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 Unpublished and locally published data on reversal of NMB are presented.ConclusionsResidual NMB has been shown to increase morbidity and mortality in humans and needs to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.     

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.

Reversal of profound rocuronium or vecuronium-induced neuromuscular block with sugammadex in isoflurane-anaesthetised dogs

This study evaluated the use of sugammadex for reversal of profound neuromuscular blockade induced with rocuronium or vecuronium in dogs. Anaesthesia was induced and maintained with isoflurane in oxygen in eight dogs on two occasions. Neuromuscular blockade was monitored using peroneal nerve stimulation and acceleromyography. Rocuronium 0.6 mg/kg or vecuronium 0.1mg/kg was administered intravenously (IV), followed 5 min later by sugammadex 8 mg/kg IV. Lag and onset time of rocuronium and vecuronium, lag time from sugammadex injection to recovery of first twitch response, recovery of T1/T0 to 25% and 75%, recovery index, and time to recovery of the train-of-four ratio (T4/T1) to 0.9 were recorded. Cardiovascular and respiratory parameters were also noted. Statistical analysis was performed using one-way ANOVA. Onset time for rocuronium (37 ± 18s; [mean ± SD]) was significantly shorter than for vecuronium (62 ± 15s) (P<0.04). No other significant differences were found between the two groups. After both rocuronium and vecuronium blockade, T4/T1 recovered to 0.9 in under 2 min after sugammadex (58.1 ± 67.8s and 98.1 ± 70.3s, respectively; P<0.32). Sugammadex can reverse profound neuromuscular blockade induced by vecuronium or rocuronium safely and rapidly in isoflurane-anaesthetised dogs.     

Observations on the neuromuscular blocking action of alcuronium in the dog and its reversal by neostigmine.

The action of alcuronium chloride on neuromuscular transmission in the dogs was investigated by electrical and mechanical methods. The mean duration of action was 70 min. Reversal of its action was produced with atropine and neostigmine.     

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.     

Effect of gentamicin administration on the neuromuscular blockade induced by atracurium in cats

Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered as an infusion to 8 anesthetized cats in which neuromuscular blockade was assessed, using the train-of-four response. Once 50% depression of the first-twitch (T1) response was achieved, the infusion was held constant for 60 minutes before being discontinued and the recovery time was determined. The time for recovery was recorded as the time for the train-of-four (T4 ratio) to increase from 50% to 75%. After recovery, atracurium infusion was reinstituted and the cats were again maintained for 60 minutes at 50% depression. A single bolus of gentamicin sulfate (2.0 mg/kg of body weight) was administered IV, and the infusion was continued for another 60 minutes before it was discontinued and the time for recovery was recorded. Within 1 minute of gentamicin administration, the mean +/- SD T1 response decreased from 49 +/- 5% to 33 +/- 8% of baseline and the T4 ratio decreased from 28 +/- 19% to 14 +/- 11%. Peak effect occurred at 5 minutes, with a T1 response of 29 +/- 6% of baseline and a T4 ratio of 13 +/- 12%. By 60 minutes after gentamicin administration, the T1 response had increased to 38 +/- 7% of baseline and the T4 ratio had increased to 21 +/- 13%. The time for recovery significantly (P less than 0.03) increased from 9.9 +/- 3.4 minutes during the control study to 18.1 +/- 10.7 minutes during the gentamicin study. In this study, gentamicin potentiated the neuromuscular blockade induced by atracurium and increased the recovery time. Residual blockade, observed after gentamicin administration was reversed with edrophonium.     

Diabetes mellitus does not affect the neuromuscular blocking action of atracurium in dogs

Objective

To compare the duration of action of atracurium in diabetic and nondiabetic dogs.

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.     

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.     

Clinical use of the neuromuscular blocking agents atracurium and pancuronium for equine anesthesia

Neuromuscular blocking agents (muscle relaxants) are useful and common adjuncts to general anesthesia for human beings, but have not been used extensively during anesthesia of large animal species. Over a 3-year period, atracurium or pancuronium were used as adjuncts to general anesthesia for 89 anesthetic procedures in 88 equids (of 18 breeds and age ranging in age from 5 weeks to 25 years) at the teaching hospital. Forty-one of the anesthetic procedures were for abdominal surgery, and orthopedic (n = 19), ophthalmologic (n = 17), thoracotomy (n = 1), and soft tissue (n = 14) procedures composed the rest. Most equids were given atracurium because it was less expensive than pancuronium. Initial dosage of either relaxant ranged from 0.12 to 0.2 mg/kg of body weight IV, and repeat doses ranged from 10 to 30 mg. Relaxants were used for as long as 205 minutes. Muscles of the face or hind limb digital extensor muscles were used to monitor relaxation. Muscles of the hind limb were more sensitive to the effects of relaxants than were muscles of the face. At the end of a surgical procedure, just prior to being taken to the recovery stall, a relaxant antagonist, edrophonium (0.5 to 1 mg/kg), was administered IV to each equid. Edrophonium caused blood pressure to increase in most of the equids. Heart rate change was variable, with approximately half the equids having no change or increased heart rate and the remainder having decreased heart rate. Recovery to standing after anesthesia was rated excellent or good for 72 equids, fair for 11, and poor for 2.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of the organophosphate trichlorfon on the neuromuscular blocking activity of atracurium in halothane-anesthetized horses

To determine whether cholinesterase inhibition by an organophosphate would influence atracurium's neuromuscular blockade, six horses were anesthetized and paralyzed with atracurium (total of five injections per horse) on experimental Day 1, then were given trichlorfon (64 mg/kg per os) 6 days later. On Day 7, horses were anesthetized and paralyzed in the same manner as on experimental Day 1. Blood was taken to measure serum cholinesterase activity prior to anesthesia on Days 1 and 7. No significant difference was noted in atracurium's neuromuscular blocking activity between the 2 experimental days (P less than 0.05), despite Day 7 cholinesterase activity that was 16% of pre-trichlorfon values. For atracurium Injections 1 and 2-5, 85 and 43 micrograms/kg of atracurium, respectively, were required to produce a 95-99% reduction in hoof twitch. The time from injection to maximum twitch reduction was approximately 9 min after Injection 1 and 5 min after subsequent injections. Time from injection to maximum twitch reduction was significantly longer for Injection 1 than Injections 2-5 on both experimental days. The time from maximum twitch reduction until 10% recovery was approximately 8 min, with no significant difference between experimental days. The time for twitch recovery from 10 to 75% was approximately 17 min for all injections. Antagonism of atracurium with edrophonium caused the twitch height to return to pre-atracurium strength in approximately 7 min. Edrophonium caused a significant increase in arterial blood pressure. Heart rate change was variable after edrophonium.(ABSTRACT TRUNCATED AT 250 WORDS)     

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 ethylene glycol-induced nephrotoxicosis in a dog

Ethylene glycol-induced nephrotoxicosis was diagnosed in a dog with acute renal failure. Histologically, the dog had proximal tubular degeneration and necrosis, intraluminal calcium oxalate crystals, generally intact tubular basement membranes, and evidence of tubular regeneration. After 20 days of peritoneal dialysis and diuresis, renal function was adequate to maintain homeostasis without supportive care. Nine weeks after onset of the ethylene glycol-induced renal failure, the dog's kidneys were histologically and functionally normal.     

A comparison of edrophonium and neostigmine for the reversal of mivacurium-induced neuromuscular blockade in sheep

The rate of reversal of neuromuscular block was compared in 36 sheep receiving either edrophonium (500 μg kg⁻¹) and atropine (80 μg kg⁻¹), neostigmine (50 μg kg⁻¹) and atropine (80 μg kg⁻¹) or saline (10 ml), using the train of four count (TO4C) recorded at n. facialis - m. levator nasolabialis. Neuromuscular block was produced with mivacurium (200 μg kg⁻¹) followed later by a single incremental dose of 70 μg kg⁻¹. Antagonists or saline were given when spontaneous recovery from the incremental dose (T04C = 1) = 1 begun. The T04C increased from 1 to 4 in all animals, in all treatment groups within 10 minutes of reversal. The T04C was 4 in all animals five minutes after edrophonium, and seven minutes after neostigmine; differences were not statistically significant. The T04C was significantly higher with edrophonium two and three minutes after antagonism compared with saline. The data show that spontaneous recovery from mivacurium is rapid in sheep, although reversal is accelerated by anticholinesterase drugs.     

Reversal of atrial tachycardia with intravenous administration of verapamil in a dog

Intravenous administration of verapamil at low dosage was effective in reversal of atrial tachycardia of unknown origin in a dog. The sinus rhythm remained normal for 24 hours before it reverted back to atrial tachycardia. A second IV administration of verapamil was effective in reversal of the atrial tachycardia, and a tapering dosage of verapamil, PO, was used to maintain normal sinus rhythm.