Critical illness polyneuropathy

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Critical illness polyneuropathy

• From
• Critical care medicine 2002 ,8 , 302310
• Authors
• Walther N.K.A. van Mook, MD, and Riquette P.M.G.
  Hulsewé-Evers, MD
• ??? ???

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Abstract

• Critical illness polyneuropathy(CIP) first
  extensively described in the early 1980s, mainly
  in patients with failure to wean from mechanical
  ventilation
• limb muscle weakness, usually more distally
  than proximally
• The facial musculature is often strikingly
  spared.
• Reduced DTR and loss of peripheral sensation to
  light touch and pin prick often
• accompanied

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• Involvement of the phrenic nerve will cause
  delayed weaning.
• electrophysiologic studies predominantly motor
  and, often to a lesser extent, sensory axonal
  polyneuropathy.
• incidence gt50 of patients in major medical
  and surgical critical care units
• The systemic inflammatory response
  syndrome(SIRS) is strongly associated with CIP
  and, among the multiorgan failure often seen in
  SIRS, CIP is thought to represent a neurologic
  manifestation of SIRS.

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• Mechanism cytokines and free radicals,
  affecting the microcirculation of the nervous
  system
• Examination of the peripheral nervous system is
  often unreliable
• the only way to establish a definitive
  diagnosis electrophysiologic studies.
• Onset 80 within 72hrs after SIRS/sepsis
• recovery was very slow weeks to months

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Epidemiology

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Diagnosis

• Clinical presentation
• Laboratory parameters
• Electrophysiologic studies
• Nerve and muscle biopsies
• Additional techniques
• Differential diagnosis

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Clinical presentation

• early stages PE unreliable due to
  encephalopathy or sedation.
• Even after the encephalopathy disappears, a
  proper and complete neurologic examination can be
  difficult to perform
• The discrepancy between grimacing of facial
  musculature in response to a painful stimulus and
  the complete absence of limb movement is often
  striking.

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• weakness usually more pronounced distally than
  proximally and is often accompanied by muscle
  atrophy.
• DTR are usually absent or decreased.
• Loss of peripheral sensation to light touch and
  pin prick and relative preservation of cranial
  nerve function also result from the syndrome.
• Lab
• mostly not diagnostic, CK only marginally
  raised or normal in most pts

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Electrophysiologic studies

• 1.sensitive tools 2.could be quantified
• NCV unchanged.
• relatively pure axonal polyneuropathy
• Reduced action potential both in motor and
  sensory nerve. (However,reduction of the CMAP may
  also be the result of severe muscle
  atrophy(motor) or tissue edema (sensory)
• spontaneous activity with fibrillations and
  positive sharp waves in a widespread distribution
  as signs of denervation

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• Apart from involvement of the chest wall
  muscles, diaphragmatic denervation in patients
  with CIP seems to play a role in ventilator
  dependency.
• One study 60 patients showed evidence of
  diaphragmatic denervation as determined by
  diaphragmatic needle EMG
• Another study 54 exhibited diaphragmatic
  denervation as determined by phrenic nerve
  conduction studies in combination with
  electromyography
• (However, this denervation is frequently
  attributable to causes other than CIP (eg,
  mediastinal pathology))

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Nerve and muscle Bx Nerve Bx

• In 1994 review Bx of 19 pts
• 15/19(79) nerve biopsies axonal pathology with
  primary axonal degeneration without
  demyelinization was found
• Distal nerves to be more severely involved,
  whereas the more central nerves like the vagal
  and was relatively spared
• No inflammatory changes have been reported in
  nerve biopsies

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• Latronico et al. 22 Pts /c CIP 14 normal
  nerves and only 8 had axonal neuropathy
• sepsis-related CIP may caused impairment of
  axonal transport and transmembrane potential in
  early stage which could not be detected by nerve
  biopsy.
• If sepsis persistented , significant axonal
  neuropathy may be seen
• Thus, the absence of histologic indicators of
  nerve damage does not exclude significant
  functional impairment

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Muscle Bx

• Atrophy of predominantly type II fibers as
  evidence of innervation loss is the most commonly
  found abnormality and is almost always present
• In several studies, muscle biopsy examination
  yielded striking abnormalities
• One prosepctive study Muscle fiber necrosis
  occurred in 30 of cases the myopathic
  changes secondary or primary

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• Coakley et al. performed muscle biopsies in 24
  pts
• No clear relation between changes in these
  biopsies and the observed neurophysiologic
  abnormalities was found. Histologic normal muscle
  was found only in patients with normal
  electrophysiologic results
• In a study by Latronico et al.
• muscle alterations were found in 23/24 pts,
  with abnormalities ranging from primary
  myopathic, neurogenic, or both.
• in a study by De Letter et al. 30patients with
  CIP, and neuropathic changes were found in 11 of
  30(37), myopathic changes in 12 of 30 (40), and
  both in 7 of 30 (30).

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• Thus sepsis- and SIRS related myopathies occur
  more frequently than previously recognized and
  sometimes in combination with CIP.
• Perhaps the term critical illness myo- and
  (poly)neuropathy is more applicable in many
  patients.

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Additional techniques

• NCV and conventional EMG hard to d/d
  neuropathy and myopathy Both low CMAP and
  frequently show spontaneous activity in the form
  of fibrillation potentials and positive sharp
  waves.
• Measurement of muscle fiber excitability by
  direct muscle stimulation and quantitativ
  electromyography is valuable in differentiating
  myopathy and neuropathy.

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Differential diagnosis

• 1.Weakness before ICU admission
• Brain and spinal cord dysfunction resulting
  from trauma, neoplasm, infection, or systemic
  illness
• worseningof preexisting diseases and
  occurrence of new diseasesof motor neurons,
  nerves, neuromuscular junction,
• 2.Weakness after ICU admission
• CIP, other ICU-acquired neuropathies,disorders
  of neuromuscular transmission, and myopathies
• Table 2 and Fig 1

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• Neuromuscular disorders of critical illness
•  
•    Critical illness polyneuropathy.
•    Delayed reversal of neuromuscular blockade.
•    Acute myopathy,
• divided into two pathogenetically distinct
  syndromes
• 1. critical illness myopathy
• 2.myopathy associated with combined use of a
• corticosteroid and a neuromuscular blocking
• drug.

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•    Delayed reversal of neuromuscular blockade.
• pancuronium and vecuronium, are normally
  cleared from the circulation within several
  hours, primarily by the liver.
• In patients with poor renal function
  ,functionally active 3-hydroxy metabolites of
  these drugs accumulate and persist in the blood.
• As a result, NM block effect may lasted one
  week after drugs DC .
• Dx 1.EMG Train of four twitch
• 2. anticholinesterase inhibitor test

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•    Acute myopathy, critical illness myopathy
• As with critical illness polyneuropathy, this
  form of acute muscle injury is strongly
  associated with sepsis and MOF
• Mechanism
• 1.direct effects of microorganism-associated
  toxins, as is observed in toxic shock syndrome
  and in occasional infections with influenza or
  other viruses .(SARS)
• 2.inflammatory mediators that are implicated
  generally in the systemic inflammatory response
  syndrome.
• Whether peripheral nerve and muscle are injured
  simultaneously by the same process, or
  independently by separate processes in the SIRS
  , remains to be determined.

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•   Myopathy associated with steroid and NM
  blocking agent
• s/s symmetrical weakness , reduced DTR
  ,reserved sensory function ,and elevated CK
  myoglobinuria for several days .
• Bx selective loss of thick (myosin)
  filaments
• First observed in asthma patient with steroid
  and NM block
• 1.weakness only in the patients who were
  treated simultaneously with both types of drugs
• .

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• 2.Muscle weakness increased dramatically in
  frequency and severity with the duration of NM
  block
• Mechanism unknown gtin rats favor acute form
  of corticosteroid-induced myopathy.

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Risk factors of CIP

• SIRS and/or sepsis
• Steroids
• Neuromuscular blocking agents
• Aminoglycoside antibiotics
• Total parenteral nutrition
• Vasopressor support
• Immune mechanisms
• Neurologic failure
• Renal replacement therapy
• Low albumin and elevated glucose levels

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SIRS and/or sepsis

• in a cohort of open-heart surgery patients,
  sepsis occurred more in patients with CIP, and
  patients with CIP suffered longer from sepsis
  than patients without CIP.
• Bacteremia was found to be an independent risk
  factor for polyneuropathy in a study by van den
  Berghe

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• Steroid
• The steroid and muscle relaxants have also been
  implicated as a cause of prolonged weakness.
• No study found evidence of a role for steroids
  in CIP
• Neuromuscular blocking agents
• NMBAs were found to be a risk factor on
  multivariate analysis in one study, but
• most studies did not find evidence for a role
  of NMBAs in CIP

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• Aminoglycoside antibiotics
• Aminoglycoside antibiotics administration was
  the only significant difference between the group
  with and the group without CIP (59 vs 19 ) in 2
  studies
• Total parenteral nutrition
• Total parenteral nutrition has been suggested
  as a risk factor for CIP
• Recently, a Garnacho-Montero et al. found TPN
  to be independently associated with CIP
  development on multivariate analysis (P 0.02).

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• Vasopressor support
• Vasopressor support for more than 3 days was an
  independent predictor of polyneuropathy on
  multivariate analysis in study by van den Berghe
  et al.
• In another prospective study, patients who
  developed CIP used significantly more epinephrine
  and norepinephrine and less dobutamine than
  patients who did not develop CIP.

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• Immune mechanisms
• The presence of Anti-GM1-ganglioside IgG of
  patients with CIP has been demonstrated
• The supposed autotoxin may disturb enzymatic
  processes of the neuron and affect axonal
  transport of nutrients and degrading products,
  causing a functional axonopathy.
• Many autotoxins have been considered
  candidates, but TNF has been of special interest
  because it plays a pivotal role in the activation
  of other cytokines in the cascade.
• However, patients with CIP had no significantly
  elevated TNF or IL6 compared with control
  subjects .

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• Neurologic failure
• In a study by Garnacho-Montero et al. GCS lt 10
  is an independent risk factor for development of
  CIP.
• Renal replacement therapy
• in the study conducted by Garnacho-Montero et
  al. Patients who had undergone renal replacement
  therapy had a lower risk of developing CIP on
  multivariate analysis
• In the most recent study
• renal replacement therapy was found to be an
• independent predictor of CIP on multivariate
  analysis

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• Low albumin and elevated glucose levels
• Low albumin and elevated glucose levels were
  mentioned in both retrospective and prospective
  studies as risk factors for CIP
• in another study(large, prospective, randomized
  ,trial ) ,intensive insulin therapy in critically
  ill patients reduced the incidence of CIP by 44,
  provided strong evidence in favor of a role for
  hyperglycemia in the pathogenesis of CIP

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Treatment

• Successful treatment of the underlying
  sepsis/SIRS remains crucial in the prevention of
  CIP
• Prevention now seems possible in many cases
  with intensive glycemic control with insulin in
  critically ill patients
• Immunoglobulins have been used as an adjuvant
  therapy for sepsis and septic shock and are
  effective in patients with Guillain-Barre
  syndrome

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• A retrospective study on the effects of early
  treatment with immunoglobulins in 33 patients who
  survived MOF or GNB sepsis suggested that this
  strategy may prevent or mitigate CIP
• But high-dose immunoglobulin dministration
  failed to alter the clinical course

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Prognosis and outcomeShort-term prognosis

• recovery will take weeks in mild cases and
  months in severe cases
• Mortality in the ICU was 2 to 3.5 times higher
  for patients with CIP versus patients without CIP
  
• CIP also have a negative influence on prognosis
  by causing weaning difficulty.

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• Long term prognosis
• Most investigators agree that there is a 50
  chance of complete recovery depending on the
  severity of the initial symptoms
• After 1 year of follow-up of 24 pts
  ,improvements were reported in all patients ,but
  severe functional handicap was noted in 5/24
  patients (22)
• Zifko determined the clinical and
  electrophysiologic profile of 13 survivors
  (median f/u 17 Ms)
• only two (15) were clinically normal ,but
  All patients still had neurophysiologic
  abnormalities

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• in one 2-year f/u study analysis in 19 patients
  with CIP
• 10 died
• 58 recovered completely
• 32 had remaining quadriparesis
• Three parameters were significantly correlated
  with poor recovery
• longer length of stay in ICU,
• longer duration of sepsis
• greater body weight loss

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Conclusions

• Sepsis and/or SIRS are the most important risk
  factors for CIP.
• CIP is a common disorder in surgical patients.
• Critical illness myopathy is increasingly
  recognized and can occur together with CIP.
• Direct muscle stimulation and quantitative EMG
  are valuable in the d/d between CIP and critical
  illness myopathy.

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• Suxamethonium should be used with caution in
  patients with CIP because of the possibility of
  the occurrence of life-threatening hyperkalemia.
• Intensive insulin therapy in the ICU to achieve
  tight glucose control can reduce the incidence of
• CIP by 44.
• Prospective research with longer follow-up
  (gt3yrs) to determine long-term outcome is
  necessary to describe rehabilitation problems
  encountered in CIP patients.

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Thanks for your attentions
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