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Edrophonium-induced asystole following neuromuscular blockade antagonism in a dog: a case report
J. vet. Anaesth. Vol. 18 (1991)
Edrophonium-induced asystole following neuromuscular blockade antagonism in a dog: a case report R. E. Clutton and S. Petersen-Jones Royal (Dick) School of Veterinary Studies, Department of Veterinary Clinical Studies, Veterinary Field Station, Easter Bush, Roslin, Midlothian EH25 9RG, UK. SUMMARY Edrophonium was used to antagonise neuromuscular block in a healthy eight-year-old dog following ophthalmic surgery; this caused arrhythmias and asystole lasting 46 secs. The complication probably occurred because of inadequate muscarinic blockade prior to antagonism. The dog made an uneventful recovery.
INTRODUCTION Fatal cardiac arrest is a relatively rare complication of neuromuscular blockade antagonism in man, but has been reported (Clutton-Brock 1949; Hill 1949; Bain and Broadbent 1949; MacIntosh 1949). However, heart rate changes and arrhythmias are not infrequent at this time (Atlee 1985). This report describes cardiac arrest caused by edrophonium following its administration to reverse neuromuscular block in a dog.
CASEHISTORY AND CLINICAL FINDINGS An eight-year-old male Jack Russel Terrier weighing 10 kg was presented with bilateral cataracts. Clinical examination revealed no other abnormalities (resting heart rate was 72 beats/min) and so the dog was anaesthetised for bilateral extracapsular cataract extraction and intraocular lens implantation. For four days prior to surgery, eye-drops containing dexamethasone, polymixin B and neomycin (Maxitrol; Alcon Laboratories [UK] Ltd., Watford, Herts) were given four times daily; the patient was on no other medication.
TREATMENT AND COURSE OF CONDITION
British Oxygen Company, Harlow, Essex) and a fresh gas flow rate of 3 litres/min was used. Neuromuscular block was monitored using the train of four stimulus pattern applied to the ulnar nerve at the level of the olecranon. Relaxation was maintained at a 90 per cent level of blockade by the infusion of a vecuronium solution (10 pg/ml). Vital signs and the electrocardiogram (Lead 11) were monitored throughout anaesthesia. Anaesthesia during surgery was largely uneventful although, 10 mins after neuromuscular block was produced and immediately before ocular manipulation began, the heart rate fell from 70 to 58 beats/min. Sinus rhythm was present and although the lingual pulse was palpable, it was not strong. Atropine (40 pg/kg bwt) was injected iv and the heart rate increased to 110 beats/min. Neuromuscular block was reversed after 1 h 36 mins (86 mins after atropine injection) using edrophonium (Tensilon; Roche Products Ltd., Welwyn Garden City, Herts) given iv at 0.5 mg/kg bwt. The level of block at this time was 90 per cent, the heart rate was 68 beats/min and sinus rhythm was present. Injection was slow; the drug volume (0.5 ml) was diluted with 0.5 ml of blood and the resulting volume injected over 1 min. Sixteen secs after the end of injection the heart rate began to fall and although sinus complexes were present, the R-R interval became progressively greater. Electrical silence followed and because no pulse was palpable, asystole was diagnosed. Atropine (40 pg/kg bwt) was injected into the cephalic vein, halothane and nitrous oxide were discontinued and the ventilatory minute volume was doubled. The animal was positioned in right lateral recumbency in preparation for external cardiac compression, but after 46 secs of asystole, a single ventricular complex was seen. Electrical silence continued for an additional 5 secs but was followed by two atrioventricular nodal escape complexes and a solitary atrial depolarisation; signals indicating atrioventricular conduction blockade. Thereafter, the heart rate increased, reaching a maximum rate of 138 beats/min within 15 secs and stabilising at 98 beats/min. Spontaneous breathing began as soon as the ventilator was switched to manual mode and later the dog made an uneventful recovery from anaesthesia and surgery.
Anaesthetic pre-medication was with acepromazine maleate (ACP; C-Vet, Bury St. Edmunds, Suffolk) 0.05 mg/kg bodyweight (bwt) and buprenorphne (Temgesic; Reckitt & Colman, Hull, Yorkshire) 10 pg/kg bwt, given intramuscularly (im).Anaesthesia was induced with 60 mg thiopentone given intravenously (iv) 30 mins later. After endotracheal intubation, anaesthesia was maintained with halothane in a 2:l nitrous oxide-oxygen mixture. Fifteen DISCUSSION minutes after induction of anaesthesia (and before surgery began) neuromuscular block was produced by vecuronium Anti-cholinesterase drugs such as edrophonium and bromide (Norcuron-Organon Laboratories, Cambridge) neostigmine cause complex chronotropic and administered at 50 pg/kg bwt iv. Ventilation was dromotropic effects by inhibiting acetylcholinesterase controlled mechanically (Manley Pulmovent Model MPP; at four points in the autonomic efferent pathway to the 42
J. vet. Anaesth. Vol. 18 (1991) ~
heart. Principally, they increase acetylcholine levels at muscarinic (parasympathetic post ganglionic) a n d nicotinic (sympathetic and parasympathetic ganglionic, sympathetic pre-ganglionic-adrenomedullary) sites. At the nicotinic receptor, the action of acetylcholine is concentration dependant; low doses cause excitation whereas higher amounts exert an inhibitory action (Atlee 1985). Anticholinesterases also cause antidromic action potentials and repetitive firing in nerves (Blaber and Bowman 1963; Blaber 1972) probably by activating a positive feedback mechanism (Bowman, Marshall, Gibb and Harbourne 1988). Cholinergic stimulation of pre-synaptic nicotinic receptors increases t h e mobilisation and release of acetylcholine. Therefore, anti-cholinesterases can initiate a cycle in which released acetylcholine promotes its own liberation. In summary, anti-cholinesterase drugs can either increase or decrease heart rate although they usually cause bradycardia and bradyarrythmias due to muscarinic activation in cardiac conducting tissue. Arrhythmias have not been reported in dogs during the antagonism of neuromuscular block. In contrast, neostigmine and edrophonium have caused cardiac arrest in man (Bain and Broadbent 1949; Clutton-Brock 1949; Hill 1949; MacIntosh 1949; Lawson 1956; Youngberg 1979) a n d a r r h y t h m i a s a p p e a r t o be relatively common. Atropine a n d neostigmine combinations have caused atrioventricular dissociation, junctional rhythm, increased P-R interval, premature atrial contractions, ectopic beats, inverted P waves, wandering pacemaker a n d premature ventricular depolarisations (Ovassapian 1969; Mirakhur, Dundee and Clarke 1977; Ostheimer 1977). Several factors influence t h e arrhythmogenic potential of a n t i cholinesterases given at this time. Bradyarrhythmias are more likely when antagonists are injected rapidly (Ovassapian 1969; Harper et al 1984) and the risk of arrhythmias is higher than normal in patients receiveing P-adrenergic a n t a g o n i s t s (Sprague 1975; Seidl and Martin 1984) catecholamine depleting d r u g s (Youngberg 1979) a n d probably calcium-entry blockers (Atlee 1985). The pharmacokinetics of concurrently administered antimuscarinic drugs also affect the electrocardiogram during antagonism. When atropine (which has a rapid onset of action) is combined w i t h slower acting neostigmine, tachycardia, tachyarrythmias or both are like 1y. Converse 1y, combining e d r o p h o n iu m (rapid onset) with glycopyrrolate (slow onset) results in bradycardia (Azar et al1983). The problems in this case a r e consistent with muscarinic p r e p o n d e r a n c e caused by excessive edrophonium, inadequate atropine or both. However, they were unexpected for several reasons. First, the dose of e d r o p h o n i u m used lies within the range currently recommended for use in dogs; Muir and Hubbell suggest that 0.55 mg/kg bwt may be repeated up to five times, whereas others recommend 0.1 to 0.2 m g / k g bwt (Sawyer 1982). Second, muscarinic blockade was no longer present even though atropine had been given 86 mins previously. In unanaesthetised
d o g s , a t r o p i n e exerts a dose-related d u r a t i o n of vagolysis on sino-atrial a n d atrioventricular nodal tissue, with doses of 25 pg/kg bwt lasting at least 120 mins (Kantelip, Alatienne, Gueorrguiev and DucheneMarullaz 1985). In the present report, muscarinic blockade was clearly not maintained by the higher dose of 40 pg/kg bwt. This is all the more surprising because edrophonium has less cardiac muscarinic activity relative t o e q u i p o t e n t doses of neostigmine a n d pyridostigmine (Morris, Cronnelly and Miller 1981), is associated with a lower incidence of muscarinic sideeffects (Bevan 1979; Kopman 1979; Cronnelly, Morris and Miller 1982) and, compared with neostigmine, normally requires significantly lower doses of either atropine or glycopyrrolate to prevent bradycardia (Mirakhur 1985). Finally, the slow injection of anticholinesterase drugs minimises the risk of arrhythmias during antagonism (Ovassapian 1969; Harper ef a l 1984). In the present report, injection was made over 1 min and there was no indication of reduced circulation time (heart rate was 68 beats/min). Muscarinic preponderance was the likely cause of arrest in this patient and, retrospectively, the exclusion of muscarinic blockers was misjudged. However, the u s e of a t r o p i n e d u r i n g the antagonism of neuromuscular block is not without risk; cardiac arrest in man following the injection of atropine-neostigmine mixtures has been attributed to the summation of the cholinergic action of neostigmine and the initial central vagal stimulation of a t r o p i n e (Mirakhur 1977). Alternatively, Jones, Deutsch a n d Turndorf (1961) r e g a r d e d s u d d e n atropine-induced sympathetic predominance to be responsible for cardiac arrest at this time. When injected before neostigmine, atropine has caused serious tachycardia and arrythmias in man (Jones ef al 1961; Ovassapian 1969) and similar changes have been reported in dogs (Clutton et ~11991). The w i d e variation in d o s e s of e d r o p h o n i u m suggested for neuromuscular blockade reversal in dogs makes it difficult to give firm recommendations (Jones 1988). Presently, we use a mixture of atropine (20 pg/kg bwt) and edrophonium (250 pg/kg bwt) injected over 30 secs. If recovery is judged to be slow or incomplete, a second dose of edrophonium (250 pg/kg bwt) is given slowly after 3 mins. To date, this regime has not caused complications.
REFERENCES Azar, I., Pham, A. N., Karambelkar, D. J. and Lear, E. (1983) The h e a r t r a t e following e d r o p h o n i u m - a t r o p i n e a n d edrophonium-glycopyrrolate mixtures. Aiicsthrsiology 59, 139-141. Atlee, J. L. (1985) P e r i o p e r a t i i i c C n v d i n c D ~ y s ~ / i y t h ~ i i i ~ s : Mechnnisins, Rrcogrtition, Mniznginriit. Year Book Medical Publishers, Chicago. p 216. Bain, W. A. a n d Broadbent, J . L. (1949) Death following neostigmine. Br. med. J. 1, 1137. Bevan, D. R . (1979) Reversal of p a n c u r o n i u m w i t h edrophonium. Aiiuestlirsin 34, 614. Blaber, L. C. a n d Bowman, W. C . (1963) Studies on the
43
1. vet. Anaesth. Vol. 18 (1991) repetitive discharges evoked in ulnar nerve and skeletal muscle after injection of anti-cholinesterase drug. Br. J. Pharmacol. 9,326-344. Blaber, L. C. (1972) The mechanism of the facilitatory action of edrophonium in cat skeletal muscle. Br. J. Pharmacol. 46, 498-507. Bowman, W. C., Marshall, I. G., Gibb, A. J. and Harbourne, A. J. (1988) Feedback control of transmitter release at the neuromuscular junction. In: Trends in Pharmacological Sciences. Volume 9. Elsevier Publications, Cambridge. p 1620. Clutton, R. E., Boyd, C., Flora, R., Payne, J. and McGrath, C. J. (1991) Autonomic a n d cardiovascular effects of neuromuscular blockade antagonism in the dog. Vet. Surg. (In press). Clutton-Brock, J. (1949) Death following neostigmine. Br. rned. J. 1,1007. Cronnelly, R., Morris, R. B. a n d Miller, R. D. (1982) Edrophonium: duration of action a n d atropine requirement in humans during halothane anaesthesia. Anesthesiology 57,261. Harper, K. W., Bali, I. M., Gibson, F. W., Carlisle, R., Black, I. H. C., Grainger, D. J. and Dundee, J. W. (1984) Reversal of neuromuscular blockade: Heart rate changes with slow injection of neostigmine and atropine mixtures. Anaesthesia 39, 772-775. Hill, M. (1949) Death after neostigmine injection. Br. med. J. 2, 601. Jones, R. E., Deutsch, S. and Turndorf, H. (1961) Effects of atropine on cardiac rhythm in conscious and anaesthetised man. Anesthesiology 22,67. Jones, R. S. (1988) Reversal of neuromdscular blockade - a review. J. Ass. vet. Anaesth. 15,80-88. Kantelip, J. P., Alatienne, M., Gueorguiev, G. and DucheneMarullaz, P. (1985) Chronotropic and dromotropic effects of atropine and hyoscine methobromide in unanaesthetised dogs. Br. J. Anaesth. 57,214-219.
F
Kopman, A. F. (1979) Edrophonium antagonism of pancuronium induced neuromuscular blockade in man: A reappraisal. Anesthesiology 51, 139-142. Lawson, J . J . (1956) Cardiac arrest following the administration of neostigmine. Br. J. Anaesth. 28,336. MacIntosh, R. R. (1949) Death following injection of neostigmine. Br. rned. J. 1,852. Mirakhur, R. K., Dundee, J. W. and Clarke, R. S. J. (1977) Glycopyrrolate-neostigmine mixture for antagonism of neuromuscular block: comparison with atropineneostigmine mixture. Br. J. Anaesth. 49,825-829. Mirakhur, R. K. (1985) Antagonism of the muscarinic effects of edrophonium with atropine or glycopyrrolate Br. J. Anaesth. 57, 1213-1216. Morris, R. B., Cronnelly, r. and Miller, R. D. (1981) Atropine requirement for edrophonium. Anesthesiology 55, A206. Muir, W. W., Hubbell, J. A. E. (1985) Handbook of Veterinary Anaesthesia. The C.V. Mosby Company. pp 108-117. Ostheimer, G. W. (1977) A comparison of glycopyrrolate and atropine d u r i n g reversal of nondepolarising neuromuscular block with neostigmine. Anesth. Analg. 56, 182-186. Ovassapian, A. (1969) Effects of administration of atropine and neostigmine in man. Anest. Analg. 48,219-223. Sawyer, D. (1982) The Practice of Small Animal Anesthesia. W. B. Saunders, Philadelphia. p 112. Seidl, D. C. and Martin, D. E. (1984) Prolonged bradycardia after neostigmine administration in a patient taking nadolol. Anesth. Analg. 63,365-367. Sprague, D. H. (1975) Severe bradycardia after neostigmine in a patient taking propranolol to control paroxysmal atrial tachycardia. Anesthesiology 42,208-210. Youngberg, J. A. (1979) Cardiac arrest following treatment of paroxysmal atrial tachycardia with edrophonium. Anesthesiology 50,234-235.
ASSOCIATION OF VETERINARY ANAESTHETISTS The aim of the Association of Veterinary Anaesthetists is to promote the study and research of anaesthesia in animals and to disseminate the results thereof to the public. To further this aim we hold regular meetings and conferences and publish the Journal of Veterinary Anaesthesia. We also are keen to promote collaboration between anaesthetists all over the world and actively encourage the establishment of diplomas and degrees in veterinary anaesthesia. The Association typically holds a 2-day meeting twice a year; one in the Spring, the other in Autumn. The programmes are varied, offering papers for a wide range of interests. The membership includes veterinarians in general practice a s well a s specialist veterinary anaesthetists, university teachers, medical anaesthetists, and scientists all with a common interest in veterinary anaesthesia and related subjects. Although based in Great Britain, we have a large membership in Europe, the North American Continent and the Antipodes. The association welcomes new members. Application forms are available from the Hon. Secretary, Dr. Andrea Nolan, Department of Veterinary Pharmacology, University of Glasgow, Bearsden Road, Glasgow G61 1QH. 1991 subscriptions: AVA members - €15 (membership includes copy of journal) Individual subscriber - €15 or €25 inc. p. & p. Library subscription - €22 or €45 inc. p. & p . (same for U.K. or foreign) 44
Edrophonium-induced asystole following neuromuscular blockade antagonism in a dog: a case report R. E. Clutton and S. Petersen-Jones Royal (Dick) School of Veterinary Studies, Department of Veterinary Clinical Studies, Veterinary Field Station, Easter Bush, Roslin, Midlothian EH25 9RG, UK. SUMMARY Edrophonium was used to antagonise neuromuscular block in a healthy eight-year-old dog following ophthalmic surgery; this caused arrhythmias and asystole lasting 46 secs. The complication probably occurred because of inadequate muscarinic blockade prior to antagonism. The dog made an uneventful recovery.
INTRODUCTION Fatal cardiac arrest is a relatively rare complication of neuromuscular blockade antagonism in man, but has been reported (Clutton-Brock 1949; Hill 1949; Bain and Broadbent 1949; MacIntosh 1949). However, heart rate changes and arrhythmias are not infrequent at this time (Atlee 1985). This report describes cardiac arrest caused by edrophonium following its administration to reverse neuromuscular block in a dog.
CASEHISTORY AND CLINICAL FINDINGS An eight-year-old male Jack Russel Terrier weighing 10 kg was presented with bilateral cataracts. Clinical examination revealed no other abnormalities (resting heart rate was 72 beats/min) and so the dog was anaesthetised for bilateral extracapsular cataract extraction and intraocular lens implantation. For four days prior to surgery, eye-drops containing dexamethasone, polymixin B and neomycin (Maxitrol; Alcon Laboratories [UK] Ltd., Watford, Herts) were given four times daily; the patient was on no other medication.
TREATMENT AND COURSE OF CONDITION
British Oxygen Company, Harlow, Essex) and a fresh gas flow rate of 3 litres/min was used. Neuromuscular block was monitored using the train of four stimulus pattern applied to the ulnar nerve at the level of the olecranon. Relaxation was maintained at a 90 per cent level of blockade by the infusion of a vecuronium solution (10 pg/ml). Vital signs and the electrocardiogram (Lead 11) were monitored throughout anaesthesia. Anaesthesia during surgery was largely uneventful although, 10 mins after neuromuscular block was produced and immediately before ocular manipulation began, the heart rate fell from 70 to 58 beats/min. Sinus rhythm was present and although the lingual pulse was palpable, it was not strong. Atropine (40 pg/kg bwt) was injected iv and the heart rate increased to 110 beats/min. Neuromuscular block was reversed after 1 h 36 mins (86 mins after atropine injection) using edrophonium (Tensilon; Roche Products Ltd., Welwyn Garden City, Herts) given iv at 0.5 mg/kg bwt. The level of block at this time was 90 per cent, the heart rate was 68 beats/min and sinus rhythm was present. Injection was slow; the drug volume (0.5 ml) was diluted with 0.5 ml of blood and the resulting volume injected over 1 min. Sixteen secs after the end of injection the heart rate began to fall and although sinus complexes were present, the R-R interval became progressively greater. Electrical silence followed and because no pulse was palpable, asystole was diagnosed. Atropine (40 pg/kg bwt) was injected into the cephalic vein, halothane and nitrous oxide were discontinued and the ventilatory minute volume was doubled. The animal was positioned in right lateral recumbency in preparation for external cardiac compression, but after 46 secs of asystole, a single ventricular complex was seen. Electrical silence continued for an additional 5 secs but was followed by two atrioventricular nodal escape complexes and a solitary atrial depolarisation; signals indicating atrioventricular conduction blockade. Thereafter, the heart rate increased, reaching a maximum rate of 138 beats/min within 15 secs and stabilising at 98 beats/min. Spontaneous breathing began as soon as the ventilator was switched to manual mode and later the dog made an uneventful recovery from anaesthesia and surgery.
Anaesthetic pre-medication was with acepromazine maleate (ACP; C-Vet, Bury St. Edmunds, Suffolk) 0.05 mg/kg bodyweight (bwt) and buprenorphne (Temgesic; Reckitt & Colman, Hull, Yorkshire) 10 pg/kg bwt, given intramuscularly (im).Anaesthesia was induced with 60 mg thiopentone given intravenously (iv) 30 mins later. After endotracheal intubation, anaesthesia was maintained with halothane in a 2:l nitrous oxide-oxygen mixture. Fifteen DISCUSSION minutes after induction of anaesthesia (and before surgery began) neuromuscular block was produced by vecuronium Anti-cholinesterase drugs such as edrophonium and bromide (Norcuron-Organon Laboratories, Cambridge) neostigmine cause complex chronotropic and administered at 50 pg/kg bwt iv. Ventilation was dromotropic effects by inhibiting acetylcholinesterase controlled mechanically (Manley Pulmovent Model MPP; at four points in the autonomic efferent pathway to the 42
J. vet. Anaesth. Vol. 18 (1991) ~
heart. Principally, they increase acetylcholine levels at muscarinic (parasympathetic post ganglionic) a n d nicotinic (sympathetic and parasympathetic ganglionic, sympathetic pre-ganglionic-adrenomedullary) sites. At the nicotinic receptor, the action of acetylcholine is concentration dependant; low doses cause excitation whereas higher amounts exert an inhibitory action (Atlee 1985). Anticholinesterases also cause antidromic action potentials and repetitive firing in nerves (Blaber and Bowman 1963; Blaber 1972) probably by activating a positive feedback mechanism (Bowman, Marshall, Gibb and Harbourne 1988). Cholinergic stimulation of pre-synaptic nicotinic receptors increases t h e mobilisation and release of acetylcholine. Therefore, anti-cholinesterases can initiate a cycle in which released acetylcholine promotes its own liberation. In summary, anti-cholinesterase drugs can either increase or decrease heart rate although they usually cause bradycardia and bradyarrythmias due to muscarinic activation in cardiac conducting tissue. Arrhythmias have not been reported in dogs during the antagonism of neuromuscular block. In contrast, neostigmine and edrophonium have caused cardiac arrest in man (Bain and Broadbent 1949; Clutton-Brock 1949; Hill 1949; MacIntosh 1949; Lawson 1956; Youngberg 1979) a n d a r r h y t h m i a s a p p e a r t o be relatively common. Atropine a n d neostigmine combinations have caused atrioventricular dissociation, junctional rhythm, increased P-R interval, premature atrial contractions, ectopic beats, inverted P waves, wandering pacemaker a n d premature ventricular depolarisations (Ovassapian 1969; Mirakhur, Dundee and Clarke 1977; Ostheimer 1977). Several factors influence t h e arrhythmogenic potential of a n t i cholinesterases given at this time. Bradyarrhythmias are more likely when antagonists are injected rapidly (Ovassapian 1969; Harper et al 1984) and the risk of arrhythmias is higher than normal in patients receiveing P-adrenergic a n t a g o n i s t s (Sprague 1975; Seidl and Martin 1984) catecholamine depleting d r u g s (Youngberg 1979) a n d probably calcium-entry blockers (Atlee 1985). The pharmacokinetics of concurrently administered antimuscarinic drugs also affect the electrocardiogram during antagonism. When atropine (which has a rapid onset of action) is combined w i t h slower acting neostigmine, tachycardia, tachyarrythmias or both are like 1y. Converse 1y, combining e d r o p h o n iu m (rapid onset) with glycopyrrolate (slow onset) results in bradycardia (Azar et al1983). The problems in this case a r e consistent with muscarinic p r e p o n d e r a n c e caused by excessive edrophonium, inadequate atropine or both. However, they were unexpected for several reasons. First, the dose of e d r o p h o n i u m used lies within the range currently recommended for use in dogs; Muir and Hubbell suggest that 0.55 mg/kg bwt may be repeated up to five times, whereas others recommend 0.1 to 0.2 m g / k g bwt (Sawyer 1982). Second, muscarinic blockade was no longer present even though atropine had been given 86 mins previously. In unanaesthetised
d o g s , a t r o p i n e exerts a dose-related d u r a t i o n of vagolysis on sino-atrial a n d atrioventricular nodal tissue, with doses of 25 pg/kg bwt lasting at least 120 mins (Kantelip, Alatienne, Gueorrguiev and DucheneMarullaz 1985). In the present report, muscarinic blockade was clearly not maintained by the higher dose of 40 pg/kg bwt. This is all the more surprising because edrophonium has less cardiac muscarinic activity relative t o e q u i p o t e n t doses of neostigmine a n d pyridostigmine (Morris, Cronnelly and Miller 1981), is associated with a lower incidence of muscarinic sideeffects (Bevan 1979; Kopman 1979; Cronnelly, Morris and Miller 1982) and, compared with neostigmine, normally requires significantly lower doses of either atropine or glycopyrrolate to prevent bradycardia (Mirakhur 1985). Finally, the slow injection of anticholinesterase drugs minimises the risk of arrhythmias during antagonism (Ovassapian 1969; Harper ef a l 1984). In the present report, injection was made over 1 min and there was no indication of reduced circulation time (heart rate was 68 beats/min). Muscarinic preponderance was the likely cause of arrest in this patient and, retrospectively, the exclusion of muscarinic blockers was misjudged. However, the u s e of a t r o p i n e d u r i n g the antagonism of neuromuscular block is not without risk; cardiac arrest in man following the injection of atropine-neostigmine mixtures has been attributed to the summation of the cholinergic action of neostigmine and the initial central vagal stimulation of a t r o p i n e (Mirakhur 1977). Alternatively, Jones, Deutsch a n d Turndorf (1961) r e g a r d e d s u d d e n atropine-induced sympathetic predominance to be responsible for cardiac arrest at this time. When injected before neostigmine, atropine has caused serious tachycardia and arrythmias in man (Jones ef al 1961; Ovassapian 1969) and similar changes have been reported in dogs (Clutton et ~11991). The w i d e variation in d o s e s of e d r o p h o n i u m suggested for neuromuscular blockade reversal in dogs makes it difficult to give firm recommendations (Jones 1988). Presently, we use a mixture of atropine (20 pg/kg bwt) and edrophonium (250 pg/kg bwt) injected over 30 secs. If recovery is judged to be slow or incomplete, a second dose of edrophonium (250 pg/kg bwt) is given slowly after 3 mins. To date, this regime has not caused complications.
REFERENCES Azar, I., Pham, A. N., Karambelkar, D. J. and Lear, E. (1983) The h e a r t r a t e following e d r o p h o n i u m - a t r o p i n e a n d edrophonium-glycopyrrolate mixtures. Aiicsthrsiology 59, 139-141. Atlee, J. L. (1985) P e r i o p e r a t i i i c C n v d i n c D ~ y s ~ / i y t h ~ i i i ~ s : Mechnnisins, Rrcogrtition, Mniznginriit. Year Book Medical Publishers, Chicago. p 216. Bain, W. A. a n d Broadbent, J . L. (1949) Death following neostigmine. Br. med. J. 1, 1137. Bevan, D. R . (1979) Reversal of p a n c u r o n i u m w i t h edrophonium. Aiiuestlirsin 34, 614. Blaber, L. C. a n d Bowman, W. C . (1963) Studies on the
43
1. vet. Anaesth. Vol. 18 (1991) repetitive discharges evoked in ulnar nerve and skeletal muscle after injection of anti-cholinesterase drug. Br. J. Pharmacol. 9,326-344. Blaber, L. C. (1972) The mechanism of the facilitatory action of edrophonium in cat skeletal muscle. Br. J. Pharmacol. 46, 498-507. Bowman, W. C., Marshall, I. G., Gibb, A. J. and Harbourne, A. J. (1988) Feedback control of transmitter release at the neuromuscular junction. In: Trends in Pharmacological Sciences. Volume 9. Elsevier Publications, Cambridge. p 1620. Clutton, R. E., Boyd, C., Flora, R., Payne, J. and McGrath, C. J. (1991) Autonomic a n d cardiovascular effects of neuromuscular blockade antagonism in the dog. Vet. Surg. (In press). Clutton-Brock, J. (1949) Death following neostigmine. Br. rned. J. 1,1007. Cronnelly, R., Morris, R. B. a n d Miller, R. D. (1982) Edrophonium: duration of action a n d atropine requirement in humans during halothane anaesthesia. Anesthesiology 57,261. Harper, K. W., Bali, I. M., Gibson, F. W., Carlisle, R., Black, I. H. C., Grainger, D. J. and Dundee, J. W. (1984) Reversal of neuromuscular blockade: Heart rate changes with slow injection of neostigmine and atropine mixtures. Anaesthesia 39, 772-775. Hill, M. (1949) Death after neostigmine injection. Br. med. J. 2, 601. Jones, R. E., Deutsch, S. and Turndorf, H. (1961) Effects of atropine on cardiac rhythm in conscious and anaesthetised man. Anesthesiology 22,67. Jones, R. S. (1988) Reversal of neuromdscular blockade - a review. J. Ass. vet. Anaesth. 15,80-88. Kantelip, J. P., Alatienne, M., Gueorguiev, G. and DucheneMarullaz, P. (1985) Chronotropic and dromotropic effects of atropine and hyoscine methobromide in unanaesthetised dogs. Br. J. Anaesth. 57,214-219.
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Kopman, A. F. (1979) Edrophonium antagonism of pancuronium induced neuromuscular blockade in man: A reappraisal. Anesthesiology 51, 139-142. Lawson, J . J . (1956) Cardiac arrest following the administration of neostigmine. Br. J. Anaesth. 28,336. MacIntosh, R. R. (1949) Death following injection of neostigmine. Br. rned. J. 1,852. Mirakhur, R. K., Dundee, J. W. and Clarke, R. S. J. (1977) Glycopyrrolate-neostigmine mixture for antagonism of neuromuscular block: comparison with atropineneostigmine mixture. Br. J. Anaesth. 49,825-829. Mirakhur, R. K. (1985) Antagonism of the muscarinic effects of edrophonium with atropine or glycopyrrolate Br. J. Anaesth. 57, 1213-1216. Morris, R. B., Cronnelly, r. and Miller, R. D. (1981) Atropine requirement for edrophonium. Anesthesiology 55, A206. Muir, W. W., Hubbell, J. A. E. (1985) Handbook of Veterinary Anaesthesia. The C.V. Mosby Company. pp 108-117. Ostheimer, G. W. (1977) A comparison of glycopyrrolate and atropine d u r i n g reversal of nondepolarising neuromuscular block with neostigmine. Anesth. Analg. 56, 182-186. Ovassapian, A. (1969) Effects of administration of atropine and neostigmine in man. Anest. Analg. 48,219-223. Sawyer, D. (1982) The Practice of Small Animal Anesthesia. W. B. Saunders, Philadelphia. p 112. Seidl, D. C. and Martin, D. E. (1984) Prolonged bradycardia after neostigmine administration in a patient taking nadolol. Anesth. Analg. 63,365-367. Sprague, D. H. (1975) Severe bradycardia after neostigmine in a patient taking propranolol to control paroxysmal atrial tachycardia. Anesthesiology 42,208-210. Youngberg, J. A. (1979) Cardiac arrest following treatment of paroxysmal atrial tachycardia with edrophonium. Anesthesiology 50,234-235.
ASSOCIATION OF VETERINARY ANAESTHETISTS The aim of the Association of Veterinary Anaesthetists is to promote the study and research of anaesthesia in animals and to disseminate the results thereof to the public. To further this aim we hold regular meetings and conferences and publish the Journal of Veterinary Anaesthesia. We also are keen to promote collaboration between anaesthetists all over the world and actively encourage the establishment of diplomas and degrees in veterinary anaesthesia. The Association typically holds a 2-day meeting twice a year; one in the Spring, the other in Autumn. The programmes are varied, offering papers for a wide range of interests. The membership includes veterinarians in general practice a s well a s specialist veterinary anaesthetists, university teachers, medical anaesthetists, and scientists all with a common interest in veterinary anaesthesia and related subjects. Although based in Great Britain, we have a large membership in Europe, the North American Continent and the Antipodes. The association welcomes new members. Application forms are available from the Hon. Secretary, Dr. Andrea Nolan, Department of Veterinary Pharmacology, University of Glasgow, Bearsden Road, Glasgow G61 1QH. 1991 subscriptions: AVA members - €15 (membership includes copy of journal) Individual subscriber - €15 or €25 inc. p. & p. Library subscription - €22 or €45 inc. p. & p . (same for U.K. or foreign) 44