Matthew, a 6-year-old male, has been feeling increasingly short of breath throughout the course of the morning. His father also notices that over the last several days he’s been appearing increasingly tired with a cough. Matthew is watching TV on the floor in the living room when his father enters the room and finds him unresponsive and apneic. He calls 9-1-1.
Paramedics respond immediately, but the response is uneventful. They arrive on scene and are met outside by the patient’s father, who takes them into the house and tells them his son has been feeling ill over the past several days but wasn’t given any medications. He also tells the crew his son has a history of myasthenia gravis.
The crew proceeds into the living room, where they encounter the patient lying on the floor in the left lateral position. His eyes are open but he’s unable to speak or provide any additional information; he appears unable to take a deep breath. On initial assessment, the patient has no evidence of stridor or drooling. He has a dusky appearance to his skin and, when he does take a breath, has clear and equal breath sounds bilaterally with no evidence of intercostal muscle usage. He’s noted to have some drooping of his eyelids and is unable to hold himself in the sitting position.
The patient is placed on a monitor and initial vitals are taken. The patient has a heart rate of 96, a respiratory rate of 9, a blood pressure of 88/52 and an oxygenation saturation of 63% on room air. While vitals are being taken, the child is placed on a pediatric non-rebreather mask at 15 Lpm, which initially improves his oxygen saturation to 96%.
In the ambulance the child quickly becomes unresponsive. He has no spontaneous respirations and his oxygen saturation decreases. The change is recognized quickly by the paramedics and bag-valve mask (BVM) ventilations are started. He also has an oral airway placed to help with delivering effective ventilations. The patient has an IV established for access and his glucose is 100. The crew decides to transport the patient to the closest hospital for further assessment and stabilization.
While en route, the patient continues to have no spontaneous respirations but has improvement in his oxygen saturation with BVM ventilation and supplemental oxygen to 95%. His heart rate remains stable. Medic 51 arrives at the receiving ED and bagging is continued into the facility. A bedside update is given and care is transitioned to ED staff.
The patient is immediately evaluated by the ED physician and nursing staff. He’s still unresponsive with no spontaneous respirations, so rapid sequence intubation (RSI) is performed. A chest X-ray is performed, which shows evidence of pneumonia with an endotracheal tube in adequate position. Post intubation, sedation and antibiotics are administered. The receiving hospital doesn’t have inpatient pediatric services, so Matthew is transferred via helicopter to the children’s hospital, where he’s admitted to the pediatric intensive care unit.
Once there, the patient receives antibiotics for the pneumonia and plasmapheresis for treatment of the myasthenia gravis and crisis. After three days, the patient begins to breathe spontaneously and no longer requires the ventilator. He’s extubated and has a full recovery. On day 8, the patient is discharged home in stable condition with no further complications.
Myasthenia gravis is a neuromuscular disorder. It can affect both the pediatric and adult patient populations, so a high level of suspicion and recognition of the disorder will lead to prompt intervention, which can be lifesaving.
Myasthenia gravis involves the development of antibodies to the acetylcholine receptor. Acetylcholine is released from the neuron at the neuromuscular junction and binds to the acetylcholine receptor on the muscle to trigger a cellular cascade leading to contraction. Antibodies destroy the receptor so that muscle contraction can’t occur as efficiently. (See Figure 1 and Figure 2 below.)
Figure 1: Normal neuromuscular junction
Figure 2: Neuromuscular junction in myasthenia gravis (note: reduced number of acetylcholine receptors)
Reproduced from Thanvi BR, Lo TC. Update on myasthenia gravis. Postgrad Med J. 2004;80(950):690—700 with permission from BMJ Publishing Group LTD.
Myasthenia gravis is a relatively uncommon disorder effecting 150—200 per 1 million individuals.1,2 However, the prevalence of the disease has been increasing over the last five decades.3,4 Myasthenia gravis occurs in a bimodal age distribution with an early peak in the second and third decades of life with a female predominance and a later peak in the sixth to eighth decade with a male predominance. The majority of patients with autoantibodies to the acetylcholine receptor have thymic abnormalities.5 Autoimmune juvenile myasthenia gravis accounts for approximately 10—15% of cases in North America.6,7
There are two primary manifestations of myasthenia gravis: ocular and generalized. In ocular myasthenia, weakness is limited to the eyelids and extraocular muscles and presents as worsening weakness and drooping throughout the course of the day. In generalized myasthenia, weakness can involve the eyelids but also involves the respiratory, limb and bulbar (mouth and throat) muscles. The hallmark of generalized myasthenia gravis is fluctuating skeletal muscle weakness often with true muscle fatigue on physical examination. Weakness is usually more pronounced in the evening hours or after exercise. For prehospital purposes, the generalized form of myasthenia gravis will be the primary focus.
Respiratory muscle weakness produces the most serious symptoms of myasthenia gravis. Weakness that leads to respiratory insufficiency is a life-threatening condition known as “myasthenic crisis.” It can occur spontaneously during the course of the disease or may be precipitated by a variety of factors including surgery, infections, certain medications, pregnancy or tapering of immunosuppression. The proportion of patients with myasthenia gravis who have at least one episode of myasthenic crisis is thought to be around 10—20%.8 Patients who develop crisis typically have increasing generalized, bulbar or respiratory weakness.9 The generalized weakness these patients develop can also limit the use of accessory muscles, making detection of respiratory distress and impending failure more difficult. Patients require intensive monitoring and often mechanical ventilation for respiratory failure. If intubation isn’t required, monitoring of respiratory muscle strength is performed frequently.
Prehospital assessment and management of the patient with myasthenia gravis and potentially crisis requires rapid assessment and supportive management. Respiratory failure is the most concerning acute presentation and these patients should be adequately oxygenated and ventilated. Patients with any bulbar muscle weakness manifesting as difficulty speaking, chewing and swallowing should raise suspicion for the development of myasthenic crisis. These patients require close and continuous monitoring including noninvasive end-tidal carbon dioxide (EtCO2) if available for hypoventilation. If the patient does become unresponsive and apneic or has an elevated EtCO2 indicating hypoventilation, BVM ventilation should be used to improve oxygenation and ventilation. If tolerated by the patient, an extraglottic airway can also be utilized.
If RSI is required in patients with respiratory failure, succinylcholine can be used as a paralytic. Unlike other neuromuscular diseases, there’s no concern for a hyperkalemic response after the administration of succinylcholine, as autoantibodies affect the acetylcholine receptors themselves and not upregulation of the receptors. However, a higher dose of the depolarizing paralytic may be necessary (1.5—2.0 mg/kg) as the destruction of acetylcholine receptors leads to succinylcholine resistance.10 Nondepolarizing agents such as vecuronium have increased sensitivity with the destruction of acetylcholine receptors, so a lower dose is required for effectiveness (0.05 mg/kg).10 Use of nondepolarizing agents may lead to prolonged paralysis so should be used with care.
Narcotic medications should also be administered cautiously. These medications don’t directly affect the disease process but have been linked with sudden death after administration.11 Due to the tendency of narcotic analgesics to produce respiratory depression, they should be used with caution in patients who have respiratory insufficiency from myasthenia gravis or other neuromuscular diseases.
With advances in therapy and intensive care management, the prognosis in myasthenic crisis has dramatically improved from a mortality rate of approximately 75% in the 1950s and 1960s to a rate of approximately 5% by the 1990s.12—14 Early recognition and supportive treatment can improve patient outcomes.
Early recognition of the complications of myasthenia gravis and myasthenic crisis can be lifesaving for patients. Close attention to impending respiratory distress and failure allows for earlier treatment. For prehospital providers, understanding how to recognize myasthenic crisis and the appropriate treatment of these patients with respiratory failure will improve patient outcomes.
1. Phillips LH 2nd. The epidemiology of myasthenia gravis. Ann N Y Acad Sci. 2003;998:407—412.
2. Heldal AT, Owe JF, Gilhus NE, et al. Seropositive myasthenia gravis: A nationwide epidemiologic study. Neurology. 2009;73(2):150—151.
3. Phillips LH. The epidemiology of myasthenia gravis. Semin Neurol. 2004;24(1):17—20.
4. Grob D, Brunner N, Namba T, et al. Lifetime course of myasthenia gravis. Muscle Nerve. 2008;37(2):141—149.
5. Drachman DB. Myasthenia gravis. N Engl J Med. 1994;330(25):1797—1810.
6. Phillips LH 2nd, Torner JC, Anderson MS, et al. The epidemiology of myasthenia gravis in central and western Virginia. Neurology. 1992;42(10):1888—1893.
7. Andrews PI. Autoimmune myasthenia gravis in childhood. Semin Neurol. 2004;24(1):101—110.
8. Wendell LC, Levine JM. Myasthenic crisis. Neurohospitalist. 2011;1(1):16—22.
9. Berrouschot J, Baumann I, Kalischewski P, et al. Therapy of myasthenic crisis. Crit Care Med. 1997;25(7):1228—1235.
10. Abel M, Eisenkraft JB. Anesthetic implications of myasthenia gravis. Mt Sinai J Med. 2002;69(1—2):31—37.
11. Grob D. Myasthenia gravis: Current status of pathogenesis, clinical manifestations and management. J Chron Dis. 1958;8(4):536—566.
12. Juel VC. Myasthenia gravis: Management of myasthenic crisis and perioperative care. Semin Neurol. 2004;24(1):75—81.
13. Mandawat A, Kaminski HJ, Cutter G, et al. Comparative analysis of therapeutic options used for myasthenia gravis. Ann Neurol. 2010;68(6):797—805.
14. Alshekhlee A, Miles JD, Katirji B, et al. Incidence and mortality rates of myasthenia gravis and myasthenic crisis in US hospitals. Neurology. 2009;72(18):1548—1554.