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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.

Stress has been shown to affect brain activity and exert potent and complex modulatory effects on pain. Several behavioral tests have shown that acute stress produces hyperalgesia, depending on the stress conditions. In the present study, we investigated the effects of single restraint stress on the tactile threshold and anxiety sensitivity in mice. Mice were evaluated for the tactile threshold using von Frey filaments and for anxiety sensitivity using the elevated plus maze (EPM) test. Tactile thresholds were lowered by both 2 and 4 hour of restraint stress, but anxiety-like behaviors were observed only after 4 hour of restraint stress in the EPM test. In addition, we found that alfaxalone, which is a positive allosteric modulator of the γ-aminobutyric acid (GABA)

Objective To compare the effects of sevoflurane, propofol and alfaxalone on the neuromuscular blockade induced by a single intravenous bolus of rocuronium in dogs. Study design A randomized, prospective, crossover experimental study. Animals A total of eight adult Beagle dogs (four female, four male), weighing 8.9–15.3 kg and aged 5–7 years. Methods The dogs were anesthetized three times with 1.25× minimum alveolar concentration of sevoflurane (SEVO treatment) and 1.25× minimum infusion rate of propofol (PROP treatment) or alfaxalone (ALFX treatment) at intervals of ≥14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC), a single bolus dose of rocuronium (1 mg kg–1) was administered intravenously. The times from rocuronium administration to achieving TOF count 0 (onset time), from achieving TOF count 0 to the reappearance of TOF count 4 (clinical blockade period), from 25% to 75% of TOFRC (recovery index) and from achieving TOF count 0 to TOF ratio/TOFRC >0.9 (total neuromuscular blockade duration) were recorded. Results The onset time and recovery index did not differ among the treatments. The median clinical blockade period was longer in the SEVO treatment [27.3 (26.0–30.3) minutes] than in PROP [16.6 (15.4–18.0) minutes; p = 0.002] and ALFX [22.4 (18.6–23.1) minutes; p = 0.017] treatments; and longer in the ALFX treatment than in the PROP treatment (p = 0.020). The mean total neuromuscular blockade duration was longer in the SEVO treatment (43.7 ± 9.9 minutes) than in PROP (25.1 ± 2.7 minutes; p Conclusions and clinical relevance Compared with alfaxalone and propofol, sevoflurane prolonged rocuronium-induced neuromuscular blockade by a significantly greater extent in dogs.

OBJECTIVE To determine the dose of alfaxalone for IM administration combined with dexmedetomidine and hydromorphone that would allow endoscopic-guided orotracheal intubation in rabbits without causing a decrease in respiratory rate or apnea. ANIMALS 15 sexually intact (9 females and 6 males) healthy Miniature Lop rabbits weighing a mean ± SD of 2.3 ± 0.3 kg and ranging in age from 4 to 9 months. PROCEDURES In a randomized, controlled clinical trial, rabbits received 0.1 mg of hydro-morphone/kg and 0.005 mg of dexmedetomidine/kg, plus alfaxalone at either 2 mg/kg (5 rabbits), 5 mg/kg (5 rabbits), or 7 mg/kg (5 rabbits). Drugs were mixed in a single syringe and administered IM. Semiquantitative rating scales were used to evaluate quality of anesthesia and intubation. Orotracheal intubation was attempted with endoscopy and confirmed by capnography. RESULTS The number of successful intubations was 0, 3, and 4 in rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. Median (range) anesthesia quality scores (scale, 0 to 12; 12 = deepest anesthesia) were 3 (2 to 5), 6 (5 to 6), and 6 (4 to 9) for rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. The median (range) intubation quality scores (scale, 0 to 3 [ie, intubation not possible to easiest intubation]) were 0 (0 to 0), 2 (0 to 3), and 2 (0 to 3) for rabbits receiving 2, 5, and 7 mg of alfaxalone/kg, respectively. None of the rabbits experienced a decrease in respiratory rate or apnea. CONCLUSIONS AND CLINICAL RELEVANCE Increasing doses of alfaxalone combined with hydromorphone and dexmedetomidine increased the success rate of endoscopic-guided orotracheal intubation. Increasing the dose of alfaxalone had no effect on respiratory rate.

The translation of new injectable anaesthetic drugs from rodent to humans remains slow, despite the realisation 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 anaesthetic neurosteroid alfaxalone. Forty rats had cannulas inserted under isoflurane anaesthesia for drug administration and sampling. Carotid artery blood samples were collected for blood gas analysis, haematology, 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 minutes. An initial NLME PK population model was used to design an adjusted alfaxalone infusion for SD females matching plasma concentrations in males and minimising 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 alphaxalone.

To compare effects of intravenous (IV) alfaxalone with ketamine-xylazine combination on anaesthetic induction, recovery and cardiopulmonary variables in mute swans. Randomized, controlled, clinical study. A group of 58 mute swans. Swans were given either alfaxalone (10 mg kg ; group A) or a combination of ketamine (12.5 mg kg ) and xylazine (0.28 mg kg ) (group KX) IV. Heart and respiratory rates, end-tidal carbon dioxide and peripheral haemoglobin oxygen saturation were recorded at 5 minute intervals during anaesthesia. Time from anaesthetic induction to intubation, from cessation of isoflurane to extubation, to lifting head, sternal recumbency and absence of head/neck ataxia were recorded. Anaesthetic and recovery quality were scored (1 = very poor; 5 = excellent). Data are presented as median (interquartile range). Significance was set at p < 0.05. In group A, 44% (12/27) of swans required mechanical ventilation for 2-14 minutes versus 3.2% (one/31) of swans in group KX (p = 0.0002). Heart rate was higher in group A than in group KX [146 (127-168) versus 65.5 (56-78) beats minute , respectively; p < 0.0001]. The isoflurane concentration required to maintain anaesthesia was higher in group A than in group KX [2.5% (2.0-3.0%) versus 1.5% (1.0-2.0%), respectively; p = 0.0001]. Time from cessation of isoflurane administration to lifting head was significantly longer in group A than in group KX [12 (9-17) versus 6 (4-7.75) minutes, respectively; p < 0.0001]. Anaesthesia quality scores were significantly better in group KX than in group A [4 (4-5) versus 4 (3-4), respectively; p = 0.0011], as were recovery scores [4 (3-5) versus 2 (2-3), respectively; p = 0.0005]. Alfaxalone is a suitable anaesthetic induction agent for use in mute swans. There is a greater incidence of postinduction apnoea and a higher incidence of agitation on recovery with alfaxalone than with ketamine-xylazine. [Abstract copyright: Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.]

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.

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.

Plethysmography is used in nonhuman primates (NHPs) to measure minute volume before aerosol exposure to an agent to calculate total time necessary in the exposure chamber. The consistency of respiratory parameters during the entire exposure time is paramount to ensuring dosing accuracy. Our study sought to validate an alfaxalone-midazolam (AM) anesthetic combination for use in aerosol studies. We hypothesized that AM would provide an adequate duration of anesthesia, achieve and maintain steady state minute volume (SSMV) for 20 min, and have anesthetic quality and side effects comparable to or better than either tiletamine-zolazepam (TZ) and ketamine-acepromazine (KA), the most common anesthetics used for this purpose currently. Two groups of NHPs, one consisting of 15 cynomolgus macaques and one of 15 rhesus macaques, received 3 intramuscular anesthetic combinations (AM, TZ, and KA), no less than one week apart. Anesthetized NHPs were placed in a plethysmograph chamber and their minute volumes were measured every 10 s to determine whether they had achieved SSMV and maintained it for at least 20 consecutive min. Achieving and reliably maintaining an SSMV for at least 20 min facilitates precise aerosol dosing of a challenge agent. Quality of anesthesia, based on the NHP's ability to achieve and maintain SSMV, was higher with AM compared with TZ and KA in both species, and AM had a longer duration of SSMV as compared with TZ and KA in cynomolgus macaques. Average SSMV was larger with AM compared with TZ in cynomolgus macaques, but larger with KA compared with AM in rhesus macaques. Duration of anesthesia was sufficient with all combinations but was longer for TZ than both AM and KA in both species. These results suggest that the AM anesthetic combination would produce the most accurate dosing for an aerosol challenge.

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.

Objective Alfaxalone is a popular veterinary anesthetic; however, research on this anesthetic in snakes has been limited to ball pythons, garter snakes and several Australian species. The objective was to evaluate the anesthetic effects of alfaxalone in corn snakes (Pantherophis guttatus), a popular pet snake. Study design Prospective, randomized crossover study. Animals A total of eight corn snakes. Methods In phase I, snakes were subcutaneously administered three doses of alfaxalone (5, 10 and 15 mg kg–1) in the cranial third of the body to determine the most effective dose. In phase II, a dose of 15 mg kg–1 was administered in the cranial and caudal thirds of the snakes to determine if injection site affected anesthesia duration. Heart rate (HR), respiratory rate (fR), righting reflex, escape response, tail pinch, needle prick and tongue flick were monitored at baseline and 5 minute intervals until the snakes fully recovered. Results Duration of anesthesia differed significantly, with higher doses lasting longer than lower doses: 5 mg kg–1 [23.8 ± 4.4 (15–30) minutes]; 10 mg kg–1 [40.6 ± 9.4 (25–55) minutes]; and 15 mg kg–1 [56.9 ± 8.4 (50–70) minutes], mean ± standard deviation (range). The tail pinch reflex was not completely lost in phase 1. There was a significant change in fR over time, but this was not related to dose. HR was not different by time or dose. Duration of anesthesia was not different after administration of alfaxalone (15 mg kg–1) in the cranial third versus the caudal third of the body; however, there was a significant decrease in HR and fR at this dose, regardless of injection site. Conclusions and clinical relevance Based on these results, alfaxalone (15 mg kg–1) provides adequate anesthesia for brief procedures or intubation; however, additional analgesia is required for painful procedures.

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 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.

Objectives To evaluate alfaxalone–midazolam anesthesia in Egyptian fruit bats (Rousettus aegyptiacus) and the effect of flumazenil administration on recovery time and quality. Study design Randomized, blinded, crossover and controlled, experimental trial. Animals A total of 10 male Egyptian fruit bats. Methods Bats were anesthetized with alfaxalone (15 mg kg−1) and midazolam (2 mg kg−1) administered subcutaneously. During anesthesia, vital signs, muscle tone and reflexes were monitored every 10 minutes. Flumazenil (0.3 mg kg−1) or saline at an equal volume was administered subcutaneously 60 minutes after anesthetic administration. Time to induction, time to first movement and recovery time (flying) were measured. Quality of induction, anesthesia and recovery were assessed on a 1–3 scale (1, poor; 2, good; 3, excellent). Results Time to induction was 4.2 ± 1.9 minutes (mean ± standard deviation), with median quality score of 2 (range, 1–3). Anesthesia quality score was 3 (1–3). During anesthesia, heart rate and respiratory frequency decreased significantly and penis relaxation, indicating muscle tone, increased significantly. Administration of flumazenil significantly reduced mean recovery time compared with saline (10 ± 5 versus 45 ± 17 minutes, respectively), and significantly improved the quality of recovery [2.5 (2–3) versus 1 (1–2), respectively]. Conclusions and clinical relevance Alfaxalone–midazolam anesthesia resulted in good induction, muscle relaxation and sufficient anesthesia to perform routine diagnostic and therapeutic procedures for approximately 40 minutes. Reversal of midazolam with flumazenil is recommended, resulting in quicker and better recovery.

To compare the anesthetic effects after intravenous administration of alfaxalone or propofol without premedication, either alfaxalone (5 mg/kg) or propofol (10 mg/kg) was administered intravenously over 120 sec in 6 cats. Each cat received the alternate treatment at least a 7-day interval. Anesthetic effects (tolerance of intubation, behavior changes and neurodepressive score) and physiological parameters were evaluated. Both treatments produced a rapid loss of consciousness, no apnea, and physiological parameters were maintained within clinically acceptable ranges apart from transient hypoxemia. The degree of hypoxemia was greater after the propofol treatment compared with the alfaxalone treatment. During the recovery period, more adverse events (ataxia, muscular tremors) were observed after the alfaxalone treatment compared with the propofol treatment.

We aimed to evaluate the induction, anesthesia, and cardiorespiratory effects of intramuscular (IM) anesthetic protocol with alfaxalone following premedication with low-dose medetomidine, butorphanol, or a combination of both (medetomidine–butorphanol) in dogs. Six healthy beagles were administered 1, 2.5, or 5 mg/kg alfaxalone IM following premedication with low-dose medetomidine (5 µg/kg; MA-IM), butorphanol (0.3 mg/kg; BA-IM), or medetomidine-butorphanol (5 µg/kg and 0.3 mg/kg, respectively; MBA-IM). Each dog received 9 treatments with minimum 7-day washout period between treatments. Dogs were allowed to breath room air during anesthetic induction. We attempted endotracheal intubation after alfaxalone administration. Alfaxalone produced a dose-dependent anesthetic effect in each anesthetic protocol. Intubation was achieved in 4 out of 6 dogs that received MA-IM and BA-IM with 2.5 mg/kg alfaxalone and in all dogs that received MBA-IM with 1, 2.5, and 5 mg/kg alfaxalone. The median durations [minimum–maximum] of accepting intubation were 79 [0–89], 97 [84–120], and 117 [84–217] min, respectively. Hypotension (mean arterial blood pressure

Objective In ungulates, α2-adrenergic agonists can decrease oxygenation possibly through alteration of pulmonary perfusion. Sodium nitroprusside can decrease pulmonary vascular resistance (PVR) and increase cardiac output ( Q ˙ t ) through vasodilation. The objective was to determine if sodium nitroprusside would improve pulmonary perfusion and attenuate the increased alveolar–arterial ( a –a) gradient resulting from medetomidine–azaperone–alfaxalone (MAA) administration. Study design Prospective, randomized, crossover study with a 2 week rest period. Animals A group of eight adult female captive white-tailed deer (Odocoileus virginianus). Methods Deer were administered MAA intramuscularly (IM), and auricular artery and pulmonary artery balloon catheters were placed. Deer spontaneously breathed air. Saline or sodium nitroprusside (0.07 mg kg–1) were administered IM 40 minutes after MAA injection. Heart rate (HR), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), pulmonary artery occlusion pressure (PAOP), right atrial pressure (RAP), Q ˙ t , arterial pH, PaCO2 and PaO2 were obtained immediately before nitroprusside injection (baseline) and 5, 10 and 15 minutes afterwards. Mixed venous blood samples were obtained at baseline and at 5 minutes. Systemic vascular resistance (SVR), PVR, intrapulmonary shunt fraction ( Q ˙ s / Q ˙ t ), a –a gradient, oxygen delivery ( D ˙ O2) and oxygen extraction ratio (O2ER) were calculated. Statistical analysis was performed with repeated measures analysis of variance with correction factors. A p value Results With nitroprusside, MAP, MPAP, PAOP, RAP, SVR and O2ER significantly decreased and HR, Q ˙ t and D ˙ O2 increased compared with baseline and between treatments. There was a significant decrease in PVR and a –a gradient and increase in PaO2 compared with baseline and saline treatment. Changes were not sustained. Conclusions and clinical relevance Nitroprusside temporarily changed hemodynamic variables, increased PaO2 and decreased a –a gradient. Nitroprusside possibly led to better pulmonary perfusion of ventilated alveoli. However, IM nitroprusside at this dose is not recommended because of severe systemic hypotension and short action.

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 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.

Alfaxalone anesthesia and residue clearance profiles in rainbow trout Alfaxalone, a synthetic neuroactive steroid, has been tested as an immersion anesthetic in ornamental fish, but its safety and efficacy in sport fish have not been investigated. In the current study, we compared the physiologic and behavioral effects of alfaxalone with those of tricaine methanesulfonate (MS222) for anesthesia of rainbow trout (Oncorhynchus mykiss) via water immersion. We also analyzed alfaxalone-exposed tissues to determine residue clearance times. Fish were anesthetized for 10 min by immersion in low-dose alfaxalone (A(low); 5 mg/L induction, 1 mg/L maintenance), high-dose alfaxalone (A(high); 5 mg/L induction, 2 mg/L maintenance), or MS222 (MS; 150 mg/L induction, 100 mg/L maintenance). Fish received all 3 treatments, separated by a washout period of at least 18 d in a blinded, complete crossover design. We hypothesized that immersion in A(low) or A(high) would provide a stable plane of anesthesia in rainbow trout, with dose-dependent time to recovery, and that opercular rates and depths of anesthesia would be equivalent to that of MS222. The time to anesthesia induction was longer for alfaxalone than MS222 but averaged less than 100 s. The time to recovery from anesthesia was also longer for alfaxalone than MS222, with significantly shorter recovery time for A(low) than for A(high). All treatments decreased opercular rate and response to noxious stimuli. Alfaxalone residue clearance was greater than 80% from all tissues within 1 h, greater than 99% from muscle within 4 h, and 100% from all tissues within 36 h after exposure. We conclude that alfaxalone immersion at 5 mg/L for induction and 2 mg/L for maintenance provides a safe, viable alternative to MS222 for the anesthesia of rainbow trout.

Objective To evaluate the effect of dexmedetomidine on alfaxalone immobilization in snakes. Study design Nonblinded, crossover study. Animals A total of eight mature common garter snakes (Thamnophis sirtalis). Methods Snakes were administered each of three treatments intracoelomically: alfaxalone (30 mg kg–1; treatment A), alfaxalone (30 mg kg–1) combined with dexmedetomidine (0.05 mg kg–1; treatment AD0.05); and alfaxalone (30 mg kg–1) combined with dexmedetomidine (0.10 mg kg–1; treatment AD0.10). A minimum of 10 days elapsed between experimental trials. Times to loss of righting reflex (LRR) and return of righting reflex (RRR) were recorded. Heart rate (HR) was recorded every 5 minutes throughout the period of LRR and averaged for each snake. Times to LRR and RRR, and mean HR in snakes that achieved LRR were reported. Results LRR occurred in eight (100%), five (63%) and three (38%) snakes in treatments A, AD0.05 and AD0.10, respectively. For all treatments, time to LRR ranged 3–20 minutes. Median (range) times to RRR were 39 (30–46), 89 (62–128) and 77 (30–185) minutes for treatments A, AD0.05 and AD0.10, respectively. In animals where righting reflex was lost, mean HR was lower in all dexmedetomidine treatments compared with treatment A. Conclusions and clinical relevance In this pilot study, alfaxalone resulted in reliable immobilization, whereas dexmedetomidine and alfaxalone combinations resulted in highly variable durations of immobilization with low HR in immobilized animals. For snakes that achieved LRR, the addition of dexmedetomidine (0.05 mg kg–1) to alfaxalone appeared to extend the period of immobilization compared with alfaxalone alone.

OBJECTIVE To evaluate SC administration of 2 sedation protocols, ketamine-midazolam (KM) and alfaxalone-midazolam (AM), in African pygmy hedgehogs (Atelerix albiventris). ANIMALS 9 healthy adult hedgehogs (5 males, 4 females). PROCEDURES A randomized, blinded, complete crossover study was performed. Sedation was induced by SC administration of either ketamine (30 mg/kg [14 mg/lb]) with midazolam (1 mg/kg [0.45 mg/lb]) or alfaxalone (3 mg/kg [1.4 mg/lb]) with midazolam (1 mg/kg), including a 2-week washout period between treatments. Flumazenil (0.05 mg/kg [0.02 mg/lb], SC) was administered 45 minutes after administration of either protocol to reverse the effects of midazolam. Physiologic variables, reflexes, and behaviors were monitored. Food intake and body weight were measured before and after sedation. RESULTS Deep sedation characterized by complete loss of the righting reflex, decreased jaw tone, decreased pelvic limb withdrawal reflex, and preservation of the palpebral reflex was produced in 7 of 9 hedgehogs after KM administration and all 9 hedgehogs after AM administration. Mean ± SD time to loss of righting reflex was 6.4 ± 2.4 minutes after KM administration and 10 ± 4.0 minutes after AM administration. Following flumazenil administration, no significant difference was found in recovery time between sedation with KM (18.8 ± 12.7 minutes) and AM (14.4 ± 7.8 minutes). No significant differences were found in respiratory rate, oxygen saturation, or body temperature between protocols, whereas heart rate was higher for sedation with KM. Both sedation protocols resulted in a transient reduction in food intake. CONCLUSIONS AND CLINICAL RELEVANCE Subcutaneous administration of KM and AM provided deep sedation that might be useful to facilitate routine, noninvasive procedures in hedgehogs.

Due to their unpredictability and variable effects, injectable anesthetic regimens in laboratory rodent species warrant refinement. In our study we sought to evaluate alfaxalone, which has gained recent popularity in veterinary medicine, alone and in combination with dexmedetomidine to evaluate their anesthetic ability in Sprague–Dawley rats when administered intraperitoneally. Three doses of alfaxalone only and 4 dose combinations of alfaxalone-dexmedetomidine were tested in males and female rats. The time to induction, anesthetic duration, pulse rate, respiratory rate, temperature, and time to recovery were recorded by a blind observer. The level of anesthesia induced by the various anesthetic protocols was assessed by using pedal withdrawal reflex to a noxious stimulus and scored according to the response. Dependent on the treatment group, atipamezole or saline was administered intraperitoneally once animals reached 60 min of anesthesia. Regardless of the dose, alfaxalone alone achieved only a sedative level of anesthesia, whereas all alfaxalone-dexmedetomidine combinations led to a surgical level of anesthesia in all animals. Anesthesia regimens using alfaxalone alone and in combination with dexmedetomidine demonstrated sex-associated differences, with female rats maintaining longer durations of sedation or anesthesia than their male counterparts. Both male and female rats displayed decreases in physiologic parameters consistent with the effects of dexmedetomidine. Given the results described herein, we recommend 20 mg/kg alfaxalone for sedation and 30 mg/kg alfaxalone combined with 0.05 mg/kg dexmedetomidine for surgical anesthesia in female rats. Appropriate doses of alfaxalone only and alfaxalone-dexmedetomidine for male rats were not determined in this study and need further evaluation.

Objective To evaluate the effect of alfaxalone and methadone administered intramuscularly (IM), with or without ketamine, on sedation and echocardiographic measurements in healthy cats. Study design A randomized, blinded, clinical study. Animals A group of 24 client-owned cats. Methods Baseline echocardiographic evaluation (bEchoCG) was performed. Cats were given IM alfaxalone (2 mg kg–1) and methadone (0.3 mg kg–1) with (AMK group) or without (AM group) ketamine (1 mg kg–1). A sedation score (0–5, indicating none to good sedation) was assigned at 5 (T5), 10 (T10) and 15 (T15) minutes after IM injection. At T15, a second echocardiographic evaluation (sEchoCG) was performed. Data are shown as median (range). Significance was p Results Finally, 21 cats were included. Sedation score was significantly higher in the AMK (11 cats) than in the AM group (10 cats): 4 (1–5) versus 0.5 (0–4) at T5 (p = 0.003); 4 (1–5) versus 1.5 (0–5) at T10 (p = 0.043); and 4 (1–5) versus 2 (0–5) at T15 (p = 0.024). All echocardiographic measurements obtained were within reference ranges. Between the groups, aortic root area (p = 0.009) and end-diastolic aortic dimension (p = 0.011) were significantly higher in the AM group at bEchoCG and sEchoCG, respectively. Within each group, values at bEchoCG and sEchoCG showed no significant differences, except for pulmonary peak velocity (0.85 m second–1; p = 0.028) in the AMK group and ejection time (154 m second; p = 0.03) in the AM group; both variables decreased after sedation. Conclusions and clinical relevance In this population of healthy cats, neither protocol produced clinically meaningful effects on the echocardiographic variables evaluated. Alfaxalone with methadone produced mild sedation, whereas the addition of 1 mg kg–1 ketamine induced adequate sedation for diagnostic procedures.

Background Anaesthesia is often required in common marmosets undergoing various procedures. The aim of this study was to evaluate anaesthetic and cardiopulmonary effects of alfaxalone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets. Methods The following treatments were repeatedly administered to seven female common marmosets: Treatment A, alfaxalone (12 mg kg-1 ) alone; treatment AK, alfaxalone (1 mg animal-1 ) plus ketamine (2.5 mg animal-1 ); treatment AMB, alfaxalone (4 mg kg-1 ), medetomidine (50 µg kg-1 ) plus butorphanol (0.3 mg kg-1 ); and treatment AMB-Ati, AMB with atipamezole at 45 minutes. Results and conclusions Marmosets became laterally recumbent and unresponsive for approximately 30 minutes in A and AK and for approximately 60 minutes in AMB. The animals showed rapid recovery following atipamezole injection in AMB-Ati. The decrease in heart rate and SpO2 was significantly greater in AMB compared to A and AK. Oxygen supplementation, anaesthetic monitors and atipamezole should be available especially when AMB is administered.

Objective To evaluate the sedative effects of two doses of alfaxalone when added to a combination of dexmedetomidine and methadone injected intramuscularly (IM) in healthy Beagles. Study design Randomized, blinded, crossover, experimental study. Animals A group of six adult Beagles. Methods Dogs were sedated on three different occasions with IM dexmedetomidine (3 μg kg–1) and methadone (0.3 mg kg–1) combined with two doses of alfaxalone (0.5 and 1 mg kg–1; A0.5 and A1, respectively) or saline (A0). Quality of sedation, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35 and 45 minutes. Pulse and respiratory rates, oxygen saturation of haemoglobin (SpO2) and noninvasive blood pressure (NIBP) were recorded every 5 minutes. Onset of sedation and duration of recumbency, response to venous catheterization and recovery quality were assessed. Physiological variables (analysis of variance) were analysed between treatments and within treatments compared with baseline (Student t test). Nonparametric data were analysed using Friedman and Cochran’s Q tests. Significance was p Results Sedation scores were significantly higher when alfaxalone was co-administered (area under the curve; p = 0.024, A0.5; p = 0.019, A1), with no differences between doses. Onset of sedation was similar, but duration of recumbency was longer in A0.5 than in A0 [median (minimum–maximum), 43 (35–54) versus 30 (20–47) minutes, p = 0.018], but not in A1. Response to venous catheterization and tail clamping, and quality of recovery (acceptable) presented no differences between treatments. A decrease in all physiological variables (compared with baseline) was observed, except for NIBP, with no differences between treatments. All dogs required oxygen supplementation due to reduced SpO2. Conclusions and clinical relevance Adding alfaxalone to methadone and dexmedetomidine enhanced sedation and duration of recumbency. Although cardiopulmonary depression was limited, oxygen supplementation is advisable.

Objective To evaluate the anesthetic and cardiopulmonary effects of xylazine–alfaxalone anesthesia in donkey foals undergoing field castration. Study design Prospective clinical study. Animals A group of seven standard donkeys aged [median (range)] 12 (10–26) weeks, weighing 47.3 (37.3–68.2) kg. Methods Donkeys were anesthetized with xylazine (1 mg kg−1) intravenously (IV) followed 3 minutes later by alfaxalone (1 mg kg−1) IV. Additional doses of xylazine (0.5 mg kg−1) and alfaxalone (0.5 mg kg−1) IV were administered as needed to maintain surgical anesthesia. Intranasal oxygen was supplemented at 3 L minute−1. Heart rate (HR), respiratory rate (fR) and mean arterial pressure (MAP) by oscillometry were recorded before drug administration and every 5 minutes after induction of anesthesia. Peripheral oxygen saturation (SpO2) was recorded every 5 minutes after induction. Time to recumbency after alfaxalone administration, time to anesthetic re-dose, time to first movement, sternal and standing after last anesthetic dose and surgery time were recorded. Induction and recovery quality were scored (1, very poor; 5, excellent). Results Median (range) induction score was 5 (1–5), and recovery score 4 (1–5). Overall, two donkeys were assigned a score of 1 (excitement) during induction or recovery. HR and MAP during the procedure did not differ from baseline. fR was decreased at 5 and 10 minutes but was not considered clinically significant. SpO2 was Conclusions and clinical relevance Xylazine–alfaxalone anesthesia resulted in adequate conditions for castration in 12 week old donkeys. While the majority of inductions and recoveries were good to excellent, significant excitement occurred in two animals and may limit the utility of this protocol for larger donkeys. Hypoxemia occurred despite intranasal oxygen supplementation.

Objective To determine the alfaxalone dose reduction during total intravenous anaesthesia (TIVA) when combined with ketamine or midazolam constant rate infusions and to assess recovery quality in healthy dogs. Study design Prospective, blinded clinical study. Animals A group of 33 healthy, client-owned dogs subjected to dental procedures. Methods After premedication with intramuscular acepromazine 0.05 mg kg-1 and methadone 0.3 mg kg-1, anaesthetic induction started with intravenous alfaxalone 0.5 mg kg-1 followed by either lactated Ringer’s solution (0.04 mL kg-1, group A), ketamine (2 mg kg-1, group AK) or midazolam (0.2 mg kg-1, group AM) and completed with alfaxalone until endotracheal intubation was achieved. Anaesthesia was maintained with alfaxalone (6 mg kg-1 hour-1), adjusted (±20%) every 5 minutes to maintain a suitable level of anaesthesia. Ketamine (0.6 mg kg-1 hour-1) or midazolam (0.4 mg kg-1 hour-1) were employed for anaesthetic maintenance in groups AK and AM, respectively. Physiological variables were monitored during anaesthesia. Times from alfaxalone discontinuation to extubation, sternal recumbency and standing position were calculated. Recovery quality and incidence of adverse events were recorded. Groups were compared using parametric analysis of variance and nonparametric (Kruskal-Wallis, Chi-square, Fisher’s exact) tests as appropriate, p Results Midazolam significantly reduced alfaxalone induction and maintenance doses (46%; p = 0.034 and 32%, p = 0.012, respectively), whereas ketamine only reduced the alfaxalone induction dose (30%; p = 0.010). Recovery quality was unacceptable in nine dogs in group A, three dogs in group AK and three dogs in group AM. Conclusions and clinical relevance Midazolam, but not ketamine, reduced the alfaxalone infusion rate, and both co-adjuvant drugs reduced the alfaxalone induction dose. Alfaxalone TIVA allowed anaesthetic maintenance for dental procedures in dogs, but the quality of anaesthetic recovery remained unacceptable irrespective of its combination with ketamine or midazolam.

Objective To characterize and compare two intramuscular drug protocols using alfaxalone and alfaxalone–medetomidine combination for the field immobilization of free-ranging koalas. Study design Blinded, randomized, comparative field study. Animals A total of 66 free-ranging koalas from the Mount Lofty Ranges, South Australia. Methods Koalas were randomly allocated into two groups. Group A animals were given alfaxalone alone at 3.5 mg kg–1. Group AM animals were given alfaxalone 2 mg kg–1 and medetomidine 40 μg kg–1, reversed with atipamezole at 0.16 mg kg–1. Blinded operators recorded heart rate (HR), respiratory rate (fR), cloacal temperature, depth of sedation and times to: first effect, sedation suitable for clinical interventions, first arousal and full recovery. Data were analysed using independent t test, Mann–Whitney U test, chi-square analysis and log-rank test at 5% level of significance. Results Suitable immobilization for clinical examination and sample collection was achieved in all animals. In groups A and AM, median time to working depth was 6.5 minutes (range: 3.4–15) and 8.1 minutes (range: 4.3–24) and time to complete recovery was 66 minutes (range: 12–138) and 34 minutes (range: 4–84), respectively, following reversal. Time to first effect was significantly shorter in group A (p = 0.013), whereas time to full arousal was significantly shorter in group AM (p = 0.007) probably due to the administration of atipamezole. Maximum HR was 117 ± 28 beats minute–1 in group A, which was a significant increase from baseline values (p Conclusions and clinical relevance Both the protocols produced immobilization, enabling clinical examination and sample collection; however, protocol AM was more suitable for field work due to shorter recovery times.

This study aimed to investigate the specific pharmacokinetic profile and effects of alfaxalone after intravenous (IV) and intramuscular (IM) administration to rabbits and evaluate the potential interaction with dexmedetomidine. The study design was a blinded, randomized crossover with a washout period of 2 weeks. Five New Zealand white rabbits were used. Each animal received single IV and IM injections of alfaxalone at a single dose of 5 mg/kg, and single IV and IM injections of alfaxalone (5 mg/kg) combined with dexmedetomidine (100 μg/kg) administered intramuscularly. Blood samples were collected at predetermined times and analysed by high-performance liquid chromatography. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation/anaesthesia scores were evaluated by a modified numerical rating scale. At pre-determined time points heart and respiratory rates were measured. Times to sternal recumbency and standing position during the recovery were recorded. Concentrations of alfaxalone alone were very similar (slighty smaller) to concentrations when alfaxalone was combined with dexmedetomidine, after both routes of administration. Dexmedetomidine enhanced and increase the duration of the sedative effects of alfaxalone. In conclusion, alfaxalone administered in rabbits provides rapid and smooth onset of sedation. After IV and IM injections of alfaxalone combined with dexmedetomidine, a longer MRT and a deeper and extended sedation have been obtained compared to alfaxalone alone. Consequently, alfaxalone alone or in combination with dexmedetomidine could be useful to achieve respectively moderate to deep sedation in rabbits.

Alfaxalone is an injectable anesthetic agent that is used in veterinary medicine for general anesthesia. We evaluated the safety and efficacy of alfaxalone delivered through continuous rate infusion by comparing ketamine–xylazine–alfaxalone (KXA) anesthesia with ketamine–xylazine (KX) anesthesia in Sprague–Dawley rats. Anesthesia was induced in male and female rats by using subcutaneous KX. After induction, rats in the KXA group received alfaxalone (10 mg/kg/h IV) for 35 min, whereas rats in the KX group did not receive alfaxalone. At the end of the trial, alfaxalone was discontinued, and xylazine was reversed in all rats by using atipamezole. Throughout anesthesia, we assessed forepaw withdrawal reflex (FPWR), hindpaw withdrawal reflex (HPWR), response to surgical stimulation, heart rate, respiratory rate, SpO2, body temperature, and time to standing. KXA produced a reliable surgical plane of anesthesia, as evidenced by the loss of both FPWR and HPWR and lack of response to surgical stimulation in all 16 rats, whereas only 6 of the 16 rats in the KX group lost HPWR. No rat in the KXA group regained a paw withdrawal reflex during alfaxalone administration, whereas 3 of the 12 rats (25%) in the KX group that reached a surgical plane of anesthesia exited that plane within the 35-min timeframe. Neither heart rate, respiratory rate, SpO2, body temperature, nor time to standing differed between KXA and KX groups; and there were no sex-associated differences in anesthesia response. These results indicate that alfaxalone (10 mg/kg/h IV) delivered through continuous rate infusion, in combination with ketamine and xylazine, provides a safe, prolonged, and reliable surgical plane of anesthesia in rats.

BACKGROUND Previous formulations of alfaxalone have shown it to be a fast-acting intravenous anesthetic with high therapeutic index. Alfaxalone has been reformulated for human use as Phaxan, an aqueous solution of 10 mg/mL of alfaxalone and 13% betadex. This study assessed the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of alfaxalone given as a bolus intravenous injection of this formulation to human male volunteers. METHODS A dose of 0.5 mg/kg (0.42-0.55 mg/kg) of alfaxalone [mean (range)] was given by single intravenous bolus injection to 12 healthy subjects. Plasma alfaxalone concentrations and bispectral index (BIS) values were analyzed using an integrated pharmacokinetic-pharmacodynamic (PKPD) model using nonlinear mixed-effects models. Effect (BIS) was described using a sigmoidal fractional maximum effect (EMAX) model. All parameters were scaled using allometry and standardized to a 70-kg person using exponents of 0.75 for clearance parameters (CL, Q2, and Q3), 1.0 for volumes (V1, V2, and V3), and 0.25 for time-related parameters half-time keo (t1/2keo). RESULTS A 3-compartment model used to fit PK data with an additional compartment, linked by t1/2keo to describe the effect compartment, yielded alfaxalone PK parameter estimates: CL: 1.08 L/min; 0.87-1.34 L/min (median; 95% confidence interval [CI]); central volume of distribution (V1): 0.99 L; 0.53-2.05 L (median; 95% CI); intercompartment CLs (Q2): 0.87 L/min; 0.32-1.71 L/min (median; 95% CI) and Q3: 0.46 L/min; 0.19-1.03 L/min (median; 95% CI); and peripheral volumes of distribution (V2): 6.36 L; 2.79-10.7 L (median; 95% CI) and V3: 19.1 L; 8.61-37.4 L (median; 95% CI). PD interrogation assumed a baseline BIS of 96, with an estimated EMAX: 0.94; 0.71-0.99 (median; 95% CI), a plasma concentration (Cp) for 50% effect (C50): 0.98 mg/L; 0.83-1.09 mg/L (median; 95% CI), and a Hill coefficient (γ): 12.1; 6.7-15 (median; 95% CI). The t1/2keo was 8 minutes; 4.70-12.8 minutes (median; 95% CI). The mean time to a BIS 50 was 0.94 minutes (standard deviation [SD] = 0.2 minutes). CONCLUSIONS After a single bolus intravenous injection, alfaxalone has a high plasma CL equal to hepatic blood flow as reported for earlier studies of bolus injections of a previous formulation of alfaxalone. The plasma levels associated with BIS values of

Objective: To describe the frequency of cardiac complications during pregnancy related to parity in women with congenital heart defects. Methods: A retrospective tertiary single-center study at the Adult Congenital Heart Disease Centre that followed 307 women with congenital heart disease during the years 1997–2015 in Gothenburg, Sweden. Ma­ternal cardiac complications were noted for each pregnancy using medical and obstetric records. The CARPREG I and modified WHO (mWHO) risk classifications were used. Twin pregnancies, miscarriages before gestational week 13, and pregnancy terminations were excluded. Results: Five hundred seventy-one deliveries and 9 late miscarriages were analyzed. The mean parity was 1.74 per woman (range 1–8). Eighty-four (14.6%) maternal cardiac complications were experienced; arrhythmia (5.7%) and heart failure (4.4%) being the most prevalent, and there was 1 maternal death. Heart failure occurred during the first pregnancy in 12 women (3.9%), in the second pregnancy in 8 women (4.3%), and in the third pregnancy in 4 women (7.7%). CARPREG I and mWHO scores were associated with an increased risk of having a cardiac complication, while parity per se was not associated. The OR for having a maternally uneventful second pregnancy if the first pregnancy was without cardiac complications was 5.47 (95% CI 1.76–16.94) after controlling for CARPREG I and mWHO scores. Conclusion: The risk of severe maternal cardiac complications during pregnancy in women with congenital heart disease is low. In this largest analysis to date with a focus on parity in 307 women, the risk classification predicts the maternal outcome more than parity per se. If the first pregnancy is uneventful, the OR is 5.5 for an uneventful second pregnancy if CARPREG I and mWHO scores remain unchanged.

OBJECTIVE To compare the cardiorespiratory effects, quality and duration of sedation of 2 subcutaneous sedation protocols for noninvasive procedures in guinea pigs (GPs). ANIMALS 24 pet GPs (15 females, 9 males) of 3 different age groups: infant (n = 8), juvenile (8), and adult (8). PROCEDURES The study design was a randomized, crossover, blinded, clinical trial with a washout period of at least 7 days between protocols. Guinea pigs were sedated SC with alfaxalone (5 mg/kg; group A) or alfaxalone (5 mg/kg) and midazolam (0.5 mg/kg; group A + M) to facilitate blood sampling, radiography, or abdominal ultrasonography. Vital parameters, hemoglobin saturation (SpO2), and sedation scores were recorded every 5 minutes. RESULTS Mean heart rate was lower in group A than group A + M (P = 0.001), and respiratory rate was significantly (P = 0.001) decreased relative to baseline during sedation in both groups. The SpO2 remained above 95% in both sedation groups. Rectal temperature was significantly (P = 0.001) lower during recovery versus baseline. Onset of sedation was shorter and the duration longer in group A + M than in group A. The duration and depth of the sedation was different between age groups (P = 0.001), being longer and deeper in adults. Bruxism, hectic movements, twitching, and some degree of hyperreactivity were observed during 41 of the 48 sedations. CLINICAL RELEVANCE Subcutaneous administration of alfaxalone provided reliable sedation for nonpainful procedures in GPs. When combined with midazolam, alfaxalone provided longer and deeper sedation that was more significant in adults than in younger patients.

To compare two commercial formulations of alfaxalone for immersion anaesthesia in laboratory zebrafish.Prospective, blinded, randomized study.A total of 20 adult Danio rerio (Tuebingen strain).Zebrafish were divided into two groups of 10 (five female, five male) and placed in individual immersion baths containing 10 mg LThere 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.Immersion anaesthesia using 10 mg L

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.

This clinical review summarises the pharmacological and anaesthetic properties of alfaxalone in the dog. Available pharmacokinetic-pharmacodynamic data and factors affecting the induction dose have been reported. Furthermore, quality of induction and recovery after alfaxalone administration, the use of alfaxalone for total intravenous anaesthesia, and its effects on the cardio-respiratory system, on laryngeal motion, on intraocular pressure and tear production have been evaluated. Finally, the use of alfaxalone in dogs undergoing caesarean section and the effect of intramuscular alfaxalone administration have been considered.

To evaluate alfaxalone for total intravenous anesthesia (TIVA) in rabbits premedicated with dexmedetomidine or dexmedetomidine and buprenorphine.Crossover study (part 1) with observational study (part 2).A total of eight New Zealand White rabbits (Oryctolagus cuniculus), four female and four male, aged 12-16 weeks and weighing 2.8-3.5 kg in part 1. Separately, four additional rabbits in part 2.Crossover study design with eight rabbits per treatment. Rabbits were administered treatment D, dexmedetomidine (0.2 mg kgThe mean ± standard deviation alfaxalone infusion rate was 9.6 ± 2.6 and 4.5 ± 1.3 mg kgPremedication with dexmedetomidine-buprenorphine combined with alfaxalone TIVA may be a viable alternative for performing abdominal surgery in the rabbit. The use of supplemental oxygen and ability to provide respiratory support are advised.

North American vipers are commonly housed in zoological institutions or studied as free-ranging populations. Because of their venomous predatory and defensive mechanism, sedation or anesthesia is frequently employed to facilitate safe handling and medical procedures, especially of the head. A new formulation of alfaxalone with proprietary preservatives was recently approved and indexed for 28-d use post-vial puncture. Pharmacodynamic effects of alfaxalone in its prior formulation have been researched in nonvenomous species, but the optimal dose and route of administration in vipers have not been reported. In part one, 10 prairie rattlesnakes (

This blinded, randomized, prospective study evaluated the sedative and physiologic effects of a combination of alfaxalone and methadone with or without midazolam in adult dogs. Sixteen dogs received methadone (0.5 mg/kg body weight) and alfaxalone (1 mg/kg body weight), either with or without midazolam (0.5 mg/kg body weight), by intramuscular injection. Quality of sedation, heart rate, respiratory rate, systolic arterial pressure, rectal temperature, arterial oxygen saturation of hemoglobin, and dose of alfaxalone required for endotracheal intubation were recorded. Sedation score increased over time in both groups; however, dogs premedicated with methadone and alfaxalone appeared significantly less sedated than dogs premedicated with midazolam at 15, 20, and 25 minutes post-injection (

This communication reports the effect of alphaxalone on motor somatosensory evoked potential (SEPs) in a rhesus macaque. The animal was deeply anaesthetised with an infusion of ketamine, medetomidine, midazolam and alfentanil. The median nerve was stimulated, and SEPs were recorded from the motor cortex. The successive administration of three doses of alphaxalone (0.5, 1 and 2 mg/kg) induced an increase of the latency time and a decrease of the amplitude of the SEPs. However, the structure of the waveforms was conserved, and hence alphaxalone might represent a suitable general anaesthetic option in neuroscience research as well as veterinary or human medicine.

Alfaxalone is an injectable neuroactive steroid anesthetic that is becoming more widely used as a sedative in a wide range of animals. The purpose of this study was to evaluate the efficacy of this drug for sedation during handling and noninvasive medical procedures in black-cheeked lovebirds (

Objectives The aim of this study was to compare the effects of butorphanol and buprenorphine, as part of a multimodal analgesic protocol, on recovery and analgesia in cats undergoing orchiectomy. Methods In a prospective, randomized, blind clinical trial, 47 adult male cats were randomly assigned to receive either butorphanol (0.3 mg/kg, n = 24) or buprenorphine (0.02 mg/kg, n = 23) in combination with dexmedetomidine (25 μg/kg) and alfaxalone (2 mg/kg) as a single intramuscular injection for the induction of general anesthesia. Isoflurane carried in oxygen was supplemented as needed during orchiectomy. All cats received lidocaine (2 mg/kg intratesticular), meloxicam (0.3 mg/kg SC) and atipamezole (125 μg/kg IM) postoperatively. Pain and sedation scales were applied at baseline, and 2, 4 and 6 h postoperatively. Time to achieve sternal recumbency and to begin eating were also recorded. Results Pain scale scores were low and showed no difference between the treatment groups at all time points ( P ⩾0.99, all time points). Four cats exceeded the analgesia intervention threshold for rescue analgesia (butorphanol, n = 3; buprenorphine, n = 1). There was no difference in sedation scores between groups at any time point ( P >0.99, all time points). Significantly more cats in the buprenorphine group (n = 12) required isoflurane than in the butorphanol group (n = 2) ( P = 0.0013; relative risk 6.3, 95% confidence interval [CI] 1.8–23.5). There was no significant difference in time to achieve sternal recumbency ( P = 0.96, 95% CI –20 to 20) between groups or in return to eating ( P = 0.48, 95% CI –92.0 to 113.5), with most cats eating within 1 h of surgery (butorphanol, 79%; buprenorphine, 83%). Conclusions and relevance There were no significant differences in analgesia or recovery between butorphanol and buprenorphine treatment groups as part of a multimodal injectable anesthetic protocol. Butorphanol is associated with superior depth of anesthesia, facilitating injectable anesthesia.