ICU Acquired Weakness (ICUAW)

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]