COMPARISON OF SUBCUTANEOUS ALFAXALONE AND SUBCUTANEOUS ALFAXALONE-DEXMEDETOMIDINE FOR SEDATION IN THE HOUSTON TOAD (ANAXYRUS HOUSTONENSIS).

The Houston toad (Anaxyrus houstonensis), a primarily terrestrial amphibian of south-central Texas, has been listed as federally endangered since 1970. Sedation is an important tool for obtaining diagnostics and providing treatment in this species. This prospective, randomized, and blinded study compared the sedative effects of SC alfaxalone (Protocol A) at approximately 12 mg/kg (median [range] = 12.70 [12.09-13.95] mg/kg] to SC alfaxalone-dexmedetomidine (Protocol AD) at approximately 12 mg/kg (median [range] = 12.68 [12.16-13.56] mg/kg) and 0.1 mg/kg (median [range] = 0.1 [0.07-0.13] mg/kg), respectively, in adult Houston toads (n = 26). Toads from Protocol AD received atipamezole SC at approximately 1 mg/kg (median [range] = 0.96 [0.75-1.25] mg/kg) 45 min postinduction, whereas toads from Protocol A received the equivalent volume of SC sterile saline at the same time point. Heart rate, gular rate, and times to first effect, loss of righting reflex, ability to position for radiographs, loss of nociception, return of righting reflex, and full recovery were recorded. A significantly greater number of toads lost righting reflex, positioned for radiographs, and lost nociception with Protocol AD compared with Protocol A. Additionally, time to return of righting reflex and time to full recovery were significantly longer with Protocol AD than with Protocol A. The protocols did not differ significantly in time to first effect, time to radiographic positioning, or time to loss of nociception. Histologic examination of four toads euthanized during the study revealed acute injection site reactions from all administered drugs, including saline. No clinical adverse reactions were observed. This study demonstrates that the combination of SC alfaxalone and dexmedetomidine results in deeper sedation than SC alfaxalone alone, but also correlates with longer recovery times despite antagonist administration.

Comparison of Two Different Alfaxalone Concentrations Combined with Midazolam to Anesthetize Cynomolgus Macaques (Macaca fascicularis) for Plethysmography.

Plethysmography is employed in nonhuman primates (NHPs) to calculate respiratory minute volume and determine the exposure time required to deliver an aerosol at the target dose. Anesthetic drugs can impact breathing parameters like steady-state minute volume (SSMV) central to aerosol dosing. Alfaxalone-midazolam mixtures (AM) provide superior parameters for plethysmography in cynomolgus macaques. An obstacle to the use of AM is the volume required to anesthetize via intramuscular injection. A more concentrated formulation of alfaxalone will reduce injection volumes and refine AM protocols. The purpose of this study was to compare AM using the Indexed 10-mg/mL (AM10) formulation compared with an investigational 40-mg/mL (AM40) formulation for IM administration in cynomolgus macaques undergoing plethysmography. We hypothesized that AM10 and AM40 would show no difference in quality of anesthesia (QA), duration of anesthesia, SSMV, accumulated minute volume (AMV), and side effects. We also hypothesized that female macaques would have a longer duration of anesthesia compared with males using both formulations. The study used 15 cynomolgus macaques comprised of 8 females and 7 males. NHPs were compared between 2 separate and randomized anesthetic events no less than one week apart. Each animal served as its own control and animals were randomized by random number generation. Anesthetized NHPs were placed in a sealed plethysmography chamber, and minute volume measurements were calculated every 10 s to determine SSMV. Once SSMV was achieved for 20 min, the trial ended. There were no statistically significant differences between AM10 and AM40 for duration of anesthesia, SSMV, AMV, side effects, or QA. AM40 had a significantly smaller injection volume. Females did not show a significantly longer median duration of anesthesia using either of the alfaxalone formulations. Overall, AM40 offers a more humane anesthetic than AM10 for plethysmography in cynomolgus macaques.

A Comparison of Three Anesthetic Drug Combinations for Use in Inducing Surgical Anesthesia in Female Guinea Pigs (Cavia porcellus).

Guinea pigs are often used in translational research, but providing them with safe and effective anesthesia is a challenge. Common methods like inhalant anesthesia and injectable ketamine/xylazine induce surgical anesthesia but can negatively affect cardiovascular, respiratory, and thermoregulatory systems and complicate the interpretation of research outcomes. Several alternative anesthetic regimens have been investigated, but none have consistently achieved a surgical plane of anesthesia. Therefore, identifying an anesthetic regimen that achieves a stable state of the surgical plane of anesthesia while preserving cardiorespiratory function would be a valuable contribution. To address this issue, we compared the efficacy of 3 anesthetic combinations in female Dunkin-Hartley guinea pigs: 1) alfaxalone, dexmedetomidine, and fentanyl (ADF); 2) alfaxalone, midazolam, and fentanyl (AMF); and 3) alfaxalone, midazolam, fentanyl, and isoflurane (AMFIso). We monitored anesthetic depth, heart rate, oxygenation, respiratory rate, respiratory effort, blood pressure, and body temperature every 15 min from injection to recovery. We also recorded the time to loss of righting reflex, duration of anesthesia, and time to achieve a surgical plane. The results showed no statistically significant differences in induction and recovery times among the groups. In the AMFIso group, 100% of the animals achieved a surgical plane of anesthesia, whereas only 10% of the animals in the AMF group reached that level. None of the animals in ADF group reached a surgical plane of anesthesia. Respiratory rate was significantly lower in the AMFIso as compared with the ADF group (P < 0.001) but was not different between the AMF and ADF groups. Temperature was significantly lower in the AMFIso group as compared with both the ADF and AMF groups (P < 0.001). In conclusion, both combinations of solely injectable anesthetics assessed in this study can be used for short, nonpainful procedures without significant cardiorespiratory depression. However, for mildly to moderately painful surgical procedures, the addition of an inhalant anesthetic like isoflurane is necessary for female guinea pigs.

Echocardiographic and hemodynamic effects of alfaxalone or dexmedetomidine based sedation protocols in cats with hypertrophic cardiomyopathy: a pilot study.

OBJECTIVE: To report the effects of alfaxalone and dexmedetomidine based sedation protocols on echocardiographic and hemodynamic variables in cats with hypertrophic cardiomyopathy (HCM) during sedation and inhalational anesthesia. STUDY DESIGN: Prospective, randomized, experimental study. ANIMALS: A group of 10 client-owned cats with subclinical HCM. METHODS: Cats were administered one of two sedative intramuscular combinations: protocol ABM (alfaxalone 2 mg kg-1, butorphanol 0.4 mg kg-1, midazolam 0.2 mg kg-1; n = 5) or protocol DBM (dexmedetomidine 8 µg kg-1, butorphanol 0.4 mg kg-1, midazolam 0.2 mg kg-1; n = 5). General anesthesia was induced with intravenous alfaxalone and maintained with isoflurane in oxygen. Echocardiographic variables and noninvasive arterial blood pressures were obtained before sedation, following sedation, and during inhalational anesthesia. Sedation scores and alfaxalone induction dose requirements were recorded. Descriptive statistics are reported for cardiovascular variables. RESULTS: During sedation, echocardiographic and hemodynamic variables remained within normal limits with protocol ABM, whereas protocol DBM was characterized by bradycardia, low cardiac index and elevated blood pressure. During isoflurane anesthesia, both protocols demonstrated similar hemodynamic performance, with heart rates of 98 ± 12 and 89 ± 11 beats min-1, cardiac index values of 68 ± 17 and 47 ± 13 mL min-1 kg-1 and Doppler blood pressures of 72 ± 15 and 79 ± 20 mmHg with protocols ABM and DBM, respectively. A reduction in myocardial velocities were also observed during atrial and ventricular contraction with both protocols during isoflurane anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: An alfaxalone based protocol offered hemodynamic stability during sedation in cats with HCM; however, both dexmedetomidine and alfaxalone based protocols resulted in clinically relevant hemodynamic compromise during isoflurane anesthesia. Further studies are required to determine optimal sedative and anesthetic protocols in cats with HCM.

A dose characterization study evaluating the pharmacodynamics and safety of a concentrated alfaxalone solution (4%) as an intramuscular sedative in dogs.

Alfaxalone is a commonly employed veterinary anaesthetic induction and sedation agent. A 4% w/v preserved, aqueous formulation of alfaxalone 'RD0387' (A4%) has recently been developed. To evaluate the sedative effects of A4%, three doses, 5 mg kg-1 (A5); 7.5 mg kg-1 (A7.5) and 10 mg kg-1 (A10) were administered intramuscularly into the epaxial musculature of six healthy adult mixed-breed dogs in an experimental, randomized, blinded, crossover study. Sedation time variables, quality of sedation (including onset of sedation and recovery), physiological variables, response to cephalic vein catheterization and frequency of undesirable events were recorded. Continuous variables were analysed between treatments (one-way ANOVA or restricted maximum likelihood modelling) and within treatments compared with baseline (Tukey's test). Categorical data were analysed between treatments (Kruskal-Wallis' test) and within treatments from baseline (Dunn's test). Significance was set at p < .05. All dogs became sedated (laterally recumbent) and sedation onset was significantly faster in groups A7.5 (9.8 ± 5.3 min) and A10 (9.1 ± 5.6 min) compared to A5 (25.6 ± 16.1 min) (p = .033, p = .027, respectively). Duration of sedation was significantly longer in A10 (168.5 ± 70.6 min) and A7.5 (143.8 ± 58 min) compared to A5 (63.8 ± 28.2 min) (p = .005 and p = .003, respectively). Dogs in A10 had a superior quality of onset of sedation compared to A5 (p = .028). Sedation scores and quality of recovery from sedation were not significantly different between doses. Two dogs (2/6) in A5 were insufficiently sedated for cephalic catheterization. Ataxia was the most frequently observed undesirable event with an overall frequency of 78% (14/18) and 89% (16/18) during sedation onset and recovery, respectively. Overall, A4% administered IM in dogs at 7.5 and 10 mg kg-1 resulted in sufficient sedation for IV catheterization in dogs. To improve the speed and quality of the sedation, it is recommended that future research focuses on combining A4% with other sedative or analgesic drugs.

Alfaxalone increases measured progesterone concentration in neutered male cats when determined by immunoreactivity.

OBJECTIVE: Alfaxalone is a commonly used anesthetic agent in small animals. In cats, alfaxalone can be administered as an IM agent to achieve clinically useful sedation or anesthesia, negating the need for IV injection in difficult patients. The molecular structure of alfaxalone is similar to the hormone progesterone (P4). It is hypothesized that alfaxalone would cross-react with the assay measuring progesterone causing a false elevation. ANIMALS: 8 healthy neutered male, domestic shorthair cats that were privately owned were enrolled in the study. METHODS: Male neutered cats were administered 3 mg/kg of alfaxalone IM. Blood samples were collected at set time points (baseline, 30 minutes, 60 minutes, 3 hours, 6 hours, and 10 hours after administration), and serum concentrations of progesterone immunoreactivity (IR) were determined using the Siemens Immulite 1000 automated immunoassay system. Statistical analysis was performed with repeated measures ANOVA and a Tukey-Cramer multiple comparisons test. A P value of < .05 was used for significance. RESULTS: Serum progesterone IR was significantly elevated at 30 minutes, 1 hour, and 3 hours (P < .05) when compared to baseline progesterone immunoreactivity. Progesterone immunoreactivity had returned to baseline by 6 hours. CLINICAL RELEVANCE: This study suggests that alfaxalone administered IM in cats may interfere with immunoassay measurement of serum progesterone for up to 6 hours. Caution should be used when interpreting serum progesterone immunoreactivity results in cats within 4 hours of alfaxalone.

Effects of alfaxalone on induction quality of inhalation anesthesia in domestic pigeons (Columba livia domestica).

Several studies have documented the effects of anesthesia on pigeons. However, previous studies using pigeons have not examined a combination of injection and inhalation anesthesia. This study aimed to evaluate the effects of intramuscular (IM) administration of alfaxalone in conjunction with mask induction on the quality of isoflurane anesthesia in healthy domestic pigeons (Columba livia domestica). In a randomized, double-blind, crossover study consisting of two phases, six healthy adult pigeons were anesthetized twice with a washout period of 7 days. In each phase, the pigeons were randomly assigned IM administration of either alfaxalone (4 mg/kg) or an equal volume of normal saline. After 20 min, anesthesia was induced with isoflurane through a face mask. Once voluntary movement of the limbs and eyelids ceased, the face mask was removed, and the trachea was intubated. The quality of anesthesia was assessed by scoring sedation prior to anesthetic induction, induction, and recovery. Heart rate, respiratory rate, cloacal temperature, and noninvasive systolic, diastolic, and mean arterial pressure were recorded before the IM injection (baseline) and during the procedure. The minimum anesthetic concentration of isoflurane was determined using the "bracketing" method. Moderate sedation (sedation scores of 2 and 3) was observed only with alfaxalone administration. In the alfaxalone group, the induction score was significantly higher (better induction quality) than in the control group (P=0.041). The combination of alfaxalone and mask induction was effective for inhalation anesthesia in pigeons.

Sedative and cardiorespiratory effects of intranasal atomized alfaxalone in Japanese White rabbits.

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 (fR), noninvasive mean arterial pressure (MAP), peripheral hemoglobin oxygen saturation (SpO2) 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 (SpO2 <90% or PaO2 <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. fR 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.

Comparison of alfaxalone and propofol on haematological and serum biochemical variables in cats undergoing radiotherapy with sevoflurane maintenance.

OBJECTIVE: To evaluate effects of repeated alfaxalone or propofol administration on haematological and serum biochemical variables in cats undergoing radiotherapy. STUDY DESIGN: Prospective, block-randomized, clinical trial. ANIMALS: A group of 39 client-owned cats. METHODS: After butorphanol (0.2 mg kg-1) and midazolam (0.1 mg kg-1) sedation, cats were randomly assigned to receive either alfaxalone or propofol for induction of anaesthesia and sevoflurane maintenance. Cats were anaesthetized daily with the same induction agent for 10-12 days. Complete blood counts, reticulocytes, Heinz body score and serum biochemistry were performed before the first treatment (T1), at T6, T10 and 3 weeks after the final treatment (T21). Cumulative induction agent dose for each cat at each time point was evaluated for an effect on Heinz body score. Data are shown as mean ± standard deviation; p < 0.05. RESULTS: At baseline there were no significant differences in signalment or blood variables between groups. A significant decrease in haematocrit of 2.3% ± 0.77 (p = 0.02) between T1-T6 and T1-T10 [mean 4.1% (± 0.78, p < 0.0001)] was detected, with a significant increase in haematocrit of 2.1% ± 0.80 (p = 0.046) between T6-T21 and 4.0% ± 0.8 (p < 0.001) between T10-T21. Heinz body score significantly increased by 1.86 ± 0.616 (p = 0.013) between T1-T10. In the propofol group, reticulocytes increased significantly between T1-T6 [mean 23,090 µL-1 ± 7670 (p = 0.02)] and T1-T10 [mean 27,440 µL-1 ± 7990 (p = 0.007)]. Mean cumulative dose at T10 was 19.65 mg kg-1 ± 5.3 and 43.4 mg kg-1 ± 14.4 for alfaxalone and propofol, respectively, with no significant effect on Heinz body formation at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Haematocrit decreased in both groups with recovery after 3 weeks. Repeated alfaxalone and propofol administration was not associated with marked haematological or serum biochemistry changes.

Effect of anesthetic induction with propofol, alfaxalone or ketamine on intraocular pressure in cats: a randomized masked clinical investigation.

OBJECTIVE: To compare the effect of propofol, alfaxalone and ketamine on intraocular pressure (IOP) in cats. STUDY DESIGN: Prospective, masked, randomized clinical trial. ANIMALS: A total of 43 ophthalmologically normal cats scheduled to undergo general anesthesia for various procedures. METHODS: Following baseline IOP measurements using applanation tonometry, anesthesia was induced with propofol (n = 15), alfaxalone (n = 14) or ketamine (n = 14) administered intravenously to effect. Then, midazolam (0.3 mg kg-1) was administered intravenously and endotracheal intubation was performed without application of topical anesthesia. The IOP was measured following each intervention. Data was analyzed using one-way anova and repeated-measures mixed design with post hoc analysis. A p-value <0.05 was considered significant. RESULTS: Mean ± standard error IOP at baseline was not different among groups (propofol, 18 ± 0.6; alfaxalone, 18 ± 0.7; ketamine, 17 ± 0.5 mmHg). Following induction of anesthesia, IOP increased significantly compared with baseline in the propofol (20 ± 0.7 mmHg), but not in the alfaxalone (19 ± 0.8 mmHg) or ketamine (16 ± 0.7 mmHg) groups. Midazolam administration resulted in significant decrease from the previous measurement in the alfaxalone group (16 ± 0.7 mmHg), but not in the propofol group (19 ± 0.7 mmHg) or the ketamine (16 ± 0.8 mmHg) group. A further decrease was measured after intubation in the alfaxalone group (15 ± 0.9 mmHg). CONCLUSIONS AND CLINICAL RELEVANCE: Propofol should be used with caution in cats predisposed to perforation or glaucoma, as any increase in IOP should be avoided.

Intramuscular alfaxalone with or without buprenorphine or hydromorphone provides sedation with minimal adverse effects in healthy rabbits (Oryctolagus cuniculus) in a randomized blinded controlled trial.

OBJECTIVE: To evaluate the effects of alfaxalone administered IM with or without buprenorphine or hydromorphone in healthy rabbits (Oryctolagus cuniculus). ANIMALS: 24 male rabbits undergoing elective orchiectomy between August 21, 2021, and November 6, 2021. PROCEDURES: In this controlled clinical trial, rabbits were randomly assigned to receive alfaxalone (4 mg/kg, IM) alone (group A; n = 8) or with buprenorphine (0.03 mg/kg, IM; group BA; 8) or hydromorphone (0.1 mg/kg, IM; group HA; 8). Vital signs and sedation scores were recorded immediately prior to (T0) and 10 minutes after (T1) treatment. Ease of IV catheter placement and pain scores were also evaluated. All rabbits received ketamine (2.5 mg/kg, IV), midazolam (0.13 mg/kg, IV), and meloxicam (0.5 mg/kg, SC) before orchiectomy but after IM treatments. Results were compared across groups with ANOVA or Fisher exact tests and across time with paired t tests. RESULTS: Sedation score, median time to recumbency, and ease of catheter placement did not differ among groups. Supraglottic airway device placement was possible for 1 rabbit in group A, 1 in group BA, and 2 in group HA. Mean respiratory rate at T1 versus T0 was significantly decreased for groups BA (63.8 vs 128.6 breaths/min) and HA (66.7 vs 123.2 breaths/min). Mean postoperative pain scores were significantly lower for rabbits in group HA (0.58), compared with those in groups A (2.25) and BA (2.06). CLINICAL RELEVANCE: All 3 treatments provided reliable sedation; however, alfaxalone (4 mg/kg, IM) combined with hydromorphone (0.1 mg/kg, IM) may be a better choice for painful procedures.

Intranasal butorphanol and midazolam administered prior to intramuscular alfaxalone provides safe and effective sedation in Quaker parrots (Myiopsitta monachus).

OBJECTIVE: To evaluate 2 doses of alfaxalone on cardiopulmonary parameters, temperature, sedation, endotracheal intubation, the incidence of muscle tremors, and radiographic positioning in Quaker parrots previously administered intranasal midazolam and butorphanol. ANIMALS: 10 healthy adult Quaker parrots (male = 5; female = 5). PROCEDURES: A randomized, masked, crossover study was conducted where birds received midazolam (2 mg/kg) and butorphanol (2 mg/kg) intranasally 15 minutes prior to a low- or high-dose of intramuscular alfaxalone: 2 mg/kg (LDA) or 5 mg/kg (HDA), respectively. Heart (HR) and respiratory rate (RR), cloacal temperature, sedation quality, and ability to position for radiographs were recorded over time. The incidence of muscle tremors and the ability to intubate were recorded. Data were compared to baseline values and between treatments where appropriate. Significance was set at P < .05. RESULTS: There were no significant differences in HR, RR, cloacal temperature, and sedation scores between treatments at any time point. Duration of time from midazolam-butorphanol administration to complete recovery from treatment administration was significantly shorter for LDA when compared to HDA (90 [60 to 195] vs 127.5 [90 to 10] minutes, respectively). Compared to baseline, sedation scores were significantly higher from T = 15 to 60 for LDA and from T = 15 to 75 for HDA. The incidence of muscle tremors was greater in HDA (9/10) than in LDA (7/10). All birds were successfully intubated and positioned for radiographs. CLINICAL RELEVANCE: The combination of intranasal midazolam-butorphanol and intramuscular alfaxalone at the doses examined was a safe and effective method for sedating Quaker parrots. LDA produced adequate sedation with a shorter time to recovery and with fewer muscle fasciculations when compared to HDA.

Alfaxalone population pharmacokinetics in the rat: Model application for pharmacokinetic and pharmacodynamic design in inbred and outbred strains and sexes.

The translation of new injectable anesthetic drugs from rodent to humans remains slow, despite the realization that reliance on the volatile agents is unsustainable from an environmental perspective. The aim of this study was to investigate the influence of rat sex and strain on the PK and PD of the anesthetic neurosteroid alfaxalone. Forty rats had cannulas inserted under isoflurane anesthesia for drug administration and sampling. Carotid artery blood samples were collected for blood gas analysis, hematology, biochemistry, and plasma concentrations of alfaxalone. Plasma samples were assayed using liquid chromatography-mass spectrometry. Compartmental non-linear mixed effects methods (NLME) models were applied to two rat populations to determine whether body weight, sex, and strain influenced PK parameters. There were significant differences between the sexes for plasma clearance, half-life and mean residence time in Lewis rats, and mean arterial blood pressure was significantly lower in the female rats at 120 min. An initial NLME PK population model was used to design an adjusted alfaxalone infusion for SD females matching plasma concentrations in males and minimizing cardiopulmonary depression but maintaining an appropriate hypnotic effect. A final NLME population model showed that alfaxalone clearance was dependent on both bodyweight and sex, whereas volume of distribution was influenced by strain. NLME PK models offer the advantage of having a single model that describes a population and therefore shares data interpretation between animals unlike the standard deterministic PK approach. This approach can be used to propose bespoke dosing regimens for optimal use of alfaxalone.

Use of alfaxalone in bearded dragons (Pogona vitticeps): optimizing pharmacodynamics and evaluating cardiogenic effects via echocardiography.

OBJECTIVE: Bearded dragons (Pogona vitticeps), a popular zoological companion species, frequently require sedation for procedures. A novel formulation of alfaxalone with preservatives was FDA approved for 28-day use after the vial is breached. Research has been performed in squamate species using alfaxalone without preservatives at various doses and routes of administration, but it is unknown whether preservatives affect quality of sedation or cardiac function. ANIMALS: 10 bearded dragons. PROCEDURES: This complete crossover study evaluated the pharmacodynamic effects of alfaxalone with preservatives administered to bearded dragons via intracoelomic (ICo; n = 10), SC (10), IM (9), and IV (9) injection at 15 mg/kg. RESULTS: Deep sedation was achieved in 9 of 10 ICo, 8 of 10 SC, 8 of 9 IM, and 9 of 9 IV administrations. Heart rate significantly decreased from baseline for ICo (P = .008; median heart rate, 46), IM (P = .018; 54), and IV (P = .033; 54) routes, but maintained within clinically acceptable limits. Respiratory rate significantly decreased from baseline for ICo (P = .011; median respiratory rate, 30), SC (P = .024; 12), IM (P = .028; 12), and IV (P = .043; 12) routes. Spontaneous ventilation was retained during all events. Time to first effects was significantly sooner with IV (0 min) administration compared with ICo (P = .02; 5 min) and IM (P = .008; 5 min). Time to loss and recovery of withdrawal, righting reflex, deep pain, and purposeful movement were not significantly different between routes of administration. End-systolic volume was the only echocardiographic parameter significantly affected by IV sedation. CLINICAL RELEVANCE: Sedation quality was most consistent via IV administration at 15 mg/kg, and minimal changes in cardiac function were observed.

A randomized clinical trial on effects of alfaxalone combined with medetomidine and midazolam in preventing stress-related neurohormonal and metabolic responses of isoflurane-anesthetized cats undergoing surgery.

OBJECTIVE: To evaluate the effects of IM and IV administration of alfaxalone alone and in combination with medetomidine, midazolam, or both on key stress-related neurohormonal and metabolic changes in isoflurane-anesthetized cats undergoing ovariohysterectomy or castration. ANIMALS: 72 client-owned mixed-breed cats undergoing ovariohysterectomy or castration between October 4, 2018, and January 10, 2020. PROCEDURES: For each type of surgery, cats were assigned to 1 of 6 premedication protocols groups, with 6 cats/group: physiologic saline (0.9% NaCl) solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IV); physiologic saline solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IM); medetomidine (50 µg/kg, IM) and alfaxalone (5 mg/kg, IV); medetomidine (50 µg/kg, IM) and alfaxalone (5 mg/kg, IM); midazolam (0.5 mg/kg, IM), medetomidine (50 µg/kg, IM), and alfaxalone (5 mg/kg, IV); or midazolam (0.5 mg/kg, IM), medetomidine (50 µg/kg, IM), and alfaxalone (5 mg/kg, IM). Venous blood was taken before pretreatment, pre- and postoperatively during anesthesia with isoflurane and oxygen, and during early and complete recovery. RESULTS: Compared with baseline concentrations, plasma adrenaline and noradrenaline concentrations decreased during anesthesia in cats premedicated with alfaxalone alone and in combination with medetomidine. The combination of medetomidine, midazolam, and alfaxalone prevented an excessive increase in catecholamines during anesthesia and surgery in cats. Postoperative plasma cortisol concentration after ovariohysterectomy was lower for cats premedicated with the combination of medetomidine and alfaxalone or the combination of medetomidine, midazolam, and alfaxalone, compared with cats premedicated with alfaxalone alone. Cats treated with combinations that included medetomidine and midazolam had hyperglycemia during anesthesia. Cats treated with medetomidine or medetomidine and midazolam in combination with alfaxalone, compared with alfaxalone alone, had lower concentrations of nonesterified fatty acids during anesthesia. Behavioral recovery scores were lower (better) for cats that received medetomidine in addition to alfaxalone, compared with alfaxalone alone. CLINICAL RELEVANCE: Results indicated that pretreatments with medetomidine and alfaxalone or with medetomidine, midazolam, and alfaxalone were useful for preventing stress-related hormonal and metabolic responses, other than hyperglycemia, during isoflurane anesthesia and surgery in cats.

Intramuscular Alfaxalone-Butorphanol-Midazolam Compared with Ketamine-Butorphanol- Midazolam in New Zealand White Rabbits.

Rabbits are a common companion animal and research subject and frequently require sedation to facilitate procedures. The objective of this study was to compare the effects of intramuscular butorphanol and midazolam combined with either alfaxalone or ketamine in rabbits. In a complete crossover study, healthy New Zealand white rabbits (n = 9; age, 6 mo) randomly received midazolam (1 mg/kg IM) and butorphanol (1 mg/kg IM) combined with either alfaxalone (2 mg/kg IM; ABM) or ketamine (5 mg/kg IM; KBM). Time to first effects, recumbency, and standing (recovery) were recorded. Every 5 min during recumbency, an investigator who was blind to treatment group collected serial physiologic parameters and sedation scores. At 5 min after rabbits became recumbent, manipulations were performed to mimic 2-view radiography and a cephalic intravenous catheter was placed. At 30 min after drug injection, flumazenil (0.05 mg/kg IM) was administered for reversal. Food consumption and fecal output were measured for 3 d after each study day. Time to standing and duration of recumbency differed significantly between groups. The median (range) of the total sedation score for ABM was 10 (8 to 10) and for KBM was 10 (6 to 10). Sham radiographs were successful in all rabbits in both groups. Physiologic parameters were not significantly different between groups over time. At 24 h after drug treatment, KBM-treated rabbits showed reduced food intake and both groups showed reduced fecal output. Total sedation scores decreased significantly over time in KBM rabbits ( P < 0.001) but not in ABM rabbits (P = 1). The duration of recumbency was significantly longer in ABM rabbits than in KBM rabbits. Both protocols produced sufficient sedation for radiograph acquisition without clinically significant adverse effects.

Anesthetic effects of alfaxalone-ketamine-midazolam and alfaxalone-ketamine-dexmedetomidine administered intramuscularly in black-tailed prairie dogs (Cynomys ludovicianus).

OBJECTIVE: To evaluate and compare the anesthetic effects of alfaxalone-ketamine-midazolam (AKM) and alfaxalone-ketamine-dexmedetomidine (AKD) in black-tailed prairie dogs (Cynomys ludovicianus). ANIMALS: 9 male black-tailed prairie dogs. PROCEDURES: Prairie dogs were anesthetized with AKM (6 mg/kg alfaxalone, 30 mg/kg ketamine, and 1.5 mg/kg midazolam) and AKD (6 mg/kg alfaxalone, 30 mg/kg ketamine, and 0.15 mg/kg dexmedetomidine) in a prospective, complete cross-over study. Atipamezole (1.5 mg/kg) after AKD or flumazenil (0.1mg/kg) after AKM was administered 45 minutes after induction of anesthesia. Onset of general anesthesia, physiologic parameters, depth of anesthesia, and time to recovery after reversal administration were evaluated for each treatment. RESULTS: Both AKM and AKD produced a deep plane of anesthesia in black-tailed prairie dogs that varied in duration. The median induction times for AKM and AKD were 82 and 60 seconds, respectively. The median recovery times for AKM and AKD were 27 and 21 minutes, respectively. There were no significant differences between protocols for induction (P = .37) and recovery (P = .51) times. All measured reflexes were absent in all animals at 5 minutes postinduction, with hindlimb reflexes returning prior to forelimb reflexes. Heart rate was lower but respiratory rate was higher in the AKD treatment. Body temperature decreased significantly for both protocols (P < .001) and was significantly lower with AKM than AKD (P < .001). CLINICAL RELEVANCE: Both AKM and AKD produced a deep plane of anesthesia in black-tailed prairie dogs. For both protocols, heat support and oxygen support are indicated.

Comparison of two formulations of alfaxalone for immersion anaesthesia in laboratory zebrafish (Daniorerio).

OBJECTIVE: To compare two commercial formulations of alfaxalone for immersion anaesthesia in laboratory zebrafish. STUDY DESIGN: Prospective, blinded, randomized study. ANIMALS: A total of 20 adult Danio rerio (Tuebingen strain). METHODS: Zebrafish were divided into two groups of 10 (five female, five male) and placed in individual immersion baths containing 10 mg L-1 of unpreserved alfaxalone (group 1) or preserved alfaxalone (group 2). Anaesthetists blinded to treatment used a composite score scale (CSS) (range 0-12) to assess fish every 30 seconds until induction of anaesthesia. Anaesthetic induction occurred when equilibrium and response to stimulus were lost. Fish were then placed in a clean water bath and scored every 60 seconds. Recovery from anaesthesia was defined as a CSS of ≤ 1. Time variables recorded were anaesthetic induction time (AIT), anaesthetic recovery time (ART) and total procedure time (TPT). Fish were observed for evidence of roupgross external pathology during the procedure. Following anaesthesia, four fish from each group were randomly chosen and euthanized for gill histopathology analysis immediately after recovery criteria were met. Data are presented as mean ± standard deviation. An independent t test was used to compare the difference in average anaesthetic time variables between groups (α = 0.05). RESULTS: There were no statistical differences between groups in reported variables. TPT, AIT and ART were 10.2 ± 1.2, 1.9 ± 0.9 and 8.3 ± 1.2 minutes for group 1 and 10.8 ± 2.9, 2.4 ± 1.2 and 8.4 ± 2.7 minutes for group 2. No gross external pathology was evident, and no fish died during the experimental period. Histopathology showed normal gill pathology and no difference between the groups. CONCLUSIONS AND CLINICAL RELEVANCE: Immersion anaesthesia using 10 mg L-1 of either formulation of alfaxalone resulted in anaesthesia of similar quality and duration.

Sedation quality of alfaxalone associated with butorphanol, methadone or pethidine in cats injected into the supraspinatus or the quadriceps muscle.

OBJECTIVES: The aim of this study was to compare the quality of sedation with three different anaesthetic protocols (alfaxalone combined with butorphanol, methadone or pethidine) administered intramuscularly in cats, and to evaluate the influence of the injection site (between supraspinatus and quadriceps muscles) on the onset and quality of sedation. METHODS: A total of 151 cats were selected for this study. Cats were sedated with alfaxalone (3 mg/kg) combined with either butorphanol (0.3 mg/kg; n = 50), methadone (0.3 mg/kg; n = 53) or pethidine (5 mg/kg; n = 48). The combination was injected intramuscularly into the supraspinatus (n = 79) or quadriceps muscle (n = 72). The data included a scoring system for the quality of sedation and physiological parameters, such as heart rate (HR), respiratory rate, body temperature and occurrence of mydriasis, monitored during the first 30 mins of anaesthesia. RESULTS: The opioid associated with alfaxalone influenced the overall sedation score, the degree of myorelaxation, the occurrence of mydriasis and HR. The overall sedation score was poorer with butorphanol than with methadone (P = 0.008), and butorphanol induced a lower degree of myorelaxation than methadone (P = 0.013). The injection into the supraspinatus showed better qualitative results for sedation and a faster onset time (in about 3 mins) than that into the quadriceps (P <0.001). HR decreased from baseline (P <0.001) and over time (P <0.001), mainly in cats of the butorphanol-supraspinatus and pethidine-quadriceps groups (P = 0.004). The occurrence of mydriasis was lower after butorphanol than after methadone and pethidine (P = 0.025), while the incidence of side effects did not differ among groups. CONCLUSIONS AND RELEVANCE: All three protocols provided a good quality of sedation and allowed performing the scheduled procedure. Moreover, the injection into the supraspinatus muscle showed superior results in all the qualitative scores of sedation and quicker onset time than that into the quadriceps muscle.

PLASMA CONCENTRATION AND PHARMACODYNAMICS OF INTRAMUSCULAR ADMINISTRATION OF ALFAXALONE IN INDIAN PEAFOWL (PAVO CRISTATUS).

Alfaxalone, a neuroactive steroid with anesthetic properties, is considered safe when used alone or in combination with other drugs for anesthesia at recommended species doses, and its use has been studied in numerous species. The objective of this study was to assess the pharmacokinetics and pharmacodynamics of IM alfaxalone in Indian peafowl (Pavo cristatus; hereafter peafowl). Eight female peafowl from one zoological institution were used. A control blood sample was obtained before administration of either 10 mg/kg (n = 4) or 20 mg/kg (n = 4) alfaxalone. Blood was collected at 5, 10, 15, 30, and 60 min after alfaxalone injection, with monitoring of sedation score, heart rate, and respiratory rate at each time point. Four peahens receiving a 10 mg/ kg dose had subjectively smoother inductions and recoveries, although sedation level was generally scored as low, with no adverse reactions noted. They were considered fully recovered by the 60-min postinjection time point, although measurable alfaxalone plasma concentrations remained present. Four peahens receiving 20 mg/kg IM experienced adverse effects including seizure-like episodes and hypersensitivity to stimuli throughout the study. This dosing group experienced prolonged recoveries consistent with high plasma concentrations (>3,000 ng/ml). Based on these results, use of 20 mg/kg IM alfaxalone as the sole anesthetic agent is not recommended in this species. Further studies should determine whether alfaxalone in conjunction with other anesthetic or analgesic agents could provide better sedation and smoother induction and recovery for peafowl and to assess the pharmacokinetics and pharmacodynamics of alfaxalone in other avian species.