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Survivors of critical illness commonly manifest weakness, neurocognitive decline, and loss of functional independence that affect their post hospital care. Targeted rehabilitation interventions to promote early mobility and reduce delirium are associated with improved ICU outcomes, and evidence supports interdisciplinary initiatives as feasible and cost-effective.

While specific nomenclature is still evolving, a consensus is emerging around a framework for ICU acquired weakness (ICUAW), which consists of two broad categories; immobility and neuromuscular dysfunction.1 This latter form has been divided into critical illness polyneuropathy (CIP) and critical illness myopathy (CIM). When these two neuromuscular disorders overlap, the proposed term is critical illness neuromyopathy (CINM).2

The presence of delirium is associated with increased mortality, longer ICU stay, and cognitive impairment extending beyond the ICU stay.3 Delirium is defined as an acute onset of change or fluctuations in mental status characterized by inattention, and either disorganized thinking or altered level of consciousness. Delirium is classified into hypoactive, hyperactive, or mixed. Hyopactive delirium is associated with a worse outcome as it is commonly misdiagnosed.

While evidence to support rehabilitation in the ICU is compelling, there is a significant gap in this established knowledge and real-world clinical practice. The implementation of an effective rehabilitation program in the ICU setting appears to be best accomplished through an interdisciplinary team approach and using a structured approach to quality improvement.


The causes of weakness in the ICU are multi-factorial and causative factors include immobility, preexisting weakness, underlying medical conditions, and ICU associated weakness (ICUAW). The underlying mechanism for neuromuscular dysfunction in ICUAW includes a combination of axonal degeneration, muscle breakdown, and sodium channel dysfunction with ensuing muscle membrane hypoexcitability.

The causes of delirium are also multi-factorial including current medical conditions, past medical history and chronic diseases, premorbid cognitive function, acute pain, medications, infection, and the ICU environment itself.

Epidemiology including risk factors and primary prevention

ICUAW is common. The reported incidence ranges from 26-65% for patients intubated for a duration of 5-7 days, and up to 67% of patients with prolonged periods of intubation (>10 days).4  Weakness persisted for at least another 7 days following extubation in an estimated 25% of those patients. In patients with ARDS, an estimated 60% develop ICUAW.4

Up to 80% of adult ICU patients on mechanical ventilation develop delirium.3 Hypoactive (44%) and mixed hypoactive/hyperactive (55%) are the most common forms. 30-80% of ICU survivors demonstrate long-term cognitive impairment.

Risk factors for developing ICUAW include severe illness, immobilization, sepsis, multi-organ failure, length of ventilator support, septic encephalopathy, hyperglycemia, older age, and exposure to vasopressin or aminoglycosides. 2,4,5 Non-modifiable risk factors for delirium include age,  premorbid dementia, history of hypertension or alcoholism, increased severity of illness, and coma.3Modifiable risk factors include prolonged immobilization, medications, in particular benzodiazepines and opiates, untreated pain, use of physical restraints and sensory deficits. 6,7

Early mobilization plays a key role in prevention of ICUAW and neurocognitive decline. Schweickert and collagues showed that patients in an early rehabilitation program with combined PT/OT had decreased delirium, reduced length of stay in the ICU (median of 2 days less), and return to function in 59% of the intervention group compared to the control group.8  Needham and colleagues found that increased PM&R consults and dedicated therapy with a team focus on decreased sedation and early mobilization improved sedation and delirium status with improved ICU and Hospital LOS. 9


The deleterious effects of immobility are familiar to physiatrist. Complications from bedrest include muscle atrophy, contractures, venous thromboembolism, insulin resistance, miscrovascular dysfunction, systemic inflammation, atelectasis, and pressure ulcers. CIP results from distal axonal degeneration secondary to microvascular dysfunction in the endoneureum.4 The ensuing edema and exposure to toxins impairs axonal function leading to eventual axonal death.  Possible channelopathy as a mechanism of injury has been proposed based on animal studies.4 CIM results from decreased protein synthesis and muscle breakdown/atrophy, with preferential loss of myosin. Inflammatory mediators including TNFα, IL-6, and IL-1 appear to play a role.4 Dysfunction of sodium channels lead to hypoexcitability of muscle membranes, contributing to weakness.4

Delirium represents a dysfunction of the brain arising from a complex interplay of risk factors including the underlying disease, polypharmacy, pain, environmental stimulation, and sleep deprivation. Despite increased reports in the medical literature, the pathophysiology of delirium is not well known.3 Potential factors that have been suggested include functional anatomic deficits, neurotransmitter dysfunction, impaired cerebral oxidative metabolism and disruption of the blood brain barrier secondary to inflammation and cytokine dysfunction.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

The hallmark of ICUAW is flaccid, symmetric weakness of muscles with greater involvement of proximal muscles compared to distal muscle groups. Facial and ocular muscles are usually spared.4 Deep tendon reflexes are variably affected. Loss of pain, temperature, and vibration may be present in cases of CIP. Due to involvement of the phrenic nerve and muscles of respiration, failure to wean from the ventilator is often a presenting symptom.2 Contributions of small fiber neuropathy and dysautonomia have been proposed as well.

Patients with prolonged ICU stays have a very high mortality rate acutely. However, survivors do make substantial functional gains. Most recover within weeks to months, reaching a stable state approximately one year later. Some studies suggest that CIM may recover faster than CIP. At 5 years, 77% of survivors returned to work. Nevertheless, most patients do not return to normal function compared to others in their age group.10  Persistent fatigue and weakness are common complaints.

Elderly patients who experience delirium however have higher hospital and overall mortality at one year as well as admission to long-term care.11 In addition the duration of delirium is an independent predictor of 3-month and 12-month cognitive decline.12

Specific secondary or associated conditions and complications

It is suggested that 3 to 11% of strength is lost for each day a patient spends in bed in an ICU setting.5 Days of bed rest are independent predictors for decreased overall function.5 The complications of prolonged immobility are myriad, and beyond the scope of this discussion. Nevertheless, it would be remiss to neglect the cardiopulmonary effects, risk of venous thromboembolism, pressure sores, contractures, osteoporosis, and fluid and electrolyte imbalances which can occur.



Weakness and delirium increase with severity of illness, and the presence of delirium is associated with increased length of stay. Delirium is independently associated with poorer outcomes in ICU patients including increased mortality, functional loss, neuro-cognitive impairments, and long-term care placement. A physiatric history includes severity of illness and ongoing evidence of delirium, identification of potential delirium promoting medications, including opiates and benzodiazepines, as well as assessment of pain. In addition, physiatrists can contribute to effective post-acute care planning and coordination. Information on the patient’s previous living situation, cognition, functional independence, social support, and availability of family and caregivers are important variables when developing post-acute care plans.

Physical examination

The PM&R physical examination highlights cognition, neuro-musculosketal exam, and physical function.

The diagnosis of delirium is made in finding an acute onset of change or fluctuations in mental status, inattention, and either disorganized thinking or altered level of consciousness. Standardized bedside exams such as the CAM-ICU can be utilized to assist in diagnosis (CAM-ICU; http://www.icudelirium.org). Cognitive functioning should also be assessed for patients without delirium. Depending on the specific circumstances, the mental status exam may include ability to follow directions, orientation, attention, language, memory, executive function, praxis, visuospacial, and general impression.13

The physical exam includes assessments of muscle strength, tone, coordination, balance, range of motion, presence of reflexes, skin, and sensation, along with relevant aspects of a general physical exam. As clinically indicated, swallowing should be assessed.

The patient’s ability to perform bed mobility, ambulation, and feeding should be assessed if clinically feasible.

The MRC (Medical Research Council) sum score is a validated screening tool that is used in the intensive care setting to diagnose ICUAW, indicated by a score less than 48.4 Wrist extension, elbow flexion, shoulder abduction, dorsiflexion, knee extension, and hip flexion are graded on a scale of 0-5 strength bilaterally for a maximum score of 60.  This method requires patient alertness and cooperation. A limitation of the test is the inability to identify cause of weakness, or to distinguish between CIP or CIM. The MRC sum score is an independent predictor of prolonged need for ventilation, prolonged ICU and hospital stay, as well as one-year mortality. 2

Hand grip strength measured by dynamometer has been shown to be an alternative to the MRC sum score, especially in patients with significant weakness who are unable to activate the proximal muscle groups required for the MRC sum score. 2,4

Functional assessment

Care must be taken with regards to patient safety and the presence of tubes, lines, and drains in the functional assessment of ICU patients. Collaborative efforts involving ICU personnel (eg. medical intensivist, respiratory therapists, nurses) and rehabilitation professionals (physicians, physical therapists, and occupation therapist) have proven helpful in comprehensive functional assessment and interventions in the ICU setting.

Laboratory studies

There are no specific laboratory studies to diagnose ICUAW. Systemic causes of weakness and neurocognitive deficits must be actively pursued including infectious causes. Serum Creatine Kinase can be elevated in cases of muscle fiber loss.  GDF-15 is a biomarker associated with development of ICUAW, which may have promising future applications in the diagnosis of ICUAW4.

Electrodiagnosis will usually show reduced amplitudes of CMAP. SNAP may or may not be reduced, and nerve conductions may be normal to near normal with widespread spontaneous denervation potentials (fibs/PSW).4  Electrodiagnosis can be limiting due to poor volitional strength, and can not distinguish between CIP and CIM.2 The addition of direct muscle stimulation to routine electromyography and nerve conduction studies has shown encouraging result in diagnosing ICU acquired weakness.

There is some literature on muscle or nerve biopsies.5 However, such tests are not practical with limited literature to warrant routine use in the ICU setting.


Imaging studies are dictated by the clinical presentation and may involve work up for underlying neurological (e.g CAT scans, MRIs, EEGs, lumbar puncture), muscloskeletal (e.g. fracture, heterotopic ossification), and rheumatologic (e.g SLE, vasculitis) issues. Ultrasound can be used to identify muscle atrophy, changes in muscle architecture, and fasiculations.4

Supplemental assessment tools

The Confusion Assessment Method for the ICU (CAM-ICU; http://www.icudelirium.org) has been a widely used delirium assessment tool in ICU research and practice. 14,15 It has been shown to have a high sensitivity and specificity for detecting delirium in non-psychiatric trained providers. Its value in clinical practice has been questioned by recent research which found a low sensitivity when comparing routine use by ICU nurses examination compared to delirium experts. In particular, a skillful examiner was more likely to diagnose hypoactive delirium.

Early predictions of outcomes

Delirium, prolonged bedrest, poor sleep hygiene, prolonged mechanical ventilation and increased use of sedative and pain medications are potentially modifiable factors of poor outcomes.


Increased numbers of rehabilitation therapists and reduction in the use of sedative and pain medications are associated with improved functional outcomes in the ICU. Environmental changes to reduce noise and to increase natural sunlight increase patient orientation and ability to participate in rehabilitation. Ongoing research by Needham et al supports the hypothesis that improvements in sleep hygiene predict improved functional outcomes.9 Bryczkowski et al found that environmental modifications to promote sleep in conjunction with medication modification and increased therapy services both reduced usage of sedative and pain medications as well as reduced ventilator days and ICU length of stay. 16

Social role and social support system

Assessments of social, financial, and caregiver resources are pivotal to effective planning following the ICU stay and acute hospitalization. In addition, early caregiver education and involvement promotes engagement with discharge planning and should facilitate the optimal long-term functional outcome.

Professional Issues

In coordination with ICU staff, rehabilitation professionals, due to their expertise in functional prognosis may have the opportunity to participate in end of life discussions. With our focus on long-term functional outcomes, we have the responsibility to advocate for safe post-acute care plans. While community discharge with family is generally preferred, the physiatrist has a responsibility to communicate to staff and family if a particular home discharge is deemed unsafe.


Available or current treatment guidelines

The safety and efficacy of early mobility and exercise of ICU patients has been well established.17 With proper training and an interdisciplinary approach, rehabilitation professionals can safely mobilize, exercise, and ambulate complex debilitated patients including those on mechanical ventilation. In addition, efforts to reduce sedative and pain medication promote improved outcomes, and initiatives to improve sleep hygiene look promising as another way to improve outcomes.16

At different disease stages

Consultants recommending an appropriate rehabilitation level of care for post discharge from a prolonged ICU stay are often faced with difficult decisions. Patients may not have the endurance to tolerate the 3 hours of daily therapy required in a comprehensive integrated inpatient rehabilitation program. There is some flexibility in the Medicare guidelines, governing Inpatient Rehabilitation Facilites [IRF] permitting 15 hours spread over 7 days rather than 5 days. Patients often are too complex medically to be safely sent to a sub acute rehabilitation in a nursing facility. Transitional care units in hospitals or long-term acute care hospital units offer other potential dispositions.

Patient & family education

The recent Pain, Agitation, and Delirium (PAD) guidelines recommended by the Society of Critical Care Medicine emphasize the critical importance of family education and empowerment to improve ICU outcomes.3 Patient and family education should include functional prognosis, education about delirium and weakness, appropriate infectious isolation precautions, and bed positioning, as well as, potentially, bedside range of motion.

Emerging/unique Interventions

Impairment-based measure:

The 6-minute walk test for endurance and the Get Up and Go (GUG) measures the ability to do sit to stand.

Measurement of Patient Outcomes:

Rehabilitation and environmental interventions in the ICU setting are associated with positive outcomes in mortality, cognition, physical functioning, and discharge destination.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Despite the established benefit of rehabilitation and environmental changes in the ICU to reduce delirium and promote function, there remains a chasm between research and practice in many ICUs. A Quality Improvement (QI) approach is useful in the implementation of rehabilitation in an ICU. Management of delirium is part of the Pain, Agitation, and Delirium (PAD) guidelines recommended by the Society of Critical Care Medicine. Regular assessment for the development of delirium using the Confusion Assessment Method for the ICU (ICU-CAM), or The Intensive Care Delirium Screening Check List (ICDSC) is supported.

One highly successful QI project with mechanically ventilated patients in the ICU used the 4 Es approach (Engage, Educate, Execute, and Evaluate).18 The initial Engagement portion highlighted interactive learning. All stakeholders (leaders, supervisors, frontline clinical staff) learned the benefits of the new initiative and the value of an interdisciplinary approach. Staff were encouraged to exchange patient anecdotes; patients returned to the ICU to share their stories; and guest lectures reviewed the current knowledge. The Education portion highlighted specific skill acquisition such as physical therapists leaning basics of ventilators and respiratory therapists demonstrating safe patient transfer techniques. The Execution of the project honed in on interventions and strategies to identified barriers. The Evaluation of the project occurred though multidisciplinary meetings structured around specified outcomes.


Cutting edge concepts and practice

Programs are now using neuromuscular electrical stimulation to facilitate muscle movement in patients who are too sedated or delirious to participate in an active exercise program.


Gaps in the evidence-based knowledge

  1. Diagnosis and quantification of ICU – acquired weakness (immobility and weakness associated with neuromuscular dysfunction).
  2. Basic and clinical research on reducing delirium.
  3. Post- ICU Functional Outcomes (cognitive and physical).
  4. Effect of physical therapy or alternative treatment on functional outcomes that are meaningful to patients compared to typical ICU management.
  5. Association of premorbid disability to development of ICUAW and overall prognosis.
  6. Strategies and equipment to mobilize patients including electrical neurostimulation, exercise equipment in bed (e.g. cycle ergometry for UE or LE), and tilt bed for bed bound patients.
  7. Neurostimulants
  8. Outcomes Research and Rehab QI in the ICU – including team functioning and patient participation.


  1. Stevens RD, Marshall SA, Cornblath DR, et al. A framework for diagnosing and classifying intensive care unit-acquired weakness. Crit Care Med. 2009;37(10 Suppl):S299-S308. doi:10.1097/CCM.0b013e3181b6ef67.
  2. Friedrich O, Reid MB, Van den Berghe G, et al. The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill. Physiol Rev. 2015;95(3):1025-1109. doi:10.1152/physrev.00028.2014.
  3. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. In: Vol 41. 2013:263-306. doi:10.1097/CCM.0b013e3182783b72.
  4. Hermans G, Van den Berghe G. Clinical review: intensive care unit acquired weakness. Critical Care. September 2016:1-9. doi:10.1186/s13054-015-0993-7.
  5. Fan E, Cheek F, Chlan L, et al. An official American Thoracic Society Clinical Practice guideline: the diagnosis of intensive care unit-acquired weakness in adults. Am J Respir Crit Care Med. 2014;190(12):1437-1446. doi:10.1164/rccm.201411-2011ST.
  6. Van Rompaey B, Elseviers MM, Schuurmans MJ, Shortridge-Baggett LM, Truijen S, Bossaert L. Risk factors for delirium in intensive care patients: a prospective cohort study. Crit Care. 2009;13(3):R77. doi:10.1186/cc7892.
  7. Aldemir M, Ozen S, Kara IH, Sir A, Baç B. Predisposing factors for delirium in the surgical intensive care unit. Critical Care. 2001;5(5):265-270.
  8. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. The Lancet. 2009;373(9678):1874-1882. doi:10.1016/S0140-6736(09)60658-9.
  9. Needham DM, Korupolu R, Zanni JM, et al. Early Physical Medicine and Rehabilitation for Patients With Acute Respiratory Failure: A Quality Improvement Project. Archives of Physical Medicine and Rehabilitation. 2010;91(4):536-542. doi:10.1016/j.apmr.2010.01.002.
  10. Herridge MS, Tansey CM, Matté A. Functional disability 5 years after acute respiratory distress syndrome. New England Journal of Medicine. 2011;364(14):1293-1304. doi:10.1056/NEJMoa1011802.
  11. Inouye SK, Bogardus ST, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340(9):669-676. doi:10.1056/NEJM199903043400901.
  12. Girard TD, Jackson JC, Pandharipande PP, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010;38(7):1513-1520. doi:10.1097/CCM.0b013e3181e47be1.
  13. Kipps CM, Hodges JR. Cognitive assessment for clinicians. J Neurol Neurosurg Psychiatr. 2005;76 Suppl 1:i22-i30. doi:10.1136/jnnp.2004.059758.
  14. ICU Delirium and Cognitive Study Group.
  15. Needham DM, Truong AD, Fan E. Technology to enhance physical rehabilitation of critically ill patients. Crit Care Med. 2009;37(10 Suppl):S436-S441. doi:10.1097/CCM.0b013e3181b6fa29.
  16. Bryczkowski SB, Lopreiato MC, Yonclas PP, Sacca JJ, Mosenthal AC. Delirium prevention program in the surgical intensive care unit improved the outcomes of older adults. J Surg Res. 2014;190(1):280-288. doi:10.1016/j.jss.2014.02.044.
  17. Bailey P, Thomsen GE, Spuhler VJ, et al. Early activity is feasible and safe in respiratory failure patients. Crit Care Med. 2007;35(1):139-145. doi:10.1097/01.CCM.0000251130.69568.87.
  18. Needham DM, Korupolu R. Rehabilitation quality improvement in an intensive care unit setting: implementation of a quality improvement model. Top Stroke Rehabil. 2010;17(4):271-281. doi:10.1310/tsr1704-271.

Other Resources

Brower RG. Consequences of bed rest. Crit Care Med. 2009;37:10:422-428.

Eijk MM, Boogaard MVD, Marum RJ, Benner P, Eikelenboom P, Honing ML. Routine use of the Confusion Assessment Method for the Intensive Care Unit: a multicenter study. Am J Resp Crit Care Med (AJRCCM); American Thoracic Society. (In press, 2011).

Ely WE, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE jr, Inouye SK. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2001;291:1753-1762.

Ely WE, Inouye SK, Bernard GR, Gordon S, Francis J, May L. Delirium in mechanically ventilated patients: validity and reliability of the Confusion Assessment Method for the Intensive Care Unit (CAMICU). JAMA. 2001;286(21):2703-2710.

Pronovost P, Berenholtz S, Needham D. Translating evidence into practice: a model for large scale knowledge translation. BMJ. 2008;337:963-966.

Zannis JM, Korupolu R, Fan E, Pradham P, Janjua K, Palmer JB. Rehabilitation therapy and outcome in acute respiratory failure: an observational pilot project. J Crit Care. 2010;25(2):254-262.

Original Version of the Topic

Dale Strasser, MD. ICU Acquired Weakness and Neurocognitive Decline. 12/27/2012.

Author Disclose

Reina Nakamura, MD
Nothing to Disclose

Peter P Yonclas, MD
Nothing to disclose