the syndrome of severe , acute , intensive care unit ( icu)-acquired neuromuscular weakness poses a common and serious diagnostic , prognostic , and therefore management issue .
it goes by various names , some of which presuppose a mechanism : acute necrotizing myopathy of intensive care , acute quadriplegic myopathy , critical care myopathy , critical illness myopathy ( cim ) , critical illness neuromuscular disease , critical illness neuromyopathy , critical illness polyneuromyopathy , critical illness polyneuropathy ( cip ) , icu - acquired paresis , quadriplegic and areflexic icu illness , rapidly evolving myopathy with myosin - deficient fibres and thick filament myopathy [ 1 - 6 ] .
the problem affects at least 1.7% of children in paediatric icus , more than half of adult patients admitted to general icus for more than 1 week and more than 70% of those with sepsis and multiorgan failure [ 7 - 9 ] .
neuromuscular weakness typically becomes apparent when an attempt is made to wean the patient from the ventilator , although there are earlier clues , which include grimacing without movement with noxious stimuli before recovery of consciousness , relative lack of movement after regaining consciousness , and ( not inevitably ) loss of deep tendon reflexes that had been present earlier .
although most cases will turn out to be critical illness polyneuromyopathy    a term that embraces cip , cim , or a combination of the two  other potential causes should not be overlooked .
1 . the algorithm illustrates the early ruling in or out of spinal cord disease ( e.g. in cases of trauma , coagulation disturbance , west nile virus infection , acute disseminated encephalomyelitis , etc . ) , and then moving on to a clinical  biochemical  electromyographic assessment . a neuromuscular transmission defect ( e.g. slow inactivation of neuromuscular blocking agents , unrecognized myasthenia gravis , or myasthenic [ lambert  eaton ] syndrome ) is easily detected with repetitive nerve stimulation , revealing either a decremental or incremental response .
neuropathies other than cip that may manifest after icu admission include guillain  barr syndrome / acute immune - mediated demyelinating polyneuropathy ( and its various subtypes ) , porphyria and recurrent chronic inflammatory demyelinating polyneuropathy .
demyelinating inflammatory neuropathies usually cause slowing of conduction velocity and conduction block on electromyographic studies and produce increased protein in the cerebrospinal fluid .
other conditions , such as inflammatory myopathies or unrecognized motor neurone disease , are not discussed here because they are usually diagnosed before admission to icu , although they sometimes present with respiratory weakness that requires icu admission .
the last step , differentiating the most common causes of icu - acquired generalized weakness ( myopathy , neuropathy , or a combination of the two ) , is practical because their prognoses differ considerably .
some cases of myopathy appear to be merely ' membranopathies ' , with normal histology and rapid recovery .
presumably , the muscle membrane becomes dysfunctional , inexcitable and leaky , allowing myoglobin to leave the muscle .
others , especially in those treated with corticosteroids and neuromuscular blocking agents , exhibit a relative loss of thick myosin filaments .
many cases show variable panfascicular necrosis , which can sometimes be widespread and severe . in general ,
the prognosis for recovery from myopathies is favourable , with most patients recovering fully within 13 months .
this takes many months and recovery is often incomplete , leaving patients with significant weakness , sensory loss , and absent reflexes distally in the lower limbs and variably more proximally .
patients with cip who fail to show significant recovery by 4 weeks are often disabled with diminished quality of life .
some older patients may fail to survive or wean from the ventilator because their recovery is so protracted and other complications ensue .
electromyography is helpful in differentiating cip from cim but it has limitations . reduced or absent sensory nerve action potentials favours a neuropathy , but sensory potentials may be difficult to record if there is considerable oedema or a pre - existing polyneuropathy ( e.g. from diabetes mellitus ) may have clouded the issue .
direct muscle stimulation ( not commonly done ) may reveal no or absent response in cim but normal responses in cip .
unfortunately , needle electrode studies of muscle can show similar features in cip and cim ; both may exhibit spontaneous activity ( fibrillations and positive sharp waves ) .
often cip and cim coexist and their relative contributions to the weakness may vary considerably when this occurs .
elevated serum creatine kinase may help to identify cim , but the peak may be missed in the membranopathy / necrotizing varieties or creatine kinase may not be significantly elevated in cases with loss of myosin filaments . to determine the relative contributions of nerve versus muscle disease in explaining weakness , muscle or both nerve and muscle biopsies
have been utilized and recommended , most recently in this issue by kerbaul and colleagues . in most cases muscle biopsy
will address the relative contribution of myopathy to the picture because the neuropathy can be adequately assessed electrophysiologically .
percutaneous muscle biopsy , although providing limited tissue , has a number of advantages over operative biopsies : greater spatial sampling , minimal bleeding , negligible infection rate ( we have had none in over 1000 biopsies ) , portability ( done at the bedside ) , no general anaesthetic , speed of performance and ease of arrangement .
nerve and muscle biopsy is seldom necessary in the icu , unless a vasculitis is suspected .
being aware of the incidence and signs of icu - acquired weakness with ventilatory failure and having an approach to such disorders will prove valuable in management .
further insights into the mechanisms of cip and cim may provide some preventive strategies that will ameliorate their severity , shorten the duration of icu stays and improve long - term outcomes .
cim = critical illness myopathy ; cip = critical illness polyneuropathy ; icu = intensive care unit .
a flow chart giving an approach to generalized weakness and/or ventilatory failure in the intensive care unit .
ck , creatine kinase ; csf , cerebrospinal fluid ; gbs , guillain  barr syndrome ; emg , electromyography ; mri , magnetic resonance imaging ; lems , lambert  eaton ( myasthenic ) syndrome ; mg , myasthenia gravis ; ncv , nerve conduction velocity studies ; n - m , neuromuscular transmission ; snaps , sensory nerve action potentials . modified from bolton and young .
 icu - acquired limb and respiratory muscle weakness is a common , serious icu syndrome , increasing in frequency with prolonged icu stay and sepsis . 
 a systematic approach facilitates precise localization of the problem within central or peripheral nervous system . 
 most cases relate to critical illness polyneuropathy or myopathy or a combination of both ( critical illness neuromyopathy ) . within the latter entity , 
 the relative contribution of neuropathy versus myopathy varies considerably among affected patients . 
 muscle enzyme testing , electromyography - nerve conduction and muscle biopsy are valuable investigative tests . 
 nerve biopsy is less commonly needed , but is useful when vascultis is suspected . 
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