Transcript Weakness in the Critically Ill Patient

Weakness in the Critically Ill
Patient
Susan M. Stickevers, MD
Program Director, Physical Medicine
& Rehabilitation, SUNY Stony Brook
Objectives
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To define the problem of ICU-associated
weakness
To outline an approach to weakness in
critically ill patients
To discuss common causes of this
phenomenon
Outline
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Diagnostic Approach
Causes of Weakness in the ICU
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Critical illness Polyneuropathy
Critical illness Myopathy:
Diffuse Non-Necrotizing Myopathy
 Thick Filament Myopathy
 Acute Necrotizing Myopathy
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Outcomes
Introduction
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Severe Muscle Weakness Common in ICU
Patients
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25 - 33% develop clinically overt weakness
50% develop electrophysiological abnormality
Consequences
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Prolonged ventilation & ICU stay
Other complications of ICU stay - pulmonary
embolism, DVT, decubiti
Death
Introduction
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Signs of Critical Illness Neuropathy /
myopathy may be incorrectly attributed to:
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Sedation
Depression
Coma
Deconditioning
Critical illness Polyneuropathy & Myopathy
are diagnoses of exclusion
Diagnostic Approach
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Think broadly!
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Long differential diagnosis, depending on the clinical
context
Examine the patient - Confirm weaknessSuspect critical illness myopathy/neuropathy if:
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Unexpected lack of ventilatory weaning
Accelerated peripheral muscle atrophy ( esp. in the
upper extremities)
Inability to hold head/limb off bed
R/O neuromuscular blockade with anticholinesterases
Diagnostic Clues
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Mental status - not affected in critical illness myopathy &
polyneuropathy
Pattern of weakness
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Symmetric, with facial sparing
If cranial nerve weakness is present – consider alternative diagnoses:
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DTRs - usually decreased in critical illness neuropathy & myopathy
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Motor Neuron Disease
Guillain Barre Syndrome
Myasthenia Gravis
Stroke
If DTRs are increased, this suggests central lesion
Delayed elevation CPK & myoglobin
Differential Diagnosis
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Spinal Cord Dysfunction
Guillain – Barre Syndrome
Motor Neuron Disease
Porphyria
Pre – Existing Neuropathy
Myasthenia Gravis
Diagnostic Clues (cont’d)
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The ICU-specific exam - ventilation!
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Clinical – increased respiratory rate, heart rate, blood
pressure
Laboratory – acidosis, hypercapnia, hypoxemia
Ventilator measurements
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Rapid Shallow Breathing Index (f/Vt > 105)
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Validated for demand-induced fatigue
Maximum inspiratory pressure (< 20 cm H2O)
Integrated indices (e.g. CROP)
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Demand vs. work of breathing
Work Up
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MRI Brain (with gadolinium contrast)
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EMG - Indications
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To rule out pontine infarct (‘locked-in’ syndrome) in
severe cases
Inability to adequately assess peripheral muscle
strength in the ICU patient
To rule out potentially treatable condition such as
myasthenia & Guillain – Barre Syndrome
Failure to improve after 3 - 4 weeks
Muscle biopsy
Critical Illness Polyneuropathy
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First described in early 1980s
Also known as neuropathy of critical illness, ICU
neuropathy
Occurs in 25% of ICU patients on average 
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Seen in 70-80% of patients with severe sepsis or
multiple organ system failure
Usual onset > 7 days after onset of critical
illness
Critical Illness Polyneuropathy
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Witt et al., Chest. 1991
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43 patients sepsis with multiple organ system
failure followed 28 days
30/43 (70%) axonal polyneuropathy on EMG
15/43 (35%) had clinical muscle dysfunction
23 survivors – all recovered neuromuscular
function
Critical Illness Polyneuropathy Definition
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Acute axonal neuropathy
Follows course of illness
Self-limited
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Recovery excellent in mild-moderate disease
Permanent disability in severe forms
Not attributable to other neurologic insult
Critical Illness Polyneuropathy Pathogenesis
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Etiology - ? Association with …
Systemic Inflammatory Response Syndrome
(SIRS) & multi – system organ failure
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Pro- inflammatory cytokines (ie TNF) released
causing increased microvascular permeability
Microcirculatory compromise of distal nerves
Axonal degeneration follows
Impaired transport of axonal proteins
Endoneural edema and/or hypoxia
Association with SIRS &….
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Only direct markers:
Increased duration of ICU stay
Increased serum glucose
Decreased serum albumin
Critical Illness Polyneuropathy –
Clinical Features
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Delayed weaning from ventilator
Sensorimotor polyneuropathy
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Generalized muscle atrophy
Flaccid paralysis
Decreased / absent DTRs – only 1/3 have normal
DTRs
Sensory abnormalities (light touch/pain)
Cranial nerves spared
Physical exam often nondiagnostic
Critical Illness Polyneuropathy Diagnosis
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Work Up
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EMG / NCS – Consistent with Sensory & Motor
Axonal Polyneuropathy
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Denervation potentials are widespread in the form of
fibrillation potentials & positive waves
Nerve conduction velocities are spared
Decreased CMAP & SNAP amplitudes
Phrenic nerve conduction studies abnormal with CMAP
amplitude ½ lower limit of normal
Nerve biopsy or autopsy – axonal degeneration
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Primarily distal
No inflammation or demyelination
Critical Illness Myopathy
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Synonyms :
- Myopathy of Critical Illness
- Intensive Care Myopathy
- Acute Quadriplegic Myopathy
- Acute Necrotizing Myopathy
ICU Myopathy Syndromes
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Similar clinical presentation to critical
illness polyneuropathy
Diffuse Non - Necrotizing Myopathy
Thick Filament Myopathy
Acute Necrotizing Myopathy
Rarer entities
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Pyomyositis – seen with pyogenic organisms
Non-Necrotizing Myopathy
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Mild changes on EMG/biopsy
CPK usually normal
Seen in association with critical illness
polyneuropathy
Critical Illness Myopathy
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Pathology
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Muscle fiber size variability & atrophy
Fatty degeneration
Fibrosis & necrosis
Inflammatory changes absent
Helliwell et al. Journal of Pathology, 1991. –
studied muscle biopsies of CIM patients
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12/31 muscle biopsies showed atrophy
15/31 showed necrosis
5/12 serial biopsies – progressive necrosis
CIM – Pathogenesis
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Mechanisms of injury related to sepsis
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Direct effect of toxins secreted by
microorganisms
Inflammatory mediators involved in
pathogenesis
IL-1, TNF, glucocorticoids – proteolysis
 Intracellular myofibrillar protein degradation
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Intramuscular immune activation
CIM or CIPN?
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Different entities found in similar patients
Postulated reasons
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Simultaneous injury from same stressors
Sequential injury – time of biopsy key
Coakley et al. Intensive Care Medicine, 1993.
23 patients evaluated with muscle biopsy & EMG
 Multiple abnormalities in 22/23
 Distal axonal degeneration, necrotizing myopathy
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A Rose by Any Other Name…
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Bednarik et al. Intensive Care Medicine,
2003.
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46 patients with >1 organ failure
EMG in all patients
Muscle biopsy in 11
 Sural nerve biopsy in 5
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Overlapping findings in most patients
Suggest ‘polyneuromyopathy’ as more
appropriate descriptor - CIPNM
Thick Filament Myopathy
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First described in association with high-dose
steroids
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Selective thick (myosin) filament loss
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Well described in asthmatics & transplant recipients
Often seen in patients on steroids in combination with
neuromuscular blocking agents
? decreased myosin transcription
Neurogenic component absent
CPK may be elevated, with or without
myoglobinuria
Thick Filament Myopathy Pathogenesis
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Mechanisms poorly understood
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Corticosteroid hypersensitivity in denervated
muscle
Neuromuscular blocking agents
 Potentiated by critical illness polyneuropathy
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?Sepsis mediated proteolysis
Disuse vulnerability
Membrane inexcitability – secondary to TNF
Thick Filament Myopathy
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Leatherman et al. Am J Respiratory
Critical Care Medicine, 1996.
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107 pts ventilated for asthma
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All received steroids, 69 also had neuromuscular
blocking agents
Weakness only in patients given both drugs
Seen with all neuromuscular blocking agents
Duration of paralysis important (85% of pts.
developed weakness if on NMBA > 72 hours)
Acute Necrotizing Myopathy
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Less common
Pathology – vacuolization/phagocytosis
Pathogenesis - ?similar to Thick Filament
Myopathy
CPK often elevated
Risk of rhabdomyolysis in this disorder
Diagnosis of Myopathy
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Physical, serum tests, EMG often negative
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Normal CPK often seen
EMG usually captures few motor units
True neuropathy vs. “functional” denervation from
end-plate myonecrosis
 Low or Normal Compound Motor Action Potentials
 Sensory Nerve Action Potentials are normal
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Muscle Biopsy
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Modality of choice
Invasive, time sensitive
Findings
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Atrophy
Selective thick (myosin) filament loss on electron
microscopy
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?Role of myosin / actin ratio
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Stibler et al. Intensive Care Medicine, 2003.
Necrosis / phagocytosis/ vacuolization
Indications to Biopsy for
Suspected CIM
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Any patient with paresis without EMG
evidence consistent with pure critical
illness polyneuropathy and …
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Normal sensory nerve studies
Low or Normal CMAP amplitudes
Little spontaneous EMG activity
Management of Critical Illness
Weakness Syndromes
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Supportive Care
Do not attempt early weaning from ventilator
Early mobilization to prevent contractures, decubiti,
deconditioning
Judicious use of steroids & neuromuscular blocking
agents
Special attention to myonecrosis if using steroids &
neuromuscular blocking agents
Watch drug metabolism / elimination factors
Work Up May Also Include :
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MRI C spine, LS spine
Repetitive Stimulation to rule out
myasthenia gravis
Phrenic Nerve studies, especially in those
who are difficult to wean from ventilator
Treatment (cont’d)
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Prevention – no specific measures
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de Letter et al. Critical Care Medicine, 2001
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APACHE III score & septic inflammatory response
syndrome were only true risk factors
van den Burghe et al. N Engl J Med. 2001
Intensive insulin therapy reduced ICU length of
stay
 Lower incidence of CIPN
 More rapid resolution
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Prognosis
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High overall ICU mortality in patients with
neuropathy / myopathy
Recovery over weeks / months in mild /
moderate disease
Slower / incomplete recovery if severe
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Slow conduction velocities associated with poor
prognosis
Fletcher et al. Critical Care Medicine, 2003
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Median follow-up 43 months after protracted ICU stay
Partial denervation >90%, pure myopathy unusual
Conclusion
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ICU-associated weakness is a real entity
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Diagnosis of exclusion
CIM & CIPN - Difficult to differentiate from each
other
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Neurogenic & myopathic components
EMG/biopsies may be helpful
No specific treatment other than supportive care and
therapy
Careful monitoring of use of neuromuscular blocking
agents & steroids
Complete recovery in most
Thanks for your attention …