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The T ensilon Test A Safe Office Procedure

HENRY J. L. VANDYK, MD,* LAUR FLORENCE, BSt

Abstract: Myasthenia gravis is now known to be an autoimmune disorder in which damage of acetylcholine receptors takes place at the post-synaptic membrane. This new knowledge has improved therapy and placed a premium on early diagnosis. To overcome ophthalmologic reluctance to perform Tensilon testing, side effects of Tensilon are reviewed and a survey of the frequency of these side effects is reported. [Key words: anticholinesterase, myasthe­nia gravis, side effects, Tensilon.] Oph­thalmology 87:210-212, 1980

Myasthenia gravis is a disease of special interest to ophthalmologists, because the initial symptom in 50 to 60% of patients is ptosis or diplopia or both1 and because the disease may mimic a number of "diagnos­tic" motility patterns (for example, pupil­sparing third nerve palsy, or internuclear ophthalmoplegia) and thus may be diagnos­tically elusive. Clinical ophthalmologists, while preoccupied with diagnosis, have watched with interest as the pathogenesis of myasthenia has been further unraveled, as the "lesion" in the myoneural junction has been discovered to lie, not on the neural side, but almost certainly on the muscle side of that junction. More specifically, the acetylcholine receptors on the post­synaptic surface of the junction (ie, on skeletal muscle cells) have been found to be damaged and reduced in number in most

From the Department of Ophthalmology,* Louisiana State University, New Orleans, and the University of Utah College of Medicine,t Salt Lake City.

Presented at the Eighty-Fourth Annual Meeting of the American Academy of Ophthalmology, San Fran­cisco, November 5-9, 1979.

Reprint requests to Henry J. L. Van Dyk, MD, LSU Eye Center, 136 South Roman Street, New Orleans, LA 70112.

myasthenics. 2 •3 Further, immune com­

plexes have been demonstrated on these acetylcholine receptors on the motor end­plate,4 and anti-acetylcholine receptor an­tibodies have been found in approximately 80% of patients with myasthenia, with the levels generally correlating with the sever­ity of the disease. 5•

6

With this new understanding of the pathogenesis of myasthenia, treatment em­phasis has shifted from attempts to improve neuromuscular transmission directly to­ward attempts to modify the defective im­mune mechanism: corticosteroids, im­munosuppressives, plasmapheresis, and thymectomy. There have been some stun­ning therapeutic successes. 5

These therapeutic advances make early diagnosis of myasthenia a matter of practi­cal importance for the patient, yet there remains some reluctance among ophthal­mologists to employ intravenous Tensilon for diagnostic testing. We believe this re­luctance stems from concern for the pa­tient's safety. Therefore, this paper reviews the side effects of Tensilon and reports the results of a survey on the frequency and severity of those side effects.

SIDE EFFECTS

The side effects of Tensilon are all di­rectly related to its pharmacologic action, that of a rapidly acting and quickly hydro­lyzed anticholinesterase. 7 Tensilon com­petes with acetylcholine for the attention of the enzyme acetylcholinesterase and it al­ways wins, albeit briefly and incompletely. Thus it is that acetylcholine briefly ac­cumulates in greater than normal amounts in ganglia, at parasympathetic nerve end­ings, and at neuromuscular junctions in all types of muscle: cardiac, smooth, and

0161-6420/80/0300/0210/$00.65 ©American Academy of Ophthalmology

striated. It is this transient excess of acetyl­choline that makes the Tensilon test work, but this same excess also produces the cholinergic side effects in what should be thought of as a brief overstimulation of the parasympathetic nervous system and vol­untary muscle. All recognized side effects are listed in Table 1.

FREQUENCY

How frequent are these side effects? The minor cholinergic effects, such as diaphoresis and inconsequential cardiac slowing, occur nearly every time a full dose of Tensilon is administered intravenously. However, the frequency of the major side effects seems to be unknown. Osserman's original description of this test in 50 pa­tients included no report of difficulty with the drug. 8 In addition, no case of Tensilon complication has been reported to the Na­tional Registry of Drug-Induced Ocular Side Effects. 9

PHYSICIAN SURVEY

To gain some information on the subject of the frequency of these side effects, I conducted a telephone survey of 25 full­time academic neuro-ophthalmologists. The only criterion for inclusion of their re­sponses was that they performed the Ten­silon test at least once a month. All per­formed the test at least that frequently, and some more frequently. These 25 physicians had a total of 267 years of faculty experi­ence with the test, for an average of 10.7 years per respondent (range: 3-24 years). No attempt was made to establish the total number of tests that each respondent had performed, since the accuracy of such "memory data" would be suspect. Instead, the time basis for frequency in this survey

Table 1. Tensilon Side Effects*

Diaphoresis Lacrimation Salivation Pupillary constriction Accommodation-myopia Tracheobronchial secretions Bronchiolar constriction Apnea Bradycardia Ventricular Asystole Hypotension Gastric and intestional secretion Abdominal cramps Involuntary defecation Fasciculations and weakness of

striated muscles

* Adapted from reference 7.

Table 2. Major Tensilon Side Effects in Survey

Probable cardiac arrest Hypotension and bradycardia (45 minutes) Apnea and unconsciousness

was simply the total years of faculty-level experience with the test.

Three instances of severe, untoward reactions were discovered by this survey (Table 2).

The case of cardiac arrest occurred in a patient over age 50. Approximately one minute after Tensilon was injected, the pa­tient became faint, then unresponsive; his pupils dilated, and no radial or precordial pulse could be obtained. Time did not per­mit electrocardiographic verification of this presumed arrest. Cardiopulmonary resus­citation was employed and the patient was revived without difficulty and without after effects.

A single case of bradycardia with symp­tomatic hypotension was also reported. Some of the clinical details were not re­called by the respondent, but it was re­membered that the cardiac rate remained under 50 beats/min for 45 minutes. Again, there were no lasting after effects.

Finally, one patient experienced diffi­culty after only 0.2 ml (2 mg) of Tensilon. She had warned the physician that she had had faintness when Tensilon was given to her in the past, but this experienced physi­cian proceeded anyway. The patient fainted and was apneic for one to two minutes, but promptly came around with intravenous at­ropine before cardiopulmonary resuscita­tion was begun.

In addition to these three cases of major side effects, 16 other instances of side ef­fects were reported, all obviously less seri­ous, yet annoying or frightening to patient and physician alike (Table 3). Considering the 13 syncopal episodes, at least two were clearly not caused by Tensilon, inasmuch as they occurred after the venipuncture but before any drug had been injected. Report­ing physicians were all aware of "veni­puncture syncope," but in the 11 other cases, drug had been injected before the fainting occurred, so that it might have been a direct drug effect.

The complication of involuntary patient defecation was so unpleasant for two of the three physicians reporting this side effect

Table 3. Minor Tensilon Side Effects in Survey

Faint, swoon, or syncope Involuntary defecation

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that they have since modified their test pro­cedure and pretreat all patients with atropine.

COMMENT

What can we learn from this survey of undesirable side effects of Tensilon? First, the side effects are decidedly uncommon, with only three major and 16 minor episodes recalled over a total of 267 years of frequent experience with the Tensilon test. Second, of the 25 respondents to this survey, only seven now routinely pretreat their patients with atropine. Because all of the major side effects (3 of 3) and most of the minor side effects (15 of 16) to Tensilon occurred in patients who had not been pre­treated with atropine, it seems probable that the routine use of atropine before Ten­silon testing might reduce the infrequent side effects of this remarkedly safe and useful diagnostic drug.

REFERENCES

1. Simpson JA. Myasthenia gravis: a new hypothe­sis. Scot Med J 1960; 5:419-36

2. Tsujihata M, Hazama R, Ishii N, Ide Y, Mori M, Takamori M. Limb muscle endplates in ocular myasthenia gravis: Quantitative ul­trastructural study. Neurology 1979; 29:654-61.

3. Fambrough OM, Drachman BD, Satyamurti S. Neuromuscular junction in myasthenia gravis: decreased acetylcholine receptors. Science 1973; 182:293-95.

4. Engel AG, Lambert EH, Howard FM. Immune complexes (lgG and C3) at the motor end-plate in myasthenia gravis: ultrastructural and light mi­croscopic localization and electrophysiologic correlations. Mayo Clin Proc 1977; 52:267-80.

5. Drachman DB. Myasthenia gravis. N Engl J Med 1978; 298:136-42, 186-93.

6. Lindstrom JM, Seybold ME, Lennon VA, Whitt­lingham S, Duane DO. Antibody to acetylcholine receptor in myasthenia gravis. Neurology 1976; 26:1 054-59.

7. Koelle GB. Anticholinesterase agents. In: Good­man LS, Gilman A, eds. Pharmacologic Bases of Therapeutics. 5th ed. New York: Macmillan. 1975. chap 22, 445-66.

8. Osserman KE, Kaplan Ll. Rapid diagnostic test for myasthenia gravis: increased muscle without fasciculations, after intravenous administration of edrophonium (Tensilon) chloride. JAMA 1952; 150:265-69.

9. Fraunfelder FT. Personal communication.