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.

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.

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.

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.

Induction of General Anesthesia With Alfaxalone in the Domestic Chicken.

Alfaxalone is a safe and effective anesthetic drug for the induction of general anesthesia in many nonavian companion animal species; however, its efficacy has not been fully evaluated in birds. In premedicated trials, the chickens were sedated with butorphanol 2 mg/kg intramuscularly and midazolam 0.5 mg/kg intramuscularly, 15 minutes before intravenous administration of alfaxalone. The chickens were classified as anesthetized if endotracheal intubation was achieved without eliciting a cough reflex, provoking no patient resistance, and with minimal glottis movement within 15 seconds after the administration of alfaxalone. Qualitative and quantitative data were recorded, including duration of anesthesia, quality of induction, quality of recovery, reflexes, time to sternal recumbency, time to standing, and time to normal behaviors. Survival analysis was used to analyze the association between alfaxalone dosage and premedication with time-related variables. Out of the evaluated doses, the lowest intravenous alfaxalone dose required to achieve anesthetic induction and endotracheal intubation in unpremedicated and premedicated chickens was 7.5 and 4 mg/kg, respectively. The duration of anesthesia for all dose rates within the study ranged from 51 seconds to 4 minutes 45 seconds. Premedication generally improved the quality of induction and recovery, but significantly (P < .001) increased the time required for the chickens to stand after being anesthetized and to return to normal behaviors. Most chickens exhibited varying degrees of hyperactivity on anesthetic induction and recovery. No postinduction apnea or deaths of the subject birds occurred during this investigation.

The effects of two intramuscular sedation protocols on echocardiographic variables in cats following sedation and blood donation.

OBJECTIVE: To compare effects of 2 IM sedation protocols, alfaxalone-butorphanol (AB) versus dexmedetomidine-butorphanol (DB), on echocardiographic (ECHO) variables in cats following sedation and blood donation. DESIGN: Experimental randomized, blinded crossover study. SETTING: University teaching hospital. ANIMALS: Eleven client-owned healthy cats. INTERVENTIONS: Cats received a baseline ECHO without sedation prior to their first donation. Cats were sedated intramuscularly with AB (alfaxalone, 2 mg/kg, and butorphanol, 0.2 mg/kg) for 1 donation and DB (dexmedetomidine, 10 µg/kg, and butorphanol 0.2, mg/kg) for another, with a minimum 6 weeks between donations. A post-sedation, post-donation ECHO was performed after each blood donation. MEASUREMENTS AND MAIN RESULTS: Eight cats completed the study. Compared to baseline, DB combined with blood donation decreased heart rate (-84/min; P < 0.0001), fractional shortening (-16.5%; P < 0.0001), ejection fraction (-21.0%; P = 0.0002), and cardiac output (-292 mL/min, P = 0.0001); AB combined with blood donation increased heart rate (+45/min; P = 0.0003) and decreased left ventricular end diastolic volume (-1.57 mL; P < 0.0001). Compared to AB, DB decreased heart rate (-129/min; P < 0.0001) and fractional shortening (-21.6%; P < 0.0001) and increased left ventricular end-systolic (+1.14 mL; P = 0.0004) and diastolic volumes (+1.93 mL; P < 0.0002). Cats administered DB had a significant increase in regurgitant flow across mitral, aortic, and pulmonic valves following blood donation (P < 0.05). One cat administered DB developed spontaneous echo contrast in the left ventricle following donation. CONCLUSIONS AND CLINICAL RELEVANCE: Compared to AB, DB had more pronounced effects on ECHO variables in cats following IM sedation and blood donation. Due to its minimal impact on ECHO variables, AB may be a more desirable sedation protocol in this population of cats.

The impact of alfaxalone, propofol and ketamine on canine peripheral blood lymphocyte cytotoxicity in vitro.

Anesthetics may worsen the outcome of patients undergoing oncologic surgery via immune suppression. This study examines the impact of propofol, ketamine, and alfaxalone on canine peripheral blood lymphocyte (PBL) cytotoxic function in vitro. PBLs isolated from healthy canine blood were cultured in the presence or absence of alfaxalone, propofol, ketamine, their carrier solutions or dexamethasone as a positive control for 20 h. There was a decrease in cytotoxicity in PBLs exposed to dexamethasone and propofol carrier compared to the control as assessed by means of a chromium-based cytotoxicity assay. The PBLs exposed to propofol carrier also showed lower cytotoxicity compared to propofol. No other significant differences were observed. Therefore, the documented effects of these anesthetics in vivo may be caused by an indirect mechanism. The lipid emulsion's significant decrease in PBL cytotoxicity may have implications for critically ill patients on total parenteral nutrition.

Sedative effects of alfaxalone and hydromorphone with or without midazolam in cats: a pilot study.

OBJECTIVES: The aim of this pilot study was to compare the quality of sedation and ease of intravenous (IV) catheter placement following sedation using two intramuscular (IM) sedation protocols in cats: hydromorphone, alfaxalone and midazolam vs hydromorphone and alfaxalone. METHODS: This was a prospective, randomized and blinded study. Cats were randomly assigned to receive an IM injection of hydromorphone (0.1 mg/kg), alfaxalone (1.5 mg/kg) and midazolam (0.2 mg/kg; HAM group), or hydromorphone (0.1 mg/kg) and alfaxalone (1.5 mg/kg; HA group). Sedation scoring (0-9, where 9 indicated maximum sedation) was performed at 0, 5, 10, 15 and 20 mins from the time of injection. At 20 mins, an IV catheter placement score (0-10, where 10 indicated least resistance) was performed. RESULTS: Twenty-one client-owned adult cats were included in this study. Sedation and IV catheter placement scores were compared between groups using Wilcoxon rank sum tests. Peak sedation was significantly higher (P = 0.002) in the HAM group (median 9; range 7-9) than in the HA group (median 7; range 3-9), and IV catheter placement scores were significantly higher (P = 0.001) in the HAM group (median 9.5; range 7-10) compared with the HA group (median 7; range 4-9). Spearman correlations were calculated between IV catheter placement score and sedation scores. There was a significant positive correlation of average sedation over time (correlation 0.83; P <0.001) and sedation at 20 mins (correlation 0.76; P <0.001) with a higher, more favorable IV catheter placement score. CONCLUSIONS AND RELEVANCE: These preliminary results suggest that the addition of midazolam to IM alfaxalone and hydromorphone produced more profound sedation and greater ease of IV catheter placement than IM alfaxalone and hydromorphone alone.

Pharmacodynamics of propofol and alfaxalone in rattlesnakes (Crotalus durissus).

To characterise the effect of two common induction agents, propofol and alfaxalone, on mean arterial blood pressure (MAP) and heart rate (HR), we equipped 19 adult South American rattlesnakes (Crotalus durissus) with an indwelling arterial catheter approximately 24 h prior to recording of baseline resting values. Then, seven snakes received alfaxalone (15 mg kg-1) intravascularly (IV) through the catheter, while groups two and three (both n = 6) received propofol (15 mg kg-1 IV). The first two groups were not handled, while the group 3 was manually restrained for 2 min for a mock injection of 0.2 ml saline into the ventral tail vein. Baseline HR was similar in all groups and handling caused a significant tachycardia (p = 0.031) in group three. When given IV to undisturbed animals, both propofol and alfaxalone induced a significant increase in HR (p = 0.0022 and p = 0.0045, respectively) lasting approximately 30 min, but with values only significantly exceeding baseline for the first 5 min for propofol and the first 10 min with alfaxalone. Handling caused a significant increase in MAP (p = 0.0313). Propofol did not affect MAP (p = 0.1064), while alfaxalone caused a marked hypertension (although only significant at 2 min; p = 0.031). Manual restraint significantly increases both HR and MAP, which may lead to a masking of true cardiovascular effects of anaesthetic agents.

Effects of alfaxalone on cerebral blood flow and intrinsic neural activity of rhesus monkeys: A comparison study with ketamine.

OBJECTIVE: Alfaxalone has been used increasingly in biomedical research and veterinary medicine of large animals in recent years. However, its effects on the cerebral blood flow (CBF) physiology and intrinsic neuronal activity of anesthetized brains remain poorly understood. METHODS: Four healthy adult rhesus monkeys were anesthetized initially with alfaxalone (0.125 mg/kg/min) or ketamine (1.6 mg/kg/min) for 50 min, then administrated with 0.8% isoflurane for 60 min. Heart rates, breathing beats, and blood pressures were continuously monitored. CBF data were collected using pseudo-continuous arterial spin-labeling (pCASL) MRI technique and rsfMRI data were collected using single-shot EPI sequence for each anesthetic. RESULTS: Both the heart rates and mean arterial pressure (MAP) remained more stable during alfaxalone infusion than those during ketamine administration. Alfaxalone reduced CBF substantially compared to ketamine anesthesia (grey matter, 65 ± 22 vs. 179 ± 38 ml/100g/min, p<0.001; white matter, 14 ± 7 vs. 26 ± 6 ml/100g/min, p < 0.05); In addition, CBF increase was seen in all selected cortical and subcortical regions of alfaxalone-pretreated monkey brains during isoflurane exposure, very different from the findings in isoflurane-exposed monkeys pretreated with ketamine. Also, alfaxalone showed suppression effects on functional connectivity of the monkey brain similar to ketamine. CONCLUSION: Alfaxalone showed strong suppression effects on CBF of the monkey brain.The residual effect of alfaxalone on CBF of isoflurane-exposed brains was evident and monotonous in all the examined brain regions when used as induction agent for inhalational anesthesia. In particular, alfaxalone showed similar suppression effect on intrinsic neuronal activity of the brain in comparison with ketamine. These findings suggest alfaxalone can be a good alternative to veterinary anesthesia in neuroimaging examination of large animal models. However, its effects on CBF and functional connectivity should be considered.

Anesthetic agents affect urodynamic parameters and anesthetic depth at doses necessary to facilitate preclinical testing in felines.

Urodynamic studies, used to understand bladder function, diagnose bladder disease, and develop treatments for dysfunctions, are ideally performed with awake subjects. However, in small and medium-sized animal models, anesthesia is often required for these procedures and can be a research confounder. This study compared the effects of select survival agents (dexmedetomidine, alfaxalone, and propofol) on urodynamic (Δpressure, bladder capacity, bladder compliance, non-voiding contractions, bladder pressure slopes) and anesthetic (change in heart rate [∆HR], average heart rate [HR], reflexes, induction/recovery times) parameters in repeated cystometrograms across five adult male cats. The urodynamic parameters under isoflurane and α-chloralose were also examined in terminal procedures for four cats. Δpressure was greatest with propofol, bladder capacity was highest with α-chloralose, non-voiding contractions were greatest with α-chloralose. Propofol and dexmedetomidine had the highest bladder pressure slopes during the initial and final portions of the cystometrograms respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller ΔHR, decreased reflexes) under dexmedetomidine, compared to propofol and alfaxalone. Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choices.

Co-induction of anaesthesia with alfaxalone and midazolam in dogs: a randomized, blinded clinical trial.

OBJECTIVE: To qualitatively assess the co-induction of anaesthesia with midazolam and alfaxalone and to determine cardiovascular or respiratory alterations compared with alfaxalone alone. STUDY DESIGN: A randomized, blinded, clinical trial. ANIMALS: A total of 29 American Society of Anesthesiologists grade I or II, client-owned dogs undergoing elective orthopaedic or soft tissue surgery. METHODS: All dogs received 0.02 mg kg-1 acepromazine and 0.3 mg kg-1 methadone intramuscularly 30 minutes prior to anaesthesia. Measurements of heart rate (HR), respiratory frequency and blood pressure (BP) were assessed pre-induction and at 0, 2 and 5 minutes post-induction. Anaesthesia was induced with 0.5 mg kg-1 alfaxalone followed by either 0.4 mg kg-1 midazolam intravenously (group M) or an equal volume of saline (group S). Conditions were assessed for intubation and further boluses of 0.25 mg kg-1 alfaxalone were given as required. Response to co-induction, ease of intubation and quality of induction were scored, and total dose of alfaxalone required for intubation was recorded. Repeated measures one-way analysis of variance with post hoc Tukey's test was used to assess within group changes over time and Student t tests were used to compare between groups. Incidence of apnoea was assessed using a Fisher's exact test. Data are shown as mean ± standard deviation. RESULTS: Group M included 14 dogs and group S 15 dogs. There was a significant difference in the total dose of alfaxalone required for intubation, 0.65 ± 0.20 mg kg-1 group M and 0.94 ± 0.26 mg kg-1 group S (p = 0.002). Apnoea occurred significantly more frequently in group M (p = 0.007). There were no clinically significant differences in HR or BP at the measured time points between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Co-induction with midazolam had significant alfaxalone-sparing effects with no clinically detectable cardiovascular changes. Apnoea is common after co-induction.

Effect of Three Different Sedatives on Electroretinography Recordings in Domestic Pigeons (Columba livia).

This study was conducted to compare the effects of 3 different sedative agents on electroretinography (ERG) in domestic pigeons (Columba livia). Six pigeons were sedated with alfaxalone, xylazine, and medetomidine at separate times with a 1-week washout period between sedative administration. After sedation with each agent, pigeons underwent the modified ERG protocol adapted from the standardized protocol for dogs. The scotopic mixed rod and cone response was recorded after 20 minutes of dark adaptation, and the photopic cone response and photopic flicker response were recorded after 10 minutes of light adaptation. Either a 1-way analysis of variance or a Kruskall-Wallis test was used to compare the a-wave and b-wave implicit time and amplitude. No significant differences were observed in the scotopic mixed rod and cone response among all 3 sedatives used. Compared with alfaxalone, medetomidine significantly prolonged the a-wave implicit time, depressed the b-wave amplitude of photopic cone response, and prolonged the peak implicit time of the photopic flicker response (P < .05). These results show that medetomidine has a depressant effect on photopic ERG in pigeons at a dosage that produces light sedation.

Effects of Intramuscular Alfaxalone/Acepromazine on Echocardiographic, Biochemical, and Blood Gas Measurements in Healthy Cats.

The effects of intramuscular injection of alfaxalone ([ALF] 5 mg/kg), acepromazine ([ACE] 0.05 mg/kg), and an ALF-ACE combination ([AA] 0.025 mg/kg ACE followed by 2.5 mg/kg ALF) on the sedation, echocardiographic, biochemical, and blood gas indexes and recovery were evaluated in seven cats. No sedation was obtained with ACE, and sedation scores were higher with ALF than with AA treatment. Compared with baseline, an increase in heart rate occurred after ACE, and all treatments caused a decrease in systemic arterial pressure. Decreased left ventricular internal dimension in diastole, end-diastolic volume of the left ventricle, stroke volume, and left atrial dimension were identified after AA. There were minimal changes in echocardiographic variables after ALF. Biochemical and blood gas analysis showed no significant changes after all treatments. Although the difference in quality of recovery between the AA and ALF treatment groups was insignificant, all cats treated with AA or ALF showed ataxia. The AA combination did not change the recovery score, and tremor and twitching were identified more frequently with AA than ALF. ALF had no significant effects on echocardiographic, biochemical, or blood gas variables. ALF could be considered a useful sedative option for diagnostic procedures and echocardiography in cats.

Alfaxalone-Xylazine Anesthesia in Laboratory Mice (Mus musculus).

Since its recent reformulation, alfaxalone has gained popularity as an injectable veterinary anesthetic, including promising studies demonstrating the use of alfaxalone-xylazine for anesthesia in mice. Here we sought to expand these studies by testing additional dose ranges, elaborating on physiologic monitoring, testing sex- and strain-associated differences, and evaluating efficacy during actual surgical conditions. C57BL/6J mice showed significant sex-associated differences in anesthetic sensitivity, with males requiring higher doses of alfaxalone (80-120 mg/kg IP alfaxalone with 10 mg/kg IP xylazine) than females (40-80 mg/kg IP alfaxalone with 10 mg/kg IP xylazine) to achieve a surgical plane of anesthesia. In addition, female outbred CD1 mice were less sensitive to alfaxalone than female inbred C57BL/6J mice. When used during actual surgery, alfaxalone-xylazine administered intraperitoneally provided adequate anesthesia for a model of orthopedic surgery, whereas the same anesthetic regimen during laparotomy resulted in unacceptably high mortality; survival during laparotomy increased when drugs were administered subcutaneously. These results indicate that alfaxalone-xylazine may be a viable option for injectable surgical anesthesia in mice, although strain- and sex-associated differences and alternative routes of administration should be considered when optimizing the anesthetic regimen for specific experimental conditions.

Comparison of the effects of alfaxalone and propofol with acepromazine, butorphanol and/or doxapram on laryngeal motion and quality of examination in dogs.

OBJECTIVE: To compare the effects of alfaxalone and propofol, with and without acepromazine and butorphanol followed by doxapram, on laryngeal motion and quality of laryngeal examination in dogs. STUDY DESIGN: Randomized, crossover, blinded study. ANIMALS: Ten female Beagle dogs, aged 11-13 months and weighing 7.2-8.6 kg. METHODS: The dogs were administered four intravenous (IV) treatments: alfaxalone (ALF), alfaxalone+acepromazine and butorphanol (ALF-AB), propofol (PRO) and propofol+AB (PRO-AB). AB doses were standardized. Dogs were anesthetized 5 minutes later by administration of alfaxalone or propofol IV to effect. Arytenoid motion during maximal inspiration and expiration was captured on video before and after IV doxapram (0.25 mg kg-1). The change in rima glottidis surface area (RGSA) was calculated to measure arytenoid motion. An investigator blinded to the treatment scored laryngeal examination quality. RESULTS: A 20% increase in RGSA was the minimal arytenoid motion that was detectable. RGSA was significantly less in ALF before doxapram compared with all other treatments. A <20% increase in RGSA was measured in eight of 10 dogs in PRO and in all dogs in ALF before doxapram. After doxapram, RGSA was significantly increased for PRO and ALF; however, 20% of dogs in PRO and 50% of dogs in ALF still had <20% increase in RGSA. A <20% increase in RGSA was measured in five of 10 dogs in PRO-AB and ALF-AB before doxapram. All dogs in PRO-AB and ALF-AB with <20% increase in RGSA before doxapram had ≥20% increase in RGSA after doxapram. Examination quality was significantly better in PRO-AB and ALF-AB. CONCLUSIONS AND CLINICAL RELEVANCE: The use of acepromazine and butorphanol improved the quality of laryngeal examination. Any negative impact on arytenoid motion caused by these premedications was overcome with doxapram. Using either propofol or alfaxalone alone is not recommended for the evaluation of arytenoid motion.

Comparison of the Sedative Effects of Alfaxalone and Butorphanol-Midazolam Administered Intramuscularly in Budgerigars (Melopsittacus undulatus).

Intramuscular (IM) administration of either alfaxalone or butorphanol with midazolam was evaluated for sedation and effects on heart and respiratory rates in budgerigars (Melopsittacus undulatus). Twenty adult budgerigars were randomly assigned to receive 1 of 2 treatments: alfaxalone at 15 mg/kg IM or butorphanol and midazolam at 2.5 mg/kg IM and 1.25 mg/kg IM, respectively. Baseline heart and respiratory rates and sedation score were collected and, after injection, time to initial effects and initial recumbency were recorded. Five minutes after injection, birds were assessed for a righting reflex, and, if absent, response to noxious stimulus was assessed by hemostat clamp on the first digit. Birds then underwent a standardized diagnostic evaluation of radiographs, jugular venipuncture, and physical examination. At the end of the physical examination, a sedation score was assigned, and birds were placed in dorsal recumbency for recovery. Times from injection to initial arousal, final recumbency, standing, and full recovery were recorded. Although time to onset of sedation was the same between groups, alfaxalone produced a shorter (P = .04) and more consistent duration of sedation (mean ± SD: 27.5 ± 5.9 minutes) compared with butorphanol-midazolam (72.0 ± 56.9 minutes). Only 3 of 10 birds receiving butorphanol-midazolam were recumbent by 5 minutes compared with 10 of 10 birds receiving alfaxalone. Radiographs were successfully obtained in 9 of 10 and 7 of 10 birds administered alfaxalone and butorphanol-midazolam, respectively. No adverse effects were observed in any bird. Intramuscular alfaxalone produces safe, effective, and reliable sedation in budgerigars and is a more consistent and shorter duration alternative to intramuscular butorphanol-midazolam.

Alphaxalone Binds in Inner Transmembrane ß+-α- Interfaces of α1ß3γ2 γ-Aminobutyric Acid Type A Receptors.

BACKGROUND: Neurosteroids like alphaxalone are potent anxiolytics, anticonvulsants, amnestics, and sedative-hypnotics, with effects linked to enhancement of γ-aminobutyric acid type A (GABAA) receptor gating in the central nervous system. Data locating neurosteroid binding sites on synaptic αßγ GABAA receptors are sparse and inconsistent. Some evidence points to outer transmembrane ß-α interfacial pockets, near sites that bind the anesthetics etomidate and propofol. Other evidence suggests that steroids bind more intracellularly in ß-α interfaces. METHODS: The authors created 12 single-residue ß3 cysteine mutations: ß3T262C and ß3T266C in ß3-M2; and ß3M283C, ß3Y284C, ß3M286C, ß3G287C, ß3F289C, ß3V290C, ß3F293C, ß3L297C, ß3E298C, and ß3F301C in ß3-M3 helices. The authors coexpressed α1 and γ2L with each mutant ß3 subunit in Xenopus oocytes and electrophysiologically tested each mutant for covalent sulfhydryl modification by the water-soluble reagent para-chloromercuribenzenesulfonate. Then, the authors assessed whether receptor-bound alphaxalone, etomidate, or propofol blocked cysteine modification, implying steric hindrance. RESULTS: Eleven mutant ß3 subunits, when coexpressed with α1 and γ2L, formed functional channels that displayed varied sensitivities to the three anesthetics. Exposure to para-chloromercuribenzenesulfonate produced irreversible functional changes in ten mutant receptors. Protection by alphaxalone was observed in receptors with ß3V290C, ß3F293C, ß3L297C, or ß3F301C mutations. Both etomidate and propofol protected receptors with ß3M286C or ß3V290C mutations. Etomidate also protected ß3F289C. In α1ß3γ2L structural homology models, all these protected residues are located in transmembrane ß-α interfaces. CONCLUSIONS: Alphaxalone binds in transmembrane ß-α pockets of synaptic GABAA receptors that are adjacent and intracellular to sites for the potent anesthetics etomidate and propofol.

Cardiovascular, respiratory and sedative effects of intramuscular alfaxalone, butorphanol and dexmedetomidine compared with ketamine, butorphanol and dexmedetomidine in healthy cats.

Objectives The aim of the study was to evaluate the cardiorespiratory effects, quality of sedation and recovery of intramuscular alfaxalone-dexmedetomidine-butorphanol (ADB) and ketamine-dexmedetomidine-butorphanol (KDB), in cats. Methods Nine adult, healthy cats (6.63 ± 1.42 kg) were enrolled in a blinded, randomized, crossover experimental design. Cats were sedated twice intramuscularly, once with ADB (alfaxalone 1 mg/kg, dexmedetomidine 0.005 mg/kg, butorphanol 0.2 mg/kg), and once with KDB (ketamine 5 mg/kg, dexmedetomidine 0.005 mg/kg, butorphanol 0.2 mg/kg), in random order. Data collected included heart rate (HR), arterial blood pressure and blood gas analysis, respiratory rate and sedation score. Analysis of variance with Bonferroni post-hoc correction was used for parametric data, and a Wilcoxon signed rank test was used for non-parametric data. Significance was set at P <0.05. Results Total sedation time was shorter for ADB (90.71 ± 15.12 mins vs 147.00 ± 47.75 mins). Peak sedation was observed within 15 mins in both groups. Quality of recovery was excellent in both groups. HR decreased over time in both groups. Diastolic and mean arterial pressure decreased over time for ADB, becoming significant after 30 mins. All cardiovascular variables were within the clinically acceptable range in both groups. Arterial partial pressure of oxygen was significantly decreased from baseline for KDB at all time points (73 ± 2.5 mmHg [9.7 ± 0.3 kPa] vs ADB 83 ± 2.6 mmHg [11 ± 0.3 kPa]). Hypoventilation was not observed. Conclusions and relevance Both protocols produced acceptable cardiovascular stability. Sedation and recovery quality were good, albeit sedation was shorter with ADB. Although oxygenation was better maintained in the ADB group, all sedated cats should receive oxygen supplementation.

Effect of blood collection by the push-pull technique from an indwelling catheter versus direct venipuncture on venous blood gas values before and after administration of alfaxalone or propofol in dogs.

OBJECTIVE To compare the effect of blood collection by a push-pull technique from an indwelling IV catheter versus direct venipuncture on venous blood gas values before and after administration of alfaxalone or propofol to dogs. DESIGN Prospective randomized clinical study. ANIMALS 30 healthy client-owned dogs that weighed ≥ 10 kg (22 lb) and were anesthetized for elective surgical procedures. PROCEDURES All dogs were premedicated with methadone (0.5 mg/kg [0.2 mg/lb], IM), and 20 to 30 minutes later, anesthesia was induced with either alfaxalone (1 to 3 mg/kg [0.5 to 1.4 mg/lb], IV to effect; n = 15) or propofol (2 to 6 mg/kg [0.9 to 2.7 mg/lb], IV to effect; 15). Immediately prior to premedication and after anesthesia induction, paired blood samples were collected from the cephalic veins; 1 by direct venipuncture and 1 by use of a push-pull technique from a 20-gauge catheter. All blood samples underwent venous blood gas analysis immediately after collection. Results were compared between sample collection techniques before and after anesthesia induction and between anesthesia induction protocols. RESULTS All results were within established reference ranges. For many variables, statistically significant but clinically irrelevant differences were detected between samples collected by direct venipuncture and those collected by the push-pull technique but not between the 2 anesthesia induction protocols. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated the push-pull technique was an acceptable method for collection of blood samples from dogs for venous blood gas analysis that could be used instead of direct venipuncture for patients with patent IV catheters.