OVERVIEW

• ICU Acquired Weakness (ICUAW) includes critical illness myopathy (CIM), critical illness polyneuropathy (CIP), or a mixture of both (myopathy is typically predominant)
• very common in the mechanically ventilated (25-60% in those mechanically ventilated for > 7 days)
• increasing body of evidence that ICUAW leads to poor quality of life and persistent weakness lasting long after ICU discharge

PATHOPHYSIOLOGY

Multifactorial pathogenesis may involve:

• axonopathy, not demyelinating
• mitochondrial dysfunction
• microvascular ischaemia
• sodium channelopathy
• catabolism
• immobility

RISK FACTORS

• sepsis
• systemic inflammation
• poor glycaemic control
• steroids
• neuromuscular blocking agents
• immobility
• malnutrition
• female sex
• pre-existing sarcopenia

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

• CXR (evidence of malignancy causing Eaton-Lambert syndrome)
• MRI of the brainstem and spine

Special tests

• Nerve conduction studies andelectromyography: 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

DIFFERENTIAL DIAGNOSIS

Key differentials of ICU-acquired weakness

• Critical illness polyneuropathy
  • presents around a week into a critical illness, typically with limb weakness and atrophy, reduced tendon reflexes, loss of peripheral sensation to touch and pain, preservation of CN function, electrophysiological studies -> motor and sensory neuropathy, biopsies -> axonal degeneration and denervation -> atrophy of muscles
• Residual paralysis
  • exclude using peripheral nerve stimulation (minimal response to TOF, PTc)
• Residual sedation
  • calculation of dose, duration and ability to clear medications (response to antagonism; naloxone, flumazenil)
• Acute myopathy
  • risk factors = neuromuscular blockage and corticosteroids, motor findings with no sensory abnormalities, CK elevated, electrophysiological testing -> myopathy, muscle biopsy -> loss of thick filaments
• Spinal cord lesions
  • associated with a sensory level and hyperreflexia
• Brain stem problems
  • cranial nerve lesions
• Guillain-Barre syndrome
  • ascending motor weakness, loss of reflexes, some peripheral sensory deficits, pain, post-viral, high protein in CSF, responsive to Ig and plasmapheresis

Differential diagnosis of rapidly progressive limb weakness (with or without respiratory failure)

• CNS
  • Encephalitis, acute disseminated encephalomyelitis, transverse myelitis, brainstem or myelum compression, leptomeningeal malignancy
• Motor neurons
  • Poliomyelitis, West Nile virus anterior myelitis, amyotrophic lateral sclerosis, progressive spinal muscular atrophy
• Plexus
  • Neuralgic amyotrophia, diabetes mellitus
• Nerve roots
  • Guillain-Barré syndrome, acute onset chronic inflammatory demyelinating neuropathy, Lyme disease, cytomegalovirus-related radiculitis, HIV-related radiculitis, leptomeningeal malignancy
• Peripheral nerves
  • Guillain-Barré syndrome, acute onset chronic inflammatory demyelinating neuropathy, iatrogenic, toxic, critical illness myopathy-neuropathy, vasculitis, diphtheria, porphyria, thiamine deficiency, porphyria, Lyme disease, metabolic or electrolyte disorders (hypokalaemia, phosphataemia or magnesaemia, hypoglycaemia)
• Neuromuscular junction
  • Myasthenia gravis, botulism, intoxication
• Muscles
  • Critical illness myopathy-neuropathy, mitochondrial disease, acute rhabdomyolysis, polymyositis, dermatomyositis

MANAGEMENT

• intensive glycaemic control
• minimise use of corticosteroids and neuromuscular blockade
• physiotherapy – consider including early mobilisation
• electrical muscular stimulation (EMS)
• minimise sedation
• electrolyte replacement
• optimise nutrition
• ventilator weaning

PROGNOSIS

Short term

• increased ventilation
• increased ICU stay
• increased mortality

Long term

• most recover to be able to walk independently
• small amount have mild disability
• 30% have severe quadriparesis, quadriplegia or paraplegia

References and Links

LITFL

• CCC — Mobilisation in ICU

Journal articles

• Deem S. Intensive-care-unit-acquired muscle weakness. Respir Care. 2006;51:(9)1042-52; discussion 1052-3. [pubmed]
• Dhand UK. Clinical approach to the weak patient in the intensive care unit. Respir Care. 2006 Sep;51(9):1024-40; discussion 1040-1. [PubMed] [Free Full Text]
• 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)1437-46. [pubmed]
• Hermans G, De Jonghe B, Bruyninckx F, Van den Berghe G. Interventions for preventing critical illness polyneuropathy and critical illness myopathy. Cochrane Database Syst Rev. 2009;(1)CD006832. [pubmed]
• Hermans G, De Jonghe B, Bruyninckx F, Van den Berghe G. Clinical review: Critical illness polyneuropathy and myopathy. Crit Care. 2008;12:(6)238. [pubmed]
• Khan J, Burnham EL, Moss M. Acquired weakness in the ICU: critical illness myopathy and polyneuropathy. Minerva Anestesiol. 2006;72:(6)401-6. [pubmed]
• Kress JP, Hall JB. ICU-acquired weakness and recovery from critical illness. N Engl J Med. 2014;370:(17)1626-35. [pubmed]
• Truong AD, Fan E, Brower RG, Needham DM. Bench-to-bedside review: mobilizing patients in the intensive care unit–from pathophysiology to clinical trials. Crit Care. 2009;13:(4)216. [pubmed] [PMC free article]