Author(s): Laurentiu Dinescu, MD, Rebecca Sussman, MD, Shruti Amin, MD, Noemi Olivero, MD
Originally published: October 2, 2015 Last updated: June 8, 2021
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Disease/ Disorder

Definition

Patients hospitalized in an intensive care unit (ICU) can develop impairments in mobility, cognition, and ability to perform activities of daily living (ADL) that result in functional decline which is associated with longer time on mechanical ventilation, longer ICU stay, and increased overall mortality.1,2,3,4,5

ICU acquired weakness (ICUAW) has become a favored term to describe “clinically detected, diffuse, symmetric weakness involving all extremities and respiratory muscles arising after the onset of critical illness”.5,6 Time of onset is important because it differentiates ICUAW from other acute neuromuscular syndromes that can cause respiratory failure and lead to ICU admission.5,7 ICUAW is associated with diaphragmatic weakness and difficulty with vent weaning due to weakness of the respiratory muscles is a common initial presenting ICUAW problem.5,8

ICUAW is a broadly defined clinical diagnosis, and should not be confused with Critical illness myopathy (CIM) or critical illness polyneuropathy (CIP), which refer to specific conditions with well-defined electrophysiologic findings.5,8,9,10 CIM and CIP can cause ICUAW and may present as overlapping syndromes. 

ICUAW, conceptually, allows a multidisciplinary team to monitor and treat clinically significant generalized weakness and decline in physical and respiratory function secondary to critical illness in the absence of a definitive diagnosis of myopathy or neuropathy. Other causes of weakness must be ruled out with a careful clinical history and thorough neurologic exam.7 Laboratory tests and imaging may help to exclude other etiologies.

A separate entity, post-intensive care syndrome (PICS), has received increasing attention, in part because advances in care delivery have led to the increased survival of patients with critical illness.3 Some ICU patients have functional impairments that persist for months or years after hospital discharge. PICS was adopted as the preferred term for this phenomenon in 2010 and is currently defined as, “new or worsening impairment in physical, cognitive, or mental health status arising and persisting after hospitalization for critical care illness”.3 Screening tools are under development and a new emphasis is being placed on serial functional assessments to address the long-term sequelae of critical illness.3 The role for rehabilitation in the ICU is expanding to cover early indications beyond acute functional decline.11

Etiology

The ICU environment is often highly stimulating while involving prolonged bed rest and immobility, and critically ill patients are often beset by disturbed sleep, inadequate nutritional intake, and pain.1,2,9,10,12,13,14 Functional decline in the ICU can occur in patients with a broad range of admitting diagnoses, and may bear a strong link to overall severity of illness, and was especially described in patients with sepsis, multiorgan failure, and encephalopathy.8 ICUAW can be viewed as the extreme form of illness-associated weakness, frequently caused by underlying and sometimes overlapping pathology such as CIP, CIM or severe disuse muscle atrophy. Hyperglycemia, mechanical ventilation, prolonged bed rest, and drug effects (glucocorticoids, neuromuscular blocking agents) have been linked to electrophysiologic and clinical signs of ICUAW.4,5,6

Epidemiology

Muscle weakness, ranging from mild limb paresis to severe tetraplegia, has been noted in up to 25% of all patients who spend seven or more days in an ICU.4 The incidence of weakness appears to rise sharply with acute respiratory failure and higher severity of critical illness. Weakness has been reported in up to 60% of patients who undergo more than one week of mechanical ventilation and up to 70% of patients diagnosed with sepsis or systemic inflammatory response syndrome. 4,8,9 The incidence approaches 100% if multiple organ failure is present.4 At ICU discharge, nearly all survivors of critical illness have impairments in one or more PICS domains, and these impairments persist in 64% and 56% of survivors at 3 and 12 months, respectively.3

Patho-anatomy/physiology

ICU patients are often on bedrest, the complications of which include disuse muscle atrophy, joint contracture, thromboembolic disease, insulin resistance, atelectasis, and skin breakdown.2,15,16

Immobility in the setting of critical illness has deleterious effects on muscle structure and function. Experimental models show a muscle mass decrease of 1.5 to 2 percent during the first 3 weeks of strictly enforced rest, primarily due to reduced size of fibers, particularly in weight-bearing muscles of the lower limbs and core.6,15 Muscle inactivity stimulates protease activation and thus leads directly to muscle breakdown, increased catabolism, and decreased contractility.6,14,16 Muscle strength can decrease by as much as 15% after two weeks of bedrest and by more than 50% after 28 days of forced limb immobilization.15

Sepsis and other critical illnesses induce metabolic and vascular derangements that damage peripheral nerves and skeletal muscles.6 Pathophysiological factors, including microvascular changes, increased membrane permeability, alterations in electrical potentials and conductivity, and cellular inflammation, coalesce and instigate precarious sequelae, which include peripheral nerves functionally approximates demyelination and axon degradation. Patients who are mechanically ventilated, under deep sedation, or receiving neuromuscular blocking agents can experience mechanical silencing, in which lack of mechanical stimulation to the muscles worsens muscle wasting.5,15,16

Acute respiratory failure requiring mechanical ventilation is associated with the development of weakness.17 Prolonged mechanical ventilation can alter diaphragmatic structure and function, leading to difficulties with breathing and ventilator weaning.5,18

Medications can inadvertently cause weakness. Neuromuscular blockers can damage the neuromuscular junction and its function. Steroids can injure muscle cells and affect muscle and nerve metabolism. Sedatives can lead to decreased muscle contraction and vascular tone and altered mobility.4,6,12

Malnutrition may contribute to neuromuscular dysfunction. Caloric and protein supplementation via artificial nutrition has not been shown to lessen the catabolic state in the early phases of critical illness, nor prevent muscle atrophy or subsequent weakness in critically ill patients.5

Disease progression

The onset of ICUAW is often insidious. Subtle muscle and functional changes often go unnoticed since detailed assessments of motor function are not the priority in critical situations. The first observed signs are often generalized muscle atrophy or difficulty with ventilator weaning. Later, limbs are flaccid, with weakness affecting lower more than upper limbs. Some patients progress to quadriparesis. Although facial weakness and ophthalmoplegia can occur, head, facial, tongue and jaw movements tend to be spared.4,8 

In cases of critical illness polyneuropathy (CIP), patients can lose distal pain, temperature, and vibratory sensation. Reflexes are often diminished or absent. In critical illness myopathy (CIM), reflexes may be normal or diminished.6,8,14,19,20

Symptom progression and severity vary. Observable declines in muscle size and function have been detected after just two weeks of immobility. Alterations in peripheral nerves are clinically evident within one to two weeks of critical illness.15,16,21  Evolution to extensive and generalized atrophy can occur over weeks to months. More severe and persisting symptoms correlate with lengthier and more intense exposure to risk factors as described above.4

Recovery is variable, and typically occurs over weeks to months; some patients do not fully recover. Even when weakness resolves, many patients experience persistent marked reduction in physical function following critical illness.4,8,14 At least 50% of ICU patients report inability to return to work due to fatigue, weakness, and overall impaired functional status one year after their critical care stay.1 More than 50% of patients demonstrate impairments in one or more PICS domains at one year post-ICU discharge.3

Specific secondary or associated conditions and complications

Functional decline is associated with increased burden and cost of care over the short and long term and is associated with longer ICU stays and higher likelihood of discharge to a nursing home or other care facility.1,4,8,22,23 It puts patients at risk of increased medical complications and decreased ability to recover independence with ADLs. Patients may report persistent weakness, poor exercise tolerance, and ongoing disability.1,10,14

Other consequences include delirium, impaired cognition, and mental health conditions. Some cognitive impairments may persist following the critical care stay.3,10 More than 15% of ICU patients later report anxiety or post-traumatic stress. These symptoms may be rooted in issues related to the illness or trauma that led to ICU stay, critical care treatment or environmental issues, or medications.3,24,25

Essentials of Assessment

History

Relevant history includes assessment of prior functional status, health history, including musculoskeletal or skin issues, and substance abuse history. This may initially be difficult to obtain given the severe and often sudden nature of critical illness.3

The ICU course includes diagnoses which led to ICU stay, severity of illness, treatment course including the use of steroids, vasopressors, mechanical ventilation, antibiotics, and the presence of metabolic derangements such as hyperglycemia.6,12

Physical examination

Vital signs: any instability, orthostasis, hyperthermia/ fever or other abnormalities.

Neurological: mental status including level of consciousness and brief cognitive screen; cranial nerves; motor, including tone and strength; sensory, including light touch, sharp/ dull, proprioception, and vibratory sense; coordination, station and gait; and muscle stretch reflexes.

Musculoskeletal: joint range of motion to identify possible contractures and muscle bulk to identify atrophy.

Skin: evaluate any healing incisions or wounds.6,12,19

Clinical functional assessment

Early performance of functional status evaluation in combination with screening for frailty following ICU admission may identify patients who are at highest risk for functional decline and those who may most benefit from therapy.3,26 Items to evaluate include swallowing, speech, self-care, mobility, functional activity tolerance, sleep, pain, and nutrition.12,27,28

The Functional Independence Measure (FIM) mobility sub scales grade ADLs and mobility on a scale of function with six designations that range from independent, standby assist/supervision, minimal assist, moderate assist, maximal assist, and total assist.26

Formal assessment for ICUAW involves the use of the Medical Research Council scale (MRC), which is a categorical scale that measures volitional muscle strength, from 0 (no appreciable contraction) to 5 (full active range of motion against maximum resistance), in 12 muscle groups.5,29 A sum score of <48/60 or mean score of 4 in all testable muscle groups indicates significant weakness consistent with ICUAW, however the test is only useful in cooperative patients.5,29  Handgrip dynamometry may also be used as a more objective measure of volitional muscle strength in cooperative patients. Scores less than 11kg in males or less than 7kg in females have been used as cut-offs to support the diagnosis of ICUAW.5,29

The Perme ICU Mobility Score is an ICU-specific tool that evaluates ambulation and mobility. Assessment categories include mental status, mobility barriers, functional strength, bed mobility, transfers, gait, and endurance. Lower scores indicate that more assistance is needed to facilitate mobility.30

Current guidelines regarding screening for PICS strongly support the use of the Montreal Cognitive Assessment (MoCA) to evaluate cognitive function and the Hospital Anxiety and Depression Scale to assess for clinically significant anxiety or depression. Additional scales, include the Impact of Event Scale-6 and the Six-Minute Walk Test, but consensus support for these screening tools is weak.3,12

Laboratory studies

  • Metabolic panel including electrolytes, glucose, renal, and liver studies.31
  • Complete blood count including white blood cell count and hemoglobin.
  • Albumin and pre-albumin levels to monitor nutritional status.32
  • Endocrine tests including workup for thyroid dysfunction and adrenal insufficiency.33
  • There are no validated biomarkers to test for ICUAW at this time, though creatinine kinase may be elevated in patients with ICUAW.6,8,19

Imaging

Chest radiographs or CT scans can aid in the diagnosis of pulmonary edema, acute respiratory distress syndrome (ARDS), atelectasis, pneumonia, or soft tissue abnormalities as alternative etiologies for difficulty weaning mechanical ventilation.34

Bedside ultrasound is a promising modality for the evaluation of the neuro-muscular system, although its reliability in ICUAW is not fully established.35 Ultrasound has been used to detect diaphragm dysfunction by measuring the muscle’s thickness and evaluating its excursion.36 Skeletal muscle changes and wasting can also be appreciated in serial ultrasound examinations of critically ill patients.37

Brain and/or spinal cord imaging may aid in the differential diagnosis to rule out other causes of weakness.19,38

Supplemental assessment tools

In practice, evaluation of mental status, strength, sensation, balance, and mobility are often obscured by critical illness and its treatment.5,6,7,8 Electrodiagnostic testing may help to support the diagnosis, but is often unavailable or difficult to perform in ICU settings.6,8 Electrodiagnostic testing should be considered if there are otherwise unexplained difficulties with ventilator weaning or weakness.19,20

In CIM, nerve conduction studies (NCS) demonstrate normal or near normal conduction velocities, normal sensory nerve action potentials (SNAPs), and normal or low amplitude compound muscle action potentials (CMAPs). Electromyography (EMG) demonstrates low amplitude, frequent motor units and abnormal/ increased insertional activity. In CIP, NCS reveal normal or near normal conduction velocities, reduced SNAP amplitudes, and reduced CMAP amplitudes. EMG demonstrates fibrillations and positive sharp waves, consistent with widespread denervation. There is often overlap between these disorders.4,6,19,20

Phrenic nerve injuries, cervical cord lesions, mononeuropathies and plexopathies, may also be revealed by electrodiagnostic studies.19,20

Early prediction of outcomes

Factors associated with poor functional outcomes include neurological and cognitive impairments, severe mobility impairment, higher severity of critical illness, multiple active and ongoing medical comorbidities, persistent sleep deprivation, and lack of a support system.4,22,27 

Early identification of persons at risk for ICUAW may help target therapeutic or preventive interventions. Functional recovery of patients with ICUAW is negatively affected by multiorgan failure, increased systemic inflammation, prolonged duration of mechanical ventilation, and bed rest. Younger patients with fewer comorbidities, normal baseline cognition, and shorter ICU stay were associated with a better recovery.39

Environmental

The impact of many facets of the ICU environment, including levels of noise, natural light, and family involvement, are being explored.27,40

Social role and support system

Post Intensive Care Syndrome – Family (PICS-F) has been defined as affecting the families of both survivors and nonsurvivors after intensive care hospitalization and can create additional challenges for patients and families.3,41 A psychosocial assessment evaluates how the current illness impacts the patient’s life, support system, and role in society.42

Professional issues

Care teams must maintain appropriate and timely dialogue with the patient, family, and critical care teams regarding the patient’s goals and preferences, the patient’s ability and willingness to participate in rehabilitation interventions, and expected functional outcomes.13,28

Rehabilitation Management and Treatments

Available or current treatment guidelines

Mobilization prevents venous stasis, deep vein thrombosis, and contractures. Therapeutic strategies for mobilization in the ICU setting allow for gradual progression of functional activities. Transferring patients from their beds to upright-seated devices maintains function of core muscles and vascular structures.2,43

General strengthening programs preserve muscle anabolic activity and prevent atrophy. Strengthening programs also address diaphragm weakness after mechanical ventilation. Trials of assisted ambulation positively affect musculoskeletal, cardiovascular, pulmonary, skin, and emotional performance.2,17,18,44

A Cochrane review found only low-quality evidence that early mobilization of critically-ill patients in ICU improves function, adverse events, muscle strength and health-related quality-of-life.45 Nevertheless, many studies suggest that early and intensive intervention by physiatrists and other rehabilitation clinicians can prevent or reduce the development of weakness via interventions during the critical care stay, even in extremely ill patients.1,4,9,15,38,46,47  These interventions may decrease time in bed and ICU and hospital lengths of stay, improve functional outcomes, and increase rates of discharge to home.22,38,47,48,49 

Given that multiple studies have documented a minimal net increase in expenses associated with rehabilitation interventions in the ICU, the low risks and potential advantages seem to favor early initiation of therapy, which may lead to lower hospital resource use and overall cost.4,17,48

Additional interventions aimed at preventing or minimizing ICUAW and functional decline involve optimizing the metabolic state, nutrition, sleep and insulin therapy protocols.14,15,27,32 The benefits and risks of high ventilator settings, deep sedation, muscle relaxants, and steroids should be carefully considered prior to their use.9

At different disease states

Rehabilitation interventions can be initiated during the acute phase of critical illness. A mobility program can begin once the patient is hemodynamically stable.10,46

Intubation should not be a contraindication to active in-bed or out-of-bed mobilization in the ICU. FiO2 less than 0.6 with a percutaneous oxygen saturation greater than 90% and a respiratory rate less than 30 breaths per minute are considered safe criteria for in- and out-of-bed mobilization if no other contraindications exist.50 Early mobilization has also been shown to be safe in patients who require extracorporeal membrane oxygenation.51,52

Therapy programs are individualized. Patient’s physiological response to the activities can guide the nature, intensity, and duration of subsequent therapy sessions. Therapies should ideally be provided daily, as tolerated, and progress from passive to active range of motion, side-to-side turning, isometric and resistance exercises in bed, sitting on the edge of the bed, transferring from bed to a chair, cycle ergometry and ambulation. Hoist therapy, tilt table, and neuromuscular electrical stimulation (E-stim) could also be used.23,28,44

E-stim can be considered for the prevention and treatment of ICUAW and in patients with chronic disease, such as advanced COPD and congestive heart failure,53,54,55,56,57 but careful evaluation and extended cardiac monitoring should be performed in patients with cardiac pacemakers or left ventricular assist device (LVAD) support.58,59 

Prone positioning can be used as an effective chest therapy strategy to increase oxygenation for patients with severe acute respiratory distress syndrome (ARDS).60,61,62

Early rehabilitation is also indicated for patients with other specific diseases. For instance, the early initiation of therapies for acute stroke patients improves post-stroke recovery and overall outcomes.63 Similar findings have been demonstrated for patients in the critical care phases of burn, traumatic brain injury, and spinal cord injury.64,65

After the ICU course is completed, patients should continue therapy interventions to optimize overall function throughout the hospital stay and next steps in care.1,2,23,38

Coordination of care

There are many obstacles to mobilizing ICU patients, including the risk of dislodging of crucial devices, ventilator settings that preclude movement, and medical or vascular access devices inserted in sites that prevent mobility.1,10 Active mobilization should be authorized by the treating physician, senior physical therapist, and nursing staff.51

Nursing and rehabilitation members may have concerns regarding patient safety or may feel uncomfortable initiating therapy in the ICU due to insufficient equipment, time, or staff. Consulting physiatrists can collaborate with the ICU and therapy teams to facilitate the development and implementation of an early mobility protocol. Such practices cultivate a hospital culture that favors the integration of early rehabilitation into the standard of care.1,10,55,66

Patient and family education

Patients and families should be included in discussions regarding ICU and rehabilitation interventions in appropriate detail, and regular updates should be provided regarding the patient’s condition and status. Patients should be educated prior to mobility and ambulation procedures. Family members may also be taught to provide a basic range of motion techniques.2,67  

The use of telehealth has been shown to improve patient care and may be used to provide education and other services to patients and families with restricted access to specialized care.68,69

Measurement of treatment outcomes

Currently there is no single robust standardized statistic used to evaluate outcomes in critically ill patients participating in early mobility protocols.45,70 Clinicians follow strength, mobility, and overall functional status over short and long-term periods.

Extremity muscle strength is measured by hand-held dynamometry or manual muscle testing. Mobility can be monitored by measuring ambulation distance or by the use of timed mobility tests, such as the Six-Minute Walk Test.71 Functional assessments, such as Barthel Activities of Daily Living Index, Katz Index, and Functional Independence Measures (FIM) also provide useful information.72 The Functional Status Score in the ICU consists of selected FIM items and communicates helpful information specific to ICU patients.46

Translation into Practice

There is a growing body of evidence supporting mobilization and rehabilitation of critically ill patients.1,43,45,46,49,51,53,57,73,74,75,76 A collaborative interdisciplinary program is needed to overcome barriers to early mobility.1,10,44,77 A strong interdisciplinary team continuously optimizes outcomes by evaluating practices that interfere with early mobility, creating strategies to allow mobility, and implementing short- and long-term plans.13,28,77

Cutting Edge/ Emerging and Unique Concepts and Practice

Custom designed technological aids help with safety and effectiveness of early mobilization, particularly for patients on mechanical ventilators. Specially designed walkers, chairs, and standing frames hold multiple pieces of ICU equipment, facilitate standing and walking activities, and optimize balance.78

Gaps in the Evidence- Based Knowledge

Controversies and gaps in the evidence-based knowledge

Even though early physical rehabilitation in the ICU has been shown to improve short-term clinical outcomes, there is a paucity of evidence to support long-term benefit and further research is needed to elucidate the optimum intensity of rehabilitation.79 It would be helpful to have a standardized outcome measure, either biometric or qualitative, to optimally evaluate and delineate the effects of an early mobility program.12,46

It is unclear if certain nutrients or antioxidants may prevent functional decline. Arginine, glutamine, and fish oil supplementation have not demonstrated conclusive benefits. Further studies are needed.16,32

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Original Version of the Topic

Diane Schretzman Mortimer, MD, James Dvorak, MD, Parisa Salehi, MD, Vasilios Kountis, DO. Rehabilitation of patients in critical care settings. 10/2/2015

Author Disclosure

Laurentiu Dinescu, MD
Nothing to Disclose

Rebecca Sussman, MD
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Shruti Amin, MD
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Noemi Olivero, MD
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