Chapter 122. Edrophonium (Tensilon) Testing

Myasthenia gravis is an autoimmune disorder that occurs when polyclonal antibodies bind to a significant number of postsynaptic acetylcholine receptors at the neuromuscular junction leading to inadequate neuromuscular transmission.1–3 It most commonly affects 10- to 30-year-old females and 70- to 90-year-old males. Multiple tests are available to diagnose myasthenia gravis.3–7 These include the use of muscle biopsies, curare, edrophonium chloride (Tensilon), electromyography, ice packs, neostigmine, nerve stimulation, and serologic testing. The edrophonium test is the most commonly used diagnostic test for myasthenia gravis.8–10 Many of these techniques are seldom used and not feasible to perform in the Emergency Department. For these reasons, only the edrophonium test and the ice pack test will be described in this chapter.

Acetylcholine is a neurotransmitter of the neuromuscular junction that is released by the presynaptic nerve terminals when stimulated.4,11 An electrical potential is produced at the myoneural end plate when sufficient numbers of the postsynaptic receptors at the neuromuscular junction are bound by the released acetylcholine. This electric potential then propagates and ultimately leads to muscle contraction. Simultaneously, acetylcholinesterase rapidly terminates the neurotransmission by metabolizing the acetylcholine in the synaptic cleft of the neuromuscular junction.

Myasthenia gravis is an autoimmune disorder that occurs when polyclonal antibodies bind to postsynaptic acetylcholine receptors at the neuromuscular junction.2–4,11 This leads to inactivation of the receptors and inadequate neuromuscular transmission. Myasthenia gravis is characterized clinically by muscle weakness that develops after repetitive muscle contraction.

Patients are divided into two clinical groups. The first includes patients who present with ocular complaints. Patients most commonly present with some degree of ocular muscle involvement. Diplopia is the most common patient complaint. Ptosis is the most visible sign noted on the physical examination. Diplopia with disconjugate gaze can be elicited by having the patient maintain a vertical gaze for approximately 3 minutes. Ptosis can also be made to worsen by having the patient maintain an upward gaze for the same duration of time. These patients may or may not have associated weakness of the pharyngeal and facial muscles that present with the complaints of dysarthria and dysphagia. These symptoms can often be elicited by having the patient count backward from 100.

The second group includes patients with proximal muscle weakness. Weakness of the limbs usually involves the proximal muscles and may be asymmetric. Weakness of the muscles can be elicited by having the patient perform repetitive exercises involving the muscle groups in question. Involvement of respiratory and pharyngeal muscles should be taken very seriously as it may lead to respiratory failure or aspiration.2,3,12–15

Edrophonium chloride is a short-acting acetylcholinesterase inhibitor (anticholinesterase) used in the diagnosis of myasthenia gravis.3,11 Its onset of action is rapid (within 1 to 2 minutes) and the duration of action is brief (2 to 5 minutes). These characteristics make it ideal to use in the Emergency Department. Edrophonium given intravenously to patients with myasthenia gravis briefly inhibits the actions of the acetylcholinesterase, thus prolonging the interaction between the acetylcholine and the postsynaptic receptors. This results in a temporary but noticeable improvement in muscle contraction.1,14 Edrophonium can rapidly, and temporarily, reverse the signs and symptoms of myasthenia gravis.

Testing is indicated when the patient's condition is suggestive of myasthenia gravis.4,5 Edrophonium chloride can be used for patients presenting with diplopia, facial muscle weakness, appendicular muscle weakness, or ptosis suggestive of myasthenia gravis. The ice pack test is reserved to evaluate patients presenting with ptosis.16–18

There is the possibility of worsening the patient's symptoms, causing respiratory distress or arrest, and cardiac dysrhythmias. Do not administer edrophonium if resuscitative equipment, Advanced Cardiac Life Support medications, and additional support personnel are not immediately available. Edrophonium should not be administered if the Physician is not properly trained in airway management and rescue techniques. Use caution when administering edrophonium if the patient's medications can cause atrioventricular node blocking or slowing of transmission (e.g., beta-blockers, calcium channel blockers, and digoxin). These can make the edrophonium associated dysrhythmias more pronounced.

Edrophonium testing is relatively contraindicated in patients with known myasthenia gravis that are taking oral pyridostigmine (Mestinon) and present with increasing weakness. The weakness may be due to insufficient drug treatment (myasthenic crisis) or too much drug treatment (cholinergic crisis).3 The terminology regarding these types of crises is controversial and beyond the scope of this chapter.19,20 The patient will improve with edrophonium testing if the etiology of the weakness is a myasthenic crisis. The symptoms will worsen with edrophonium testing if the etiology of the weakness is a cholinergic crisis. Consult a Neurologist, for these reasons, prior to performing an edrophonium test on a patient with myasthenia gravis who is already taking oral anticholinergic medications.

A patient with known myasthenia gravis complaining of respiratory distress should be assessed and managed similar to any other patient with respiratory compromise. An edrophonium test is contraindicated if it is being used to improve a patient's respiratory distress. A cholinergic crisis treated with edrophonium can further compromise the patient's respiratory status, possible leading to a respiratory arrest.

The use of edrophonium is contraindicated in pregnancy. It may induce the patient into preterm labor. A neostigmine test is safer if testing is required. Testing should be performed only after consultation with an Obstetrician and a Neurologist.

Edrophonium testing is relatively contraindicated in patients with asthma, bronchospastic disease, cardiac dysrhythmias, or if a group of muscles that are weak are not easily observable. Edrophonium testing should be deferred in favor of neurological consultation and consideration of other testing methods.

• 10 mg edrophonium chloride (Tensilon)
• Tuberculin syringe
• 10 mL syringe containing 9 mL of sterile normal saline
• Intravenous access with normal saline solution attached to the IV catheter
• Cardiac monitor
• Pulse oximeter
• Noninvasive blood pressure monitor
• Supplemental nasal oxygen
• Resuscitative equipment and medications
• Digital camera
• Ice pack, ice cubes, or instant cold packs

Explain the risks, benefits, and potential complications to the patient and/or their representative. Obtain a signed consent for the procedure. Place the patient sitting upright or supine in a bed. Obtain intravenous access. Apply supplemental oxygen, pulse oximetry, cardiac monitoring, and noninvasive blood pressure monitoring. Resuscitative equipment and medication must be immediately available if required.

Identify a group of muscles that can easily be observed and monitored for improvement of function. If possible, the muscle group to be tested should be fatigued. For example, have the patient look upward for 3 minutes to accentuate ptosis. Muscle groups of the extremities can be exercised for several minutes until the patient experiences fatigue. Take a picture, if a camera is available, of the muscle group to be observed after it has been fatigued. This is the “before” photograph.

Prepare the edrophonium chloride. It is essential that the edrophonium concentration be accurate regardless of who (i.e., Emergency Physician, Nurse, or Pharmacist) prepares the solution. It is supplied in a concentration of 10 mg/mL. Using sterile technique, transfer 10 mg (1 mL of 10 mg/mL) of edrophonium into a syringe containing 9 mL of sterile normal saline. The resulting solution will contain 1 mg of edrophonium chloride per mL of fluid. Verify the concentration of the edrophonium solution prior to use, especially if it was made by someone else.

Administer the edrophonium soon after the weakened muscle is identified, carefully noted, and fatigued. Ideally, one person should administer the medication while another person observes the patient for the effects of the edrophonium chloride. It may be administered in increasing doses up to a total of 10 mg. Inject 1 mg (1 mL) of edrophonium chloride intravenously followed by a saline flush. Physical improvement in the observed muscle group should be seen within 30 seconds to 2 minutes if the edrophonium is effective. Muscle improvements will revert to their original state after 2 to 3 minutes. The test is concluded if there is a positive response to the edrophonium in the observed muscle group. Inject 3 mg (3 mL) of edrophonium chloride intravenously followed by a saline flush if there is no improvement after the first dose. The test is concluded if improvement is seen in the muscle group. Inject the remaining 6 mg (6 mL) of the edrophonium chloride intravenously followed by a saline flush if there is no response within 2 to 3 minutes after the second dose. The test is considered negative and concluded if there is no response to the third dose of edrophonium (total of 10 mg). A negative test argues against myasthenia gravis, but does not completely exclude the diagnosis.13,15

Some Neurologists prefer to give the entire 10 mg (10 mL) dose of edrophonium chloride as a single intravenous bolus and observe the muscle group for improvement. This has the potential to cause significant bradycardia and is not recommended.

The total dose of edrophonium to administer to children is 0.15 mg/kg, not to exceed 10 mg of edrophonium.5 An initial dose of 1 mg is appropriate for children. Administer subsequent doses of 1 to 2 mg to a maximum of 0.15 mg/kg or 10 mg of edrophonium.

Ice Pack Test for Ocular Myasthenia Gravis

The ice pack test can be used to diagnose patients with ocular signs of myasthenia gravis.16–18 This test is reserved for the patient presenting with ptosis and/or diplopia suggestive of myasthenia gravis. The basis of this test is the finding that patients with myasthenia gravis have symptoms that worsen in warm weather and that improve in cold weather. Based on this clinical observation, studies have shown that placement of a bag of ice directly over the eyes of myasthenia patients with ptosis actually relieved the symptoms and signs of ocular myasthenia gravis.16,17 This test is quick, simple, inexpensive, and easy to perform in the Emergency Department. It has none of the potential complications associated with the intravenous administration of edrophonium chloride. There are no contraindications to performing in this test.

Place a bag of ice directly over the eye with ptosis and/or diplopia for 2 minutes or until the patient is no longer able to tolerate the cold. An alternative to an ice pack is ice cubes placed in a glove or instant cold packs that are activated by compression. Remove the ice pack from the eye and observe the patient for any improvement in the ptosis or diplopia. A clear improvement of the ptosis indicates a positive test. This test may be limited by the patient's intolerance to the ice pack.

These tests can be positive and confirm the diagnosis of myasthenia gravis. Objective findings of improved muscle function must be observed to identify the test as positive. It is very common to observe fasciculations of the facial muscles or tongue after the intravenous administration of edrophonium chloride. Muscle fasciculations are not considered a positive test. The patient having the subjective feeling of “feeling better” without objective evidence of improved muscle function is also not considered a positive test. Document improvement by taking a photograph. This is the “after” photograph. Place both the “before” and “after” photographs in the patient's medical record.

The patient may be safely discharged if they are ambulatory and without respiratory distress. All patients with suspected or proven myasthenia gravis should be referred to their Primary Care Physician and a Neurologist for further evaluation and management.

Muscarinic side effects can be seen due to the prolonged cholinergic stimulation in patients hypersensitive to edrophonium chloride. These effects include increased salivation, increased lacrimation, and miosis. Some patients may experience bradycardia, junctional rhythms, and ventricular dysrhythmias due to the increased vagal effects of the prolonged acetylcholine stimulation of the heart.11 Older patients may experience a resultant postural syncope. These effects are usually transient and self-limited. Intravenous atropine in low doses (0.5 mg) is effective to counteract any of the above symptomatology.

There are no complications associated with the proper use of the ice pack test. Leaving the ice pack on the eyelids too long can result in a frostbite injury.

Myasthenia gravis is an autoimmune disease that results in muscle weakness. The edrophonium test allows for a rapid, simple, and safe way to diagnose myasthenia gravis in the Emergency Department. The ice pack test for ocular myasthenia gravis offers a simple alternative to diagnose myasthenia gravis. Obtain prompt Neurological consultation for all patients presenting with signs and symptoms suggestive of myasthenia gravis.