Consultant Teachings No. 1: Acute Neuromuscular Respiratory Failure

Clinical Scenario: You are working in EM 2. It’s 3 AM and a 32 year old woman is roomed with the chief complaint of shortness of breath. She has been getting progressively more short of breath for the past 2 days. She’s also noticed that she just can’t keep her eyes open, though her right eyelid droops more than her left. You notice her head is falling forward. When you question her about that, she says she has had trouble holding it up for 4 days. Your general exam is normal, with no wheezing and normal heart sounds. Her neuro exam shows weakness on eye closure, neck flexion, and neck extension. She has no weakness anywhere else.

Clinical Question: How should acute neuromuscular respiratory failure be evaluated and managed?

Literature Review:
Neuromuscular respiratory failure is relatively rare but constitutes a medical emergency with significant morbidity and mortality, particularly with delays in recognition. The most common causes are acute inflammatory demyelinating polyneuropathy (e.g. Guillain-Barre syndrome, GBS) myasthenia gravis (MG), motor neuron disease (e.g. amyotrophic lateral sclerosis, ALS) and some forms of myopathy. A study in Northern Ireland found the causes of acute respiratory failure due to neuromuscular conditions were GBS (62%), MG (18%), ALS (9%), then a variety of other conditions (2, 3). Early recognition of these conditions by history and physical exam, combined with specific bedside testing, can help appropriately triage and manage these patients. GBS has an incidence of 1-4 per 100,000 and represents the most common cause of acute paralysis. It is also often missed early in the disease, with patient’s requiring an average of 2 ED visits before diagnosis [1]. GBS can progress from symptom onset to respiratory failure in 48 hours, so early identification is important. The mechanism of respiratory failure is loss of activity of the diaphragm and accessory muscles of respiration, and can often be complicated by aspiration due to craniobulbar weakness. The diaphragm is innervated by the phrenic nerve, derived from the C3-5 nerve roots (remember: “C3, 4, and 5 keep you alive”).

The initial evaluation should begin with a careful history, including the time from symptom onset to ED presentation. When taking the history, it is important to ask specifically about:

1) Drooping eyes (ptosis)

2) Double vision (diplopia)

3) Change in speech (breathy or nasal)

4) Difficulty swallowing including nasal regurgitation (food/liquid coming out the nose)

5) Fatigue with chewing

6) Head drop (inability to support their head)

All of these can be findings of bulbar and high cervical spine pathology, and can be warning signs for impending respiratory failure. The history should also include characterization of weakness in other places (i.e. leg or arm weakness), sensory symptoms (ascending numbness or paresthesias) and autonomic symptoms (new-onset orthostatic symptoms, bowel or bladder retention/incontinence, changes in sexual functioning).

On physical exam, after doing a routine medical exam, specifically test:

1) Eye movements (looking for impairment of extraocular musculature)

2) Eye closure strength

3) Mouth closure strength

4) Tongue strength and palate elevation

5) Assess for a weak cough

6) Neck flexion and extension strength

7) Breath count (ask the patient to count up at a rate of one number per second after taking a full breath. This is a crude estimate of vital capacity, with each number being ~100 ml.)

Numbers 1-5 detect craniobulbar weakness. Neck flexion and extension are well correlated with diaphragmatic strength. Neck flexion weakness correlates with impaired respiratory function, while neck extension weakness should be considered a warning sign of impending respiratory failure.

Laboratory testing: History and exam should guide testing, but a full set of screening labs is generally appropriate (CBC, BMP, HFP). Other bloodwork that can be obtained include CK, TSH, and ESR [4].

Respiratory therapy should measure forced vital capacity (FVC) and negative inspiratory force (NIF). FVC < 20 ml/kg (~ 1- 1.5L) or NIF < -30 cm H20 are warning signs for impending respiratory failure [5].  It is important to discuss the effort provided and the quality of the lip seal with the respiratory therapist that performs the testing.

If there is evidence of severe diaphragmatic weakness (very weak neck extension or low NIF/FVC), it is reasonable to check an ABG or VBG for hypercapnea and a respiratory acidosis, consistent with inadequate ventilation.


If there are signs of impending respiratory failure, it is important to determine if non-invasive ventilation (e.g. BiPAP) or intubation and mechanical ventilation is most appropriate. This is a decision that should be made with the consulting neurologist and with the admitting ICU. However, if the objective findings (NIF/FVC and ABG) or trajectory (rapid deterioration) are poor, it is reasonable to electively intubate in the ED instead of an emergent intubation in the ICU.  Concurrent craniobulbar weakness and/or a weak cough are relative contraindications for use of non-invasive ventilation given the increased risk of aspiration.


Intubation in patients with neuromuscular weakness carries special risks.   In myasthenia gravis, due to a complex interaction between the number of ACh receptors at the neuromuscular junction, antibodies inhibiting those receptors, and the effects of treatment such as plasmapheresis and enzyme inhibitors, neuromuscular blockade can have unpredictable effects.

Image source: http://jama.jamanetwork.com/article.aspx?articleid=200737

Myasthenia patients have net loss of AChR at the neuromuscular junction (see Figure), making these patients relatively resistant to succinylcholine.  However, in cases where myasthenic crisis is treated with plasmapharesis, which also incidentally rcmoves the enzymes required for breakdown of paralytic agents, patients can have very  prolonged neuromuscular blockade.  While the effect of succinylcholine can go either way, patients with myasthenia gravis can be extremely sensitive to nondepolarizing blockade (one study found that the effective dose of vecuronium in MG was 1/5 that in controls) [6,7].

 In addition to the unpredictable effects of neuromuscular agents, patients with neuromuscular weakness is general are at higher risk of developing critical illness myopathy following exposure to paralytics. Avoidance of any paralytic is the goal when intubating a patient with MG, so consider using topical lidocaine with a sedative such as propofol [8]. Patients with GBS often develop significant autonomic dysfunction, with concomitant extreme swings in blood pressure and heart rate [9]. Autonomic dysfunction can be exacerbated during intubation. It is important to avoid treating these swings in blood pressure and/or heart rate unless there is evidence of end organ damage. Treating these rapid swings places the patient at a high risk of iatrogenic injury when their blood pressure or heart rate spontaneously rebounds and this rebound is exaggerated by the medications provided.

Clinical Take home:1) Have a high index of suspicion for neurologic causes of respiratory failure.
2) Check craniobulbar and neck flexion/extension strength in patients in whom you suspect neuromuscular pathology.
3) Check NIF/FVC and an ABG on any patient with a suspected neuromuscular condition and dyspnea.
4) Intubate with a reduced dose of non-depolarizing agent or preferably no paralytics at all
5) Expect heart rate and blood pressure swings, especially during intubation. Don’t treat them unless there is end-organ damage, as they are likely to spontaneously resolve.

Submitted by Alex Dietz, Neurology PGY-3
Additional Review by Jennifer Griffith
Faculty Reviewed by Robert C. Bucelli (Neurology)

Everyday EBM Editor: Maia Dorsett

References:
[1]Noto A, Marcolini E. Select topics in neurocritical care. Emerg Med Clin North Am 2014;32:927-938.
[2]Carr AS, Hoeritzauer AI, Kee R, et al. Acute neuromuscular respiratory failure: a population-based study of aetiology and outcome in Northern Ireland. Postgrad Med J 2014;90:201-204.
[3]Pfeffer G, Povitz M, Gibson GJ, Chinnery PF. Diagnosis of muscle diseases presenting with early respiratory failure. J Neurol 2014.
[4]Flower O, Bowles C, Wijdicks E, Weingart SD, Smith WS. Emergency neurological life support: acute non-traumatic weakness. Neurocrit Care 2012;17 Suppl 1:S79-95.
[5]Lawn ND, Fletcher DD, Henderson RD, Wolter TD, Wijdicks EF. Anticipating mechanical ventilation in Guillain-Barré syndrome. Arch Neurol 2001;58:893-898.
[6] Roppolo, L. P., & Walters, K. (2004). Airway management in neurological emergencies. Neurocritical care, 1(4), 405-414.
[7]Martyn JA, White DA, Gronert GA, Jaffe RS, Ward JM. Up-and-down regulation of skeletal muscle acetylcholine receptors. Effects on neuromuscular blockers. Anesthesiology 1992;76:822-843.
[8]Della Rocca G, Coccia C, Diana L, et al. Propofol or sevoflurane anesthesia without muscle relaxants allow the early extubation of myasthenic patients. Can J Anaesth 2003;50:547-552.
[9]Rabinstein AA, Wijdicks EF. Warning signs of imminent respiratory failure in neurological patients. Semin Neurol 2003;23:97-104.