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.     

Twitch potentiation: a potential source of error during neuromuscular monitoring with acceleromyography in anesthetized dogs

ObjectiveTo measure twitch potentiation (the staircase phenomenon) in anesthetized dogs, and assess its relevance during neuromuscular monitoring with acceleromyography (AMG).Study designRandomized, prospective clinical trial.AnimalsSixteen dogs undergoing ovariohysterectomy.MethodsUnder isoflurane anesthesia, neuromuscular function was monitored with train-of-four (TOF) stimuli every 15 seconds and quantified by AMG. Neuromuscular blockade (NMB) was produced with 0.15 mg kg^?1 atracurium IV. Dogs were randomly divided into two groups; a potentiation group (PG) in which TOF stimulation was applied for 20 minutes before atracurium was administered; and a control group (CG) where no such time was allowed. In both groups, the AMG was calibrated (at tCAL) just before atracurium was administered. TOF stimulation continued throughout the experiment in all dogs. The height of the first twitch (T₁) (expressed as a fraction of T₁ at tCAL) and train-of-four ratio (TOFR) were recorded until TOFR returned to ≥90%.ResultsIn PG, T₁ increased significantly (p = 0.0078) from a median of 102% (range, 95, 109) at baseline to 118% (100, 142) at 20 minutes. In PG, no difference was found between T₁ at tCAL (immediately before atracurium administration) and T₁ when neuromuscular transmission returned (p = 0.42). In the CG, T₁ increased significantly between tCAL and the time neuromuscular transmission returned (p = 0.027). TOFR did not increase during twitch potentiation (all p = 0.32).Conclusions and clinical relevanceT₁ increased significantly during 20 minutes of uninterrupted TOF stimulation in the absence of NMB, establishing that twitch potentiation occurs in anesthetized dogs. With no time for potentiation, T₁ increased during the course of recovery from NMB; this phenomenon introduces a bias in T₁ measurements and could affect studies reporting potency and duration of NMB based on T₁ or single twitches. TOFR was unaltered by potentiation emphasizing its clinical usefulness for excluding post-operative residual NMB.     

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.     

Determination of the effective dosage of tiletamine–zolazepam–ketamine–xylazine,with or without methadone,in dogs

ObjectiveTo determine the effective dosage of the combination tiletamine–zolazepam–ketamine–xylazine (TKX), with or without methadone, in dogs.Study designProspective, randomized, experimental study.AnimalsA total of 29 dogs.MethodsDogs were randomly administered TKX (group TKX, n = 13) or combined with 0.3 mg kg^–1 of methadone (group TKXM, n = 16) intramuscularly. The TKX solution contained tiletamine (50 mg mL^–1), zolazepam (50 mg mL^–1), ketamine (80 mg mL^–1) and xylazine (20 mg mL^–1). The effective dosages for immobility in 50% and 95% of the population (ED₅₀ and ED₉₅) were estimated using the up-and-down method. Approximately 20 minutes after drug administration, a skin incision was performed and the response was judged as positive or negative if the dogs moved or did not move, respectively. The TKX volume for the subsequent dog in the same group was increased or decreased by 0.005 mL kg^–1 if the response of the previous dog was positive or negative, respectively. Heart and respiratory rates, and sedation/anesthesia scores (range 0–21) were recorded before and 15 minutes after drug administration.ResultsEstimated ED₅₀ and ED₉₅ (95% confidence intervals) were: TKX, 0.025 (0.020–0.029) and 0.026 (0.010–0.042) mL kg^–1; TKXM, 0.022 (0.018–0.025) and 0.033 (0.017–0.049) mL kg^–1. Median (interquartile range) scores for sedation/anesthesia were 17 (16–18) and 17 (15–20), and times until lateral recumbency were 5 (4–6) and 6 (4–10) minutes in TKX and TKXM, respectively (p > 0.05). In both groups heart and respiratory rates decreased, but values remained acceptable for anesthetized dogs.Conclusions and clinical relevanceThe results provide a guide for volumes of TKX and TKXM in dogs requiring restraint for minimally invasive procedures. Inclusion of methadone in the TKX combination did not influence ED₅₀.     

Alfaxalone for total intravenous anaesthesia in dogs undergoing ovariohysterectomy: a comparison of premedication with acepromazine or dexmedetomidine

ObjectiveTo describe alfaxalone total intravenous anaesthesia (TIVA) following premedication with buprenorphine and either acepromazine (ACP) or dexmedetomidine (DEX) in bitches undergoing ovariohysterectomy.Study designProspective, randomised, clinical study.AnimalsThirty-eight healthy female dogs.MethodsFollowing intramuscular buprenorphine (20 μg kg^?1) and acepromazine (0.05 mg kg^?1) or dexmedetomidine (approximately 10 μg kg^?1, adjusted for body surface area), anaesthesia was induced and maintained with intravenous alfaxalone. Oxygen was administered via a suitable anaesthetic circuit. Alfaxalone infusion rate (initially 0.07 mg kg^?1 minute^?1) was adjusted to maintain adequate anaesthetic depth based on clinical assessment. Alfaxalone boluses were given if required. Ventilation was assisted if necessary. Alfaxalone dose and physiologic parameters were recorded every 5 minutes. Depth of sedation after premedication, induction quality and recovery duration and quality were scored. A Student's t-test, Mann–Whitney U and Chi-squared tests determined the significance of differences between groups. Data are presented as mean ± SD or median (range). Significance was defined as p < 0.05.ResultsThere were no differences between groups in demographics; induction quality; induction (1.5 ± 0.57 mg kg^?1) and total bolus doses [1.2 (0 – 6.3) mg kg^?1] of alfaxalone; anaesthesia duration (131 ± 18 minutes); or time to extubation [16.6 (3–50) minutes]. DEX dogs were more sedated than ACP dogs. Alfaxalone infusion rate was significantly lower in DEX [0.08 (0.06–0.19) mg kg^?1 minute^?1] than ACP dogs [0.11 (0.07–0.33) mg kg^?1 minute^?1]. Cardiovascular variables increased significantly during ovarian and cervical ligation and wound closure compared to baseline values in both groups. Apnoea and hypoventilation were common and not significantly different between groups. Arterial haemoglobin oxygen saturation remained above 95% in all animals. Recovery quality scores were significantly poorer for DEX than for ACP dogs.Conclusions and clinical relevanceAlfaxalone TIVA is an effective anaesthetic for surgical procedures but, in the protocol of this study, causes respiratory depression at infusion rates required for surgery.     

Sedative effects of two doses of alfaxalone in combination with methadone and a low dose of dexmedetomidine in healthy Beagles

ObjectiveTo evaluate the sedative effects of two doses of alfaxalone when added to a combination of dexmedetomidine and methadone injected intramuscularly (IM) in healthy Beagles.Study designRandomized, blinded, crossover, experimental study.AnimalsA group of six adult Beagles.MethodsDogs were sedated on three different occasions with IM dexmedetomidine (3 μg kg^–1) and methadone (0.3 mg kg^–1) combined with two doses of alfaxalone (0.5 and 1 mg kg^–1; A0.5 and A1, respectively) or saline (A0). Quality of sedation, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35 and 45 minutes. Pulse and respiratory rates, oxygen saturation of haemoglobin (SpO₂) and noninvasive blood pressure (NIBP) were recorded every 5 minutes. Onset of sedation and duration of recumbency, response to venous catheterization and recovery quality were assessed. Physiological variables (analysis of variance) were analysed between treatments and within treatments compared with baseline (Student t test). Nonparametric data were analysed using Friedman and Cochran’s Q tests. Significance was p < 0.05.ResultsSedation scores were significantly higher when alfaxalone was co-administered (area under the curve; p = 0.024, A0.5; p = 0.019, A1), with no differences between doses. Onset of sedation was similar, but duration of recumbency was longer in A0.5 than in A0 [median (minimum–maximum), 43 (35–54) versus 30 (20–47) minutes, p = 0.018], but not in A1. Response to venous catheterization and tail clamping, and quality of recovery (acceptable) presented no differences between treatments. A decrease in all physiological variables (compared with baseline) was observed, except for NIBP, with no differences between treatments. All dogs required oxygen supplementation due to reduced SpO₂.Conclusions and clinical relevanceAdding alfaxalone to methadone and dexmedetomidine enhanced sedation and duration of recumbency. Although cardiopulmonary depression was limited, oxygen supplementation is advisable.     

Comparison of the neuromuscular blocking effects of cisatracurium during isoflurane or propofol anesthesia in dogs

ObjectiveTo compare the neuromuscular blocking effects of cisatracurium during isoflurane versus propofol anesthesia in dogs.Study designProspective, randomized study.AnimalsA total of 20 healthy, client-owned dogs (16 females, four males) weighing 12.5–22 kg and aged 1–8 years.MethodsDogs undergoing elective surgery were randomized in equal numbers to an isoflurane (ISO) or propofol (PPF) group. Other drugs used during anesthesia were equal between groups. Single-twitch (ST) stimulation was used to monitor neuromuscular response. After recording the baseline ST (T0), cumulative doses of cisatracurium (0.05 mg kg^–1) were administered intravenously until ST/T0 ≤5%. Effective doses 50 (ED₅₀) and 95 (ED₉₅) of cisatracurium in each group were calculated from group dose-response curves. Recovery of ST (TR) was defined as spontaneous recovery of ST to 80–120% of T0 remaining stable for 2 minutes. The ST after each dose of cisatracurium, duration 25% (time after the last dose until 25% recovery of TR), recovery index (time to recovery from 25% to 75% of TR) and duration to TR (time after the last dose until recovery of TR) were recorded.ResultsIncremental doses of cisatracurium, median (range), were 2 (1–3) in ISO and 4 (2–5) in PPF to achieve ≥95% depression of ST/T0 (p < 0.01). ED₅₀ and ED₉₅ were 20 μg kg^–1 and 117 μg kg^–1 in ISO and 128 μg kg^–1 and 167 μg kg^–1 in PPF, respectively. The duration 25%, recovery index and duration to TR, median (range), were longer in ISO [22.6 (10.3–24.3), 5.3 (3.0–7.8) and 36.1 (20.1–49.7) minutes, respectively] than in PPF [10.2 (6.8–16.5), 3.0 (2.0–3.8) and 17.7 (14.2–28.7) minutes, respectively] (p < 0.01).Conclusions and clinical relevanceCisatracurium-induced neuromuscular blockade was significantly enhanced and prolonged by isoflurane compared with propofol.     

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.     

The pharmacokinetics and pharmacodynamics of the injectable anaesthetic alfaxalone in the horse

ObjectiveTo determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin.Study designProspective experimental study.AnimalsTen (five male and five female), adult, healthy, Standardbred horses.MethodsHorses were premedicated with acepromazine (0.03 mg kg^?1 IV). Twenty minutes later they received xylazine (1 mg kg^?1 IV), then after 5 minutes, guaiphenesin (35 mg kg^?1 IV) followed immediately by IV induction of anaesthesia with alfaxalone (1 mg kg^?1). Cardiorespiratory variables (pulse rate, respiratory rate, pulse oximetry) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and plasma concentrations of alfaxalone were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. The quality of anaesthetic induction and recovery was scored on a scale of 1–5 (1 very poor, 5 excellent).ResultsThe median (range) induction and recovery scores were 4 (3–5) (good: horse slowly and moderately gently attained recumbency with minimal or no rigidity or paddling) and 4 (1–5) (good: horse stood on first attempt with some knuckling and ataxia) respectively. The monitored cardiopulmonary variables were within the range expected for clinical equine anaesthesia. The mean ± SD durations of anaesthesia from induction to sternal recumbency and from induction to standing were 42.7 ± 8.4 and 47 ± 9.6 minutes, respectively. The mean ± SD plasma elimination half life (t_1/2), plasma clearance (Clp) and volume of distribution (V_d) for alfaxalone were 33.4 minutes, 37.1 ± 11.1 mL minute^?1 kg^?1 and 1.6 ± 0.4 L kg^?1, respectively.Conclusions and clinical relevanceAlfaxalone, in a 2-hydroxypropyl-beta-cyclodextrin formulation, provides anaesthesia with a short duration of recumbency that is characterised by a smooth induction and satisfactory recovery in the horse. As in other species, alfaxalone is rapidly cleared from the plasma in the horse.     

Evaluating the efficacy of alfaxalone in corn snakes (Pantherophis guttatus)

ObjectiveAlfaxalone is a popular veterinary anesthetic; however, research on this anesthetic in snakes has been limited to ball pythons, garter snakes and several Australian species. The objective was to evaluate the anesthetic effects of alfaxalone in corn snakes (Pantherophis guttatus), a popular pet snake.Study designProspective, randomized crossover study.AnimalsA total of eight corn snakes.MethodsIn phase I, snakes were subcutaneously administered three doses of alfaxalone (5, 10 and 15 mg kg^–1) in the cranial third of the body to determine the most effective dose. In phase II, a dose of 15 mg kg^–1 was administered in the cranial and caudal thirds of the snakes to determine if injection site affected anesthesia duration. Heart rate (HR), respiratory rate (f_R), righting reflex, escape response, tail pinch, needle prick and tongue flick were monitored at baseline and 5 minute intervals until the snakes fully recovered.ResultsDuration of anesthesia differed significantly, with higher doses lasting longer than lower doses: 5 mg kg^–1 [23.8 ± 4.4 (15–30) minutes]; 10 mg kg^–1 [40.6 ± 9.4 (25–55) minutes]; and 15 mg kg^–1 [56.9 ± 8.4 (50–70) minutes], mean ± standard deviation (range). The tail pinch reflex was not completely lost in phase 1. There was a significant change in f_R over time, but this was not related to dose. HR was not different by time or dose. Duration of anesthesia was not different after administration of alfaxalone (15 mg kg^–1) in the cranial third versus the caudal third of the body; however, there was a significant decrease in HR and f_R at this dose, regardless of injection site.Conclusions and clinical relevanceBased on these results, alfaxalone (15 mg kg^–1) provides adequate anesthesia for brief procedures or intubation; however, additional analgesia is required for painful procedures.     

The effects of medetomidine on the action of vecuronium in dogs anaesthetized with halothane and nitrous oxide

ObjectiveTo quantify the effects of medetomidine on the onset and duration of vecuronium-induced neuromuscular blockade in dogs.Study designRandomized, prospective clinical study.AnimalsTwenty-four, healthy, client-owned dogs of different breeds, aged between 6 months and 10 years and weighing between 5.0 and 40.0 kg undergoing elective surgery.MethodsDogs were randomly allocated to two groups. Pre-anaesthetic medication in group M+ was intramuscular acepromazine (ACP) 25 μg kg⁻¹, morphine 0.5 mg kg⁻¹ and medetomidine 5 μg kg⁻¹. Group M− received ACP and morphine only, at the same dose rate. After induction with thiopental, anaesthesia was maintained with halothane in oxygen and nitrous oxide. End-tidal halothane concentration was maintained at 1.1%. Neuromuscular blockade was produced with intravenous vecuronium (50 μg kg⁻¹) and monitored using a train of four stimulus applied at the ulnar nerve. The times taken for loss and reappearance of the four evoked responses (twitches [T]) were recorded. Normal and nonparametric data were analysed with an independent t-test and Mann-Whitney's U-test, respectively.ResultsThe fourth twitch (T4) disappeared at similar times in each group: 107 ± 19; [72–132] (mean ± SD; [range]) seconds in M+ and 98 ± 17 [72–120] seconds in M− dogs. The first twitch (T1) was lost at 116 ± 15; [96–132] seconds in group M+ and 109 ± 19; [72–132] seconds in M−. The fourth twitch returned significantly earlier in M+ dogs: 20.8 ± 3.8 [14–28] minutes compared with 23.8 ± 2.7 [20–27] minutes (p = 0.032). The duration of drug effect (T4 absent) was significantly shorter (p = 0.027) in M+ (18.9 ± 3.7 minutes) compared with M− dogs (22.2 ± 2.9 minutes). The recovery rate (interval between reappearance of T1 and T4) was significantly more rapid (p = 0.0003) in medetomidine recipients (3.0 ± 1.2 versus 5.2 ± 1.3 minutes).Conclusion and clinical relevance Medetomidine 5 μg kg⁻¹ as pre-anaesthetic medication shortened the duration of effect of vecuronium in halothane-anaesthetized dogs and accelerated recovery, but did not affect the onset time. These changes are of limited clinical significance.     

Evaluation of xylazine–alfaxalone anesthesia for field castration in donkey foals

ObjectiveTo evaluate the anesthetic and cardiopulmonary effects of xylazine–alfaxalone anesthesia in donkey foals undergoing field castration.Study designProspective clinical study.AnimalsA group of seven standard donkeys aged [median (range)] 12 (10–26) weeks, weighing 47.3 (37.3–68.2) kg.MethodsDonkeys were anesthetized with xylazine (1 mg kg⁻¹) intravenously (IV) followed 3 minutes later by alfaxalone (1 mg kg⁻¹) IV. Additional doses of xylazine (0.5 mg kg⁻¹) and alfaxalone (0.5 mg kg⁻¹) IV were administered as needed to maintain surgical anesthesia. Intranasal oxygen was supplemented at 3 L minute⁻¹. Heart rate (HR), respiratory rate (f_R) and mean arterial pressure (MAP) by oscillometry were recorded before drug administration and every 5 minutes after induction of anesthesia. Peripheral oxygen saturation (SpO₂) was recorded every 5 minutes after induction. Time to recumbency after alfaxalone administration, time to anesthetic re-dose, time to first movement, sternal and standing after last anesthetic dose and surgery time were recorded. Induction and recovery quality were scored (1, very poor; 5, excellent).ResultsMedian (range) induction score was 5 (1–5), and recovery score 4 (1–5). Overall, two donkeys were assigned a score of 1 (excitement) during induction or recovery. HR and MAP during the procedure did not differ from baseline. f_R was decreased at 5 and 10 minutes but was not considered clinically significant. SpO₂ was <90% at one time point in two animals.Conclusions and clinical relevanceXylazine–alfaxalone anesthesia resulted in adequate conditions for castration in 12 week old donkeys. While the majority of inductions and recoveries were good to excellent, significant excitement occurred in two animals and may limit the utility of this protocol for larger donkeys. Hypoxemia occurred despite intranasal oxygen supplementation.     

Effects of ketamine or midazolam continuous rate infusions on alfaxalone total intravenous anaesthesia requirements and recovery quality in healthy dogs: a randomized clinical trial

ObjectiveTo determine the alfaxalone dose reduction during total intravenous anaesthesia (TIVA) when combined with ketamine or midazolam constant rate infusions and to assess recovery quality in healthy dogs.Study designProspective, blinded clinical study.AnimalsA group of 33 healthy, client-owned dogs subjected to dental procedures.MethodsAfter premedication with intramuscular acepromazine 0.05 mg kg^-1 and methadone 0.3 mg kg^-1, anaesthetic induction started with intravenous alfaxalone 0.5 mg kg^-1 followed by either lactated Ringer’s solution (0.04 mL kg^-1, group A), ketamine (2 mg kg^-1, group AK) or midazolam (0.2 mg kg^-1, group AM) and completed with alfaxalone until endotracheal intubation was achieved. Anaesthesia was maintained with alfaxalone (6 mg kg^-1 hour^-1), adjusted (±20%) every 5 minutes to maintain a suitable level of anaesthesia. Ketamine (0.6 mg kg^-1 hour^-1) or midazolam (0.4 mg kg^-1 hour^-1) were employed for anaesthetic maintenance in groups AK and AM, respectively. Physiological variables were monitored during anaesthesia. Times from alfaxalone discontinuation to extubation, sternal recumbency and standing position were calculated. Recovery quality and incidence of adverse events were recorded. Groups were compared using parametric analysis of variance and nonparametric (Kruskal-Wallis, Chi-square, Fisher’s exact) tests as appropriate, p < 0.05.ResultsMidazolam significantly reduced alfaxalone induction and maintenance doses (46%; p = 0.034 and 32%, p = 0.012, respectively), whereas ketamine only reduced the alfaxalone induction dose (30%; p = 0.010). Recovery quality was unacceptable in nine dogs in group A, three dogs in group AK and three dogs in group AM.Conclusions and clinical relevanceMidazolam, but not ketamine, reduced the alfaxalone infusion rate, and both co-adjuvant drugs reduced the alfaxalone induction dose. Alfaxalone TIVA allowed anaesthetic maintenance for dental procedures in dogs, but the quality of anaesthetic recovery remained unacceptable irrespective of its combination with ketamine or midazolam.     

Evaluation of alfaxalone total intravenous anesthesia in rabbits (Oryctolagus cuniculus) premedicated with dexmedetomidine or dexmedetomidine and buprenorphine

ObjectiveTo evaluate alfaxalone for total intravenous anesthesia (TIVA) in rabbits premedicated with dexmedetomidine or dexmedetomidine and buprenorphine.Study designCrossover study (part 1) with observational study (part 2).AnimalsA total of eight New Zealand White rabbits (Oryctolagus cuniculus), four female and four male, aged 12–16 weeks and weighing 2.8–3.5 kg in part 1. Separately, four additional rabbits in part 2.MethodsCrossover study design with eight rabbits per treatment. Rabbits were administered treatment D, dexmedetomidine (0.2 mg kg^–1), or treatment DB, dexmedetomidine (0.1 mg kg^–1) and buprenorphine (0.05 mg kg^–1) intramuscularly. Anesthesia was induced with alfaxalone intravenously until a supraglottic airway device was placed to deliver 100% oxygen. Anesthesia was maintained with alfaxalone (TIVA). Infusion rates were adjusted to achieve an absent pedal withdrawal reflex. Heart rate, respiratory rate, noninvasive blood pressure, end-tidal carbon dioxide partial pressure and peripheral hemoglobin oxygen saturation (SpO₂) were recorded every 5 minutes. Subsequently, four rabbits underwent ovariohysterectomy using treatment DB and alfaxalone TIVA.ResultsThe mean ± standard deviation alfaxalone infusion rate was 9.6 ± 2.6 and 4.5 ± 1.3 mg kg^–1 hour^–1 for treatments D and DB, respectively. In both treatments, blood pressure remained within acceptable range and SpO₂ was > 95%. Postinduction apnea and respiratory depression were observed in both treatments and managed with manual positive pressure ventilation. Four separate rabbits underwent successful ovariohysterectomy with treatment DB and alfaxalone TIVA. One rabbit required supplementation with inhalant anesthesia; three rabbits were successfully maintained using alfaxalone TIVA alone.Conclusions and clinical relevancePremedication with dexmedetomidine–buprenorphine combined with alfaxalone TIVA may be a viable alternative for performing abdominal surgery in the rabbit. The use of supplemental oxygen and ability to provide respiratory support are advised.     

Field immobilization using alfaxalone and alfaxalone–medetomidine in free-ranging koalas (Phascolarctos cinereus): a randomized comparative study

ObjectiveTo characterize and compare two intramuscular drug protocols using alfaxalone and alfaxalone–medetomidine combination for the field immobilization of free-ranging koalas.Study designBlinded, randomized, comparative field study.AnimalsA total of 66 free-ranging koalas from the Mount Lofty Ranges, South Australia.MethodsKoalas were randomly allocated into two groups. Group A animals were given alfaxalone alone at 3.5 mg kg^–1. Group AM animals were given alfaxalone 2 mg kg^–1 and medetomidine 40 μg kg^–1, reversed with atipamezole at 0.16 mg kg^–1. Blinded operators recorded heart rate (HR), respiratory rate (f_R), cloacal temperature, depth of sedation and times to: first effect, sedation suitable for clinical interventions, first arousal and full recovery. Data were analysed using independent t test, Mann–Whitney U test, chi-square analysis and log-rank test at 5% level of significance.ResultsSuitable immobilization for clinical examination and sample collection was achieved in all animals. In groups A and AM, median time to working depth was 6.5 minutes (range: 3.4–15) and 8.1 minutes (range: 4.3–24) and time to complete recovery was 66 minutes (range: 12–138) and 34 minutes (range: 4–84), respectively, following reversal. Time to first effect was significantly shorter in group A (p = 0.013), whereas time to full arousal was significantly shorter in group AM (p = 0.007) probably due to the administration of atipamezole. Maximum HR was 117 ± 28 beats minute^–1 in group A, which was a significant increase from baseline values (p < 0.0001), whereas group AM showed a significant tachypnoea of 67 ± 25 (normal f_R 10–15; p < 0.0001).Conclusions and clinical relevanceBoth the protocols produced immobilization, enabling clinical examination and sample collection; however, protocol AM was more suitable for field work due to shorter recovery times.     

The post-tetanic count during vecuronium-induced neuromuscular blockade in halothane-anaesthetized dogs

ObjectiveTo evaluate the post‐tetanic count (PTC) for predicting the return of reversible neuromuscular blockade at the n. facialis–m. nasolabialis (nF–mNL) and n. ulnaris–mm. carpi flexorii (nU–mCF) nerve‐muscle units (NMUs) during profound vecuronium neuromuscular blockade in halothane‐anaesthetized dogs.Study designRandomized, prospective, experimental study.AnimalsTwenty‐five dogs (seven male 18 female) undergoing surgery; mean age: 4.8 years; mean body weight 22 kg.MethodsThirty minutes after acepromazine (0.05 mg kg^?1) and morphine (0.5 mg kg^?1) pre‐medication, anaesthesia was induced with intravenous (IV) thiopental and maintained with halothane, N₂O and O₂. The lungs were mechanically ventilated and end‐tidal halothane concentration (Fe′_HAL) maintained at 1.04%. Neuromuscular transmission was monitored using the train‐of‐four count (TOFC) at one nF–mNL and both nU–mCF units. Vecuronium (50 µg kg^?1 IV) was injected after 15 minutes constant Fe′_HAL. When the first twitch (T1) at both nU–mCF units had disappeared (t = 0) one (randomly allocated) ulnar nerve was stimulated every 5 minutes using PTC; TOF stimulation continued at the other sites. The PTC was plotted against the interval between recording time and T1's reappearance at the other NMUs.ResultsAt t = 0, the mean PTC in the contralateral nU–mCF unit was 18 (range 0–20). Mean PTC was a minimum at t = 5, rising to the maximum (20) at 25 minutes. Six dogs were vecuronium‐resistant as monitored by PTC. Excluding data from these revealed a strong negative relationship between ulnar PTC and the time taken for T1's return at the facial (r = ?0.7018; p < 0.00001) and contralateral ulnar (r = ?0.8409; p < 0.00001) NMUs.Conclusion and clinical relevancePost‐tetanic count monitoring beginning >5 minutes after the TOFC at nU–mCF = 0 provided a reliable estimate of T1's return at ulnar and facial NMUs.     

Comparison between intravenous lidocaine and fentanyl on cough reflex and sympathetic response during endotracheal intubation in dogs

ObjectiveTo compare the effects of intravenous (IV) lidocaine and fentanyl on the cough reflex and autonomic response during endotracheal intubation in dogs.Study designRandomized, blinded, superiority clinical trial.AnimalsA total of 46 client-owned dogs undergoing magnetic resonance imaging.MethodsAfter intramuscular methadone (0.2 mg kg^–1), dogs were randomized to be administered either IV lidocaine (2 mg kg^–1; group L) or fentanyl (7 μg kg^–1; group F). After 5 minutes, alfaxalone was administered until endotracheal intubation was possible (1 mg kg^–1 IV over 40 seconds followed by 0.4 mg kg^–1 increments to effect). Total dose of alfaxalone was recorded and cough reflex at endotracheal intubation was scored. Heart rate (HR) was continuously recorded, Doppler systolic arterial blood pressure (SAP) was measured every 20 seconds. Vasovagal tonus index (VVTI) and changes (Δ) in HR, SAP and VVTI between pre-intubation and intubation were calculated. Groups were compared using univariate and multivariate analysis. Statistical significance was set as p < 0.05.ResultsGroup F included 22 dogs and group L 24 dogs. The mean (± standard deviation) alfaxalone dose was 1.1 (± 0.2) and 1.35 (± 0.3) mg kg^–1 in groups F and L, respectively (p = 0.0008). At intubation, cough was more likely in group L (odds ratio = 11.3; 95% confidence intervals, 2.1 – 94.2; p = 0.01) and HR increased in 87.5% and 54.5% of groups L and F, respectively (p = 0.02). The median (range) ΔHR between pre-intubation and intubation was higher (13.1%; – 4.3 to + 55.1) in group L (p = 0.0021). Between groups, SAP and VVTI were similar.Conclusion and clinical relevanceAt the stated doses, whilst reducing the alfaxalone dose, fentanyl is superior to lidocaine in suppressing the cough reflex and blunting the increase in HR at endotracheal intubation in dogs premedicated with methadone.     

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.     

The effect of low dose rocuronium bromide on eyeball position, muscle relaxation, and ventilation in dogs

A central eyeball position is often required during sedation or anaesthesia to facilitate examination of the eye. However, use of neuromuscular blockade to produce a central eye position may result in depressed ventilation. This study evaluated the eyeball position, muscle relaxation and changes in ventilation during general anaesthesia after the IV administration of 0.1 mg kg^?1 rocuronium. With client consent, 12 dogs of different breeds, body mass 27.2 ± 11.8 kg, aged 5.6 ± 2.8 years (mean ± SD) were anaesthetized for ocular examination. Pre‐anaesthetic medication was 0.01 mg kg^?1 medetomidine and 0.2 mg kg^?1 butorphanol IV. Anaesthesia was induced with propofol to effect and maintained with 10 mg kg^?1 hour^?1 propofol by infusion. The dogs were placed in left lateral recumbency, their trachea intubated and connected to a circle breathing system (Fi O₂ = 1.0). All dogs breathed spontaneously. The superficial peroneal nerve of the right hind leg was stimulated every 15 seconds with a train‐of‐four (TOF) stimulation pattern and neuromuscular function was assessed with an acceleromyograph (TOF‐Guard). Adequacy of ventilation was measured with the Ventrak 1550. After 10 minutes of anaesthesia to allow stabilisation of baseline values, 0.1 mg kg^?1 rocuronium was administered IV. Minute volume (Vm ), tidal volume (Vt ), respiratory rate (RR), Pe ′CO₂ and maximal depression of T1 and TOF ratio were measured. Data were analysed using a paired t‐test. The changes in the eyeball position were recorded. A total of 100 ± 33 seconds after the injection of rocuronium, T1 was maximally depressed to 62 ± 21% and the TOF ratio to 42 ± 18% of baseline values. Both variables returned to baseline after 366 ± 132 seconds (T1) and 478 ± 111 seconds (TOF). There was no significant reduction in Vm (2.32 ± 1.1 L minute^?1), Vt (124.1 ± 69.3 mL) and RR (10 ± 3.8 breaths minute^?1) and no increase in Pe ′CO₂ (6.5 ± 2.1 kPa (48.8 ± 16.1 mm Hg)) throughout the procedure. The eyeball rotated to a central position 35 ± 7 seconds after rocuronium IV and remained there for a minimum of 20 ± 7 minutes in all dogs. We conclude that rocuronium at a dose of 0.1 mg kg^?1 can be administered to dogs IV with minimal changes in ventilatory variables. The eyeball is fixed in a central position for at least 20 minutes, which greatly facilitates clinical examination.