Repouso da junção neuromuscular no tratamento de crises miastênicas e colinérgicas

Assis, J. Lamartine de; Saraiva, Paulo A. P.

doi:10.1590/S0004-282X1968000200001

Resumos

Os autores trataram 18 crises miastênicas e colinérgicas desenvolvidas em 12 pacientes com forma generalizada e severa de miastenia grave, mediante o "repouso" da junção neuromuscular. Êste foi conseguido, em um grupo de 6 enfermos, pela suspensão das drogas anticolinesterásicas, emprego da respiração artificial e alimentação por sonda nasogástrica — "repouso relativo". Outro grupo de 6 pacientes foi submetido ao "repouso absoluto" da junção neuromuscular, mediante o uso da respiração artificial, alimentação por sonda nasogástrica e curarização prolongada pela galamina. Em mais de 50% das crises observaram-se melhoras imediatas e acentuadas com o método de tratamento pelo "repouso" da junção neuromuscular, ao lado de redução significativa da taxa de mortalidade nas crises. A evolução mostrou que os pacientes que responderam melhor durante e logo após o tratamento da crise, tiveram, também, melhor evolução ulterior. Dos 12 enfermos somente um era portador de timoma e, mesmo nesse paciente, a evolução foi satisfatória. A sensibilidade inicial ao curare foi muito grande em todos os doentes submetidos à curarização prolongada, mas, em prazo relativamente curto (alguns dias), esta hipersensibilidade diminuiu sensivelmente. Apesar de todos os cuidados, as infecções respiratórias foram a regra, exigindo tratamento enérgico e bem orientado.

The neuromuscular junction rest method was employed in the treatment of 18 myasthenic and cholinergic crisis occurring in 12 patients with severe forms of myasthenia gravis. Six of these patients received a "relative rest" and other six patients received an "absolute rest" treatment. In the first group of patients the method consisted essentially in withdrawal of anticholinesterase therapy and mechanical respiratory support with early performance of traqueostomy and use of the intermitente positive pressure breathing (I.P.P.B.) with cuffed traqueostomy tube. The patients of second group, in addition to this management, were submitted to prolonged curarization by galamine (Flaxedil by intramuscular injection); all of them presented an initial curare supersensitivity which always decreased shortly. In both methods the reinstitution of the drug therapy was progressive. The respirator weanned of progressively and the patients were kept under observation for adequate ventilation. The doses were variable but subsequent doses of antimyasthenic medications were determined by clinical findings and response to the tensilon or prostigmine tests. The doses were increased or decreased accordingly in each individual case, rapid changes of drug doses to perfect adjustment being undesirable in this transition period. Partial or temporary remission occurred in some patients. Others were able to sustain satisfactory ventilation for a long period or definitively. Most of the crisis improved and most of the patients benefited from the therapeutic method of the neuromuscular junction rest. There was a remarkable reduction in the mortality rate from the crisis. One patient had a thymoma which was malignant; in spite of this the evolution of this case has been good after the treatment. Those patients who had immediate good response to the treatment of the crisis had a favorable fellow up, even a complete remission. Respiratory infections were very common in spite of all cares. Culture of tracheal secretions and wound exsudates were made. Bactericidal and broad-spectrum antibiotics were used, depending of the laboratory report cf patient's sensitivity. Physiotherapy besides other prophylactic measures was used against bronchopneumonia. Atelectasis was a common complication in the crisis and all efforts to prevent it were made, including daily clinical examination of pulmonary conditions, Vt,, blood pressure and bed side chest films. The routine use of atropine sulfate promoved inspissation of bronchial secretions, plugging of the bronchi, and attendant atelectasis, infection and bronchopneumonia. Exceptionally, steroids or bronchoscopy had been used.

Repouso da junção neuromuscular no tratamento de crises miastênicas e colinérgicas

Management of the myasthenic and cholinergic crisis by neuromuscular junction rest

J. Lamartine de Assis^I; Paulo A. P. Saraiva^II

^IDocente-Livre de Neurologia. Faculdade de Medicina da Universidade de São Paulo

^IIMédico Chefe da Unidade de Paralisia Infantil. Faculdade de Medicina da Universidade de São Paulo

RESUMO

Os autores trataram 18 crises miastênicas e colinérgicas desenvolvidas em 12 pacientes com forma generalizada e severa de miastenia grave, mediante o "repouso" da junção neuromuscular. Êste foi conseguido, em um grupo de 6 enfermos, pela suspensão das drogas anticolinesterásicas, emprego da respiração artificial e alimentação por sonda nasogástrica "repouso relativo". Outro grupo de 6 pacientes foi submetido ao "repouso absoluto" da junção neuromuscular, mediante o uso da respiração artificial, alimentação por sonda nasogástrica e curarização prolongada pela galamina. Em mais de 50% das crises observaram-se melhoras imediatas e acentuadas com o método de tratamento pelo "repouso" da junção neuromuscular, ao lado de redução significativa da taxa de mortalidade nas crises.

A evolução mostrou que os pacientes que responderam melhor durante e logo após o tratamento da crise, tiveram, também, melhor evolução ulterior. Dos 12 enfermos somente um era portador de timoma e, mesmo nesse paciente, a evolução foi satisfatória.

A sensibilidade inicial ao curare foi muito grande em todos os doentes submetidos à curarização prolongada, mas, em prazo relativamente curto (alguns dias), esta hipersensibilidade diminuiu sensivelmente.

Apesar de todos os cuidados, as infecções respiratórias foram a regra, exigindo tratamento enérgico e bem orientado.

SUMMARY

The neuromuscular junction rest method was employed in the treatment of 18 myasthenic and cholinergic crisis occurring in 12 patients with severe forms of myasthenia gravis. Six of these patients received a "relative rest" and other six patients received an "absolute rest" treatment. In the first group of patients the method consisted essentially in withdrawal of anticholinesterase therapy and mechanical respiratory support with early performance of traqueostomy and use of the intermitente positive pressure breathing (I.P.P.B.) with cuffed traqueostomy tube. The patients of second group, in addition to this management, were submitted to prolonged curarization by galamine (Flaxedil by intramuscular injection); all of them presented an initial curare supersensitivity which always decreased shortly.

In both methods the reinstitution of the drug therapy was progressive. The respirator weanned of progressively and the patients were kept under observation for adequate ventilation. The doses were variable but subsequent doses of antimyasthenic medications were determined by clinical findings and response to the tensilon or prostigmine tests. The doses were increased or decreased accordingly in each individual case, rapid changes of drug doses to perfect adjustment being undesirable in this transition period. Partial or temporary remission occurred in some patients. Others were able to sustain satisfactory ventilation for a long period or definitively.

Most of the crisis improved and most of the patients benefited from the therapeutic method of the neuromuscular junction rest. There was a remarkable reduction in the mortality rate from the crisis. One patient had a thymoma which was malignant; in spite of this the evolution of this case has been good after the treatment. Those patients who had immediate good response to the treatment of the crisis had a favorable fellow up, even a complete remission.

Respiratory infections were very common in spite of all cares. Culture of tracheal secretions and wound exsudates were made. Bactericidal and broad-spectrum antibiotics were used, depending of the laboratory report cf patient's sensitivity. Physiotherapy besides other prophylactic measures was used against bronchopneumonia. Atelectasis was a common complication in the crisis and all efforts to prevent it were made, including daily clinical examination of pulmonary conditions, Vt,, blood pressure and bed side chest films. The routine use of atropine sulfate promoved inspissation of bronchial secretions, plugging of the bronchi, and attendant atelectasis, infection and bronchopneumonia. Exceptionally, steroids or bronchoscopy had been used.

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Clínica Neurológica Faculdade de Medicina da Universidade de São Paulo Caixa Postal 3461 São Paulo, SP, Brasil.

1. ASSIS, J. L. Tratamento das formas severas da miastenia grave pelo ACTH por via intravenosa. Arq. Neuro-Psiquiat. (Săo Paulo) 18:359-382, 1960.
2. BURNS, B. D. & PATON, W. D. Depolarization of the motor end-plate by decamethonium and acetylcholine. J. Physiol. 115:41-73, 1951.
3. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. The action of decamathonium iodide in myasthenia gravis. J. Neurol. Psychiat. 15:129-133, 1552.
4. CHURCHILL-DAVIDSON, H. C. Myasthenic crisis. Therapeutic use of d-tutocurarine. Lancet 273:1221-1224, 1957.
5. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. Neuromuscular transmission in myasthenia gravis. J. Physiol. Lond. 122:252-263, 1953.
6. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. Neuromuscular transmission in myasthenia gravis. Amer. J. Med. 19:691-692, 1955.
7. CHURCHILL-DAVIDSON, H. C. Discussion on myasthenia gravis Proc. Roy. Soc. Med. 49:793-795, 1956.
8. EMMELIN, N. Supersensitivity following "pharmacological denervation". Pharmacological Rev. 13:17-37, 1961.
9. GROB, D. & JOHNS, R. J. Use of oximes in the treatment of intoxication by anticholinesterase compounds in patients with myasthenia gravis. Amer. J. Med. 24:512-518, 1958.
10. GROB, D.; JOHNS, R. J. & HARVEY, A. M. Alteration in neuromuscular transmission in myasthenia gravis as determined by studies of drug action. Amer. J. Med. 19:684-690, 1955.
11. GROB, D. & JOHNS, R. J. Use of oximes in the treatment of intoxication by anticholinesterase compounds in normal subjects. Amer. J. Med. 24:497-511, 1958.
12. GROB, D.; JOHNS, R. J. & HARVEY, A. M. Studies in neuromuscular function: introduction and methods. Bull. Jonhs Hopkins Hosp. 99:115-124, 1956.
13. GROB, D.; JOHNS, R. J. & HARVEY, A. M. Studies in neuromuscular function: stimulating and depressant effects of acetylcholine and choline in normal subjects. Bull. Jonhs Hopkins Hosp. 99:136-152, 1956.
14. GROB, D.; JOHNS, R. J. & HARVEY, A. M. Studies in neuromuscular function: stimulating and depressant effects of acethylcholine and choline in patients with myasthenia gravis and their relationship to the defect in neuromuscular transmission. Bull. Johns Hopkins Hosp. 99:153-181, 1956.
15. HUTTER, O. F. Effects of choline on neuromuscular transmission in the cat. J. Physiol. 117:241-250, 1952.
16. JEWELL, P. A. & ZAINIS, E. J. A differentiation between red and white muscle in the cat based on response to neuromuscular blocking substances. J. Physiol. 124:417-428, 1954.
17. JOHNS, R. J.; GROB, D. & HARVEY, A. M. Studies in neuromuscular function. Effects of nerve stimulation in normal subjects and in patients with myasthenia gravis. Bull. Johns Hopkins Hosp. 99:125-135, 1956.
18. HOWARD Jr., F. N. Treatment of myasthenia gravis and other diseases with a defect in neuromuscular transmission. InModern Treatment. Harper & Row, New York, vol. 3, n.o2, 1966, págs. 278-297.
19. OSSERMANN, K. E. & GENKINS, G. Studies in myasthenia gravis: reduction in mortality rate after crisis. J. Amer. Med. Ass 183:97-101, 1963.
20. SMITH, C. M.; COHEN, H. C; PELIKAN, E. W. & UNNA, K. R. Mode of action of antagonists to curare. J. Pharmacol, a. Exper. Therap. 105:391-399, 1952.
21. VAN NAANEN, E. F. The antagonism between acetylcholine and the curare alkaloids, d-tubocurare, c-curarine-I; c-toxiferine-II and B-erythoidine on the rectus abdominis of the frog. J. Pharmacol, a Experi. Therap. 99:255-264, 1950
22. ZAIMIS, E J. Motor end-plate differences as a determining factor in the mode of action of neuromuscular blocking substances. J. Physiol. 122.238-251, 1953.
23. ZANINI, A. C. Alteraçőes funcionais da junçăo neuromuscular provocadas em ratos pela administraçăo diária e prolongada de um agente curarizante. Arq. Neuro-Psiquiat. (Săo Paulo) 25:112-123, 1967.

Datas de Publicação

Publicação nesta coleção
14 Maio 2013
Data do Fascículo
Jun 1968

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ASSIS, J. L. Tratamento das formas severas da miastenia grave pelo ACTH por via intravenosa. Arq. Neuro-Psiquiat. (Săo Paulo) 18:359-382, 1960.

[2] 2. BURNS, B. D. & PATON, W. D. Depolarization of the motor end-plate by decamethonium and acetylcholine. J. Physiol. 115:41-73, 1951.

[3] 3. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. The action of decamathonium iodide in myasthenia gravis. J. Neurol. Psychiat. 15:129-133, 1552.

[4] 4. CHURCHILL-DAVIDSON, H. C. Myasthenic crisis. Therapeutic use of d-tutocurarine. Lancet 273:1221-1224, 1957.

[5] 5. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. Neuromuscular transmission in myasthenia gravis. J. Physiol. Lond. 122:252-263, 1953.

[6] 6. CHURCHILL-DAVIDSON, H. C. & RICHARDSON, A. T. Neuromuscular transmission in myasthenia gravis. Amer. J. Med. 19:691-692, 1955.

[7] 7. CHURCHILL-DAVIDSON, H. C. Discussion on myasthenia gravis Proc. Roy. Soc. Med. 49:793-795, 1956.

[8] 8. EMMELIN, N. Supersensitivity following "pharmacological denervation". Pharmacological Rev. 13:17-37, 1961.

[9] 9. GROB, D. & JOHNS, R. J. Use of oximes in the treatment of intoxication by anticholinesterase compounds in patients with myasthenia gravis. Amer. J. Med. 24:512-518, 1958.

[10] 10. GROB, D.; JOHNS, R. J. & HARVEY, A. M. Alteration in neuromuscular transmission in myasthenia gravis as determined by studies of drug action. Amer. J. Med. 19:684-690, 1955.

[11] 11. GROB, D. & JOHNS, R. J. Use of oximes in the treatment of intoxication by anticholinesterase compounds in normal subjects. Amer. J. Med. 24:497-511, 1958.

[12] 12. GROB, D.; JOHNS, R. J. & HARVEY, A. M. Studies in neuromuscular function: introduction and methods. Bull. Jonhs Hopkins Hosp. 99:115-124, 1956.

[13] 13. GROB, D.; JOHNS, R. J. & HARVEY, A. M. Studies in neuromuscular function: stimulating and depressant effects of acetylcholine and choline in normal subjects. Bull. Jonhs Hopkins Hosp. 99:136-152, 1956.

[14] 14. GROB, D.; JOHNS, R. J. & HARVEY, A. M. Studies in neuromuscular function: stimulating and depressant effects of acethylcholine and choline in patients with myasthenia gravis and their relationship to the defect in neuromuscular transmission. Bull. Johns Hopkins Hosp. 99:153-181, 1956.

[15] 15. HUTTER, O. F. Effects of choline on neuromuscular transmission in the cat. J. Physiol. 117:241-250, 1952.

[16] 16. JEWELL, P. A. & ZAINIS, E. J. A differentiation between red and white muscle in the cat based on response to neuromuscular blocking substances. J. Physiol. 124:417-428, 1954.

[17] 17. JOHNS, R. J.; GROB, D. & HARVEY, A. M. Studies in neuromuscular function. Effects of nerve stimulation in normal subjects and in patients with myasthenia gravis. Bull. Johns Hopkins Hosp. 99:125-135, 1956.

[18] 18. HOWARD Jr., F. N. Treatment of myasthenia gravis and other diseases with a defect in neuromuscular transmission. InModern Treatment. Harper & Row, New York, vol. 3, n.o2, 1966, págs. 278-297.

[19] 19. OSSERMANN, K. E. & GENKINS, G. Studies in myasthenia gravis: reduction in mortality rate after crisis. J. Amer. Med. Ass 183:97-101, 1963.

[20] 20. SMITH, C. M.; COHEN, H. C; PELIKAN, E. W. & UNNA, K. R. Mode of action of antagonists to curare. J. Pharmacol, a. Exper. Therap. 105:391-399, 1952.

[21] 21. VAN NAANEN, E. F. The antagonism between acetylcholine and the curare alkaloids, d-tubocurare, c-curarine-I; c-toxiferine-II and B-erythoidine on the rectus abdominis of the frog. J. Pharmacol, a Experi. Therap. 99:255-264, 1950

[22] 22. ZAIMIS, E J. Motor end-plate differences as a determining factor in the mode of action of neuromuscular blocking substances. J. Physiol. 122.238-251, 1953.

[23] 23. ZANINI, A. C. Alteraçőes funcionais da junçăo neuromuscular provocadas em ratos pela administraçăo diária e prolongada de um agente curarizante. Arq. Neuro-Psiquiat. (Săo Paulo) 25:112-123, 1967.