ICU acquired weakness (ICUAW)

Intensive care unit-acquired weakness (ICUAW) is an increasingly recognised and important clinical consequence of critical illness. It is associated with significant morbidity and mortality. It is estimated that 13 to 20 million people annually require life support in intensive care units (ICUs) worldwide. It is estimated that between 30% and 57% of patients staying in the ICU longer than 7 days will be diagnosed with this condition.

Definition and classification:

Intensive care unit-acquired weakness (ICUAW) is an acute clinical weakness that occurs in approximately 50% of ICU patients and is directly attributable to their critical care stay where other causes of weakness have been excluded.

The condition is characterized by diffuse limb and respiratory muscle weakness with a relative sparing of the cranial/facial muscles and the autonomic nervous system. Patients with ICUAW are classified into three conditions: critical illness polyneuropathy (CIP), critical illness myopathy (CIM) or critical illness neuromyopathy (CINM) based on clinical criteria and further defined by electrophysiological studies and muscle biopsies.

The distinction between CIP and CIM depends on electrophysiological or histological evidence of peripheral nerve or muscle fiber dysfunction, respectively. Considerable overlap between the two syndromes makes differentiation difficult. Although CIP and CIM may continue to impact outcomes in survivors of critical care long after ICU discharge, the effects of CIP may be more persistent.

Pathophysiology

The pathophysiological mechanisms underlying ICUAW are thought to be multifactorial, and various processes have been proposed. The dysfunctional microcirculation characteristically associated with sepsis and critical illness may lead to neuronal injury and axonal degeneration. This axonal damage may be particularly important in the development of CIN. The oxidative stress associated with systemic inflammation has also been suggested as an important mechanism responsible for ICUAW. Other proposed mechanisms include sodium channel inactivation and mitochondrial dysfunction, as well as protease-mediated muscle breakdown. None of these mechanisms is mutually exclusive and it is likely that all play their part to varying degrees.

 

ICUAW is often a manifestation of immobility or a systemic inflammatory response syndrome, especially in long-term ventilated patients who have had systemic sepsis/multi-organ failure or exposure to high-dose corticosteroids, neuromuscular blockers or hyperglycaemia.

It is associated with prolonged weaning from mechanical ventilation, increased mortality/length of ICU stay and long-term disability.

It is characterized by symmetric limb and respiratory muscle weakness that spares the facial and ocular muscles.  ICUAW is associated with difficulty weaning off the ventilator and increased long term morbidity and mortality.

The underlying mechanism for neuromuscular dysfunction in ICUAW includes a combination of axonal degeneration, mitochondrial damage, muscle breakdown, and sodium channel dysfunction with ensuing muscle membrane hypo-excitability.

According to the literature, the risk factors can be classified according to ‘probable’ or ‘possible’

Risk factors for CIP, CIM and CINM

Probable Possible
Severe sepsis/septic shock Age
Multiorgan failure Female gender
Prolonged mechanical ventilation/bed rest Severity of illness on admission
Increasing duration of SIRS Admission APACHE II score
Increasing duration of multiorgan failure Hypoalbuminaemia
Hyperglycaemia Hyperosmolality
Parenteral nutrition
Renal replacement therapy
Vasopressors
Corticosteroids
Neuromuscular blocking agents
Aminoglycosides

CLINICAL FEATURES

  • onset is typically about 1 week into a critical illness
  • Sensation is preserved (deficits can be present with axonopathy; difficult to assess in ICU due edema and coma)
  • Symmetrical deficits
  • Mostly proximal weakness
  • Reflexes are present, though diminished
  • CSF findings are normal
  • Cranial nerve function and autonomic nervous system function are usually intact
  • CK may be raised if myopathy is present
  • Nerve conduction studies (if performed) show normal conduction velocities with decreased compound muscle action potentials (CMAPs)
  • score of <48 on the MRC sum score (MRC-SS) of muscle strength is diagnostic of ICUAW

INVESTIGATIONS

Investigations are often not necessary, however they may be required depending on the possible differential diagnoses and implications for management and prognosis

Laboratory

  • CK (mildly elevated – and transiently so – in critical illness myopathy (not so with critical illness neuropathy)
  • UEC
  • B12 level
  • Acetylcholine receptor antibodies (for myasthenia gravis)
  • Inflammatory markers (e.g. CRP)
  • Lumbar puncture

Imaging

  • Chest X ray
  • MRI of the brainstem and spine

Special tests

  • Nerve conduction studies and electromyography: CIP shows sensorimotor axonopathy with decreased compound muscle action potentials (CMAP) and sensory-nerve action potentials, but preserved conduction velocities (CV). CIM shows reduced amplitude and increased duration of CMAPs. ICUAW often is a mixture of CIP and CIM.
  • Muscle biopsy if no satisfactory explanation is found

An average score of < 48 on the Medical Research Council (MRC) scale is one of the important diagnostic criteria for ICUAW.

Strength of Muscle Groups for the following motions: Strength grades
Shoulder abduction 5 = normal muscle strength/power
Elbow flexion 4 = active movement against gravity with resistance
Wrist extension 3 = active movement against gravity
Hip flexion 2 = active movement with gravity eliminated
Knee extension 1 = flicker/trace muscle contraction
Ankle dorsiflexion 0 = no active muscle contraction

The MRC score is highly reliable in patients with Guillain–Barre syndrome, with successful implementation in critically ill patients

Treatment:

The main emphasis is on delivering excellent quality supportive ICU care, no specific intervention has been shown to improve outcome. An awareness of the condition and its ‘probable’ and ‘possible’ risk factors may be helpful in order to minimize the patient to their exposure. Early treatment of sepsis, aiming for normoglycaemia according to NICE-SUGAR guidance, judicious use of inotropes/vasopressors, corticosteroids and muscle relaxants cannot be over emphasized. To avoid muscle immobility, minimizing the level of sedation as well as introducing daily sedation interruptions may be of benefit.

It is important that the assessment of muscle strength forms part of the daily routine assessment of critically ill patients. Immobility should not be viewed as a benign inevitability occurring when patients are admitted and early mobilization and physiotherapy schedules should be commenced as soon as possible.

Early mobilization being the key to success, it is imperative to implement it in the early stages based on high index of suspicion of ICUAW.

Rehabilitation plays an essential role in combating the ICUAW and it’s distant effect termed post intensive care syndrome (PICS).

Prognosis

ICUAW can lead to difficulty weaning a patient from a mechanical ventilator and is associated with increased length of ICU stay, increased morbidity (ventilator associated pneumonia, deep vein thrombosis and pulmonary embolism) and mortality.

It can lead to prolonged rehabilitation where improvement in weakness can take weeks to months, as re-innervation and or new muscle growth occurs.

Prognosis is difficult to accurately describe but estimates approximate that up to 60% of patients diagnosed with ICUAW will die within the first year; of the survivors, approximately 70% recover fully to premorbid baseline levels of functioning and 30% remain with varying degrees of persistent disability.

References:

  1. Christopher Taylor, Intensive care unit acquired weakness, Neurointensive care, Vol 25, issue 1, December 2023
  2. Wenkang Wang, et al; Intensive care unit acquired weakness: A review of recent progress with a look toward the future; Front. Med; Vol 7, 2020
  3. Sarah E Jolley, et al; ICU acquired weakness; Chest 2016, Nov; 150 (5): 1129-1140
  4. S Bloch, et al; Molecular mechanisms of intensive care unit acquired weakness; European Respiratory Journal; 2021:39: 1000-1011.
  5. Richard Appleton, John Kinsella; Intensive care unit acquired weakness; British Journal of Anesthesia; January 2022