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.

Alfaxalone does not have long-term effects on goldfish pyramidal neuron action potential properties or GABAA receptor currents.

Anesthetics have varying physiological effects, but most notably alter ion channel kinetics. Alfaxalone is a rapid induction and washout neuroactive anesthetic, which potentiates γ-aminobutyric acid (GABA)-activated GABAA receptor (GABAA-R) currents. This study aims to identify any long-term effects of alfaxalone sedation on pyramidal neuron action potential and GABAA-R properties, to determine if its impact on neuronal function can be reversed in a sufficiently short timeframe to allow for same-day electrophysiological studies in goldfish brain. The goldfish (Carassius auratus) is an anoxia-tolerant vertebrate and is a useful model to study anoxia tolerance mechanisms. The results show that alfaxalone sedation did not significantly impact action potential properties. Additionally, the acute application of alfaxalone onto naive brain slices caused the potentiation of whole-cell GABAA-R current decay time and area under the curve. Following whole-animal sedation with alfaxalone, a 3-h wash of brain slices in alfaxalone-free saline, with saline exchanged every 30 min, was required to remove any potentiating impact of alfaxalone on GABAA-R whole-cell currents. These results demonstrate that alfaxalone is an effective anesthetic for same-day electrophysiological experiments with goldfish brain slices.

Subcutaneous Alfaxalone-XylazineBuprenorphine for Surgical Anesthesia and Echocardiographic Evaluation of Mice (Mus musculus).

Alfaxalone is a commonly used injectable anesthetic in dogs and cats due to its minimal cardiovascular side effects. Data for its use in mice are limited and demonstrate strain- and sex-associated differences in dose-response relationships. We performed a dose-comparison study of alfaxalone-xylazine-buprenorphine (AXB) in Crl: CFW (SW) mice. Subcutaneous injection of 50 mg/kg alfaxalone-10 mg/kg xylazine-0.1 mg/kg buprenorphine HCl consistently achieved a surgical plane of anesthesia (loss of toe pinch) for 48.6 ± 4.7 and 60.8 ± 9.6 min in females and males, respectively. The same dose and route of AXB induced a surgical plane of anesthesia in C57Bl/6NCrl (females: 42.3 ± 11.2 min; males: 51.6 ± 12.3 min), NCr-Foxn1nu (females: 76.8 ± 32.5 min; males: 80.0 ± 1.2 min), and NOD. Cg-Prkdc SCID Il2rg tm1Wjl /SzJCr (females: 56.0 ± 37.2 min and males: 61.2 ± 10.2 min) mice. We found no significant difference in the duration of the surgical plane of anesthesia between males and females within the mouse strains Crl: CFW (SW), C57Bl/6NCrl, NCr-Foxn1nu, and NOD. Cg-PrkdcSCID Il2rgtm1Wjl /SzJCr. We next performed an echocardiography study (n = 5 per group) of Crl: CFW (SW) mice ( n = 5 per group) to compare subcutaneous AXB anesthesia with that produced by intraperitoneal injection of 100 mg/kg ketamine and 10 mg/kg xylazine (KX). AXB induced significantly less bradycardia (295.4 ± 29 bpm) than KX (185.8 ± 38.9 bpm) did, with no significant differences in cardiac output, ejection fraction, end-diastolic volume, end-systolic volume, or fractional shortening. These results suggest that subcutaneous administration of AXB is a viable alternative to KX for inducing a surgical plane of anesthesia in Crl: CFW (SW), C57Bl/6NCrl, NCr-Foxn1nu, and NOD. Cg-PrkdcSCID Il2rgtm1Wjl /SzJCr mice, regardless of sex. AXB may also be a better injectable anesthetic option as compared with KX for avoiding adverse cardiac effects in mice.

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.

Comparison of Tricaine Methanesulfonate (MS-222) and Alfaxalone Anesthesia in Zebrafish (Danio rerio).

The research use of zebrafish has risen exponentially over the past decade while anesthetic options have remained largely unchanged.6 ricaine methanesulfonate (MS-222) is widely accepted as an anesthetic for routine husbandry procedures, however it has limitations and safety concerns. 11 A greater variety of effective anesthetic options for surgical procedures would be advantageous for the research community. Adult zebrafish were randomly assigned to one of the following groups (n = 10, 5 males and 5 females): 200 mg/L MS-222; 6-, 10-, 13-, and 16-mg/L alfaxalone, and control. All zebrafish in the MS-222 group reached a surgical plane of anesthesia within 95 ± 32 s. By contrast, only 2 of 10, 1 of 10, 0 of 10, and 0 of 4 of the 6, 10, 13, and 16 mg/L alfaxalone groups, respectively, reached a surgical plane of anesthesia within the allotted 10-min period. Recovery time was also significantly slower in the alfaxalone groups as compared with MS-222, with some fish taking greater than 10 min to recover. In addition, 33 of 34 zebrafish (the 16 mg/L group was not completed due to safety concerns) in the alfaxalone groups lost opercular movements for greater than one minute during their anesthetic event and had to be removed to the recovery tank. The results demonstrated that alfaxalone was unable to provide a reliable and safe surgical plane of anesthesia at any of the drug doses tested. Therefore, we recommend alfaxalone not be used as an anesthetic for painful procedures on zebrafish and conclude that MS-222 remains a more viable anesthetic for immersion anesthesia in zebrafish.

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.

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.

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.

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.

Long duration anaesthesia in pigs with an infusion of alfaxalone and dexmedetomidine.

Pigs are commonly maintained on total intravenous anaesthesia when used in comparative medical research to study controlled manual ventilation of the lung. In this case study, four pigs were anaesthetised with a total intravenous anaesthetic infusion of alfaxalone and dexmedetomidine for up to 24 h whilst being mechanically ventilated. Cardiovascular parameters, blood gas values and body temperature were minimally affected throughout the anaesthetic period. Additional analgesia is recommended when utilising this drug combination for procedures that involve noxious stimuli.

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.

Comparison between propofol and alfaxalone anesthesia for the evaluation of laryngeal function in healthy dogs utilizing computerized software.

Laryngeal paralysis is a well-documented cause of upper respiratory tract obstruction in canines. Diagnosis of laryngeal paralysis is usually made by visual evaluation of laryngeal motion whilst patients are under a light-plane of anesthesia. However, in human studies of laryngeal function evaluation, it has been shown that subjective scoring can lead to significant interobserver variance, which may cause false diagnosis. In this study, we propose to introduce a more objective method of assessing laryngeal function using GlotAnTools and Tracker software to directly measure laryngeal motion in anaesthetized patients. Additionally, two anesthetic agents, alfaxalone and propofol, were compared in this study to assess their relative effect on laryngeal motion and thus their suitability for use in this diagnostic process. This study was a two-stage, cross-over, 1:1 randomization, with two active treatment arms. Ten beagles (10-18 months, five males and five females) were exposed to both anesthetic agents and laryngeal motion was recorded using videoendoscopy. GlotAnTools and Tracker software were applied to the recorded images to measure glottal gap area (A) and length (L). A normalized measure of laryngeal function-computed as A/L-was created, representing the "elongatedness" of the rima glottidis. The glottal gap area was significantly reduced in dogs receiving alfaxalone. This study objectively establishes that alfaxalone impacted laryngeal motion significantly more than propofol and confirms the capability of these computational methods to detect differences in laryngeal motion.

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.