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1.

Objective

To characterize alfaxalone administered subcutaneously (SC) in guinea pigs, both alone and in combination with dexmedetomidine and buprenorphine.

Study design

Prospective, blinded, crossover study.

Animals

A total of 15 healthy female guinea pigs weighing 400–600 g.

Methods

Alfaxalone (10, 20 and 40 mg kg?1) was administered SC to three guinea pigs as a pilot dose-finding study. Alfaxalone (20 mg kg?1; A20) was selected for comparison against combination protocols of alfaxalone (15 and 20 mg kg?1) with dexmedetomidine (0.25 mg kg?1) and buprenorphine (0.05 mg kg?1; A15DB, A20DB). Each protocol was randomly administered to 12 guinea pigs separated by ≥7 days. Time and quality of induction and recovery, heart rate, respiratory rate, peripheral hemoglobin oxygen saturation, rectal temperature, pedal withdrawal reflex and adverse effects were recorded.

Results

The median time to induction for A20, A15DB and A20DB was 6.8–8.0 minutes with no significant difference between treatments. Mean duration of recumbency for A20 was 73.6 ± 19.6 minutes. Recumbency duration for A15DB and A20DB extended to 90 minutes, at which time dexmedetomidine was antagonized using atipamezole (0.025 mg kg?1 SC). Physiological variables were within normal limits with the exception of one animal that died 45 minutes following treatment with A20DB. Pedal withdrawal reflex remained intact with all treatments. Minor side effects such as twitching or bruxism occurred sporadically with treatment A20 but not with A15DB and A20DB.

Conclusions and clinical relevance

SC alfaxalone produced uncomplicated sedation that may be recommended for nonpainful procedures that do not require complete immobility. The addition of dexmedetomidine and buprenorphine increased the duration of sedation and immobility, but did not result in general anesthesia. This combination sedation protocol may be useful for nonpainful procedures requiring extended immobility.  相似文献   

2.

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   

3.

Objective

To assess quality of sedation following intramuscular (IM) injection of two doses of alfaxalone in combination with butorphanol in cats.

Study design

Prospective, randomized, ‘blinded’ clinical study.

Animals

A total of 38 cats undergoing diagnostic imaging or noninvasive procedures.

Methods

Cats were allocated randomly to be administered butorphanol 0.2 mg kg?1 combined with alfaxalone 2 mg kg?1 (group AB2) or 5 mg kg?1 (group AB5) IM. If sedation was inadequate, alfaxalone 2 mg kg?1 IM was administered and cats were excluded from further analysis. Temperament [1 (friendly) to 5 (aggressive)], response to injection, sedation score at 2, 6, 8, 15, 20, 30, 40, 50 and 60 minutes, overall sedation quality scored after data collection [1 (excellent) to 4 (inadequate)] and recovery quality were assessed. Heart rate (HR), respiratory rate (fR) and arterial haemoglobin saturation (SpO2) were recorded every 5 minutes. Groups were compared using t tests and Mann–Whitney U tests. Sedation was analysed using two-way anova, and additional alfaxalone using Fisher's exact test (p < 0.05).

Results

Groups were similar for sex, age, body mass and response to injection. Temperament score was lower in group AB2 [2 (1–3)] compared to AB5 [3 (1–5)] (p = 0.006). Group AB5 had better sedation at 6, 8, 20 and 30 minutes and overall sedation quality was better in AB5 [1 (1–3)], compared to AB2 [3 (1–4)] (p = 0.0001). Additional alfaxalone was required for 11 cats in AB2 and two in AB5 (p = 0.005). Recovery quality, HR, fR and SpO2 were similar. Seven cats required oxygen supplementation. Complete recovery times were shorter in AB2 (81.8 ± 24.3 versus 126.6 ± 33.3 minutes; p = 0.009). Twitching was the most common adverse event.

Conclusions and clinical relevance

In combination with butorphanol, IM alfaxalone at 5 mg kg?1 provided better quality sedation than 2 mg kg?1. Monitoring of SpO2 is recommended.  相似文献   

4.

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   

5.

Objective

To describe the sedative and physiologic effects of two doses of alfaxalone administered intramuscularly in dogs.

Study design

Randomized, blinded, crossover experimental trial.

Animals

Ten adult mixed-breed dogs.

Methods

Dogs were assigned randomly to be administered one of three intramuscular injections [saline 0.1 mL kg?1 (S), alfaxalone 1 mg kg?1 (A1) or alfaxalone 2 mg kg?1 (A2)] on three occasions. Heart rate (HR), respiratory rate (fR) and sedation score were assessed before injection (T0) and at 5 (T5), 10 (T10), 15 (T15), 20 (T20), 30 (T30), 45 (T45) and 60 (T60) minutes postinjection. Rectal temperature was determined at T0 and T60. Adverse events occurring between the time of injection and T60 were recorded.

Results

Sedation scores were higher in group A2 at T15 and T30 compared with group S. There were no additional differences between groups in sedation score. The A2 group had higher sedation scores at T15, T20 and T30 compared with T0. The A1 group had higher sedation scores at T10 and T30 compared with T0. Temperature was lower in groups A1 and A2 compared with S at T60, but was not clinically significant. There were no differences between or within groups in HR or fR. Adverse effects were observed in both A1 and A2 groups. These included ataxia (17/20), auditory hyperesthesia (5/20), visual disturbance (5/20), pacing (4/20) and tremor (3/20).

Conclusions and clinical relevance

While alfaxalone at 2 mg kg?1 intramuscularly resulted in greater median sedation scores compared with saline, the range was high and adverse effects frequent. Neither protocol alone can be recommended for providing sedation in healthy dogs.  相似文献   

6.

Objective

To investigate the clinical and physiological effects of intravenous (IV) alfaxalone alone or in combination with buprenorphine, butorphanol or tramadol premedication in marmosets.

Study design

Prospective, randomized, blinded, crossover design.

Animals

Nine healthy marmosets (391 ± 48 g, 3.7 ± 2.2 years old).

Methods

Meloxicam 0.20 mg kg?1 subcutaneously, atropine 0.05 mg kg?1 intramuscularly (IM) and either buprenorphine 20 μg kg?1 IM (BUP-A), butorphanol 0.2 mg kg?1 IM (BUT-A), tramadol 1.5 mg kg?1 IM (TRA-A) or no additional drug (control) were administered to all marmosets as premedication. After 1 hour, anaesthesia was induced with 16 mg kg?1 alfaxalone IV. All animals received all protocols. The order of protocol allocation was randomized with a minimum 28 day wash-out period. During anaesthesia, respiratory and pulse rates, rectal temperature, haemoglobin oxygen saturation, arterial blood pressure, palpebral and pedal withdrawal reflexes and degree of muscle relaxation were assessed and recorded every 5 minutes. Quality of induction and recovery were assessed. Duration of induction, immobilization and recovery were recorded. Blood samples were analysed for aspartate aminotransferase, creatine kinase and lactate dehydrogenase concentrations. The protocols were compared using paired t tests, Wilcoxon's signed-rank test with Bonferroni's corrections and linear mixed effect models where appropriate.

Results

Out of nine animals, apnoea was noted in eight animals administered protocol BUP-A and two animals administered protocol BUT-A. With TRA-A and control protocols, apnoea was not observed. No other significant differences in any of the parameters were found; however, low arterial blood pressures and hypoxia occurred in TRA-A.

Conclusions and clinical relevance

Our study employing different premedications suggests that the previously published dose of 16 mg kg?1 alfaxalone is too high when used with premedication because we found a high incidence of complications including apnoea (BUP-A), hypotension and hypoxaemia (TRA-A). Appropriate monitoring and countermeasures are recommended.  相似文献   

7.

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   

8.

Objective

To compare dexmedetomidine–midazolam with alfaxalone–midazolam for sedation in leopard geckos (Eublepharis macularius).

Study design

Prospective, randomized, blinded, complete crossover study.

Animals

Nine healthy adult leopard geckos.

Methods

Geckos were administered a combination of dexmedetomidine (0.1 mg kg?1) and midazolam (1.0 mg kg?1; treatment D–M) or alfaxalone (15 mg kg?1) and midazolam (1.0 mg kg?1; treatment A–M) subcutaneously craniodorsal to a thoracic limb. Heart rate (HR), respiratory rate (fR), righting reflex, palpebral reflex, superficial and deep pain reflexes, jaw tone and escape response were assessed every 5 minutes until reversal. Conditions for intubation and response to needle prick were evaluated. Antagonist drugs [flumazenil (0.05 mg kg?1) ± atipamezole (1.0 mg kg?1)] were administered subcutaneously, craniodorsal to the contralateral thoracic limb, 45 minutes after initial injection, and animals were monitored until recovery.

Results

HR, but not fR, decreased significantly over time in both treatments. HR was significantly lower than baseline at all time points in D–M and for all but the 5 and 10 minute time points in A–M. HR was significantly higher in A–M at all time points after drug administration when compared with D–M. Sedation scores between protocols were similar for most time points. All animals in A–M lost righting reflex compared with seven out of nine (78%) geckos in D–M. Geckos in A–M lost righting reflex for significantly longer time. Mean ± standard deviation time to recovery after antagonist administration was 6.1 ± 2.2 minutes for D–M and 56 ± 29 minutes for A–M, and these times were significantly different.

Conclusions and clinical relevance

Combination D–M or A–M provided sedation of a level expected to allow physical examinations and venipuncture in leopard geckos. A–M provided a faster onset of sedation compared with D–M. Recovery was significantly faster following antagonist reversal of D–M, compared with A–M.  相似文献   

9.

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   

10.
11.

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   

12.

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   

13.
14.

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   

15.

Objective

To compare postoperative analgesia following either intraperitoneal (IP) ropivacaine or bupivacaine in dogs undergoing ovariohysterectomy (OVH) in the scope of multimodal analgesia.

Study design

Prospective, randomized, blinded clinical study.

Animals

A total of 45 privately owned dogs undergoing OVH, aged 37 ± 28 months and weighing 11.3 ± 4.5 kg.

Methods

Dogs were premedicated with acepromazine (0.05 mg kg?1) and morphine (0.5 mg kg?1) intramuscularly (IM). Anaesthesia was induced with alfaxalone and maintained with isoflurane in oxygen. Carprofen (4 mg kg?1) was injected subcutaneously after intubation. Dogs were randomly assigned to receive either bupivacaine (group B; 3 mg kg?1) or ropivacaine (group R; 3 mg kg?1) IP prior to complete closure of the linea alba. At 0.5, 1, 2, 4, 6 and 8 hours after extubation, sedation and postoperative pain were assessed, using the short form of the Glasgow Composite Pain scale (GCPS-SF), a dynamic interactive visual analogue scale (DIVAS), and mechanical nociceptive threshold (MNT) measurement. Rescue morphine (0.2 mg kg?1) was administered in case of ≥ 5/20 or ≥ 6/24 in the GCPS-SF and/or >40 mm in the DIVAS. Parametric data were compared using the t test; nonparametric data were analysed with the two-sample Wilcoxon test (p < 0.05).

Results

The GCPS-SF score was significantly higher in group R at 8 hours. There was no other significant difference regarding sedation or analgesia between the groups. Rescue analgesia was administered to 15 dogs (R: 9/22; B: 6/22), with no significant difference between the groups. MNT values decreased in both groups at all time points when compared to baseline. No adverse effects were observed.

Conclusions and clinical relevance

Ropivacaine or bupivacaine IP in combination with morphine IM and carprofen SC provided comparable postoperative analgesia in dogs after OVH for 6 hours. However, the anaesthetic protocol used did not prevent the administration of rescue analgesia in 41% of animals.  相似文献   

16.

Objective

To evaluate the anaesthetic effects of three different alfaxalone doses to induce anaesthesia in goldfish.

Study design

Prospective, randomized, clinical study.

Animals

Thirty goldfish undergoing skin scraping, gill examination and stool collection.

Methods

Each fish was transferred to an individual 4 L induction tank and randomly allocated into one of three groups (n = 10), in which alfaxalone was administered at concentrations of 6, 7 or 9 mg L–1. The depth of anaesthesia was evaluated by approach reaction, equilibrium, opercular movement and reaction to tactile stimuli. Sedation, light anaesthesia, surgical anaesthesia and recovery times were recorded. Data were analyzed with analysis of variance. A p value <0.05 was considered significant.

Results

Surgical anaesthesia was achieved in all fish. Goldfish induced with alfaxalone 7 and 9 mg L–1 showed a mild excitement phase. Time to sedation of the 6 mg L–1 dose (5.89 ± 0.40 minutes) was significantly longer compared to the 7 mg L–1 (3.97 ± 0.40 minutes) and 9 mg L–1 doses (3.94 ± 0.40 minutes). Times to light anaesthesia and surgical anaesthesia of the 9 mg L–1 dose (7.65 ± 1.04 and 9.60 ± 1.84 minutes, respectively) were significantly faster compared with those of the 6 mg L–1 dose (13.79 ± 1.04 and 19.75 ± 1.84 minutes, respectively) and the 7 mg L–1 dose (13.55 ± 1.04 and 21.24 ± 1.84 minutes, respectively). No significant differences were recorded in recovery time. Cessation of opercular movement was recorded in two fish induced with 7 mg L–1 and in two induced with 9 mg L–1. No mortality occurred.

Conclusions

and clinical relevance Alfaxalone is a reliable agent for immersion anaesthesia in goldfish. Immersion in water containing 6 mg alfaxalone L–1 provided smooth induction of anaesthesia, and no obvious side effects were encountered. Higher doses shortened induction time and caused respiratory depression and excitatory movements.  相似文献   

17.

Objective

To evaluate the dose-sparing effect of midazolam or diazepam on the dose of alfaxalone required to achieve endotracheal intubation in premedicated dogs.

Study design

Prospective, randomized, ‘blinded’, controlled clinical trial.

Animals

Ninety healthy dogs anaesthetized for elective surgery or diagnostic procedures.

Methods

Saline (0.1 mL kg–1), or midazolam or diazepam (0.2, 0.3, 0.4 or 0.5 mg kg–1) intravenously (IV) was randomly assigned; investigators were unaware of group designation. After premedication with IV acepromazine 0.01 mg kg–1 and methadone 0.2 mg kg–1, the degree of sedation was assessed. Alfaxalone (0.5 mg kg–1) was administered IV, followed by the assigned treatment. Further alfaxalone was administered until endotracheal intubation could be performed. Ease of endotracheal intubation, pulse rate and arterial blood pressure were assessed. General linear models were used to examine the effect of treatment drug and dose on induction dose of alfaxalone with Tukey’s post hoc tests. Incidence of adverse reactions was assessed with chi-square tests.

Results

There were no significant differences between groups with regard to demographic data or sedation. Median (range) induction dose of alfaxalone in the saline group was 0.74 (0.43–1.26) mg kg–1 compared with 0.5 (0.46–0.75) mg kg–1 and 0.5 (0.42–1.2) mg kg–1 for the midazolam and diazepam groups, respectively. Midazolam 0.3 and 0.5 mg kg–1 (p = 0.005 and 0.044, respectively) and diazepam 0.4 mg kg–1 (p = 0.032) reduced the alfaxalone dose compared with saline. Adverse effects were not significantly different between groups. Midazolam 0.2, 0.3, 0.4 and 0.5 mg kg–1 (p < 0.044, p = 0.001, p = 0.007, p = 0.044, respectively) and diazepam 0.2 and 0.5 mg kg–1 (p = 0.025 and p = 0.025) improved intubation score compared with saline.

Conclusion and clinical relevance

Midazolam 0.3 and 0.5 mg kg–1 and diazepam 0.4 mg kg–1 coadministered at anaesthetic induction allow alfaxalone dose reduction in healthy dogs. Use of benzodiazepines improved the ease of endotracheal intubation.  相似文献   

18.

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   

19.

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   

20.

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   

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