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.     

Interaction between atracurium and suxamethonium in the dog

The depolarising muscle relaxant suxamethonium (0.3 mg kg-1) and the non-depolarising relaxant atracurium (0.6 mg kg-1) were administered to four dogs. In the first series of experiments atracurium was administered, followed at 50 per cent return of neuromuscular activity by suxamethonium. At 50 per cent return of activity atropine and neostigmine were administered to reverse the block. In the second series of experiments the sequence was reversed and atracurium was administered after suxamethonium. At 50 per cent recovery atropine and neostigmine were given. In the first series of experiments it was demonstrated that the prior administration of atracurium reduced the duration of action of suxamethonium. However, in the second series it was shown that the prior administration of suxamethonium had no significant effect on the duration of action of atracurium.     

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.     

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.     

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.     

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.     

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.     

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.     

Autonomic and Cardiovascular Effects of Neuromuscular Blockade Antagonism in the Dog

Autonomic and cardiovascular changes were studied when neuromuscular blockade was antagonized in 96 dogs with one of eight anticholinesterase-antimuscarinic drug combinations. Neostigmine (50 or 100 micrograms/kg) was administered before or after atropine (40 micrograms/kg) or glycopyrrolate (10 micrograms/kg). The high dose of neostigmine (100 micrograms/kg) caused bradyarrhythmias, salivation, and signs of bronchosecretion when used with either antimuscarinic agent and irrespective of the administration sequence. The heart rate increased, but not significantly, when atropine was injected before either dose of neostigmine. This did not occur when this administration sequence was reversed. Arrhythmias and cardiovascular and autonomic changes did not occur when glycopyrrolate was injected before or after neostigmine at 50 micrograms/kg.     

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.     

Failure to reverse prolonged vecuronium-induced neuromuscular blockade with edrophonium in an anesthetized dog

A case of prolonged muscle relaxation after vecuronium in an anesthetized dog is presented. After using peripheral nerve stimulation to confirm partial recovery of neuromuscular transmission, administration of 0.5 mg/kg IV of intravenous edrophonium failed to complete the reversal process. Subsequent administration of neostigmine resulted in complete recovery from blockade. Without monitoring neuromuscular function with a peripheral nerve stimulator until reversal was complete, it was very likely this patient would have been extubated with incomplete neuromuscular transmission. Several factors affecting the duration of neuromuscular blockade and its reversal are addressed.     

Antagonism of pancuronium neuromuscular blockade in halothane-anesthetized ponies using neostigmine and edrophonium

Efficacy of neostigmine (0.04 mg/kg of body weight) and edrophonium (1 mg/kg), as antagonists for pancuronium neuromuscular blockade in halothane-anesthetized ponies, was evaluated. Neostigmine and edrophonium were satisfactory antagonists, with edrophonium having a significantly (P less than 0.01) more rapid onset of action than did neostigmine. Muscarinic activity of neostigmine and edrophonium was also evaluated. Neither antagonist was administered with atropine. Gastrointestinal effects, increased salivation, and increased airway secretions were minimal with edrophonium, but were marked after neostigmine. Blood pressure increased within 1 to 2 minutes of antagonist administration. Heart rate decreased after edrophonium injection, but this occurred after blood pressure increase. Heart rate increased or did not change after neostigmine administration.     

Speed of reversal of vecuronium neuromuscular block with different doses of neostigmine in anesthetized dogs

Objectives

Neostigmine is routinely used to reverse non-depolarizing neuromuscular block. Given its indirect mechanism, a plateau may exist whereby increasing doses of neostigmine do not result in clinical benefit. This study was designed to measure the speed of reversal of vecuronium-induced neuromuscular block in isoflurane-anesthetized dogs after the administration of three doses of neostigmine as used in clinical practice.

The effects of propofol, isoflurane and sevoflurane on vecuronium infusion rates for surgical muscle relaxation in dogs

OBJECTIVE: To compare the constant rate infusion (CRI) of vecuronium required to maintain a level of neuromuscular blockade adequate for major surgeries, e.g. thoracotomy or laparotomy, in dogs anaesthetized with a CRI of fentanyl and either propofol, isoflurane or sevoflurane. STUDY DESIGN: Prospective, randomized, cross-over study. ANIMALS: Thirteen male beagles (age, 9-22 months; body mass 6.3-11.3 kg). MATERIALS AND METHODS: Dogs were anaesthetized with propofol (24 mg kg(-1) hour(-1) IV CRI; group P), isoflurane (1.3% end-tidal concentration; group I) or sevoflurane (2.3% end-tidal concentration; group S) with fentanyl (5 microg kg(-1) hour(-1) IV, CRI). Sixty to seventy minutes after induction of anaesthesia, vecuronium was administered at a rate of 0.4, 0.3 and 0.2 mg kg(-1) hour(-1) in groups P, I and S respectively. To determine the degree of neuromuscular block, a peripheral nerve was stimulated electrically using the train-of-four (TO4) stimulus pattern. Evoked muscle contractions were evaluated using a neuromuscular monitoring device. Once the TO4 ratio reached 0, the continuous infusion rate was decreased and adjusted to maintain a TO4 count of 1. Continuous infusion was continued for 2 hours. The infusion rate of vecuronium was recorded 20, 40, 60, 80, 100 and 120 minutes after the start of infusion. RESULTS: The mean continuous infusion rates of vecuronium during stable infusion were 0.22 +/- 0.04 (mean +/- SD), 0.10 +/- 0.02 and 0.09 +/- 0.02 mg kg(-1) hour(-1) in groups P, I and S respectively. There were statistically significant differences between the rates in groups P and I and between the rates in groups P and S. Conclusions and clinical relevance In healthy dogs, the recommended maintenance infusion rate of vecuronium is 0.2 mg kg(-1) hour(-1) under CRI propofol-fentanyl anaesthesia and 0.1 mg kg(-1) hour(-1) during CRI fentanyl-isoflurane or sevoflurane anaesthesia.     

Pharmacokinetics of ceftazidime in sheep and its penetration into tissue and peritoneal fluids

Serum, tissue and peritoneal fluid concentrations of ceftazidime were studied in ewes after intravenous, intramuscular and subcutaneous administration at 50 mg kg-1 bodyweight. Tissue and peritoneal cages were implanted in the animals studied. After intravenous bolus administration, the mean serum concentration versus time profile was best described by a two-compartment open model. The distribution rate constant (alpha) was 3.5 +/- 1.1 h-1 and the half-life (t 1/2 alpha) 0.22 +/- 0.09 hour. The elimination rate constant (beta) was 0.43 +/- 0.04 h-1 and half-life (t 1/2 beta) 1.6 +/- 0.2 hours. The area under the curve was 275.7 +/- 84.0 micrograms.ml-1 h. The volume of distribution as steady state was 356.1 +/- 208.0 ml kg-1. The penetration ratio into tissue fluid was 62.6 +/- 15.1 per cent and into peritoneal fluid 61.1 +/- 16.5 per cent. After intramuscular injection, the elimination half-life was 1.7 +/- 0.2 hours, the area under the curve was 228.7 +/- 43.3 micrograms.ml-1 h. and the elimination rate constant was 0.42 +/- 0.05 h-1. The penetration ratio into tissue fluid was 68.5 +/- 37.3 per cent and into peritoneal fluid 73.3 +/- 34.4 per cent. After subcutaneous injection, the elimination half-life was 1.8 +/- 0.5 hours, the area under the curve was 231.8 +/- 65.6 micrograms.ml-1 h. and the elimination constant was 0.41 +/- 0.10 h-1. The penetration ratio into tissue fluid was 47.2 +/- 3.5 per cent and into peritoneal fluid 58.1 +/- 15.6 per cent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypotension produced by rapid intravenous administration of chloramphenicol in anaesthetised dogs

Rapid intravenous administration (60 mg s-1) of chloramphenicol (50 mg kg-1) in a 40 per cent w/v polyethylene glycol (400 to 600), 30 per cent ethyl alcohol, 2 per cent benzyl alcohol and 28 per cent distilled water vehicle produced a transient but significant decrease in systemic arterial blood pressure and heart rate with no effect on central venous pressure in sodium pentobarbital anaesthetised dogs. The vehicle alone had no significant effect on any of the parameters studied. Various approaches including the use of anticholinergic, antihistaminergic, antiadrenergic and ganglion blocking drugs failed to attenuate chloramphenicol induced hypotension and bradycardia. However, the hypertensive response to bilateral carotid arterial occlusion was significantly attenuated by rapid intravenous administration of chloramphenicol. The results clearly indicate that chloramphenicol itself, but not its vehicle, is responsible for the severe hypotension and bradycardia. These results also suggest that chloramphenicol-induced hypotension and bradycardia might be mediated peripherally via vasodilation due to its direct effect on vascular smooth muscle and centrally via interruption of the baroreceptor reflex pathway.     

Evaluation of sedative and cardiorespiratory effects of romifidine and romifidine-butorphanol in cats

OBJECTIVE: To determine sedative and cardiorespiratory effects of romifidine alone and romifidine in combination with butorphanol and effects of preemptive atropine administration in cats sedated with romifidine-butorphanol. DESIGN: Randomized crossover study. ANIMALS: 6 healthy adult cats. PROCEDURES: Cats were given saline (0.9% NaCl) solution followed by romifidine alone (100 microg/kg [45.4 microg/lb], i.m.), saline solution followed by a combination of romifidine (40 microg/kg [18.1 microg/lb], i.m.) and butorphanol (0.2 mg/kg [0.09 mg/lb], i.m.), or atropine (0.04 mg/kg [0.02 mg/lb], s.c.) followed by romifidine (40 microg/kg, i.m.) and butorphanol (0.2 mg/kg, i.m.). Treatments were administered in random order, with > or = 1 week between treatments. Physiologic variables were determined before and after drug administration. Time to recumbency, duration of recumbency, time to recover from sedation, and subjective evaluation of sedation, muscle relaxation, and analgesia were assessed. RESULTS: Bradycardia developed in all cats that received saline solution and romifidine-butorphanol or romifidine alone. Preemptive administration of atropine prevented bradycardia for 50 minutes in cats given romifidine-butorphanol. Oxyhemoglobin saturation was significantly decreased 10 minutes after romifidine-butorphanol administration in atropine-treated cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that administration of romifidine alone or romifidine-butorphanol causes a significant decrease in heart rate and that preemptive administration of atropine in cats sedated with romifidine-butorphanol effectively prevents bradycardia for 50 minutes.     

Clinical observations on the use of vecuronium as a muscle relaxant in the dog

The use of the non-depolarizing muscle relaxant vecuronium bromide is described in 21 dogs undergoing a variety of surgical procedures under general anaesthesia. An initial dose of 0.1 mg kg^-1 proved effective and produced an initial block of 25 minutes duration. Incremental doses of 0.04 mg kg^-1 were used and up to six increments were shown to be non-cumulative. No untoward side-effects were observed with the use of this drug in the dog.     

Haemodynamic differences between pancuronium and vecuronium in an experimental pig model

ObjectiveTo compare baseline cardiovascular function in anesthetised pigs using either pancuronium or vecuronium as a neuromuscular blocker.Study designRetrospective, non-randomized comparison.AnimalsNorwegian Land Race pigs (Sus scrofa domesticus) weighing mean 42 ± SD 3 kg.MethodsOne hundred and sixteen animals from four different research protocols premedicated with identical doses of ketamine, diazepam, atropine and isoflurane, and anaesthetised with pentobarbital, fentanyl, midazolam and N₂O were arranged into three uniform groups with respect to neuromuscular blocking agent: pancuronium bolus of 0.063 mg kg⁻¹ followed by 0.14 mg kg⁻¹ hour⁻¹ (n = 54), low-dose vecuronium 0.4 mg kg⁻¹/0.2 mg kg⁻¹ hour⁻¹ (n = 29) and high-dose vecuronium 0.6 mg kg⁻¹/0.3 mg kg⁻¹ hour⁻¹ (n = 33).ResultsThe majority of cardiovascular parameters demonstrated no significant differences between groups. For heart rate, there was an overall group difference, p = 0.036. Dromotropy was low in the pancuronium group, with an increased normalised PR-interval compared to the high-dose vecuronium group, median 0.200 interquartile range (0.190, 0.215) versus 0.182 (0.166, 0.199), p < 0.05. Left ventricular compliance was increased in pancuronium-treated animals, demonstrated as a reduction in the nonlinear end-diastolic pressure volume relationship β compared to both vecuronium groups, 0.021 (0.016, 0.025) versus 0.031 (0.025, 0.046) and 0.031 (0.022, 0.048), p < 0.05. The linear end-diastolic pressure volume relationship EDPVR_lin was reduced as well in the pancuronium group, compared to the low-dose vecuronium group, 0.131 (0.116, 0.169) versus 0.181 (0.148, 0.247), p < 0.05.ConclusionsThere are only minor haemodynamic differences when using pancuronium compared to vecuronium in the fentanyl-pentobarbital-midazolam-N₂O anesthetised domestic pigs. Furthermore, increasing doses of vecuronium have minimal haemodynamic effects.Clinical relevanceExperimental studies in pigs using either pancuronium or vecuronium as a neuromuscular blocking agent are comparable with regard to cardiac and haemodynamic performance.