weakness in the critically ill patient susan m. stickevers, md program director, physical medicine...
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Weakness in the Critically Ill Patient
Susan M. Stickevers, MD
Program Director, Physical Medicine & Rehabilitation, SUNY Stony Brook
Objectives
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
Diagnostic Approach Causes of Weakness in the ICU
Critical illness Polyneuropathy Critical illness Myopathy:
Diffuse Non-Necrotizing Myopathy Thick Filament Myopathy Acute Necrotizing Myopathy
Outcomes
Introduction
Severe Muscle Weakness Common in ICU Patients 25 - 33% develop clinically overt weakness 50% develop electrophysiological abnormality
Consequences Prolonged ventilation & ICU stay Other complications of ICU stay - pulmonary
embolism, DVT, decubiti Death
Introduction
Signs of Critical Illness Neuropathy / myopathy may be incorrectly attributed to: Sedation Depression Coma Deconditioning
Critical illness Polyneuropathy & Myopathy are diagnoses of exclusion
Diagnostic Approach
Think broadly! Long differential diagnosis, depending on the clinical
context Examine the patient - Confirm weakness- Suspect critical illness myopathy/neuropathy if:
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
Mental status - not affected in critical illness myopathy & polyneuropathy
Pattern of weakness Symmetric, with facial sparing If cranial nerve weakness is present – consider alternative diagnoses:
Motor Neuron Disease Guillain Barre Syndrome Myasthenia Gravis Stroke
DTRs - usually decreased in critical illness neuropathy & myopathy If DTRs are increased, this suggests central lesion
Delayed elevation CPK & myoglobin
Differential Diagnosis
Spinal Cord Dysfunction Guillain – Barre Syndrome Motor Neuron Disease Porphyria Pre – Existing Neuropathy Myasthenia Gravis
Diagnostic Clues (cont’d)
The ICU-specific exam - ventilation! Clinical – increased respiratory rate, heart rate, blood
pressure Laboratory – acidosis, hypercapnia, hypoxemia Ventilator measurements
Rapid Shallow Breathing Index (f/Vt > 105) Validated for demand-induced fatigue
Maximum inspiratory pressure (< 20 cm H2O) Integrated indices (e.g. CROP)
Demand vs. work of breathing
Work Up
MRI Brain (with gadolinium contrast) To rule out pontine infarct (‘locked-in’ syndrome) in
severe cases EMG - Indications
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
First described in early 1980s Also known as neuropathy of critical illness, ICU
neuropathy Occurs in 25% of ICU patients on average -
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
Witt et al., Chest. 1991 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
Acute axonal neuropathy Follows course of illness Self-limited
Recovery excellent in mild-moderate disease Permanent disability in severe forms
Not attributable to other neurologic insult
Critical Illness Polyneuropathy - Pathogenesis
Etiology - ? Association with … Systemic Inflammatory Response Syndrome
(SIRS) & multi – system organ failure 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 &….
Only direct markers: Increased duration of ICU stay Increased serum glucose Decreased serum albumin
Critical Illness Polyneuropathy – Clinical Features
Delayed weaning from ventilator Sensorimotor polyneuropathy
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
Work Up EMG / NCS – Consistent with Sensory & Motor
Axonal Polyneuropathy 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
Primarily distal No inflammation or demyelination
Critical Illness Myopathy
Synonyms :
- Myopathy of Critical Illness
- Intensive Care Myopathy
- Acute Quadriplegic Myopathy
- Acute Necrotizing Myopathy
ICU Myopathy Syndromes
Similar clinical presentation to critical illness polyneuropathy
Diffuse Non - Necrotizing Myopathy Thick Filament Myopathy Acute Necrotizing Myopathy Rarer entities
Pyomyositis – seen with pyogenic organisms
Non-Necrotizing Myopathy
Mild changes on EMG/biopsy CPK usually normal Seen in association with critical illness
polyneuropathy
Critical Illness Myopathy
Pathology 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 12/31 muscle biopsies showed atrophy 15/31 showed necrosis 5/12 serial biopsies – progressive necrosis
CIM – Pathogenesis
Mechanisms of injury related to sepsis Direct effect of toxins secreted by
microorganisms Inflammatory mediators involved in
pathogenesis IL-1, TNF, glucocorticoids – proteolysis Intracellular myofibrillar protein degradation
Intramuscular immune activation
CIM or CIPN?
Different entities found in similar patients Postulated reasons
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
A Rose by Any Other Name…
Bednarik et al. Intensive Care Medicine, 2003. 46 patients with >1 organ failure EMG in all patients
Muscle biopsy in 11 Sural nerve biopsy in 5
Overlapping findings in most patients Suggest ‘polyneuromyopathy’ as more
appropriate descriptor - CIPNM
Thick Filament Myopathy
First described in association with high-dose steroids Well described in asthmatics & transplant recipients Often seen in patients on steroids in combination with
neuromuscular blocking agents Selective thick (myosin) filament loss
? decreased myosin transcription Neurogenic component absent CPK may be elevated, with or without
myoglobinuria
Thick Filament Myopathy - Pathogenesis
Mechanisms poorly understood Corticosteroid hypersensitivity in denervated
muscle Neuromuscular blocking agents Potentiated by critical illness polyneuropathy
?Sepsis mediated proteolysis Disuse vulnerability Membrane inexcitability – secondary to TNF
Thick Filament Myopathy
Leatherman et al. Am J Respiratory Critical Care Medicine, 1996. 107 pts ventilated for asthma
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
Less common Pathology – vacuolization/phagocytosis Pathogenesis - ?similar to Thick Filament
Myopathy CPK often elevated Risk of rhabdomyolysis in this disorder
Diagnosis of Myopathy
Physical, serum tests, EMG often negative 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
Muscle Biopsy
Modality of choice Invasive, time sensitive Findings
Atrophy Selective thick (myosin) filament loss on electron
microscopy ?Role of myosin / actin ratio
Stibler et al. Intensive Care Medicine, 2003.
Necrosis / phagocytosis/ vacuolization
Indications to Biopsy for Suspected CIM
Any patient with paresis without EMG evidence consistent with pure critical illness polyneuropathy and … Normal sensory nerve studies Low or Normal CMAP amplitudes Little spontaneous EMG activity
Management of Critical Illness Weakness Syndromes
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 :
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)
Prevention – no specific measures de Letter et al. Critical Care Medicine, 2001
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
Prognosis
High overall ICU mortality in patients with neuropathy / myopathy
Recovery over weeks / months in mild / moderate disease
Slower / incomplete recovery if severe Slow conduction velocities associated with poor
prognosis Fletcher et al. Critical Care Medicine, 2003
Median follow-up 43 months after protracted ICU stay Partial denervation >90%, pure myopathy unusual
Conclusion
ICU-associated weakness is a real entity Neurogenic & myopathic components
Diagnosis of exclusion CIM & CIPN - Difficult to differentiate from each
other 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
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