SUXAMETHONIUM AND MHS MUSCLE

SUXAMETHONIUM AND MHS MUSCLE

BRITISH JOURNAL OF ANAESTHESIA 596 P. J. DUNBAR Spokane REFERENCES 1. Wildsmith JAW. Intrathecal or extradural: which approach for surgery? British...

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BRITISH JOURNAL OF ANAESTHESIA

596

P. J. DUNBAR

Spokane REFERENCES 1. Wildsmith JAW. Intrathecal or extradural: which approach for surgery? British Journal of Anaesthesia 1987; 59: 397-398. 2. Di Fazio CA, Carron H, Grosslight KR. Comparison of pH-adjusted lidocaine solutions for epidural anesthesia. Anesthesia and Analgesia 1986; 65: 760-764. 3. Flatten H, Rodt S, Rosland JV. Postoperative headaches in young patients after spinal anaesthesia. Anaesthesia 1987; 42: 202-205.

SUXAMETHONIUM AND MHS MUSCLE Sir,—Results of an interesting study from Dr Denborough's laboratory [1] produced a conclusion that pure suxamethonium chloride does not induce in vitro contracture of muscle from malignant hyperthermia susceptible (MHS) pigs. In a most convincing way, the study provided evidence to show that concentrations of preservatives contained in commercial preparations of suxamethonium were capable of producing the contracture effects previously ascribed to suxamethonium applied to human [2] and pig [3] MHS muscle. Our laboratory is an MH diagnostic and research unit with considerable experience with in vitro contracture testing of human (> 250) and pig (> 200) skeletal muscle. Recently, we have re-initiated studies on the use of suxamethonium for in vitro diagnostic contracture testing for MHS. Among five MHS human patients with phenotype H [4] diagnosis, two had muscle that produced contracture responses to in vitro application of suxamethonium 50 mmol litre"1 or less, prepared from crystalline material purchased from Sigma Chemical, U.S.A. (fig. 1). These two patients (A and B, figure 1) are brothers and their mother's muscle, also phenotype H, was not exposed to suxamethonium 50 mmol litre"1, but did have 0.25-g contracture when exposed to suxamethonium 5 mmol litre"1. The other three MH patients are not related. Gracilis

rrn±H FIG. 1. Suxamethonium (Sux.)-induced in vitro contracture of MHS human skeletal muscle. In patient A, three different muscle fascicles were exposed to suxamethonium 2, 10 and 50 mmol litre"1 at arrows indicated by 1 under each panel. After the suxamethonium contracture, 3% halothane was bubbled through the muscle bath, and contracture occurred in each fasicle. Patient B, brother of patient A, had a contracture response to suxamethonium 50 mmol litre"1 alone that was relatively large and not totally reversed. Two other fascicles from patient B responded similarly to addition of suxamethonium 50 mmol litre"1.

muscle biopsied from four MHS, phenotype H pigs also had in vitro contracture response to suxamethonium 50 mmol litre"1 and a typical response is illustrated in figure 2. The contracture responses observed in pigs differed from those in MHS human muscle in that two phases occurred (fig. 2). Immediately after application of suxamethonium, the MHS pig muscle produced a contracture with rapid onset and relatively fast reversal. This contracture phase was then followed by a second contracture with slower onset and without reversal during the observed time before halothane was added (fig. 2). It is tempting to speculate that the initial contracture is related to the primary depolarizing effect of suxamethonium, and the second contracture is produced by some other suxamethonium effect. Galloway and Denborough [1] state that motor end-plates do not exist in bundles of muscle fibres and quote a reference [5] that does not support such a notion. Even though these in vitro muscle preparations are directly stimulated, it is possible that some indirect nerve stimulation can be contributory, albeit only to a small percentage. It is possible, as suggested by the authors, that in vivo, the muscle activating effect of suxamethonium during depolarization could initiate events producing the abnormal release of Ca8+ in MHS muscle. A similar mechanism could be occurring in vitro or suxamethonium could have a secondary

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5 and 15 min) and adequate duration for the outpatient orthopaedic proceedures that we are undertaking. We have also administered carbonated mepivacaine with adrenaline which has been adequate for 2 h or more of surgery before a further dose. We have noted that, using extradural blockade, tourniquet pain appears to be less of a problem than in patients who have intrathecal block. In addition, a percentage of patients having intrathecal blockade have delayed discharge from the outpatient unit as a result of difficulty in urination, whereas this appears to be less of a problem with extradural blocks. In summary, we have evolved a regimen of using extradural block for individuals who are younger than 40 years or so, and reserve subarachnoid block for subjects in the middle and later years of life, when the incidence of spinal headache is much lower [3] and the technical difficulty of obtaining satisfactory extradural block is greater. We feel that 2 % mepivacaine is an ideal agent for extradural use and one which has a very rapid onset when used with bicarbonate, and a low rate of complications. In addition, the extradural route has a greater degree of acceptability with some patients as there appears to be a considerable number of individuals who feel reassured that they are not having a ' spinal' anaesthetic!

CORRESPONDENCE

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effect on skeletal muscle that contributes to the abnormal response in MHS muscle. Further studies are needed to clarify these effects of suxamethonium on MHS muscle. The impact of genetic influences should also be considered, as not all MHS muscle treated in vitro responds abnormally to suxamethonium. It may also be that the MH susceptibility of the animals used in Galloway and Denborough's study differed from those used by us. Finally, the 50-mmol litre"1 concentration of suxamethonium used in this study is far in excess of clinical concentrations. Therefore, we do not know if the contractures observed are relevant to actions of the drug under clinical usage. However, halothane, which potentiates the contracture effects of suxamethonium in vitro, or some other potent inhalation anaesthetic probably augments the in vivo effects of suxamethonium, since the agents are usually present together in clinical usage. T. E. NELSON

Galveston REFERENCES 1. Galloway GJ, Denborough MA. Suxamethonium chloride and malignant hyperpy rexia. British Journal of Anaesthesia 1986; 58: 447. 2. Moulds RFW, Denborough MA. Identification of susceptibility to malignant hyperpyrexia. British Medical Journal 1974; 2: 245. 3. Okumura F, Crocker BD, Denborough MA. Identification of susceptibility to malignant hyperpyrexia in swine. British Journal of Anaesthesia 1979; 51: 171. 4. Nelson TE, Flewellen EH, Gloyna DF. Spectrum of susceptibility to malignant hyperthermia—diagnostic dilemma. Anesthesia and Analgesia 1983; 62: 545. 5. Gronert GA, Theye RA. Pathophysiology of hyperkalemia induced by succinylcholine. Anesthesiology 1975; 43: 88.

LIFE-THREATENING REACTION TO ATRACURIUM Sir,—In medicine it is perhaps unwise always to accept advice appearing in the journals. The June 1987 edition of the British Journal of Anaesthesia contained the following statements: "modification in anaesthetic technique based on a history of

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FIG. 2. Suxamethonium (Sux.)-induced in vitro contracture of MHS pig skeletal muscle. At arrow 1, suxaraethonium 50 mmol litre"1 produced a small contracture that was rapidly reversed, and a slower tonic contracture followed. At arrow 2, addition of 3 % halothane produced an additional large contracture.

allergy, atopy or asthma is unlikely to reduce the likelihood of severe clinical anaphylaxis" [1]; and "provided due care is taken to avoid mixing of drugs, atracurium may be used in patients with a history of asthma or allergic reactions" [2]. I wish to report a severe reaction to atracurium in a patient with a history of asthma and atopy. A 21-year-old, 60-kg female was admitted with a 2-week history of lower abdominal pain and vaginal bleeding. An ultrasound examination suggested a possible ectopic pregnancy. There was no clinical suggestion of intra-abdominal bleeding. The patient gave a history of eczema and asthma from the age of 14 yr and used a salbutamol inhaler on an infrequent basis to treat acute attacks of bronchospasm. She had never been admitted to hospital with this condition. She had received general anaesthesia on two previous occasions, the first 9 years earlier for appendicectomy. On that occasion the following agents were used: thiopentone, alcuronium, morphine, nitrous oxide, halothane, neostigmine and atropine. The anaesthetic was uneventful. The second occasion was 2 years previously for a minor gynaecological procedure. She received thiopentone, nitrous oxide and halothane without recorded incident. On examination on the present admission, the patient was in good general health: heart rate 70 beat min"1, arterial pressure 120/60 mg Hg. Auscultation revealed normal breath sounds with no wheeze, even on forced expiration. She had last used her inhaler 3 days before this admission. Chest radiograph was normal. Premedication was diazepam 10 mg by mouth 1 h before coming to theatre. At that time the patient had been fasted for 8 h. She came to the anaesthetic room in a relaxed state. A 19-gauge cannula (Wallace Y-can) was inserted to a vein on the dorsum of the hand. Fentanyl 120 ug with droperidol 1 mg were injected and flushed through with saline. The lungs were preoxygenated for 3 min following this, with no apparent problem. At this time arterial pressure was 130/70 mm Hg, heart rate 75 beat min"1. Atracurium 35 mg was given over approximately a 10-s period. During this injection the patient coughed several times with a distinctive "barking cough". (Sale [3], Thompson [4] and Bowie [5] all noted this type of cough in patients who subsequently developed anaphylactoid reactions.) On completion of the injection of atracurium, propofol 150 mg was given through the same cannula. Ninety seconds after the administration of atracurium, laryngoscopy was performed and, in line with previous experience with this sequence of neuromuscular blocker-propofol, the vocal cords were widely abducted and intubation with an 8.5 Clearway tracheal tube did not provoke any coughing or movement. Attempted ventilation using a Mapleson A breathing system revealed severe bronchospasm. There was no possibility of tube obstruction. Systolic arterial pressure had decreased to 50 mm Hg, the ECG trace showed heart rate 90 beat min"1, sinus rhythm. Within 1 min, despite attempted hand ventilation with 100% oxygen, the patient had become cyanosed and her arterial pressure was unrecordable, with no palpable carotid pulses, although ECG showed a rate of 40 beat min"1. A working diagnosis of anaphylactic-anaphylactoid reaction was made and 6 ml of adrenaline 1:10000 was injected down the tracheal tube. At the same time as an internal jugular central line was inserted, hydrocortisone 400 mg and aminophylline 250 mg were given via the peripheral cannula through which Haemaccel was given under pressure. A further 4 ml of adrenaline 1:10000 was given via the central line in view of the lack of initial response to the above therapy. Attempted ventilation with 100% oxygen was continued throughout.