Effect of Ketorolac Tromethamine on Atracurium-Induced Neuromuscular Blockade in Anesthetized Dogs

Objective —The purpose of this study was to determine the effect of ketorolac tromethamine or placebo on the neuromuscular blockade induced by an infusion of atracurium in isoflurane-anesthetized dogs. Design —Randomized, controlled trial. Animals —Six healthy, adult mixed-breed dogs (five female, one male) weighing 24.8 ± 2.8 kg. Methods —Dogs were studied on two occasions with a minimum of 7 days between studies. Dogs were induced with 5% isoflurane in oxygen and maintained with 1.6 ± minimum alveolar concentration (MAC) end-tidal isoflurane. Neuromuscular blockade was assessed using the train of-four response. Once 50% depression of the first twitch (T₁) was achieved, the atracurium infusion rate was held constant for 30 minutes. Then ketorolac, 0.5 mg/kg, or the same volume of placebo (0.9% sodium chloride solution) was administered intravenously and the atracurium infusion maintained for an additional 60 minutes. Before and at 2, 5, 10, 15, 30, and 60 minutes after ketorolac or placebo, the percent depression of T₁ and the fourth twitch to the first twitch (T₄/T₁) ratio were recorded. The atracurium infusion was discontinued and the time for T₁ to recover from 50% to 75% of its original value was recorded. At 75% T₁, edrophonium, 0.5 mg/kg intravenously, was administered to antagonize the residual blockade. Results —There was no significant difference in T₁%, T₄/T₁ ratio, or recovery time after ketorolac administration compared with placebo. Conclusions —Ketorolac, 0.5 mg/kg intravenously, has no significant effect on either atracuriuminduced neuromuscular blockade or recovery time for T₁ in isoflurane-anesthetized dogs. Clinical Relevance —The concurrent use of atracurium should not be a contraindication for the administration of ketorolac for intraoperative or postoperative analgesia.     

Use of rocuronium administered by continuous infusion in dogs

OBJECTIVE: A clinical trial to determine whether continuous infusion administration technique was suitable for maintaining neuromuscular blockade with rocuronium bromide in dogs. ANIMALS: Twenty-two dogs, 10 males and 12 females, median age 2 years 4 months, median weight 32 kg undergoing elective surgical procedures under general anaesthesia: ASA classification I or II. MATERIALS AND METHODS: After induction of anaesthesia, neuromuscular function was evaluated using train-of-four (TOF) stimulation of the dorsal buccal branch of the facial nerve. A bolus dose of 0.5 mg kg(-1) rocuronium was administered intravenously and an infusion of 0.2 mg kg(-1) hour(-1) was started immediately. Neuromuscular blockade was assessed visually by counting the number of twitches observed during TOF stimulation repeated at 10-second intervals. RESULTS: The bolus dose of rocuronium abolished the response to TOF stimulation in 21 of the 22 dogs. The median onset time of neuromuscular blockade (complete loss of all four twitches) was 82 seconds (range 38-184 seconds). Median infusion duration was 76 minutes (range 20.3-146 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: This protocol of rocuronium administration was considered to be effective in dogs. Constant infusion of rocuronium is easily applicable to clinical practice and further work is required on infusion titration.     

Effects of atracurium administered by continuous intravenous infusion in halothane-anesthetized horses

Atracurium (0.4 mg/ml in isotonic NaCl solution) was administered by IV infusion to 7 healthy adult horses for 2 hours. Over the 2-hour period, a 95 to 99% reduction of train-of-four hoof-twitch response was maintained by 0.17 +/- 0.01 mg of atracurium/kg of body weight/h, for a total of 161 +/- 6 mg of atracurium (mean +/- SEM) for horses 1 to 4, 6, and 7. Horse 5, a mare in estrus, required 0.49 mg of atracurium/kg/h to maintain comparable relaxation. Hoof-twitch recovery time from 10 to 75% of baseline strength was 19.8 +/- 2.5 minutes for all horses. The 10 to 75% recovery time for horse 5 was 18 minutes. Recovery time from discontinuation of halothane until standing was 86 +/- 14 minutes (range, 55 to 165 minutes). Horse 5 had a 165-minute recovery. Regarding recovery from anesthesia, 3 recoveries were rated as excellent, 1 recovery good, and 2 recoveries as fair. Horse 5 laid quietly until she stood with 1 strong, smooth effort.     

Duration of action and hemodynamic properties of mivacurium chloride in dogs anesthetized with halothane.

OBJECTIVE: To describe onset and duration of neuromuscular blockade induced by mivacurium chloride and its associated hemodynamic effects at 3 dosages in healthy dogs. ANIMALS: 7 Labrador Retrievers. PROCEDURE: Anesthesia was induced with thiopental and maintained with halothane in oxygen, and dogs were mechanically ventilated to end-tidal P(CO)2 between 35 and 40 mm Hg. Core temperature, end-tidal P(CO)2, and halothane concentration were kept constant throughout the experiment. Neuromuscular function was assessed by evaluation of the train-of-four response to a supramaximal electrical stimulus of 2 Hz applied to the ulnar nerve every 10 seconds. Blood for determination of plasma cholinesterase activity was obtained prior to administration of mivacurium, a bolus of which was administered IV, using a randomized Latin-square design for dosages of 0.01, 0.02, and 0.05 mg/kg of body weight. RESULTS: All dogs had typical plasma cholinesterase activity. After administration of mivacurium, differences were not evident between groups in heart rate, systolic, mean, or diastolic blood pressure, change at any time in heart rate, systolic, mean, or diastolic blood pressure, or pH. Interval from onset to 100% neuromuscular blockade was 3.92+/-1.70, 2.42+/-0.53, and 1.63+/-0.25 minutes at dosages of 0.01, 0.02, and 0.05 mg/kg, respectively. Duration of measurable neuromuscular blockade was 33.72+/-12.73, 65.38+/-12.82, and 151.0+/-38.50 minutes, respectively. Time of onset and duration of effect differed significantly among dosages. CONCLUSIONS AND CLINICAL RELEVANCE: Mivacurium provides good hemodynamic stability at the dosages tested. In dogs, this drug has a rapid onset and long duration of effect.     

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.     

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.     

A clinical study of the effects of rocuronium in isoflurane-anaesthetized cats

OBJECTIVE: To evaluate the neuromuscular blocking and chronotropic effects of rocuronium bromide in cats anaesthetized for surgery. STUDY DESIGN: Prospective clinical trial. ANIMALS: Twenty-two healthy cats of mixed breed presented for ovariectomy (n = 13) or castration (n = 9). Mean body mass (+/-SD) was 3.6 +/- 0.65 kg and mean age was 10.25 +/- 2.63 months. METHODS: Anaesthesia was induced with intravenous (IV) midazolam (0.3 mg kg(-1)), ketamine (3 mg kg(-1)) and butorphanol (0.4 mg kg(-1)). Tracheal intubation was performed and anaesthesia was maintained with isoflurane delivered in 100% oxygen. Neuromuscular function was monitored using acceleromyography applied at the ulnar nerve. This was stimulated by using the train-of-four (TOF) stimulus pattern (2 Hz) delivered every 15 seconds. The first train was made to establish baseline values for the first twitch (T1) and the TOF-ratio (T4:T1). Rocuronium (0.6 mg kg(-1) IV) was given and the following periods were recorded beginning at the end of injection: (1) lag time (LT) - to the first signs of T1 depression; (2) onset time (OT) - to the total ablation of T1; (3) duration of action (T1(25)) - to 25% recovery of the baseline value for T1; (4) T1(50)- to 50% baseline T1 restoration; (5) to TOF-ratios of 0.7 and 0.9. The time taken for T1 to recover from 75% to 25% depression (T1(25-75)) was also recorded. Heart rate (HR) was taken every minute for 15 minutes, beginning 5 minutes before rocuronium was injected. RESULTS: Rocuronium (0.6 mg kg(-1)) had a mean LT of 15.0 +/- 0 seconds, OT of 46 +/- 11 seconds and T1(25) of 13.2 +/- 2.7 minutes. The mean time for TOF 0.7 and 0.9 was 17.3 +/- 5.4 and 20.7 +/- 5.4 minutes respectively. The mean T1(25-75) was 4.8 +/- 2.4 minutes. No significant changes in HR were observed at any of the time intervals recorded. CONCLUSION: Rocuronium is an effective nondepolarizing muscle relaxant in the cat under the clinical conditions of this study. It has a rapid onset, a short duration of action and did not cause significant changes in HR.     

Effects of sevoflurane,propofol or alfaxalone on neuromuscular blockade produced by a single intravenous bolus of rocuronium in dogs

ObjectiveTo compare the effects of sevoflurane, propofol and alfaxalone on the neuromuscular blockade induced by a single intravenous bolus of rocuronium in dogs.Study designA randomized, prospective, crossover experimental study.AnimalsA total of eight adult Beagle dogs (four female, four male), weighing 8.9–15.3 kg and aged 5–7 years.MethodsThe dogs were anesthetized three times with 1.25× minimum alveolar concentration of sevoflurane (SEVO treatment) and 1.25× minimum infusion rate of propofol (PROP treatment) or alfaxalone (ALFX treatment) at intervals of ≥14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC), a single bolus dose of rocuronium (1 mg kg^–1) was administered intravenously. The times from rocuronium administration to achieving TOF count 0 (onset time), from achieving TOF count 0 to the reappearance of TOF count 4 (clinical blockade period), from 25% to 75% of TOFRC (recovery index) and from achieving TOF count 0 to TOF ratio/TOFRC >0.9 (total neuromuscular blockade duration) were recorded.ResultsThe onset time and recovery index did not differ among the treatments. The median clinical blockade period was longer in the SEVO treatment [27.3 (26.0–30.3) minutes] than in PROP [16.6 (15.4–18.0) minutes; p = 0.002] and ALFX [22.4 (18.6–23.1) minutes; p = 0.017] treatments; and longer in the ALFX treatment than in the PROP treatment (p = 0.020). The mean total neuromuscular blockade duration was longer in the SEVO treatment (43.7 ± 9.9 minutes) than in PROP (25.1 ± 2.7 minutes; p < 0.001) and ALFX (32.5 ± 8.4 minutes; p = 0.036) treatments.Conclusions and clinical relevanceCompared with alfaxalone and propofol, sevoflurane prolonged rocuronium-induced neuromuscular blockade by a significantly greater extent in dogs.     

Respiratory Depressant and Skeletal Muscle Relaxant Effects of Low-Dose Pancuronium Bromide in Spontaneously Breathing, Isoflurane-Anesthetized Dogs

Objective—To assess and compare the respiratory depressant and skeletal muscle relaxant effects of two low doses of a nondepolarizing neuromuscular blocker, pancuronium bromide. To determine if a “low dose” of pancuronium bromide can produce selective skeletal muscle relaxation in extraocular muscles sufficient to perform intraocular surgery while sparing or minimizing depression of muscles of ventilation. Study Design—Blinded, randomized crossover, placebo controlled study. Animals—Six healthy, adult mongrel dogs weighing 20.8 ±1.9 kg. Methods—Spontaneously breathing, isoflurane-anesthetized dogs received 0.02 mg/kg pancuronium bromide, intravenously (IV), (high dose [HD]), 0.01 mg/kg pancuronium bromide, IV, (low dose [LD]), or saline placebo IV in a blinded, randomized crossover study. Indices of patient ventilation including tidal volume (Vt), respiratory rate (RR), and minute ventilation (V_E) were recorded throughout the study period. Serial arterial blood gas analyses were performed at timed intervals. Neuromuscular blockade of skeletal muscle was assessed at timed intervals with train-of-four stimulus/response ratios. Eye position scores, based on the degree of ocular rotation from a neutral gaze axis, were assigned by an ophthalmologist who was blinded to the treatment given. Results—Vt and V_E in HD dogs decreased by 82% from baseline after administration of pancuronium bromide. Similarly, Vt and V_E in LD dogs decreased 40% and 55%, respectively. Decreased ventilation in HD dogs corresponded with significant (P< .05) neuromuscular blockade, as indicated by train-of-four ratio less than 75% between 0 and 60 minutes. Eye position scores in HD and LD dogs were suitable for intraocular surgery between 0 and 60 minutes. Eye position scores in five of six control dogs were unsuitable for intraocular surgery at any time period. Conclusions—LD dogs experienced only transient, mild to moderate respiratory depression compared with HD dogs, which experienced prolonged, moderate to severe respiratory depression. Both LD and HD dogs acquired and maintained eye position scores suitable for intraocular surgery between 0 to 60 minutes. A “low dose” of pancuronium bromide, which would provide adequate extraocular muscle relaxation while minimizing ventilatory depression, was not identified. Clinical Relevance—All patients receiving any dose of neuromuscular blocking agents should be closely monitored and receive ventilatory assistance as needed.     

The effect of low dose rocuronium on globe position, muscle relaxation and ventilation in dogs: a clinical study

OBJECTIVE: The purpose of this study was to evaluate globe position, muscle relaxation and changes in ventilatory parameters after intravenous administration of 0.1 mg/kg rocuronium. STUDY DESIGN: Prospective clinical study. ANIMAL STUDIED: Sixteen dogs of different breeds, with a body weight of 22.1 +/- 13 kg and age of 5.6 +/- 2.8 years (mean +/- SD), were anesthetized for a short ophthalmic examination requiring central position of the globe. PROCEDURES: All dogs were premedicated with 0.005 mg/kg medetomidine and 0.1 mg/kg methadone IV. Anesthesia was induced with propofol to effect and maintained with 10 mg/kg/h propofol by continuous rate infusion. Following endotracheal intubation all dogs breathed 100% oxygen via an anesthetic circle system. Neuromuscular function was assessed with an acceleromyograph (TOF-Guard, Organon Teknika NV, Turnhout, Belgium) and by stimulation of the nervus peroneus superficialis. The ventilation parameters were measured using spirometry and capnography. After baseline measurements 0.1 mg/kg rocuronium was administered IV. Minute volume (MV), tidal volume (Vt), respiratory rate (RR), end expiratory carbon dioxide concentration (PE'CO(2)) and maximal depression of the response of the first twitch (T1) of train-of-four (TOF) stimulation and train-of-four ratio (TOFR) was measured. The change in the position of the globe was recorded. RESULTS: T1 decreased to 61 +/- 18% and the TOF ratio to 45 +/- 21% of baseline values. Both parameters returned to baseline after 9 min. There was no significant reduction in MV, TV and RR and no increase in PE'CO(2). The globe rotated to a central position of 45 +/- 7.7 s after administration of rocuronium and remained there for 23 +/- 10.8 min in all dogs. CONCLUSION: Rocuronium administered intravenously at a dose of 0.1 mg/kg to dogs causes a central position of the globe but minimal impairment of ventilation parameters.     

Neuromuscular and cardiovascular effects of atracurium administered to healthy horses anesthetized with halothane

Neuromuscular and cardiovascular effects of atracurium, a nondepolarizing neuromuscular blocking agent, were evaluated in 10 halothane-anesthetized adult horses. Hind limb digital extensor tension (hoof twitch) was measured with a strain gauge to quantitate the muscle relaxant effects of atracurium. Response of facial muscles was compared with hoof twitch. Five injections of atracurium were given. Initial mean (+/- SEM) dosage of 0.07 +/- 0.01 mg of atracurium/kg of body weight caused 98.6 +/- 0.8% reduction of the preinjection hoof twitch. Subsequent dosages of 0.04 +/- 0.003 mg/kg induced a degree of relaxation similar to that induced by the initial dose. Duration of paralysis from maximal effect to 10% recovery of twitch was 12.2 +/- 1.5 minutes for the first injection. This was significantly (P less than 0.05) different from subsequent paralysis periods, which lasted approximately 7 minutes. The 10% to 75% recovery time after all injections was similar-approximately 16 minutes. The facial muscles were less affected objectively by atracurium than was the hind limb. Atracurium did not cause cardiovascular changes. When the hoof twitch had recovered to 95% of its tension before atracurium administration, 0.5 mg of edrophonium/kg, was given to antagonize neuromuscular blockade. Within 5 minutes of edrophonium administration, twitch tension exceeded that measured before atracurium administrations. Within 2 minutes of edrophonium administration, blood pressure began to increase and continued to increase approximately 10 mm of Hg above the value measured before edrophonium administration. Heart rate was not affected by edrophonium. Other muscarinic side effects of edrophonium were not observed. Of the 10 horses, 9 had good, unremarkable recovery to standing position. One horse had a violent recovery period.     

Pharmacokinetics of gentamicin in cats given Escherichia coli endotoxin

Nineteen cats were given 3 mg of gentamicin sulfate/kg of body weight by rapid IV, SC, or IM injection for baseline values. Serum concentration of gentamicin vs time data were analyzed using a noncompartmental model based on statistical moment theory. One week later, each cat was given 0.5 microgram of Escherichia coli endotoxin/kg, IV. After cats had an increase in rectal temperature of at least 1 C, 3 mg of gentamicin/kg was administered by the same route used the previous week. Serum concentration of gentamicin vs time data were analyzed, and pharmacokinetic values were compared with base-line values. For IV studies, the half-life (t1/2) of gentamicin and the mean residence time were significantly different (P less than 0.05) compared with base line, whereas the total body clearance and apparent volume of distribution at steady state were not. The harmonic mean +/- pseudo SD for the t1/2 of gentamicin after IV administration was 76.8 +/- 12.6 minutes for base line and was 65.2 +/- 12.2 minutes in the same cats given endotoxin. The t1/2 of gentamicin after SC administration was 74.6 +/- 6.2 minutes for base line and was 65.2 +/- 13.6 minutes in the same cats given endotoxin. After IM administration, the t1/2 of gentamicin was 60.3 +/- 10 minutes for base line and was 59.7 +/- 13.6 minutes in the same cats given endotoxin. After IV administration of gentamicin, the arithmetic mean +/- SD for the mean residence time was 102.4 +/- 16.1 minutes for base line vs 79.2 +/- 18.4 minutes in the same cats given endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical observations on the use of the muscle relaxant rocuronium bromide in the dog

This study was designed to evaluate the effectiveness of neuromuscular blockade with rocuronium bromide (rocuronium) in eighty dogs anaesthetised for a variety of surgical procedures. Rocuronium 0.3 or 0.6 mg/kg (G03 and G06) was administered intravenously (IV) and neuromuscular function was monitored with an acceleromyograph. Lag time (LT) was >1 min in both groups. Onset time (OT) was 2+/-0.9 and 1.1+/-0.6 min in the groups given 0.3 and 0.6 mg/kg, respectively. There was a significantly longer time of action with 0.6 mg/kg in contrast to 0.3 mg/kg rocuronium. Time of no response (TonR) was 9.1+/-4.9-16.9+/-6.1 min in the groups given 0.3 and 0.6 mg/kg, respectively. The time from the end of injection until 25% recovery of the first twitch from the baseline value (T1(25)) was 13.8+/-5.5 and 22.3+/-6.7 min in the groups given 0.3 and 0.6 mg/kg, respectively. T1(25-75) was similar in both groups. Total recovery to baseline values was achieved in 23.8+/-6.6 and 31.9+/-6.5 min in the groups given 0.3 and 0.6 mg/kg, respectively (P<0.05). Premedication, maintenance agent, body position and stimulation site had no significant influence on the pharmacodynamic parameters in both groups. It was concluded that rocuronium is an effective non-depolarising muscle relaxant in the dog under clinical conditions.     

Neuromuscular Effects of Doxacurium Chloride in Isoflurane-Anesthetized Dogs

Objective—To determine the neuromuscular effects of doxacurium chloride and to construct a dose-response curve for the drug in isoflurane-anesthetized dogs. Design—Randomized, controlled trial. Animals—Six healthy, adult, mixed-breed dogs (five female, one male) weighing 24.8 ° 2.8 kg. Methods—Anesthesia was induced with isoflurane in oxygen and maintained with 1.9% to 2.3% end-tidal isoflurane concentration. Paco₂ was maintained between 35 and 45 mm Hg with mechanical ventilation. Mechanomyography was used to quantitate the evoked twitch response of the paw after supramaximal train-of-four stimulation of the superficial peroneal nerve. After baseline values were recorded, the dogs received one of three doses of doxacurium (2.0, 3.5, 4.5 μg/kg of body weight) or a saline placebo intravenously in random order. All dogs received all treatments with at least 7 days between studies. After drug administration, the degree of maximal first twitch depression compared with baseline (T,%) was recorded. Dose-response relations of doxacurium were plotted in log dose-probit format and analyzed by linear regression to determine effective dose (ED₅₀ and ED₉₀) values for doxacurium. Results—The median log dose-probit response curve showed good data correlation (r= .999) with estimates of the ED₅₀ (2.1 μg/kg) and ED₉₀ (3.5 μg/kg) for doxacurium in isoflurane-anesthetized dogs. Mean ± SD values for T₁% (first twitch tension compared with baseline) at maximal depression after drug administration, onset (time from drug administration to maximal depression of T₁%), duration (time from maximal depression of T₁% to 25% recovery of T₁%), and recovery (time from 25% to 75% recovery of T₁%) times were 92%± 4%, 40 ± 5 minutes, 108 ± 31 minutes, and 42 ± 11 minutes for dogs treated with 3.5 μg/kg of doxacurium and 94%± 7%, 41 ± 8 minutes, 111 ± 33 minutes, and 37 ± 10 minutes for dogs treated with 4.5 μg/kg of doxacurium. Conclusion and Clinical Relevance—We conclude that doxacurium is a long-acting neuromuscular blocking agent with a slow onset of action. Doxacurium can be used to provide muscle relaxation for long surgical procedures in isoflurane-anesthetized dogs. Interpatient variability, particularly of duration of drug action, may exist in the neuromuscular response to the administration of doxacurium in dogs.     

The effect of the duration of propofol administration on recovery from anesthesia in cats

OBJECTIVE: To determine the effect of induction, a 30-minute, and a 150-minute infusion of propofol on the rate of recovery in cats. STUDY DESIGN: Randomized, cross-over, prospective experimental study. ANIMALS: Six healthy adult spayed female cats (mean 4.3, range 2-7 years old) weighing 3.9 +/- 0.5 kg. METHODS: Cats received each of three treatments: anesthetic induction with propofol (T1), induction followed by a 30-minute infusion (T30) and induction followed by a 150-minute infusion (T150). Propofol infusions were increased or decreased to maintain a sluggish pedal withdrawal reflex. Animals were monitored throughout the anesthetic period and during the recovery. Venous blood samples were collected from a central venous catheter before anesthesia and at 30 minutes for the 30-minute infusion and at 30, 60, 90, 120 and 150 minutes for the 150-minute infusion. The ability of the cat to lift its head, crawl, stand and walk without ataxia was recorded at 5, 10, 20, 40, 60, 80, 120, 160, 180, 210 and 240 minutes after the completion of propofol administration. Data from physiological values were analyzed using either a Student's t-test (30-minute infusion) or an anova (150-minute infusion). A nonparametric Friedman test (and post-hoc Tukey's Studentized range test) was used to determine whether there were differences in the time taken to recover. Results were considered significant if p < 0.05. RESULTS: Time taken to walk without ataxia was significantly greater in T150 (148 +/- 40 minutes) compared with T1 (80 +/- 15 minutes) and T30 (74 +/- 26 minutes). (No other recovery times were significantly different). Anesthesia with propofol was accompanied by a moderate but significant respiratory depression and a decrease in PCV and total protein. CONCLUSIONS AND CLINICAL RELEVANCE: Prolonged anesthesia with propofol in healthy cats may be associated with a delayed recovery.     

Use of rocuronium for endotracheal intubation of North American Gulf Coast box turtles

OBJECTIVE: To determine whether rocuronium, a reversible neuromuscular blocking agent, would provide safe, short-term immobilization to facilitate endotracheal intubation in turtles. DESIGN: Prospective study. ANIMALS: 30 healthy adult Gulf Coast box turtles. PROCEDURE: Turtles were given rocuronium, and responses were recorded every 3 minutes. Times to onset of effects, intubation, and recovery were recorded and analyzed for associations with dose and patient characteristics to determine an optimal dose range. Neostigmine and glycopyrrolate were given to augment recovery from neuromuscular blockade. RESULTS: Rocuronium administered at a dose of 0.25 to 0.5 mg/kg (0.11 to 0.23 mg/lb), IM, permitted intubation; lower doses were not effective. Mean +/- SD time to loss of the palpebral reflex was 6.4 +/- 4.0 minutes, and mean time to intubation was 9.2 +/- 6.4 minutes. Mean time to return of the palpebral reflex was 44 +/- 13.2 minutes, and mean time to walking was 55 +/- 16.6 minutes. Time to onset of effects was not associated with dose, but recovery times were prolonged with higher doses of rocuronium. Cardiac arrhythmias were observed in 13 (43%) turtles. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of rocuronium at a dose of 0.25 to 0.5 mg/kg is a safe and effective adjunct to general anesthesia in Gulf Coast box turtles. Because rocuronium does not provide any analgesic or sedative effects, the duration of neuromuscular blockade without anesthesia should be minimized to avoid undue distress.     

Xylazine premedication does not modify the onset and duration of cisatracurium blockade in anaesthetized dogs

The purpose of this study was to evaluate the effect of xylazine as premedication on the onset time and duration of cisatracurium neuromuscular blockade in anaesthetized dogs. This study was carried out on 12 healthy dogs aged 0.5-6 years and weighing 9-26 kg undergoing various elective surgical procedures. The dogs were randomly divided into two groups of t (test) and c (control), with six dogs each. In group t, premedication was conducted using acepromazine maleate 0.3 mg kg(-1) and xylazine 0.3 mg kg(-1) and in group c only acepromazine (same dose) was injected intramuscularly 20 min before general anaesthesia. After induction with thiopental, anaesthesia was maintained with halothane in oxygen to deliver an end-tidal halothane concentration of 1.1%. Neuromuscular blockade was induced with cisatracurium 0.2 mg kg(-1) and monitored using the train-of-four (TOF) stimulation pattern applied at the ulnar nerve. The onset time of cisatracurium blockade was 195 +/- 85.44 s in test and 153.3 +/- 38.16 s in control group. The duration of neuromuscular blockade was 24.8 +/- 4.79 min in t and 28.3 +/- 5.46 min in the c group. Statistical analysis of the data showed no significant difference between groups in terms of onset and duration of neuromuscular blockade.     

Glucose tolerance and insulin response in normal-weight and obese cats

Glucose tolerance and insulin response were evaluated in 9 normal-weight and 6 obese cats after IV administration of 0.5 g of glucose/kg of body weight. Blood samples for glucose and insulin determinations were collected immediately prior to and 2.5, 5, 7.5, 10, 15, 30, 45, 60, 90, and 120 minutes after glucose infusion. Baseline glucose concentrations were not significantly different between normal-weight and obese cats; however, mean +/- SEM glucose tolerance was significantly impaired in obese vs normal-weight cats after glucose infusion (half time for glucose disappearance in serum--77 +/- 7 vs 51 +/- 4 minutes, P less than 0.01; glucose disappearance coefficient--0.95 +/- 0.10 vs 1.44 +/- 0.10%/min, P less than 0.01; insulinogenic index--0.20 +/- 0.02 vs 0.12 +/- 0.01, P less than 0.005, respectively). Baseline serum insulin concentrations were not significantly different between obese and normal-weight cats. Insulin peak response after glucose infusion was significantly (P less than 0.005) greater in obese than in normal-weight cats. Insulin secretion during the first 60 minutes (P less than 0.02), second 60 minutes (P less than 0.001), and total 120 minutes (P less than 0.0003) after glucose infusion was also significantly greater in obese than in normal-weight cats. Most insulin was secreted during the first hour after glucose infusion in normal-weight cats and during the second hour in obese cats. The impaired glucose tolerance and altered insulin response to glucose infusion in the obese cats was believed to be attributable to deleterious effects of obesity on insulin action and beta-cell responsiveness to stimuli (ie, glucose).     

Observations on the muscle relaxant rocuronium bromide in the horse--a dose-response study

OBJECTIVE: To investigate the onset and duration of neuromuscular blockade of rocuronium bromide and its associated haemodynamic effects at three doses in healthy horses. STUDY DESIGN: Prospective, randomized experimental study. ANIMALS: Seven adult horses aged 3-20 (mean 10.3) years and weighing 466 +/- 44 (mean +/- SD) kg. METHODS: Horses were anaesthetized three times with at least 2 weeks between. They were pre-medicated with 0.6 mg kg(-1) xylazine and 0.01 mg kg(-1) butorphanol i.v.. Anaesthesia was induced with 2.2 mg kg(-1) ketamine and 0.1 mg kg(-1) diazepam i.v.. Following orotracheal intubation anaesthesia was maintained with isoflurane in 100% oxygen. Intermittent positive pressure ventilation was initiated and the horses were ventilated at a respiratory rate (fr) of 4-8 breaths minute(-1). Neuromuscular function was monitored with an acceleromyograph. The peroneal nerve was stimulated with train-of-four (TOF) mode at 2 Hz every 15 seconds. Each horse received, in randomly assigned order, one of the three doses of rocuronium: 0.2 mg kg(-1) (D02), 0.4 mg kg(-1) (D04) or 0.6 mg kg(-1) (D06) i.v.. Lag time, onset time, time of no response, duration of action and the TOF ratio 0.7 and 0.9 were measured. Recovery time (T1(25-75)) was calculated. Vital parameters were recorded at 5-minute intervals on a standard anaesthetic record form. RESULTS: Rocuronium produced a dose-dependent duration of action in isoflurane-anaesthetized horses. 100% block was observed in D04 and D06 but not in D02, in which the maximum decrease of the first twitch of TOF attained was 91.5 +/- 16.5%. Time to T1(25) was 13.1 +/- 5.5 minutes, 38.6 +/- 10.1 minutes and 55 +/- 9.8 minutes in D02, D04 and D06 respectively. There was a significantly shorter time for TOFR 0.9 with 0.2 mg kg(-1) compared with 0.4 and 0.6 mg kg(-1) rocuronium. T1(25-75) in D04 and D6 was not statistically significantly different. Heart rate, systolic, diastolic and mean arterial blood pressure increased slightly during the observation period. CONCLUSION: Rocuronium is an effective nondepolarizing muscle relaxant in horses under isoflurane anaesthesia. It had a dose-dependent onset and duration of action. Rocuronium did not produce significant changes in the measured cardiovascular parameters.     

Comparison between acceleromyography and visual assessment of train-of-four for monitoring neuromuscular blockade in horses undergoing surgery

ObjectiveTo compare acceleromyography (AMG) with visual assessment of train-of-four (TOF) for monitoring neuromuscular blockade and detecting residual muscle paralysis in horses receiving atracurium.Study designProspective, controlled clinical study.AnimalsNine adult, client-owned horses weighing 577 (436, 727) kg (median, minimum, maximum) and ASA physical status I–II, admitted for surgery.MethodsAn electrical nerve stimulator was used to stimulate the peroneal nerve with TOFs at 1 minute intervals. Before and after atracurium administration (0.15 mg kg⁻¹, IV), the number of twitches observed (TOF count, or TOFc) was assessed visually. When four twitches were seen (i.e., TOFc = 4) presence or absence of fade by visual assessment was recorded. Simultaneously, the response to each TOF was assessed by AMG; this measured TOFc, and twitch fade using TOF ratio (TOFR; ratio of fourth to first twitch). The anesthetist performing the visual evaluation was blinded to the AMG readings. Recovery from neuromuscular blockade was defined as the absence of fade by visual inspection or a TOFR ≥90% by AMG.ResultsDuring onset of action of the drug, fade was first detected 4 (1, 8) minutes earlier by AMG (p = 0.008). Maximal blockade started at 6 (3, 17) minutes by visual assessment and 9 (3, 25) minutes by AMG (not significantly different). Only four horses achieved complete neuromuscular blockade (TOFc of zero by both methods); in those four horses AMG did not detect the start of the return of neuromuscular transmission before visual assessment. Visual assessment indicated the return of four twitches with no fade 12 (8, 42) minutes before AMG gave a TOFR of ≥90% (p = 0.004).Conclusion and clinical relevance There was no substantial advantage for AMG in detecting the onset of atracurium-induced neuromuscular blockade. However, AMG detected residual blockade when visual assessment of TOF did not. Application of AMG is likely to reduce the incidence of residual blockade.