eMedicine Specialties > Emergency Medicine > Neurology

Myasthenia Gravis: Treatment & Medication

Author: William D Goldenberg, MD, Clinical Assistant Instructor, Department of Emergency Medicine, Kings County Hospital Center and SUNY Downstate Medical Center
Coauthor(s): Richard H Sinert, DO, Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center
Contributor Information and Disclosures

Updated: Jan 30, 2009

Treatment

Prehospital Care

• Field personnel should recognize generalized muscle weakness of any etiology as a potential cause of respiratory failure.
• Patients with generalized weakness require transport to the hospital, and provisions for active airway intervention should be made en route.
• Patients in frank respiratory arrest should be intubated and ventilated prior to transport, if possible.
• Suctioning of pulmonary secretions may be required to adequately ventilate the patient.
• Supplemental oxygen is indicated in all cases, and intravenous access is desirable prior to initiating transport.

Emergency Department Care

Patients with myasthenia gravis (MG) who are in respiratory distress may be experiencing a myasthenic crisis or a cholinergic crisis. Before these possibilities can be differentiated, ensuring adequate ventilation and oxygenation is important. Patients with myasthenic crisis can develop apnea very suddenly, and they must be observed closely. Evidence of respiratory failure may be noted on ABG determination, pulmonary function tests, or pulse oximetry.

• Airway maneuvers
  • Open the airway by suctioning secretions after positioning the jaw and tongue.
  • Administer high-flow oxygen, and measure oxygen saturation by pulse oximetry.
  • If respirations remain inadequate, ventilate by bag-valve mask while preparing to intubate.
  • In the patient without an intact gag reflex, an oral airway may be placed.
  • Endotracheal intubation⁴
    • Rapid sequence intubation should be modified because depolarizing paralytic agents (eg, succinylcholine) have less predictable results in patients with myasthenia gravis. The relative lack of ACh receptors makes these patients relatively resistant to succinylcholine; therefore, higher doses must be used to induce paralysis. Once paralysis is achieved, it may be prolonged.
    • A rapid-onset nondepolarizing agent (ie, rocuronium, vecuronium) is the preferred paralytic agent for these patients. Although nondepolarizing agents delay the onset of paralysis, compared with succinylcholine, these medications do not result in unwanted prolonged paralysis.
    • Following paralysis, intubation is accomplished as usual. ABG sampling guides ventilator settings.
• Preliminary studies suggest that bilevel positive airway pressure (BiPAP) can prevent intubation in patients with myasthenic crisis without overt hypercapnia and should be considered in the patient who can be closely monitored.^4,9 Hypercapnia present at the time of BiPAP initiation predicted failure and the need to proceed to endotracheal intubation.¹⁰
• Once the airway is secured, investigation into the cause of the exacerbation of myasthenia gravis may proceed, with the most common reason for an exacerbation being inadequate treatment with cholinesterase inhibitors. Differentiation from cholinergic crisis can proceed as described above.
  • In less severely ill patients, oral pyridostigmine can be administered until clinical improvement is seen. The patient should be closely observed and monitored during this trial. Other reasons for the exacerbation can then be investigated. Infection: Although patients with myasthenia gravis can develop any common infection that can result in decompensation, the most likely source of infection is pulmonary. Cultures of blood, sputum, and urine may be indicated on an individual basis. Chest radiography is important in detecting pneumonia. Appropriate broad-spectrum antibiotics are indicated for sepsis and pneumonia. It is important to consider that fluoroquinolones and antibiotics may adversely affect cholinergic transmission in patients with myasthenia gravis, and these antibiotics should be avoided if possible.
  • Fever: Patients with myasthenia gravis are sensitive to high temperatures (core or ambient), and their muscle strength can improve when temperature is lowered with cooling measures or antipyretics.
• Reports indicate that thymectomy results in complete remission of the disease in up to 35% of patients.

Consultations

• Emergent consultation with a neurologist is indicated.
• Patients with severe exacerbations requiring intubation and mechanical ventilation are managed in an intensive care setting with appropriate consultation.

Medication

Myasthenia gravis (MG) is controllable with cholinesterase-inhibiting medications. Edrophonium primarily is used as a diagnostic tool because its half-life is so brief. Pyridostigmine is used for long-term maintenance. High doses of corticosteroids commonly are used to suppress autoimmunity. Patients with myasthenia gravis also may be taking other immunosuppressive drugs (eg, azathioprine, cyclosporine). Adverse effects of these medications must be considered in assessing the clinical picture. Bronchodilators may be useful in overcoming the bronchospasm associated with a cholinergic crisis.

Cholinesterase inhibitors

These agents increase the amount of available ACh at the myoneural junction by inhibiting the degradation of ACh. A wide variability exists in the effective dose, depending on the severity and current activity of the disease and the presence of other factors that influence cholinergic transmission (eg, certain antibiotics, antidysrhythmic medications, impaired renal function).^7,11

Most patients are able to titrate the dosage of their medication to control the symptoms of the disease, but severe exacerbations can occur in patients with previously well-controlled disease.¹¹

Edrophonium (Tensilon, Enlon, Reversol)

Primarily used as diagnostic tool to predict the response to longer-acting cholinesterase inhibitors. As with other cholinesterase inhibitors, it decreases metabolism of ACh, increasing the cholinergic effect at the myoneural junction (Pacuzzi, 2001).

Pyridostigmine (Mestinon, Regonol) (Keesey, 2004; Saperstein, 2004)

Acts in smooth muscle, CNS, and secretory glands where it blocks the action of ACh at parasympathetic sites. Longer-acting cholinesterase inhibitor used for maintenance therapy.

Neostigmine (Prostigmin)

Longer-acting cholinesterase inhibitor that can be used when edrophonium is effective. Inhibits destruction of ACh by acetylcholinesterase, which facilitates the transmission of impulses across the myoneural junction.

Corticosteroids

These agents are used to treat idiopathic and acquired autoimmune disorders. They have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

There is no significant evidence from RCTs to show the effectiveness of steroids whatever the severity of the disease, the dosage, or the route of administration in the use for MG.¹²  “However, numerous observational studies strongly support the efficacy of corticosteroid and therefore many experts conclude that corticosteroids are the mainstay of the treatment for MG.”¹²

Prednisone (Deltasone, Orasone, Sterapred)

Effective in decreasing the severity of exacerbations of MG by suppressing the formation of autoantibodies. However, clinical effects often are not seen for several weeks. Some experts believe that the long-term administration of prednisone is beneficial, but others use the drug only during acute exacerbations to limit the adverse effects of chronic steroid use. Lowest effective dose should be used on a long-term basis. Because of the delayed onset of effects, steroids are not recommended for routine use in the ED. Patients who are taking long-term moderate or high doses of steroids may have suppressed adrenal function and may require stress doses (hydrocortisone 100 mg IV in an adult) during acute exacerbations (Saperstein, 2004).

Methylprednisolone (Solu-Medrol)

May be used in place of prednisone in patients who are intubated and in those unable to tolerate oral intake. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Beta-agonist bronchodilators

These agents are used to alleviate the respiratory distress and bronchospasm resulting from cholinergic medications used to treat myasthenia gravis.

Albuterol, salbutamol (Proventil, Ventolin)

Standard unit doses of beta-agonist nebulizer treatment may improve respirations in a cholinergic crisis. Continuous beta-agonist nebulizer treatment may be indicated in severe cases. Otherwise, the standard dosing regimen of 2 puffs from a metered dose inhaler or 2.5-5 mg nebulized q4-6h often will suffice in achieving bronchodilation.

Anticholinergic bronchodilators

These agents cause the reversal of cholinergic medication effects that induce bronchospasm. These drugs can act synergistically or independently with beta-agonists to produce bronchodilation. They are quaternary amines, and they are poorly absorbed across the pulmonary epithelium. As a result, they have minimal systemic side effects.

Ipratropium (Atrovent)

Chemically related to atropine. Has antisecretory properties, and when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa.

Glycopyrrolate (Robinul)

Acts in smooth muscle, CNS, and secretory glands where it blocks the action of acetylcholine at parasympathetic sites.

Immunomodulators

Most of the studies reviewed had few participants and found it difficult to assess the efficacy of the addition of immunosuppressive therapy to the previous regimens of corticosteroids and cholinesterase inhibitors. As a result “good RCT data on the use of immunosuppressive agents as monotherapy or dual therapy with steroids are absent.”¹³ However, limited evidence indicates that ciclosporin and cyclophosphamide improve symptoms in MG and decrease the amount of corticosteroid usage. “The more common drugs used in MG- azathioprine, MMG, and tacrolimus, show no clear benefit in use.”¹³

Azathioprine (Imuran)

Imidazolyl derivative of 6-mercaptopurine. Many of the biological effects are similar to those of parent compound. Both compounds are eliminated rapidly from blood and are oxidized or methylated in erythrocytes and liver. No azathioprine or mercaptopurine is detectable in urine 8 h after taken.
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. Mechanism whereby azathioprine affects autoimmune diseases unknown. Works primarily on T cells. Suppresses hypersensitivities of cell-mediated type and causes variable alterations in antibody production. Immunosuppressive, delayed hypersensitivity, and cellular cytotoxicity tests are suppressed to a greater degree than antibody responses. Works very slowly; may require 6-12 mo of trial prior to effect. Up to 10% of patients may have idiosyncratic reaction disallowing use. Do not allow WBC count to drop below 3000/mL or lymphocyte count to drop below 1000/mL.
Available in tablet form for oral administration or in 100-mg vials for IV injection.

Cyclosporine (Neoral, Sandimmune)

An 11-amino acid cyclic peptide and natural product of fungi. Acts on T-cell replication and activity.
Specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting helper T-cell function. Preferential and reversible inhibition of T lymphocytes in G0 or G1 phase of cell cycle suggested.
Binds to cyclophilin, an intracellular protein, which, in turn, prevents formation of interleukin 2 and the subsequent recruitment of activated T cells.
Has about 30% bioavailability, but there is marked interindividual variability. Specifically inhibits T-lymphocyte function with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that drug be present during first 24 h of antigenic exposure.
Suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-vs-host disease) for a variety of organs.

Immune Globulins

Usually used on admitted patients and rarely started in the ED. IVIG is recommended for MG crisis, in patients with severe weakness poorly controlled with other agents, or in lieu of plasma exchange at a dose of 1 g/kg.^14,3 RCT demonstrated the efficacy of IVIG versus placebo in moderate or severe MG worsening into crisis, but does not exhibit value in mild disease.¹⁵  Data do not support or refute a role for IVIG in chronic MG.³ To be included in the studies with IVIG, patients were required to be auto-antibody positive. Therefore, the use of IVIG in a seronegative patient is not supported by the literature.³

Immune globulin intravenous (Carimune, Gammagard S/D, Gammar-P, Gamunex, Polygam S/D)

High-dose IVIg successfully treats MG. Like plasma exchange, has rapid onset of action, but effects last only short time. Best used in crisis management (eg, myasthenic crisis and perioperative period).

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