Home Educatione-Learning ICU-Acquired Weakness, Sedation, and Immobility
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ICU-Acquired Weakness, Sedation, and Immobility

PCCSU Volume 25, Lesson 28


The American College of Chest Physicians offers this lesson as a review of a previously offered self-study program. The program provides information on pulmonary, critical care, and sleep medicine issues. CME is no longer available for the PCCSU program.


  • Update your knowledge and understanding of pulmonary medicine topics.
  • Update your knowledge and understanding of critical care medicine topics.
  • Update your knowledge and understanding of sleep medicine topics.
  • Learn clinically useful practice procedures.

CME Availability

Effective July 1, 2013, PCCSU Volume 25 is available for review purposes only.

Effective December 31, 2012, PCCSU Volume 24 is available for review purposes only.

Effective December 31, 2011, PCCU Volume 23 is available for review purposes only. CME credit for this volume is no longer being offered

Effective December 31, 2010, PCCU Volume 22 is available for review purposes only. CME credit for this volume is no longer being offered.

Accreditation Statement

The American College of Chest Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CME Statement

Credit no longer available as of July 1, 2013.

Disclosure Statement

The American College of Chest Physicians (CHEST) remains strongly committed to providing the best available evidence-based clinical information to participants of this educational activity and requires an open disclosure of any potential conflict of interest identified by our faculty members. It is not the intent of CHEST to eliminate all situations of potential conflict of interest, but rather to enable those who are working with CHEST to recognize situations that may be subject to question by others. All disclosed conflicts of interest are reviewed by the educational activity course director/chair, the Education Committee, or the Conflict of Interest Review Committee to ensure that such situations are properly evaluated and, if necessary, resolved. The CHEST educational standards pertaining to conflict of interest are intended to maintain the professional autonomy of the clinical experts inherent in promoting a balanced presentation of science. Through our review process, all CHEST CME activities are ensured of independent, objective, scientifically balanced presentations of information. Disclosure of any or no relationships will be made available for all educational activities.

CME Availability

Volume 25 Through June 30, 2013
Volume 24 Through December 31, 2012
Volume 23 Through December 31, 2011
Volume 22 Through December 31, 2010

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PCCSU Volume 25 Editorial Board

Steven A. Sahn, MD, FCCP

Director, Division of Pulmonary and Critical Care Medicine, Allergy, and Clinical Immunology
Medical University of South Carolina
Charleston, SC

Dr. Sahn has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Deputy Editor
Richard A. Matthay, MD, FCCP

Professor of Medicine
Section of Pulmonary and Critical Care Medicine
Yale University School of Medicine
New Haven, CT

Dr. Matthay has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Alejandro C. Arroliga, MD, FCCP
Professor of Medicine
Texas A&M Health Science Center
College of Medicine
Temple, TX

Dr. Arroliga has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Paul D. Blanc, MD, FCCP
Professor of Medicine
University of California, San Francisco
San Francisco, CA

Dr. Blanc has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health, Flight Attendants Medical Research Institute – university grant monies
University of California San Francisco, US Environmental Protection Agency, California Environmental Protection Agency Air Resources Board – consultant fee
Habonim-Dror Foundation Board of Trustees – fiduciary position

Guillermo A. do Pico, MD, FCCP
Professor of Medicine
University of Wisconsin Medical School
Madison, WI

Dr. do Pico has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Ware G. Kuschner, MD, FCCP
Associate Professor of Medicine
Stanford University School of Medicine
Palo Alto, CA

Dr. Kuschner has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Teofilo Lee-Chiong, MD, FCCP
Associate Professor of Medicine
National Jewish Medical Center
Denver, CO

Dr. Lee-Chiong has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health – grant monies (from sources other than industry)
Covidien, Respironics, Inc. – grant monies (from industry-related sources)
Elsevier – consultant fee

Margaret Pisani, MD, MPH, FCCP
Assistant Professor of Medicine
Yale University School of Medicine
New Haven, CT

Dr. Pisani has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Stephen I. Rennard, MD, FCCP
Professor of Medicine
University of Nebraska Medical Center
Omaha, NE

Dr. Rennard has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

AstraZeneca, Biomark, Centocor, Novartis – grant monies (from industry-related sources)

Almirall, Aradigm, AstraZeneca, Boehringer Ingelheim, Defined Health, Dey Pharma, Eaton Associates, GlaxoSmithKline, Medacrop, Mpex, Novartis, Nycomed, Otsuka, Pfizer, Pulmatrix, Theravance, United Biosource, Uptake Medical, VantagePoint – consultant fee/advisory committee

AstraZeneca, Network for Continuing Medical Education, Novartis, Pfizer, SOMA – speaker bureau

Ex Officio
Gary R. Epler, MD, FCCP

Clinical Associate Professor of Medicine
Harvard Medical School
Brigham & Women's Hospital
Boston, MA

Dr. Epler has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Lilly Rodriguez
ACCP Staff Liaison

By Rita N. Bakhru, MD; and William D. Schweickert, MD

Dr. Bakhru is a fellow in Pulmonary/Critical Care Medicine; and Dr. Schweickert is Assistant Professor of Medicine, University of Pennsylvania, Philadelphia, PA.

Drs. Bakhru and Schweickert have disclosed no significant relationships with the companies/organizations whose products or services may be discussed within this chapter.


  1. Review the epidemiology of weakness in critically ill patients.
  2. Describe the relationship between immobility, sedation, and ICU-acquired weakness.
  3. Detail pivotal clinical studies of early exercise and mobilization in ICU patients.
  4. Provide tips for practical implementation of an early exercise and mobilization program, including criteria for consultation, therapy progression, and tracking outcomes.

Key words: critical illness; exercise; ICU-acquired weakness; ICU; immobility; mobilization; occupational therapy; physical therapy; sedation

Abbreviations: ICU-AW = ICU-acquired weakness; MICU = medical ICU; PT = physical therapy; OT = occupational therapy; RICU = respiratory ICU; ROM = range of motion

In the last quarter-century, research developments have led to improvements in diagnosis and resuscitation of critically ill patients. With these improvements, survival for many populations of critically ill patients has increased.1-3 ICU outcomes research has proliferated, documenting substantial morbidity in survivors, including general deconditioning, muscle weakness, dyspnea, depression, anxiety, and reduced health-related quality of life.4 These injuries have been demonstrable in general populations of ICU patients; however, the catalyst for widespread attention has been the comprehensive observations of a cohort of survivors of ARDS, the prototype of severe critical illness.5 In this cohort study of 109 survivors, Herridge and colleagues5 found that 12 months after discharge, all patients reported poor function due to a loss of muscle bulk, proximal weakness, and fatigue; patients had reduced endurance; and only 49% of patients had returned to work. At 5 years, the survivors had continued perceptions of weakness and loss of muscle bulk paired with reduced 6-min walk distance.6 Furthermore, 51% of patients had developed physician-diagnosed depression and/or anxiety. The observed reductions in functional performance, exercise capacity, and quality of life in ICU survivors indicate the need for rehabilitation following critical illness but also underscore the demand for interventions to prevent or attenuate weakness acquired during the ICU stay.

ICU-Acquired Weakness, Sedation, and Immobility

Clinicians have long recognized the evolution of weakness in critically ill patients. The first comprehensive investigations began in the 1980s and incorporated electrophysiologic testing and muscle biopsy to delineate the injury.7-10 Since that time, critical illness myopathy and polyneuropathy have been detailed, including the commonality of their overlap (particularly in sepsis).11 In routine clinical practice, infrequent biopsy and electrophysiologic testing have prompted the embrace of ICU-acquired weakness (ICU-AW) as a syndrome encompassing generalized diffuse flaccidity after onset of critical illness defined by standard functional muscle tests.12

The occurrence of ICU-AW varies substantially depending on the patient case mix, diagnostic method used, and the timing of examination. De Jonghe and coworkers13 found clinically significant ICU-AW in 25% of patients who had undergone mechanical ventilation for at least 7 days. However, this result was limited by a sizable number of patients who could not be tested for muscle strength because of death or transfer prior to awakening. In contrast, electrophysiologic testing can be conducted in the unresponsive patient and has resulted in reports of higher incidences of acquired neuromuscular disease in similar cohorts. For example, a prospective study of 50 patients undergoing mechanical ventilation for more than 7 days documented critical illness polyneuropathy in 58%.14 In 2007, Stevens and colleagues15 conducted a systematic review incorporating 24 eligible studies on adult ICU patients with sepsis, multiorgan failure, or prolonged mechanical ventilation who were evaluated both clinically and via electrophysiologic testing. Neuromuscular dysfunction was identified in 655 of 1,421 patients (46%) and was associated with prolonged duration of mechanical ventilation and length of ICU and hospital stay. Although commonly associated with increased severity of illness, this acquired muscle weakness is independently associated with both weaning failure16 and, most importantly, increased mortality.17

Factors such as systemic inflammation, medications (particularly neuromuscular blocking agents and steroids), electrolyte disturbances, and immobility have been implicated in the pathogenesis of ICU-AW.12,18 The current information derives largely from prospective cohort studies of patients in which multivariate analyses are used to assess independent risk factors. Although no one has systematically measured immobility in critical illness, clinicians acknowledge its presence during the earliest days of critical illness and its commonality during deep sedation, specific mechanical ventilation strategies (eg, high-frequency oscillatory ventilation), and other advanced support (eg, continuous hemodialysis).

Indirect data suggest that deep sedation and bed rest may potentiate ICU-AW. For example, de Jonghe and colleagues16 found that the duration of mechanical ventilation prior to “awakening” was a significant risk factor for ICU-AW, independent of the duration of multiple organ failure. Clinical trials of sedative minimization strategies, including protocol-guided administration and daily interruption of continuous sedation, have yielded more engaged patients, fewer bed sores, less need for tracheostomy, and a trend toward more patients going home.3,19,20 Finally, repeated daily passive mobilization of a single leg, via the application of a continuous passive range of motion machine, limited muscle atrophy in sedated and paralyzed mechanically ventilated patients.21

The detriment of immobilization and deconditioning are extrapolated from studies on young healthy persons put on bed rest. Study participants exhibit changes in mood and loss of coordination, muscle strength, balance, and work tolerance.22 Specifically, strict bed rest results in skeletal muscle strength declining 1% to 1.5% per day.23,24 Limb casting models of immobilization suggest that the decline may be more significant, reaching as high as 5% to 6% per day.25-29 When these findings occur in aging or chronically ill patients with sarcopenia, it can culminate in profound muscle decrement. When whole muscle groups are considered, the antigravity muscles (legs, trunk, and neck) selectively atrophy to a greater extent.24 This finding may be very relevant to ICU survivors, as these muscles maintain posture and foster transfer and ambulation. Given this context, outcome studies must incorporate measures of both strength and function.

Studies of Early Exercise and Mobilization in ICU Patients

Mobility has been recognized as a component of primary, secondary, and tertiary prevention of overall disease morbidity and mortality. Early ambulation was first introduced for inpatients during World War II in an effort to expedite soldiers’ recovery and return to the battlefield.30 Since then, early mobilization has yielded improved outcomes in such varied conditions as community-acquired pneumonia and orthopedic surgery.31,32 Given the known morbidity of ICU survivorship, clinical researchers have targeted the avoidance of bed rest as a potential opportunity to affect the quality of life for survivors. These trials, summarized below, highlight the feasibility of early exercise and mobilization despite ongoing critical illness. Although most studies are limited to single-center experiences and focus selectively on patients undergoing mechanical ventilation, the results are likely generalizable to broader populations of critically ill patients.

The safety and feasibility of early mobilization during mechanical ventilation was best captured by Bailey and colleagues’ 2007 descriptive cohort study.33 Conducted in the respiratory ICU (RICU) of LDS Hospital in Salt Lake City, the study followed 103 patients who had been critically ill for an average of 10 days. Patients began exercise once they responded to verbal stimulation and were stable from both a respiratory and cardiovascular standpoint (defined as Fio2 ≤ 0.6, positive end-expiratory pressure ≤10 cm H2O, absence of orthostatic hypotension, and no requirement for catecholamine drip). The exercise team, including a physical therapist, respiratory therapist, nurse, and critical care technician, focused training on three activities: sitting on the edge of the bed, sitting in a chair after bed transfer, and ambulating. At RICU discharge, 77% of patients were able to ambulate, including 69% able to ambulate >30.5 m (100 ft); 15% of patients able to sit in a chair, and 5% of patients able to sit at the edge of the bed. Only 14 of the 1,449 activity events, including 593 conducted during intubation, resulted in predefined adverse events. Specifically, there were five falls to the knees without injury, four systolic blood pressures <90 mm Hg, one systolic blood pressure >200 mm Hg, three desaturations to <80%, and one nasal feeding tube removal.

To further the proof of the LDS Hospital unit’s success, they studied the performance levels of 104 mechanically ventilated patients within a 2-day window before and after transfer to their RICU.34 Within 24 hours of arrival, patients underwent more intense physical activities than conducted previously; for example, ambulation increased from 11% before transfer to 41% within 48 hours. Multivariable logistic regression demonstrated that transfer to the authors’ RICU was independently associated with the likelihood of ambulation. This study was the first indication that a unit-based culture of early mobilization could significantly influence patient functional performance.

The first prospective comparison between early exercise and mobilization compared with usual care was published in 2008 by Morris and colleagues.35 In this study, mechanically ventilated medical ICU (MICU) patients were enrolled in a nonrandomized block allocation to either usual care (n = 165) or early mobilization (n = 165). In this study, the “mobility team” (physical therapist, nurse, and nurse assistant) used a detailed protocol for a stepwise increase in therapy based on patient participation and tolerance, spanning passive range of motion (ROM) to active ROM exercise, sitting, transfers, and finally, ambulation. All patients enrolled within 48 hours of intubation underwent protocol-guided sedation, ventilator liberation, glycemic control, and sepsis resuscitation. Eighty percent of patients in the intervention group underwent at least one therapy session compared with only 47% of patients in the usual care group (P < .001). Patients in the intervention group were quicker to get out of bed (8.5 vs 13.7 d; P < .001) and had a reduced hospital length of stay (14.9 vs 17.2 d; P = .05). Recently, the 1-year outcomes of the 280 hospital survivors from the initial 330-patient cohort were reported.36 A review of hospital records and patient questionnaires demonstrated that 132 patients were readmitted or died within 1 year, 126 patients were alive and had not been readmitted, and 22 were lost to follow-up. In multivariate analysis, the lack of early ICU mobility was independently associated with readmission(s) or death during the first year. Although the causes of readmission and death were not specified, these findings suggest a more durable benefit enacted by early ICU mobility.

In 2009, Schweickert and colleagues37 reported on a prospective, dual-center, randomized clinical trial of very early mobilization. A total of 104 MICU patients were enrolled within 72 hours of the onset of respiratory failure requiring mechanical ventilation. Patients were randomly assigned to an intervention group (n = 49) that received mandated, progressive physical therapy (PT) and occupational therapy (OT) or a control group (n=55) of patients who received PT and OT as ordered by their primary team. All patients were managed with protocols for daily sedation interruption, weaning from mechanical ventilation, nutrition, and glucose control. The dual-therapist team treated patients with exercises such as sitting at the edge of the bed, engaging in simulated activities of daily living, transfer training, and ambulation. Patients in the intervention group underwent therapy on 87% of days in the study and started therapy at a median of 1.5 days after intubation, compared with 7.4 days in the control group (P < .001). Within 4 days, 76% of intervention patients were sitting at the edge of the bed, 33% were standing and transferring to a chair, and 15% were ambulating. At hospital discharge, intervention patients had a higher rate of return to independent functional status (59% vs 35%; P = .02) and a greater walk distance, and they were more likely to be discharged to home (43% vs 24%; P = .06). Additionally, intervention patients experienced a reduced duration of delirium (2 days vs 4 days; P = .03), more ventilator-free days (23.5 days vs 21.1 days; P = .05), but no significant difference in ICU or hospital length of stay.

Implementing the combined interventions of sedation minimization and early mobilization may yield the most striking effects for an individual ICU’s outcomes. In 2010, Needham and colleagues38 reported on their quality improvement project to improve outcomes in patients undergoing mechanical ventilation for ≥4 days. In the pre-intervention phase, patients were deeply sedated during 58% of all patient-days and were either deeply sedated or delirious on more than 85% of all patient-days. As a result, only 24% of patients had consultations for PT or OT while in the MICU. The study interventions included education on sedation and mobilization practices, augmentation of therapist staffing, promotion of physiatry and neurology consultation, and provision of regular feedback to clinicians on these practices. In the post-intervention period, patients were less sedated and less delirious, received more therapy services, and exhibited improved functional mobility. Additionally, administrative data on all MICU patients demonstrated reductions in lengths of stay in the ICU (2.1 days) and hospital (3.1 days).

Finally, Burtin and colleagues39 investigated the possibility that technology might help to enhance ICU-based rehabilitation. In their study of patients with prolonged ICU stays (enrollment began after ICU day 5), patients were randomly assigned to early exercise using a bedside cycle ergometer in addition to standard PT or to PT alone. Intervention patients were strapped into the cycle’s pedals to permit both passive and active cycling during sessions conducted 5 days per week. At hospital discharge, patients in the intervention group exhibited a longer 6-minute walk distance, higher survey scores on physical function, and greater quadriceps force. Patients tolerated the 425 cycling sessions well without serious adverse events. Only 16 sessions had to be ended early because of oxygen desaturation and blood pressure changes.

Practical Implementation of an Exercise and Mobilization Program

Rehabilitation activities in ICUs have traditionally been better organized in RICUs or weaning centers. In general, patients in these selected environments often have attained convalescence from the acute phase of illness and require less sedation; the majority are candidates for therapy services. Accordingly, therapy consultation is expected for all patients and there are enough therapists on staff to meet the PT and OT demands. To translate early exercise and mobilization to the acute-care ICU, programs must have (1) a clearly defined strategy for managing patient pain, agitation, and delirium; (2) criteria for PT consultation; (3) standardized PT management schemes; and (4) metrics for PT performance.

To accrue the benefits of early exercise and mobilization, the patient should be as engaged as possible and tethered to the smallest number of devices possible (Fig 1). As a result, protocols to guide sedation minimization and early recognition of readiness for extubation are essential. Most ICUs implementing early exercise and mobilization programs should consider establishing such protocols at the onset. Hallmarks of successful sedation programs include the utilization of a reproducible, validated scale (eg, Richmond Agitation and Sedation Scale),40,41 an established sedation target prescribed daily with nurse-led titration of drug administration,42 and the incorporation of daily interruption of continuous sedative infusions.20 Similarly, a respiratory therapy–driven protocol to guide assessment of readiness testing, weaning, and extubation has proven beneficial43; pairing this with sedation interruption has yielded demonstrable improvements.3

Figure 1. Depiction of a 28-year-old man with advanced cystic fibrosis on day 5 of respiratory failure. He is walking while receiving mechanical ventilation via an oral endotracheal tube. He is accompanied by his nurse, respiratory therapist, physical therapist, and wife.

Given the common scarcity of therapy resources in the ICU, some consideration should be given to appropriate consultation practices for PT and/or OT services. We propose a unique set of criteria, focusing on the cardiovascular, pulmonary, and neurologic systems, called the MOVE criteria (Table 1), which may serve to help nontherapy clinicians identify ICU patients who are appropriate candidates for PT consultation. These criteria, in accordance with prior literature on mobilization of patients undergoing mechanical ventilation,33,35,37,38 are simply a stepping stone. As we suggest here, ROM in the comatose patient may be best performed by nontherapist clinicians (eg, nurses, nurse assistants) and potentially augmented by patient family members. Alternatively, advanced programs may use such equipment as the cycle ergometer.39 Furthermore, evidence has shown that exercise and mobilization can be conducted in contexts of greater ventilator dependence.37 We advocate further liberalization of the oxygenation criterion based on institutional comfort. Finally, the criteria are purposefully “lean” and may not be restrictive enough for general practice (eg, GI bleeding). Future studies to validate these criteria are needed.

Table 1Proposed MOVE Criteria to Guide Physical Therapy Consultation Based on Prior Clinical Trials of Exercise and Mobilization





Myocardial stability

No evidence of active myocardial ischemia
Stable heart rate and cardiac rhythm


Oxygenation adequate

Fio2 ≤ 0.6
Positive end-expiratory pressure ≤ 10


Vasopressor use minimal

Minimal vasopressor(s)
No increase in dose of any vasopressor for ≥2 h


Engages to voice

Patient responsive to voice (eg, Richmond Agitation-Sedation Scale score
≥ –3)40

Once patients have been deemed ready to begin mobilization, it should proceed in a logical, stepwise fashion. Activity and exercise should be targeted at the appropriate intensity and with the appropriate exercise modality. Investigators have proposed detailed approaches to the progression of activities based on levels of patient consciousness, cooperation, and functional status. Figure 2 is a general guide for emerging programs. Acutely ill, comatose patients receive passive ROM, muscle stretching, splinting as needed, and body positioning. Once they are interactive, patients can increase their level of activity progressing from active ROM to sitting at the edge of the bed, transferring to a chair, marching in place, and then ambulating. Standing and walking frames enable the patient to mobilize safely with attachments for bags, lines, and leads that cannot be disconnected. For the patient with advanced weakness, standing aids and tilt tables enhance physiologic responses as a modality to promote early mobilization of critically ill patients.

Figure 2. Schematic depicting functional progression of physiotherapy. Intensity and exercise modality are guided by three domains: the domains of interaction, body positioning, and physiotherapy. PROM = passive range of motion; AAROM = assisted transfer to edge of bed; AROM = active range of motion.

Importantly, a measure of success is necessary. All units beginning an exercise program will want to track standard ICU metrics, such as the duration of mechanical ventilation and the ICU and hospital lengths of stay. To better understand the specific strength and function outcomes of ICU patients, we advocate adoption of the Functional Status Score for the ICU (FSS-ICU), as proposed by Denehy and colleagues.44 The scoring system, based on the validated Functional Independence Measurement,45,46 rates activities between 1 (total assist) and 7 (complete independence). Recognizing that most ICU patients can perform a limited number of functional activities, five activities are selected for measurement: rolling, transferring from supine to sitting position, sitting at the edge of the bed, transferring from sitting to standing position, and ambulation. These four tasks plus ambulation are combined in the cumulative FSS-ICU, which is a simple sum of the five individual scores. Additionally, investigators advocate measuring the duration of unsupported sitting at the edge of the bed and the maximum distance walked. Tracking these outcomes may help to translate the success of an expanding program.


An aging population combined with increasing numbers of patients needing and seeking ICU services creates an environment in which critical care delivery must be optimal. Research investigations have proven that specific supportive strategies (eg, low tidal volume ventilation, goal-directed sepsis resuscitation) as well as ICU structure, such as daily rounds by a multidisciplinary team,47 are associated with improved mortality rates for ICU patients. The implementation of an early exercise and mobilization program spans both, requiring the intricacy of individual process delivery combined with the infrastructure for detailed communication across disciplines. Physicians, nurses, respiratory therapists, physical therapists, and occupational therapists must generate team plans to promote wakefulness, assess readiness for ventilator liberation, and negotiate competing procedures and testing while seeking to maximize daily physiotherapy.

Clinical trials have shown these programs to be safe and feasible at individual centers. Importantly, mobilization protocols have demonstrable benefit for short-term patient outcomes, including improvements in functional performance and brain function as well as earlier ICU and hospital discharge. Future research needs to address the dose of therapy and specific exercise strategies for the general population. Furthermore, the impact of these interventions on long-term outcomes must be better understood to meet the needs of our expanding survivor population.


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