Download NeuroMuscular Diseases in Critically Ill Patients

NEUROMUSCULAR DISORDERS
IN CRITICALLY ILL PATIENTS
Dr. Pratyusha Alamuri
Internal Medicine & Critical Care
• Neuromuscular disorders (NMDs) in critical
care may be divided into :
those that precipitate admission to the ICU
those that arise during ICU management
(ICUAW)
GUILLIAN-BARRE SYNDROME
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Introduction
Presentation (Clinical features)
Diagnosis
Monitoring
Treatment
Complications
Prognosis
INTRODUCTION
• is an acute inflammatory demyelinating
polyneuropathy that most often presents with
ascending symmetrical weakness beginning in
the lower extremities.
CLINICAL SIGNS & SYMPTOMS:
• Depressed or absent reflexes
• ~10% of patients, weakness may be first noted in the upper
extremities or facial muscles.
• +Sensory involvement; peripheral paresthesias as the initial
symptom.
• Aching discomfort in the lower back
• Weakness evolves over days to weeks
• Autonomic dysfunction is common in patients with GBS,
occurring in 70% of patients: brady- or tachyarrhythmias,
orthostatic hypotension, hypertension, or abnormal sweating.
• Excluding trauma, GBS is the most common cause for acute
flaccid paralysis in previously healthy people.
DIAGNOSIS
• Clinical symptoms
• Nerve conduction study
o Demyelinating polyneuropathy
• CSF analysis
o Albumino-cytologic dissociation
• MRI Spine (to rule out spinal disorders)
Suggest otherwise ...???
• Diagnoses other than GBS should be more
aggressively considered if :
(1) reflexes remain intact despite weakness
(areflexia is present in ~90% of patients when
weakness is fully developed)
(2) the distribution of weakness is highly
asymmetric;
(3) fever is present during the initial presentation;
(4) The electrodiagnostic features are not indicative
of an acquired demyelinating polyneuropathy
MANAGEMENT
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20/30/40 rule
Intravenous Immunoglobulin
Plasma Exchange
Steroids have a role in CIDP only
MRC sum score
MRC SUM SCORE
•Deltoid
•Biceps
•Wrist extensor
•Ileopsoas
•Quadriceps femoris
•Tibialis anterior
PROGNOSIS
• Approximately two-thirds of patients experience mild
residual long-term deficits.
• 10% to 20% of patients recover completely. Severe
disability may persist in as many as 20% of patients,
and 3% to 8% of patients will die as a result of
pneumonia, acute respiratory distress syndrome,
sepsis, pulmonary emboli, or cardiac arrest.
• Sudden death has been observed in patients with
severe autonomic dysfunction.
• The mortality rate of patients with GBS who require
mechanical ventilation may be as high as 20%.
MYASTHENIA GRAVIS
Myasthenia gravis (MG) is an acquired autoimmune
disorder of neuromuscular junction transmission
characterized by:
• muscle weakness
• progressive muscle fatigue with repetitive use &
• improvement in strength after rest
• Ocular muscle involvement - Ptosis and diplopia
• Facial muscle weakness (difficulty in smiling, an
appearance referred to as the “myasthenic sneer.”
• Bulbar muscle impairment results in dysarthria and
difficulty in both chewing and swallowing, with an
increase in the riskfor aspiration.
IMMUNOPATHOGENESIS
• Has been relatively well defined, with
identification of auto-antibodies that bind to the
acetylcholine receptor (Ach R), resulting in a
significant reduction in the number of available
receptors at the neuromuscular junction, thereby
impairing neuromuscular transmission.
• Auto-antibodies to muscle specific receptor
tyrosine kinase (MusK) have also been identified
in patients with MG.
Conditions associated with MG:
• Thymic hyperplasia or thymoma
• Autoimmune disorders:
• SLE
• RA
• Thyroiditis
• Graves disease.
• The subset of patients who are Ach R antibody
negative and MusK antibody positive are:
more often female with an oculobulbar
pattern
respiratory and proximal muscle weakness
lack of thymic abnormalities, limited response
to acetylcholinesterase inhibitors
responsive to treatment with PE and IVIg.
MG – Diagnosis
Centers on three principal studies:
• positive anticholinesterase test (rapid and
transient improvement in strength after
administration of edrophonium) in patients with
obvious ptosis or ophthalmoparesis;
• presence of acetylcholine receptor antibodies in
the serum;
• electrophysiologic studies that are indicative of a
disorder of the neuromuscular junction, with a
decremental response in compound action
potentials to repetitive nerve stimulation
TREATMENT
• FIRST LINE AGENTS (AchE Inhibitors)
• IMMUNOMODULATING THERAPY
• SURGERY
FIRST LINE AGENTS
• Anticholinesterase medications to increase
the concentration of acetylcholine available
for receptor binding.
• Pyridostigmine: 30–60 mg P/O three to four
times daily.
• The maximum useful dose of pyridostigmine
rarely exceeds 120 mg every 4–6 h during
daytime.
SECOND LINE AGENTS
• Corticosteroids are indicated for patients who have
responded poorly to anticholinesterase drugs and have
already undergone thymectomy.
• Corticosteroid use results in a remission or marked
improvement in approximately 75% of patients with
MG.
• Often introduced with the patient in the hospital, since
weakness may initially be aggravated.
• The dose of corticosteroids is determined on an
individual basis, but an initial high daily dose (eg,
prednisone, 60–100 mg orally daily) can gradually be
tapered to a relatively low maintenance level as
improvement occurs; total withdrawal is difficult,
however.
SECOND LINE AGENTS
• Azathioprine may also be effective. The usual
dose is 2–3 mg/kg orally daily after a lower
initial dose.
• Mycophenolate mofetil or cyclosporine is
typically reserved for more refractory cases.
• Cyclosporine, Azathioprine & mycophenolate
(have a more delayed onset of action).
• Cyclophosphamide
MYASTHENIC CRISIS
• rapid and severe decline in respiratory muscle function
(diaphragmatic involvement)
• mortality of 4% to 13%.
• Triggers for myasthenic crises:
 Infection (M/C)
 Medication changes, withdrawal of anticholinesterase
drugs, drugs that impair neuromuscular transmission
 Electrolyte abnormalities
 Trauma / surgery / pregnancy
• Plasmapheresis or IVIG therapy (have similar efficacy)
 for managing acute crisis
 in patients with major disability
 stabilizing patients before thymectomy
SURGERY
Thymectomy :
• leads to symptomatic benefit or remission
• should be considered in all patients younger
than age 60, unless weakness is restricted to
the extraocular muscles.
• If the disease is of recent onset and only
slowly progressive, operation is sometimes
delayed for a year or so, in the hope that
spontaneous remission will occur.
LAMBERT-EATON SYNDROME
• Eaton-Lambert syndrome is an uncommon disorder of
neuromuscular transmission, which may be confused
with MG.
• The Eaton-Lambert syndrome is associated with
neoplastic disease in approximately 50% of patients
(most commonly small cell carcinoma).
• In contrast to patients with MG, the compound muscle
action potential demonstrates a significant incremental
increase following repetitive nerve stimulation or
maximal isometric muscle activation in patients with
the Eaton-Lambert syndrome.
AMYOTROPHIC LATERAL SCLEROSIS
• ALS is the most common form of progressive
motor neuron disease.
• Neurodegenerative disease (Death of
UMN/LMN)
• The most devastating of the neurodegenerative disorders.
• No treatment arrests the underlying
pathologic process in ALS.
• The drug Riluzole (100 mg/d) was approved
for ALS because it produces a modest
lengthening of survival.
• Predominantly supportive care.
BOTULISM
• Botulism results in a toxin-mediated
irreversible inhibition of neuromuscular
transmission
• Clostridia - anaerobic gram-positive organisms
that form subterminal
• 4 syndromes: Wound/Food/Infantile/Adult
Botulism
Presents as:
• Acute symmetric descending paralysis, which
typically begins with bulbar and eye muscle
impairment.
• Bilateral and symmetrical cranial nerve
involvement is characteristic.
• The early bulbar involvement of botulism
initially may be confused with the MillerFischer variant of GBS.
FOOD-BORNE BOTULISM
• Botulism is not typically accompanied by fever, altered mental
status or sensory abnormalities.
• Nausea, Vomitings, abdominal pain.
• “Dozen Ds” of signs and symptoms:
 dry mouth, diplopia (indicating involvement of cranial nerve III, IV,
or VI), dilated pupils, droopy eyelids (ptosis), droopy face,
diminished gag reflex, dysphagia, dysarthria, dysphonia, difficulty
lifting head, descending paralysis (usually symmetric and flaccid)
and dyspnea from diaphragmatic paralysis.
• Early treatment with an antitoxin directed against the neurotoxin
derived from Clostridium botulinum. 20 mL (1 vial) IV infusion;
dilute further with 0.9% NaCl to 1:10 ratio before administering. 0.5
mL/min for initial 30 minutes
• Progressive respiratory failure with need for mechanical ventilation
occurs in approximately 25% of patients with botulism.
WOUND BOTULISM
• Suspect wounds and abscesses should be cleaned,
debrided, and drained promptly.
• C. botulinum is susceptible to penicillins and various
other antimicrobial agents.
PERIODIC PARALYSIS
• Electrolyte abnormalities must be considered in the
differential of progressive neuromuscular weakness.
• Marked hypokalemia can lead to generalized muscle
weakness.
• Most causes of hypokalemia develop gradually and
weakness is uncommon at potassium levels above 2.5
mEq/L.
• With familial hypokalemic familial periodic paralysis,
potassium levels fall abruptly and clinical manifestations
may be evident at higher values.
• Hyperkalemia can also lead to weakness, as can
hypophosphatemia.
• Finally, marked elevation in serum magnesium levels or
severe hypocalcemia may impair neuromuscular
transmission by inhibiting the release of acetycholine.
Organophosphate Poisoning
• Organophosphate toxicity inhibits acetylcholinesterase
resulting in markedly elevated acetylcholine concentrations
in the neuromuscular junction.
• Organophosphate toxicity may result from ingestion
(accidental or intentional), skin contact with absorption, or
inhalation (eg, Sarin nerve gas).
• Patients typically present with both muscarinic
(bradycardia, bronchospasm, lacrimation) and nicotinic
(hypertension, mydriasis, tachycardia, weakness)
symptoms. Delirium is also common.
• Treatment:
 Atropine targets the muscarinic manifestations
 pralidoxime (hydrolyzes organophosphate from
acetylcholinesterase) treats both muscarinic and nicotinic
manifestations.
ICU ACQUIRED WEAKNESS
(ICUAW)
ICUAW defined as an MRC
sumscore of less than 48
Clinical features suggesting ICUAW
• Onset of weakness is after the acute presentation
• Clinical context includes acute, severe illness requiring
either prolonged mechanical ventilation, or sepsis and
multiorgan support
• Exclude direct effects of sedation or NMB
• Normal cognition presence of flaccid, symmetrical motor
weakness (with muscle wasting) affecting limbs and
respiratory muscles, but sparing cranial nerves
• Reflexes are absent if a primarily neuropathic pathology, or
reduced/absent if primarily a myopathic pathology.
• Sensation may be affected with primarily neuropathic
lesions
• Muscle strength grade (using Medical Research Council
sum score – see text) <48/60
CRITICAL ILLNESS POLYNEUROPATHY
• This acute, diffuse, mainly motor neuropathy is
probably the commonest of these disorders.
• Presents in the recovery phase of a severe
systemic illness with persistent quadriparetic
weakness, hyporeflexia and difficulty in weaning
from respiratory support.
• Specific association with severe sepsis and MODS.
• Histological and electrophysiological features are
consistent with axonal degeneration.
• The mortality in this group is high, presumably
reflecting that of the underlying condition.
CRITICAL ILLNESS MYOPATHY
• This disorder is linked with asthma and with the use of
corticosteroids, NMBA and, less convincingly,
aminoglycosides and beta-adrenergic agonists.
• Reflexes are preserved except in severe cases, as is
sensation.
• Elevated blood CPK concentrations are often seen.
• A few patients have a more severe, fulminant form
with very high CPK levels, frank rhabdomyolysis and,
rarely, renal failure.
• Electrophysiological findings are somewhat variable,
though muscle necrosis is usually apparent on
histology.