Hospital Medicine

ICU-acquired weakness

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I. What every physician needs to know.

Intensive care unit (ICU) acquired weakness is the acute onset of neuromuscular and functional impairment in the critically ill for which there is no alternative etiology other than critical illness. It is a diagnosis of exclusion and is characterized by symmetric, generalized limb and/or diaphragmatic weakness that typically spares the cranial nerves. Generalized weakness impairs patient mobility and has been associated with prolonged mechanical ventilation, increased length of stay, increased mortality, and poor functional outcomes. Early physical and occupational therapy in the ICU (beginning on the first day of ICU admission regardless of mechanical ventilation status) is the most promising therapy to improve functional outcomes among patients at risk for ICU-acquired weakness.

This syndrome has many different descriptors over the years. The most common alternative names for ICU-acquired weakness include critical illness myopathy, critical illness polyneuropathy, and critical illness polyneuromyopathy. Additional descriptions of ICU-acquired weakness include critically ill polyneuropathy, critical illness neuropathy, critical illness myopathy and/or neuropathy, ICU-acquired paresis, and intensive care unit-acquired neuromyopathy.

II. Diagnostic Confirmation: Are you sure your patient has ICU-acquired weakness

Recently proposed diagnostic criteria for ICU-acquired weakness include:

  1. Generalized weakness developing after the onset of critical illness

  2. Weakness is diffuse, involving both proximal and distal muscles, symmetric, flaccid, and generally spares cranial nerves

  3. Medical Research Council (MRC) sum score less than 48, or mean MRC score less than 4 in all testable muscles groups noted on at least two occasions separated by more than 24 hours

  4. Dependence on mechanical ventilation

  5. Causes of weakness not related to the underlying critical illness have been excluded.

Minimum criteria for diagnosing ICU-acquired weakness is 1, 2, 3 or 4, and 5.

According to the above diagnostic criteria, the detection of ICU-acquired weakness can be made with an assessment of a patient’s maximum strength according to the Medical Research Council score. The Medical Research Council score is a validated clinical assessment that systematically grades patient effort. MRC examination should be routinely performed serially throughout the ICU stay. The patient’s effort is graded on a scale of 0 to 5 in three functional muscle groups of each extremity (upper extremity: wrist flexion, forearm flexion, shoulder abduction; lower extremity: ankle dorsiflexion, knee extension, hip flexion):

  • Grade 5: Muscle contracts normally against full resistance.

  • Grade 4: Muscle strength is reduced but muscle contraction can still move joint against resistance.

  • Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed. As an example, the elbow can be moved from full extension to full flexion starting with the arm hanging down at the side.

  • Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane.

  • Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle.

  • Grade 0: No movement is observed.

A. History Part I: Pattern Recognition:

ICU-acquired weakness, as its name suggests, is weakness whose onset becomes apparent following the onset of critical illness. Importantly, symptoms of weakness that precede the onset of critical illness should prompt the clinician to consider alternative diagnoses. ICU-acquired weakness is characterized by generalized limb weakness that may include both the upper and lower extremities, and typically spares the cranial nerves (although not always). In addition, this condition is often characterized by diaphragmatic weakness that becomes apparent with rapid-shallow breathing during spontaneous breathing trials and/or prolonged failure to successfully extubate patients. ICU-acquired weakness is a diagnosis of exclusion, and should be considered after the clinician has considered and ruled out alternative etiologies by means of history, physical exam, and appropriate diagnostic studies.

In addition to the clinical exam, clinicians may recognize the presence of primary risk factors among affected patients. These have been described in a variety of cohort studies. The strongest risk factor across studies include the severity of illness and/or a diagnosis of sepsis. In addition, patients at increased risk include those mechanically ventilated, exposed to glucocorticoids or neuromuscular blockers, in receipt of higher doses of sedation/analgesia, or experiencing hyperglycemia. The presence of these exposures are not required to make a diagnosis of ICU-acquired weakness.

B. History Part 2: Prevalence:

ICU-acquired weakness is highly prevalent. Estimates for prevalence depend somewhat on the diagnostic definition as well as the population of interest. Using a clinical diagnostic strategy, the prevalence of ICU-acquired weakness has been estimates at around 25% among patients whom required mechanical ventilation for 7 or more days. More sensitive diagnostic strategies using electrophysiological techniques indicate a greater prevalence (~58%) among similar patients. The prevalence varies by severity of illness as well, with a 60% prevalence of clinically apparent ICU-acquired weakness among patients with acute respiratory distress syndrome.

C. History Part 3: Competing diagnoses that can mimic ICU-acquired weakness

The diagnosis of ICU-acquired weakness, although common, is a diagnosis of exclusion. A variety of nervous system and myopathic disorders may present in the ICU and mimic the findings of ICU-acquired weakness. As some of these conditions are treatable, it is critical that hospital clinicians consider (and workup when indicated) these diagnoses prior to diagnosing a patient with ICU-acquired weakness. Conditions may arise from lesions of the brain, brainstem, anterior horn cell, neuromuscular junction, and peripheral neuropathies. In addition, conditions may represent myelopathies and muscle disorders. These conditions may be worsening of a pre-existing condition or more commonly a condition that is independent of critical illness, yet presents in the hospitalized setting (such as Guillain-Barré syndrome or myasthenia gravis).

Careful history and physical exam can exclude many conditions, whereas, additional studies (including neuroimaging, electromyography, nerve conduction studies, infectious workup, inflammatory serologies, cerebral spinal fluid analysis) and specialist consultation (for example, neurology, rheumatology, infectious disease, psychiatry) may be of value in the case of continued diagnostic uncertainty.

D. Physical Examination Findings.

Physical examination of alert patients able to follow commands is notable for symmetric weakness and a decrease in tone that may affect all extremities, especially the lower limbs. Diaphragmatic muscles are commonly affected. During spontaneous breathing trials, a rapid shallow breathing pattern may be observed as well as diminished forced vital capacity and negative inspiratory force. Muscles innervated by cranial nerves are usually intact. Deep tendon reflexes may be normal, decreased, or absent, and are typically symmetric unless in the presence of a pre-existing or co-existing corticospinal tract lesions. It should be noted that none of the physical exam findings are specific to ICU-acquired weakness, and alternative diagnoses should always be considered.

E. What diagnostic tests should be performed?

ICU-acquired weakness is a clinical diagnosis that depends upon the presence of generalized weakness and/or dependence upon mechanical ventilation in the absence of other conditions that may explain the condition. One can apply the diagnostic criteria as outlined in Section II above. Importantly, the clinical diagnostic approach is limited by the consciousness and cooperation of the patient, which may be uncertain if the patient is concurrently receiving sedatives, analgesics, neuromuscular blocking agents, or suffering from coma, delirium, or a metabolic encephalopathy. When possible, offending neuromuscular and sedative agents should be stopped or reduced. Neuromuscular testing may be best assessed in the context of a spontaneous awaking trial. If suspicion is high, and adequate clinical diagnostic testing cannot be performed, electrophysiological testing offers alternative means to diagnose neuropathic and myelopathic derangements that are consistent with ICU-acquired weakness.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Laboratory studies are not directly required for the diagnosis of ICU-acquired weakness, although may be indirectly needed upon assessing and ruling out alternative diagnostic possibilities. The ordering of laboratory testing should be driven by history and physical examination findings that suggest the presence of an infectious, inflammatory, endocrine, malignant, or paraneoplastic cause of acute weakness in the critically ill patient. In addition, muscle biopsy can be considered for suspicion of underlying muscle disorder.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Although not necessary for the diagnosis of ICU-acquired weakness, in the case of high suspicion, coupled with the inability to make a clinical assessment, the use of electrophysiological testing is an alternative approach to diagnose neuromuscular dysfunction. Electrophysiological testing can predict ICU-acquired weakness with high sensitivity and specificity, and it provides additional detail with regards to the etiology of the weakness (e.g. nerve, muscle, or both).

As with laboratory studies, additional imaging studies are not directly required to diagnosis ICU-acquired weakness, although they may be indirectly needed to assess and rule out alternative diagnostic possibilities. The ordering of imaging testing should be driven by history and physical examination findings that suggest the presence of an intracranial or spinal cord pathology that may explain a patient’s acute weakness (e.g. cranial nerve finding, fixed or focal motor deficits, new unilateral or bilateral positive Babinski’s sign, persistent decrease in consciousness in absence of sedation).

A simplified diagnostic framework proposed by Schweikert et al. provides a foundation for considering the use of additional laboratory, pathology, and imaging testing. The first step includes the performance of daily spontaneous awaking trials with interruption of sedation. Patients who do not awaken, despite interruption of sedation, should prompt further central nervous system (CNS) studies. For those patients that awaken, a neurologic exam including the use of MRC criteria should be performed.

A normal exam should prompt continued observation, without further workup unless indicated by alternative exam findings. Focal, unilateral deficits should prompt additional electrophysiologic or CNS studies, whereas symmetric weakness should be followed with serial examination. For patients with symmetric weakness, additional studies may be considered for those with continued fixed neurologic deficits, or if the history and physical exam is suggestive of alternative diagnostic possibilities.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

ICU-acquired weakness is a diagnosis that can be made on clinical grounds alone and does not necessarily require additional laboratory or imaging studies. Sedative agents should be interrupted followed by clinical evaluation prior to the consideration of electrophysiological or CNS studies. Additional tests are clearly warranted when clinical suspicion of alternative etiologies (e.g. infection, autoimmune, malignancy) is high enough and/or when patients exhibit focal deficits and persistent changes in consciousness despite the absence of sedation.

III. Default Management.

Management for ICU-acquired weakness should begin before the onset of symptoms. Prevention is the key to this disorder, with the most promising therapy being reduced exposure to sedative agents (e.g. daily spontaneous awakening trials) and early physical and occupational therapy for ICU patients, even while mechanically ventilated and/or in the presence of intravascular indwelling devices.

A. Immediate management.

Although the presence of ventilators and intravascular devices may present as physical and psychological barriers to early mobility, a growing number of studies have demonstrated the feasibility, safety, and efficacy of early mobility from the first day of ICU admission. In combination with routine coordinated awakening (i.e. sedation holiday) and breathing trials, patients will experience marked improvements in functional independence along with substantial reductions in mechanical ventilation duration, ICU length of stay, and days of delirium.

Early mobility is a critical part of a recently proposed bundle of measures aimed towards reducing both cognitive and functional impairment in ICU survivors. The ‘ABCDE’ bundle includes coordinating protocolized awakening and breathing coordination, choosing appropriate sedation (i.e. avoidance of benzodiazepines), delirium monitoring, and early mobilization. These synergistic processes work toward liberating patients from sedative and mechanical ventilation, key barriers towards effective early mobilization, and conceivably independently reduce the development of ICU-acquired weakness.

Recent data with smaller patient samples also suggest the potential benefit of electrical stimulation of muscles in the ICU for preserving muscle mass and preventing ICU-acquired weakness. Although prospective clinical trial data is not currently available to confirm the benefits, experts support limiting patients' exposure to corticosteroids and neuromuscular blocking agents, drugs that have been identified as risk factors in numerous cohort studies. Similarly, glycemic control may reduce the risk of ICU-acquired weakness, but there remains controversy with regard to the appropriate target range across differing ICU populations. Adequate nutritional intake is advocated, although the role of nutritional supplementation is unclear at this point.

B. Physical Examination Tips to Guide Management.

Serial neurologic assessment should be routinely performed in the ICU, including the incorporation of the MRC examination (see section II) into routine practice. Evidence of asymmetric and localized findings should prompt alternative diagnostic considerations and trigger additional neuroimaging. The presence of cranial nerve findings, although these rarely occur with ICU-acquired weakness, should also prompt considerations of intracerebral or brainstem pathology.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.


D. Long-term management.

Patients with ICU-acquired weakness commonly leave the hospital with significant functional impairments and often require institutional care. Continued physical rehabilitation and comprehensive rehabilitation for patients who have suffered prolonged mechanical ventilation is recommended to improve outcomes, although the efficacy and outcomes of rehabilitation after critical illness is less well established.

E. Common Pitfalls and Side-Effects of Management

The most common pitfall in the management of ICU-acquired weakness is withholding beneficial early mobility. Although physical therapy targeted toward ICU patients is increasingly common, it is still provided to a minority of ICU patients. Among patients in a “usual care” arm of a trial testing early ICU mobilization, only 47% of patients had any physical therapy. In another study of critically ill patients, 20% received no physical activity and 15% only received passive range of motion exercises during their ICU stay.

There are many barriers to the delivery of early mobility, including competing processes of care, lack of early mobilization care planning, and inadequate technology and/or collaboration. Caregivers may also be concerned about the possibility of triggering an adverse event such as physiologic stress (e.g. hypoxia or ischemia), unplanned extubation, or removal of vascular access. In addition, staff may be concerned about the adequacy of patient comfort and psychological wellbeing. To overcome these barriers, providers must understand the poor outcomes associated with prolonged bed rest coupled with the published efficacy of early mobility in critically ill patients, upon following safety criteria for initiating and continuing physical therapy.

An additional pitfall is providing excessive sedation to the patient. In the effort to address patient comfort, caregivers may unintentionally expose patients to harmful sedatives that prolong mechanical ventilation, increase the risk for delirium, and prevent patient participation in early mobility exercises. Early mobility will be far easier to achieve in ICUs that implement sedation protocols that incorporate daily spontaneous awakening trials and use validated sedation measurement instruments to provide target-based sedation to minimize exposure to sedation and neuromuscular blocking agents. The default sedation target for ICU patients should be wakefulness or light sedation, except in clinical circumstances where deeper sedation may be required (such as with patients that have active seizures, increased intracranial pressure, or a need for neuromuscular blockade).

Pohlman et al. recently published safety criteria that they have successfully implemented for the initiation and continuation of physical and occupational therapy in critically ill patients (including mechanically ventilated patients, patients with delirium, patients on sedatives, and those with intravascular catheters) beginning on the first day of ICU admission. Following their protocol, adverse events (e.g., desaturation, agitation/discomfort) were uncommon and therapy was discontinued prematurely in only 4% of all sessions, most commonly due to patient-ventilator asynchrony or agitation. The criteria they used for initiation and continuation are as follows:

Contraindications to initiating physical and occupational therapy

  • Mean arterial pressure less than 65

  • Heart rate less than 40 beats per minute, greater than 130 beats per minute

  • Respiratory rate less than 5 breaths per minute, greater than 40 breaths per minute

  • Pulse oximetry less than 88%

  • Evidence of elevated intracranial pressure

  • Active gastrointestinal blood loss

  • Active myocardial ischemia

  • Actively undergoing a procedure

  • Patient agitation requiring increased sedative administration in the last 30 minutes

  • Insecure airway (device)

Adverse events—contraindications to continuing physical and occupational therapy

  • Mean arterial pressure less than 65

  • Heart rate less than 40 beats per minute, greater than 130 beats per minute

  • Respiratory rate less than 5 breaths per minute, greater than 40 breaths per minute

  • Pulse oximetry less than 88%

  • Marked ventilator dyssynchrony

  • Patient distress

    • Evidenced by nonverbal cues, gestures

    • Physically combative

  • New arrhythmia

  • Concern for myocardial ischemia

  • Concern for airway device integrity

  • Fall to knees

  • Endotracheal tube removal

IV. Management with Co-Morbidities

A. Renal Insufficiency.

No change in standard management.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease

No change in standard managment.

E. Diabetes or other Endocrine issues

Ideal glycemic control for critically ill patients remains a controversial topic with regard to appropriate patient selection and best targeted glucose level, but some trials have demonstrated that tighter control of blood sugars is associated with a reduction in the incidence of ICU-acquired weakness. Prevention of ICU-acquired weakness by specific algorithms to control blood sugars to any given range has not been demonstrated.

F. Malignancy

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc).

Limiting critically ill patients’ exposure to corticosteroids is a generally recommended approach to limit the adverse effects on the peripheral nervous system. Clinicians must frequently titrate the dose of corticosteroids to find the dose that balances the risks of corticosteroids (including muscle weakness) with the benefits of the anti-inflammatory response. Clinicians may also consider the use of steroid sparing immunosuppressive agents when indicated and in consultation with the appropriate specialist.

H. Primary Lung Disease (COPD, Asthma, ILD)

No change in standard management.

I. Gastrointestinal or Nutrition Issues

No change in standard management.

J. Hematologic or Coagulation Issues

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment

No change in standard management.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

If a patient has ICU-acquired weakness, this should be clearly documented in the chart as well as on sign-out documentation. In addition, the extent and severity of weakness should be well documented so that receiving practitioners will be better able to diagnose any relevant changes in neurologic function (e.g. focal findings) that may prompt further neurologic workup.

B. Anticipated Length of Stay.

ICU-acquired weakness is associated with a more than two to threefold increase in the risk of prolonged mechanical ventilation (i.e. more than seven days of mechanical ventilation) in comparison to non-affected patients. This, of course, leads to similar increases in ICU and hospital length of stay.

C. When is the Patient Ready for Discharge.

Discharge from the ICU will be limited by the ability to wean the patient from mechanical ventilation, which is substantially increased among patients experiencing ICU-acquired weakness. In some cases, patients may require prolonged weaning and continued care at a long-term acute care facility.

D. Arranging for Clinic Follow-up

Although there are no guidelines to direct post-discharge follow-up, it should be recognized that patients with ICU-acquired weakness are at marked increased risk for long-term functional impairment. Patients should be considered for continued physical and occupational therapy following discharge, tailored to maximize recovery back towards their pre-hospital status.

1. When should clinic follow up be arranged and with whom.

There are currently no standards for follow-up among patients who experience ICU-acquired weakness. Follow-up should be tailored to the severity of patients at discharge. Physical therapy should be continued immediately following discharge, whether it be at an acute rehabilitation facility, an outpatient rehabilitation specialists, or at home depending on the severity. Typically, patients receiving care in an intensive care unit should follow-up very soon (e.g. within a week) with their primary doctor or an ICU/hospital discharge clinic. Additional appointments should be considered with pulmonology as well as rehabilitation specialists.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

No additional testing is required.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

Patients should continue to have their functional progress monitored by means of both physical strength testing as well as by an assessment of their activities of daily living.

E. Placement Considerations.

Using the optimal methods of rehabilitation will be essential to enhance functional recovery after ICU management. Patients with prolonged mechanical ventilation and ICU-acquired weakness will often require continued care in a long-term acute care facility, acute rehab hospital, or a sub-acute nursing facility.

F. Prognosis and Patient Counseling.

Patients who suffer from ICU-acquired weakness are vulnerable and at increased risk for a variety of poor outcomes. It has been observed that patients may be at increased risk of prolonged mechanical ventilation, prolonged hospital length of stay, and, in one study, an almost eight times greater odds of mortality. Effects of ICU weakness persist well after hospital discharge with 60% of patients experiencing continued muscle dysfunction up to one year after illness, along with muscle atrophy and peripheral neuropathy. Survivors of critical illness experience functional impairment even five years following that illness, with ICU-acquired weakness playing an important contributing role.

Short-term prognosis is improved among patients who receive early mobility and protocolized sedation strategies, with reduced mortality, reduced ICU length of stay, increased functional abilities, and decreased need for continued skilled nursing or inpatient rehabilitation care. Improvements in long-term prognosis with these strategies implemented after hospitalization are unknown at this time.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.

There are currently no Joint Commission or Centers for Medicare and Medicaid Services (CMS) measures that address ICU-acquired weakness. With regards to internal performance improvement, several strategies are suggested.

In order to identify ICU-acquired weakness, ICUs should implement a validated measure of strength assessment (such as the Medical Research Council score) that can be serially assessed and documented in the medical record.

To maximize participation of patients with physical therapy (and in accordance with guidelines set forth by the Society of Critical Care Medicine) ICUs should implement sedation protocols (if not already in place) that address the coordination of spontaneous awaking and breathing trials, implement delirium and sedation monitoring using validated instruments, and adjust sedation according to goal targets of wakefulness or light sedation except for circumstances that require deeper sedation.

Patients will benefit significantly from the development and implementation of early mobilization protocols.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Preventive processes of care are key to reducing the burden of ICU-acquired weakness, and these must include early mobilization and protocolized sedation strategies that reduce exposure to sedatives (such as the ABCDE protocol, see Section IIIA). Although no specific measures have been directly linked with reduced readmission, such protocols are theoretically important strategies towards reducing the risk of readmission in the high-risk ICU population.

VII. What's the evidence?

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