Neuromuscular Disorders in ICU

Suresh Ramasubban MBBS, FACP, FCCP

AB-Internal Medicine/Pulmonary/Critical
Care Medicine
Apollo Hospitals, Kolkata
Objectives

Neuromuscular disorders requiring ICU

admission
ICU acquired Neuromuscular disorders
Intro

Three major tasks:

• Assess stability, signs of imminent resp failure
• Generate differential diagnosis
• Knowledge of localisation
• Knowledge of major disorders
• Determine management
Disorders presenting with weakness

UMN Lesions
Motor cortex
Corticospinal tract
Anterior Horn cell disease
Peripheral nerves
NM Junction
Muscle
Physical Exam
Major Disorders
Level of motor unit Disorders causing rapidly progressing weakness
Motor neuron ALS
Poliomyelitis, West Nile virus
Peripheral nerve Guillain-Barre syndrome/AIDP
Tick paralysis
Diphtheric, porphyric, arsenic neuropathy
Shellfish poisoning
Neuromuscular Myasthenia gravis
junction Botulism
Lambert-Eaten myasthenic syndrome
Hypermagnesemia
Muscle Acquired: Dermato- and polymyositis,
Myoglobinuric myopathy, Hypokalemic paralysis,
Toxic myopathy, Acute myopathy of intensive
care
Genetic disorders: X-linked dystrophies, myotonic
dystrophy, acid maltase deficiency, mitochondrial
Muscle Examination
Disorders presenting with Weakness&
Respiratory failure (NM Disorders suspected)

GBS (20-30%)
MG (15-28%)
PM/DM
OP
Tetanus
Botulism
Snake Bite
Periodic Paralysis
Respiratory Muscle weakness due to
NM disease-Clinical manifestation
Respiratory muscle weakness (inspiratory,
expiratory, upper airway) can cause
Inadequate Ventilation
Nocturnal Hypoventilation
Ineffective cough
It can also be associated with bulbar
dysfunction
Inadequate Ventilation

Principal Cause of insufficient ventilation is

weakness of the inspiratory muscles
Weak inspiratory muscles lead to decreased
tidal volume
Compensation by increased Respiratory rate
Manifests with dyspnea, accessory muscle
use and thoracoabdominal paradox.
Hypoxemia

Insufficent ventilation itself causes

hypoxemia
Lack of sigh leads to atelectasis and shunting
leading to hypoxemia
Nocturnal Hypoventilation

Upper airway collapse during sleep and

hypoventilation during REM
Manifests as OSA
Bulbar dysfunction

Impairment of upper airway muscles

Symptoms are difficulty swallowing,
dysarthria, dysphagia, weak mastication,
facial weakness.
Increased risk of aspiration
Ineffective cough

Weakness of upper airway, inspiratory and

expiratory muscles
NM disease Requiring ICU admission

Respiratory muscle impairment is the most

common reason for admission to the ICU in
patients with NM disorders.
Paucity of symptoms even with respiratory
muscle impairment
Objective Respiratory muscle function
assessment
Assess Respiratory Status

• Tests in ER
– MIP
– MEP
– FVC
– ABG
• 20/30/40 rule
– VC: 20 ml/kg
– MIP: -30cmH20
– MEP: +40cm H20
Objective Respiratory Muscle Function
Parameters
MIP
• Maximum effort at Residual volume
• 70 cm H2O for women and 100 cm H2O for men
MEP
• Maximal effort at TLC
• 100 cm H2O for women and 150cm for men
VC
• 50ml/kg
• Below 30ml/kg, elimination of secretions & coughing is
impaired
Assessment of oropharyngeal function-clinical
MG

Autoimmune disorder caused by antibodies

directed against the Acetylcholine receptor
of skeletal muscle
2:1 female to male predominance
Bimodal age distribution
Classification

Auto-immune – two forms

• Acquired anti-AChR Abs (85%)
• Acquired anti-MuSK Abs, a muscle-specific TK
• 40-50% of anti-AChR seronegative pts
Congenital
• Heterogeneous group (pre or post-synaptic)
• Of note: do not affect respiratory muscles therefore do
not present with myasthenic crisis
Clinical Features

• Painless, fatigable weakness of voluntary

muscles
– Repeated activity  progressive paresis
– Rest  restoration of strength (at least partial)
• Usually insidious onset
– May occur more rapidly after precipitant (stress,
infection)
• Association with thymic abnormalities
– 10-15% thymoma
– 50-70% thymic lymphoid hyperplasia
Clinical Features
• Presenting symptoms:
Diplopia 50-64%
Ptosis 50-64%
Generalised weakness 35%
Leg weakness 10%
Fatigue 9%
Respiratory failure 1%

• MuSK-MG
– Younger women
– Predominantly facial, bulbar and respiratory weakness
– Relatively mild limb weakness
Severity Classification
Myasthenic crisis

Defined as respiratory failure requiring

mechanical ventilation
Bulbar Myasthenia also included
Occurs in 15-20% of patients
Mechanism of disease

Anatomically, the pathology of MG occurs at

the postsynaptic neuromuscular junction
Precipitating factors
Drugs that can exacerbate Weakness in MG
D/D
Cholinergic crisis

Skeletal muscle weakness associated with

excessive secretions, diarrhea, sweating,
bradycardia, fasciculations and
improvement after discontinuation of
anticholinesterase medication.
Key to differentiation between myasthenic
and cholinergic crisis
is pupil size, which should be small or
pinpoint in cholinergic crisis.
Clinical presentation and
pathophysiology

Respiratory muscle weakness

• Leads to impaired lung expansion, hypoventilation
and a weak cough
Oropharyngeal weakness
• Leads to aspiration of secretions and inability to
clear the upper airways
Diagnostic testing

Antibody testing
• AchR Antibody-80% of generalized MG, only 50% of
ocular MG
Edrophonium testing
• Subjective, unless clear ptosis or extraocular movement
abnormality
• FVC measurement may be more relevant
EMG & NCV
• Single fiber EMG and repetitive testing enhance sensitivity
• Increased time from stimulation to muscle contraction
• Decremental response in CMAP to repetitive stimulation
Management

Assess adequacy of ventilation and need for

immediate intubation
Ventilatory management

Nasotracheal versus orotracheal intubation

Avoid all cholinergic medications
Promote lung expansion and atelectasis
• Larger TV??
• Larger PEEP???
Sedation with short acting agents with
frequent daily interuptions.
Preexisting myasthenic weakness, do not try
to correct PCO2
Anticholinesterase Therapy

It should be discontinued as long as MG

patients remain on ventilator to avoid
excessive secretions that may worsen
atelectasis and lung consolidation
Weaning

Weaning is to be initiated when

• Strength is improving
• VC > 10ml/kg
• NIF > -20 cm
• Oxygenation is normal
Weaning best with daily PS trials. Once
tolerating greater than 4 hours of PS, levels
of PS can be reduced by 1-3 cm every day
Failed weaning

Predictors are
• Preintubation serum bicarbonate > 30mg/dl
• Peak VC post intubation < 25ml/kg
• Age > 50 years
Immunotherapy in ICU

Plasmapheresis and IVIG

• Mainstay is Plasmapheresis
• It removes AchR abs as well as other circulating
complements and cytokines
• Early initiation leads to better outcomes
• Five exchanges of 2-3 litres every 24-48hours
GBS

Flu like symptom or diarrheal illness that

occurs 1-3 week before the onset of
symptoms in two thirds of patients.
Associated with
CMV
Campylobacter
GBS

GBS is an immune mediated damage of

Myelin Sheath
Immune theory based on neuropathologic
observation of perivascular infiltration in
association with segmental demyelination
and myelin splitting.
Typical Symptoms & Signs

• Sensory
– Paresthesias and slight numbness distally earliest Sx
– Reduced proprioception and vibration sense (1 wk)
• Motor
– Weakness
• Evolves symmetrically over days to 1-2
weeks
• Usually LE before UE, proximal + distal
• +/- trunk, intercostal, neck, cranial muscles
– Progresses to total motor paralysis and respiratory failure
in 5% of cases
Typical Symptoms & Signs

• Reflexes
– Reduced and then absent
• Autonomic dysregulation
– Sinus tachycardia/bradycardia, facial flushing, labile
BP, excess or loss of sweating, urinary retention
– Usually do not persist for >er 1 wk
• Other
– Myalgias (50%) in hips, thighs, back
Variants
• Fisher syndrome
– Ophthalmoplegia, ataxia, areflexia
– +/- bilateral facial nerve paresis
– Associated with anti-GQ1b Ab
• Acute motor sensory axonal neuropathy (5% of GBS cases)
– Severe and diffuse axonal damage
– Abrupt and explosive onset
– Severe paralysis, minor sensory features
– Slow and poor recovery
• Pandysautonomia
– Severe orthostatic hypotension, anhidrosis, dry eyes and mouth, fixed pupils,
arrhythmia, bowel/bladder dysfunction
– Areflexia without somatic motor/sensory involvement
• Other variants:
– Initial cervico-brachial-pharyngeal muscle involvement
– Generalised ataxia without dysarthria or nystagmus
– Facial and abducens weakness, distal paresthesias, proximal leg weakness
Laboratory Findings

• Most important: CSF, EMG

• CSF
– Normal pressure
– Protein
• Early (1st 2 days): Usually normal (>85%)
• Later: High (66% in 1st week, 82% in 2nd week)
• Amount not correlated with clinical course or
prognosis
– Acellular or few lymphocytes
• 10% : 10-50 lymphocytes, decreases over 2-3 days;
if not: other Dx
– Oligoclonal bands (10-30%)
Laboratory Findings

EMG
• Abnormalities seen within first week of sx
• Reduction in motor amplitude
• Slowed conduction velocities
• Conduction block in motor nerves
• Prolonged distal latencies (distal conduction block)
• Prolonged/absent F-responses (involvement of proximal
parts of nerves and roots)
Laboratory Findings

Hematology
• Abnormal only with infection or other disorder
Biochemistry
• Mild-severe SIADH in 7-26%
Liver enzymes
• Elevated <10% reflecting CMV or EBV infection
ESR: Normal unless co-existing process
Diagnostic Criteria
• National Institute of Neurological Disorders and Stroke (NINDS) criteria are
based on expert consensus.
• Required features include:
– Progressive weakness of more than one limb, ranging from minimal weakness of the legs to
total paralysis of all four limbs, the trunk, bulbar and facial muscles, and external
ophthalmoplegia
– Areflexia. While universal areflexia is typical, distal areflexia with hyporeflexia at the knees and
biceps will suffice if other features are consistent.
• Supportive features include:
– Progression of symptoms over days to four weeks
– Relative symmetry
– Mild sensory symptoms or signs
– Cranial nerve involvement, especially bilateral facial nerve weakness
– Recovery starting two to four weeks after progression halts
– Autonomic dysfunction
– No fever at the onset
– Elevated protein in CSF with a cell count <10 mm3
– Electrodiagnostic abnormalities consistent with GBS
Differential Diagnosis

• Features suggesting another diagnosis:

– Sensory level, severe bladder or bowel dysfunction
 Spinal cord syndrome
– Marked asymmetry  Mononeuritis
multiplex/vasculitis
– CSF pleocytosis  Infectious disorders: viral, HIV,
lyme, poliomyelitis
– Very slow nerve conduction velocities, multiple
relapses or chronic course -> CIDP
– Persistent abdominal pain and psychiatric signs 
Acute intermittent porphyria
Intubation in GBS
Autonomic dysfunction

Dysautonomia is an important cause of death

Risk factors are tetraplegia, respiratory failure,
bulbar involvement
Manifestation is tachy/brady and labile BP
Daily pulse change > 50 predicts high cardiac
risk of death
Patients with dyaautonomia should be nursed
with HOB at 90 degrees
Prolonged suctioning is recoomended esp
without oxygen in patients with dysautonomia
Management

• General:
– Recommend admission for observation
• Can deteriorate rapidly in first days of presentation
• M&M: Respiratory failure, dysautonomia
• 25% will require mechanical ventilation
• Respiratory
– Measure MIP/MEP/FVC
• Decision to intubate should be based on
downward trend
– Other measures of respiratory status same
• Counting to 20, strength of NF
Management

• Dysautonomia
– 10% develop hypotension
• Volume, +/- pressors
– Hypertension
• IV labetolol
• Other complications
– Adynamic ileus
– PE
– Aspiration
Management

PLEX and IVIG

• No difference in efficacy between the two
• Indications for prompt initiation
• Respiratory failure
• Bulbar involvement
• Inability to walk without assistance
• Usually see these signs day 5-10
• May occur anywhere from day 1 – week 3
Steroids
• No proven benefit
PLEX

• Regimen: 4-6 treatments on alternate days

• Established usefulness in evolving phase
• If treated within 2 wks onset
– Decrease in LOS, ventilation, time to independent
ambulation by approx. half
• Value less clear if started later than 2 wks
after initial symptoms
• Predictors of response
– Age
– Preservation of motor CMAP amplitudes pre-PLEX
IVIG

Dose: 0.4 gm/kg/day x 5 consecutive days

Cheaper, easier to administer
Rare complications
• Renal failure, proteinuria, pulmonary edema
• Asceptic meningitis
• Anaphylaxis in IgA deficiency
Course and Prognosis

• Progressive symptoms : 1-4 weeks

• Plateau: 2-4 weeks
• Recovery: A few weeks to months
• Recurrence: 5-10%
• Mortality
– 3-5%
– Cardiac arrest, ARDS, PTX, HemoTX, PE
• Pronounced disability: 10%
– Clinical prognostic indicators
• Greater age
• Rapid evolution; early and prolonged ventilatory assistance, rapid
course
• Lack of treatment with IVIG or plasma exchange
– Laboratory
• EMG: severely reduced CMAP and widespread denervation
Dermatomyositis & Polymyositis

Idiopathic inflammatory disorders which

usually present with progressive
symmetrical muscle weakness over several
months
Proximal muscles more affected
Elevated Skeletal muscle enzymes
EMG findings of myopathy
Muscle biopsy with varaible degrees of type I
an II fiber necrosis and inflammation
Skin changes of Dermatomyositis

Heliotropic changes
Gottron’s sign
Cardiac complication of DM/PM

Tachyaarythmias
Conduction abnormalities
Dilated cardiomyopathy
PAH
• Cardiomyopathy related
• Respiratory failure related
• Primary pulmonary hypertension
Respiratory Complications of PM/DM

Abnormal central respiratory drive

Pharyngeal muscle impairment
Respiratory muscle weakness
ILD
Pneumonia-aspiration
Drug induced lung disease
ICU acquired Weakness

Wasting syndromes associated with

protracted infection have long been
recognized.
Osler commented on the “ rapid loss of flesh”
Major cause of morbidity for survivors of
critical illness
Prolongs duration of ICU stay, hospitalization,
costs.
Weaning failure
ICU Acquired Weakness

Variations in terminology and nosology

characterize this literature
Critical illness polyneuropathy (CIP)and
critical illness myopathy (CIM), have been
defined by advanced neuromuscular
testing and muscle biopsy that are not
performed routinely in critical care.
Overreaching term for neuromuscular
disease in the critically ill is ICU acquired
weakness (ICU-AW)
Clinical Presentation

Two bedside contexts

Most commonly, the clinician struggling to
liberate a patient from mechanical
ventilation will entertain the diagnosis of
weakness
The second bedside context involves the
patient with such profound weakness
despite return of sensorium that causes of
quadriplegia are entertained
Clinical presentation

Physical examination is dependent on the

cooperation and maximal effort of the
patient, an aspect of bedside assessment
that can be confounded by sedation,
delirium, encephalopathy & other ICU
influences on cortical brain function.
Symmetric motor deficits in all limbs ranging
from paresis to true quadriplegia
D/D

Once a weakness syndrome is entertained,

clinicians must clearly establish the
absence of a NM condition that began
before admission to the ICU.
Categories of ICU-AW

CIP
• Sensorimotor axonopathy with decreased
compound muscle action potential (CMAP) and
sensory nerve action potential yet normal nerve
conduction velocities
CIM
• EMG during voluntary contraction exhibits a
characteristic pattern of abundant low amplitude,
short duration polyphasic units with early recruitment
• Muscle bipsy with selective loss of muosin is
pathognomonic.
Differentiating CIM and CIP

Direct muscle stimulation

• Both conditions demonstrate reduced nerve evoked
CMAP amplitude , yet denervated muscle (as in
CIP) should retain electrical excitability on direct
stimulation.
• CIM patients have reduced CMAP’s with both nerve
and direct muscle stimulated testing
ICU-AW

Significant Overlap between CIP and CIM,

thus term CIPNM has been used.
ICU-AW
• MRC score < 48 is a good discriminator
• All these patients had sensory motor axonopathy
and histologc features of primary myopathic
changes
Diagnostic Algorithm
Epidemiology

De jonghe has shown a 25% incidence of ICU-

AW in patients ventilated > 7 days.
This is an underestimate as many patients
have poor mental status which precludes
good assessment of NM strength ptior to
death
NCV/EMG related incidence is very high,
ranging from 50-100%
Outcomes

Short term outcomes

• Prolonged mechanical Ventilation: 2 studies have
demonstrated Significantly longer duration of ventilation
in patients with ICU-AW
• Increased Mortality: 2 studies have shown increased
mortality in the CIP group
Long term outcomes
• Muscle wasting and weakness are common
• Complete functional recovery at 6 months occurred in
68% with CIP. Severe disability persisted in 28%
• Milder disabilities like glove and stocking sensory loss,
muscle atrophy and foot drops were common
Risk Factors

Systemic Inflammation
Medications
Electrolyte disturbance
Immobility
Systemic Inflammation

Strongly correlated with SIRS, Sepsis &

MSOF
Letter et al in prospective study has
demonstrated that high APACHE III score
and presence of SIRS were associated with
the development of CIPNM
Mechanism is not very clear but low level
inflammation in the muscles of critically ill
patients is responsible for CIPNM
Medications

Corticosteroids
• Most widely studied and strongest association for ICU-AW
• Animal studies have shown selective fast fiber damage with
steroids.
• The two hit model of fast fiber damage due to steroids and
denervation injury in critical illness (StatusAsthmaticus) explains
the profound weakness
• Lack of benefit of Meduri protocol in ARDS is also due to muscle
weakness.

NMBA’s
• Prolonged NM blockade
• Simultaneous high dose steroids
Glycemic Control

Van den bergh study demonstrated 50%

reduction in evolution of CIP
In medically ill patients the presevation of
neuromuscular function with tight sugar
control is not proven
Immobility

Duration of Mechanical ventilation prior to

awakening is a significant risk factor,
independent of duration of MSOF
Immobility alone does not cause muscle
atrophy, Associated with critical illness
only.
Prevention/Treatment
Summary

Weakness in the ICU needs to be evaluated

carefully
Respiratory Muscle function Should be
objectively Assessed
Early ventilation in NM disorders
Prevention of ICU acquired weakness is the
key