# Early mobilization in patients with aneurysmal subarachnoid haemorrhage may im-prove functional status and reduce cerebral vasospasm rate: a systematic review with meta-analysis

Adéla Foudhaili, Brice Leclere, Florence Martinache, Anthony Chauvin, Damien Vitiello, Benjamin G Chousterman

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## ► To cite this version:

Adéla Foudhaili, Brice Leclere, Florence Martinache, Anthony Chauvin, Damien Vitiello, et al.. Early mobilization in patients with aneurysmal subarachnoid haemorrhage may im-prove functional status and reduce cerebral vasospasm rate: a systematic review with meta-analysis. Journal of Rehabilitation Medicine, 2024, 56, 10.2340/jrm.v56.41225. [https://doi.org/10.5335239v1](https://doi.org/10.5335239v1)

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# EARLY MOBILIZATION IN PATIENTS WITH ANEURYSMAL SUBARACHNOID HAEMORRHAGE MAY IMPROVE FUNCTIONAL STATUS AND REDUCE CEREBRAL VASOSPASM RATE: A SYSTEMATIC REVIEW WITH META-ANALYSIS

Adela FOUDHAILI, PT¹⁻³, Brice LECLERE, MD, PhD⁴, Florence MARTINACHE, PT⁵⁻⁷, Anthony CHAUVIN, MD, PhD²,⁸, Damien VITIELLO, PhD³ and Benjamin G. CHOUSTERMAN, MD, PhD²,⁹

From the ¹Department of Physical Medicine and Rehabilitation, AP-HP, CHU Lariboisière, Paris, ²Université Paris Cité, Inserm, MASCOT, Paris, ³Université Paris Cité, Institut des Sciences du Sport-Santé de Paris, Paris, ⁴Nantes Université, CHU Nantes, IICiMed, UR 1155, Nantes, ⁵Université Paris-Saclay, CIAMS, Orsay, ⁶Techno Concept, Manosque, ⁷Department of Anesthesiology and Critical Care, AP-HP, CHU Bicêtre, Le-Kremlin-Bicêtre, ⁸Department of Emergency, AP-HP, CHU Lariboisière, Paris, and ⁹Department of Anesthesiology and Critical Care, CHU Lariboisière, AP-HP, Paris, France

**Objective:** The primary aim of this study was to evaluate the safety and efficacy of early mobilization in patients with aneurysmal subarachnoid haemorrhage.

**Design:** Systematic review with meta-analysis of randomized controlled studies and observational studies.

**Patients:** Patients with aneurysmal subarachnoid haemorrhage.

**Methods:** PubMed, Embase, CINAHL, Web of Science, Pedro, and the Cochrane Library databases were searched. A systematic review and meta-analysis were performed. Screening and data extraction were performed by 2 independent reviewers.

**Results:** Sixteen studies involving 1,757 patients were included. Meta-analysis of the data estimated that early mobilization improved mRS score at discharge (mean difference -1.39, 95% CI -2.51 to -0.28, I²=86%) and at 3 months (mean difference -1.10, 95% CI -1.54 to -0.66, I²=7%). Early mobilization was associated with a reduction in cerebral vasospasm rate, both radiological (OR 0.66, 95% CI 0.45 to 0.96, I²=7%) and clinical (OR 0.44, 95% CI 0.27 to 0.72, I²=8%); 6% of mobilization sessions involved adverse events, mostly haemodynamic changes.

**Conclusion:** This review found moderate-quality evidence supporting the safety and effectiveness of early mobilization in patients with SAH. Further randomized controlled trials are needed to identify the appropriate mobilization strategy and confirm these results.

**Key words:** critical care; early ambulation; physical therapy modalities; subarachnoid haemorrhage; systematic review; functional status; vasospasm.

Submitted Jul 25, 2024. Accepted after revision Oct 2, 2024

Published Oct 18, 2024. DOI: 10.2340/jrm.v56.41225

J Rehabil Med 2024; 56: jrm41225.

Correspondence address: Adela Foudhaili, Department of Anesthesiology and Critical Care, CHU Lariboisière, AP-HP, F-75010 Paris, France.
E-mail: adela.foudhaili@aphp.fr

Subarachnoid haemorrhage (SAH) is a severe neurological condition, associated with high mortality and morbidity rates (1). While mortality has improved over the past decades, survivors still report significant

## LAY ABSTRACT

Early mobilization of patients admitted to the intensive care unit is now considered standard of care. However, for neurocritical patients, including those with subarachnoid haemorrhage (SAH), it remains unclear whether implementing early mobilization is safe and beneficial. This systematic review aimed to evaluate the safety and efficacy of early mobilization in this population. Several databases were screened to extract eligible articles, and 16 articles were included in this review. The results indicate that early mobilization in patients with SAH appears to be safe, not associated with major safety events, and improves the odds of functional independence. Standardization of the mobilization procedure seems essential to guarantee safety. However, the quality of evidence is moderate and warrants further studies to confirm these findings.

disabilities and limitations in activities of daily living. About 20% of survivors are not fully independent 1 year after SAH, and 25% still have activity restrictions, such as difficulties returning to work (2, 3). After several years, patients with SAH still report limitations in participation in activities of daily living and work, and cognitive deficits. These patients also suffer from mood disorders, severe fatigue, and reduced quality of life (4–7).

The management of patients with SAH is complex, often requiring admission to intensive care units (ICUs) for close monitoring and treatment of potential complications. Over the past decades, the therapeutic approach to aneurysmal SAH has undergone major advancements. In contrast, the question of early mobilization of patients with SAH remains a relatively unexplored yet crucial area. The 2023 American Heart Association/American Stroke Association (AHA/ASA) recommendations on the management of patients with SAH advocate the implementation of an early mobilization protocol to improve functional outcome (8). However, these recommendations do not specify the mobilization modalities to be applied. It has been shown that the timing, intensity, and frequency of mobilization have a major impact on functional
prognosis (9, 10). Identifying the optimal approach to mobilization is therefore essential.

In this context, this systematic review and meta-analysis aims to determine the impact of different early mobilization strategies of patients with SAH on (1) physical function and physical performance tasks; (2) cognitive function; (3) psychological state; (4) health-related quality of life; (5) adverse events related to mobilization; and (6) neurological complications.

## METHODS

This systematic review with meta-analysis was reported in accordance with the PRISMA statement (Preferred reporting Items for Systematic Reviews and Meta-analyses) and was pre-registered on PROSPERO (International prospective register of systematic reviews) with registration number CRD42022298976.

### Identification and selection of studies

The literature search was designed by the authors with assistance from a medical librarian. The search was executed in PubMed, Embase, CINAHL, Web of Science, Pedro, and the Cochrane Library databases in February 2022 and repeated prior to completion of analysis to identify studies that would have been published after the initial search. The last search was performed in February 2024. Snowballing and reverse snowballing were carried out to identify any other existing studies. The detailed search strategy can be found in the Supplementary Appendix.

### Criteria for considering studies

**Types of studies.** We searched for randomized controlled trials, non-randomized controlled trials, and observational studies written in English or French and published from 2001 to February 2024.

**Types of patients.** Adult patients with aneurysmal subarachnoid haemorrhage.

**Interventions.** Studies were selected for inclusion if they evaluated patients with aneurysmal subarachnoid haemorrhage who received early mobilization delivered by any members of the team. We considered interventions consisting of mobilization carried out earlier than those received by the control group, where applicable. Mobilization could be passive, assisted active, or active mobilizations, including but not restricted to passive/active exercises in bed, bed mobility training, dangling, passive/active transfers, passive/active exercises sitting out of bed, pre-gait exercises, ambulation. The comparator, where applicable, should have consisted of delayed mobilization or no mobilization.

We excluded case report studies, studies of mixed neurological populations, and studies that focused exclusively on head-of-bed changes.

**Types of outcome measures.** Eligible studies were those that reported at least 1 of the following endpoints: measures of physical function or physical performance tasks, cognitive function, psychological state, health-related quality of life or well-being, the occurrence of neurological complications, and adverse events related to mobilization.

Outcomes were categorized as follows:

* Physical function (defined as the ability to perform everyday activities) or physical performance tasks measured by a validated scale (e.g., Functional Independence Measure (FIM), Barthel Index, modified Rankin scale, walking tests, mobility scores) at discharge or during patient follow-up.

* Cognitive function measured by a validated scale (e.g., Montreal Cognitive Assessment [MoCA], Mini-Mental State Examination [MMSE]) at discharge or during patient follow-up.

* Psychological state measured by a validated scale (e.g., the Hospital Anxiety and Depression Scale [HADS], Impact of Events Scale [revised]) at discharge, or during patient follow-up.

* Health-related quality of life or well-being measured by a validated scale (e.g., Quality of Life in Neurological Disorders [Neuro-QoL], EuroQoL-5 Dimensions, 36-Item Short Form Survey [SF-36]) during patient follow-up.

* Neurological complications (neurological deterioration, cerebral vasospasm, delayed cerebral ischaemia, hydrocephalus, rebleeding from a ruptured aneurysm) occurring during the stay.

* Adverse events (haemodynamic instability, increase in intracranial pressure, falls, accidental dislodgement of lines such as extra-ventricular or lumbar drain) related to mobilization.

### Selection of studies

A 4-stage screening process was used to select relevant studies. In the first stage, citations retrieved by the searches were exported to reference management software for screening and duplicate removal (11). In the second stage, 1 reviewer (AF) screened all titles for eligibility. In the third stage, titles and abstracts were independently evaluated by 2 reviewers (AF and FM). In the fourth stage, the full text of each potentially eligible study was assessed by 2 reviewers (AF and FM). Disagreements were resolved by discussion.

### Data extraction and quality assessment

Two reviewers independently performed data extraction using a standardized data extraction form. The Plotdigitizer software (https://plotdigitizer.com/) was used to estimate numerical results when results were presented only as figures (12). Authors of eligible studies were contacted for clarification of methodology and results in the case of unpublished or missing data. One of the included studies was co-authored by 3 of the authors on this paper; therefore, 2 external reviewers completed data extraction and quality assessment using the same standardized data extraction form (13).

Two authors (AF and FM) independently assessed study quality using the Cochrane risk of bias tool for the RCTs and an adapted version of the Newcastle-Ottawa scale for observational studies (14). Any other potential bias was also reported. Any discrepancies in assessments of risk of bias were resolved with consensus.

### Data synthesis and analysis

When sufficient data were available, meta-analysis was performed. We considered studies where early mobilization was initiated within 7 days after SAH onset. One study considered a 2-week delay and was therefore excluded from the meta-analysis (15). For dichotomous variables, a pooled odds ratio with 95% confidence intervals (CI) was calculated. For continuous variables a pooled estimate of mean difference (MD) with 95% CI was calculated. All the meta-analyses included a random effect to account for between-study statistical heterogeneity.
Authors were contacted to collect parametric data (means and standard deviations) when missing. For the adverse event rate, a pooled incidence was estimated. This was not possible for device dislodgement and intracranial pressure increase, as the total number of mobilization sessions during which a patient wore such a device was not reported.

The I² statistic was estimated to evaluate the amount of between-study heterogeneity and Cochran's Q test was performed to assess its statistical significance. Given the low number of studies for each meta-analysis, we were unable to assess the risk of publication bias. All meta-analysis was conducted using R version 4.2.0 (2022-04-22 ucrit), meta package version 7.0.1 (R Foundation for Statistical Computing, Vienna, Austria). When there were insufficient data to perform a meta-analysis, the results of the included studies were reported descriptively.

For both meta-analysis and descriptive reporting of results, when there were more than 2 groups, pooling was performed to compare the group with the earliest mobilization initiation or highest mobilization level with the others. For descriptive reporting, means and standard deviations were recalculated before performing Student's t-test. For categorical data, proportions were summed, and Fisher's or a χ² test was performed.

## RESULTS

### Flow of trials through the review

A total of 4,034 citations were identified, with 833 removed during de-duplication, resulting in 3,201 unique citations screened and 83 full-text publications reviewed (Fig. 1). After excluding 71 publications (47 with an inadequate population, 6 with an inadequate intervention, 15 in the form of conference abstracts, 1 letter, 1 commentary, 1 study protocol), we were able to

include 12 studies. Four eligible studies were published after the initial screening. No further eligible articles were found from snowballing and reverse snowballing.

### Characteristics of included trials

Characteristics of the 16 included studies are outlined in Table I. The 16 publications included 1 randomized controlled trial, 7 before-after studies (retrospective, prospective, or ambispective), 5 retrospective cohorts, 2 case series, and 1 case-control study. Most studies were conducted in Japan (n=5) and the United States (n=5), with others in Norway (n=3), China (n=1), France (n=1), and Serbia (n=1). All were monocentric except for 1 study conducted in 5 hospitals (16). Most studies investigated the impact of the implementation of an early mobilization programme, the others compared 2 or more different mobilization initiation times or mobilization levels/intensities. The case-control study investigated the association between cerebral vasospasm and early mobilization (16).

Three studies were part of the same project and their populations overlapped, but as they assessed different outcomes we decided to include all 3 of them (17–19). Two studies were carried out by the same team, with no overlapping populations, and both were included (20, 21). Two other studies were carried out by the same team. The first compared a mobilization protocol led by physiotherapists (PT) and occupational therapists (OT) with standard care and was included as is (22). The

<figure><img src="image_3.png" /><figcaption>**Fig. 1.** Flow of studies through the review. From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71. https://doi.org/10.1136/bmj.n71</figcaption></figure>
<table><caption>**Table I.** Characteristics of included studies</caption><thead><tr><th rowspan="2">Study (year)</th><th rowspan="2">Objectives</th><th rowspan="2">Location</th><th rowspan="2">Type of study</th><th rowspan="2">Setting</th><th rowspan="2">Pathology</th><th colspan="2">Total population</th><th colspan="2">Control group</th><th colspan="2">Intervention</th><th rowspan="2">Mean time to mobilization</th><th rowspan="2">Group differences</th></tr><tr><th>Sample size</th><th>Age</th><th>Good grade/ Poor grade SAH ratio</th><th>Male (%)</th><th>Description</th><th>n</th><th>Male (%)</th><th>Description</th></tr></thead><tbody><tr><td>Foudhaili (2023)</td><td>To evaluate the impact of early out-of-bed mobilization of SAH patients on functional independence at 3 months and cerebral vasospasm</td><td>France</td><td>Retrospective cohort</td><td>Surgical intensive care unit, University Hospital</td><td>Aneurysmal SAH</td><td>179</td><td>53 [44-61]</td><td>69/31</td><td>148</td><td>30%</td><td>Out-of-bed mobilization &gt; D4</td><td>31</td><td>36%</td><td>Out-of-bed mobilization ≤ D4</td><td>≤ D4</td><td>Intervention group: lower grade SAH (p&lt;0.05), less EVD (p=0.001), extubated earlier (p&lt;0.01)</td></tr><tr><td>Karic (2014), J Disab</td><td>To describe the content and feasibility of early rehabilitation adapted to SAH patients</td><td>Norway</td><td>Case series</td><td>Neuro-intermediate ward of the neurosurgical department, University Hospital</td><td>Aneurysmal SAH</td><td>37</td><td>58 [35-74]</td><td>89/11</td><td>-</td><td>-</td><td>None</td><td>37</td><td>29%</td><td>A 7-step mobilization algorithm</td><td>D3</td><td>No differences reported</td></tr><tr><td>Karic (2016), J Neurosurg</td><td>To assess the impact of early rehabilitation on global functional outcome 1 year after SAH</td><td>Norway</td><td>Before-after study</td><td>Neuro-intermediate ward of the neurosurgical department, University Hospital</td><td>Aneurysmal SAH</td><td>171</td><td>56 [25-81]</td><td>80/20</td><td>77</td><td>36%</td><td>Standard care</td><td>94</td><td>30%</td><td>A 7-step mobilization algorithm</td><td>D7</td><td>No differences reported</td></tr><tr><td>Karic (2016), J Rehabil Med</td><td>To evaluate the effect of early mobilization and rehabilitation on complications during the acute phase after SAH</td><td>Norway</td><td>Before-after study</td><td>Neuro-intermediate ward of the neurosurgical department, University Hospital</td><td>Aneurysmal SAH</td><td>168</td><td>55 [25-81]</td><td>83/17</td><td>76</td><td>37%</td><td>Standard care, not protocolized</td><td>92</td><td>30%</td><td>A 7-step mobilization algorithm</td><td>D7.4 in poor-grade; D0.9 in reported good-grade</td><td>No differences reported</td></tr><tr><td>Milovanovic (2016)</td><td>To assess the impact of early verticalization of SAH patients on early postoperative complications, occurrence of vasospasm and occurrence of motor deficits</td><td>Serbia</td><td>Randomized controlled trial</td><td>Neurosurgery clinic</td><td>Aneurysmal SAH, classified as grade I, II, or III on the Hunt and Hess scale</td><td>65</td><td>53 [25-71]</td><td>100/0</td><td>34</td><td>32%</td><td>Verticalization initiated from D12 post bleeding</td><td>31</td><td>32%</td><td>Verticalization initiated on days 2-5 post bleeding</td><td>&lt; D5</td><td>Intervention group: non-statistically significant tendency for more pneumonia, fever, meningitis, wound dehiscence</td></tr><tr><td>Meyer (2017)</td><td>To assess the feasibility, safety, and outcome of an early mobility protocol for patients with SAH with an EVD</td><td>USA</td><td>Before-after study</td><td>Neuro-ICU, University Hospital</td><td>Aneurysmal SAH with EVD</td><td>45</td><td>58</td><td>85/15</td><td>19</td><td>10%</td><td>Strict bedrest while EVD in place</td><td>26</td><td>15%</td><td>Mobilization algorithm</td><td>D6.5</td><td>No differences reported</td></tr><tr><td>Okamura (2021)</td><td>To investigate the relationship between early mobilization and home discharge and functional status in patients with SAH</td><td>Japan</td><td>Retrospective cohort</td><td>Hospital</td><td>Aneurysmal SAH</td><td>35</td><td>66 ± 14</td><td>63/37</td><td>13</td><td>36%</td><td>Participation in walking rehabilitation &gt; D14</td><td>22</td><td>39%</td><td>Participation in walking rehabilitation ≤ D14</td><td>D4.2</td><td>Intervention group: lower grade SAH (p&lt;0.001)</td></tr></tbody></table>

(Continued)
<table><caption>Table I. (Continued) Characteristics of included studies</caption><thead><tr><th rowspan="2">Study (year)</th><th rowspan="2">Objectives</th><th rowspan="2">Location</th><th rowspan="2">Type of study</th><th rowspan="2">Setting</th><th rowspan="2">Pathology</th><th colspan="2">Total population</th><th colspan="2">Control group</th><th colspan="2">Intervention</th><th rowspan="2">Mean time to mobilization</th><th rowspan="2">Group differences</th></tr><tr><th>Sample size</th><th>Age</th><th>Good grade/grade/grade SAH ratio</th><th>Male (%)</th><th>Description</th><th>n</th><th>Male (%)</th><th>Description</th></tr></thead><tbody><tr><td>Olkowski (2013)</td><td>To examine the safety and feasibility of an early mobilization programme for patients with aneurysmal SAH</td><td>USA</td><td>Before-after study</td><td>Neurosurgical ICU, Hospital</td><td>Aneurysmal SAH</td><td>25</td><td>55.6±11.8</td><td>88/12</td><td>-</td><td>-</td><td>-</td><td>25</td><td>24%</td><td>Early mobilization programme</td><td>D3.2</td><td>No differences reported</td></tr><tr><td>Olkowski (2015)</td><td>To determine the impact of an early mobilization programme for patients with aneurysmal SAH on function and hospital length of stay</td><td>USA</td><td>Case series</td><td>Neurosurgical ICU, Hospital</td><td>Aneurysmal SAH</td><td>93</td><td>54</td><td>74/26</td><td>38</td><td>26%</td><td>Standard care</td><td>55</td><td>36%</td><td>Early mobilization programme</td><td>D4.2</td><td>No differences reported</td></tr><tr><td>Riordan (2015)</td><td>To investigate the effect of early mobilization using mild exercise in patients with SAH after securization of the aneurysm</td><td>USA</td><td>Retrospective cohort</td><td>University hospital</td><td>Aneurysmal SAH</td><td>80</td><td>56</td><td>82/18</td><td>58</td><td>29%</td><td>Fusion of: initiation of active physical therapy within D4-D9, D10-D19, ≥D20</td><td>22</td><td>27%</td><td>Initiation of active physical therapy &lt;D4</td><td>&lt;D4</td><td>Intervention group</td></tr><tr><td>Shimamura (2014)</td><td>To investigate the effect of early ambulation on outcome in advanced-age SAH</td><td>Japan</td><td>Retrospective cohort</td><td>Department of Neurosurgery, University Hospital</td><td>Aneurysmal SAH, age &gt;70 years old</td><td>71</td><td>76 [70-87]</td><td>100/0</td><td>45</td><td>ns</td><td>Fusion of: ambulation within D6-D10, D11-D15, &lt;D15</td><td>26</td><td>ns</td><td>Ambulation &lt;D6</td><td>&lt;D6</td><td>No differences reported</td></tr><tr><td>Takara (2022)</td><td>To investigate the association between initiating mobilization within 7 days after onset and symptomatic cerebral vasospasm in patients with aneurysmal SAH</td><td>Japan</td><td>Case control study</td><td>Five hospitals</td><td>Aneurysmal SAH</td><td>510</td><td>&lt;65: 53%<br/>≥65: 47%</td><td>70/30</td><td>453</td><td>29%</td><td>No symptomatic cerebral vasospasm group</td><td>57</td><td>26%</td><td>Symptomatic cerebral vasospasm group</td><td>NA</td><td>No SCV group: lower grade SAH (p&lt;0.01)</td></tr><tr><td>Uemura (2018)</td><td>To investigate the impact of sitting position within 13 days after surgery and the level of activities of daily living and discharge destination in SAH patients</td><td>Japan</td><td>Retrospective cohort</td><td>Department of Neurosurgery, University Hospital</td><td>Aneurysmal SAH, middle-aged and elderly patients</td><td>43</td><td>67</td><td>51/49</td><td>21</td><td>19%</td><td>Fusion of: DA group: bedrest until D13; DS group: bedrest with head-up position until D13</td><td>22</td><td>14%</td><td>Early sitting group: sitting out-of-bed &lt;D13</td><td>&lt;D13</td><td>Intervention group: more coiling operation (p&lt;0.05), lower NIHSS score (p&lt;0.05)</td></tr><tr><td>Yang (2023)</td><td>To evaluate the validity, safety, and feasibility of ICF-based early progressive mobilization in patients with severe aneurysmal SAH</td><td>China</td><td>Before-after study</td><td>Neurosurgical ICU, University Hospital</td><td>Aneurysmal SAH patients, Hunt and Hess III-IV, mechanically ventilated &gt;48 h</td><td>68</td><td>69</td><td>63/37</td><td>34</td><td>41%</td><td>Passive joint movement</td><td>34</td><td>32%</td><td>ICF-based early progressive mobilization</td><td>D3</td><td>No differences reported</td></tr></tbody></table>

(Continued)
<table><caption>Table I. (Continued) Characteristics of included studies</caption><thead><tr><th rowspan="2">Study (year)</th><th rowspan="2">Objectives</th><th rowspan="2">Location</th><th rowspan="2">Type of study</th><th rowspan="2">Setting</th><th rowspan="2">Pathology</th><th colspan="2">Total population</th><th colspan="2">Control group</th><th colspan="4">Intervention</th></tr><tr><th>Sample size</th><th>Age</th><th>Male (%)</th><th>Male (%)</th><th>n</th><th>Description</th><th>Mean time to mobilization</th><th>Description</th><th>Group differences</th></tr><tr><th></th><th></th><th></th><th></th><th></th><th></th><th></th><th>Good grade/ Poor grade SAH ratio</th><th>n</th><th>Male (%)</th><th>Male (%)</th><th>n</th><th>Early rehabilitation programme</th><th>DS</th><th>Intervention group: more endovascular treatment (p&lt;0.001)</th></tr></thead><tbody><tr><td>Yokobatake (2022)</td><td>To investigate the impact of early rehabilitation for patients with aneurysmal SAH on the occurrence of complications, disuse complications, and independence at 90 days post-onset</td><td>Japan</td><td>Before-after study</td><td>Tertiary hospital centre</td><td>aneurysmal SAH</td><td>111</td><td>68 [56-80]</td><td>57/43</td><td>55</td><td>31%</td><td>Standard care</td><td>56</td><td>29%</td><td></td></tr><tr><td>Young (2019)</td><td>To determine whether a nurse-driven mobilization protocol would result in safe and more frequent mobilization than institutional standard care.</td><td>USA</td><td>Before-after study</td><td>Neuro-ICU, University Hospital</td><td>SAH with EVD</td><td>32</td><td>56 [33-90]</td><td>88/12</td><td>15</td><td>31%</td><td>2 groups: standard care, and PT/OT-driven mobilization protocol</td><td>17</td><td>53%</td><td>Nurse-driven mobilization protocol</td><td>D4.9</td><td>No differences reported</td></tr></tbody></table>

EVD: external ventricular derivation; ICU: intensive care unit; SCV: symptomatic cerebral vasospasm.

second compared a nurse-driven protocol with both standard care and the PT/OT-driven protocol (23). As the authors did not report a difference between the time to initiation of the PT/OT protocol and the nurse-led protocol, only the comparison of the nurse-led protocol with standard care was reported in this study.

Three studies involved more than 2 groups with different mobilization initiation times (24, 25), or different mobilization levels (15). Whenever possible group pooling was performed as described in the Methods section.

## Quality assessment of included studies

The risk of bias of the RCT was moderate (Fig. 2). The method of randomization and/or concealment was not clearly described, and blinding of assessors was unlikely. The study protocol was neither available in a trial registry nor published. It is uncertain whether the study was sufficiently powered and the statistical analyses adequate. No details were given regarding the mobilization protocol safety criteria and patient screening.

Assessment of the 15 other studies demonstrated a low to moderate risk of bias (Tables II and III). Most studies were representative of patients with SAH receiving mobilization and ascertainment of exposure to mobilization was described in all studies. Some of the retrospective studies reported significant between-group differences in the severity of SAH, with patients who were mobilized early being less severe. Most studies performed adjustments for confounders in their analysis.

## Characteristics of the participants

The studies included a total of 1,733 patients, and study cohorts ranged from 25 to 510 patients (median 70). Key characteristics of participants are outlined in Table I. The mean age of participants ranged from 52 to 76 years. Most patients were women. Thirteen of 16 studies (81%) included patients with SAH of any grade, 2 studies excluded patients with poor-grade SAH (24, 26) and 1 excluded patients with Hunt and Hess I and II SAH (27). Overall, 15 out of 16 studies had a good grade to poor grade SAH ratio in favour of good grade, with the majority of studies including more than 70% of patients with good grade SAH. The last study had a good-grade/poor-grade ratio of 51/49(15). Fourteen of 16 studies (90%) included patients with SAH of any age; the remaining studies included middle-aged and elderly patients (15, 24).

## Characteristics of the mobilization strategies

There was heterogeneity in multiple aspects of the interventions throughout the 16 included studies.
<figure><img src="image_4.png" /><figcaption>**Fig. 2.** Risk of bias assessment of randomized, controlled trials. It is uncertain whether the study was sufficiently powered and the statistical analyses adequate. \*Very little detail given regarding the mobilization protocol, including safety assessment for initiating mobilization and cancellation criteria.</figcaption></figure>

Nine studies evaluated mobilization algorithms or programmes (Table IV) (17–23, 27, 28). The timing for initiating mobilization, when reported, did not exceed 24 h after the aneurysm repair or admission (17–21, 23, 28).

Mobilization always began only after the aneurysm had been secured, or in the absence of an underlying aneurysm. Daily assessment for initiating mobilization included the absence of symptomatic cerebral vasospasm, stability of haemodynamic and respiratory parameters, no intracranial hypertension, and stable neurological examination or imaging. Ischaemia, rebleeding, new neurological symptoms, or fluctuations in

neurological examination led to a pause or setback in the mobilization programmes. In studies evaluating patients with external ventricular drain (EVD), tolerance to EVD clamping was also required, as well as verification that the EVD was securely fixed prior to mobilization.

The starting level of exercise varied from in-bed exercises to edge-of-bed sitting and mobilization progressed once the previous step had been well tolerated. All studies defined monitoring parameters and criteria for stopping mobilization mostly including haemodynamic and respiratory instability, an increase of intracranial pressure (ICP), acute change in neurological examination, and signs of intolerance (nausea,

<table><caption>**Table II.** Risk of bias assessment of cohorts</caption><caption>Cohort</caption><thead><tr><th rowspan="2">Study</th><th colspan="3">Selection</th><th colspan="3">Comparability</th><th colspan="2">Outcome</th></tr><tr><th>Representativeness of the exposed cohort</th><th>Selection of the non-exposed cohort</th><th>Ascertainment of exposure</th><th>Outcome was not present at start</th><th>Comparability of cohorts</th><th>Assessment of outcome</th><th>Follow-up long enough for outcomes to occur</th><th>Adequacy of follow up of cohorts</th></tr></thead><tbody><tr><td>Foudhaili, 2023</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td></tr><tr><td>Karic, Disability and Rehabilitation, 2014</td><td>*</td><td>NA</td><td>*</td><td>*</td><td>NA</td><td>*</td><td>*</td><td>NA</td></tr><tr><td>Karic, Journal of Neurosurgery, 2016</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td></tr><tr><td>Karic, Journal of Rehabilitation Medicine, 2016</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td></tr><tr><td>Moyer, 2017</td><td>*</td><td>NA</td><td>*</td><td>*</td><td>NA</td><td>*</td><td>*</td><td>NA</td></tr><tr><td>Okamura, 2021</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td></tr><tr><td>Olkowski, Physical Therapy, 2013</td><td>*</td><td>NA</td><td>*</td><td>*</td><td>NA</td><td>*</td><td>*</td><td>NA</td></tr><tr><td>Olkowski, Journal of Acute Care Physical Therapy, 2015</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td></tr><tr><td>Riordan, 2015</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td></tr><tr><td>Shimamura, 2014</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td></tr><tr><td>Uemura, 2018</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td></tr><tr><td>Yang, 2023</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td></tr><tr><td>Yokobatake, 2022</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td></tr><tr><td>Young, 2019</td><td>*</td><td>NA</td><td>*</td><td>*</td><td>NA</td><td>*</td><td>*</td><td>*</td></tr></tbody></table>

NA: not applicable.
<table><caption>**Table III.** Risk of bias assessment of case-control study</caption><thead><tr><th rowspan="3">Reference</th><th colspan="8">Case control</th></tr><tr><th colspan="4">Selection</th><th colspan="2">Comparability</th><th colspan="2">Exposure</th></tr><tr><th>Adequate<br>definition of<br>patient cases</th><th>Representativeness<br>of patient cases</th><th>Selection of<br>controls</th><th>Definition of<br>controls</th><th>Comparability<br>of cases and<br>controls</th><th>Ascertainment<br>of exposure</th><th>Same ascertainment<br>method for<br>participants</th><th>Non-<br>response<br>rate</th></tr></thead><tbody><tr><td>Takara, 2022</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td><td>*</td></tr></tbody></table>

vomiting, headache). Mobilization steps, frequency, duration, and intensity varied greatly across studies.

Mobilization involved physiotherapists in all studies, and most of the time occupational therapists and/or nurses. Two studies indicated that staff must be qualified and/or trained (22, 28), and 1 study specified that physiotherapists must have more than 3 years' experience in critical care (27).

In the cohort studies, case-control study, and randomized controlled trial, the mobilization modalities and timeframe defining the early mobilization group varied widely.

### Effects of early mobilization on physical function and physical performance tasks in patients with subarachnoid haemorrhage

Six out of 16 studies reported measures of physical function or physical performance tasks (13, 15, 18, 24, 28, 29). The timeframes and outcomes reported were diverse (Table V). Three studies reported functional status at ICU discharge assessed by modified Rankin Scale (mRS) score (13, 28, 29). Pooled analysis demonstrated a significant improvement in functional status favouring early mobilization (MD -1.39, 95% CI -2.51 to -0.28, I²=86%) (Fig. 3). Two studies reported 3 months functional status assessed by mRS score (13, 28). Pooled analysis demonstrated a significant improvement in functional status favouring early mobilization (MD -1.10, 95% CI -1.54 to -0.66, I²=7%) (Fig. 4).

### Effects of early mobilization on cognitive function in patients with subarachnoid haemorrhage

Three out of 16 studies reported measures of cognitive function (15, 24, 26). The outcomes and timeframes reported varied (Table VI). Meta-analysis could not be performed.

The RCT found a significant decrease in cognitive function in the early verticalization group at discharge and 1 month but no difference at 3 months using the MMSE score (26). One study found no difference in cognitive function at discharge using the cognitive FIM (15). The last study focused on elderly patients and reported that early ambulation was associated with a decrease in the rate of dementia at 1 month using the Revised-Hasegawa Dementia Scale (24).

### Effects of early mobilization on psychological status in patients with subarachnoid haemorrhage

Only the RCT reported psychological outcomes (26). Meta-analysis could not be performed.

A significant increase in depression rate in the early verticalization group was found at discharge, 1 month, and 3 months using the Zung scale for self-rating depression. A significant increase in anxiety rate was found at 1 month and 3 months using the Zung scale for self-rating anxiety. No between-group difference was found at discharge.

### Effects of early mobilization on neurological complications in patients with subarachnoid haemorrhage

**Cerebral vasospasm.** Eleven out of 16 studies assessed the impact of early mobilization on cerebral vasospasm occurrence. The studies either reported the total number of vasospasms (13, 21) and/or differentiated between symptomatic and asymptomatic vasospasms (19, 25, 27), only reported symptomatic vasospasms (16, 24, 28, 29), or did not specify (15, 26). Seven studies reported clinical or symptomatic vasospasms (16, 18, 24, 25, 27-29). In a pooled analysis, patients in the early mobilization group had a lower probability of presenting symptomatic vasospasm (OR 0.44, 95% CI 0.27 to 0.72, I²=8%) (Fig. 5). Five studies reported radiographic vasospasm (18, 21, 25, 27, 28). In a pooled analysis, patients in the early mobilization group had a lower probability of presenting radiographic vasospasm (OR 0.66, 95% CI 0.45 to 0.96, I²=7%) (Fig. 6).

**Delayed cerebral ischemia.** Two out of 16 studies assessed the impact of early mobilization on cerebral ischaemia rate. Pooled analysis demonstrated no significant difference between the 2 groups (OR 1.70, 95% CI 0.20 to 14.31, I²=91%) (Fig. 7).

**Hydrocephalus.** Four out of 16 studies assessed the impact of early mobilization on hydrocephalus rate, 3 of which were included in the meta-analysis. Pooled analysis demonstrated no significant difference between the 2 groups (OR 0.59, 95% CI 0.30 to 1.14, I²=0%) (Fig. 8).

**Rebleeding after aneurysm repair.** Three out of 16 studies assessed the impact of early mobilization on rebleeding occurrence (Table VII) (19, 28, 29). Due to
<table><caption>**Table V.** Effects of mobilization on physical function and physical performance tasks</caption><thead><tr><th rowspan="2">Study (year)</th><th rowspan="2">Outcome measure</th><th rowspan="2">Timepoint</th><th colspan="5">Mean ± standard deviation, median (IQR) or n (%)</th><th rowspan="2">Comments</th></tr><tr><th>Intervention</th><th>n</th><th>Comparator</th><th>n</th><th>p-value</th></tr></thead><tbody><tr><td>Okamura (2021)</td><td>AI</td><td>Discharge</td><td>1.9 ± 1.8</td><td>13</td><td>6.7 ± 2.5</td><td>22</td><td><strong>&lt;0.001</strong></td><td>Ambulatory index: 0 = Asymptomatic; Fully active; 9 = Restricted to wheelchair; unable to transfer self independently</td></tr><tr><td>Yokobatake (2022)</td><td>Barthel Index</td><td>Discharge</td><td>63 (14–100)</td><td>56</td><td>40 (5–70)</td><td>55</td><td><strong>0.03</strong></td><td>Barthel index: 0 = fully dependent; 100 = fully independent</td></tr><tr><td>Okamura (2021)</td><td>FAC</td><td>Discharge</td><td>4.2 ± 0.9</td><td>13</td><td>1.2 ± 1.5</td><td>22</td><td><strong>&lt;0.001</strong></td><td>Functional ambulation classification: 0 = absolute inability to walk even with external help; 5 = normal deambulation</td></tr><tr><td>Yokobatake (2022)</td><td>FAC</td><td>Discharge</td><td>3 (1–4)</td><td>56</td><td>2 (0–4)</td><td>55</td><td><strong>0.04</strong></td><td>Functional ambulation classification: 0 = absolute inability to walk even with external help; 5 = normal deambulation</td></tr><tr><td>Okamura (2021)</td><td>GOS</td><td>Discharge</td><td>4.5 ± 0.7</td><td>13</td><td>3.0 ± 0.6</td><td>22</td><td><strong>&lt;0.001</strong></td><td>GOS: 1 = dead; 5 = good recovery</td></tr><tr><td>Uemura (2018)</td><td>Motor FIM efficacy</td><td>Discharge</td><td>1.93 ± 1.13</td><td>22</td><td>0.73 ± 0.94</td><td>21</td><td><strong>&lt;0.001</strong></td><td>Motor FIM efficacy = discharge motor FIM – 4th day motor FIM</td></tr><tr><td>Okamura (2021)</td><td>mRS</td><td>Discharge</td><td>1.5 ± 1.4</td><td>13</td><td>4.1 ± 0.8</td><td>22</td><td><strong>&lt;0.001</strong></td><td>Modified Rankin Scale: 0 = fully independent; 6 = death</td></tr><tr><td>Yokobatake (2022)</td><td>mRS</td><td>Discharge</td><td>3 (1–4)</td><td>56</td><td>4 (2–5)</td><td>55</td><td><strong>0.02</strong></td><td>Modified Rankin Scale: 0 = fully independent; 6 = death</td></tr><tr><td>Foudhaili (2023)</td><td>mRS</td><td>Discharge</td><td>2 (1–3)</td><td>31</td><td>3 (1–4)</td><td>148</td><td><strong>0.007</strong></td><td>Modified Rankin Scale: 0 = fully independent; 6 = death</td></tr><tr><td>Shimamura (2014)</td><td>GOS: GOS > 3</td><td>30 days</td><td>23 (88%)</td><td>26</td><td>24 (53%)</td><td>45</td><td><strong>0.0036</strong></td><td>GOS: 1 = dead; 5 = good recovery</td></tr><tr><td>Yokobatake (2022)</td><td>Barthel Index</td><td>90 days</td><td>98 (40–100)</td><td>56</td><td>70 (5–100)</td><td>55</td><td><strong>0.048</strong></td><td>Barthel index: 0 = fully dependent; 100 = fully independent</td></tr><tr><td>Yokobatake (2022)</td><td>FAC</td><td>90 days</td><td>5 (2–5)</td><td>56</td><td>3 (1–5)</td><td>55</td><td><strong>0.03</strong></td><td>Functional ambulation classification: 0 = absolute inability to walk even with external help; 5 = normal deambulation</td></tr><tr><td>Foudhaili (2023)</td><td>mRS: mRS < 3</td><td>90 days</td><td>26 (84%)</td><td>31</td><td>83 (56%)</td><td>148</td><td><strong>0.004</strong></td><td>Modified Rankin Scale: 0 = fully independent; 6 = death</td></tr><tr><td>Yokobatake (2022)</td><td>mRS</td><td>90 days</td><td>2 (0–4)</td><td>56</td><td>3 (1–5)</td><td>55</td><td><strong>0.01</strong></td><td>Modified Rankin Scale: 0 = fully independent; 6 = death</td></tr><tr><td>Foudhaili (2023)</td><td>mRS</td><td>90 days</td><td>1 (0–2)</td><td>31</td><td>2 (1–4)</td><td>148</td><td><strong>0.004</strong></td><td>Modified Rankin Scale: 0 = fully independent; 6 = death</td></tr></tbody></table>

AI: ambulatory index; FAC: functional ambulation classification; FIM: functional independence measure; GOS: Glasgow outcome scale; mRS: modified Rankin Scale. Bold values mean statistical significance (p < 0.05).

the limited number of events in both groups, no meta-analysis was performed.

### Adverse events related to early mobilization

Six studies examined the safety of early mobilization (17, 19, 20, 22, 23, 27), of which 4 reported the number of mobilization sessions (20, 22, 23, 27). They included a total of 134 patients and 900 mobilization sessions with 24 reported safety events, for a cumulative incidence of 6% (Fig. 9).

Haemodynamic changes were the most reported type of safety event (n=21; 2.3%). They consisted of 11 hypotensive episodes (MAP < 70 mmHg, 2 without definition), 7 hypertensive episodes (MAP > 120 mm Hg), and 3 heart rate changes (1 HR > 130 bpm, 2 HR changes > 20%) (20, 22, 27). Two respiratory events (0.2%) and 1 neurologic change (0.1%) were reported (22). No fall was reported during the 900 mobilization sessions.

For the events that could not be meta-analysed, the number of events reported were: 9 non-invasive

<figure><img src="image_5.png" /></figure>

Heterogeneity: $\chi^2 = 14.16$ ($P < .001$), $I^2 = 86\%$

<figure><img src="image_6.png" /><figcaption>**Fig. 3.** Forest plot of effect of early mobilization on physical function at discharge. CI: confidence interval; MD: mean difference.</figcaption></figure>

Heterogeneity: $\chi^2 = 1.08$ ($P = .30$), $I^2 = 7\%$

<caption>**Fig. 4.** Forest plot of effect of early mobilization on physical function at 3 months.</caption>
<table><caption>**Table VI.** Effects of mobilization on cognitive function and performances</caption><thead><tr><th rowspan="2">Study (year)</th><th rowspan="2">Outcome measure</th><th rowspan="2">Timepoint</th><th colspan="5">Mean ± standard deviation, median (IQR) or n (%)</th><th rowspan="2">Comments</th></tr><tr><th>Intervention</th><th>n</th><th>Comparator</th><th>n</th><th>p-value</th></tr></thead><tbody><tr><td>Milovanovic (2016)</td><td>MMSE No cognitive problems: MMSE > 24</td><td>Discharge</td><td>14 (41.2%)</td><td>34</td><td>19 (61.3%)</td><td>31</td><td><strong>0.04</strong></td><td></td></tr><tr><td>Uemura (2018)</td><td>Cognitive FIM efficacy</td><td>Discharge</td><td>1.64 ± 1.25</td><td>22</td><td>0.46 ± 1.36</td><td>21</td><td>0.46</td><td>Cognitive FIM efficacy = discharge cognitive FIM 4th day cognitive FIM</td></tr><tr><td>Milovanovic (2016)</td><td>MMSE No cognitive problems: MMSE > = 24</td><td>30 days</td><td>22 (64.7%)</td><td>34</td><td>26 (83.9%)</td><td>31</td><td><strong>0.025</strong></td><td></td></tr><tr><td>Shimamura (2014)</td><td>Revised-Hasegawa Dementia Scale No dementia: HDS-R > 20</td><td>30 days</td><td>16 (61.5%)</td><td>26</td><td>11 (24.4%)</td><td>45</td><td><strong>0.019</strong></td><td>Highest HDS-R score is 30 and HDS-R threshold is 21. Three categories of dementia were established: severe (0-10), moderate (11-20), and normal (21-30)</td></tr><tr><td>Milovanovic (2016)</td><td>MMSE No cognitive problems: MMSE > 24</td><td>90 days</td><td>28 (82.4%)</td><td>34</td><td>28 (90.3%)</td><td>31</td><td>0.073</td><td></td></tr></tbody></table>

HDS-R: Hasegawa Dementia Scale; MMSE: Mini Mental State Examination. Bold values mean statistical significance (p < 0.05).

<figure><img src="image_7.png" /></figure>

Heterogeneity: $\chi_5^2 = 5.43$ (P = .37), $I^2 = 8\%$

**Fig. 5.** Forest plot of effect of early mobilization on clinical vasospasm.

<figure><img src="image_8.png" /></figure>

Heterogeneity: $\chi_4^2 = 4.32$ (P = .36), $I^2 = 7\%$

**Fig. 6.** Forest plot of effect of early mobilization on radiological vasospasm.

<figure><img src="image_9.png" /></figure>

Heterogeneity: $\chi_1^2 = 11.75$ (P < .001), $I^2 = 91\%$

**Fig. 7.** Forest plot of effect of early mobilization on cerebral ischaemia.

<figure><img src="image_10.png" /></figure>

Heterogeneity: $\chi_2^2 = 1.11$ (P = .57), $I^2 = 0\%$

**Fig. 8.** Forest plot of effect of early mobilization on hydrocephalus.
<table><caption>**Table VII.** Rebleeding events</caption><thead><tr><th>Study (year)</th><th>Intervention</th><th>n</th><th>Comparator</th><th>n</th><th>p-value</th></tr></thead><tbody><tr><td>Karic (2016), J Neurosurg</td><td>0 (0%)</td><td>94</td><td>0 (0%)</td><td>77</td><td><strong>&gt;0.05</strong></td></tr><tr><td>Okamura (2021)</td><td>0 (0%)</td><td>13</td><td>0 (0%)</td><td>22</td><td><strong>&gt;0.05</strong></td></tr><tr><td>Yokobatake (2022)</td><td>1 (2%)</td><td>56</td><td>0 (0%)</td><td>55</td><td><strong>&gt;0.05</strong></td></tr></tbody></table>

Bold values mean statistical significance ($p < 0.05$).

line removals, 4 invasive line removals, 4 increases in ICP, and 9 other events (pain, fatigue, headache, drain malfunction, tracheostomy tube out of midline, feeding tube unfasten). Regarding the ICP increase, 2 of the 4 events were reported as not being associated with a decrease in cerebral perfusion pressure below 60 mmHg (27). No details were given for the 2 remaining events (22, 23).

*Effects of early mobilization on health-related quality of life or well-being in patients with subarachnoid haemorrhage*

None of the included studies reported the impact of early mobilization on health-related quality of life or well-being.

DISCUSSION

In this systematic review and meta-analysis, we found that the implementation of early mobilization in patients with subarachnoid haemorrhage could be associated with better clinical outcomes including improved functional status assessed by mRS score at hospital discharge and at 3 months. Early mobilization was also associated with a decrease in both radiological and clinical vasospasm rates without changes in the rate of cerebral ischaemia. Adverse events occurred in 6% of mobilization sessions, the majority of which were minor haemodynamic changes. These results suggest that early mobilization could be associated with improved outcomes in SAH patients and should therefore be adequately tested in further interventional trials.

Early mobilization of intensive care patients is now widely recommended and integrated into the standard of care (30). It has shown numerous beneficial effects on physical and cognitive functions (31–33). However, results are sometimes discordant, with negative trials

and concerns over safety (34). Optimal timing and modalities have yet to be defined. In the case of brain-injured patients, the safety concerns are even greater and addressing the timing, intensity, and frequency of mobilization is crucial. Indeed, the results of the AVERT trial really called into question the very early mobilization in brain-injured patients (35). Early mobilization in SAH patients must balance the potential benefits of enhancing neuroplasticity and functional recovery with the risks of exacerbating vasospasm, delayed cerebral ischaemia, and increasing the ischaemic penumbra zone (36). However, the 2023 AHA/ASA recommendations called for the implementation of an early mobilization protocol for patients with SAH to improve functional outcome (8). The level of recommendation is moderate, and the modalities of mobilization were not specified (8). Practice surveys have shown that mobilization is highly heterogeneous, ranging from prolonged bed-rest to early ambulation, and limited by several safety concerns (13, 37, 38). In this review, the mobilization strategies were secured by investigators with daily verification of eligibility criteria for mobilization, monitoring of clinical and physiological parameters, and progressiveness. This is consistent with the assumption of Paton et al. that intensive, maximalist mobilization could generate a higher rate of adverse events than progressive mobilization (39).

In this review, adverse events were reported in 6% of mobilization sessions. In the general ICU population, 2 meta-analyses reported an adverse event rate of less than 3% (14, 39). It is difficult to compare these rates, due to the lack of clarity in the definition of adverse events in the present included studies. It can be assumed that more haemodynamic changes are expected in neurocritical patients, especially as they are often confined to bed for several days, favouring sympathetic system maladaptation and orthostatic intolerance (40, 41). However, the clinical impact of these changes

<figure><img src="image_11.png" /><figcaption>**Fig. 9.** Pooled incidence of adverse events related to mobilization.</figcaption></figure>
remains to be evaluated. The evaluation of adverse events in the context of early and increased mobilization is difficult; increasing mobilization will likely increase mobilization-related adverse events (42). Nevertheless, this must be weighed against the impact of mobilization on functional results and the multiple complications of bed rest, such as thromboembolic events, pressure sores, neuromuscular, respiratory, and cardiovascular complications (43).

Among the safety concerns reported in the aforementioned surveys – and therefore obstacles to mobilization – were the presence of vasospasm and the fear that mobilization would generate or promote it (37, 38, 44). Interestingly, the present review did not find any protocol contraindicating mobilization in the presence of asymptomatic vasospasm. Combined with the fact that early mobilization was associated with a reduction in the frequency of vasospasm, these results could help to overcome these barriers.

This meta-analysis is to our knowledge the first to suggest that early mobilization in patients with SAH is associated with lower rates of radiological and clinical vasospasm and improved functional status at discharge and at 3 months. Two systematic reviews examining the mobilization of patients with SAH were identified. The first, a Cochrane review, targeted randomized controlled trials including patients with unsecured aneurysms, and found no eligible studies (45). The second, published in 2023, by Morello et al. had inclusion criteria similar to those used in the present study (46). They found no difference in functional status assessed by mRS score at hospital discharge (46). The contrast between our results is potentially attributable to an error in the reporting of results from Foudhaili et al. showing improved functional status in the early mobilization group (13). Morello et al. showed a significant decrease in radiographic vasospasm rate, whereas no difference was found in clinical vasospasm. The difference in our results could stem from the inclusion by Morello et al. of the negative randomized controlled trial that we chose to exclude in the absence of a clear definition of vasospasm (26). They also studied adverse events, defined as mortality, pneumonia, and thrombosis rate, and did not find any between-group differences (46). Last, they showed a significant decrease in hospital length of stay, which suggests that early mobilization in SAH patients could have economic benefits (46).

## Limitations

The present review presents several limitations. As previously stated, the definition of early mobilization is still highly variable (47). In this review, studies were included if the intervention group had mobilization

occurring earlier than the comparator. Our meta-analysis focused on interventions initiated within the first 7 days after SAH onset. In the ICU general population, early mobilization is commonly defined as initiated within the first 72 h (48). It is therefore debatable whether these interventions can be described as early or not. However, it should be borne in mind that neurological populations may present additional characteristics that initially hinder mobilization, compared with the general population (49). Interestingly, the 9 studies that involved a mobilization protocol initiated mobilization within 24 h after ICU admission or aneurysm repair, similar to practices in the general ICU population (31, 32).

Regarding the quality of the included studies, our review included only 1 randomized controlled trial, with moderate risk of bias, and uncontrolled cohorts or historical control group trials with low to moderate risk of bias. Regarding the randomized controlled trial, in addition to the biases assessed by the Cochrane risk of bias tool, the statistical power and quality of the statistical analyses are questionable. In addition, unusual characteristics were found in their population, such as a high frequency of postoperative meningitis. The description of the medical management and mobilization procedure was also very succinct, and the latter did not seem to include any of the safety measures described above. This may have contributed to it being the only negative trial in this review. Hence, its contribution to the body of evidence should be interpreted cautiously. More generally, most trials had small sample sizes and were monocentric. There was also considerable heterogeneity in mobilization procedures, whether in terms of time to initiation, type of mobilization, or dosage. The AVERT results suggest that dosage and time to first mobilization play a crucial role in achieving favourable functional outcome (9). These parameters therefore need to be determined as part of future clinical trials and clearly described to ensure their reproducibility and enable their inclusion in future clinical guidelines. There was also significant heterogeneity in the judgement criteria used, which limited the number of studies included in each meta-analysis. The results of this meta-analysis should therefore be viewed with caution.

Last, we were not able to assess the effect of early mobilization on cognitive status and quality of life of patients with SAH due to a lack of data. Despite functional recovery, patients with SAH report cognitive impairment, anxiety, depression, activity limitations, and impaired quality of life (50, 51). The mRS score correlates poorly with these parameters (51). Future clinical trials should use appropriate scales to assess the impact of early mobilization on cognitive and psychological status and quality of life.
## Conclusion

This systematic review and meta-analysis found that the implementation of early mobilization in patients with subarachnoid haemorrhage was associated with better clinical outcomes including improved functional status and decreased rate of cerebral vasospasm. The rate of adverse events occurring during mobilization was around 6% in the early mobilization group, mainly mild events. These results suggest that early mobilization could be associated with improved outcomes in SAH patients and should therefore be adequately tested in interventional trials.

## ACKNOWLEDGEMENTS

The authors would like to thank Colin Sidre for his help in developing the research strategies.

**Funding/financial support:** This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Adela Foudhaili receives an institutional grant from Assistance Publique-Hôpitaux de Paris (AP-HP) for her PhD.

## REFERENCES

1. Lovelock CE, Rinkel GJE, Rothwell PM. Time trends in outcome of subarachnoid hemorrhage: population-based study and systematic review. Neurology 2010; 74: 1494-1501. https://doi.org/10.1212/WNL.0b013e3181dd42b3

2. Molyneux A, Kerr R. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomized trial. J Stroke Cerebrovasc Dis 2002; 11: 304-314. https://doi.org/10.1053/jscd.2002.130390

3. Kruisheer EM, Huenges Wajer IMC, Visser-Meily JMA, Post MWM. Course of participation after subarachnoid hemorrhage. J Stroke Cerebrovasc Dis 2017; 26: 1000-1006. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.11.124

4. Al-Khindi T, Macdonald RL, Schweizer TA. Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke 2010; 41: e519-e36. https://doi.org/10.1161/STROKEAHA.110.581975

5. Seule M, Oswald D, Muroi C, Brandi G, Keller E. Outcome, return to work and health-related costs after aneurysmal subarachnoid hemorrhage. Neurocrit Care 2020; 33: 49-57. https://doi.org/10.1007/s12028-019-00905-2

6. Passier PECA, Visser-Meily JMA, Rinkel GJE, Lindeman E, Post MWM. Life satisfaction and return to work after aneurysmal subarachnoid hemorrhage. J Stroke Cerebrovasc Dis 2011; 20: 324-329. https://doi.org/10.1016/j.jstrokecerebrovasdis.2010.02.001

7. Tang WK, Wang L, Tsoi KK, Kim JM, Lee S-J, Kim JS. Anxiety after subarachnoid hemorrhage: a systematic review and meta-analysis. J Affect Disord Rep 2021; 3: 100060. https://doi.org/10.1016/j.jadr.2020.100060

8. Hoh BL, Ko NU, Amin-Hanjani S, Hsiang-Yi Chou S, Cruz-Flores S, Dangayach NS, et al. 2023 Guideline for the management of patients with aneurysmal subarachnoid hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke 2023; 54: e314-e370. https://doi.org/10.1161/STR.000000000000436

9. Bernhardt J, Churilov L, Ellery F, Collier J, Chamberlain J, Langhorne P, et al. Prespecified dose-response analysis for A Very Early Rehabilitation Trial (AVERT). Neurology 2016; 86: 2138-2145. https://doi.org/10.1212/WNL.0000000000002459

10. Scheffenbichler FT, Teja B, Wongtangman K, Mazwi N, Waak K, Schaller SJ, et al. Effects of the level and duration of mobilization therapy in the surgical ICU on the loss of the ability to live independently: an international prospective cohort study. Crit Care Med 2021; 49: e247-e257. https://doi.org/10.1097/CCM.0000000000004808

11. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan: a web and mobile app for systematic reviews. Syst Rev 2016; 5: 210. https://doi.org/10.1186/s13643-016-0384-4

12. PlotDigitizer [Serial on the Internet]. Available from: https://plotdigitizer.com/

13. Foudhaili A, Barthélémy R, Collet M, De Roquetaillade C, Kerever S, Vitiello D, et al. Impact of early out-of-bed mobilization on functional outcome in patients with aneurysmal subarachnoid hemorrhage: a retrospective cohort study. World Neurosurg 2023; 175: e278-e287. https://doi.org/10.1016/j.wneu.2023.03.073

14. Nydahl P, Sricharoenchai T, Chandra S, Kundt FS, Huang M, Fischill M, et al. Safety of patient mobilization and rehabilitation in the intensive care unit: systematic review with meta-analysis. Ann Am Thorac Soc 2017; 14: 766-777. https://doi.org/10.1513/AnnalsATS.201611-843SR

15. Uemura M, Inoue T, Kuwata S, Yoshikawa Y, Matsumoto H, Hirata Y. Taking a sitting position within 13 days of subarachnoid hemorrhage onset prevents decline in the ability to perform activities of daily living and shortens hospitalization duration. Int J Disabil Hum Dev 2018; 17: 517-524.

16. Takara H, Kohatsu Y, Suzuki S, Satoh S, Abe Y, Miyazato S, et al. Initiating mobilization is not associated with symptomatic cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage: a retrospective multicenter case-control study. Phys Ther Res 2022; 25: 134-142. https://doi.org/10.1298/ptr.E10205

17. Karic T, Sorteberg A, Haug Nordenmark T, Becker F, Roe C. Early rehabilitation in patients with acute aneurysmal subarachnoid hemorrhage. Disabil Rehabil 2015; 37: 1446-1454. https://doi.org/10.3109/09638288.2014.966162

18. Karic T, Roe C, Nordenmark T, Becker F, Sorteberg A. Impact of early mobilization and rehabilitation on global functional outcome one year after aneurysmal subarachnoid hemorrhage. J Rehabil Med 2016; 48: 676-682. https://doi.org/10.2340/16501977-2121

19. Karic T, Røe C, Nordenmark TH, Becker F, Sorteberg W, Sorteberg A. Effect of early mobilization and rehabilitation on complications in aneurysmal subarachnoid hemorrhage. J Neurosurg 2017; 126: 518-526. https://doi.org/10.3171/2015.12.JNS151744

20. Olkowski BF, Devine MA, Slotnick LE, Veznedaroglu E, Liebman KM, Arcaro ML, et al. Safety and feasibility of an early mobilization program for patients with aneurysmal subarachnoid hemorrhage. Phys Ther 2013; 93: 208-215. https://doi.org/10.2522/ptj.20110334

21. Olkowski BF, Binning MJ, Sanfillippo G, Arcaro ML, Slotnick LE, Veznedaroglu E, et al. Early mobilization in aneurysmal subarachnoid hemorrhage accelerates recovery and reduces length of stay. J Acute Care Phys Ther 2015; 6: 47-55. https://doi.org/10.1097/JAT.0000000000000008

22. Moyer M, Young B, Wilensky EM, Borst J, Pino W, Hart M, et al. Implementation of an early mobility pathway in neurointensive care unit patients with external ventricular devices. J Neurosci Nurs 2017; 49: 102-107. https://doi.org/10.1097/JNN.0000000000000258

23. Young B, Moyer M, Pino W, Kung D, Zager E, Kumar MA. Safety and feasibility of early mobilization in patients with subarachnoid hemorrhage and external ventricular drain. Neurocrit Care 2019; 31: 88-96. https://doi.org/10.1007/s12028-019-00670-2

24. Shimamura N, Matsuda N, Satou J, Nakano T, Ohkuma H. Early ambulation produces favorable outcome and
nondemential state in aneurysmal subarachnoid hemorrhage patients older than 70 years of age. World Neurosurg 2014; 81: 330-334. https://doi.org/10.1016/j.wneu.2012.12.007

25. Riordan MA, Kyle M, Dedeo C, Villwock MR, Bauer M, Vallano ML, et al. Mild exercise reduces cerebral vasospasm after aneurysm subarachnoid hemorrhage: a retrospective clinical study and correlation with laboratory investigation. Acta Neurochir Suppl 2015; 120: 55-61. https://doi.org/10.1007/978-3-319-04981-6_10

26. Milovanovic A, Grujicic D, Bogosavljevic V, Jokovic M, Mujovic N, Petronic Markovic I. Efficacy of early rehabilitation after surgical repair of acute aneurysmal subarachnoid hemorrhage: outcomes after verticalization on day 2-5 versus day 12 post-bleeding. Turk Neurosurg 2016; 27: 867-873. https://doi.org/10.5137/1019-5149. JTN.17711-16.1

27. Yang X, Cao L, Zhang T, Qu X, Chen W, Cheng W, et al. More is less: effect of ICF-based early progressive mobilization on severe aneurysmal subarachnoid hemorrhage in the NICU. Front Neurol 2022; 13: 951071. https://doi.org/10.3389/fneur.2022.951071

28. Yokobatake K, Ohta T, Kitaoka H, Nishimura S, Kashima K, Yasuoka M, et al. Safety of early rehabilitation in patients with aneurysmal subarachnoid hemorrhage: a retrospective cohort study. J Stroke Cerebrovasc Dis 2022; 31: 106751. https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106751

29. Okamura M, Konishi M, Sagara A, Shimizu Y, Nakamura T. Impact of early mobilization on discharge disposition and functional status in patients with subarachnoid hemorrhage: a retrospective cohort study. Medicine (Baltimore) 2021; 100: e28171. https://doi.org/10.1097/MD.00000000000028171

30. Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med 2018; 46: e825. https://doi.org/10.1097/CCM.00000000000003299

31. Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009; 373: 1874-1882. https://doi.org/10.1016/S0140-6736(09)60658-9

32. Schaller SJ, Anstey M, Blobner M, Edrich T, Grabitz SD, Gradwohl-Matis I, et al. Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet 2016; 388: 1377-1388. https://doi.org/10.1016/S0140-6736(16)31637-3

33. Patel BK, Wolfe KS, Patel SB, Dugan KC, Esbrook CL, Pawlik AJ, et al. Effect of early mobilisation on long-term cognitive impairment in critical illness in the USA: a randomised controlled trial. Lancet Respir Med 2023; 11: 563-572. https://doi.org/10.1016/S2213-2600(22)00489-1

34. TEAM Study Investigators and the ANZICS Clinical Trials Group. Early active mobilization during mechanical ventilation in the ICU. N Engl J Med 2022; 387: 1747-1758. https://doi.org/10.1056/NEJMoa2209083

35. AVERT Trial Collaboration group. Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial. Lancet 2015; 386: 46-55. https://doi.org/10.1016/S0140-6736(15)60690-0

36. Marzolini S, Robertson AD, Oh P, Goodman JM, Corbett D, Du X, et al. Aerobic training and mobilization early post-stroke: cautions and considerations. Front Neurol 2019; 10: 1187. https://doi.org/10.3389/fneur.2019.01187

37. Hernandez, Sabrina, Thomas P, Udy A, Hodgson C. Early mobilisation of patients in the acute hospital setting following aneurysmal subarachnoid haemorrhage: a survey of current physiotherapy practice. N Z J Physiother 2019; 46: 113-132. https://doi.org/10.15619/NZJP/46.3.04

38. Hossain I, Younsi A, Castaño Leon AM, Lippa L, Tóth P, Terpolilli N, et al. Huge variability in restrictions of mobilization for patients with aneurysmal subarachnoid hemorrhage: a European survey of practice. Brain Spine 2023; 3: 101731. https://doi.org/10.1016/j.bas.2023.101731

39. Paton M, Chan S, Serpa Neto A, Tipping CJ, Stratton A, Lane R, et al. Association of active mobilisation variables with adverse events and mortality in patients requiring mechanical ventilation in the intensive care unit: a systematic review and meta-analysis. Lancet Respir Med 2024; 12: 386-398. https://doi.org/10.1016/S2213-2600(24)00011-0

40. Topp R, Ditmyer M, King K, Doherty K, Hornyk J. The effect of bed rest and potential of prehabilitation on patients in the intensive care unit. AACN Clin Issues 2002; 13: 263-276. https://doi.org/10.1097/00044067-200205000-00011

41. Parry SM, Puthucheary ZA. The impact of extended bed rest on the musculoskeletal system in the critical care environment. Extreme Physiol Med 2015; 4: 16. https://doi.org/10.1186/s13728-015-0036-7

42. Eggmann S, Nydahl P, Gosselink R, Bissett B. We need to talk about adverse events during physical rehabilitation in critical care trials. eClinicalMedicine 2024; 68: 102439. https://doi.org/10.1016/j.eclinm.2024.102439

43. Brower RG. Consequences of bed rest. Crit Care Med 2009; 37: S422-S428. https://doi.org/10.1097/CCM.0b013e3181b6e30a

44. Foudhaili A, Vitiello D, Chousterman BG. Early mobilization of patients with subarachnoid haemorrhage: a national survey of French intensive care units. J Rehabil Med 2024; 56: jrm17734. https://doi.org/10.2340/jrm.v56.17734

45. Ma Z, Wang Q, Liu M. Early versus delayed mobilisation for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2013: CD008346. https://doi.org/10.1002/14651858.CD008346.pub2

46. Morello A, Spinello A, Staartjes VE, Bue EL, Garbossa D, Germans MR, et al. Early versus delayed mobilization after aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of efficacy and safety. Neurosurg Focus 2023; 55: E11.

47. Clarissa C, Salisbury L, Rodgers S, Kean S. Early mobilisation in mechanically ventilated patients: a systematic integrative review of definitions and activities. J Intensive Care 2019; 7: 3. https://doi.org/10.1186/s40560-018-0355-z

48. Bein Th, Bischoff M, Brückner U, Gebhardt K, Henzler D, Hermes C, et al. S2e guideline: positioning and early mobilisation in prophylaxis or therapy of pulmonary disorders. Anaesthesist 2015; 64: 1-26. https://doi.org/10.1007/s00101-015-0071-1

49. Hodgson CL, Stiller K, Needham DM, Tipping CJ, Harrold M, Baldwin CE, et al. Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults. Crit Care 2014; 18: 658. https://doi.org/10.1186/s13054-014-0658-y

50. Custal C, Koehn J, Borutta M, Krochen A, Brandner S, Eyüpoglu IY, et al. Beyond functional impairment: redefining favorable outcome in patients with subarachnoid hemorrhage. Cerebrovasc Dis 2021; 50: 729-737. https://doi.org/10.1159/000517242

51. Kim DH, Haney CL, Van Ginhoven G. Utility of outcome measures after treatment for intracranial aneurysms: a prospective trial involving 520 patients. Stroke 2005; 36: 792-796. https://doi.org/10.1161/01.STR.0000157594.58180.97