Rehabilitation of Patients in Critical Care Settings

Disease/Disorder

Definition

ICU acquired weakness (ICUAW) is defined as clinically detected, diffuse, symmetric weakness involving all extremities and respiratory muscles arising after the onset of critical illness. It can result in impaired mobility and performance of activities of daily living (ADLs) resulting in overall functional decline.^1,2 The development of ICUAW, leading to such impairments, is further associated with prolonged mechanical ventilation dependence, ICU length of stay, and increased overall mortality.^1,3,4,5,6 Time of onset is critical and can distinguish ICUAW from other acute neuromuscular syndromes which lead to respiratory failure and subsequent ICU admission.¹

ICUAW is a broadly defined clinical diagnosis not to be confused with Critical Illness Myopathy (CIM) and Critical Illness Polyneuropathy (CIP), specific conditions with well-defined electrophysiologic findings. However, CIM and CIP can result in ICUAW and may present as overlapping syndromes.^1,5 Conceptually, ICUAW provides a framework for multidisciplinary teams to monitor, prevent, and treat clinically significant generalized weakness and decline in physical and respiratory function secondary to critical illness. Other causes of weakness must be ruled out with a careful clinical history and thorough neurological exam. Laboratory tests and imaging may help exclude other etiologies.⁷

The Post-Intensive Care Syndrome (PICS) was initially described in 2010 as a “new or worsening impairment in physical, cognitive, or mental health status arising from and persisting after hospitalization for critical care illness”. It has since garnered increasing attention as medical advances improving ICU mortality have resulted in a growing population demonstrating significant impairment following critical illness.³ PICS can persist for months to years post-discharge. There may be some correlation between patients who develop ICUAW and those who develop PICS, as ICUAW can result in increased healthcare utilization, decreased quality of life, and decreased probability of return to home, in addition to previously mentioned association with prolonged mechanical ventilation, prolonged length of stay, increased mortality. However, no studies have clearly demonstrated that ICUAW is a predictor or precursor of PICS.^4,8

Etiology

The ICU environment is highly stimulating while simultaneously involving prolonged bed rest and immobility, and critically ill patients are often beset by disturbed sleep, inadequate nutritional intake, and pain.⁹ Functional decline in the ICU can occur regardless of admitting diagnoses, though it is most strongly associated with severity of illness.⁵ 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 (e.g., glucocorticoids, neuromuscular blocking agents) have also been linked to electrophysiologic and clinical signs of ICUAW.^1,2

Epidemiology

Muscle weakness, ranging from mild monoparesis to severe tetraplegia has been noted in 25-100% of all patients who spend seven or more days in an ICU.² 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 with over one week of mechanical ventilation and up to 70% of patients diagnosed with sepsis or systemic inflammatory response syndrome.⁵ Incidence approaches 100% if multiple organ failure is present.⁷ At ICU discharge, nearly all survivors of critical illness have impairments in one or more of the three PICS domains – physical, cognitive, and emotional – and these impairments persist in 64% and 56% of survivors at three and twelve months, respectively.³

Patho-anatomy/physiology

Classically, ICU patients have been kept on bedrest, the complications of which include disuse muscle atrophy, joint contracture, thromboembolic disease, insulin resistance, atelectasis, and skin breakdown.⁷ Immobility of critical illness has deleterious effects on muscle structure and function. Studies have demonstrated a 1-1.5% decrease in  total muscle mass per day and up to a 50% decrease in total muscle mass over 2 weeks of immobility, with a significant increase in mortality occurring amongst those with more than a 40% loss in muscle mass.^10,11 This is primarily due to reduced muscle fiber size, particularly in weight-bearing muscles of the lower limbs and core.² Muscle inactivity also stimulates protease activation and thus leads directly to muscle breakdown, increased catabolism, and decreased contractility.² CIM, specifically, is identifiable microscopically by its preferential myosin proteolysis.⁷ 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.^2,15

Sepsis and other critical illnesses similarly induce metabolic and vascular derangements which damage peripheral nerves and skeletal muscles.² The complex biochemical milieu resulting from critical illness also result in channelopathies which impair neuronal transmission and muscular contraction, further promoting the development of ICUAW. Patients who are mechanically ventilated, under deep sedation, or receiving neuromuscular blocking agents can experience mechanical silencing, wherein lack of mechanical stimulation to the muscles worsens muscle wasting.¹ Further, prolonged mechanical ventilation can alter diaphragmatic structure and function, leading to difficulties with breathing and ventilator weaning.¹

Medications can inadvertently cause weakness. Neuromuscular blockers can damage the neuromuscular junction and its function and increase its susceptibility to corticosteroid-mediated muscle weakness.⁶ Steroids can injure muscle cells and impair muscle and nerve metabolism, but they have demonstrated a protective effect against ICUAW, likely secondary to their impact on the underlying severity of illness.⁷ Sedatives can lead to decreased muscle contraction and vascular tone, leading to altered mobility.²

Malnutrition may contribute to neuromuscular dysfunction, though 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.¹

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 the lower more than the upper limbs. Some patients progress to quadriparesis. Although facial weakness and ophthalmoplegia can occur, movements of the head, facial, tongue, and jaw tend to be spared.^5,6,7 

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.^2,5,6

Symptom progression and severity vary. Observable declines in muscle size and function have been detected after just two weeks of immobility, but observation can be obscured by dependent limb edema.⁶ Alterations in peripheral nerves are clinically evident within one to two weeks of critical illness.⁷ Evolution to extensive and generalized muscular 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.⁷ 

Recovery is variable and typically occurs over weeks to months; some patients do not fully recover. Even when weakness resolves, many patients experience a persistent marked reduction in physical function following critical illness.⁵ At least 50% of ICU patients report inability to return to work due to fatigue, weakness, or overall impaired functional status one year after their critical care stay.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, as well as both longer ICU stays and an increased likelihood of discharge to a skilled nursing facility or other care facility.⁵ 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.³

Delirium is extremely common among ICU patients.¹² Sedatives, especially benzodiazepines, are independently associated with both the development and severity of delirium. Additional factors associated with the development of delirium include frequent assessments, impaired sleep (especially Stage 3 and REM), altered circadian rhythm, lab draws, and environmental factors. Sleep-promoting protocols are universally recommended for ICU patients, but no specific medication management is currently recommended.⁹ Delirium is independently associated with increased morbidity and mortality and often leads to persistently impaired cognition.^3,8 PTSD, anxiety, and depression are frequently reported by ICU survivors. 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, ICU environmental issues, or medications.³

Essentials of Assessment

History

Relevant history includes assessment of prior functional status, health history (including musculoskeletal or skin issues), and social history (including substance abuse history). This may initially be difficult to obtain given the severe and often sudden nature of critical illness.The ICU course includes diagnoses that led to ICU stay, treatment before ICU arrival, severity of illness, treatment course (including the use of steroids, vasopressors, mechanical ventilation, paralytics, and antibiotics), and the presence of metabolic derangements such as hyperglycemia.²

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 if applicable; 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.²

Clinical functional assessment

All ICU patients should be assessed for the appropriateness of early mobility every day, but resources and staffing limit the ability to offer rehabilitative services to every patient every day.  Early performance of functional status evaluation combined with screening for frailty following ICU admission may identify patients at the highest risk for functional decline and those who may benefit most from therapy.^3,14 A comprehensive evaluation should include swallow, speech, self-care, mobility, functional activity tolerance, sleep, pain, and nutrition.⁷ Pre-ICU factors such as age, comorbidities and frailty, patient/proxy reporting of ADL function and mobility, and pre-ICU trajectories for muscle mass and physical functioning should also be assessed.⁴

Formal assessment for ICUAW involves the use of the Medical Research Council scale (MRC), a categorical scale measuring volitional muscle strength from 0 (no appreciable contraction) to 5 (full active range of motion against maximum resistance) in 12 muscle groups.¹ A sum score of <48/60 or a mean score of 4 in all testable muscle groups indicates significant weakness and is consistent with ICUAW. However, the test is only useful in alert and cooperative patients. Within this limitation, this assessment has great inter- and intra-rater reliability and is a widely accepted clinical scale for ICUAW.¹ Handgrip dynamometry may also be used as a more objective measure of volitional muscle strength in cooperative patients and has been inversely linked to both mortality and accelerated aging.¹⁵ Dynamometry scores less than 11 kg in males or less than 7 kg in females have been used as cutoffs to support the diagnosis of ICUAW in the absence of another neurological disorder.¹

The evaluation of physical functioning is complex and influenced by multiple interrelated factors, making identification of the optimal ICU functional measure elusive. Many instruments used in settings outside the ICU are not appropriate in the ICU, partly because of floor and ceiling effects – high floor effects indicate an instrument is too difficult, limiting its ability to detect a change in the physical functioning of patients. The four recommended physical functioning tools in the ICU are: Physical Function in ICU Test-Scored (PFIT), Functional Status Score for the ICU (FSS-ICU), Chelsea Critical Care Physical Assessment Tool, and Johns Hopkins ICU Mobility Scale. Of these, the most frequently utilized is the Johns Hopkins ICU Mobility Scale because it does not require any extra training or equipment, helps inform the next steps of physical therapy intervention, and can be incorporated into nursing workflow for daily mobility goals when a therapy session is not feasible on any given day. The Perme ICU Mobility Score is another unique measure because it integrates mental status, mobility barriers, functional strength, bed mobility, transfers, gait, and endurance.⁴

The CAM-ICU is a well-validated assessment of delirium, but it is difficult to track and intervene upon due to its binary scoring. The CAM-ICU 7 utilizes the CAM-ICU and RASS to assess severity of delirium. This measure was validated against another delirium severity assessment that has not been implemented in the ICU due to difficult interpretation with mechanically ventilated patients. Further research is necessary to evaluate its efficacy in evaluating and treating delirium in the ICU.¹² 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

Laboratory studies

• Metabolic panel; including electrolytes, glucose, renal, and liver studies.
• Complete blood count; including white blood cell count and hemoglobin.
• Nutritional markers; including albumin and pre-albumin.
• Endocrine tests; including workup for thyroid dysfunction and adrenal insufficiency.
• There are no validated biomarkers to test for ICUAW. However, inflammatory markers such as creatine kinase, erythrocyte sedimentation rate, and auto-antibodies may prove useful as part of the general workup.⁹

Imaging

Neuromuscular ultrasound (NMUS) is a promising modality for the evaluation of the neuromuscular system and can be performed rapidly at the bedside. Its utilization is especially useful in patients unable to participate in an examination. Protocols have been developed for NMUS utilization in evaluation of critical illness myopathy, utilizing grading scales such as the Heckmatt system. Ultrasound has been used to detect diaphragm dysfunction by measuring its thickness, excursion, and general appearance. Though these developments are promising, they too need further validation.¹⁶

Brain and/or spinal cord imaging may aid in the differential diagnosis to rule out other causes of weakness.⁶ Similarly the brachial or lumbosacral plexus could be imaged in the appropriate clinical setting to assess for a focal neurologic condition in these regions.

Supplemental assessment tools

In practice, the evaluation of mental status, strength, sensation, balance, and mobility is often obscured by critical illness and its treatment.^1,2,5 Electrodiagnostic testing may help to support the diagnosis, but it is often unavailable or difficult to perform in ICU settings.^2,5 Still, it should be considered if there are otherwise unexplained difficulties with ventilator weaning or weakness.

In CIM, nerve conduction studies (NCS) are largely normal except for potentially low-amplitude compound muscle action potentials (CMAPs). Electromyography (EMG) demonstrates low amplitude, frequent motor units, early recruitment, 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.²

ICUAW should only be diagnosed in the absence of other identifiable causes of weakness. A broad differential diagnosis is helpful in ruling out other etiologies.⁶

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.² 

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, early initiation of mobility/rehabilitation, and shorter ICU stay were associated with a better recovery.^8,17

Environmental

The impact of many facets of the ICU environment, including levels of noise, natural light, and family involvement, is being explored.^8,9 Current recommendations suggest maintaining daytime wakefulness and promoting sleep at night. Bundling care (assessments, medication administration, and lab draws) is one environmental intervention that should be attempted whenever possible. ICU diaries can be filled out by patients, family members, or medical team members. They can help provide context for patients and improve rates of anxiety/PTSD following discharge. ³

Social role and support system

Post Intensive Care Syndrome – Family (PICS-F) has been described as affecting the families of both survivors and non-survivors after intensive care hospitalization and can create additional challenges for patients and families. A psychosocial assessment evaluates how the current illness impacts the patient’s life, support system, and role in society. Support groups and other resources should be sought as appropriate for those who are impacted.³

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.

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 the function of core muscles and vascular structures.¹⁸ 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.^8,10,11

The A-F Bundle, initially developed by Wes Ely and colleagues in 2010, is a collection of six nurse-driven interventions carried out by the multidisciplinary ICU team that have demonstrated improvement in many important clinical outcomes, including mortality, ICU and hospital length of stay, and functional status. The efficacy of the bundle is directly related to the number of interventions utilized.⁸ Of these six interventions, the most underutilized is early mobility, especially among mechanically ventilated patients.¹³ Despite the predicted benefits, early studies failed to demonstrate a clear benefit of early mobility within the ICU. This prompted further evaluation of what early mobility should entail and how to evaluate its effect, which resulted in different iterations of ICU mobility protocols and quality improvement projects to improve adherence to this part of the bundle. Subsequent meta-analyses have demonstrated the efficacy of early mobility, with the greatest effect derived when initiated within 48-72 hours of ICU admission, especially in mechanically ventilated patients who are at the greatest risk of ICUAW and PICS.^11,19

Other studies have looked at both early and very early mobilization and outcomes for stroke patients with mixed results. Studies looking at early mobilization, defined as mobilization less than 72 hours of admission, showed improved functional independence measures (FIM) motor scores (P<0.03).²⁰ Studies on very early mobilization (VEM), defined as mobilization less than 24 hours of admission, showed varied results on outcomes. Those using the Barthel Index or FIM scores favored VEM, while those measuring the modified Rankin Scale did not.^21,22 Similar findings have been demonstrated for patients in the critical care phases of burn, traumatic brain injury, and spinal cord injury.²³

Given that multiple studies have documented minimal net increases 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. ⁹

Additional interventions aimed at preventing or minimizing ICUAW and functional decline involve optimizing the metabolic state, nutrition, sleep and insulin therapy protocols.⁷ The benefits and risks of high ventilator settings, deep sedation, muscle relaxants, and steroids should be carefully considered prior to their use.

At different disease states

The A-F bundle is designed to apply to every ICU patient every day. Thus, rehabilitation interventions can and should be initiated early during the acute phase of critical illness. A mobility program can begin once the patient is hemodynamically stable.⁸ Early mobility is safe in the vast majority of patients, including those on stable mechanical ventilation settings and ECMO, as described in an expert consensus statement in 2014.²⁴

Therapy programs are individualized interventions. A 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) can also be considered as adjunct therapy options.^8,10,11

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, but careful evaluation and extended cardiac monitoring should be performed in patients with cardiac pacemakers or left ventricular assist device (LVAD) support.^25,26 

Following their ICU course, patients should continue therapy interventions to optimize overall function throughout the hospital stay and the next stages of care.²

Coordination of care

There are many obstacles to mobilizing ICU patients, including the risk of dislodging crucial devices, ventilator settings that preclude movement, and medical or vascular access devices inserted in sites that prevent mobility.Active mobilization should be authorized by the treating physician, senior physical therapist, and nursing staff.⁸

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.²⁶

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 basic range of motion techniques. 

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.²⁷

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.^3,11,19 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 with timed mobility tests such as the Six-Minute Walk Test. Functional assessments such as Barthel Activities of Daily Living Index, Katz Index, and Functional Independence Measures (FIM) also provide useful information.²⁸ The recent mandated shift of mobility and self-care Quality Indicators for inpatient rehabilitation facilities has not been similarly mandated for acute care hospitals, but may be used in the acute care or ICU setting and have certainly become a focus of ICU research. These Quality Indicators, as mandated for IRF by section GG of the Functional Abilities and Goals of the Improving Post-Acute Care Transformation Act, were implemented in 2019 by the Center for Medicaid Services as a replacement for FIM.^29,30

Translation into practice

There is a growing body of evidence supporting the mobilization and rehabilitation of critically ill patients.^{8,11,18,19,25} A collaborative interdisciplinary program is needed to overcome barriers to early mobility. 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.^10,13,19

Cutting Edge/Emerging and Unique Concepts and Practice

Custom-designed technological aids help with the 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.¹⁰

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.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.⁴

Closing Remarks

Critical Care, like Rehabilitation, is a relatively new field, with its origins in the early to mid 20^th century. Though these fields typically operate on opposite ends of the acuity spectrum, they are inexorably intertwined. With an ever-growing survivor population, the focus of critical care research has shifted to patient-centered outcomes, including function, which opens the door for physiatrists to add extraordinary value. As a specialty, Physical Medicine and Rehabilitation (PM&R) is uniquely suited to follow these patients through their recovery. We can and should educate patients, their families, and the ICU team about different aspects of rehabilitation and what to expect from the process; this is instrumental in guiding family meetings and goals-of-care conversations. As data and practice patterns regarding ICU mobility and rehabilitation continue to evolve, our expertise will be paramount in curating the most appropriate interventions. Further research is essential to further elucidate just how impactful PM&R can be within critical care, but it is clear that the future is bright.

References

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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

Previous Revision(s) of the Topic

Laurentiu Dinescu, MD, Rebecca Sussman, MD, Shruti Amin, MD, Noemi Olivero, MD. Rehabilitation of Patients in Critical Care Settings. 6/8/2021

Author Disclosure

Daniel A. Goodman, MD, MS
Nothing to Disclose

James R. Devanney, DO
Nothing to Disclose

Alexander Brahmsteadt, DO
Nothing to Disclose

Benjamin Ballard
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Sung-Hoon Park
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Ryan Stork, MD
Nothing to Disclose

Michael V. Nguyen, MD, MPH
Nothing to Disclose