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.     

Observations on the neuromuscular blocking action of pipecuronium in the dog

Pipecuronium bromide is a nondepolarising muscle relaxant which is an analogue of pancuronium. Doses of 0.025 and 0.05 mg kg-1 produced neuromuscular block in the anaesthetised dog. Previous work would suggest that the drug has minimal effects on the cardiovascular system. However, a dose of 0.05 mg kg-1 produced a profound hypotension in one dog on one occasion. The neuromuscular blocking action of the drug would appear to be extremely variable as indicated by the wide range of the results. The neuromuscular block was readily reversible with neostigmine preceded by atropine.     

Recovery from neuromuscular block in dogs: restoration of spontaneous ventilation does not exclude residual blockade

ObjectiveTo evaluate if return of spontaneous ventilation to pre-relaxation values indicates complete recovery from neuromuscular blockade.Study designProspective, with each individual acting as its own control.AnimalsTen healthy adult female Beagle dogs weighing 6.2–9.4 kg.MethodsDogs were anesthetized with propofol, dexemedetomidine and isoflurane. Spontaneous ventilation was assessed by measuring end-tidal CO₂, expired tidal volume, peak inspiratory flow, respiratory rate and minute ventilation. Vecuronium 25 μg kg^?1 IV was administered and neuromuscular block was evaluated by measuring the train-of-four (TOF) ratio with acceleromyography in the hind limb. During spontaneous recovery from neuromuscular block, the TOF ratio when each ventilatory variable returned to baseline was recorded.ResultsThis dose of vecuronium produced moderate neuromuscular block in all dogs, with TOF ratio values of 0–18% at maximal block. Expired tidal volume, peak inspiratory flow and minute ventilation returned to pre-relaxation values when the median TOF ratio was ≤ 20%. The median TOF ratio was 42% when the end-tidal CO₂ returned to pre-relaxation values.Conclusions and clinical relevanceSignificant residual neuromuscular block could be measured at the hind limb with acceleromyography when ventilation had spontaneously returned to pre-vecuronium values. Monitoring spontaneous ventilation, including end-tidal CO₂, expired tidal volume, peak inspiratory flow or minute ventilation cannot be used as a surrogate for objective neuromuscular monitoring, and this practice may increase the risk of postoperative residual paralysis.     

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.     

Causes for species difference in acute toxicity of chlorocholine chloride]

Chlorocholine chloride (CCC) inhibits neuromuscular transduction of excitation and, consequently, leads to respiratory arrest in cases of acute intoxication. An account is given of the relationships between neuromuscularly blocking activity and acute toxicity of CCC. Several animal species and pharmacological models are used to produce evidence to the effect that CCC-caused inhibition of neuromuscular transmission of excitation is characterised by parameters typical of block due to depolarisation. The differentiated sensitivity of species to depolarising neuromuscular blockers is thought to be the decisive cause of species differences regarding acute toxicity of CCC. Conclusions are discussed which may be derived from the above findings regarding acute CCC toxicity to man and agricultural animal.     

Muscle relaxants in canine anaesthesia 2: Clinical application

There are a variety of factors which are likely to influence the action of muscle relaxants in canine anaesthesia. These include age, body temperature and muscle diseases. Of the anaesthetic agents it is only the inhalational anaesthetic agents which significantly increase the duration of action of muscle relaxants. Antibiotic therapy particularly with the aminoglycoside antibiotics is likely to increase their duration of action. The indications for the use of muscle relaxants and the main contraindications such as the absence of anaesthetic equipment and the inability to ensure unconsciousness are discussed. The choice of anaesthetic technique together with a discussion on the premedication induction and maintenance of anaesthesia are important factors when using relaxants as is the technique of artificial ventilation. The various advantages and disadvantages of neuromuscular block monitoring are discussed as is the reversal of neuromuscular block.     

Observations of the potency and duration of vecuronium in isoflurane-anesthetized horses

ObjectiveTo evaluate the potency and duration of three subparalyzing doses of vecuronium (VEC) in isoflurane-anesthetized horses.Study designProspective experimental study.AnimalsThirteen healthy adult horses undergoing arthroscopic surgery.MethodsDuring isoflurane anesthesia, horses received one of three doses of vecuronium (25, 50, or 100 μg kg^?1). Neuromuscular transmission was monitored with acceleromyography (AMG) with train-of-four (TOF) stimulation of the radial nerve. Maximal depression of the first twitch (T1), and onset time were recorded for each dose. Recovery time to a TOF ratio >90% was also evaluated.ResultsVecuronium 25 μg kg^?1 produced no observable T1 depression in four horses. VEC 50 μg kg^?1 (n = 5) produced a maximal T1 depression of [median (min, max)] 41 (20, 71) % in four horses, and no neuromuscular block was seen in the fifth. VEC 100 μg kg^?1 was given to four horses and produced a T1 depression of 73 (64, 78) %. Of the four horses in which VEC 50 μg kg^?1 produced a measurable neuromuscular block, three recovered spontaneously 43 (40, 52) minutes after VEC administration; a fourth subject received edrophonium to reverse residual block at the end of the surgery. Spontaneous recovery after VEC 100 μg kg^?1 occurred by 112 minutes in one horse, and had to be facilitated by edrophonium in the remaining three horses, more than 2 hours after VEC had been given.Conclusions and clinical relevanceA dose of 100 μg kg^?1 VEC in isoflurane anesthetized horses failed to produce complete paralysis. The partial neuromuscular block lasted at least 2 hours after this dose had been administered. Edrophonium was required to reverse the neuromuscular block in three of four horses. It is likely that more than 100 μg kg^?1 VEC would be necessary for complete neuromuscular blockade in horses, and that this dose will last >2 hours.     

Interactions between pipecuronium and suxamethonium in the dog

The depolarising muscle relaxant suxamethonium (0.3 mg kg-1) and the non-depolarising muscle relaxant pipecuronium (0.05 mg kg-1) were administered to four dogs. In the first series of experiments pipecuronium was administered intravenously, followed at 50 per cent of return of neuromuscular activity by suxamethonium. At 50 per cent return of activity atropine and neostigmine were administered to reverse the neuromuscular block. In the second series the sequence was reversed and pipecuronium was administered after suxamethonium. At 50 per cent recovery atropine and neostigmine were given. In the first series of experiments the time for the onset of suxamethonium block was significantly increased after prior administration of pipecuronium. However, in the second series of experiments the prior administration of suxamethonium had no significant effect on the duration of action of pipecuronium.     

Evaluation of a three-axial acceleromyography monitor in dogs compared with mechanomyography

ObjectiveTo compare the ratio of the train-of-four (TOF) and double burst stimulation (DBS) obtained with three-axial acceleromyography (AMG) and mechanomyography (MMG) in dogs during recovery from a rocuronium-induced neuromuscular block.Study designProspective, randomized, experimental study.AnimalsA total of six intact healthy adult male Beagle dogs, weighing 9.1 ± 1.9 kg and aged 3–5 years.MethodsDogs were anesthetized with intravenous (IV) dexmedetomidine and propofol, and isoflurane in oxygen. Neuromuscular function was measured with AMG and MMG in the contralateral thoracic limbs. Rocuronium (0.5 mg kg^–1) was administered IV, and the TOF and DBS ratios measured. During neuromuscular block offset, MMG values were recorded when AMG first reached ratios of 0.9 and 1.0. True recovery from neuromuscular block was determined as MMG ratio ≥ 0.9. The false-positive (AMG ≥ 0.9 or 1.0, and MMG ratio < 0.9) rate was determined. Paired values were compared, and bias and limits of agreement were calculated. Receiver operating characteristic (ROC) curves were created.ResultsWhen AMG first reached 0.9 and 1.0 during recovery, MMG values were lower (p < 0.040). When AMG reached 0.9, the false-positive rate was 29% with TOF and 27% with DBS. It decreased to 12% (TOF) and 11% (DBS) when a ratio of 1.0 was used. AMG values were higher than paired MMG values (p < 0.001). The AMG overestimated MMG by 24% and 22% for TOF and DBS, respectively. Areas under the ROC curves (95% confidence interval) were 0.91 (0.89, 0.94) and 0.86 (0.81, 0.94) for TOF and DBS, respectively.Conclusionsand clinical relevance The three-axial AMG monitor overestimated neuromuscular function and, in some cases, indicated adequate recovery despite the MMG ratio being < 0.9. A TOF or DBS ratio of at least 1.0 should be considered when monitoring recovery of neuromuscular block with this AMG device.     

Edrophonium-induced asystole following neuromuscular blockade antagonism in a dog: a case report

Edrophonium was used to antagonise neuromuscular block in a healthy eight-year-old dog following ophthalmic surgery; this caused arrhythmias and asystole lasting 46 sees. The complication probably occurred because of inadequate muscarinic blockade prior to antagonism. The dog made an uneventful recovery.     

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 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.     

Differences between acceleromyography and electromyography during neuromuscular function monitoring in anesthetized Beagle dogs

ObjectiveQuantitative neuromuscular monitoring is essential for studies of potency and duration of neuromuscular blocking agents, and for detecting residual paralysis in anesthetized patients. This investigation evaluates whether there are systematic differences between acceleromyography (AMG) and electromyography (EMG); two quantitative methods for monitoring neuromuscular block.Study designProspective.AnimalsTen healthy Beagle dogs.MethodsDogs were anesthetized with isoflurane and dexmedetomidine. Both ulnar nerves were stimulated with a train-of-four (TOF) pattern every 15 seconds. The magnitude of the first twitch (T1) and the TOF ratio (magnitude of T4/T1; TOFR) were quantified simultaneously with AMG and EMG, applied randomly to each extremity. The extent of maximal block (T1 depression) and onset time were measured by AMG and EMG during TOF monitoring after the administration of cisatracurium (0.05 mg kg⁻¹). In addition, recovery of T1 to 25% and 75%, the recovery index (time between T1 of 25% and 75%), and recovery of the TOFR to 0.9 were used to characterize recovery from cisatracurium and were compared between monitors. Regression and Bland-Altman plots for T1 and TOFR were also created.ResultsMaximal block and onset time were not different between monitors. Time to recovery of T1 to 25% and 75%, and time to TOF ratio 0.9 was significantly shorter with AMG. The recovery index was not different between monitors. When the TOFR returned to 0.9 with AMG, EMG still measured considerable residual block (TOFR 0.47).Conclusions and clinical relevanceElectromyography consistently detected residual NMB when recovery from NMB was complete as assessed by AMG.     

Reversal of atracurium neuromuscular block with neostigmine in the dog

A dose response relationship and the time of onset to 50 per cent and 100 per cent peak action were investigated for neostigmine reversal of atracurium in the dog. Two levels of neuromuscular block were used, 10 per cent and 50 per cent of the first twitch of the train of four. The ED50 from the first group was 0.1 mg kg-1 and for the second group was 0.019 mg kg-1. There was little difference between the onset times at the two levels of block. It is concluded that the main factor in determining the dose of neostigmine is the depth of the initial blockade.     

Vecuronium infusion in the dog

The non-depolarising muscle relaxant vecuronium bromide was administered to 20 dogs undergoing a variety of surgical procedures under general anaesthesia. An initial dose of 0–1 mg/kg was administered and followed by an infusion of 0–1 mg/kg/hour. Reversal of the neuromuscular block was carried out with neostigmine and atropine.     

Survey of how different groups of veterinarians manage the use of neuromuscular blocking agents in anesthetized dogs

Objective

To analyze practice habits associated with the use, reversal and monitoring of nondepolarizing neuromuscular blocking agents (NMBAs) in dogs by different groups of veterinarians.

Electrocardiographic abnormalities associated with tetanus in two dogs

Bradycardia, sinus arrest, and second-degree atrioventricular block developed in 2 dogs with tetanus. Clinical signs attributable to bradycardia were not apparent. Administration of atropine resulted in resolution of the arrhythmias. Both dogs responded well to supportive treatment; the bradycardia resolved within 4 days of onset without specific treatment. Tetanus should be included in the differential diagnosis when increased neuromuscular excitability and bradycardia are evident, as is found in toxicity with acetylcholinesterase inhibitors, increased intracranial pressure, and other neurologic disorders.     

Evaluation of neostigmine antagonism at different levels of vecuronium-induced neuromuscular blockade in isoflurane anesthetized dogs

Residual neuromuscular block (NMB) during recovery from general anesthesia may be minimized by antagonizing NMB with neostigmine. We examined neostigmine for restoring neuromuscular function when administered at 2 levels of vecuronium-induced NMB in dogs. Eight healthy adult dogs received vecuronium 0.1 mg/kg body weight (BW), IV, during isoflurane anesthesia. Recovery from vecuronium occurred spontaneously (control group; C), or was enhanced with neostigmine, 0.04 mg/kg BW, IV, administered when 2 (N2) or 4 (N4) responses to train-of-four (TOF) stimulation were first observed. Duration of NMB was significantly shorter for N2 and N4 than for C. The period of complete NMB was equal for all groups; differences were observed during the recovery phase of NMB. Time of neostigmine-enhanced recovery was significantly shorter for N4 than N2, but overall duration of NMB was not reduced. Recovery from NMB was faster with neostigmine. There is no clinical advantage in delaying neostigmine administration once 2 responses to TOF are present.     

Isoflurane potentiates metocurine via peripheral not central nervous system action

Inhalational anaesthetics potentiate neuromuscular blocking drugs. The exact sites are not known, but may include the central nervous system, the neuromuscular junction or muscle. Anaesthetic action in the brain could potentiate neuromuscular block directly, or indirectly by altering plasma catecholamine concentrations. In 5 goats anaesthetised with fentanyl and pentobarbitone, an experimental preparation was used in which isoflurane (end-tidal/exhaust 1.2–1.3%) was selectively delivered to either the torso (via the lungs) or brain (via an oxygenator/roller pump) during a stable ?60% metocurine blockade (?= 4–8 μg/min). Bilateral evoked gastrocnemius muscle twitch was accomplished with electrical stimulation (0.1 Hz) of the sciatic nerves, one of which was cut proximal to the stimulation site; output from the force transducer was digitised and stored on a computer. Blood samples were taken for metocurine, noradrenaline and adrenaline analysis. When isoflurane was added to the brain, % depression of the muscle twitch was unchanged at 64 ± 13% on the uncut side; the cut side was also unchanged. When isoflurane was added to the torso, % depression increased from 68 ± 14% to 82 ± 12% (P < 0.05) on the uncut side and from 68 ± 8% to 81 ± 5% on the cut side (P < 0.05). Metocurine concentration in the torso decreased slightly when isoflurane was added to the torso (133 ± 19 ng/ml to 121 ± 18 ng/ml, P < 0.05) and increased slightly when isoflurane was added to the head (116 ± 31 ng/ml to 136 ± 31 ng/ml, P < 0.05). There were no significant changes in noradrenaline or adrenaline concentrations. These data suggest that the periphery (neuromuscular junction or muscle) is the important site where isoflurane potentiates metocurine-induced neuromuscular blockade.     

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.