Hypoventilation following oxygen administration associated with alfaxalone-dexmedetomidine-midazolam anesthesia in New Zealand White rabbits.

OBJECTIVE: To investigate the relationship between oxygen administration and ventilation in rabbits administered intramuscular alfaxalone-dexmedetomidine-midazolam. STUDY DESIGN: Prospective, randomized, blinded study. ANIMALS: A total of 25 New Zealand White rabbits, weighing 3.1-5.9 kg and aged 1 year. METHODS: Rabbits were anesthetized with intramuscular alfaxalone (4 mg kg-1), dexmedetomidine (0.1 mg kg-1) and midazolam (0.2 mg kg-1) and randomized to wait 5 (n = 8) or 10 (n = 8) minutes between drug injection and oxygen (100%) administration (facemask, 1 L minute-1). A control group (n = 9) was administered medical air 10 minutes after drug injection. Immediately before (PREoxy/air5/10) and 2 minutes after oxygen or medical air (POSToxy/air5/10), respiratory rate (fR), pH, PaCO2, PaO2, bicarbonate and base excess were recorded by an investigator blinded to treatment allocation. Data [median (range)] were analyzed with Wilcoxon, Mann-Whitney U and Kruskal-Wallis tests and p < 0.05 considered significant. RESULTS: Hypoxemia (PaO2 < 88 mmHg, 11.7 kPa) was observed at all PRE times: PREoxy5 [71 (61-81) mmHg, 9.5 (8.1-10.8) kPa], PREoxy10 [58 (36-80) mmHg, 7.7 (4.8-10.7) kPa] and PREair10 [48 (32-64) mmHg, 6.4 (4.3-8.5) kPa]. Hypoxemia persisted when breathing air: POSTair10 [49 (33-66) mmHg, 6.5 (4.4-8.8) kPa]. Oxygen administration corrected hypoxemia but was associated with decreased fR (>70%; p = 0.016, both groups) and hypercapnia (p = 0.016, both groups). Two rabbits (one per oxygen treatment group) were apneic (no thoracic movements for 2.0-2.5 minutes) following oxygen administration. fR was unchanged when breathing air (p = 0.5). PaCO2 was higher when breathing oxygen than air (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Early oxygen administration resolved anesthesia-induced hypoxemia; however, fR decreased and PaCO2 increased indicating that hypoxemic respiratory drive is an important contributor to ventilation using the studied drug combination.

EVALUATION OF TWO ANESTHETIC COMBINATIONS IN LOWLAND NYALA (TRAGELAPHUS ANGASII).

Fourteen lowland nyala (Tragelaphus angasii) in managed care were successfully anesthetized for a total of 17 anesthetic events using either a combination of butorphanol (0.75 ± 0.15 mg/kg), azaperone (0.25 ± 0.05 mg/kg), and medetomidine (0.30 ± 0.06 mg/kg) (BAM) or medetomidine (0.17 ± 0.01 mg/kg), azaperone (0.22 ± 0.02 mg/kg), and alfaxalone (0.52 ± 0.08 mg/kg) (MAA) delivered intramuscularly via dart. Mean time to initial effect, sternal recumbency, lateral recumbency, handling, and intubation were recorded. The nyala were maintained in sternal recumbency with supplemental oxygenation until 60 min after initial injection. Cardiopulmonary effects were recorded every 5 min after handling until reversal. Arterial blood samples were collected every 15 min for analysis. Level of sedation and quality of recovery were scored. Anesthesia was antagonized with atipamezole (at 5 mg per mg of medetomidine) for both protocols and naltrexone (at 2 mg per mg of butorphanol) for the BAM protocol delivered intramuscularly via hand injection. Mean time to extubation, head control, and standing post reversal were recorded. No hyperthermia, acidemia, apnea, or tachycardia occurred; however, animals did display hypoxemia. Two animals in the BAM cohort required supplementation to facilitate handling. These drug combinations provided satisfactory levels of sedation in most cases for safe handling and minor procedures in lowland nyala under managed care.

Clinical measurements performed during alfaxalone total intravenous anaesthesia for radiography and neurophysiological investigations in dogs.

OBJECTIVE: To describe clinically relevant, physiological measurements collected during a 3 hour duration of alfaxalone total intravenous anaesthesia. STUDY DESIGN: Case series. ANIMALS: A total of 112 client-owned middle-aged or older dogs. METHODS: Dogs were premedicated with intramuscular acepromazine (0.03 mg kg-1). Anaesthesia was induced and subsequently maintained for up to 3 hours with alfaxalone administered intravenously. Dogs breathed 100% oxygen via an endotracheal tube. Heart rate, respiratory rate and blood pressure were evaluated 30 minutes after administration of acepromazine and used as baseline values for comparisons of intra-anaesthetic data. Blood glucose was measured 1 week prior to anaesthesia and every hour during alfaxalone anaesthesia. Quality and duration of recovery were recorded. Mean data for physiological variables were compared over three time points-before induction of anaesthesia, for the first hour of anaesthesia and from 60 minutes to discontinuation of anaesthesia. RESULTS: Mean induction dose of alfaxalone was 1.4 mg kg-1 [95% confidence interval (CI) 1.3-1.5). Post induction apnoea for >60 seconds occurred in 13 (11.6%) dogs. Mean alfaxalone infusion rate during the first 60 minutes of anaesthesia was 0.099 mg kg-1 minute-1; mean infusion rate was 0.092 mg kg-1 minute-1 from 60 minutes until discontinuation of anaesthesia. Heart rate was well maintained; hypotension (mean arterial blood pressure < 60 mmHg) was encountered in 23 (21%) dogs. Blood glucose levels did not alter during anaesthesia. Median time between discontinuation of alfaxalone infusion and extubation was 17 (7-35 minutes), time to assuming sternal recumbency was 75 (58-110 minutes), and time to standing was 109 (88-140 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone infusion provided effective anaesthesia in this population. In a minority of cases, respiratory and haemodynamic support of the patient was required.

Sedative effects of intramuscular alfaxalone in pet guinea pigs (Cavia porcellus).

OBJECTIVE: To evaluate the efficacy and side effects of alfaxalone administered intramuscularly (IM) as a sedative agent in guinea pigs undergoing survey radiographs. STUDY DESIGN: Prospective clinical trial. ANIMALS: A total of 30 client-owned guinea pigs. METHODS: Following baseline assessments, 5 mg kg-1 alfaxalone was administered IM. Heart rate, arterial haemoglobin oxygen saturation, respiratory rate, rectal body temperature, palpebral reflex, response to toe and ear pinch, righting reflex, posture, jaw tone and reaction to manipulation were assessed before and after sedation at 5-minute intervals. The time elapsed from onset of sedation to return of locomotion and coordinated limb movements, the quality of recovery and the occurrence of undesired effects were observed and recorded. RESULTS: The mean ± standard deviation onset of sedation was 2.7 ± 0.6 minutes. The physiological variables remained within normal ranges until completion of the procedure. Palpebral reflex and responsiveness to both ear and toe pinch were maintained during sedation. Neither hypoxaemia nor hypothermia was observed. The duration of sedation was 29.3 ± 3.2 minutes. Sedation and recovery were uneventful, and adverse effects were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: In conclusion, 5 mg kg-1 of IM alfaxalone represents a valuable sedation protocol for healthy guinea pigs undergoing minor noninvasive procedures. Further trials are required to investigate its cardiovascular effects, clinical usefulness in unhealthy patients and its combined use with analgesics for procedures associated with nociception.

Challenges of bringing a new sedative to market!

PURPOSE OF REVIEW: The current review examines the success and failures of the development of new hypnotic compounds for the human market. One of the important aspects is that one of the key present agents, propofol, is considered by many anaesthesiologists as 'the ideal'. However, all drugs have adverse or side-effects. RECENT FINDINGS: The last 30 years since the introduction of propofol has seen many new compounds evaluated; but as at the present time, only three agents may achieve a pivotal position in the market - fospropofol (a sedative agent which may have a role in endoscopic surgery); remimazolam (a short-acting benzodiazepine) whose development is also being focused on the sedation rather than anaesthesia market; and the pregnane steroid, alfaxalone (an anaesthetic agent first introduced in 1972, but withdrawn in 1984 because of adverse allergic reactions to the solvent, Cremophor EL) now solvented in a cyclodextrin. SUMMARY: Studies of these three agents thus far have shown that none of them has any major adverse side-effects; all have properties which warrant further clinical evaluation.

Hypoxemia after single-shot anesthesia in common marmosets.

BACKGROUND: It remains unknown how single-shot anesthesia influences physical parameters, especially respiratory function and blood oxygen level of common marmosets (Callithrix jacchus) which came to be used for laboratory research. METHODS: We measured blood oxygen levels, both before and after oxygenation, in 13 common marmosets under two single-shot anesthesia conditions: ketamine/xylazine/atropine and alphaxalone. RESULTS AND CONCLUSIONS: We found that SpO2 values decreased to about 80% in the ketamine/xylazine/atropine protocol and fell just below 90% in the alphaxalone protocol. We observed a clear decrease in PaO2 values under the anesthetized condition compared to the awake condition. Our data indicate that single-shot anesthesia may cause hypoxemia in marmosets. Previous studies on other non-human primate have reported no SpO2 decrease and hypoxemia; thus, our experiment suggests that marmosets may have a more fragile respiratory system and require intensive veterinary care during anesthesia.

Postinduction apnoea in dogs premedicated with acepromazine or dexmedetomidine and anaesthetized with alfaxalone or propofol.

OBJECTIVE: To compare incidence and duration of postinduction apnoea in dogs after premedication with methadone and acepromazine (MA) or methadone and dexmedetomidine (MD) followed by induction with propofol (P) or alfaxalone (A). STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: A total of 32 American Society of Anesthesiologists class I dogs (15 females, 17 males), aged between 4 months and 4 years, weighing between 3 and 46 kg. METHODS: Dogs were randomly allocated to be administered MA+P, MA+A, MD+P or MD+A (methadone 0.5 mg kg-1 and acepromazine 0.05 mg kg-1 or dexmedetomidine 5 µg kg-1). Induction agents were administered intravenously via syringe driver (P at 4 mg kg-1 minute-1 or A at 2 mg kg-1 minute-1) until successful endotracheal intubation and the endotracheal tube connected to a circle system with oxygen flow at 2 L minute-1. Oxygen saturation of haemoglobin (SpO2), end tidal partial pressure of carbon dioxide and respiratory rate were monitored continuously. If apnoea (≥ 30 seconds without breathing) occurred, the duration until first spontaneous breath was measured. If SpO2 decreased below 90% the experiment was stopped and manual ventilation initiated. Data were analysed with general linear models with significance set at p ≤ 0.05. RESULTS: There was no statistical difference in the incidence (11 of 16 dogs in A groups and 12 of 16 dogs in P groups), or mean ± standard deviation duration (A groups 125 ± 113 seconds, P groups 119 ± 109 seconds) of apnoea. The SpO2 of one dog in the MD+P group decreased below 90% during the apnoeic period. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol and alfaxalone both cause postinduction apnoea and the incidence and duration of apnoea is not influenced by the use of acepromazine or dexmedetomidine in premedication. Monitoring of respiration is recommended when using these premedication and induction agent combinations.

Effect of rate of administration of propofol or alfaxalone on induction dose requirements and occurrence of apnea in dogs.

OBJECTIVE: To evaluate the effect of rate of administration of propofol or alfaxalone on induction dose requirements and incidence of postinduction apnea (PIA) in dogs following premedication with methadone and dexmedetomidine. STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: Thirty-two healthy American Society of Anesthesiologists class I client-owned dogs (seven females, 25 males), aged between 5 and 54 months, weighing between 2.0 and 48.2 kg. METHODS: Dogs were premedicated intramuscularly with 0.5 mg kg-1 methadone and 5 µg kg-1 dexmedetomidine. Thirty minutes after premedication, dogs were preoxygenated for 5 minutes before the induction agent was administered intravenously via a syringe driver until orotracheal intubation was achieved. Dogs were randomized to receive alfaxalone 0.5 mg kg-1 minute-1 (A-Slow), alfaxalone 2 mg kg-1 minute-1 (A-Fast), propofol 1 mg kg-1 minute-1 (P-Slow), or propofol 4 mg kg-1 minute-1 (P-Fast). Oxygen saturation of hemoglobin (SpO2), end-tidal carbon dioxide and respiratory rate were monitored. If PIA (≥30 seconds without a breath) occurred, the time to the first spontaneous breath was measured. If SpO2 decreased below 90%, the experiment was stopped and manual ventilation initiated. RESULTS: The mean±standard deviation induction doses of alfaxalone and propofol were lower in the A-Slow [A-Slow 0.9±0.3 mg kg-1, A-Fast 2.2±0.5 mg kg-1 (p≤0.001)] and P-Slow [P-Slow 1.8±0.6 mg kg-1, P-Fast 4.1±0.7 mg kg-1 (p≤0.001)] groups, respectively. The incidence of PIA was 25% for the A-Slow and P-Slow groups and 100% for the A-Fast and P-Fast groups (p = 0.007). CONCLUSIONS AND CLINICAL RELEVANCE: Both propofol and alfaxalone following methadone and dexmedetomidine premedication caused PIA. Induction dose requirement and incidence of PIA were affected by the rate of administration of both drugs. When possible, propofol and alfaxalone doses should be reduced and administered slowly to reduce PIA.

Cardiovascular effects, induction and recovery characteristics and alfaxalone dose assessment in alfaxalone versus alfaxalone-fentanyl total intravenous anaesthesia in dogs.

OBJECTIVE: To compare cardiovascular effects and anaesthetic quality of alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI) when used for total intravenous anaesthesia (TIVA) in dogs. STUDY DESIGN: Prospective, blinded, randomized, experimental study. ANIMALS: A group of 12 intact female dogs. METHODS: Following intramuscular dexmedetomidine (10 µg kg-1) and methadone (0.1 mg kg-1) administration, anaesthesia was induced intravenously with alfaxalone (2 mg kg-1) (group AP) or alfaxalone (2 mg kg-1) preceded by fentanyl (2 µg kg-1) (group AF). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg-1 minute-1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI of fentanyl (10 µg kg-1 hour-1) (group AF). The alfaxalone VRI was adjusted every 5 minutes, based on clinical assessment. Cardiovascular parameters (recorded every 5 minutes) and recovery characteristics (using a numerical rating scale) were compared between groups. A mixed model statistical approach was used to compare the mean VRI alfaxalone dose and cardiovascular parameters between groups; recovery scores were analysed using the Wilcoxon rank-sum test (α = 0.05). RESULTS: The mean CRI alfaxalone dose for anaesthetic maintenance differed significantly between treatments [0.16 ± 0.01 mg kg-1 minute-1 (group AP) versus 0.13 ± 0.01 mg kg-1 minute-1 (group AF)]. Overall heart rate, systolic, mean and diastolic arterial pressures were lower in group AF than in group AP (p < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality scores did not differ significantly and were poor in both groups. CONCLUSIONS AND CLINICAL RELEVANCE: In combination with a fentanyl CRI, an alfaxalone TIVA provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl results in a significant dose reduction. The quality of anaesthetic recovery remains poor.

Clinical efficacy and cardiorespiratory effects of intramuscular administration of alfaxalone alone or in combination with dexmedetomidine in cats.

OBJECTIVE: To investigate the sedative, anaesthetic and cardiorespiratory effects of intramuscular (IM) administration of alfaxalone alone or in combination with dexmedetomidine in cats. STUDY DESIGN: Blinded, randomized crossover study with a washout period of 15 days. ANIMALS: Seven adult cats, weighing 3.5 ± 0.7 kg. METHODS: Cats were assigned randomly to each of three treatments: A5 (alfaxalone 5 mg kg(-1) ), D20 A5 (dexmedetomidine 20 µg kg(-1) and alfaxalone 5 mg kg(-1) ) and D40 A5 (dexmedetomidine 40 µg kg(-1) and alfaxalone 5 mg kg(-1) ). Drugs were administered IM into the epaxial muscles. Sedation or anaesthesia scores were evaluated by a modified numerical rating scale. Times to extubation, head-lift, sternal recumbency and standing were recorded. Heart and respiratory rates, systolic arterial pressure, arterial oxygen saturation of haemoglobin, end-tidal carbon dioxide tension and rectal temperature were measured at 5, 10, 15, 20, 30, 45, 60, 90, 120 and 150 minutes after drug administration. Adverse events were recorded. Data were analysed by one-way anova with Tukey's post-hoc test for parametric values and, for non-normally distributed parameters, a Kruskal-Wallis test and Mann-Whitney U-test for two independent samples (p < 0.05). RESULTS: Sedation scores were significantly different among the treatments. Cats in A5 were deeply sedated, whereas cats administered dexmedetomidine were anaesthetized. The onset of action and the duration of anaesthesia were related to the dose of dexmedetomidine. Cardiorespiratory parameters remained stable in the A5 group. Lower heart rates, higher systolic blood pressures and occasional low pulse oximetry readings were observed in the dexmedetomidine groups. A limited number of adverse events (hyperkinesia, emesis) occurred during recovery. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered IM induced sedation in cats. The addition of dexmedetomidine to alfaxalone induced general anaesthesia with a mild decrease in the heart rate and arterial oxygen saturation of haemoglobin.

A Phase 1c Trial Comparing the Efficacy and Safety of a New Aqueous Formulation of Alphaxalone with Propofol.

BACKGROUND: Phaxan™ (PHAX, Chemic Labs, Canton, MA) is an aqueous solution of 10 mg/mL alphaxalone and 13% 7-sulfobutylether ß-cyclodextrin (betadex). In preclinical studies, PHAX is a fast onset-offset IV anesthetic like propofol, but causes less cardiovascular depression. This first-in-man study was designed to find the anesthetic dose of PHAX and to compare it with an equivalent dose of propofol for safety, efficacy, and quality of recovery from anesthesia and sedation. METHODS: The study adhered to compliance with Good Clinical Practices regulations (clinical trials registry number, ACTRN12611000343909). This randomized, double-blind study compared PHAX and propofol using a Bayesian algorithm to determine dose equivalence for effects on the bispectral index (BIS). Male volunteers, ASA physical status I, gave written informed consent (n = 12 per group; PHAX or propofol). Parameters assessed for 80 minutes after drug injection (single bolus dose) were pain on injection, involuntary movement, BIS, blood pressure, need for airway support, and, as measures of recovery from sedation, the Richmond Agitation and Sedation Scale and the Digit Symbol Substitution Test. Arterial blood was withdrawn for biochemistry, hematology, and complement levels. RESULTS: No subject complained of pain on injection with PHAX, whereas 8 of the 12 subjects given propofol did. Nine PHAX and 8 propofol subjects reached BIS values of ≤50: median (interquartile range [IQR]) mg/kg dose = 0.5 (0.5-0.6) for PHAX and 2.9 (2.4-3.0) for propofol. The lowest median BIS reached was 27 to 28 for both agents with no significant differences between them for timing of onset and recovery of BIS. The concomitant median changes in systolic and diastolic blood pressures were -11% vs -19% for systolic and -25% vs -37% for diastolic in PHAX- and propofol-treated subjects, respectively. Nine of the 12 propofol-treated subjects and none of 12 PHAX-treated subjects required airway support. For subjects reaching an equivalent BIS of ≤50: a Richmond Agitation and Sedation Scale score of 0 was reached at a median of 5 (IQR, 5-10) and 15 (IQR, 10-20) minutes after PHAX and propofol, respectively; BIS returned to 90 at a mean of 21 (SD, 10.1) and 21 (SD, 9.2) minutes after PHAX and propofol, respectively; and Digit Symbol Substitution Test scores returned to predrug injection values at median of 50 (IQR, 35-72.5) and 42.5 (IQR, 35-76.3) minutes after PHAX and propofol, respectively. There was no increase in C3 and C4 complement fractions after either drug. CONCLUSIONS: PHAX causes fast-onset, short-duration anesthesia with fast cognitive recovery similar to propofol, but with less cardiovascular depression, or airway obstruction and no pain on injection.

Cardiovascular function during maintenance of anaesthesia with isoflurane or alfaxalone infusion in greyhounds experiencing blood loss.

OBJECTIVE: To compare adequacy of oxygen delivery and severity of shock during maintenance of anaesthesia with isoflurane or alfaxalone infusion in greyhounds experiencing blood loss. STUDY DESIGN: Prospective, randomised study. ANIMALS: Twenty-four greyhounds (ASA I). METHODS: All greyhounds were premedicated with methadone (0.2 mg kg(-1) ) intramuscularly. Anaesthesia was induced with alfaxalone 2.5 mg kg(-1) intravenously. Following endotracheal intubation, the dogs were connected to an anaesthetic circle circuit delivering oxygen. Dogs were allocated to receive inhaled isoflurane or an intravenous infusion of alfaxalone for maintenance of anaesthesia. Isoflurane was initially administered to achieve an end-tidal concentration of 1.4% and alfaxalone was initially administered at 0.13 mg kg(-1)  minute(-1) . The dose of isoflurane or alfaxalone was adjusted during instrumentation to produce a clinically equivalent depth of anaesthesia. All dogs were mechanically ventilated to normocapnia (Pa CO2 35-40 mmHg; 4.67-5.33 kPa). Passive warming maintained core body temperature between 37 and 38 °C. Measured and calculated indices of cardiovascular function, including mean arterial blood pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI), oxygen delivery index (D˙O2I), oxygen consumption index (V˙O2I) and oxygen extraction ratio (OER), were determined at baseline (60 minutes after start of anaesthesia) and after removal of 32 mL kg(-1) and 48 mL kg(-1) of blood. RESULTS: In all dogs, blood loss resulted in a significant decrease in MAP, CI, D˙O2 , and a significant increase in SVRI, V˙O2I , and OER. The changes in each of the indices did not differ significantly between dogs receiving isoflurane and dogs receiving alfaxalone. CONCLUSION AND CLINICAL RELEVANCE: No difference in oxygen delivery or severity of shock was observed when either inhaled isoflurane or intravenous alfaxalone infusion was used for maintenance of anaesthesia in greyhounds experiencing blood loss. There appears to be no clinical advantage to choosing one anaesthetic agent for maintenance of anaesthesia over the other in a dog experiencing blood loss.

Alfaxalone for total intravenous anaesthesia in dogs undergoing ovariohysterectomy: a comparison of premedication with acepromazine or dexmedetomidine.

OBJECTIVE: To describe alfaxalone total intravenous anaesthesia (TIVA) following premedication with buprenorphine and either acepromazine (ACP) or dexmedetomidine (DEX) in bitches undergoing ovariohysterectomy. STUDY DESIGN: Prospective, randomised, clinical study. ANIMALS: Thirty-eight healthy female dogs. METHODS: Following intramuscular buprenorphine (20 µg kg(-1) ) and acepromazine (0.05 mg kg(-1) ) or dexmedetomidine (approximately 10 µg kg(-1) , adjusted for body surface area), anaesthesia was induced and maintained with intravenous alfaxalone. Oxygen was administered via a suitable anaesthetic circuit. Alfaxalone infusion rate (initially 0.07 mg kg(-1) minute(-1) ) was adjusted to maintain adequate anaesthetic depth based on clinical assessment. Alfaxalone boluses were given if required. Ventilation was assisted if necessary. Alfaxalone dose and physiologic parameters were recorded every 5 minutes. Depth of sedation after premedication, induction quality and recovery duration and quality were scored. A Student's t-test, Mann-Whitney U and Chi-squared tests determined the significance of differences between groups. Data are presented as mean ± SD or median (range). Significance was defined as p < 0.05. RESULTS: There were no differences between groups in demographics; induction quality; induction (1.5 ± 0.57 mg kg(-1) ) and total bolus doses [1.2 (0 - 6.3) mg kg(-1) ] of alfaxalone; anaesthesia duration (131 ± 18 minutes); or time to extubation [16.6 (3-50) minutes]. DEX dogs were more sedated than ACP dogs. Alfaxalone infusion rate was significantly lower in DEX [0.08 (0.06-0.19) mg kg(-1) minute(-1) ] than ACP dogs [0.11 (0.07-0.33) mg kg(-1) minute(-1) ]. Cardiovascular variables increased significantly during ovarian and cervical ligation and wound closure compared to baseline values in both groups. Apnoea and hypoventilation were common and not significantly different between groups. Arterial haemoglobin oxygen saturation remained above 95% in all animals. Recovery quality scores were significantly poorer for DEX than for ACP dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone TIVA is an effective anaesthetic for surgical procedures but, in the protocol of this study, causes respiratory depression at infusion rates required for surgery.

Comparison of pain on injection during induction of anaesthesia with alfaxalone and two formulations of propofol in dogs.

OBJECTIVE: To compare the incidence of pain during injection of three intravenous induction agents in dogs. STUDY DESIGN: Prospective, crossover, randomized, blinded, clinical study. ANIMALS: Thirty dogs requiring anaesthesia for radiotherapy. METHODS: Dogs were anaesthetized on three occasions at weekly intervals. An IV cephalic catheter was placed, flushed with saline and alfentanil 0.01 mg kg(-1) and atropine 0.02 mg kg(-1) administered. After 30 seconds either: propofol lipid macroemulsion (Drug(P) ), propofol lipid-free microemulsion (Drug(PC) ) or alfaxalone (Drug(A)) was administered over 60 seconds. Each induction agent was administered once to each dog. Induction was recorded by video and reviewed by an assessor, unaware of treatment. Catheter placement (number of attempts, site, size and recent vein use) were recorded. Behavioural changes associated with pain or excitation, were recorded. Severity of pain on injection was recorded (mild, moderate or severe pain). Incidence of pain was analysed using logistic regression, excitation using McNemar's test (p < 0.05) and association of pain with induction agent and catheter placement using the Akaike Information Criterion (AIC). RESULTS: No dogs reacted to saline or Drug(A,) thus Drug(A) was excluded from analysis. Pain on injection occurred in six dogs (20%) with Drug(PC) and one dog (3.3%) with Drug(P). Pain was severe in four dogs with Drug(PC). Drug(P) resulted in a trend for reduced risk of pain compared to Drug(PC) (p = 0.076, odds ratio [confidence intervals] 0.14 [0.027-0.86]). Both propofol formulations resulted in greater risk of excitation than Drug(A) (p = 0.0003, odds ratio 4.5 [1.86-10.90]). Induction agent was associated with pain, whilst catheter placement was not. One dog developed facial oedema and one other dog skin necrosis adjacent to the catheter site following Drug(PC.) The study was terminated early due to ethical concerns about the severity of reactions with Drug(PC). conclusions and clinical relevance: Drug(PC) was associated with clinically relevant moderate to severe pain behaviour whilst Drug(A) and Drug(P) were not.

Clinical efficacy and cardiorespiratory effects of alfaxalone, or diazepam/fentanyl for induction of anaesthesia in dogs that are a poor anaesthetic risk.

OBJECTIVE: To evaluate the clinical efficacy and cardiorespiratory effects of alfaxalone as an anaesthetic induction agent in dogs with moderate to severe systemic disease. STUDY DESIGN: Randomized prospective clinical study. ANIMALS: Forty dogs of physical status ASA III-V referred for various surgical procedures. METHODS: Dogs were pre-medicated with intramuscular methadone (0.2 mg kg(-1) ) and allocated randomly to one of two treatment groups for induction of anaesthesia: alfaxalone (ALF) 1-2 mg kg(-1) administered intravenously (IV) over 60 seconds or fentanyl 5 µg kg(-1) with diazepam 0.2 mg kg(-1) ± propofol 1-2 mg kg(-1) (FDP) IV to allow endotracheal intubation. Anaesthesia was maintained with isoflurane in oxygen and fentanyl infusion following both treatments. All dogs were mechanically ventilated to maintain normocapnia. Systolic blood pressure (SAP) was measured by Doppler ultrasound before and immediately after anaesthetic induction, but before isoflurane administration. Parameters recorded every 5 minutes throughout subsequent anaesthesia were heart and respiratory rates, end-tidal partial pressure of carbon dioxide and isoflurane, oxygen saturation of haemoglobin and invasive systolic, diastolic and mean arterial blood pressure. Quality of anaesthetic induction and recovery were recorded. Continuous variables were assessed for normality and analyzed with the Mann Whitney U test. Repeated measures were log transformed and analyzed with repeated measures anova (p<0.05). RESULTS: Treatment groups were similar for continuous and categorical data. Anaesthetic induction quality was good following both treatments. Pre-induction and post-induction systolic blood pressure did not differ between treatments and there was no significant change after induction. The parameters measured throughout the subsequent anaesthetic procedures did not differ between treatments. Quality of recovery was very, quite or moderately smooth. CONCLUSIONS AND CLINICAL RELEVANCE: Induction of anaesthesia with alfaxalone resulted in similar cardiorespiratory effects when compared to the fentanyl-diazepam-propofol combination and is a clinically acceptable induction agent in sick dogs.

Anaphylaxis associated with intravenous administration of alphaxalone in a dog.

CASE REPORT: We describe the clinical signs and management of a case of anaphylaxis in a dog after intravenous administration of alphaxalone (Alfaxan®, Jurox, NSW, Aust), which has not been previously published. A female spayed cattle dog undergoing routine imaging for forelimb lameness was induced with Alfaxan after receiving sedation with acepromazine and methadone 70 min prior. Immediately after intravenous administration of Alfaxan, the dog exhibited vomiting and diarrhoea associated with acute hypotension. Gallbladder wall oedema was visualised consistent with anaphylaxis. The dog responded to rapid volume expansion. Adrenaline was not required. The dog made a full recovery within 6 h of the reaction and was re-anaesthetised 3 days later without incident, using propofol as the induction agent. CONCLUSION: To our knowledge, this is the first published case of anaphylaxis associated with intravenous Alfaxan in the dog. The APVMA reporting of reactions in small animals from 2003 to 2013 of Alfaxan is consistent with this case report's finding involving the respiratory, circulatory and gastrointestinal systems.

Etomidate and other non-barbiturates.

It is today generally accepted that anesthetics act by binding directly to sensitive target proteins. For certain intravenous anesthetics, such as propofol, barbiturates, and etomidate, the major target for anesthetic effect has been identified as the gamma-aminobutyric acid type A (GABA(A)) receptor, with particular subunits playing a crucial role. Etomidate, an intravenous imidazole general anesthetic, is thought to produce anesthesia by modulating or activating ionotropic Cl(-)-permeable GABA(A) receptors. For the less potent steroid anesthetic agents the picture is less clear, although a relatively small number of targets have been identified as being the most likely candidates. In this review, we summarize the most relevant clinical and experimental pharmacological properties of these intravenous anesthetics, the molecular targets mediating other endpoints of the anesthetic state in vivo, and the work that led to the identification of the GABA(A) receptor as the key target for etomidate and aminosteroids.

Cardiopulmonary Effects of a Partial Intravenous Anesthesia Technique for Laboratory Swine.

Various anesthetic protocols are used in laboratory swine, each with specific advantages and disadvantages. Partial intravenous anesthetic techniques (PIVA) help minimize dose-dependent cardiopulmonary effects of inhalant drugs. The aim of this study was to determine the cardiopulmonary effects of a PIVA in laboratory swine. In a prospective, nonrandomized clinical study, 8 healthy juvenile Landrace-White pigs were premedicated with azaperone (0.20 ± 0.20 mg/kg IM), dexmedetomidine (0.02 ± 0.002 mg/kg IM), and alfaxalone (2.0 ± 0.20 mg/kg IM), and anesthesia was induced with intravenous alfaxalone. Anesthesia was maintained by using constant-rate infusion of dexmedetomidine (2 µg/kg/h) and alfaxalone (25 µg/kg/min) in combination with isoflurane. After the fraction of expired isoflurane was adjusted to 1.1% to 1.5%, respiratory rate, heart rate, systemic and pulmonary arterial pressure, central venous pressure, cardiac output, bispectral index, systemic vascular resistance, and arterial and mixed venous blood gases were recorded every 10 min for 60 min. Statistical analysis consisted of repeated-measures one-way ANOVA. Significant decreases occurred in heart rate, pulmonary mean arterial pressure, pulmonary diastolic pressure, partial pressure of arterial oxygen, partial pressure of venous oxygen; significant increases occurred in respiratory rate, minute volume index, diastolic arterial blood pressure, systemic vascular resistance, and arterial pH over time. We consider that the observed statistically significant cardiopulmonary changes were clinically important and that the PIVA protocol provided hemodynamic and respiratory stability for short-term anesthesia of laboratory swine.