ICU MANAGEMENT OF

MYASTHENIA GRAVIS
Consultant : Dr.INDU MOHINI SEN
Moderator : Dr. SUNIL THAKUR
Dr.SUDHAKAR
Dr.DINESH KUMAR K K
Myasthenia Gravis in the ICU:
 MYASTHENIC CRISIS

Myasthenic crisis - development of neuromuscular respiratory

failure from myasthenia gravis that requires mechanical

ventilation or endotracheal intubation for airway protection.
 Myasthenic patients in whom post-operative extubation has

been delayed beyon 24 h because of respiratory weakness are

also considered to be in crisis
MuSK-MG >AChR-MG .
PREDICTORS OF ICU NEED FOR A
MYASTHENIA GRAVIS PATIENT

Non-ocular initial symptoms

infection-triggered

 higher MGFA (Myasthenia Gravis Foundation

of America)
 RESPIRATORY PARAMETERS IN
MYASTHENIA CRISIS
 A VC (vital capacity) of less than 1 L (or <20-25 mL/kg)

 NIF(negative inspiratory force) of <20 cm H2O indicates

significant respiratory weakness

 PEF(positive expiratory force) of <40 cm H2O may indicate crisis.
 BEDSIDE TEST

recruitment of accessory muscles indicates significant

inspiratory muscle weakness.

A weak cough or difficulty counting to 20 in a single breath

signifies weakness of the expiratory muscles

 MYASTHENIC CRISIS
EPIDEMIOLOGY
 Fifteen to 20% of myasthenic patients are affected by myasthenic

crisis.
 Myasthenic crisis may be the initial presentation of MG in one-fifth

of patients
 Overall, women are twice as likely as men to be affected.

 AGE<55 affects women 4:1,AGE> 55 affects women and men

equally.
 EPIDEMIOLOGY
Mean ICU stay with ventilatory support – 17 days.

Advances in mechanical ventilation and critical care have

reduced the mortality rate from from 42% to 6%.

 Currently, mortality is 4% and is primarily the result of

comorbid medical conditions.

 PRECIPITATING FACTORS
 poor control of generalized disease  systemic infections often involving

 medical treatment for bulbar the respiratory tract

myasthenia (steroids and  aspiration

anticholinesterases)  surgery
 concomitant use of certain antibiotics
 triggers for crisis –
 muscle relaxants
emotional stress, hot environment,
 benzodiazepines,
sudden elevation of body temperature
 b-blockers and iodinated
 Hyperthyroidism,
radiocontrast agents
 Predisposing Drugs
Antimicrobials
Aminoglycosides (amikacin, gentamicin, streptomycin);
Macrolides (doxycycline, erythromycin, minocycline,
oxytetracycline, tetracycline, azithromycin, telithromycin)
Quinolones (ciprofloxacin, ofloxacin, norfloxacin)
Antimalarials (chloroquine, hydroxychloroquine, quinine)
Urinary antiseptic: nalidixic acid
 Anticonvulsants : Phenytoin and carbamazepine
 Antipsychotics : Neuroleptics (phenothiazines, sulpiride, atypical
like clozapine)
 Predisposing Drugs
Cardiovascular agents ; b-blockers (all, including topical
b-blocker, e.g. timolol eye drops and combined alpha and
b-blocker, e.g. labetolol)
Calcium channel blockers (verapamil, nifedipine)
Class I anti-arrhythmic drugs (quinidine, procainamide)
Others
Neuromuscular-blocking agents
Local anaesthetics (lignocaine)
Muscle relaxants (long-acting bezodiazepines,
baclofen)
Iodinated radiocontrast agents
Botulinum toxin
 Osserman s classification
• (1)Localized, non-progressive disease (ocular myasthenia)
(2) generalized, gradual onset disease (involving more than
one group of striated muscles, both skeletal and bulbar)
(3) Acute fulminant generalized disease with severe bulbar
involvement
(4) Late severe disease (usually developing 2 years or
more after symptoms in category 1 or 2)
(5) Muscle atrophy (not due to disuse) in late generalized
disease, restricted to skeletal muscles and usually related to
the duration of the disease and clinical severity
(myasthenic myopathy)
 The categories 3 and 4 in the Osserman classification of
myasthenia gravis are predisposed to myasthenia crisis
 Myasthenia Gravis Foundation of
America classification
 Class I: ocular myasthenia, also may have
weakness of eye closure
Class II: mild weakness of non-ocular muscles
Class III: moderate weakness of non-ocular
muscles
Class IV: severe weakness of non-ocular
muscles
Class V: requiring intubation, with or without
mechanical ventilation
 Class V is predisposed to myasthenia crisis
 Principles of management of myasthenic
crisis
 General

Airway assistance and ventilation

Discontinue anticholinesterases and any
offending drug
(e.g. antibiotic, b-blocker)
Cardiac monitoring
Identify and treat infection
Prophylaxis for deep vein thrombosis
 Cont…
 Initiate specific treatment

Specific treatment

 Plasma exchange (removal of 1–1.5 times plasma volume on

each session)

 Alternatively, human intravenous immunoglobulin (400

mg//day for 5 days); and

 High dose corticosteroids (prednisolone 1 mg/kg/day)

Abnormal laboratory values that could affect muscle strength

should also be corrected.

Potassium, magnesium, and phosphate depletion can all

exacerbate myasthenic crisis and should be repleted.

Hematocrit less than 30% might affect weakness by

decreasing oxygen-carrying capacity.

 Adequate nutrition is important to avoid a negative energy

balance and worsening of muscle strength

Comparison of Intravenous Immunoglobulin to
Plasma Exchange
IVIg PE

Dose 400 mg/kg 5 d One plasma exchange every

other day over 10 d
Response Improvement in 4-5 d; effect Improvement in 2 d;
for 4-8 wk effect for 3-4 wk
Advantages More readily available Faster treatment response

Disadvantages Slower treatment response Need for special venous

access, equipment, and
personnel
Contraindications IgA deficiency Hemodynamic instability,
unstable coronary disease,
current internal bleeding
Serious Aseptic meningitis, cardiac Hemodynamic instability,
Complications arrhythmia, cardiac arrhythmia,
thrombocytopenia, myocardial
CORTICOSTEROIDS IN MYASTHENIA
CRISIS
 Corticosteroids are used in conjunction with IVIg and Prednisolone.

 High-dose prednisone (60-100 mg daily or 1-1.5 mg/kg/d) may be

initiated concurrently with IVIg or Prednisolone

 Prednisone begins to work after 2 weeks, at which point the effects of

PE and IVIg are waning.

 Initiation of prednisone may be deferred until after the patient is

extubated if the patient is rapidly improving with IVIg or PE treatment.

 Cont…..

 Initial worsening from high-dose prednisone is treated with

continued ventilatory support.

 Worsening of symptoms with the initiation of corticosteroids is not

predictive of overall response to corticosteroids.

 Once the patient has begun to show improvement, the prednisone

dose can be decreased and gradually converted to alternate-day

dosing.
 Cyclosporine may be considered after initiation of IVIg or PE in

patients who cannot tolerate or who are refractory to

corticosteroids.

 Onset of action of cyclosporine is 1-2 months.

 Other immunomodulating agents, azathioprine and

mycophenolate, are not useful in myasthenic crisis because of

their long latency of action.

 USE OF CONTINUOUS
ANTICHOLINESTERASE
Controversial, risk of cardiac complications

(arrhythmia and myocardial infarction).

Coronary vasospasm from excessive anticholinergic

treatment is known to be an iatrogenic cause of

myocardial infarction in myasthenia gravis.
 Increased salivary and gastric secretions, which

may increase the risk of aspiration pneumonia.

 Complications in the Management of
Myasthenic Crisis
 Fever is the most common complication associated with

myasthenic crisis.
 Infectious complications include pneumonia, bronchitis,

urinary tract infections, Clostridium difficile colitis,

bacteremia, and sepsis
 deep vein thrombosis

 cardiac complications including congestive heart failure,

acute myocardial infarction, arrhythmias, and cardiac arrest.

THYMUS IN MYASTHENIA CRISIS
 Thymic hyperplasia is common in young myasthenic patients

with positive AChR antibodies, especially women.

 Thymic tumors, found in 15% of patients with MG and in 32%

of patients with myasthenic crisis, should be treated with

thymectomy.

 Patients with non-thymomatous MG can consider thymectomy

to improve the likelihood of improvement or remission of the

disease.
 THYMECTOMY IN MG.
There are two indications for thymectomy in MG.

The first is for the 10% of patients who have an associated

thymoma which are potentially locally invasive.

The second is in younger patients with generalised
myasthenia where thymectomy is performed to treat the
underlying disease process.
 A recent study has suggested that, contrary to previous

belief, age is not an important factor in predicting favourable

outcome of MG post-thymectomy.
 THYMECTOMY IN
MG
Approximately 80% of patients experience an improvement

in their MG after thymectomy.

Patients need to be medically optimise prior to surgery and

muscle relaxants should be avoided.

The benefits take months or even years to become apparent.

 In centres with experience in the management of

perioperative patients with myasthenia gravis, thymectomy
is a relatively safe procedure.
Cont….
 Postoperative myasthenic crisis is common after

thymectomy; the incidence ranges from 12% to 34%.

 Postoperative crisis in these patients has been related to a

history of myasthenic crisis, preoperative presence of

bulbar weakness, preoperative serum AChR antibody levels

>100 nmol/L, and intraoperative blood loss of >1 L

Cholinergic crisis
 Ddx of myasthenic crisis

 Results from excessive intake of cholinesterase inhibitors

like neostigmine and pyridostigmine

 Clinical features are due to excess of acetyl choline in

nicotinic and muscuranic receptors.

 Nicotinic overstimulation results in involuntary twitching,

fasciculations, finally leading to flacid muscle paralysis and

at times respiratory arrest.
Cont….
 Muscuranic overstimulation causes bronchospasm with

wheezing, bronchorrhea, miosis and the SLUDGE syndrome

(salivation, lacrimation, urinary incontinence, diarrhoea, GI

upset and hypermotility, emesis).However, these findings are

not inevitably present.

 Despite muscle weakness , deep tendon reflexes are preserved.

Tensilon test
• To diff cholinergic and myasthenic crisis
• Edrophonium is an AChE inhibitor
• Rapid onset (30s) and short duration of action (about 5
minutes)
• 10 mg of edrophonium (0.15-0.2 mg/kg) used
• Focus on a weak muscle group and evaluate for change
• Initial dose of 2mg given IV. If no change, give additional
8mg IV
• Beware of cholinergic effects (nausea, diarrhea, salivation,
fasiculations, bradycardia)
• Have atropine at bedside
 In case of myasthenic crisis - some improvement in muscle

strength

 Cholinergic crisis shows no increase in muscle strength and

there will be worsening of symptoms and respiratory distress

 Treatment of choinergic crisis
 Discontinuation of all cholinergic medications including AChE

inhibitors .
 The immediate use of atropine is also recommended,
muscarinic effects are controlled with IV atropine sulfate (1 to
2 mg) followed by IM atropine sulfate every 2 to 4 hours.
 Mechanical ventilation may be required if respiration is

severely depressed.
 Cholinergic crisis in
myasthenic patients

uncommon in present scenario.
 The clinical features are sufficiently distinct from myasthenic crisis

 No ptosis,

small pupils,
muscle fasciculations,
hypersalivation,
bradycardia,
diarrhoea,
bowel and bladder incontinence.
VENTILATORY OPTIONS
NIV- BIPAP
ENDOTRACHEAL INTUBATION.
GUIDELINES FOR MECHANICAL
VENTILATION IN NMD
Full or partial support

Negative or positive pressure ventilation

Non-invasive or invasive ventilation

Assist/control mode(CMV)

Volume-control ventilation

Tidal volume-7 to 10 ml/kg while maintaining

Pplateau<30 cm H20.
F=8 to 16 breaths/min

Inspiratory flow rates≥60 lit/min to meet patient need

PEEP=5cmof H20 may be needed to relieve dyspnea.

Fio2=0.21
 NIV- BIPAP

 Noninvasive ventilation (NIV) may be used to prevent intubation or

reintubation of patients in myasthenic crisis.

 With bilevel positive airway pressure (BiPAP), positive pressure is

applied during both phases of respiration, enhancing airflow and

alleviating the work of breathing during inspiration and preventing

airway collapse and atelectasis during expiration.

 Cont…..
 In patients who are initially managed with NIV, endotracheal intubation and

mechanical ventilation should be initiated if the patient has continued or

worsening shortness of breath, increased work of breathing, tachypnea, or

hypercapnea.

 Independent predictors of NIV success are

A serum bicarbonate <30 mmol/L and

APACHE II score <6.22

 An independent predictor of NIV failure is hypercapnia (PCO2 >45mm Hg)

 Advantages of NIV
Initial use of NIV is associated with a shorter duration of
ventilatory support.
 Patients treated initially with NIV require ventilatory support for
a median of 4 days versus 9 days in those patients initially
intubated.
 In addition, these patients spend one-third less time in the ICU
and in the hospital.
 In 2 studies, NIV prevented reintubation in 70% of patients.
One retrospective cohort study found no difference in pulmonary
complications between those supported with NIV and those
supported with endotracheal intubation
 In patients successfully supported with NIV, there were
significantly fewer pulmonary complications
 ENDOTRACHEAL
INTUBATION
 Respiratory support is imperative in the management of

myasthenic crisis.

 Two-thirds to 90% of patients with myasthenic crisis require

intubation and mechanical ventilation.

 Over 20% of patients require intubation during evaluation in the

emergency department

 60% are intubated after admission to an intensive care unit.

 Cont…….
Elective intubation of a myasthenic patient with

impending respiratory failure is favored over emergent

intubation.
Once intubated, patients should be placed on an assisted

ventilator setting
Tidal volumes of 8-10 cc/kg ideal body weight

Pressure support of 8-15 cm H2O to prevent atelectasis

and to minimize the work of breathing.

 ENDOTRACHEAL
INTUBATION.
 3 independent risk factors for prolonged intubation i.e (>14 days)

in myasthenia crisis.

Age >50 years

Peak vital capacity <25 mL/kg on post-intubation days 1 to 6

A serum bicarbonate greater than or equal to 30 mmol/l

 88% of the patients with all 3 risk factors had prolonged

intubation
PREDICTORS OF EXTUBATION
FAILURE IN MYASTHENIA GRAVIS

Male sex

Previous crisis

Atelectasis

Intubation for more than 10 days were associated with

failure to extubate the patient

 PREDICTORS OF EXTUBATION
FAILURE IN MYASTHENIA GRAVIS
Atelectasis was the only variable associated with increased

likelihood of extubation failure and reintubation.

In fact, atelectasis was uniformly present in patients who

required reintubation.
This finding is concordant with a study that identified
atelectasis as the strongest predictor of reintubation among
26 episodes of MC
PATIENTS WHO REQUIRED
REINTUBATION
Lower pH

Lower FVC on extubation,

Atelectasis, and BiPAP use after extubation

Younger patients tended to have a greater risk of

requiring reintubation.
 Recent advances in MG

 Mycophenolate mofetil has the advantage of being relatively less toxic

compared to other immunosuppressant drugs and does improve treatment
resistant MG patients.
 Rituximab is a human/ mouse chimeric anti-CD20 monoclonal antibody
that has been used to treat B cell malignancies such as non-Hodgkin’s
lymphoma as well as autoimmune diseases such as systemic lupus
erythematosus.
 There are case reports of it being effective in treatment-resistant MG.

 Etanercept is a recombinant human tumour necrosis factor-alpha receptor

antagonist
 Recent advances in MG

 TNF has been implicated in the pathogenesis of MG.

 It may be effective in treatment resistant-MG associated with low

levels of interleukin-6 and interferon-gamma.

 CT-guided injection of ethanol in the thymus has been

demonstrated to be effective, minimally invasive, and safe in the

treatment of MG.
 SUMMAR
Y
 Myasthenic crisis is a common complication of MG.
 The advent of positive pressure ventilation in the 1960s has decreased
mortality and remains the cornerstone of management.
 The majority of patients with myasthenic crisis require endotracheal intubation
and mechanical ventilation.
 A select group of patients might benefit from NIV to avoid initial intubation or
reintubation.
 Factors precipitating myasthenic crisis should be quickly identified and
promptly mitigated; half of these patients have no identifiable precipitant.
 Typically, anticholinesterase inhibitors are discontinued to avoid excessive
secretions while the patient is experiencing respiratory failure.
 Both PE and IVIg, in conjunction with prednisone, may be used to treat
myasthenic crisis.
 Thymectomy remains part of treatment in patients with thymic tumors, but the
role of surgery in nonthymomatous MG needs further investigations
 Guideline references
1. Hess DR,Kacmarek RM:Essentials of mechanical
ventilation,2nded,Newyork,2002,McGrawHill.

2. Hess DR,MacIntyre,NR: Mechanical ventilation. Respiratory care principles and

practices,Sudbury,Mass.,2011,Jones and Bartlet Learning.

3. Shelledly DC:Initiating and adjusting ventilatory support. In Wilkins RL,Stoller

JK,Kacmarek RM,editors:Egan’s fundamentals of respiratory care,ed 9,St
Louis,2009,Mosby.

4. Slutsky AS:Ventilator-induced lung injury:from barotrauma to biotrauma.Respir Care 2005;

50:646-659.

5. Slutsky AS:Consensus conference on mechanical ventilation.Northbrook,Ill,jan 27-

30,1994,Intensive Care Med 20:64.

6. MacIntyre NR,Branson RD:Mechanical ventilation,ed 2,Philaldelphia,2008,W.B.Saunders

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M. Wijdicks, MD; Alejandro A. Rabinstein, MD
MYASTHENIA CRISIS DOI: 10.1177/1941875210382918
The Neurohospitalist 2011 1: 16 Linda C. Wendell and Joshua
M. Levine
 Myasthenic crisis A. CHAUDHURI and P.O. BEHAN From
the Essex Centre for Neurological Sciences and Division of
Clinical Neurosciences, University of Glasgow, Scotland, UK
 A review of myasthenia gravis: Pathogenesis, clinical
features and treatment Current Anaesthesia & Critical Care
(2007) 18, 15–23