Neuromuscular Emergencies

Hanni Bouma

Objectives

Discuss the approach to neuromuscular respiratory failure– Signs & Symptoms– Differential diagnosis– When to intubate

Brief overview of GBS & MG

Case 1

26 yo previously healthy F p/w tingling in feet since 1 week ago. Two days later noticed difficulty climbing stairs, followed by weakness of her arms. She is areflexic.

What percentage of patients with her disease develop resp failure?

Case 1

A) 5% B) 10 to 20% C) 25 to 50% D) 70 to 85%

Case 2

73 yo M adm w/ 3-month history of progressive proximal weakness

1 day after muscle biopsy, noticed on rounds to be breathless

What are we likely to see if this patient is in resp failure?

Case 2

A) Significant accessory muscle use B) Pt complaining that “I can’t breathe!” C) Shallow breaths; weak cough; neck flexor

weakness D) Able to count to 40 in a single breath

Case 3

63 yo M with limb-onset ALS since 2007 p/w choking sensation, difficulty “getting air in”

Not on home BiPAP No prior aspiration pneumonias; no fever, no

leukocytosis

Case 3

Case 3

Case 3

Which of the following are you LEAST likely to find in this patient?

A) FVC 1.1 L, MIP -20, MEP 30 B) MEP 40, MIP unable to complete C) pH 7.35, pCO2 60, bicarb 36 D) FVC 4 L, MIP -90, MEP 100

What can cause generalized weakness leading to resp failure?

Spinal cord lesion– Cervical cord compression, transverse myelitis

Motor neuron lesion– ALS

Peripheral nerve lesion– GBS, CIDP, critical illness polyneuropathy, Lyme disease, tick

paralysis, toxic NMJ disorder

– MG, LEMS, botulism, organophosphate poisoning Muscle lesion

– Polymyositis, dermatomyositis, critical illness myopathy, hyperthyroidism, congenital myopathy (muscular dystrophy), mitochrondrial myopathy

Mechanisms of NM resp failure

1) Upper airway obstruction:– Facial, oropharyngeal, laryngeal weakness mechanical

obstruction in supine position– impaired swallowing/secretion clearance aspiration

2) Inspiratory muscle weakness atelectasis V/Q mismatch hypoxia

3) Expiratory muscle weakness weak cough/poor secretion clearance aspiration & pneumonia

4) Acute complications PE, pneumonia, etc.

History

Time course?– progressive weakness over hours to days GBS– fluctuating weakness (on an hourly basis) present for

weeks/months MG Distribution of weakness?

– Proximal > distal (MG & GBS)– Ascending in GBS– Initally EOM/oropharyngeal muscle weakness, then

generalizes in botulism Sensory Sx.?

– Distal paresthesias common in GBS– No sensory inv’t in MG

History

Pain?– Low backache frequently in GBS; neck pain: C-spine

lesion? Antecedent illness?

– 60% of GBS triggered by viral URT illness or C.jejuni gastro– 40% of myasthenic crises triggered by infection

Medications Exposure to fertilizers & pesticides?

– Organophosphate poisoning Recent diet

– Botulism from home-canned goods

Exam: Signs of resp failure

Tachycardia Rapid, shallow breathing Stridor Weak cough, nasal voice, pooling of saliva (signs of bulbar

dysfunction) Orthopnea (abnormal if VC drops >10% supine) Staccato speech = the need to pause between words Abdominal paradox = diaphragm weakness weakness of neck & trapezius muscles (parallels diaphragm

weakness) Single-breath count: ask them to inhale fully & count from 1 to

50. If <25, sign of severe impairment of VC

Mehta, S. “Neuromuscular disease causing acute respiratory failure.” Respiratory Care, 2006. 51 (9): 1016-1023.

Focused exam

HEENT: – look for pooled secretions– Swallow test – Dysphonia (nasal voice from palatal paralysis)– Dysarthria

Lungs Diaphragm: observe/palpate for normal, outward

abdominal movement with inspiration Cough strength Count test (1 to 50)

Neuro exam

CNs– Pupils:

Reactivity may be lost in botulism or Miller-Fisher variant of GBS– EOM:

weakness + ptosis characteristic of MG, but also seen in MF, botulism, etc.– Face, palate, tongue, & neck strength

Motor exam: – Fasciculations? (ALS, organophosphate poisoning); tone; power (distribution of

weakness? Fatigable weakness?) Sensory:

– Distal sensory loss in GBS– Sensory level at C-spine level w/ quadriparesis = C-spine lesion

Coordination:– Ataxia in MF variant of GBS

Reflexes:– Areflexia in GBS; usually preserved reflexes in MG

Investigations

Bedside PFTs: “20/30/40 rule”– Vital capacity (max exhaled volume after full inspiration).

Normal = 60 ml/kg (4 L in 70 kg person). VC < 20 ml/kg (or 1 L) means intubation

– Max inspiratory pressure. Index of ability to avoid atelectasis. Normal = <-50 cm H2O. MIP >-30 means intubation

– Max expiratory pressure. Index of ability to cough/clear secretions. Normal >60 cm H2O. MEP <40 means intubation

– PFTs may be low if inadequate mouth closure from facial palsy, and may fluctuate in MG

Investigations

ABG: – Hypercarbia (PCO2 > 45 mmHg) =

hypoventilation

* PCO2 often normal or low until late in NM resp failure

– Hypoxia (PO2 < 75 mmHg) = V/Q mismatch usually atelectasis or pneumonia in this setting

Investigations

Basic labs (CBC, SMA-10, LFTs, CK) CXR EKG (electrolyte D/O; GBS ass’d w/

dysautonomia arrhythmias)

General care

Electrolytes: low potassium, high magnesium & low phosphate exacerbate muscle weakness

Serial PFTs (MIP/MEP/FVC) bid to qid Chest physio, suctioning & incentive spirometry DVT prophylaxis HOB elevation NPO if bulbar weakness; NG or Dobhoff feeding Bowel/bladder: paralysis predisposes to

constipation; GBS pts may have urinary retention

Determine:

– If resp failure is imminent– If ICU should be involved– What is the localization?

Predictors of need for MV

20/30/40 rule or a reduction in VC, MIP, MEP by >30% PO2 <70 mmHg on RA or PCO2 >50 mmHg w/ acidosis Dysarthria, dysphagia, impaired gag reflex In GBS:

– Time from onset to admission < 7 days– Inability to cough– Inability to stand– Inability to lift elbows or head– LFT increases– Presence of autonomic dysfxn

Sharshar T, Chevret S, Bourdain F, Raphael JC. Early predictors of mechanical ventilation in Guillain-Barre´ syndrome. Crit Care Med 2003;31(1):278–283.

Intubation: things to think about

Code status? Identify imminent resp failure early to avoid

emergency intubation– Minimizes atelectasis/pneumonia– Minimizes complications of intubation specific to GBS &

MG: Dysautonomia: can cause severe bradycardia, BP shifts,

profound hypotension w/ sedatives Denervated muscle: can cause fatal hyperkalemia with use of

succinylcholine Avoid depolarizing NM blockers Small doses of benzos

NPPV?

Few studies on its use in GBS & MG Inappropriate if upper airway function

severely impaired or hypercapnic resp failure

GBS

Most common cause of acute or subacute gen’d paralysis

Monophasic AIDP: autoimmune attack against surface antigens on peripheral nerves

Develops 5 days to 3 weeks after resp/GI infection in 60%

– Campylobacter jejuni (26%)– Viral URTI, influenza– EBV, CMV, VZV, HIV, hep A & B, coxsackie

Other precipitants: immunization, pregnancy, surgery, Hodgkin’s disease

Presentation

Sensory: – distal paresthesias/numbness (earliest Sx.)– Reduced vibration/proprioception

Motor:– Symmetric; evolves over days to 1-2 wks– Ascending: LE before UE; proximal> distal– May progress to involve trunk, intercostals, neck, bulbar, B/L FNs– Median duration from onset to max weakness 12 days

Reflexes: reduced, then absent Autonomic instability:

– Sinus tachy/brady, arrhythmias, labile BP (esp hypertension), urinary retention, anhydrosis

Other: low backache very common, myalgias

Investigations

EMG:– Reduced conduction velocities– Loss of F waves– Conduction block in motor nerves– Reduced motor amplitudes: 2° axonal damage worse Px.

CSF: – High protein (may be normal in first 2 days)– No cells or few lymphs

10% have 10-50 lymphs

Management

Admit for observation (potential for deterioration) Determine if resp failure imminent Dysautonomia: most frequently sustained HTN &

tachycardia– Esp in older pts w/ CAD, consider Labetolol– Hypotension in 10% fluids, pressors

PLEX (4-6 Rx. q1-2d) & IVIG (0.4g/kg/d x 5 d):– Equally effective– PLEX useful in first 2 weeks; benefit less clear after that– Steroids no proven benefit

Course

Progression over 1-4 weeks Plateau: 2-4 months Recovery: few wks to months Mortality 3-5% Poor prognosis:

– Resp failure requiring intubation – Advanced age– Very low distal motor amplitudes (axonal damage)– Rapidly progressive weakness over 1 week

MG

Ab-mediated attack on nicotinic Ach rec defective transmission across NMJ

Bimodal: F 20-30 yo; M 50-60 yo 2 autoimmune forms

– Ach receptor Ab+: 80% with generalized MG & 50% with ocular MG

– Anti-MuSK Ab+: 50% of patients who are Ach rec Ab negative; typically female with prominent bulbar weakness

Presentation

Motor:– Fluctuating, fatigable weakness involving eyes (90%),

face/neck/oropharynx (80%), limbs (60%)– Limbs rarely affected in isolation– Rest restores strength (at least partially)– Usually insidious onset

Sensory: normal Reflexes: preserved Thymic abnormalities:

– Malignant thymoma in 10-15% (more severe disease)– Thymic hyperplasia in 50-70%

Myasthenic Crisis

Defined by resp failure requiring ventilatory assistance

Occurs in 20-30%; mortality 5% Common precipitants:

– Infection in 40% (esp respiratory)– Pregnancy– Medications– Aspiration– Surgery– Emotional upset, hot environment

Drugs that exacerbate MG

Antibiotics:– Aminoglycosides (genta, tobra)– Fluroquinolones (cipro)– Macrolides (erythromycin, azithro, tetracycline, doxycycline)

Cardiac:– All beta-blockers– Calcium channel blockers– Class I anti-arrhythmics (quinidine, procainamide)

Anticonvulsants:– Phenytoin, CBZ

Antipsychotics, lithium Thyroid hormones Magnesium toxicity Iodinated contrast agents Muscle relaxants

– Baclofen– Long-acting benzos

**Too much anticholinesterase

Investigations

Ach receptor Abs Anti-MuSK Abs EMG:

– Repetitive nerve stimulation: >10% decrement in amplitude betw 1st & 5th CMAP

Sens/spec 90% when weak, proximal muscles stimulated; <50% sens in pts w/o limb weakness

– Single-fiber: “jitter” (variation in time interval betw firing of muscle fibers in same motor unit)

Sens >95% for MG but not specific Edrophonium (Tensilon) test:

– Not recommended in suspected crisis

Management

Determine if resp failure imminent Stop exacerbating meds Treat infection Symptomatic therapy (mild-moderate weakness):

– Cholinesterase inhibitors (Mestinon) Short-term disease suppression:

– To hasten clinical improvement in hospitalized pts w/ crisis or impending crisis; pre-operatively; chronic refractory disease

– PLEX: improvement w/i days, but lasts only 2-4 wks– IVIG: benefit may last up to 30 days– Comparable benefits

Long-term immunosuppression:– When weakness is inadequately controlled by Mestinon– Prednisone – Azathioprine (if steroid failure or excessive SE)

Key points

20/30/40 rule Identify pts at risk for resp failure EARLY to

avoid emergency intubation Don’t wait for pts to complain of SOB before

doing bedside PFTs