Passive Lower Extremity Cycling to Combat ICU Acquired Weakness An Evidence Based Analysis

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1 University of New Mexico UNM Digital Repository Doctor of Physical Therapy Capstones Spring Passive Lower Extremity Cycling to Combat ICU Acquired Weakness An Evidence Based Analysis Summer B. Shelley University of New Mexico, Follow this and additional works at: Recommended Citation Shelley, Summer B.. "Passive Lower Extremity Cycling to Combat ICU Acquired Weakness An Evidence Based Analysis." (2017). This Capstone is brought to you for free and open access by UNM Digital Repository. It has been accepted for inclusion in Doctor of Physical Therapy Capstones by an authorized administrator of UNM Digital Repository. For more information, please contact

2 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness An Evidence Based Analysis By: Summer Shelley Doctoral Candidate University of New Mexico School of Medicine Division of Physical Therapy Class of 2017 Advisor: Tiffany Enache, PT, DPT Approved by the Division of Physical Therapy, School of Medicine, University of New Mexico in partial fulfillment of the requirements for the degree of Doctor of Physical Therapy

3 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 2 Table of Contents Abstract SECTION 1: Background and Purpose of PICO Question.4 SECTION 2: Case Description....7 SECTION 3: Evidence Based Analysis...9 Search Methodology....9 Systematic Literature Review Process...10 Articles Included for Analysis...14 Article Summaries Articles Analyzed Summary Article Analysis Worksheets Discussion.. 69 Conclusion.72 References.. 74

4 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 3 Abstract Background: Patients who are critically ill face severe muscle weakness and physical deconditioning due to prolonged immobility during their stay in the hospital, specifically in the intensive care unit (ICU). This impairment is commonly termed ICU acquired weakness (ICUAW) and subsequently leads to disability and prolonged rehabilitation after discharge from the ICU. Recent studies have found early physical therapy intervention for patients can be beneficial in attenuating decrease in function frequently associated with ICU admission. Purpose: The first purpose of this project is to present a case study of an individual who experienced significant decreases in strength and physical function while critically ill and bedridden in a hospital ICU. The second purpose of this project is to investigate a physical therapy intervention that could potentially address this patient s impairments by analyzing evidence based literature regarding the following PICO question: In patients who are critically ill and receiving mechanical ventilation, is passive lower extremity cycling more effective at attenuating ICUAW as compared to standard passive range of motion? Case Description: The patient was a 61-year-old female admitted to the ICU with acute respiratory distress syndrome and past medical history significant for chronic kidney disease, diabetes, morbid obesity and hypertension. Initially, this patient was placed in a RotoProne to provide prone ventilation for improved oxygenation. After returning to supine positioning and extubation, the patient presented to physical therapy moderately sedated, with a tracheostomy for mechanical ventilation and impaired bilateral upper extremity and lower extremity strength, all of which affected her gross mobility. Outcomes: Over the course of her six-week stay in the medical/surgical ICU, this patient demonstrated gradual improvements in strength and ability to participate in mobility tasks as compared to her status when initially evaluated by physical therapy. Goals set by the student physical therapist to be achieved within two weeks were met, however, the patient s progress was slow and she regressed after her initial success with therapy. Thus, this patient did not progress to participation in weight bearing mobilization activities. With minimal progress in function, this patient was discharged from the medical/surgical ICU and transferred to the cardio/respiratory ICU where her care was continued by physical therapists overseeing this floor. Discussion: This case presentation describes a patient admitted to the ICU with acute respiratory distress syndrome and receiving mechanical ventilation to maintain sufficient oxygen perfusion. The purpose of this evidence-based literature analysis was to investigate whether this patient would have benefitted from passive cycle ergometry to maintain the muscle integrity and range of motion necessary for higher functional mobility skills once the patient achieved medical stability. Recent studies have looked at the potential benefits of early mobility for patients who are critically ill. Within the realm of early mobility, several studies investigated the feasibility of passive lower extremity cycle ergometry as an intervention for patients who are unable to participate in active mobility activities. Few adverse events have been associated with this intervention demonstrating its safety, however, results regarding the efficacy of lower extremity cycle ergometry in attenuating ICUAW are few and inconclusive, necessitating further investigation.

5 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 4 SECTION 1: Background and Purpose of PICO Question Intensive care unit acquired weakness (ICUAW) is weakness that occurs in patients after admission to the intensive care unit (ICU), with no plausible cause other than the multi-factorial processes involved in critical illness. The initial presentation is typically flaccid weakness particularly in prominent lower extremities and proximal hip and shoulder girdles as well as sensory impairment in some patients 1. Reviews of the effect of inactivity on muscle strength have noted that skeletal muscle strength may decline by 1% to 1.5% per day of strict bed rest 2. Approximately 50% of adults in the ICU who receive prolonged mechanical ventilation and have multi-organ failure or sepsis develop ICUAW, affecting women four times more frequently than men 1. In the majority of cases of critical illness, passive range of motion is the only feasible type of exercise to perform with patients who are deeply sedated and mechanically ventilated. It is a technique that is widely used by physical therapists in the treatment of patients in the ICU, although there is controversial data supporting its benefits 2. Passive range of motion can be defined as a repeated movement of a patient s joint within its normal range without the patient s use of the involved extremity 3. Theoretically, passive range of motion is used to maintain range of movement, decrease synovial fluid stasis by producing fluctuations in intra-articular pressure, prevent contractures and promote function 2. Synovial fluid provides nutrition to the joint and movement of synovial fluid within the joint space depends upon active or passive movement of the joint 2. Joint immobility leads to stasis of the synovial fluid, which can cause increased intraarticular fluid volume and pressure, leading to an increase in pain and decreased joint range of motion 2.

6 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 5 Early mobility has been shown to lead to improvements in physical function and decreased delirium in patients who are critically ill, whether it be passive or active mobility 4. There is often a delay in the commencement of therapy due to the inability of patients to participate due to sedation or delirium. Consequently, there is increased interest in the use of assistive technology to aid early rehabilitation without the need for volitional patient engagement 5. A cycle ergometer is a stationary cycling apparatus with a mechanism that can alter the work done by the person who is exercising. With bedside cycle ergometers, patients can participate in exercise passively, active-assisted, or actively with varying degrees of resistance. Because the cycle ergometer can be a completely passive intervention, its use may be feasible for patients who are sedated or immobile, and those who cannot tolerate out-of-bed activities such as standing, transferring to a chair, or walking 6. Passive cycling has also been researched regarding its effectiveness in the rehabilitation of persons who have suffered a neurological insult such as a stroke or spinal cord injury. Research has shown passive cycling and passive cycling with functional electrical stimulation to be beneficial in accelerating recovery of motor function in patients who have hemiparesis 7. One study looked at the efficacy of passive cycling as a potential neurorehabilitative intervention for patients with spinal cord injuries who are too weak or medically unstable to repeatedly practice active movements. The study found that passive cycling elicited sensory inputs to activate cortical structures and induce cortical plasticity changes, leading to improved lower limb motor performance 8. Common early mobility activities that are implemented to reduce ICUAW include bed mobility such as rolling and supine to sit transitioning, edge of bed sitting, standing, and eventually, walking. However, patients who are critically ill, such as the patient presented in this case study, are often unable to follow commands and actively participate in mobilization, making

7 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 6 them unsuitable for the aforementioned activities and more appropriate for passive mobilization. A study investigating the benefits of early mobilization in the critically ill population found that patients who are sedated and unresponsive may still benefit from passive activities such as sitting in a sling hoist chair or tilt table 9. These activities potentially minimize orthostatic intolerance, which can occur after just 24 hours of bed rest 9. However, these interventions require several medical personnel to perform, require out of bed maneuvering of the patient which is not always possible, and the required instruments may not be readily available in many hospitals. Hence, the utilization of a bedside cycle ergometer to provide passive motion of the lower extremities is a potential technology whose efficacy in attenuating ICUAW should be investigated. The patient that is the inspiration for the investigation of this PICO question was a morbidly obese 61-year-old female admitted to the medical/surgical ICU with a diagnosis of acute respiratory distress syndrome. This patient was not medically stable or sufficiently alert to attempt early mobilization activities such as supine active exercises or sitting on the edge of the bed, which are typically the first mobility techniques physical therapists attempt with patients who are critically. Thus, the need arose for an intervention that could be performed with few medical personnel and with a patient that was unable to consistently follow single step commands or initiate muscle contractions greater than trace. Therefore, the interest in the following PICO question presented itself: In patients who are critically ill and receiving mechanical ventilation, is passive lower extremity cycling more effective at attenuating ICUAW as compared to standard passive range of motion?

8 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 7 SECTION 2: Case Description The patient that inspired the investigation of passive lower extremity cycle ergometry as an early mobilization technique was a morbidly obese 61-year-old female admitted to the medical/surgical ICU with a diagnosis of acute respiratory distress syndrome. She presented for an initial physical therapy evaluation under moderate sedation and having been extubated earlier that day. At the time of evaluation, the patient had a tracheostomy and was receiving positive pressure support of 9 cmh2o and 60% fraction of inspired oxygen from the mechanical ventilator. Prior to this, the patient had been in a RotoProne bed for six days to decrease her work of breathing and increase whole body oxygenation during the acute phase of her illness. The patient s daughter was present at the bedside during the physical therapy evaluation and reported that prior to this hospital admission, the patient was living alone and was independent with activities of daily living and functional mobility tasks. The physical therapist determined that the patient had impaired cognition most likely due to her current level of sedation as well as delirium associated with her illness, was able to follow single step commands less than 50% of the time, and was unable to produce muscle contractions greater than 1/5 on a manual muscle testing scale. The patient was not medically stable or sufficiently alert to attempt early mobilization activities such as supine active exercises or sitting on the edge of the bed, which are typically the first mobility techniques physical therapists attempt with patients who are critically ill. Nevertheless, physical therapists were faced with the task of increasing this patient s strength, balance and functional mobility. In this particular hospital setting, the physical therapist and student physical therapist seeing this patient were also overseeing the therapy provided to 44 other medical/surgical ICU patients and 15 patients on the medical/surgical floor. Because of

9 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 8 large patient loads such as this in level one trauma hospitals, lower potential patients are often provided less time and personnel-intensive interventions such as passive range of motion, dependent rolling in bed, and positioning in bed. Thus, the need arose for an intervention that could be performed with few medical personnel and a patient that is unable to consistently follow single step commands or initiate muscle contractions greater than 1/5. Therefore, the interest in the following PICO question presented itself: In patients who are critically ill and receiving mechanical ventilation, is passive lower extremity cycling more effective at attenuating ICUAW as compared to standard passive range of motion?

10 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 9 SECTION 3: Evidence Based Analysis Search Methodology: The following search methodology was performed to answer the following PICO question: In patients who are critically ill and receiving mechanical ventilation, is passive lower extremity cycling more effective at attenuating ICUAW as compared to standard passive range of motion? The databases searched included PubMed, PEDro, Cochrane Library, and Web of Science. Search terms were identical for each database and included the terms: critical illness AND cycle ergometry, critical illness AND passive cycling, critical illness AND cycling, mechanical ventilation AND cycle ergometry, mechanical ventilation AND passive cycling, mechanical ventilation AND cycling, intensive care unit AND cycle ergometry, intensive care unit AND passive cycling, and intensive care unit AND cycling. See Table 3 beginning on the next page for database search details as well as articles included and excluded from evidence based analysis.

11 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 10 Systematic Literature Review Process: Search Terms critical illness AND cycle ergometry Number of Articles Excluded PubMed (modifiers: past 10 years, humans and full text) 14 2 were protocols for future studies, 10 did not address PICO question. Included 1 potential articles for analysis: Feasibility and safety of in-bed cycling for physical rehabilitation in the intensive care unit 1 potential reference article: Technology to enhance physical rehabilitation of critically ill patients. critical illness AND passive cycling critical illness AND cycling mechanical ventilation AND cycle ergometry mechanical ventilation AND passive cycling mechanical ventilation AND cycling 3 1 did not address PICO question 25 1 was a protocol for a future study, 20 did not address PICO question, 3 articles had been identified in prior search 31 2 were protocols for a future study, 28 did not address PICO question, 1 article had been identified in prior search 3 2 did not address PICO question, 1 article had been identified in prior search 83 1 was a protocol for a future study, 80 did not address PICO question, 2 articles had been identified in prior search 2 potential articles for analysis: (1) Very early passive cycling exercise in mechanically ventilated critically ill patients: physiological and safety aspects--a case series, (2) Early exercise in critically ill patients enhances short-term functional recovery. 1 potential article for analysis: Functional electrical stimulation with cycling in the critically ill: a pilot casematched control study. 0 potential articles 0 potential articles 0 potential articles

12 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 11 intensive care unit AND cycle ergometry intensive care unit AND passive cycling intensive care unit AND cycling critical illness AND cycle ergometry critical illness AND passive cycling critical illness AND cycling mechanical ventilation AND cycle ergometry mechanical ventilation AND passive cycling mechanical ventilation AND cycling intensive care unit AND cycle ergometry intensive care unit AND 9 1 was a protocol for a future study, 5 did not address PICO question, 3 articles had been identified in prior search 2 1 did not address PICO question, 1 article had been identified in prior search did not address PICO question, 2 articles had been identified in prior search 0 potential articles 0 potential articles 1 potential article: Early ambulation using a cycle ergometer on quadriceps muscle morphology in mechanically ventilated critically ILL patients in the intensive care unit: a randomized controlled trial PEDro potential article for analysis: Physical rehabilitation interventions for adult patients during critical illness: an overview of systematic reviews potential articles potential articles potential article for analysis: Motor physical therapy in hospitalized patients in an intensive care unit: a systematic review potential articles 1 1 did not address PICO question 2 2 had been identified in prior search 1 1 article had been identified in prior search 0 potential articles 0 potential articles 0 potential articles

13 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 12 passive cycling intensive care unit AND cycling critical illness AND cycle ergometry critical illness AND passive cycling critical illness AND cycling mechanical ventilation AND cycle ergometry mechanical ventilation AND passive cycling mechanical ventilation AND cycling intensive care unit AND cycle ergometry intensive care unit AND passive cycling intensive care unit AND cycling 1 1 article had been identified in prior search Cochrane Library 1 1 did not address PICO question 6 5 did not address PICO question did not address PICO question 2 2 did not address PICO question 9 8 did not address PICO question, 1 article had been identified in prior search did not address PICO question, 1 article had been identified in prior search 1 1 did not address PICO question 8 7 did not address PICO question, 1 article had been identified in prior search did not address PICO question, 1 article had been identified in prior search Web of Science (modifier: past 10 years) 0 potential articles 0 potential articles 1 potential reference article: Interventions for preventing critical illness polyneuropathy and critical illness myopathy 1 potential article for analysis: Physical rehabilitation for critical illness myopathy and neuropathy (not selected as study regarded active ergometry) 0 potential articles 0 potential articles 0 potential articles 0 potential articles 0 potential articles 1 potential reference article: Early intervention (mobilization or active exercise) for critically ill patients in the intensive care unit

14 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 13 critical illness AND cycle ergometry critical illness AND passive cycling critical illness AND cycling mechanical ventilation AND cycle ergometry mechanical ventilation AND passive cycling mechanical ventilation AND cycling intensive care unit AND cycle ergometry intensive care unit AND passive cycling intensive care unit AND cycling 10 2 was a protocol for a future study, 4 did not address PICO question, 3 articles had been identified in prior search 6 1 was a protocol for a future study, 2 did not address PICO question, 3 articles had been identified in prior search 1 potential article for analysis: Characterization of the use of a cycle ergometer to assist in the physical therapy treatment of critically ill patients (not selected as study regarded active ergometry) 0 potential articles 317 Too many results 0 potential articles 17 2 were protocols for a future study, 14 did not address PICO question, 1 articles had been identified in prior search 33 1 was a protocol for a future study, 29 did not address PICO question, 2 articles had been identified in prior search 0 potential articles 1 potential article for analysis: Hemodynamic and metabolic effects of passive leg movement in mechanically ventilated patients. 1,092 Too many results 0 potential articles 11 2 was a protocol for a future study, 5 did not address PICO question, 4 articles had been identified in prior search 11 1 was a protocol for a future study, 6 did not address PICO question, 3 articles had been identified in prior search 0 potential articles 1 potential article for analysis: Sparing of muscle mass and function by passive loading in an experimental intensive care unit model (not selected due to unilateral passive loading) 855 Too many results 0 potential articles

15 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 14 Articles Included for Analysis: 1. Pires-Neto et al (2013) 2. Parry et al (2014) 3. Kho et al (2015) 4. Burtin et al (2009) 5. Connolly et al (2016) 6. Savi et al (2010) 7. Santos et al (2015) 8. Pinheiro et al (2012)

16 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 15 Article Summaries Reference #1: Pires-Neto CR, Kawaguchi FY, Hirota SA, et al. Very Early Passive Cycling Exercise in Mechanically Ventilated Critically Ill Patients: Physiological and Safety Aspects - A Case Series. Plos ONE Journal. 2013;8(9):e Oxford Level of Evidence: 2c Pedro Score: 3/10 Purpose: Research has shown that application of early mobilization in patients who are critically ill can improve patient outcomes. Research has also shown that a daily cycling exercise started day five after ICU admission is feasible and can enhance functional capacity after hospital discharge. In this study, researchers verified the physiological changes and safety of an earlier cycling intervention (< 72 hours of mechanical ventilation) in patients who are critically ill. Methods: 19 hemodynamically stable and deeply sedated patients were enrolled in a single 20- minute passive leg cycling exercise using an electric cycle ergometer within the first 72 hours of mechanical ventilation. A minute-by-minute evaluation of hemodynamic, respiratory and metabolic variables was undertaken before, during and after the exercise. Analyzed variables included the following: cardiac output, systemic vascular resistance, central venous blood oxygen saturation, respiratory rate and tidal volume, oxygen consumption, carbon dioxide production and blood lactate levels. Results: There were no clinically relevant changes in any of the analyzed variables during the exercise, and two minor adverse events unrelated to hemodynamic instability were observed. Bottom Line: This very early (< 72 hours after ICU admission and initiation of mechanical ventilation) passive cycling exercise in patients who were sedated, critically ill, and mechanically ventilated was considered safe and was not associated with significant alterations in hemodynamic, respiratory or metabolic variables, indicating that passive cycling does not present a hazard to patient health when implemented.

17 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 16 Reference #2: Parry S, Berney S, Warrillow S, et al. Functional electrical stimulation with cycling in the critically ill: A pilot case-matched control study. Journal of Critical Care. 2014;29(4):695.e1-695.e7. Oxford Level of Evidence: 2b Pedro Score: 5/10 Purpose: To determine the safety and feasibility of functional electrical stimulation (FES)- cycling in patients who are critically ill. Also, to compare subjects in the intervention group to case-matched controls in order to determine the impact of FES-cycling on functional recovery and delirium by assessing awakening, time to reach functional milestones, and incidence and duration of delirium. Methods: This study identified 16 adult patients in the ICU with sepsis, ventilated for > 48 hours and in the ICU for at least four days were included. Eight subjects underwent FES-cycling in addition to usual care physical therapy and were compared to eight case-matched control individuals. The case-matched controls were identified retrospectively to match the demographics of the subjects in the intervention group. Results: One minor adverse event was recorded. 69 out of total possible 95 FES sessions (73%) were completed. A visible or palpable contraction was present 80% of the time. There was an improvement in physical function in ICU test score of 3.9/10 points in the intervention cohort with faster recovery of functional milestones when compared to patients in the case-matched control group. This study also found a shorter duration of delirium in the intervention cohort compared to their case-matched control. Bottom Line: The delivery of FES-cycling is safe and feasible. The preliminary findings suggest that FES-cycling may improve function and reduce delirium. This study found benefits regarding functional mobility recovery, however, further research is required to confirm the efficacy of FES-cycling for its use with patients who are critically ill.

18 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 17 Reference #3: Kho M, Martin R, Toonstra A, et al. Feasibility and safety of in-bed cycling for physical rehabilitation in the intensive care unit. Journal of Critical Care. 2015;30(6):1419.e e5. Oxford Level of Evidence: 2b Pedro Score: 5/10 Purpose: With a projected increase in the number of patients who are critically ill requiring rehabilitation and a concurrent projected decrease in the number of physical therapists available to provide care, effective and efficient rehabilitation interventions are needed. The purpose of this study was to evaluate the feasibility and safety of in-bed cycle ergometry as part of routine ICU physical therapy practice. Methods: Over the course of six months, this study prospectively identified all patients admitted to a 16-bed medical ICU receiving cycling by a physical therapist, prospectively collected data on 12 different potential safety events, and retrospectively conducted a chart review to obtain specific details of each cycling session. Results: 688 patients received physical therapy interventions and 181 (26%) received a total of 541 cycling sessions. The mean age was 57 (+/- 17) years, and 103 (57%) were male. The median time from medical ICU admission to first physical therapy intervention and first cycling session was 2 and 4 days, respectively, with a median cycling session duration of 25 minutes. On cycling days, the proportion of patients receiving mechanical ventilation, vasopressor infusions, and continuous renal replacement therapy was 80%, 8%, and 7%, respectively. Bottom Line: Time to physical therapy intervention in the ICU is longer for patients with higher versus lower severity of illness and organ failure scores. Use of in-bed cycling as part of routine physical therapy interventions for patients in the ICU is feasible and appears safe. The optimal timing for the initiation of passive cycle ergometry and indications for its use are not yet known. Further study of the potential benefits of early in-bed cycling is needed.

19 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 18 Reference #4: Burtin C, Clerckx B, Robbeets C, et al. Early exercise in critically ill patients enhances short-term functional recovery. Critical Care Medicine Journal. 2009;37(9): Oxford Level of Evidence: 1b PEDro Score: 4/10 Purpose: A prolonged stay in the ICU is associated with muscle dysfunction, which may contribute to impaired functional status up to one year after hospital discharge. The purpose of this study was to investigate whether a daily exercise session using a bedside cycle ergometer is a safe and effective intervention in attenuating the decrease in exercise capacity, functional status, and quadriceps force associated with prolonged ICU stays. Methods: 90 patients with critical illness were included in this randomized controlled trial as soon as their cardiorespiratory condition allowed bedside cycling exercise (starting from day 5). Control and intervention groups received respiratory physiotherapy and a daily standardized passive or active motion session of upper and lower limbs. In addition, the treatment group performed a passive or active exercise training session for 20 minutes per day using a bedside ergometer. Results: At ICU discharge, quadriceps force and functional status were not different between groups. At hospital discharge, 6-minute walking distance, isometric quadriceps force, and the subjective feeling of functional well-being (as measured with Physical Functioning item of the Short Form 36 Health Survey questionnaire) were significantly higher in the treatment group (p <.05). Bottom Line: Early exercise training, such as passive cycle ergometry, for patients who are critically ill demonstrated enhanced recovery of functional exercise capacity, self-perceived functional status, and muscle force at hospital discharge.

20 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 19 Reference #5: Connolly B, O Neill B, Salisbury L, et al. Physical rehabilitation interventions for adult patients during critical illness: an overview of systematic reviews. Thorax Journal. 2016;71: Oxford Level of Evidence: 2a Pedro Score: N/A Purpose: Physical rehabilitation interventions aim to ameliorate the effects of critical illnessassociated muscle dysfunction for individuals who survive the illness. This article conducted an overview of systematic reviews evaluating the effect of these interventions across the continuum of recovery. Methods: Six electronic databases (Cochrane Library, CENTRAL, DARE, Medline, Embase, and Cinahl) were searched. Two review authors independently screened articles for eligibility and conducted data extraction and quality appraisal. Reporting quality was assessed and the Grading of Recommendations Assessment, Development and Evaluation approach applied to summarize overall quality of evidence. Results: Five eligible systematic reviews were included in this overview. Reporting quality of the reviews was judged as medium to high. Two reviews reported the beneficial effects of physical therapy commencing during ICU admission in improving critical illness polyneuropathy/myopathy, quality of life, mortality and healthcare utilization. These interventions included early mobilization, cycle ergometry and electrical muscle stimulation. Two reviews reported beneficial effects of electrical muscle stimulation delivered in the ICU for improving muscle strength, muscle structure and critical illness polyneuropathy/myopathy. One review reported insufficient evidence of the benefits of physical rehabilitation post-icu. Bottom Line: Patients derive short-term benefits from physical rehabilitation delivered during ICU admission, but there is insufficient evidence of effects from interventions delivered post- ICU discharge.

21 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 20 Reference #6: Savi A, Maia CP, Dias AS, et al. Hemodynamic and metabolic effects of passive leg movement in mechanically ventilated patients. Revista Brasileria De Terapia Intensiva. 2010;22(4): Oxford Level of Evidence: 2c PEDro Score: 4/10 Purpose: Limb movements, passively performed by a physiotherapist, have been shown to result in significant increases in metabolic and hemodynamic variables in patients who are critically ill. The objective of this study was to determine whether passive cycling leg movement increases hemodynamic and metabolic variables in patients who are sedated and dependent on mechanical ventilation. Methods: Five patients who were sedated and dependent on mechanical ventilation in an 18-bed intensive care unit of a university hospital were evaluated. Passive cycling leg movements were performed for 10 minutes at a rate of 30 movements per minute. Complete hemodynamic data were recorded and arterial and mixed venous blood sample were collected five minutes before and after five minutes after the maneuver completion. Results: All patients had increased oxygen consumption (VO2). The VO2 increase occurred with a concomitant drop in mixed venous blood saturation (SvO2), likely from both oxygen extraction ratio and cardiac index increase. Bottom Line: Passive cycling leg movements may influence hemodynamic and metabolic status in patients who are sedated and dependent on mechanical ventilation. This study identified an SvO2 drop in the sample population. SvO2 is a clinical marker of systemic oxygen use, and its measurement is part of the monitoring routine for patients who are critically ill. The O2 demand increase during passive cycling leg movement shows that this intervention is able to increase the oxygen consumptions in sedated, mechanically ventilated patients. This can be interpreted to mean that passive cycling produces an exercise-like response due to increased muscular activity.

22 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 21 Reference #7: Santos LJ, Lemos F A, Bianchi T, et al. Early ambulation using a cycle ergometer on quadriceps muscle morphology in mechanically ventilated critically ILL patients in the intensive care unit: a randomized controlled trial. Intensive Care Medicine Experimental. 2015;3(Suppl 1):A551. Oxford Level of Evidence: 1b Pedro Score: 7/10 Purpose: To evaluate and compare the effects of early ambulation using a bedside cycle ergometer with conventional physical therapy on the thickness and architecture of the quadriceps muscle in patients who are and receiving invasive mechanical ventilation. Methods: Single-blind randomized controlled trial was conducted in a hospital ICU. 42 patients receiving mechanical ventilation for 24 to 48 hours who were hospitalized for no longer than one week and had no restriction of lower limb movements. After randomization, passive cycling exercise for the lower extremities was performed once daily for 20 minutes, at 20 revolutions per minute, until extubation or day 7 of the protocol plus conventional physical therapy in the intervention group. Bronchial hygiene maneuvers and passive exercises for the upper and lower extremities were performed twice daily for 30 minutes in both groups. Results: 32 patients were included in the final analysis. The intervention group showed no difference in the cross-sectional thickness of the quadriceps muscle or in the vastus lateralis fascicle length, pennation angle and muscle thickness as assessed by ultrasound before and after the protocol. Bottom Line: There was preservation of muscle thickness and architecture in the acute phase of ICU stay. However, the addition of exercise using a cycle ergometer to conventional physical therapy did not change the outcomes analyzed.

23 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 22 Reference #8: Pinheiro AR, Christofoletti G. Motor physical therapy in hospitalized patients in an intensive care unit: a systematic review. Revista Brasileria De Terapia Intensiva. 2012;24(2): Oxford Level of Evidence: 2a Pedro Score: N/A Purpose: To analyze the outcomes achieved by motor physical therapy in patients who are critically ill admitted to intensive care units. Methods: A systematic literature review was performed and the search involved the LILACS, SciELO, MedLine, EMBASE and Cochrane databases, using the keywords intensive care unit, physiotherapy, physical therapy, mobility, mobilization and randomized controlled trials. Two researchers screened the articles independently and included works that addressed the effect of physical therapy on patients who are critically ill. Results: From an initial analysis of 67 potentially relevant articles, only 8 met the selection criteria and addressed the outcomes of electrostimulation, cycle ergometry and kinesiotherapy techniques. The sample sizes ranged from 8 to 101 subjects, with mean ages between 52 and 79 years. All patients were undergoing invasive mechanical ventilation. Among the analyzed articles, six reported significant benefits of motor physical therapy, such as improvement in peripheral muscle strength, respiratory capacity and functionality, in patients who are critically ill. Bottom Line: With this systematic review, it is possible to conclude that motor physical therapy is a feasible and safe therapy for patients who are critically ill and can minimize the deleterious effects of prolonged immobilization. Approaches involving electrostimulation, cycle ergometry and kinesiotherapy showed positive responses in patients under intensive care. Available evidence regarding the impact of motor physical therapy on length of stay in intensive care units and on mortality is still scarce, and further study in this area is warranted.

24 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 23 Articles Analyzed Summary Article Oxford Level of Evidence PEDro Score General Purpose of Study Outcomes Measure Results Yes/No to Help Answer PICO Question Pires- Neto et al (2013) Parry et al (2014) Kho et al (2015) 2c 3/10 To verify the physiological changes and safety of an early passive cycling intervention (< 72 hours of mechanical ventilation) in patients who are critically ill. 2b 5/10 To determine the safety and feasibility of functional electrical stimulation (FES)-cycling in patients who are critically ill. 2b 5/10 To evaluate the feasibility and safety of in-bed cycle ergometry as part of routine ICU Cardiac output, systemic vascular resistance, central venous blood oxygen saturation, respiratory rate and tidal volume, oxygen consumption, carbon dioxide production and blood lactate levels. Time to reach functional milestones and incidence and duration of delirium. Number of safety events. There were no clinically relevant changes in any of the analyzed variables during the exercise. An improvement in physical function in ICU test score of 3.9/10 points in the intervention cohort with faster recovery of functional milestones and a shorter duration of delirium in the intervention cohort. A single safety event was reported, yielding a 0.2% event rate. Yes Yes Yes

25 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 24 Burtin et al (2009) physical therapy practice. 1b 4/10 To investigate whether a daily exercise session using a bedside cycle ergometer is a safe and effective intervention in attenuating the decrease in exercise capacity, functional status, and quadriceps force associated with prolonged ICU stays. 6-min walking distance, isometric quadriceps force, and the subjective feeling of functional well-being (measured with Physical Functioning item of the Short Form 36 Health Survey questionnaire). 6-min walking distance at hospital discharge increase, the subjective feeling of functional wellbeing scored higher, and the quadriceps force improved more between ICU discharge and hospital discharge in the treatment group. Yes

26 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 25 Connolly et al (2016) 2a N/A To provide an overview of systematic reviews evaluating the effect of physical therapy on muscle dysfunction in patients who are critically ill. Muscle strength, muscle structure, decrease in critical illness polyneuropathy and myopathy, quality of life, and mortality. Patients derive benefits in all of the outcome measure categories from physical therapy interventions in the ICU including early mobilization, cycle ergometry and electrical muscle stimulation. Yes Savi et al (2010) 2c 4/10 To determine whether passive cycling leg movement increases hemodynamic and metabolic variables in sedated, mechanical ventilationdependent patients. VO2 and SvO2 All patients had increased oxygen consumption (VO2). The VO2 increase occurred with a concomitant drop in mixed venous blood saturation (SvO2). SvO2 is a clinical marker of systemic oxygen use, and its demand increase during passive cycling could indicate that this intervention causes similar No

27 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 26 Santos et al (2015) Pinheiro et al (2012) 1b 7/10 To evaluate and compare the effects of early ambulation using a bedside cycle ergometer with conventional physical therapy on the thickness and architecture of the quadriceps muscle in patients who are critically ill and receiving invasive mechanical ventilation. 2a N/A To analyze the outcomes achieved by motor physical therapy in patients who are critically ill admitted to intensive care units. Cross-sectional thickness of the quadriceps muscle or in the vastus lateralis fascicle length, pennation angle and muscle thickness (as assessed by ultrasound). Improvement in peripheral muscle strength, respiratory capacity and functionality in patients who are critically ill. muscle activity as in active range of motion activities. The intervention group showed no difference in the crosssectional thickness of the quadriceps muscle or in the vastus lateralis fascicle length, pennation angle or muscle thickness as compared to the control group. 6 articles reported significant benefits of motor physical therapy, such as improvement in peripheral muscle strength, respiratory capacity and functionality, concluding that motor physical therapy is a Yes Yes

28 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 27 feasible and safe therapy for patients who are critically ill and can minimize the deleterious effects of prolonged immobilization.

29 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 28 Article Analysis Worksheets Reference #1 Citation: Pires-Neto CR, Kawaguchi FY, Hirota SA, et al. Very Early Passive Cycling Exercise in Mechanically Ventilated Critically Ill Patients: Physiological and Safety Aspects - A Case Series. Plos ONE Journal. 2013;8(9):e Oxford Level of Evidence: 2c PEDro Score: 3/10 Is the purpose and background information sufficient? Study Purpose Yes. The study notes that if an early mobility Stated clearly? intervention is not undertaken in the ICU, the Usually stated briefly in abstract and in rates of hospital readmission and death during greater detail in introduction. May be phrased the first year after hospital discharge increase. as a question or hypothesis. Thus, because early mobilization is associated A clear statement helps you determine if topic with better clinical outcomes for ICU patients, is important, relevant and of interest to you. the hypothesis is that an earlier intervention Consider how the study can be applied to PT might further improve clinical outcomes. This and/or your own situation. What is the study admits that previous studies have purpose of this study? looked at cycling in ICU patients, however, the intervention was initiated 14 days after ICU admission. The primary objective of this study is to evaluate the hemodynamic, respiratory and metabolic effects of a cycling exercise performed during the first 72 hours Literature Relevant background presented? A review of the literature should provide background for the study by synthesizing relevant information such as previous research and gaps in current knowledge, along with the clinical importance of the topic. Describe the justification of the need for this study Does the research design have internal validity? of mechanical ventilation. Yes. The article presents thorough background information as to why this study is relevant to early physical therapy intervention in the ICU. The article states that there has been research performed concluding that early mobilization in the ICU is beneficial for patient recovery. Also, the presence of previous research regarding the use of cycle ergometry as a possible mode of early mobilization. However, no study had yet looked at mobilization earlier than 14 days after ICU admittance. Thus, the efficacy of passive cycling within 24, 48, or 72 hours of patient admittance to the ICU is unknown.

30 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness 29 Discuss possible threats to internal validity in the research design. Include: Assignment Attrition History Instrumentation Maturation Testing Compensatory Equalization of treatments Compensatory rivalry Statistical Regression This study utilized a convenience sample of only 19 subjects. Small sample size and subjects that were found at the convenience of the researchers decrease the strength of the findings because the data collected cannot be generalized as broadly to the population under question. Additionally, subjects and researchers in this study were not blinded which can lead to bias in either the patient or the researcher providing therapy and collecting data. Are the results of this therapeutic trial valid? 1. Did the investigators randomly No, there was no control group for this study. assign subjects to treatment groups? 19 subjects were included from a a. If no, describe what was done convenience sample of mechanically b. What are the potential ventilated patients. Initially, 268 patients met consequences of this the inclusion criteria of being mechanically assignment process for the ventilated less than 72 hours, however, other study s results? exclusion criteria such as lower limb tumor, DVT, or enrollment in another research protocol reduced the number of subjects included to 19. The main comparison that this study made was against another study in which researchers had waited 14 days before attempting cycle ergometry intervention. The results of this study were not compared to a control group. When there is no control group, and the subjects are from a convenience sample, external validity of the findings is decreased as well as the research 2. Were the groups similar at the start of the trial? Did they report the demographics of the study groups? a. If they were not similar what differences existed? validity. Patient sex, age, and height were presented in the study. Demographics were approximately 50% male, 50% female and generally around the same height. However, the age range reported was 55 +/- 17 years, which is a fairly broad age range. The patients were similar regarding their level of sedation and mechanical ventilation support.

31 Passive Lower Extremity Cycling to Combat ICU Acquired Weakness Did the subjects know to which treatment group they were assign? a. If yes, what are the potential consequences of the subjects knowledge for this study s results 4. Did the investigators know who was being assigned to which group prior to the allocation? a. If they were not blind, what are the potential consequences of this knowledge for the study s results? 5. Were the groups managed equally, apart from the actual experimental treatment? a. If not, what are the potential consequences of this knowledge for the study s results? 6. Was the subject follow-up time sufficiently long to answer the question(s) posed by the research? a. If not, what are the potential consequences of this knowledge for the study s results? The intervention subjects, or the power of attorney, were required to sign an agreement to participate in the intervention. As there was no random assignment or control group in this study, yes, the subjects and their families were aware of the intervention they were receiving as a subject in this study. The potential impact of this is that the patient/family may try harder and the therapists involved may provide additional support to increase the patient s progress compared to usual care patients, or the patients in the study under comparison. Yes. The investigators were aware of the patients included in the convenience sample and receiving the cycle ergometry intervention. Potential consequences of not blinding the therapist to the subjects receiving the intervention is offering more or better quality therapy to the patients in the intervention group compared to usual care physical therapy provided. The article does not state whether the intervention is the only change in care the subjects received. However, because there was no control group in this study and the results of this study were compared to the results of another study, we can assume that the patients were not treated completely equally. Thus, there is ambiguity in the generalization of the results and validity in comparing the results of this study to the results of another study. No. The article does not state the subject follow-up time or amount of at which point in time the subjects were discharged from the study. The reader can assume that at most, the subjects were only involved in the intervention while deeply sedated and receiving mechanical ventilation, as these were the goals of the study, to determine the safety of passive cycling under these conditions. I do not think the subject followup time was sufficient, as data was analyzed only immediately prior to, during, and after the intervention. Thus the study s findings are