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1.
Wendy A. Goodwin Kirby Pasloske Helen L. Keates Millaganamada Gedara Ranasinghe Solomon Woldeyohannes Nigel Perkins 《Veterinary anaesthesia and analgesia》2019,46(2):188-199
Objective
To determine the suitability of alfaxalone total intravenous (IV) anaesthesia in horses and concurrently evaluate infusion rates, cardiovascular effects, pharmacokinetics and the quality of the anaesthetic recovery period.Study design
Prospective, experimental study.Animals
Eight Standardbred horses.Methods
Horses were premedicated with IV acepromazine (0.03 mg kg–1) and xylazine (1 mg kg–1) and anaesthesia was induced with guaifenesin (35 mg kg–1) and alfaxalone (1 mg kg–1). Anaesthesia was maintained for 180 minutes using an IV infusion of alfaxalone at a rate determined by a horse’s response to a supramaximal electrical noxious stimulus. Venous blood samples were regularly collected to determine alfaxalone plasma concentrations and for pharmacokinetic analysis. Cardiopulmonary variables were monitored and the quality of the anaesthetic recovery period scored.Results
The median (range) alfaxalone infusion rate was 3.1 (2.4–4.3) mg kg–1 hour–1. The mean ± standard deviation plasma elimination half-life, plasma clearance and volume of distribution for alfaxalone were 41 minutes, 25 ± 6.3 mL minute–1 kg–1 and 1.6 ± 0.5 L kg–1, respectively. During anaesthesia, mean arterial blood pressure was maintained above 70 mmHg in all horses. Cardiac index reached a minimum value (68% of baseline values) immediately after induction of anaesthesia and was maintained between 74% and 90% of baseline values for the remainder of the anaesthetic protocol. Following the cessation of the alfaxalone infusion, six of eight horses exhibited muscle tremors and paddling. All horses stood without incident on the first or second attempt with a median recovery score of 4.5 (good to excellent).Conclusions and clinical relevance
Anaesthesia in horses can be maintained with an infusion of alfaxalone at approximately 3 mg kg–1 hour–1. The alfaxalone infusion rates used resulted in minimal haemodynamic changes and good recovery quality. Mean alfaxalone plasma concentration was stable over the infusion period and clearance rates were similar to previously published single-dose alfaxalone studies in horses. 相似文献2.
Eugenio Gaudio Laura Voltan Giulia Maria De Benedictis 《Veterinary anaesthesia and analgesia》2018,45(3):351-356
Objective
To evaluate the clinical effects and quality of sedation, induction, maintenance and recovery in Lemur catta after dexmedetomidine–butorphanol–midazolam sedation and alfaxalone anaesthesia.Study design
Prospective, observational study.Animals
Six male L. catta weighing 3.0 ± 0.6 kg undergoing surgical castration.Methods
Lemurs were sedated with intramuscular dexmedetomidine (0.015 mg kg?1), butorphanol (0.2 mg kg?1) and midazolam (0.2 mg kg?1). Anaesthesia was induced with intravenous alfaxalone 0.5 mg kg?1 over 60 seconds; further boluses were administered until tracheal intubation was feasible and final dose recorded. Alfaxalone continuous infusion was used to maintain anaesthesia. Atipamezole (0.15 mg kg?1) was administered during recovery. The quality of sedation, induction, intubation, maintenance and recovery was assessed using a scoring system. Physiological parameters were recorded during sedation, maintenance and recovery.Results
Sedation was achieved in 13.6 ± 5.6 minutes and no reactions were observed during handling or venepuncture. The mean dose of alfaxalone required for induction and maintenance was 2.09 ± 0.65 and 0.08 ± 0.02 mg kg?1 minute?1, respectively. Quality of induction, intubation and maintenance was good in almost all animals. Mild self-limiting muscle twitching was observed after alfaxalone administration in three animals. Cardiorespiratory function was stable in all animals but one. One lemur showed respiratory depression and required oxygen administration and manual ventilation. The mean maintenance time was 29.2 ± 7.4 minutes. The mean times from the end of alfaxalone administration to extubation, atipamezole administration and full recovery were: 15.3 ± 8.0, 22.2 ± 4.6 and 60.0 ± 8.4 minutes, respectively. Recovery was considered good in all animals.Conclusions and clinical relevance
Dexmedetomidine–butorphanol–midazolam combination provided reliable sedation and adequate muscle relaxation in L. catta. Alfaxalone proved to be a useful drug for induction and maintenance of anaesthesia and might be considered an option for injectable anaesthesia in lemurs. 相似文献3.
Sarah E. Bigby Jennifer E. Carter Sébastien Bauquier Thierry Beths 《Veterinary anaesthesia and analgesia》2017,44(4):905-909
Objective
The evaluation of alfaxalone as a premedication agent and intravenous anaesthetic in pigs.Study design
Prospective, clinical trial.Animals
Nine healthy, 6–8-week-old female Landrace pigs weighing 22.2 ± 1.0 kg, undergoing epidural catheter placement.Methods
All pigs were premedicated with 4 mg kg?1 alfaxalone, 40 μg kg?1 medetomidine and 0.4 mg kg?1 butorphanol administered in the cervical musculature. Sedation was subjectively scored by the same observer from 1 (no sedation) to 10 (profound sedation) prior to induction of anaesthesia with alfaxalone intravenously to effect. All pigs were maintained on alfaxalone infusions with the rate of administration adjusted to maintain appropriate anaesthetic depth. Quality of induction was scored from 1 (poor) to 3 (smooth) and basic cardiorespiratory variables were recorded every 5 minutes during anaesthesia. Results are reported as mean ± standard deviation or median (range) as appropriate.Results
Sedation scores were 9 (7–10). Inductions were smooth in all pigs and cardiovascular variables remained within normal limits for the duration of anaesthesia. The induction dose of alfaxalone was 0.9 (0.0–2.3) mg kg?1. Three pigs did not require additional alfaxalone after premedication to facilitate intubation.Conclusions and clinical relevance
Intramuscular alfaxalone in combination with medetomidine and butorphanol produced moderate to deep sedation in pigs. Alfaxalone produced satisfactory induction and maintenance of anaesthesia with minimal cardiovascular side effects. Appropriate monitoring of pigs premedicated with this protocol is required as some pigs may become anaesthetized after intramuscular administration of this combination of drugs. 相似文献4.
Lauren E. James Catherine JA. Williams Mads F. Bertelsen Tobias Wang 《Veterinary anaesthesia and analgesia》2018,45(3):329-337
Objective
To characterise the minimum dose of intramuscular alfaxalone required to facilitate intubation for mechanical ventilation, and to investigate the impact of cranial versus caudal injection on anaesthetic depth.Study design
Randomised crossover study.Animals
Six healthy juvenile ball pythons (Python regius).Methods
Three dosages (10, 20 and 30 mg kg–1) of alfaxalone were administered to each python in a caudal location with a minimum 2 weeks washout. Induction and recovery were monitored by assessing muscle tone, righting reflex, response to a noxious stimulus and the ability to intubate. A subsequent experiment assessed the influence of injection site by comparing administration of 20 mg kg–1 alfaxalone in a cranial location (1 cm cranial to the heart) with the caudal site. Respiration rate was monitored throughout, and when intubation was possible, snakes were mechanically ventilated.Results
Regardless of dose and injection site, maximum effect was reached within 10.0 ± 2.7 minutes. When administered at the caudal injection site, intubation was only successful after a dosage of 30 mg kg-1, which is higher than in previous reports for other reptiles. However, intubation was possible in all cases after 7.2 ± 1.6 minutes upon cranial administration of 20 mg kg–1, and anaesthetic duration was significantly lengthened (p < 0.001). Both 30 mg kg–1 at the caudal site and 20 mg kg–1 at the cranial site led to apnoea approximately 10 minutes post-injection, at which time the snakes were intubated and mechanically ventilated.Conclusions and clinical relevance
Alfaxalone provided rapid, smooth induction when administered intramuscularly to pythons, and may serve as a useful induction agent prior to provision of volatile anaesthetics. The same dosage injected in the cranial site led to deeper anaesthesia than when injected caudally, suggesting that shunting to the liver and first-pass metabolism of alfaxalone occur when injected caudally, via the renal portal system. 相似文献5.
Katherine J. Bennett Reza Seddighi Kaitlin A. Moorhead Kristin Messenger Sherry K. Cox Xiaocun Sun Kirby Pasloske Bruno H. Pypendop Thomas J. Doherty 《Veterinary anaesthesia and analgesia》2019,46(2):173-181
Objective
To determine the effect of fentanyl on the induction dose and minimum infusion rate of alfaxalone required to prevent movement in response to a noxious stimulus (MIRNM) in dogs.Study design
Experimental crossover design.Animals
A group of six healthy, adult, intact female mixed-breed dogs, weighing 19.7 ± 1.3 kg.Methods
Dogs were randomly administered one of three treatments at weekly intervals: premedication with 0.9% saline (treatment A), fentanyl 5 μg kg–1 (treatment ALF) or fentanyl 10 μg kg–1 (treatment AHF), administered intravenously over 5 minutes. Anesthesia was induced 5 minutes later with incremental doses of alfaxalone to achieve intubation and was maintained for 90 minutes in A with alfaxalone (0.12 mg kg–1 minute–1), in ALF with alfaxalone (0.09 mg kg–1 minute–1) and fentanyl (0.1 μg kg–1 minute–1) and in AHF with alfaxalone (0.06 mg kg–1 minute–1) and fentanyl (0.2 μg kg–1 minute–1). The alfaxalone infusion was increased or decreased by 0.006 mg kg–1 minute–1 based on positive or negative response to antebrachium stimulation (50 V, 50 Hz, 10 ms). Data were analyzed using a mixed-model anova and presented as least squares means ± standard error.Results
Alfaxalone induction doses were 3.50 ± 0.13 (A), 2.17 ± 0.10 (ALF) and 1.67 ± 0.10 mg kg–1 (AHF) and differed among treatments (p < 0.05). Alfaxalone MIRNM was 0.17 ± 0.01 (A), 0.10 ± 0.01 (ALF) and 0.07 ± 0.01 mg kg–1 minute–1 (AHF) and differed among treatments. ALF and AHF decreased the MIRNM by 44 ± 8% and 62 ± 5%, respectively (p < 0.05). Plasma alfaxalone concentrations at MIRNM were 5.82 ± 0.48 (A), 4.40 ± 0.34 (ALF) and 2.28 ± 0.09 μg mL–1 (AHF).Conclusions and clinical relevance
Fentanyl, at the doses studied, significantly decreased the alfaxalone induction dose and MIRNM. 相似文献6.
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8.
Carlos Ros Carme Soler Alejandra García de Carellán Mateo 《Veterinary anaesthesia and analgesia》2017,44(5):1085-1090
Objective
To compare the effects of general anaesthesia using sevoflurane or alfaxalone on the brainstem auditory evoked response (BAER) test in adult healthy cats.Study design
Prospective, clinical, ‘blinded’, crossover study.Animals
Ten feral adult healthy cats.Methods
Premedication consisted of dexmedetomidine (0.01 mg kg–1) intramuscularly (IM). The first general anaesthesia was induced and maintained with sevoflurane (treatment S) for physical examination, BAER test, complete blood tests, thoracic radiographs and abdominal ultrasound. The second general anaesthesia was induced with alfaxalone (treatment A) IM (2 mg kg–1) and maintained with alfaxalone (10 mg kg–1 hour–1) for the BAER test, followed by neutering surgery.The BAER recordings were compared for differences in latencies, amplitudes and waveform morphology. Data were analysed using Student's t test and Wilcoxon rank test for paired samples for parametric and non-parametric data, respectively. Statistical significance was set at p < 0.05.Results
General anaesthesia was uneventful; normal BAER comprising five peaks could be identified in both treatments. Mean ± SD latencies were 1.05 ± 0.09, 1.83 ± 0.11, 2.52 ± 0.19, 3.43 ± 0.17 and 4.39 ± 0.15 ms and 1.03 ± 0.04, 1.81 ± 0.73, 2.53 ± 0.15, 3.37 ± 0.13 and 4.33 ± 0.13 ms in treatments S and A, respectively. Median (interquartile range) amplitudes were 2.83 (0.67), 1.27 (0.41), 0.30 (0.40), 1.05 (0.82), 0.61 (0.38) microvolts and 2.84 (1.21), 1.49 (1.18), 0.26 (0.32), 0.91 (0.50) and 0.92 (0.64) microvolts in treatments S and A, respectively. There were no statistically significant differences in mean latencies or median amplitudes between both the anaesthetics.Conclusions and clinical relevance
This study demonstrates that there were no statistically significant differences between both the anaesthetics on the BAER test in adult healthy cats. Moreover, two possible anaesthetic protocols are described for cats undergoing this electrodiagnostic test. 相似文献9.
Bruno H. Pypendop M.G. Ranasinghe Kirby Pasloske 《Veterinary anaesthesia and analgesia》2018,45(5):630-639
Objectives
To determine the context-sensitive half-time of alfaxalone following intravenous infusions of various durations. To estimate the time necessary for plasma concentration to decrease by up to 95%.Study design
Prospective randomized and simulation studies.Animals
A group of six 1-year-old male castrated research cats.Methods
Cats were instrumented with catheters in a jugular and a medial saphenous vein. Alfaxalone was administered using a target-controlled infusion system, to target a plasma alfaxalone concentration of 7.6 mg L–1. The infusion lasted 30 (n = 2), 60 (n = 2) or 240 (n = 2) minutes. Blood samples were collected prior to drug administration, and at several times during and up to 8 hours after the infusion, for the determination of plasma alfaxalone concentration using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to each time–concentration profile, and a population model was fitted to data from all individuals. The context-sensitive half-time was determined from each individual model. In addition, times for plasma alfaxalone concentration to decrease by 50–95% following bolus administration and target-controlled infusions or continuous rate infusions of 0.5–8 hours were estimated by simulation using the population model.Results
Context-sensitive half-times were 2 and 8, 6 and 9, and 18 and 20 minutes for the 30, 60 and 240 minutes, respectively. Time for plasma alfaxalone concentration to decrease by 90% was predicted to range from 7 to 120 or 113 minutes following a bolus to an 8 hour target-controlled or continuous rate infusion, respectively.Conclusion and clinical relevance
Recovery time from alfaxalone anesthesia in cats is predicted to be influenced by the duration of target-controlled infusion. 相似文献10.
Bruno H. Pypendop M.G. Ranasinghe Kirby Pasloske 《Veterinary anaesthesia and analgesia》2018,45(4):459-466
Objective
To compare the performance of an alfaxalone constant rate intravenous (IV) infusion versus a 3-step IV infusion, both following a loading dose, for the maintenance of a target plasma alfaxalone concentration of 7.6 mg L–1 (effective plasma alfaxalone concentration for immobility in 99% of the population) in cats.Study design
Prospective randomized crossover study.Animals
A group of six healthy, adult male neutered cats.Methods
Catheters were placed in a jugular vein for blood sampling and in a medial saphenous vein for drug administration. An IV bolus of alfaxalone (2 mg kg–1) was administered, followed by either 0.2 mg kg?1 minute?1 for 240 minutes (single infusion; SI) or 0.4 mg kg?1 minute?1 for 10 minutes, then 0.3 mg kg?1 minute?1 for 30 minutes, and then 0.2 mg kg?1 minute?1 for 200 minutes (3-step infusion; 3-step). Plasma alfaxalone concentration was measured at six time points during the infusions. Measures of performance were calculated for each infusion regimen and compared using the paired Wilcoxon signed-rank test.Results
Median (range) absolute performance error, divergence, median prediction error and wobble were 15 (8–19)%, ?8 (?12 to ?6)% hour?1, ?12 (?19 to ?7)% and 10 (8–19)%, respectively, in the SI treatment, and 6 (2–16)%, 0 (?13 to 2)% hour?1, 1 (?16 to 4)% and 4 (3–6)% respectively, in the 3-step treatment and were significantly smaller in the 3-step treatment than in the SI treatment.Conclusion and clinical relevance
After IV administration of a bolus dose, a 3-step infusion regimen can better maintain stable plasma alfaxalone concentrations close to the target concentration than a single constant rate infusion. 相似文献11.
Bruno H. Pypendop Kristine T. Siao M.G. Ranasinghe Kirby Pasloske 《Veterinary anaesthesia and analgesia》2018,45(3):269-277
Objective
To determine the effective plasma alfaxalone concentration for the production of immobility in cats.Study design
Prospective up-and-down study.Animals
Sixteen 1–2 year old male castrated research cats.Methods
Cats were instrumented with catheters in a jugular and a medial saphenous vein. Alfaxalone was administered via the medial saphenous catheter, using a target-controlled infusion system. The infusion lasted for approximately 32 minutes. A noxious stimulus (tail clamp) was applied 30 minutes after starting the alfaxalone infusion, until the cat moved or 60 seconds had elapsed, whichever occurred first. The target alfaxalone concentration was set at 5 mg L?1 in the first cat and increased or decreased by 1 mg L?1 in subsequent cats, if the previous cat had moved or not moved in response to stimulation, respectively. This was continued until six independent crossovers (different responses in pairs of subsequent cats) had been observed. Blood samples were collected before alfaxalone administration, and 15 and 31 minutes after starting the administration, for the determination of plasma alfaxalone concentration using liquid chromatography/tandem mass spectrometry. The alfaxalone concentration yielding a probability of immobility in 50% (EC50), 95% (EC95) and 99% (EC99) of the population, and their respective 95% Wald confidence intervals were calculated.Results
The EC50, EC95 and EC99 for alfaxalone-induced immobility were 3.7 (2.4–4.9), 6.2 (4.7–) and 7.6 (5.5–) mg L?1, respectively.Conclusions and clinical relevance
The effective plasma alfaxalone concentration for immobility in cats was determined. This value will help in the design of pharmacokinetic-based dosing regimens. 相似文献12.
Daisy Norgate Gert Ter Haar Nicola Kulendra Kata Orsolya Veres-Nyéki 《Veterinary anaesthesia and analgesia》2018,45(6):729-736
Objective
To compare the effect of propofol and alfaxalone on laryngeal motion under a light plane of anaesthesia in nonbrachycephalic and brachycephalic dogs anaesthetized for nonemergency procedures.Study design
Prospective, randomized clinical trial.Animals
A total of 48 client-owned dogs (24 nonbrachycephalic and 24 brachycephalic).Methods
A standardized premedication of methadone (0.2 mg kg?1) and acepromazine (0.01 mg kg?1) was administered intramuscularly. Dogs were randomly assigned to be induced with increments of propofol (1–4 mg kg?1) or alfaxalone (0.5–2 mg kg?1). Laryngeal assessment was performed under a light plane of anaesthesia by a surgeon (GTH) who was unaware of the induction protocol. Laryngeal movement was assessed as either being present when abduction of the laryngeal cartilages upon inspiration was identified, or absent when abduction was not recognized. Simultaneously, a 60-second video was recorded. The same surgeon (GTH) and an additional surgeon (NK) re-evaluated the videos 1 month later. Categorical comparisons were studied using Chi square and Fisher’s exact test where appropriate. Pairwise evaluation of agreement between scorers was undertaken with the kappa statistic (κ).Results
There were no significant differences (p > 0.05) identified between the presence or absence of laryngeal motion between dogs administered propofol or alfaxalone, as well as when analysing nonbrachycephalic and brachycephalic dogs separately. The majority of dogs (>75%) maintained some degree of laryngeal motion with both protocols. Agreement between assessors was excellent (κ = 0.822).Conclusions
Alfaxalone maintained laryngeal motion similarly to propofol in nonbrachycephalic and brachycephalic dogs.Clinical relevance
Both agents would appear appropriate for allowing assessment of laryngeal motion in nonbrachycephalic and brachycephalic dogs. The assessment technique of subjective evaluation of laryngeal motion via peroral laryngoscopy under a light plane of anaesthesia produced consistent results amongst assessors, regardless of the induction agent used. 相似文献13.
PenTing Liao Melissa Sinclair Alexander Valverde Cornelia Mosley Heather Chalmers Shawn Mackenzie Brad Hanna 《Veterinary anaesthesia and analgesia》2017,44(5):1016-1026
Objectives
To compare propofol and alfaxalone, with or without midazolam, for induction of anesthesia in fentanyl-sedated dogs, and to assess recovery from total intravenous anesthesia (TIVA).Study design
Prospective, incomplete, Latin-square study.Animals
Ten dogs weighing 24.5 ± 3.1 kg (mean ± standard deviation).Methods
Dogs were randomly assigned to four treatments: treatment P-M, propofol (1 mg kg?1) and midazolam (0.3 mg kg?1); treatment P-S, propofol and saline; treatment A-M, alfaxalone (0.5 mg kg?1) and midazolam; treatment A-S, alfaxalone and saline, administered intravenously (IV) 10 minutes after fentanyl (7 μg kg?1) IV. Additional propofol or alfaxalone were administered as necessary for endotracheal intubation. TIVA was maintained for 35–55 minutes by infusions of propofol or alfaxalone. Scores were assigned for quality of sedation, induction, extubation and recovery. The drug doses required for intubation and TIVA, times from sedation to end of TIVA, end anesthesia to extubation and to standing were recorded. Analysis included a general linear mixed model with post hoc analysis (p < 0.05).Results
Significant differences were detected in the quality of induction, better in A-M than A-S and P-S, and in P-M than P-S; in total intubation dose, lower in P-M (1.5 mg kg?1) than P-S (2.1 mg kg?1), and A-M (0.62 mg kg?1) than A-S (0.98 mg kg?1); and lower TIVA rate in P-M (268 μg kg?1 minute?1) than P-S (310 μg kg?1 minute?1). TIVA rate was similar in A-M and A-S (83 and 87 μg kg?1 minute?1, respectively). Time to standing was longer after alfaxalone than propofol, but was not influenced by midazolam.Conclusions and clinical relevance
Addition of midazolam reduced the induction doses of propofol and alfaxalone and improved the quality of induction in fentanyl-sedated dogs. The dose rate of propofol for TIVA was decreased. 相似文献14.
Ana Zapata Francisco G. Laredo Mayte Escobar Amalia Agut Marta Soler Eliseo Belda 《Veterinary anaesthesia and analgesia》2018,45(5):609-617
Objective
To study the effect of alternating the order of midazolam and alfaxalone administration on the incidence of behavioural changes, alfaxalone induction dose and some cardiorespiratory variables in healthy dogs.Study design
Prospective, randomized, controlled, clinical trial.Animals
A total of 33 client-owned dogs undergoing elective procedures.Methods
Following intramuscular acepromazine (0.02 mg kg?1) and morphine (0.4 mg kg?1) premedication, anaesthesia was induced intravenously (IV) with a co-induction of either midazolam (0.25 mg kg?1) prior to alfaxalone (0.5 mg kg?1; group MA), or alfaxalone followed by midazolam at identical doses (group AM). The control group (CA) was administered normal saline IV prior to alfaxalone administration. Additional alfaxalone (0.25 mg kg?1 increments) was administered as required in all groups until orotracheal intubation was possible. Changes in behaviour, quality of induction, ease of intubation and incidence of adverse events at induction were recorded. Heart rate (HR), respiratory rate (fR) and systolic arterial blood pressure (SAP) were measured before treatments (baseline values), 30 minutes after premedication and at 0, 2, 5 and 10 minutes postintubation.Results
The incidence of excitement was higher in group MA compared with groups CA (p = 0.005) and AM (p = 0.013). The mean induction dose of alfaxalone was lower in group AM compared with group CA (p = 0.003). Quality of induction and ease of intubation were similar among groups. Mean HR values decreased after premedication and increased after alfaxalone administration in all groups. Mean SAP values were similar between groups. The number of animals that required manual ventilation was higher in the MA group.Conclusions and clinical relevance
Despite a lower occurrence of adverse events at induction in group AM compared with group MA and a reduction of alfaxalone dose requirement in group AM compared with group CA, the use of an alfaxalone–midazolam co-induction does not seem to produce any cardiovascular or respiratory benefits in healthy dogs. 相似文献15.
Dario d&#x;Ovidio Francesco Marino Emilio Noviello Enrico Lanaro Paolo Monticelli Chiara Adami 《Veterinary anaesthesia and analgesia》2018,45(2):183-189
Objective
To evaluate the efficacy and side effects of alfaxalone administered intramuscularly (IM) as a sedative agent in guinea pigs undergoing survey radiographs.Study design
Prospective clinical trial.Animals
A total of 30 client-owned guinea pigs.Methods
Following baseline assessments, 5 mg kg?1 alfaxalone was administered IM. Heart rate, arterial haemoglobin oxygen saturation, respiratory rate, rectal body temperature, palpebral reflex, response to toe and ear pinch, righting reflex, posture, jaw tone and reaction to manipulation were assessed before and after sedation at 5-minute intervals. The time elapsed from onset of sedation to return of locomotion and coordinated limb movements, the quality of recovery and the occurrence of undesired effects were observed and recorded.Results
The mean ± standard deviation onset of sedation was 2.7 ± 0.6 minutes. The physiological variables remained within normal ranges until completion of the procedure. Palpebral reflex and responsiveness to both ear and toe pinch were maintained during sedation. Neither hypoxaemia nor hypothermia was observed. The duration of sedation was 29.3 ± 3.2 minutes. Sedation and recovery were uneventful, and adverse effects were not observed.Conclusions and clinical relevance
In conclusion, 5 mg kg?1 of IM alfaxalone represents a valuable sedation protocol for healthy guinea pigs undergoing minor noninvasive procedures. Further trials are required to investigate its cardiovascular effects, clinical usefulness in unhealthy patients and its combined use with analgesics for procedures associated with nociception. 相似文献16.
Objective
To characterise, as a clinical study, the pharmacokinetics and pharmacodynamics and describe the hypnotic effect of the neurosteroid alfaxalone (3α-hydroxy-5 α-pregnane-11, 20-dione) formulated with 2-hydroxypropyl-β-cyclodextrin in male and female rats.Study design
Prospective, experimental laboratory study.Animals
A total of 12 (six male and six female) adult, aged-matched Sprague Dawley rats.Methods
Surgery and instrumentation was performed under isoflurane anaesthesia in an oxygen/nitrous oxide mixture (1:2) and local anaesthetic infiltration. All animals received a loading dose (1.67 mg kg?1 minute?1) for 2.5 minutes followed by a constant rate infusion (0.75 mg kg?1 minute?1) for 120 minutes of alfaxalone. Isoflurane and nitrous oxide was discontinued 2.5 minutes after the alfaxalone infusion started. Cardiorespiratory variables (heart rate, respiratory rate, arterial blood pressure and end tidal carbon dioxide tension) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Carotid artery blood samples were collected at strategic time points for blood gas analysis, haematology, biochemistry, and plasma concentrations of alfaxalone. Plasma samples were assayed using liquid chromatography-mass spectrometry.Results
There were significant differences between the sexes for plasma clearance (p = 0.0008), half-life (p = 0.0268) and mean residence time (p = 0.027). Mean arterial blood pressure was significantly higher in the male rats (p = 0.0255).Conclusions and clinical relevance
This study confirms that alfaxalone solubilised in 2-hydroxypropyl-β-cyclodextrin provides excellent total intravenous anaesthesia in rats. Sex-based differences in pharmacokinetics and pharmacodynamics were demonstrated and must be considered when designing biomedical research models using alfaxalone. 相似文献17.
Jill K Maney H Edward Durham Kathleen P Goucher Erika L Little 《Veterinary anaesthesia and analgesia》2018,45(4):539-544
Objective
To compare the induction and recovery characteristics and selected cardiopulmonary variables of midazolam–alfaxalone or midazolam–ketamine in donkeys sedated with xylazine.Study design
Randomized, blinded, crossover experimental trial.Animals
A group of seven adult male castrated donkeys weighing 164 ± 14 kg.Methods
Donkeys were randomly administered midazolam (0.05 mg kg?1) and alfaxalone (1 mg kg?1) or midazolam (0.05 mg kg?1) and ketamine (2.2 mg kg?1) intravenously following sedation with xylazine, with ≥ 7 days between treatments. Donkeys were not endotracheally intubated and breathed room air. Time to lateral recumbency, first movement, sternal recumbency and standing were recorded. Induction and recovery were assigned scores between 1 (very poor) and 5 (excellent). Heart rate (HR), respiratory rate (fR), invasive arterial blood pressures and arterial blood gases were measured before induction and every 5 minutes following induction until first movement.Results
Time to lateral recumbency (mean ± standard deviation) was shorter after alfaxalone (29 ± 10 seconds) compared with ketamine (51 ± 9 seconds; p = 0.01). Time to first movement was the same between treatments (27 versus 23 minutes). Time to standing was longer with alfaxalone (58 ± 15 minutes) compared with ketamine (33 ± 8 minutes; p = 0.01). Recovery score [median (range)] was of lower quality with alfaxalone [3 (2–5)] compared with ketamine [5 (3–5); p = 0.03]. There were no differences in HR, fR or arterial pressures between treatments. No clinically important differences in blood gases were identified between treatments. Five of seven donkeys administered alfaxalone became hypoxemic (PaO2 <60 mmHg; 8.0 kPa) and all donkeys administered ketamine became hypoxemic (p = 0.13).Conclusions and clinical relevance
Both midazolam–alfaxalone and midazolam–ketamine produced acceptable anesthetic induction and recovery in donkeys after xylazine sedation. Hypoxemia occurred with both treatments. 相似文献18.
Setefilla Quirós-Carmona Rocío Navarrete Juan M. Domínguez María del Mar Granados Rafael J. Gómez-Villamandos Pilar Muñoz-Rascón Daniel Aguilar Francisco J. Funes Juan Morgaz 《Veterinary anaesthesia and analgesia》2017,44(2):228-236
Objective
To determine the effects of two dexmedetomidine continuous rate infusions on the minimum infusion rate of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent haemodynamic and recovery effects in Greyhounds undergoing laparoscopic ovariohysterectomy.Study design
Prospective, randomized and blinded clinical study.Animals
Twenty-four female Greyhounds.Methods
Dogs were premedicated with dexmedetomidine 3 μg kg?1 and methadone 0.3 mg kg?1 intramuscularly. Anaesthesia was induced with IV alfaxalone to effect and maintained with a TIVA mixture of alfaxalone in combination with two different doses of dexmedetomidine (0.5 μg kg?1 hour?1 or 1 μg kg?1 hour?1; groups DEX0.5 and DEX1, respectively). The alfaxalone starting dose rate was 0.07 mg kg?1 minute?1 and was adjusted (± 0.02 mg kg?1 minute?1) every 5 minutes to maintain a suitable depth of anaesthesia. A rescue alfaxalone bolus (0.5 mg kg?1 IV) was administered if dogs moved or swallowed. The number of rescue boluses was recorded. Heart rate, arterial blood pressure and arterial blood gas were monitored. Qualities of sedation, induction and recovery were scored. Differences between groups were tested for statistical significance using a Student’s t test or Mann–Whitney U test as appropriate.Results
There were no differences between groups in sedation, induction and recovery quality, the median (range) induction dose of alfaxalone [DEX0.5: 2.2 (1.9–2.5) mg kg?1; DEX1: 1.8 (1.2–2.9) mg kg?1], total dose of alfaxalone rescue boluses [DEX0.5: 21.0 (12.5–38.8) mg; DEX1: 22.5 (15.5–30.6) mg] or rate of alfaxalone (DEX0.5: 0.12 ± 0.04 mg kg?1 minute?1; DEX1: 0.12 ± 0.03 mg kg?1 minute?1).Conclusions and clinical relevance
Co-administration of dexmedetomidine 1 μg kg?1 hour?1 failed to reduce the dose rate of alfaxalone compared with dexmedetomidine 0.5 μg kg?1 hour?1 in Greyhounds undergoing laparoscopic ovariohysterectomy. The authors recommend an alfaxalone starting dose rate of 0.1 mg kg?1 minute?1. Recovery quality was good in the majority of dogs. 相似文献19.
Kirk A. Muñoz Sheilah A. Robertson Deborah V. Wilson 《Veterinary anaesthesia and analgesia》2017,44(4):766-774
Objective
To determine the intubation dose and select physiologic effects of alfaxalone alone or in combination with midazolam or ketamine in dogs.Study design
Prospective, clinical study.Animals
Fifty-three healthy client-owned dogs [mean ± standard deviation (SD)] 5.1 ± 1.8 years, 27 ± 15.4 kg, scheduled for elective orthopedic surgery.Methods
After premedication with acepromazine (0.02 mg kg–1) and hydromorphone (0.1 mg kg–1) intramuscularly, alfaxalone (0.25 mg kg–1) was administered intravenously over 15 seconds followed immediately by 0.9% saline (AS), midazolam (0.3 mg kg–1; AM), ketamine (1 mg kg–1; AK1), or ketamine (2 mg kg–1; AK2). Additional alfaxalone (0.25 mg kg–1 increments) was administered as required to permit endotracheal intubation. The incidence of apnea and the time from intubation until spontaneous movement were recorded. Heart rate (HR) and blood pressure were recorded 15 minutes after premedication, after intubation and 2, 5, 10 and 15 minutes thereafter. Blood was collected for measurement of serum glucose and insulin concentrations before induction, after intubation and at 2, 5, 10 and 50 minutes. Data were analyzed by split-plot anova with Bonferroni adjustment for the number of group comparisons.Results
Mean ± SD alfaxalone mg kg–1 doses required for endotracheal intubation were AS (1.0 ± 0.4), AM (0.4 ± 0.2), AK1 (0.5 ± 0.3) and AK2 (0.5 ± 0.4) (p = 0.0005). Differences in cardiopulmonary variables among groups were minor; HR decreased in AS, while in other groups, HR increased transiently postintubation. Incidence of apnea in AS was 54% with no significant difference among groups. Midazolam significantly prolonged time from intubation until spontaneous movement (p < 0.002).Conclusions and clinical relevance
Midazolam and ketamine reduced the alfaxalone dose required for endotracheal intubation. Serum glucose and insulin concentrations were not influenced by administration of alfaxalone alone or when administered with midazolam or ketamine. 相似文献20.
Yishai Kushnir Noa Toledano Liat Cohen Tali Bdolah-Abram Yael Shilo-Benjamini 《Veterinary anaesthesia and analgesia》2017,44(2):346-355