Muscle relaxants in canine anaesthesia 1: History and the drugs

The history of the introduction of muscle relaxants into medical and veterinary anaesthesia is discussed. It is interesting to note that the compounds were used in animals for therapeutic purposes some 100 years before their introduction into human anaesthetic practice. The concept of the triad approach to anaesthesia by separate consideration of the three components of narcosis, reflex depression and muscle relaxation is considered. The properties of the depolarising and non-depolarising muscle relaxant drugs are described. The only depolarising relaxant which is in common use is suxamethonium which produces an initial depolarisation of the muscle end-plate which is accompanied by fasciculation of muscle and is non-reversible. There are a number of non-depolarising or competitive muscle relaxants which are available for use in the dog. They are reversible by anticholinesterase drugs and are potentiated by volatile anaesthetic agents. The properties of the more recently introduced compounds atracurium besylate and vecuronium bromide are considered in the light of their differences when compared with the older compounds.     

Neuromuscular blocking agents in equine anesthesia

In summary, neuromuscular blocking agents can be used safely and to advantage in equine anesthesia. Muscle-relaxant use in equine anesthesia has been helped by the development of new relaxants such as atracurium, which has a reliable and reproducible duration of action. There are certain cases that benefit particularly by the use of relaxants but their use is not limited to these cases. These cases involve horses that experience persistent movement and hypotension during anesthesia, are undergoing ophthalmic or abdominal surgery or fracture repair, or are severely ill. Horses receiving muscle relaxants during anesthesia require mechanical ventilation, and neuromuscular blockade should be monitored with a peripheral-nerve stimulator.     

Newer neuromuscular blockers. Is the practitioner ready for muscle relaxants?

Current research on the development of new neuromuscular blocking agents is directed towards producing agents that have a rapid onset of action and predictable duration of action and recovery times, with minimal hemodynamic effects. For the veterinary practitioner, these newer agents should be considered when muscle relaxation is required for certain surgical procedures. Care must be taken to monitor paralyzed patients appropriately to ensure adequate ventilation and anesthetic depth. Vigilant monitoring should exist during the recovery period for the development of muscle weakness from residual blockade and the ability to reverse the effects of neuromuscular blockade. The use of neuromuscular blocking agents in veterinary patients should continue to increase as newer drugs and better monitoring techniques are developed.     

Reversal of neuromuscular block in companion animals

ObjectiveTo review the evidence regarding the reversal of neuromuscular block (NMB) in companion animals with emphasis on the development and use of newer agents.Database usedData sources include scientific reviews and original research publications in both human and veterinary literature using Pubmed and Scopus as search data bases. Unpublished and locally published data on reversal of NMB are presented.ConclusionsResidual NMB has been shown to increase morbidity and mortality in humans and needs to be avoided. It can be detected only by adequate neuromuscular monitoring. The proper use of reversal agents avoids residual NMB and recurarization should not occur. Anticholinesterase inhibitors, such as edrophonium and neostigmine have been used to reverse NMB when the need for this has been established. Reversal is influenced by several factors and a number of undesirable side- effects of these drugs have been reported. Sugammadex, a γ-cyclodextrin, which was designed specifically to encapsulate rocuronium, is more rapid in its actions, has fewer side effects and can reverse profound NMB induced by aminosteroidal muscle relaxants.     

Neuromuscular blocking action of vecuronium in the dog and its reversal by neostigmine

Vecuronium bromide is one of a new series of competitive or nondepolarising muscle relaxants which is closely related chemically to pancuronium. Doses of 0.06, 0.1 and 0.2 mg kg-1 produced neuromuscular block in the anaesthetised dog. There were no observable effects on arterial blood pressure. The neuromuscular block was readily reversible with neostigmine preceded by atropine.     

Interactions between vecuronium and suxamethonium in the dog

The non-depolarising muscle relaxant vecuronium (0.2 mg kg-1) was administered to four dogs. At 50 per cent return of neuromuscular activity, as measured by the train-of-four technique, the depolarising muscle relaxant suxamethonium (0.3 mg kg-1) was injected intravenously. At 50 per cent return of neuromuscular activity reversal of the block was achieved with atropine and neostigmine. The duration of action of suxamethonium was reduced by the prior administration of vecuronium. In the second series of experiments the order of administration of the suxamethonium and vecuronium was reversed. Suxamethonium (0.3 mg kg-1) was administered first and at 50 per cent recovery vecuronium (0.2 mg kg-1) was given. At 50 per cent recovery of the twitch response after vecuronium administration the block was reversed with atropine and neostigmine. The previous administration of suxamethonium prolonged the duration of the vecuronium induced neuromuscular block.     

Epidural analgesia in the dog and cat

SUMMARY: A brief outline of the history of epidural analgesia is followed by a review of the anatomy of the epidural space with particular reference to epidural block. The technique of epidural injection in the dog is described as are the indications for the technique. These include the provision of anaesthesia for such procedures as orthopaedic surgery of the hind limb and caesarian section. The cardiovascular effects of epidural block are discussed and suggestions are made for the prevention of hypotension. The various drugs and their combinations which may be used for epidural administration are outlined. The commonest used local anaesthetic agents are bupivacaine and lidocaine. Epidural administration of opioid drugs is a relatively new technique which is used to provide intra- and post-operative analgesia. Morphine is the drug of choice for this indication.The use of other classes of drugs, such as the alpha 2 agonists and ketamine, are also considered. A variety of side-effects, contra-indications and complications are described together with methods for reducing their incidence and effects.     

The clinical use of the neuromuscular blocking agent rocuronium in dogs

Objective The aim of this study was to characterize the onset and duration of action of the aminosteroid muscle relaxant rocuronium in dogs under clinical conditions. Study design Prospective single dose trial. Animals Twenty‐three dogs aged between 6 months and 12 years, weighing between 5.5 and 61.5 kg admitted to the University of Liverpool Small Animal Hospital between January and March 2000, and undergoing elective surgical procedures under general anaesthesia. Materials and methods Following induction of general anaesthesia, neuromuscular function was evaluated using train‐of‐four (TOF) stimulation. An initial dose of 0.4 mg kg^?1 rocuronium was administered intravenously (IV) and neuromuscular blockade was monitored by visually assessing the number of responses (twitches) to TOF stimulation (train‐of‐four count: TOFC). Incremental doses of 0.16 mg kg^?1 rocuronium were administered as indicated, when at least two twitches of the TOFC had returned. Results Rocuronium (0.4 mg kg^?1) abolished all responses to TOF stimulation in all dogs. The mean time to onset of neuromuscular blockade (complete abolition of all twitches) was 98 ± 52 seconds. Neuromuscular blockade (absence of all twitches to return of all four) lasted 32.3 ± 8.2 minutes. Incremental doses of 0.16 mg kg^?1 had a mean duration of action of 20.8 ± 4.9 minutes and up to seven increments were shown to be noncumulative. The effects of rocuronium were readily antagonized with neostigmine and atropine. Small transient increases in arterial blood pressure, which occurred in three dogs after the administration of rocuronium, were the only cardiovascular side‐effects observed. Conclusions Rocuronium is an effective nondepolarizing neuromuscular blocking agent in the dog, with a rapid onset of neuromuscular block after intravenous administration and an intermediate duration of action. Clinical relevance Rocuronium produced a neuromuscular block with similar characteristics to those obtained with vecuronium, thus apparently offering little advantage over vecuronium. However, its availability in aqueous solution and a longer shelf‐life increases convenience.     

Depth of anaesthesia

One hundred and fifty years after the first general anaesthetic in 1846 our knowledge about the mechanisms of general anaesthetics is still very sparse. The concept ‘depth of anaesthesia’ was introduced by John Snow (1847). He described ‘5° of narcotism’. Because one single agent had to provide all the components of general anaesthesia, the main problem for the anaesthetist was to avoid morbidity and mortality associated with excessively deep anaesthesia. The introduction of curare in 1942 allowed muscle relaxation required for surgery during a lighter level of anaesthesia, but also changed the emphasis from the problem of too deep anaesthesia and death, to too light anaesthesia and litigation. The problem of awareness during general anaesthesia with muscle relaxants provided the main impetus for monitoring depth of anaesthesia. During daily clinical practice the anaesthesiologist relies on clinical signs to evaluate anaesthetic depth, although several studies have shown a poor correlation between the 2 (Cullen et al. 1972; Evans and Davies 1984; Russell 1993). Different methods have been used in attempts to measure anaesthetic depth (Evans and Davies 1984; Stanski 1994), but none have been developed to a state where they can be used routinely in the operating theatre. This review will cover some of the parameters used to evaluate anaesthetic depth.     

Influence of sodium taurocholate on the potency and duration of action of some neuromuscular blocking agents

The effect of sodium taurocholate (S. T.) on the contractile response of rat-phrenic nerve diaphragm, frog's musculus rectus abdominis and frog's musculus gastrocnemius sciatic nerve preparation was studied. Moreover, interaction of S. T. with neuromuscular blockers are carried out, too. S. T. was found to have a dose-dependent reduction in the contractile response of the tested preparation. On the other hand, the inhibitory effect induced by S. T. did not block or alter the stimulatory effect of either acetylcholine or prostigmine. Trials were made to estimate the potency of S. T. in a comparison with other skeletal muscle relaxant drugs. In this respect S. T. exhibited a more potent effect than gallamine. In contrast, other skeletal muscle relaxants (dtubocurarine, atracurium, pancuronium and succinylcholine) were highly potent. There was also a marked synergistic effect between S. T. and other neuromuscular agents.     

Atracurium infusion in the dog

The non-depolarizing muscle relaxant atracurium was administered to 25 dogs undergoing a variety of surgical procedures under general anaesthesia. An initial dose of 0–5 mg/kg was administered and when the block began to wear off an infusion was begun. A dose of 0–5 mg/kg/hr was administered by a simple infusion technique. Reversal of the neuromuscular block was carried out with either neostigmine or edrophonium preceded by atropine.     

The influence of anaesthesia on bronchography in dogs

The spread of the contrast medium, Dionosil Aqueous (Glaxo),* in the bronchi of three healthy dogs was investigated under a variety of anaesthetic techniques. The most reliable results were obtained when intermittent positive pressure ventilation (IPPV) was applied following anaesthetic techniques incorporating the use of neuromuscular blocking agents. Good results were also obtained using trichloroethylene anaesthesia. The reliability of results obtained using relaxant techniques was confirmed in clinical cases.     

Preliminary studies on the use of propofol in the domestic pigeon (Columba livia)

The anaesthetic propofol was investigated in domestic pigeons (Columba livia). The agent was administrated intravenously, in one group of birds as an adjunct to ketamine hydrochloride, and careful monitoring was performed. The dose of 14 mg kg-1 of propofol was based on allometric scaling for its use as a sole agent. Propofol anaesthesia was characterised by smooth rapid induction and good muscle relaxation but was only of short duration, ranging from two to seven minutes, and seemed to cause a marked respiratory depression. Indeed, a very narrow safety margin for propofol was observed in pigeons when ventilation was not assisted. The agent may have applications in avian anaesthesia but these are likely to be limited.     

Anaesthetic regimes for cataract removal in the dog

Dogs scheduled for elective removal of non-diabetic cataracts were assigned to one of four anaesthetic regimes. Thiopentone (Intraval Sodium; RMB Animal Health) or propofol (Rapinovet; Coopers Pitman-Moore) was used as the induction agent and with each agent half the animals were paralysed with vecuronium (Nor-curon; Organon Teknika) and ventilated mechanically, and half breathed spontaneously. Anaesthesia was maintained with halothane (Halothane-M&B; RMB Animal Health) and nitrous oxide (BOC) in oxygen. The use of muscle relaxants significantly improved the eye position and significantly reduced the lowest halothane vaporiser setting used during anaesthesia. Propofol produced a significantly shorter recovery time than thiopentone.     

Epidural anaesthesia using lignocaine, bupivacaine or a mixture of lignocaine and bupivacaine in dogs

The time to loss of interdigital reflex, duration of action, duration of muscle relaxation and cardiorespiratory effects were compared after epidural block using lignocaine, bupivacaine or a combination of lignocaine and bupivacaine in dogs. Dogs were pre-medicated with methotrimeprazine, anaesthesia was induced with thiopentone, in order to facilitate epidural puncture, and a lumbosacral epidural block was performed. Body temperature fell after pre-medication, thiopentone and epidural anaesthesia. Minimal changes were observed in arterial O₂ saturation, end tidal CO₂, respiratory rate, heart rate and mean arterial blood pressure. The combination of bupivacaine with lignocaine produced a shorter time to loss of interdigital reflex than bupivacaine alone, longer analgesia than lignocaine alone and longer muscle relaxation than either lignocaine or bupivacaine. The combination appeared to be the best choice when surgical time is prolonged.     

Evaluation of the anaesthetic effects of combinations of ketamine, medetomidine, romifidine and butorphanol in European badgers (Meles meles)

OBJECTIVE: To evaluate the effects of three anaesthetic combinations in adult European badgers (Meles meles). STUDY DESIGN: Prospective, randomized, blinded, experimental trial. ANIMALS: Sixteen captive adult badgers. METHODS: The badgers were each anaesthetized by intramuscular injection using the three techniques assigned in random order: romifidine 0.18 mg kg(-1), ketamine 10 mg kg(-1) and butorphanol 0.1 mg kg(-1) (RKB); medetomidine 0.1 mg kg(-1), ketamine 9 mg kg(-1) and butorphanol 0.1 mg kg(-1) (MKB); and medetomidine 0.1 mg kg(-1) and ketamine 10 mg kg(-1) (MK). Initial drug doses were calculated based on a body mass of 10 kg. Additional anaesthetic requirements, time to drug effect, duration of action and recovery from anaesthesia were recorded. Heart rate and rhythm, respiratory rate and rhythm, rectal and subcutaneous microchip temperature and oxygen saturation were recorded every 5 minutes. Depth of anaesthesia was assessed using: muscle tone; palpebral and pedal reflexes; and tongue relaxation at these time points. Blood samples and a tracheal aspirate were obtained under anaesthesia. Atipamezole was administered if the badger had not recovered within 60 minutes Parametric data were analysed using anova for repeated measures, and nonparametric data using Friedman's, and Cochran's Q tests: p < 0.05 was considered significant. RESULTS: All combinations produced good or excellent muscle relaxation throughout the anaesthetic period. RKB had the shortest duration of anaesthesia (16.8 minutes compared with MKB 25.9 minutes and MK 25.5 minutes) and antagonism was not required. RKB depressed respiratory rate less than MK and MKB. There was no significant difference between techniques for heart rate and rhythm. CONCLUSIONS AND CLINICAL RELEVANCE: All combinations provided anaesthetic conditions suitable for sampling and identification procedures in adult badgers. The RKB protocol provided a significantly shorter period of anaesthesia when compared with the combinations containing medetomidine.     

Neuromuscular block monitoring after the administration of 1 mg/kg intravenous cis‐atracurium in the anaesthetized pig

Neuromuscular blocking agents should be included as part of a balanced anaesthetic protocol to improve anaesthetic management, although doses are not always established for each species. Cis‐atracurium is a benzylisoquinolinium neuromuscular blocking agent with an intermediate duration of action devoid of significant adverse effects previously used in pigs with a wide dosage range. Cis‐atracurium was administered at 1 mg/kg bolus to sixteen pigs to establish its time profile and effects. The pigs were premedicated intramuscularly with 4 mg/kg azaperone, 8 mg/kg ketamine and 0.2 mg/kg morphine IM and maintained with isoflurane in oxygen. After cis‐atracurium administration, neuromuscular monitoring via acceleromyography was started until the recovery of the 90% of the train of four ratio. Complete decrease in the train of four ratio was accomplished in eleven pigs. Onset of action was 70 s, with a recovery of the fourth twitch at 26 min and a recovery of a train of four ratio greater than 90% in 60 min. In conclusion, 1 mg/kg intravenous cis‐atracurium in the pig allowed for a rapid onset of action and a complete recovery after 60 min although high variability in the time profile is seen.     

Physiological effects of total intravenous surgical anaesthesia using detomidine-guaiphenesin-ketamine in horses

A combination of detomidine, guaiphenesin and ketamine was used to maintain anaesthesia for surgery in 38 horses and ponies. Cardiovascular and respiratory depression were minimal and surgical conditions were excellent. Recovery was smooth in most cases but prolonged and ataxic in some pregnant pony mares. Plasma cortisol concentration decreased during anaesthesia, even when major surgery was performed. This suggests that the anaesthetic technique does not itself induce a stress response and may suppress it. Anaesthesia was straightforward in all cases and the technique appears to have potential as an alternative to anaesthetic maintenance with volatile agents. The pharmacokinetics of the infusion are unknown and require investigation, particularly in pregnant animals.     

Anaesthesia in two species of large Australian skink

The use of ketamine hydrochloride and sodium pentobarbitone in the anaesthesia of two species of Australian skink was examined. The effects of ketamine at ambient temperatures of 15 degrees C and 30 degrees C were studied. Ketamine produced consistent responses up to and including anaesthesia at dose rates of 170 to 230 mg/kg at 30 degrees C. The effect of temperature on the anaesthetic dose, respiratory and cardiac rates, muscle relaxation, analgesia and the onset and duration of anaesthesia was examined. Respiration in both species was depressed but heart rate was increased in Bobtail skinks (Tiliqua rugosa) and depressed in King's skinks (Egernia kingii). Muscle relaxation was good when anaesthetic doses were given. Generally, the onset and duration of anaesthesia were extended at 15 degrees C while the dose rates required for this effect were reduced. Although there was individual variation in the response to ketamine, it was found to be a useful and practical agent for the anaesthesia of large skinks. Pentobarbitone was found to be unsuitable as an anaesthetic agent because it produced inconsistent results and several fatalities.     

Clinical observations on the use of the muscle relaxant atracurium in the dog

The use of the new neuromuscular blocking agent, atracurium besylate, is described in 22 dogs undergoing a variety of surgical procedures under general anaesthesia. An initial dose of 0.5 mg/kg proved effective and produced a block of 40 min duration. Incremental doses of 0.2 mg/kg were used. Reversal of the neuromuscular block by neostigmine preceded by atropine was rapid and effective. No untoward side-effects were observed with this drug.