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Background: The intramuscular (IM) administration of 7.5-10 mg/kg of alfaxalone produces anesthetic effects that enable endotracheal intubation with mild cardiorespiratory depression in dogs. However, the effects of IM co-administration of medetomidine, butorphanol, and alfaxalone on cardiorespiratory function under inhalation anesthesia have not been studied., Aim: To assess the cardiorespiratory function following the IM co-administration of 5 μg/kg of medetomidine, 0.3 mg/kg of butorphanol, and 2.5 mg/kg of alfaxalone (MBA) in dogs anesthetized with sevoflurane., Methods: Seven intact healthy Beagles (three males and four females, aged 3-6 years old and weighing 10.0-18.1 kg) anesthetized with a predetermined minimum alveolar concentration (MAC) of sevoflurane were included in this study. The baseline cardiorespiratory variable values were recorded using the thermodilution method with a pulmonary artery catheter after stabilization for 15 minutes at 1.3 times their individual sevoflurane MAC. The cardiorespiratory variables were measured again following the IM administration of MBA. Data are expressed as median [interquartile range] and compared with the corresponding baseline values using the Friedman test and Sheff's method. A p < 0.05 was considered statistically significant., Results: The intramuscular administration of MBA transiently decreased the cardiac index [baseline: 3.46 (3.18-3.69), 5 minutes: 1.67 (1.57-1.75) l/minute/m 2 : p < 0.001], respiratory frequency, and arterial pH. In contrast, it increased the systemic vascular resistance index [baseline: 5,367 (3,589-6,617), 5 minutes:10,197 (9,955-15,005) dynes second/cm 5 /m 2 : p = 0.0092], mean pulmonary arterial pressure, and arterial partial pressure of carbon dioxide., Conclusion: The intramuscular administration of MBA in dogs anesthetized with sevoflurane transiently decreased cardiac output due to vasoconstriction. Although spontaneous breathing was maintained, MBA administration resulted in respiratory acidosis due to hypoventilation. Thus, it is important to administer MBA with caution to dogs with insufficient cardiovascular function. In addition, ventilatory support is recommended., Competing Interests: The authors declare that there is no conflict of interest.

Objective: To investigate the sedative and cardiorespiratory effects of intranasal atomization (INA) of alfaxalone using a mucosal atomization device in Japanese White rabbits., Study Design: Randomized, prospective, crossover study., Animals: A total of eight healthy female rabbits, weighing 3.6-4.3 kg and aged 12-24 months., Methods: Each rabbit was randomly assigned to four INA treatments administered 7 days apart: Control treatment, 0.15 mL 0.9% saline in both nostrils; treatment INA0.3, 0.15 mL 4% alfaxalone in both nostrils; treatment INA0.6, 0.3 mL 4% alfaxalone in both nostrils; treatment INA0.9, 0.3 mL 4% alfaxalone in left, then right, then left nostril. Sedation was scored 0-13 using a composite measure scoring system for rabbits. Simultaneously, pulse rate (PR), respiratory rate (f R ), noninvasive mean arterial pressure (MAP), peripheral hemoglobin oxygen saturation (SpO 2 ) and arterial blood gases were measured until 120 minutes. The rabbits breathed room air during the experiment and were administered flow-by oxygen when hypoxemia (SpO 2 <90% or PaO 2 <60 mmHg; 8.0 kPa) developed. Data were analyzed using the Fisher's exact test and the Friedman test (p < 0.05)., Results: No rabbit was sedated in treatments Control and INA0.3. All rabbits in treatment INA0.9 developed loss of righting reflex for 15 (10-20) minutes [median (25th-75th percentile)]. Sedation score significantly increased from 5 to 30 minutes in treatments INA0.6 and INA0.9 with maximum scores of 2 (1-4) and 9 (9-9), respectively. f R decreased in an alfaxalone dose-dependent manner and one rabbit developed hypoxemia in treatment INA0.9. No significant changes were observed in PR and MAP., Conclusions and Clinical Relevance: INA alfaxalone resulted in dose-dependent sedation and respiratory depression in Japanese White rabbits to values considered not clinically relevant. Further investigation of INA alfaxalone in combination with other drugs is warranted., (Copyright © 2023 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

We aimed to evaluate the induction, anesthesia, and cardiorespiratory effects of intramuscular (IM) anesthetic protocol with alfaxalone following premedication with low-dose medetomidine, butorphanol, or a combination of both (medetomidine-butorphanol) in dogs. Six healthy beagles were administered 1, 2.5, or 5 mg/kg alfaxalone IM following premedication with low-dose medetomidine (5 µg/kg; MA-IM), butorphanol (0.3 mg/kg; BA-IM), or medetomidine-butorphanol (5 µg/kg and 0.3 mg/kg, respectively; MBA-IM). Each dog received 9 treatments with minimum 7-day washout period between treatments. Dogs were allowed to breath room air during anesthetic induction. We attempted endotracheal intubation after alfaxalone administration. Alfaxalone produced a dose-dependent anesthetic effect in each anesthetic protocol. Intubation was achieved in 4 out of 6 dogs that received MA-IM and BA-IM with 2.5 mg/kg alfaxalone and in all dogs that received MBA-IM with 1, 2.5, and 5 mg/kg alfaxalone. The median durations [minimum-maximum] of accepting intubation were 79 [0-89], 97 [84-120], and 117 [84-217] min, respectively. Hypotension (mean arterial blood pressure <60 mmHg) did not develop, but bradycardia (heart rate <60 beats/min) was observed in all dogs that received the MA-IM and MBA-IM protocols. Severe hypoxemia (percutaneous arterial oxygen saturation <90%) developed in 2 dogs that received MBA-IM with 5 mg/kg alfaxalone. We consider that the MA-IM and BA-IM protocols with ≥2.5 mg/kg alfaxalone and the MBA-IM protocol with 1-2.5 mg/kg alfaxalone could provide clinically useful and effective anesthesia without causing severe cardiorespiratory depression in healthy dogs.

To evaluate sedative and physiological effects of low dose intramuscular (IM) alfaxalone, six healthy rabbits were administered single IM doses of alfaxalone at 1mg/kg (IM1), 2.5 mg/kg (IM2.5), or 5 mg/kg (IM5) with a minimum of 7-day washout period. Sedative effects were subjectively evaluated using a composite measure scoring system (maximum sedation score of 16) and pulse rate, respiratory rate, non-invasive blood pressure, and percutaneous oxygen-hemoglobin saturation were measured before and after IM alfaxalone. Loss of righting reflex (LRR) was achieved in all rabbits after IM2.5 and IM5 treatments but in only three rabbits after IM1 treatment. Median (interquartile range) times to LRR were 16 min (15-17), 6 min (6-6), and 4 min (4-4), and median durations of LRR were 0.5 min (0-7), 22.5 min (19-27), and 53 min (48-58) after IM1, IM2.5, and IM5 treatments, respectively. The duration of LRR after IM5 treatment was significantly longer than those after IM1and IM2.5 treatments (P<0.01). Median value of total sedation scores peaked at 10 min [score 3.5 (3-4)], from 10 min [score 13.5 (12-14)] to 15 min [score 13.5 (12-14)], and from 10 min [score 15 (12-15)] to 15 min [score 15 (14-15)] after IM1, IM2.5, and IM5 treatments, respectively. No rabbit showed circulatory depression and apnea although respiratory rate decreased after IM 2.5 and IM5 treatments. In conclusion, alfaxalone produced a dose-dependent sedative effect and a deep sedation was achieved by alfaxalone at 2.5 mg/kg IM in rabbits.

The pharmacological effects of intramuscular (IM) administration of alfaxalone combined with medetomidine and butorphanol were evaluated in 6 healthy beagle dogs. Each dog received three treatments with a minimum 10-day interval between treatments. The dogs received an IM injection of alfaxalone 2.5 mg/kg (ALFX), medetomidine 2.5 µg/kg and butorphanol 0.25 mg/kg (MB), or their combination (MBA) 1 hr after the recovery from their instrumentation. Endotracheal intubation was attempted, and dogs were allowed to breath room air. Neuro-depressive effects (behavior changes and subjective scores) and cardiorespiratory parameters (rectal temperature, heart rate, respiratory rate, direct blood pressure, central venous pressure and blood gases) were evaluated before and at 2 to 120 min after IM treatment. Each dog became lateral recumbency, except for two dogs administered the MB treatment. The duration was longer in the MBA treatment compared with the ALFX treatment (100 ± 48 min vs 46 ± 13 min). Maintenance of the endotracheal tube lasted for 60 ± 24 min in five dogs administered the MBA treatment and for 20 min in one dog administered the ALFX treatment. Cardiorespiratory variables were maintained within clinically acceptable ranges, although decreases in heart and respiratory rates, and increases in central venous pressure occurred after the MBA and MB treatments. The MBA treatment provided an anesthetic effect that permitted endotracheal intubation without severe cardiorespiratory depression in healthy dogs.

The sedative effects of intramuscular (IM) alfaxalone in 2-hydroxypropyl-beta-cyclodextrin (alfaxalone-HPCD) were evaluated in cats. The cats were treated with alfaxalone-HPCD in five occasions with a minimum 14-day interval between treatments: an IM injection of 1.0 mg/kg (IM1), 2.5 mg/kg (IM2.5), 5 mg/kg (IM5) or 10 mg/kg (IM10), or an intravenous injection of 5 mg/kg (IV5). The sedative effects were evaluated subjectively using a composite measurement scoring system (a maximum score of 16). Cardio-respiratory variables were measured non-invasively. The median sedation scores peaked at 10 min (score 9), 15 min (score 14), 10 min (score 16), 10 to 20 min (score 16) and 2 to 5 min (score 16) after the IM1, IM2.5, IM5, IM10 and IV5 treatments, respectively. The IM5 treatment produced longer lasting sedation, compared to the IV5 treatment. Durations of maintenance of lateral recumbency after the IM10 treatment (115 ± 22 min) were longer than those after the IM2.5 (40 ± 15 min), IM5 (76 ± 21 min) and IV5 treatments (50 ± 5 min). Cardio-respiratory variables remained within clinically acceptable ranges, except for each one cat that showed hypotension (<60 mmHg) after the IM10 and IV5 treatments. Tremors, ataxia and opisthotonus-like posture were observed during the early recovery period after the IM2.5, IM5, IM10 and IV5 treatments. In conclusion, IM alfaxalone-HPCD produced dose-dependent and clinically relevant sedative effect at 2.5 to 10 mg/kg in healthy cats. Hypotension may occur at higher IM doses of alfaxalone-HPCD.