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THE MYOTONIC RESPONSE TO SUXAMETHONIUM
Brit. J. Anaesth. (1967), 39, 815
THE MYOTONIC RESPONSE TO SUXAMETHONIUM BY
R. E. THTEL
Department of Anaesthesia, Royal Brisbane Hospital, Queensland, Australia SUMMARY
Among the less common diseases which may lead to an altered or dangerous response to anaesthesia are three hereditary muscle disorders comprising the myotonic syndrome. Kaufman in 1960 described the anaesthetic hazards involved, and included in his account an instance of generalized myotonia due to decamethonium. Subsequently, Paterson (1962) described a case of generalized myotonia caused by suxamethonium. In each of these patients it was not possible to inflate the lungs during the myotonic spasm. It is the purpose of this paper to describe another instance of generalized myotonic spasm caused by suxamethonium, and to offer from further observations a possible explanation of the mechanisms involved. THE MYOTONIC SYNDROME
The differing clinical features are briefly presented (Caughey and Myrianthopoulos, 1963). Dystrophia myotonica. This is characterized by myotonia, muscle wasting, and such other features as cataract, premature frontal baldness, gonadal atrophy, hyperostosis cranii, disorders of cardiac conduction, and endocrine dysfunction. The onset is usually in the third decade, with myotonia of varying severity being often the earliest symptom. Subsequent muscle wasting and weakness occur in a pattern involving the facial muscles (myopathic facies), the Present address: Cairns Base Hospital, Queensland, Australia.
muscles of mastication, the sternomastoids, the thenar and forearm muscles, and the quadriceps and dorsiflexors of the feet. Respiratory impairment may result from wasting of the intercostals, the diaphragm, and the abdominal muscles. Myotonia disappears from wasted muscles. Death may occur in the sixth or seventh decade from inhalation pneumonia, suddenly with cardiac failure, or from intercurrent illness or infection. Myotonia congenita (Thomsen's disease). Myotonia and some hypertrophy of voluntary muscle are the cardinal features. The myotonia appears usually in childhood, occurs with strong effort, interferes with sport, and is widespread (cf. hands, forearms and tongue in dystrophia myotonica). The hypertrophy involves the masseters, the neck muscles, the spinati, deltoids, biceps, forearms and thenar muscles, and the calves, thighs and glutei. Dystrophic changes do not occur. Paramyotonia congenita. This is rare, with myotonia and/or weakness induced by cold and relieved by heat and exercise. The relationship of the three disorders to each other is uncertain. Evidence in favour of their being manifestations of a single disease is provided by their common mode of autosomal dominant transmission, the occurrence of intermediate clinical types as in the case reported below, and the description of more than one type of myotonia in the same family.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 28, 2015
A survey of the reported responses of myotonic patients to depolarizing relaxants reveals the variable incidence and extent of induced myotonia. Generalized myotonia due to suxamethonium is described in a patient with myotonia congenita and, from subsequent investigations during a second operation, the action of the drug is clarified. Such a myotonic response is attributed to fasciculation, and a normal depolarizing block was demonstrated with continued administration of the drug. Suggestions are made for the anaesthetic management of such patients.
BRITISH JOURNAL OF ANAESTHESIA
816 MYOTONIA
REPORTED EFFECTS OF DEPOLARIZING RELAXANTS
From a survey of published reports (table I) it becomes evident that myotonia is by no means an inevitable or predictable complication of the use of depolarizing relaxants. Talmadge and McKechnie (1959) attributed the myotonic spasm in their case to reflex straining on the endotracheal tube. They concluded that suxamethonium controls this tetanic state, and that the "neuromuscular defect" in myotonics appears not to alter the pharmacological response to suxamethonium. Paterson (1962) gives the only description of generalized myotonia with suxamethonium. No muscular paralysis followed the periods of myotonia and he observed the most marked spasm
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 28, 2015
The common feature, myotonia, consists of delayed relaxation of skeletal muscle following contraction. Myotonia may be elicited by voluntary contraction, mechanical stimulation (such as tapping of the muscle), electrical stimulation of nerve or muscle, and chemical stimulation by altered electrolyte concentrations. Aggravation of the myotonia occurs with cold and emotion. The site of the defect appears to be beyond the neuromuscular junction in the muscle fibre itself. Mechanical myotonia is uninfluenced by spinal anaesthesia (Grund, 1919), nerve block or section, curare or decamethonium (Geshwind and Simpson, 1955). Raised serum potassium concentration and neostigmine are claimed to increase the myotonic response in humans (Kennedy and Wolf, 1937), although Landau (1952) detected no significant change with neostigmine. Ether, despite its muscle-relaxing properties, was reported to cause irregular respiration and troublesome general muscular spasm in a case of myotonia congenita (Johnson and Marshall, 1915). Myotonia may cause respiratory distress by spasm of respiratory muscles, particularly following depolarizing relaxants, while persistent spasm of abdominal muscles due to reflex straining or forcible retraction may interfere with surgery. In the treatment of myotonia, Leyburn and Walton (1959), by comparing quinine, prednisone, and procaine amide, found that the last two were equally effective, and better than quinine in relieving myotonia.
after bis third and largest dose. Respiration had returned between successive doses. He pointed out that this reaction occurred in a case of myotonia congenita with minimal myotonic symptoms, whereas Kaufman (1960) had thought suxamethonium spasm more likely if myotonia was clinically marked. (That generalized myotonia can occur when clinical symptoms are localized may be an interesting illustration of total voluntary muscle involvement by the genetic abnormality.) Despite the difficulty in achieving intubation reported by Haley (1962) in relation to the second patient, the author stated that "the response to depolarizing relaxants in this series was entirely unremarkable". Cobham and Davis (1964) administered suxamethonium to their patient because of troublesome abdominal muscle spasm under a sensory epidural block. In view of this evidence of the presence of myotonia, they found the behaviour of their patient "unexpected and puzzling", thinking myotonia more likely than relaxation, and concluding that this was an atypical response to suxamethonium. In none of these cases was there any mention of current medical treatment for the myotonia at the time the patients came to surgery. At this hospital, twelve cases of dystrophia myotonica have been admitted during the last three years. Five of them underwent surgery. Of these, two received an inhalation anaesthetic, one was intubated uneventfully under suxamethonium but did not develop his first myotonic symptoms until five months later, another showed no evidence of myotonia with 150 mg of suxamethonium, and no anaesthetic record is available for the other. From these reports die following points emerge: (1) Myotonic spasm, both local and generalized, has followed the administration of depolarizing relaxants. (2) Suxamethonium has elicited a normal response in myotonics, and has been used to provide prolonged satisfactory relaxation. (3) Suxamethonium has been used to terminate myotonic spasm. (4) A relationship may exist between dosage and severity of spasm in any one patient.
817
THE MYOTONIC RESPONSE TO SUXAMETHONIUM TABLE I
Reported effects of depolarizing relaxant* m myotonia. Author
Diagnosis and response
Bourke and Zuck, 1957
Suxamethonium 50 mg
Dystrophia myotonica. Normal relaxation.
Talmadge and McKechnie, 1959
Suxamethonium 40 mg
Dystrophia myotonica. Easy intubation, generalized spasm as respiration returned. Spasm relieved by suxamethonium 10 mg. "Optimal" relaxation maintained.
10 m g x 2 0.2% infusion Total dose 160 mg Richardson, 1959
Decamethonium
Myotonic spasm with respiratory distress.
Kaufman, 1960
Suxamethonium Suxamethonium 30 mg
Dystrophia myotonica. Uneventful. Dystrophia myotonica. Myotonia of hands for 1 minute. No suggestion of myotonia of respiratory muscles. Dystrophia myotonica. Normal response. Dystrophia myotonica. Normal response.
Intermittent suxamethonium Suxamethonium Paterson, 1962
Suxamethonium 50 mgX2
Myotonia congenita. Generalized myotonia without fasciculation with each dose. Duration about 3 minutes. Unable to inflate during spasm.
75 mg Haley, 1962
Suxamethonium infusion 0.2% Suxamethonium 60 mg Repeat 40 mg Suxamethonium 260 mg for induction Suxamethonium infusion 0.1% Total dose 1300 mg
Cobham and Davis, 1964
Suxamethonium 40 mg Suxamethonium infusion 250 mg
Dystrophia myotonica. Normal response, postoperative muscle spasm. Same patient. Normal response. Dystrophia myotonica. No fasciculation, inadequate relaxation, unable to extend neck, jaw not relaxed, numerous attempts at intubation. Good relaxation. Treated as dual block at end of operation.
Dystrophia myotonica. Abdominal muscle spasm relieved by suxamethonium with typical brief period of relaxation, easy intubation. Good relaxation. Treated as dual block at end of operation.
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Drug
818
FIG. 1 Patient described in report: myotonia congenita.
upper limb reflexes and normal lower limb reflexes. No myotonia could be demonstrated. No deterioration in muscle status was observed over the 2$ years. Radiographs of skull, hands and feet, barium swallow and electrocardiogram were all normal. He was thought to have an apparently non-progressive familial muscular dystrophy with some pseudohypertrophic features. In August 1965 he underwent right cervical sympathectomy. Premedication consisted of hyoscine 0.4 mg, papaveretum 20 mg. Anaesthesia was induced using thiopentone 400 mg and this was followed by suxamethonium 100 mg. Within a minute generalized
myotonic spasm developed without prior fasciculation. His facial muscles were contracted, his jaw was immovable. The limbs were flexed, the abdomen rigid, and the spine and neck slightly arched. The state of myotonia persisted but inflation with oxygen by facepiece expanded the upper chest and sufficed to maintain pulse and colour. His jaw could be opened a little after about 2 minutes but intubation was impossible. Because of doubt that suxamethonium had in fact been given, a further 50 mg dose was injected, but did not lead to any apparent change in his condition. Inflation was continued until intubation became possible about 4 minutes after the first injection. After several inflations strong spontaneous respiration recommenced. Anaesthesia was subsequently maintained uneventfully using nitrous oxide, oxygen, and halothane 1 per cent. Slow fasciculation was noted in his exposed neck muscles during surgery. Postoperatively he had no muscle pains or other complaints. The right hand became warm and dry. Further enquiry into his symptoms revealed tightness and knotting of limb muscles with resultant weakness during exertion. This dated from the time when he first walked as an infant, and was said to be worse in cold weather, particularly in his fingers. It prevented him from engaging in sports. Myotonia was demonstrable only in his eyelids. When this patient returned for a left cervical sympathectomy, an attempt was made to demonstrate the effects of sustained administration of suxamethonium. Further investigations were made into dose-response relationships, and into the effects of repeated doses at intervals sufficient for complete recovery of muscle function to take place. Second anaesthetic. Premedication: papaveretum 20 mg, hyoscine 0.4 mg. 8.45 a.m.: induction with thiopentone 350 mg. A normal apnoeic pause was followed by resumption of quiet breathing. Anaesthesia was deepened with nitrous oxide, oxygen and halothane by facepiece. The cords were sprayed with 4 per cent lignocaine. 9.00: easy intubation with a cuffed tube. Halothane was turned off and anaesthesia maintained with nitrous oxide, oxygen, and pethidine 15 mg intravenously. 9.17: 0.2 per cent suxamethonium infusion was started at 40 drops/min. 9.20: spasm appeared without fasciculation in the face, eyelids, jaw, abdominal wall, and limbs. Breathing continued with diminished excursion. 9.21: infusion rate increased to 60 drops/min. This caused a sharp increase in the strength of spasm and shallower respiration. 9.22: infusion rate reduced to 40 drops/min. The spasm subsided until by 9.24 it involved only the hands and limbs. 9.25: a single dose of 30 mg of suxamethonium caused, within 30 seconds, a strong generalized spasm with flexed limbs, tight jaw and eyelids, rigid abdomen and apnoea. The lungs were easily inflatable. No fasciculation was observed. 9.27: the spasm decreased and the infusion was increased to 60 drops/min. 9.29: shallow breathing between inflations, relaxed in all but arms and feet. 9.30: infusion increased to 120 drops/min. 9.31: breathing shallow, musculature relaxed. 9.33: apnoeic, flaccid relaxation. A further rapid
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CASE REPORT A man, aged 24, weighing 142 lb. (fig. 1), sought treatment in November 1962 for chronic palmar and plantar hyperhidrosis with dyshidriotic eczema. In July 1965 bilateral cervical sympathectomy was recommended. His history included stiffness and non-progressive weakness of ringers and upper and lower limbs, occasional dysphagia associated with the limb stiffness, mild myotonia; and congenital squint without diplopia. On examination he was found to have myopathic facies and convergent right strabismus, normal lens, pupils, and fundi, average-sized testes, well developed but slightly weak sternomastoids, well developed trunk and proximal limb muscles, cold moist small hands with poorly developed intrinsic muscles and a weak grip, absent
BRITISH JOURNAL OF ANAESTHESIA
THE MYOTONIC RESPONSE TO SUXAMETHONIUM
throughout the muscle mass. It seems reasonable to suggest that in those myotonic subjects who "fasciculate", the individual muscle fibres respond, not by a brief but by a prolonged or myotonic contraction. As a result, there is rapid progressive involvement of whole muscles into the state of spasm described. Normal relaxation after a single dose of suxamethonium in a patient with myotonia may, on the other hand, represent an absent or minimal fasciculation response. Harrison (1965) points out that minor localized fasciculation is easily overlooked, and it is quite possible that an unremarked DISCUSSION minor fasciculation-induccd myotonia occurred in The myotonic episodes in this patient were attri- some of the patients reported in table I. Normal buted directly to the action of suxamethonium, fasciculation has not been reported after suxameand from the observations made during the second thonium in any myotonic. One might anticipate, anaesthetic the following conclusions are drawn: then, that sustained administration of suxamethon(1) Myotonic spasm precipitated by suxameth- ium would result in normal neuromuscular block onium was not prolonged by continued action of and relaxation as soon as the intrinsic muscle this drug. The spasm subsided over a few minutes contraction subsided. This was demonstrated in to reveal an apparently normal depolarizing block the case report, and Haley's report of his second with full muscle relaxation. case might also be interpreted as supporting this. (2) After single doses, the relaxation time of The unusual type of fasciculation seen in the the myotonic muscle exceeded the time normally pectoral muscles with the last dose of suxamerequired for enzymatic destruction of suxameth- thonium, provides two additional points in favour onium. In consequence, no period of apnoeic of the theory that myotonic spasm is a conrelaxation followed the myotonia. sequence of muscle fasciculation peculiar to this (3) Small doses of suxamethonium caused less abnormal muscle. First it indicates that this subpronounced spasm than large doses. ject is one whose muscles fasciculate in response (4) Myotonic spasm returned with doses of to suxamethonium. Second, the slightly prolonged suxamethonium given subsequent to return of contractions noted during fasciculation in this muscle function (in Paterson's case, the interval portion of muscle support the idea that myotonic was little more than that required for return of spasm represents summation through delayed respiration). relaxation of fasciculant contractions. Harrison Kaufman (1960) thought suxamethonium might (1965) has shown that visible fasciculation can aggravate myotonia by the elevation in serum recur with a second dose of suxamethonium at potassium shown to occur in animals by Paton intervals as short as 3 or 4 minutes after return of (1956). The timing of this effect and myotonic muscle function. This would explain the recureffect of decamethonium combine against this rence of myotonic spasm at the short intervals theory. reported in Paterson's case. Suxamethonium and decamethonium have the common effect of precipitating muscle fascicula- Implications for anaesthetic management. tion during the initial endplate depolarization. The response of myotonic patients to depolarizThis occurs in varying degree and is clinically ing relaxants is unpredictable. The degree of visible only in a proportion of normal subjects clinical myotonia or type of disease is, apparently, with suxamethonium and more rarely with deca- no guide. These relaxants are best avoided because methonium. It represents the visible, transient, of potential respiratory muscle spasm and conand scattered contractions of small groups of sequent anoxia. The use of non-depolarizing muscle fibres as progressive depolarization spreads relaxants is not contraindicated, being mindful of
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dose of suxamethonium 30 mg given now was without visible effect. 9.36: infusion stopped. 9.40: full respiration at 12 b.pjn. Left cervical sympathectomy and sternomastoid biopsy were performed under nitrous oxide, oxygen and halothane 1 per cent. Muscle fasciculation in the sternomastoid due to surgical stimulation was again seen. 10.35: halothane turned off. End of operation. At 10.45 a further rapid dose of suxamethonium 30 mg caused, after 30 seconds, a generalized spasm lasting 90 seconds. During the latter 60 seconds, coarse slowlyrelaxing fasciculation was observed in the pectoral muscles. The patient was extubated and woke at 11.00 a.m. The total dose of suxamethonium was 290 mg.
819
820
BRITISH JOURNAL OF ANAESTHESIA
The question of diagnosis. In this patient firm diagnosis was rendered difficult, despite the probable clinical diagnosis of myotonia congenita, by the results of electromyography and muscle biopsy. The opinion expressed on electromyographic sampling of each abductor pollicis brevis stated: "There is a definite myotonia and the appearances on muscle contraction suggest the presence of myopathy: the diagnosis is probably dystrophia myotonica." Muscle biopsy showed changes present "more in favour of myotonic dystrophy than of myotonia congenita". His family history is important (fig. 2). He is the third eldest of the brothers, all of whom have well developed musculature. The age of onset and nature of the disorder is similar in all affected members. The normal sisters are very athletic.
FIG. 2 Family genetic incidence. = patient,n =male, O=female, cross-hatched=affected.
There is no family history of cataract or baldness. None have had an anaesthetic or operation, or have ever sought medical diagnosis or treatment for their disability. It was thought worth while to notify members of the family (some of whom live interstate or abroad) of the diagnosis of myotonia, and of the importance of acquainting surgeon and anaesthetist with their condition pre-operatively. ACKNOWLEDGEMENTS
I wish to thank Dr. D. Friend and Dr. K. Hayes, whose patient this was, for their co-operation and help. My appreciation is offered to Dr. M. Eadie, Dr. Ruth Molphy, and Dr. Beric Jackson for their encouragement and advice. Permission to publish details of patient records was kindly granted by Dr. A. D. D. Pye. REFERENCES
Bourke, T. D., and Zuck, D. (1957). Thiopentone in dystrophia myotonica. Brit. J. Anaesth., 29, 35. Caughey, J. E., and Myrianthopoulos, N. C. (1963). Dystrophia Myotonica and Related Disorders. Springfield: Thomas. Cobham, I. G., and Davis, H. S. (1964). Anesthesia for muscle dystrophy patients. Anesth. Analg. Curr. Res., 43, 22. Geshwind, K, and Simpson, J. A. (1955). Procaine amide in the treatment of myotonia. Brain, 78, 81. Grund, G. (1919). Ueber myokymbche Kontraktur. Dtsch. Z. Nervenheilk., 64, 102. Haley, F. C. (1962). Anaesthesia in dystrophia myotonia. Canad. Anaesth. Soc. J., 9, 270. Harrison, G. A. (1965). The incidence of visible muscular fasciculations following a second dose of suxamethonium chloride. Brit. J. Anaesth., 37, 129. Johnson, W., and Marshall, G. (1915). Observations on Thomsen's disease. Quart. J. med., 8, 114. Kaufman, L. (1960). Anaesthesia in dystrophia myotonica. Proc. roy. Soc. Med., 53, 183. Kennedy, F., and Wolf, A. (1937). Experiments with quinine and prostigmin in treatment of myotonia and myasthenia. Arch. Neurol. Psychiat. {Chicago), 37, 68. Landau, W. M. (1952). The essential mechanism in myotonia: an electromyographic study. Neurology (Aftnneap.), 2, 369. Leyburn, P., and Walton, J. M. (1959). The treatment of myotonia. Brain, 82, 81. Paterson, I. S. (1962). Generalized myotonia following suxamethonium. Brit. J. Anaesth., 34, 340. Paton, W. D. M. (1956). Mode of action of neuromuscular blocking agents. Brit. J. Anaesth., 28, 475. Richardson, A. T. (1959). Personal communication to Kaufman, L. Talmadge, E. A., and McKechnie, F. B. (1959). Anesthetic management of patient with myotonia dystrophica. Anesthesiology, 20, 717.
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the importance of adequate reversal in the presence of muscular wasting and weakness. If suxamethonium is used, an initial test dose of 5 mg might be expected, by any evidence of minor spasm, to indicate the likelihood of major spasm with a paralyzing dose. Pre-operative procaine amide should reduce relaxation time towards normal, and seems a desirable part of preparation for surgery in these patients. Intravenous hydrocortisone may be effective in the relief of myotonia during surgery, without the dangerous side effects of intravenous procaine amide. Halothane poses one potential disadvantage, in that the shivering and rigidity often seen postoperatively, might well precipitate dangerous myotonia.
THE MYOTONIC RESPONSE TO SUXAMETHONIUM
821
DIE MYOTONISCHE REAKTION AUF SUXAMETHONIUM
LA REACTION MYOTONIQUE AU SUXAMETHONIUM
ZUSAMMENFASSUNG
In einer Ubersicht iiber die beschriebenen Reaktionen von Patienten mit Myotonie auf depolarisierende Relaxantien wird das unterschiedliche Auftreten und der Umfang einer kiinstlich ausgelosten Myotonie aufgezeigt. An einem Patienten mit Myotonie congenita wird eine generalisierte Myotonie nach Verabreichung von Suxamethonium beschrieben. SpStere Untersuchungen wahrend einer zweiten Operation erklaren die Wirkungsweise der Substanz. Eine solche myotonischc Reaktion wird fascilcularen Kontraktionen zugeschrieben. Bei fortgesetzter Verabreichung des Mittels liefi sich eine normale Depolarisationsblockade nachweisen. Vorschlage zur Durchfuhrung der Narkose bei solchen Patienten werden gemacht.
GLASGOW AND WEST OF SCOTLAND SOCIETY OF ANAESTHETISTS 1968
Syllabus 1967-68
TUESDAY, JANUARY 9
Symposium on Neuroleptanalgesia.
1967
DR.
SHEILA
JENNETT,
University
of
Glasgow. DR. C. PRYS-ROBERTS, University of
SATURDAY, OCTOBER 21 (5.15 pjn.)
Joint meeting in Glasgow with Edinburgh and East of Scotland Society of Anaesthetists. "Myasthenia Gravis and the Anaesthetist." PROF.
J.
A.
SIMPSON,
University
Glasgow.
of
Oxford. DR.
G.
BARRY
SMITH,
The
London
Hospital. MONDAY, FEBRUARY 12
Members' Night. Staff of Department of Anaesthetics, Killearn Hospital. MONDAY, MARCH 18
Presidential Address. DR. A. HARVEY GRANAT. MONDAY, APRIL 1
Annual General Meeting.
TUESDAY, DECEMBER 5
"The Physiology of Pain." DR. J. CLUTTON-BROCK, Bristol.
SATURDAY, APRIL 6
Visit to Falkirk and District Royal Infirmary.
Unless shown otherwise, meetings will be held at the Royal College of Physicians and Surgeons, 242 St. Vincent Street, at 8.15 pjn. Tea will be served from 7.45 p.m. Notice of each meeting will be sent to members.
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SOMMAIRE
Un aprrcu dcs reactions rapportees chez des patients myotoniques qui avaient recu des relachants dipolarisants, revile l'incidence et l'etendue variables de la myotomie causee. Une myotonie generalisee, due au suxamethonium, a etc decrite chez un patient avec myotonie congenitale, et l'action du medicament a iti mise en evidence par des Etudes au cours d'une seconde operation. Une reaction myotonique pareille est attribute a une fasciculation, et un block d£polarisant normal a etc demontrf sous administration continue du medicament. Certaines suggestions pour l'anesthesic de pareils patients sont avancees.
THE MYOTONIC RESPONSE TO SUXAMETHONIUM BY
R. E. THTEL
Department of Anaesthesia, Royal Brisbane Hospital, Queensland, Australia SUMMARY
Among the less common diseases which may lead to an altered or dangerous response to anaesthesia are three hereditary muscle disorders comprising the myotonic syndrome. Kaufman in 1960 described the anaesthetic hazards involved, and included in his account an instance of generalized myotonia due to decamethonium. Subsequently, Paterson (1962) described a case of generalized myotonia caused by suxamethonium. In each of these patients it was not possible to inflate the lungs during the myotonic spasm. It is the purpose of this paper to describe another instance of generalized myotonic spasm caused by suxamethonium, and to offer from further observations a possible explanation of the mechanisms involved. THE MYOTONIC SYNDROME
The differing clinical features are briefly presented (Caughey and Myrianthopoulos, 1963). Dystrophia myotonica. This is characterized by myotonia, muscle wasting, and such other features as cataract, premature frontal baldness, gonadal atrophy, hyperostosis cranii, disorders of cardiac conduction, and endocrine dysfunction. The onset is usually in the third decade, with myotonia of varying severity being often the earliest symptom. Subsequent muscle wasting and weakness occur in a pattern involving the facial muscles (myopathic facies), the Present address: Cairns Base Hospital, Queensland, Australia.
muscles of mastication, the sternomastoids, the thenar and forearm muscles, and the quadriceps and dorsiflexors of the feet. Respiratory impairment may result from wasting of the intercostals, the diaphragm, and the abdominal muscles. Myotonia disappears from wasted muscles. Death may occur in the sixth or seventh decade from inhalation pneumonia, suddenly with cardiac failure, or from intercurrent illness or infection. Myotonia congenita (Thomsen's disease). Myotonia and some hypertrophy of voluntary muscle are the cardinal features. The myotonia appears usually in childhood, occurs with strong effort, interferes with sport, and is widespread (cf. hands, forearms and tongue in dystrophia myotonica). The hypertrophy involves the masseters, the neck muscles, the spinati, deltoids, biceps, forearms and thenar muscles, and the calves, thighs and glutei. Dystrophic changes do not occur. Paramyotonia congenita. This is rare, with myotonia and/or weakness induced by cold and relieved by heat and exercise. The relationship of the three disorders to each other is uncertain. Evidence in favour of their being manifestations of a single disease is provided by their common mode of autosomal dominant transmission, the occurrence of intermediate clinical types as in the case reported below, and the description of more than one type of myotonia in the same family.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 28, 2015
A survey of the reported responses of myotonic patients to depolarizing relaxants reveals the variable incidence and extent of induced myotonia. Generalized myotonia due to suxamethonium is described in a patient with myotonia congenita and, from subsequent investigations during a second operation, the action of the drug is clarified. Such a myotonic response is attributed to fasciculation, and a normal depolarizing block was demonstrated with continued administration of the drug. Suggestions are made for the anaesthetic management of such patients.
BRITISH JOURNAL OF ANAESTHESIA
816 MYOTONIA
REPORTED EFFECTS OF DEPOLARIZING RELAXANTS
From a survey of published reports (table I) it becomes evident that myotonia is by no means an inevitable or predictable complication of the use of depolarizing relaxants. Talmadge and McKechnie (1959) attributed the myotonic spasm in their case to reflex straining on the endotracheal tube. They concluded that suxamethonium controls this tetanic state, and that the "neuromuscular defect" in myotonics appears not to alter the pharmacological response to suxamethonium. Paterson (1962) gives the only description of generalized myotonia with suxamethonium. No muscular paralysis followed the periods of myotonia and he observed the most marked spasm
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 28, 2015
The common feature, myotonia, consists of delayed relaxation of skeletal muscle following contraction. Myotonia may be elicited by voluntary contraction, mechanical stimulation (such as tapping of the muscle), electrical stimulation of nerve or muscle, and chemical stimulation by altered electrolyte concentrations. Aggravation of the myotonia occurs with cold and emotion. The site of the defect appears to be beyond the neuromuscular junction in the muscle fibre itself. Mechanical myotonia is uninfluenced by spinal anaesthesia (Grund, 1919), nerve block or section, curare or decamethonium (Geshwind and Simpson, 1955). Raised serum potassium concentration and neostigmine are claimed to increase the myotonic response in humans (Kennedy and Wolf, 1937), although Landau (1952) detected no significant change with neostigmine. Ether, despite its muscle-relaxing properties, was reported to cause irregular respiration and troublesome general muscular spasm in a case of myotonia congenita (Johnson and Marshall, 1915). Myotonia may cause respiratory distress by spasm of respiratory muscles, particularly following depolarizing relaxants, while persistent spasm of abdominal muscles due to reflex straining or forcible retraction may interfere with surgery. In the treatment of myotonia, Leyburn and Walton (1959), by comparing quinine, prednisone, and procaine amide, found that the last two were equally effective, and better than quinine in relieving myotonia.
after bis third and largest dose. Respiration had returned between successive doses. He pointed out that this reaction occurred in a case of myotonia congenita with minimal myotonic symptoms, whereas Kaufman (1960) had thought suxamethonium spasm more likely if myotonia was clinically marked. (That generalized myotonia can occur when clinical symptoms are localized may be an interesting illustration of total voluntary muscle involvement by the genetic abnormality.) Despite the difficulty in achieving intubation reported by Haley (1962) in relation to the second patient, the author stated that "the response to depolarizing relaxants in this series was entirely unremarkable". Cobham and Davis (1964) administered suxamethonium to their patient because of troublesome abdominal muscle spasm under a sensory epidural block. In view of this evidence of the presence of myotonia, they found the behaviour of their patient "unexpected and puzzling", thinking myotonia more likely than relaxation, and concluding that this was an atypical response to suxamethonium. In none of these cases was there any mention of current medical treatment for the myotonia at the time the patients came to surgery. At this hospital, twelve cases of dystrophia myotonica have been admitted during the last three years. Five of them underwent surgery. Of these, two received an inhalation anaesthetic, one was intubated uneventfully under suxamethonium but did not develop his first myotonic symptoms until five months later, another showed no evidence of myotonia with 150 mg of suxamethonium, and no anaesthetic record is available for the other. From these reports die following points emerge: (1) Myotonic spasm, both local and generalized, has followed the administration of depolarizing relaxants. (2) Suxamethonium has elicited a normal response in myotonics, and has been used to provide prolonged satisfactory relaxation. (3) Suxamethonium has been used to terminate myotonic spasm. (4) A relationship may exist between dosage and severity of spasm in any one patient.
817
THE MYOTONIC RESPONSE TO SUXAMETHONIUM TABLE I
Reported effects of depolarizing relaxant* m myotonia. Author
Diagnosis and response
Bourke and Zuck, 1957
Suxamethonium 50 mg
Dystrophia myotonica. Normal relaxation.
Talmadge and McKechnie, 1959
Suxamethonium 40 mg
Dystrophia myotonica. Easy intubation, generalized spasm as respiration returned. Spasm relieved by suxamethonium 10 mg. "Optimal" relaxation maintained.
10 m g x 2 0.2% infusion Total dose 160 mg Richardson, 1959
Decamethonium
Myotonic spasm with respiratory distress.
Kaufman, 1960
Suxamethonium Suxamethonium 30 mg
Dystrophia myotonica. Uneventful. Dystrophia myotonica. Myotonia of hands for 1 minute. No suggestion of myotonia of respiratory muscles. Dystrophia myotonica. Normal response. Dystrophia myotonica. Normal response.
Intermittent suxamethonium Suxamethonium Paterson, 1962
Suxamethonium 50 mgX2
Myotonia congenita. Generalized myotonia without fasciculation with each dose. Duration about 3 minutes. Unable to inflate during spasm.
75 mg Haley, 1962
Suxamethonium infusion 0.2% Suxamethonium 60 mg Repeat 40 mg Suxamethonium 260 mg for induction Suxamethonium infusion 0.1% Total dose 1300 mg
Cobham and Davis, 1964
Suxamethonium 40 mg Suxamethonium infusion 250 mg
Dystrophia myotonica. Normal response, postoperative muscle spasm. Same patient. Normal response. Dystrophia myotonica. No fasciculation, inadequate relaxation, unable to extend neck, jaw not relaxed, numerous attempts at intubation. Good relaxation. Treated as dual block at end of operation.
Dystrophia myotonica. Abdominal muscle spasm relieved by suxamethonium with typical brief period of relaxation, easy intubation. Good relaxation. Treated as dual block at end of operation.
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Drug
818
FIG. 1 Patient described in report: myotonia congenita.
upper limb reflexes and normal lower limb reflexes. No myotonia could be demonstrated. No deterioration in muscle status was observed over the 2$ years. Radiographs of skull, hands and feet, barium swallow and electrocardiogram were all normal. He was thought to have an apparently non-progressive familial muscular dystrophy with some pseudohypertrophic features. In August 1965 he underwent right cervical sympathectomy. Premedication consisted of hyoscine 0.4 mg, papaveretum 20 mg. Anaesthesia was induced using thiopentone 400 mg and this was followed by suxamethonium 100 mg. Within a minute generalized
myotonic spasm developed without prior fasciculation. His facial muscles were contracted, his jaw was immovable. The limbs were flexed, the abdomen rigid, and the spine and neck slightly arched. The state of myotonia persisted but inflation with oxygen by facepiece expanded the upper chest and sufficed to maintain pulse and colour. His jaw could be opened a little after about 2 minutes but intubation was impossible. Because of doubt that suxamethonium had in fact been given, a further 50 mg dose was injected, but did not lead to any apparent change in his condition. Inflation was continued until intubation became possible about 4 minutes after the first injection. After several inflations strong spontaneous respiration recommenced. Anaesthesia was subsequently maintained uneventfully using nitrous oxide, oxygen, and halothane 1 per cent. Slow fasciculation was noted in his exposed neck muscles during surgery. Postoperatively he had no muscle pains or other complaints. The right hand became warm and dry. Further enquiry into his symptoms revealed tightness and knotting of limb muscles with resultant weakness during exertion. This dated from the time when he first walked as an infant, and was said to be worse in cold weather, particularly in his fingers. It prevented him from engaging in sports. Myotonia was demonstrable only in his eyelids. When this patient returned for a left cervical sympathectomy, an attempt was made to demonstrate the effects of sustained administration of suxamethonium. Further investigations were made into dose-response relationships, and into the effects of repeated doses at intervals sufficient for complete recovery of muscle function to take place. Second anaesthetic. Premedication: papaveretum 20 mg, hyoscine 0.4 mg. 8.45 a.m.: induction with thiopentone 350 mg. A normal apnoeic pause was followed by resumption of quiet breathing. Anaesthesia was deepened with nitrous oxide, oxygen and halothane by facepiece. The cords were sprayed with 4 per cent lignocaine. 9.00: easy intubation with a cuffed tube. Halothane was turned off and anaesthesia maintained with nitrous oxide, oxygen, and pethidine 15 mg intravenously. 9.17: 0.2 per cent suxamethonium infusion was started at 40 drops/min. 9.20: spasm appeared without fasciculation in the face, eyelids, jaw, abdominal wall, and limbs. Breathing continued with diminished excursion. 9.21: infusion rate increased to 60 drops/min. This caused a sharp increase in the strength of spasm and shallower respiration. 9.22: infusion rate reduced to 40 drops/min. The spasm subsided until by 9.24 it involved only the hands and limbs. 9.25: a single dose of 30 mg of suxamethonium caused, within 30 seconds, a strong generalized spasm with flexed limbs, tight jaw and eyelids, rigid abdomen and apnoea. The lungs were easily inflatable. No fasciculation was observed. 9.27: the spasm decreased and the infusion was increased to 60 drops/min. 9.29: shallow breathing between inflations, relaxed in all but arms and feet. 9.30: infusion increased to 120 drops/min. 9.31: breathing shallow, musculature relaxed. 9.33: apnoeic, flaccid relaxation. A further rapid
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CASE REPORT A man, aged 24, weighing 142 lb. (fig. 1), sought treatment in November 1962 for chronic palmar and plantar hyperhidrosis with dyshidriotic eczema. In July 1965 bilateral cervical sympathectomy was recommended. His history included stiffness and non-progressive weakness of ringers and upper and lower limbs, occasional dysphagia associated with the limb stiffness, mild myotonia; and congenital squint without diplopia. On examination he was found to have myopathic facies and convergent right strabismus, normal lens, pupils, and fundi, average-sized testes, well developed but slightly weak sternomastoids, well developed trunk and proximal limb muscles, cold moist small hands with poorly developed intrinsic muscles and a weak grip, absent
BRITISH JOURNAL OF ANAESTHESIA
THE MYOTONIC RESPONSE TO SUXAMETHONIUM
throughout the muscle mass. It seems reasonable to suggest that in those myotonic subjects who "fasciculate", the individual muscle fibres respond, not by a brief but by a prolonged or myotonic contraction. As a result, there is rapid progressive involvement of whole muscles into the state of spasm described. Normal relaxation after a single dose of suxamethonium in a patient with myotonia may, on the other hand, represent an absent or minimal fasciculation response. Harrison (1965) points out that minor localized fasciculation is easily overlooked, and it is quite possible that an unremarked DISCUSSION minor fasciculation-induccd myotonia occurred in The myotonic episodes in this patient were attri- some of the patients reported in table I. Normal buted directly to the action of suxamethonium, fasciculation has not been reported after suxameand from the observations made during the second thonium in any myotonic. One might anticipate, anaesthetic the following conclusions are drawn: then, that sustained administration of suxamethon(1) Myotonic spasm precipitated by suxameth- ium would result in normal neuromuscular block onium was not prolonged by continued action of and relaxation as soon as the intrinsic muscle this drug. The spasm subsided over a few minutes contraction subsided. This was demonstrated in to reveal an apparently normal depolarizing block the case report, and Haley's report of his second with full muscle relaxation. case might also be interpreted as supporting this. (2) After single doses, the relaxation time of The unusual type of fasciculation seen in the the myotonic muscle exceeded the time normally pectoral muscles with the last dose of suxamerequired for enzymatic destruction of suxameth- thonium, provides two additional points in favour onium. In consequence, no period of apnoeic of the theory that myotonic spasm is a conrelaxation followed the myotonia. sequence of muscle fasciculation peculiar to this (3) Small doses of suxamethonium caused less abnormal muscle. First it indicates that this subpronounced spasm than large doses. ject is one whose muscles fasciculate in response (4) Myotonic spasm returned with doses of to suxamethonium. Second, the slightly prolonged suxamethonium given subsequent to return of contractions noted during fasciculation in this muscle function (in Paterson's case, the interval portion of muscle support the idea that myotonic was little more than that required for return of spasm represents summation through delayed respiration). relaxation of fasciculant contractions. Harrison Kaufman (1960) thought suxamethonium might (1965) has shown that visible fasciculation can aggravate myotonia by the elevation in serum recur with a second dose of suxamethonium at potassium shown to occur in animals by Paton intervals as short as 3 or 4 minutes after return of (1956). The timing of this effect and myotonic muscle function. This would explain the recureffect of decamethonium combine against this rence of myotonic spasm at the short intervals theory. reported in Paterson's case. Suxamethonium and decamethonium have the common effect of precipitating muscle fascicula- Implications for anaesthetic management. tion during the initial endplate depolarization. The response of myotonic patients to depolarizThis occurs in varying degree and is clinically ing relaxants is unpredictable. The degree of visible only in a proportion of normal subjects clinical myotonia or type of disease is, apparently, with suxamethonium and more rarely with deca- no guide. These relaxants are best avoided because methonium. It represents the visible, transient, of potential respiratory muscle spasm and conand scattered contractions of small groups of sequent anoxia. The use of non-depolarizing muscle fibres as progressive depolarization spreads relaxants is not contraindicated, being mindful of
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dose of suxamethonium 30 mg given now was without visible effect. 9.36: infusion stopped. 9.40: full respiration at 12 b.pjn. Left cervical sympathectomy and sternomastoid biopsy were performed under nitrous oxide, oxygen and halothane 1 per cent. Muscle fasciculation in the sternomastoid due to surgical stimulation was again seen. 10.35: halothane turned off. End of operation. At 10.45 a further rapid dose of suxamethonium 30 mg caused, after 30 seconds, a generalized spasm lasting 90 seconds. During the latter 60 seconds, coarse slowlyrelaxing fasciculation was observed in the pectoral muscles. The patient was extubated and woke at 11.00 a.m. The total dose of suxamethonium was 290 mg.
819
820
BRITISH JOURNAL OF ANAESTHESIA
The question of diagnosis. In this patient firm diagnosis was rendered difficult, despite the probable clinical diagnosis of myotonia congenita, by the results of electromyography and muscle biopsy. The opinion expressed on electromyographic sampling of each abductor pollicis brevis stated: "There is a definite myotonia and the appearances on muscle contraction suggest the presence of myopathy: the diagnosis is probably dystrophia myotonica." Muscle biopsy showed changes present "more in favour of myotonic dystrophy than of myotonia congenita". His family history is important (fig. 2). He is the third eldest of the brothers, all of whom have well developed musculature. The age of onset and nature of the disorder is similar in all affected members. The normal sisters are very athletic.
FIG. 2 Family genetic incidence. = patient,n =male, O=female, cross-hatched=affected.
There is no family history of cataract or baldness. None have had an anaesthetic or operation, or have ever sought medical diagnosis or treatment for their disability. It was thought worth while to notify members of the family (some of whom live interstate or abroad) of the diagnosis of myotonia, and of the importance of acquainting surgeon and anaesthetist with their condition pre-operatively. ACKNOWLEDGEMENTS
I wish to thank Dr. D. Friend and Dr. K. Hayes, whose patient this was, for their co-operation and help. My appreciation is offered to Dr. M. Eadie, Dr. Ruth Molphy, and Dr. Beric Jackson for their encouragement and advice. Permission to publish details of patient records was kindly granted by Dr. A. D. D. Pye. REFERENCES
Bourke, T. D., and Zuck, D. (1957). Thiopentone in dystrophia myotonica. Brit. J. Anaesth., 29, 35. Caughey, J. E., and Myrianthopoulos, N. C. (1963). Dystrophia Myotonica and Related Disorders. Springfield: Thomas. Cobham, I. G., and Davis, H. S. (1964). Anesthesia for muscle dystrophy patients. Anesth. Analg. Curr. Res., 43, 22. Geshwind, K, and Simpson, J. A. (1955). Procaine amide in the treatment of myotonia. Brain, 78, 81. Grund, G. (1919). Ueber myokymbche Kontraktur. Dtsch. Z. Nervenheilk., 64, 102. Haley, F. C. (1962). Anaesthesia in dystrophia myotonia. Canad. Anaesth. Soc. J., 9, 270. Harrison, G. A. (1965). The incidence of visible muscular fasciculations following a second dose of suxamethonium chloride. Brit. J. Anaesth., 37, 129. Johnson, W., and Marshall, G. (1915). Observations on Thomsen's disease. Quart. J. med., 8, 114. Kaufman, L. (1960). Anaesthesia in dystrophia myotonica. Proc. roy. Soc. Med., 53, 183. Kennedy, F., and Wolf, A. (1937). Experiments with quinine and prostigmin in treatment of myotonia and myasthenia. Arch. Neurol. Psychiat. {Chicago), 37, 68. Landau, W. M. (1952). The essential mechanism in myotonia: an electromyographic study. Neurology (Aftnneap.), 2, 369. Leyburn, P., and Walton, J. M. (1959). The treatment of myotonia. Brain, 82, 81. Paterson, I. S. (1962). Generalized myotonia following suxamethonium. Brit. J. Anaesth., 34, 340. Paton, W. D. M. (1956). Mode of action of neuromuscular blocking agents. Brit. J. Anaesth., 28, 475. Richardson, A. T. (1959). Personal communication to Kaufman, L. Talmadge, E. A., and McKechnie, F. B. (1959). Anesthetic management of patient with myotonia dystrophica. Anesthesiology, 20, 717.
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the importance of adequate reversal in the presence of muscular wasting and weakness. If suxamethonium is used, an initial test dose of 5 mg might be expected, by any evidence of minor spasm, to indicate the likelihood of major spasm with a paralyzing dose. Pre-operative procaine amide should reduce relaxation time towards normal, and seems a desirable part of preparation for surgery in these patients. Intravenous hydrocortisone may be effective in the relief of myotonia during surgery, without the dangerous side effects of intravenous procaine amide. Halothane poses one potential disadvantage, in that the shivering and rigidity often seen postoperatively, might well precipitate dangerous myotonia.
THE MYOTONIC RESPONSE TO SUXAMETHONIUM
821
DIE MYOTONISCHE REAKTION AUF SUXAMETHONIUM
LA REACTION MYOTONIQUE AU SUXAMETHONIUM
ZUSAMMENFASSUNG
In einer Ubersicht iiber die beschriebenen Reaktionen von Patienten mit Myotonie auf depolarisierende Relaxantien wird das unterschiedliche Auftreten und der Umfang einer kiinstlich ausgelosten Myotonie aufgezeigt. An einem Patienten mit Myotonie congenita wird eine generalisierte Myotonie nach Verabreichung von Suxamethonium beschrieben. SpStere Untersuchungen wahrend einer zweiten Operation erklaren die Wirkungsweise der Substanz. Eine solche myotonischc Reaktion wird fascilcularen Kontraktionen zugeschrieben. Bei fortgesetzter Verabreichung des Mittels liefi sich eine normale Depolarisationsblockade nachweisen. Vorschlage zur Durchfuhrung der Narkose bei solchen Patienten werden gemacht.
GLASGOW AND WEST OF SCOTLAND SOCIETY OF ANAESTHETISTS 1968
Syllabus 1967-68
TUESDAY, JANUARY 9
Symposium on Neuroleptanalgesia.
1967
DR.
SHEILA
JENNETT,
University
of
Glasgow. DR. C. PRYS-ROBERTS, University of
SATURDAY, OCTOBER 21 (5.15 pjn.)
Joint meeting in Glasgow with Edinburgh and East of Scotland Society of Anaesthetists. "Myasthenia Gravis and the Anaesthetist." PROF.
J.
A.
SIMPSON,
University
Glasgow.
of
Oxford. DR.
G.
BARRY
SMITH,
The
London
Hospital. MONDAY, FEBRUARY 12
Members' Night. Staff of Department of Anaesthetics, Killearn Hospital. MONDAY, MARCH 18
Presidential Address. DR. A. HARVEY GRANAT. MONDAY, APRIL 1
Annual General Meeting.
TUESDAY, DECEMBER 5
"The Physiology of Pain." DR. J. CLUTTON-BROCK, Bristol.
SATURDAY, APRIL 6
Visit to Falkirk and District Royal Infirmary.
Unless shown otherwise, meetings will be held at the Royal College of Physicians and Surgeons, 242 St. Vincent Street, at 8.15 pjn. Tea will be served from 7.45 p.m. Notice of each meeting will be sent to members.
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SOMMAIRE
Un aprrcu dcs reactions rapportees chez des patients myotoniques qui avaient recu des relachants dipolarisants, revile l'incidence et l'etendue variables de la myotomie causee. Une myotonie generalisee, due au suxamethonium, a etc decrite chez un patient avec myotonie congenitale, et l'action du medicament a iti mise en evidence par des Etudes au cours d'une seconde operation. Une reaction myotonique pareille est attribute a une fasciculation, et un block d£polarisant normal a etc demontrf sous administration continue du medicament. Certaines suggestions pour l'anesthesic de pareils patients sont avancees.