpage>
      <lpage>8</lpage>
      <history>
        <date date-type="received">
          <day>27</day>
          <month>03</month>
          <year>2022</year>
        </date>
        <date date-type="accepted">
          <day>28</day>
          <month>04</month>
          <year>2022</year>
        </date>
        <date date-type="online">
          <day>02</day>
          <month>05</month>
          <year>2022</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>© </copyright-statement>
        <copyright-year>2022</copyright-year>
        <copyright-holder>Ling Wang, et al.</copyright-holder>
        <license xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <self-uri xlink:href="http://openaccesspub.org/jhhr/article/1816">This article is available from http://openaccesspub.org/jhhr/article/1816</self-uri>
      <abstract>
        <p>Early active mobilisation and                        rehabilitation in the intensive care unit (ICU) is being used to prevent the long-term functional consequences of critical illness, sepsis patients need early rehabilitation treatment. Individualized rehabilitation is a safe and effective approach for patients with sepsis. This review aimed to              introduce the necessity of rehabilitation for              patients with sepsis in the ICU, the composition of the rehabilitation team, the time to begin                          rehabilitation, the focus of rehabilitation, and the main approaches. </p>
      </abstract>
      <kwd-group>
        <kwd>Sepsis</kwd>
        <kwd>rehabilitation</kwd>
        <kwd>progress</kwd>
        <kwd>intensive care unit</kwd>
        <kwd>ICU-acquired weakness</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="0"/>
        <page-count count="8"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec id="idm1842998700" sec-type="intro">
      <title>Introduction</title>
      <p>Sepsis is a life-threatening organ dysfunction that is caused by a patient’s maladaptive response to infection<xref ref-type="bibr" rid="ridm1843099188">1</xref>.Anti-infection therapy and organ function supportive therapy are two focuses of the intensive care unit (ICU). However, recent observational                studies have shown ICU processes to be inadequate for the treatment of sepsis: among survivors of               sepsis, more patients have serious sequelae <xref ref-type="bibr" rid="ridm1843102140">2</xref><xref ref-type="bibr" rid="ridm1843112156">3</xref><xref ref-type="bibr" rid="ridm1843169460">4</xref>, while 50% of sepsis patients also have serious               psychological problems <xref ref-type="bibr" rid="ridm1842961972">5</xref><xref ref-type="bibr" rid="ridm1842956932">6</xref>. Finally, sepsis patients have more difficulty returning to the community. During ICU treatment, sepsis patients have a                 significantly increased chance of developing                  thromboembolism <xref ref-type="bibr" rid="ridm1842944620">7</xref>. Limb restraints when applied to the patient for the purpose of safety significantly reduce limb muscle strength <xref ref-type="bibr" rid="ridm1842945844">8</xref>, which is a negative outcome for many sepsis patients. The use of           sedatives has allowed for greater compliance to            medical standards in the treatment of sepsis, but it has also brought its own complications. Several             factors can lead to the decline of physiological               function of patients with sepsis, while incidence of ICU-acquired weakness (ICU-AW) also increases among patients with sepsis <xref ref-type="bibr" rid="ridm1842934668">9</xref>. Rehabilitation may be           associated with a reduced risk of 10-year mortality in the subset of patients with particularly long ICU courses<xref ref-type="bibr" rid="ridm1842935244">10</xref>. Early exercise is of great significance to the rehabilitation of patients with sepsis<xref ref-type="bibr" rid="ridm1842923684">11</xref>. ICU treatment not only is used to rescue patients from life-threatening organ failure, but also provides comprehensive and effective help for         patients to return to the community. Rehabilitation               therapy is essential for patients with sepsis. Studies have shown that early rehabilitation can reduce the occurrence of delirium, shorten the duration of delirium, reduce the use of sedative drugs, reduce the time of mechanical             ventilation, improve heart and lung function, and maintain limb muscle strength <xref ref-type="bibr" rid="ridm1842922892">12</xref><xref ref-type="bibr" rid="ridm1842917348">13</xref><xref ref-type="bibr" rid="ridm1842916268">14</xref><xref ref-type="bibr" rid="ridm1842914180">15</xref><xref ref-type="bibr" rid="ridm1842885300">16</xref>. Therefore, early rehabilitation is an effective method for patients to maintain                       physiological function. This review discusses                           rehabilitation treatment of sepsis patients in ICU. It is           intended to inform guidance for clinical practice. <xref ref-type="fig" rid="idm1850598212">Figure 2</xref></p>
      <sec id="idm1842995820">
        <title>Sepsis leads to ICU-AW</title>
        <p>ICU-AW occurs in 1 million patients every                   year <xref ref-type="bibr" rid="ridm1842934668">9</xref>.In patients with sepsis that leads to multiple organ             dysfunction, the incidence of ICU-AW can be as high as 100% <xref ref-type="bibr" rid="ridm1842882996">17</xref>. Animal studies have shown that sepsis can lead to severe skeletal muscle protein loss, muscle atrophy and muscle weakness, as well as diaphragm and skeletal                muscle dysfunction. Diaphragm and skeletal muscle               dysfunction are the main causes of ICU-AW in sepsis               patients <xref ref-type="bibr" rid="ridm1842880980">18</xref>. Mechanical ventilation, insufficient nutrition intake, and long-term immobilization are involved in the occurrence of ICU-AW.</p>
      </sec>
      <sec id="idm1842997260">
        <title>Timing of Rehabilitation for Sepsis Patients in ICU</title>
        <p>Guidelines have suggested that for patients with respiratory failure that have normal hemodynamics and stability in respiratory function, rehabilitation treatment can be performed <xref ref-type="bibr" rid="ridm1842876084">19</xref>. One study reported that once the hemodynamics of patients with sepsis mechanical                   ventilation are stable and appropriate ventilator             parameters are set, such as the concentration of inhaled oxygen ≤ 0.6, positive end expiratory pressure &lt; 10 cmH<sub>2</sub>O, rehabilitation activities should be encouraged <xref ref-type="bibr" rid="ridm1842890844">20</xref>. Another study suggested that lung rehabilitation of             patients with mechanical ventilation can be started 48 - 72 hours after entering the ICU <xref ref-type="bibr" rid="ridm1842887676">21</xref>. Three studies contended that once the condition of critically ill patients was                 relatively stable, rehabilitation should be started as soon as possible, preferably within 72 hours, in which case             patients benefit significantly better than delayed                      intervention <xref ref-type="bibr" rid="ridm1842866636">22</xref><xref ref-type="bibr" rid="ridm1842864188">23</xref><xref ref-type="bibr" rid="ridm1842858644">24</xref>. Moreover, patients can walk on the ground during mechanical ventilation; tracheal intubation was not a contraindication for early rehabilitation exercise <xref ref-type="bibr" rid="ridm1842856196">25</xref>. During the rehabilitation period, if vital signs fluctuate to such a degree that it deteriorates and endangers the patient’s life, then it is recommended to suspend the                  rehabilitation treatment <xref ref-type="bibr" rid="ridm1842866636">22</xref><xref ref-type="bibr" rid="ridm1842841716">26</xref>.</p>
      </sec>
      <sec id="idm1842995316">
        <title>Rehabilitation Goals of Sepsis Patients in ICU</title>
        <p>The goal of rehabilitation is to enable a disabled patient to recover their function to the maximum extent that they can, and to return to the community. In the             process of rehabilitation, each stage may have a different set of goals for the patient. Rehabilitation is for training patients to improve their function and adapt to the                environment, while it also requires the participation of care-members, colleagues, and friends to assist them with a successful return to the community <xref ref-type="bibr" rid="ridm1842838620">27</xref>.</p>
      </sec>
      <sec id="idm1842995388">
        <title>Development of Rehabilitation Plan for Sepsis Patients </title>
        <p>The formulation of a rehabilitation plan and the evaluation of the rehabilitation of ICU sepsis patients are benefited by ICU doctors and rehabilitation doctors                 working together. ICU doctors will ideally provide effective organ function support, especially respiration and                  circulation, thus ensuring the stability of vital signs during rehabilitation. Likewise, rehabilitation physicians may perform effective rehabilitation methods according to the patient's condition and preferences, while fully                    considering the benefits and potential risks of each                 rehabilitation approach. If there is a change in the             patient's condition, the intensity and quantity of                       rehabilitation measures can be modified accordingly. ICU doctors and rehabilitation physicians are better served by adopting daily evaluation strategies such as to develop personalized rehabilitation programs that are suitable for patients <xref ref-type="bibr" rid="ridm1842866636">22</xref><xref ref-type="bibr" rid="ridm1842858644">24</xref>.</p>
      </sec>
      <sec id="idm1842997188">
        <title>ICU Rehabilitation Team</title>
        <p>Rehabilitation medicine often adopts the "multidisciplinary cooperation clinical rehabilitation              integration" rehabilitation model <xref ref-type="bibr" rid="ridm1842833796">28</xref><xref ref-type="bibr" rid="ridm1842831852">29</xref><xref ref-type="bibr" rid="ridm1842827676">30</xref>. That is to say: this model informs clinicians that they should approach               rehabilitation by forming a rehabilitation team.               The coordinator of the ICU rehabilitation team is usually a doctor of critical care medicine, and its members include ICU doctors and nurses, rehabilitation doctors,                         rehabilitation therapists, rehabilitation nurses, respiratory therapists, and psychologists. The rehabilitation team in China also includes traditional Chinese medicine                    physiotherapists. <xref ref-type="fig" rid="idm1850591660">Figure 1</xref></p>
        <fig id="idm1850591660">
          <label>Figure 1.</label>
          <caption>
            <title> Impact of delayed ICU rehabilitation in early sepsis. This diagram illustrates the sequential impact of delayed rehabilitation for patients with sepsis as a result of the          inflammatory process and the detrimental short and long –term out comes.</title>
          </caption>
          <graphic xlink:href="images/image1.jpg" mime-subtype="jpg"/>
        </fig>
        <fig id="idm1850598212">
          <label>Figure 2.</label>
          <caption>
            <title> Cumulative incidences of mortality among intensive care            survivors of sepsis</title>
          </caption>
          <graphic xlink:href="images/image2.jpg" mime-subtype="jpg"/>
        </fig>
      </sec>
      <sec id="idm1842994596">
        <title>Rehabilitation Measures for Sepsis</title>
        <p>Commonly used rehabilitation techniques include physical therapy, occupational therapy, psychological counseling and treatment, rehabilitation engineering,             rehabilitation nursing, and the physical therapy of                 traditional Chinese medicine. Patients who are able to     cooperate with treatment are benefited by engaging in active rehabilitation training as early as possible, and            patients who are unable to cooperate are benefited by taking passive rehabilitation training measures. Lung              rehabilitation, heart rehabilitation, psychological                     rehabilitation, and limb function exercise of sepsis                   patients are the focus of rehabilitation treatment <xref ref-type="bibr" rid="ridm1842819860">31</xref><xref ref-type="bibr" rid="ridm1842813812">32</xref>.</p>
      </sec>
      <sec id="idm1843000068">
        <title>Psychological Rehabilitation</title>
        <p>Psychological intervention provides emotional support for patients and helps them relieve psychological pressure. At present, there is no unified standard or model for psychological intervention <xref ref-type="bibr" rid="ridm1842811724">33</xref><xref ref-type="bibr" rid="ridm1842808412">34</xref><xref ref-type="bibr" rid="ridm1842804092">35</xref>. Intervention methods include drug therapy and psychotherapy, usually as                combined measures. A study showed that psychological intervention can improve the psychological discomfort reaction of ICU patients and improve the treatment                compliance of patients <xref ref-type="bibr" rid="ridm1842800420">36</xref>. A psychological intervention study conducted by ICU in a hospital in Italy showed that the incidence rate of PTSD decreased significantly within 12 months after discharge from psychological                     intervention, which was more conducive to the patient’s return to social life <xref ref-type="bibr" rid="ridm1842797900">37</xref>. An ICU diary can document the experience of patients in ICU; it can help patients fill in the significant loss in memory, and it puts delusional memory in a context, which is also conducive to psychological               rehabilitation <xref ref-type="bibr" rid="ridm1842793724">38</xref>. A randomized clinical trial conducted in 24 ICUs in the UK showed that preventive psychological intervention in ICU not only significantly reduced delirium and fantasy during ICU, but also reduced mental illness after ICU <xref ref-type="bibr" rid="ridm1842789476">39</xref>.</p>
      </sec>
      <sec id="idm1842999996">
        <title>Physical Function Exercise</title>
        <p>The main components of exercise include passive and active exercise in bed, sitting in bed, muscle strength training, bedside standing, and walking <xref ref-type="bibr" rid="ridm1842764764">40</xref>. Early exercise is more conducive to the recovery of cardiopulmonary function, and it leads to a reduction in the time on                     mechanical ventilation <xref ref-type="bibr" rid="ridm1842760876">41</xref>. Researchers have applied an electric rehabilitation machine, combined with functional exercise, to patients with severe pneumonia in order to improve their respiratory function, shorten the duration of mechanical ventilation and their ICU stay <xref ref-type="bibr" rid="ridm1842759076">42</xref>. For                   patients who are alert, clinicians can attempt to transition them from passive movement to active movement, that is: the care team can gradually carry out rehabilitation                  training with the patient by having the patient sit beside the bed, sit in a chair beside the bed, and stand beside the bed <xref ref-type="bibr" rid="ridm1842755332">43</xref>. When the patient’s muscle strength is greater than or equal to grade 4, they can walk indoors with walking aids or wheelchairs such as to exercise the function of their lower limbs <xref ref-type="bibr" rid="ridm1842751228">44</xref>. For patients who are not able to              cooperate, lateral rotation therapy can be used to prevent soft tissue and joint contracture, peripheral nerve                   compression and other injuries. For patients who cannot move autonomously after coma or sedation, the joints of their limbs can be moved passively while the patient is lying on the bed. Appropriate interruption of patients’  sedation and rehabilitation training can help reduce the incidence of ICU-AW <xref ref-type="bibr" rid="ridm1842755332">43</xref>. For alert patients, their legs can be lifted to perform movements akin to riding a bicycle, which increases lower limb muscle strength. Researchers have used the dynamometer to provide resistance                 exercise training for patients, and the trained patients’ muscle strength is enhanced, while their physical function is also improved when they leave the hospital <xref ref-type="bibr" rid="ridm1842745756">45</xref>.</p>
      </sec>
      <sec id="idm1843001220">
        <title>Other Rehabilitation Measures</title>
        <p>Neuromuscular electrical stimulation is a             low-frequency electrical therapy which can prevent                muscle atrophy by stimulating nerve fibers to activate  motor neurons, thereby increasing blood flow and                 contractile force of muscle <xref ref-type="bibr" rid="ridm1842743956">46</xref><xref ref-type="bibr" rid="ridm1842771100">47</xref>. Early acupoint electrical stimulation can improve lower limb muscle strength of patients with sepsis acquired weakness <xref ref-type="bibr" rid="ridm1842770812">48</xref>. Chinese               massage therapy has an advantage in its strong physical penetration despite being non-invasive. Chinese massage therapy stimulates local muscle contraction, promotes blood circulation, and improves neuromuscular                    excitability. Finally, Chinese massage therapy also dredges channels and collaterals, thereby taking the whole body into account <xref ref-type="bibr" rid="ridm1842707644">49</xref>.</p>
      </sec>
    </sec>
    <sec id="idm1843000716">
      <title>Funding</title>
      <p>Guizhou Science and Technology Support                 Plan（<sup>2020</sup> 4Y139）;Qiandongnan Miao and Dong                    Autonomous Prefecture Science and Technology Support Plan（<sup>2021</sup>12）;Cultivation of High-Level Innovative Talents in Guizhou Province</p>
    </sec>
    <sec id="idm1843000644" sec-type="conclusions">
      <title>Conclusion</title>
      <p>Individualized rehabilitation is a safe and                   effective approach for patients with sepsis. Rehabilitation therapy can improve exercise endurance,                                 cardiopulmonary function, and pulmonary function, and it can reduce ICU-related complications. Rehabilitation measure is an important means to realize the successful return of sepsis patients to the community. There remains significant work to be done in the application of                           rehabilitation medicine to the field of sepsis.</p>
    </sec>
  </body>
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