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

ObjectiveTo compare the incidence of pain during injection of three intravenous induction agents in dogs.Study designProspective, crossover, randomized, blinded, clinical study.AnimalsThirty dogs requiring anaesthesia for radiotherapy.MethodsDogs 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).ResultsNo 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 relevanceDrug_PC was associated with clinically relevant moderate to severe pain behaviour whilst Drug_A and Drug_P were not.     

Comparison of two intravenous anesthetic infusion regimens for alfaxalone in cats

Objective

To compare the performance of an alfaxalone constant rate intravenous (IV) infusion versus a 3-step IV infusion, both following a loading dose, for the maintenance of a target plasma alfaxalone concentration of 7.6 mg L^–1 (effective plasma alfaxalone concentration for immobility in 99% of the population) in cats.

An evaluation of anaesthetic induction in healthy dogs using rapid intravenous injection of propofol or alfaxalone

ObjectiveTo evaluate quality of anaesthetic induction and cardiorespiratory effects following rapid intravenous (IV) injection of propofol or alfaxalone.Study designProspective, randomised, blinded clinical study.AnimalsSixty healthy dogs (ASA I/II) anaesthetized for elective surgery or diagnostic procedures.MethodsPremedication was intramuscular acepromazine (0.03 mg kg^?1) and meperidine (pethidine) (3 mg kg^?1). For anaesthetic induction dogs received either 3 mg kg^?1 propofol (Group P) or 1.5 mg kg^?1 alfaxalone (Group A) by rapid IV injection. Heart rate (HR), respiratory rate (f_R) and oscillometric arterial pressures were recorded prior to induction, at endotracheal intubation and at 3 and 5 minutes post-intubation. The occurrence of post-induction apnoea or hypotension was recorded. Pre-induction sedation and aspects of induction quality were scored using 4 point scales. Data were analysed using Chi-squared tests, two sample t-tests and general linear model mixed effect anova (p < 0.05).ResultsThere were no significant differences between groups with respect to sex, age, body weight, f_R, post-induction apnoea, arterial pressures, hypotension, SpO₂, sedation score or quality of induction scores. Groups behaved differently over time with respect to HR. On induction HR decreased in Group P (?2 ± 28 beats minute^?1) but increased in Group A (14 ± 33 beats minute^?1) the difference being significant (p = 0.047). However HR change following premedication also differed between groups (p = 0.006). Arterial pressures decreased significantly over time in both groups and transient hypotension occurred in eight dogs (five in Group P, three in Group A). Post-induction apnoea occurred in 31 dogs (17 in Group P, 14 in Group A). Additional drug was required to achieve endotracheal intubation in two dogs.Conclusions and Clinical relevanceRapid IV injection of propofol or alfaxalone provided suitable conditions for endotracheal intubation in healthy dogs but post-induction apnoea was observed commonly.     

The effect of the duration of propofol administration on recovery from anesthesia in cats

OBJECTIVE: To determine the effect of induction, a 30-minute, and a 150-minute infusion of propofol on the rate of recovery in cats. STUDY DESIGN: Randomized, cross-over, prospective experimental study. ANIMALS: Six healthy adult spayed female cats (mean 4.3, range 2-7 years old) weighing 3.9 +/- 0.5 kg. METHODS: Cats received each of three treatments: anesthetic induction with propofol (T1), induction followed by a 30-minute infusion (T30) and induction followed by a 150-minute infusion (T150). Propofol infusions were increased or decreased to maintain a sluggish pedal withdrawal reflex. Animals were monitored throughout the anesthetic period and during the recovery. Venous blood samples were collected from a central venous catheter before anesthesia and at 30 minutes for the 30-minute infusion and at 30, 60, 90, 120 and 150 minutes for the 150-minute infusion. The ability of the cat to lift its head, crawl, stand and walk without ataxia was recorded at 5, 10, 20, 40, 60, 80, 120, 160, 180, 210 and 240 minutes after the completion of propofol administration. Data from physiological values were analyzed using either a Student's t-test (30-minute infusion) or an anova (150-minute infusion). A nonparametric Friedman test (and post-hoc Tukey's Studentized range test) was used to determine whether there were differences in the time taken to recover. Results were considered significant if p < 0.05. RESULTS: Time taken to walk without ataxia was significantly greater in T150 (148 +/- 40 minutes) compared with T1 (80 +/- 15 minutes) and T30 (74 +/- 26 minutes). (No other recovery times were significantly different). Anesthesia with propofol was accompanied by a moderate but significant respiratory depression and a decrease in PCV and total protein. CONCLUSIONS AND CLINICAL RELEVANCE: Prolonged anesthesia with propofol in healthy cats may be associated with a delayed recovery.     

Effective plasma alfaxalone concentration to produce immobility in male neutered cats

Objective

To determine the effective plasma alfaxalone concentration for the production of immobility in cats.

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).

Pharmacokinetics of alfaxalone infusions,context-sensitive half-time and recovery times in male neutered cats

Objectives

To determine the context-sensitive half-time of alfaxalone following intravenous infusions of various durations. To estimate the time necessary for plasma concentration to decrease by up to 95%.

Intramuscular injection of alfaxalone in combination with butorphanol for sedation in cats

Objective

To assess quality of sedation following intramuscular (IM) injection of two doses of alfaxalone in combination with butorphanol in cats.

Comparison of the brainstem auditory evoked responses during sevoflurane or alfaxalone anaesthesia in adult cats

Objective

To compare the effects of general anaesthesia using sevoflurane or alfaxalone on the brainstem auditory evoked response (BAER) test in adult healthy cats.

Immersion anaesthesia in goldfish (Carassius auratus) with three concentrations of alfaxalone

Objective

To evaluate the anaesthetic effects of three different alfaxalone doses to induce anaesthesia in goldfish.

Immersion and branchial/transcutaneous irrigation anaesthesia with alfaxalone in a Mexican axolotl

IntroductionImmersion anaesthetic techniques are commonly used in amphibian species. Alfaxalone has been reported as an immersion anaesthetic in fish but not amphibians.Case history and examinationA Mexican 56 g axolotl was presented with a 3 day history of anorexia. Anaesthesia was required for the surgical retrieval of two gastric foreign bodies. Prior to anaesthesia, on visual inspection the axolotl was bright and active. Branchial and gular respiratory movements occurred at approximately 24 respirations minute^?1 and heart rate was approximately 52 beats minute^?1.ManagementThe axolotl was exposed to increasing concentrations (up to 5 mg L^?1) of alfaxalone (Alfaxan; Vetóquinol, UK) in a water bath. After becoming sedated the axolotl was removed from the water bath. Anaesthesia was induced and maintained with alfaxalone (5 mg L^?1) via continuous irrigation of the gills (branchial) and skin (cutaneous) with additional 30 μL drops of alfaxalone (10 mg mL^?1) administered branchially as required. Endoscopy and surgery were performed to remove two gastric foreign bodies. Branchial and gular respiratory movements persisted at what was considered an appropriate anaesthetic depth. Anaesthetic depth could be rapidly deepened by branchial irrigation of alfaxalone solutions and lightened by irrigation using fresh water. Anaesthesia lasted approximately 1 hour and recovery was rapid (within 15 minutes). Recovery was assisted through branchial and cutaneous irrigation with fresh water.Follow-upNo obvious adverse effects of anaesthesia were observed immediately post-anaesthesia or, according to the owner, in the following week.ConclusionsAxolotls can be anaesthetized using alfaxalone administered via immersion and branchial/transcutaneous irrigation offering an alternative technique for anaesthetising axolotls for clinical and research purposes.     

Fentanyl or midazolam for co-induction of anaesthesia with propofol in dogs

ObjectivePropofol may cause adverse effects (e.g. apnoea, hypotension) at induction of anaesthesia. Co-induction of anaesthesia may reduce propofol requirements. The effect of fentanyl or midazolam on propofol dose requirements and cardiorespiratory parameters was studied.Study designRandomized, controlled, blinded clinical study.AnimalsSixty-six client owned dogs (35 male, 31 female, ASA I-II, age 6–120 months, body mass 4.7–48.0 kg) were selected.MethodsPre-medication with acepromazine (0.025 mg kg⁻¹) and morphine (0.25 mg kg⁻¹) was administered by intramuscular injection. After 30 minutes group fentanyl-propofol (FP) received fentanyl (2 μg kg⁻¹), group midazolam-propofol (MP) midazolam (0.2 mg kg⁻¹) injected over 30 seconds via a cephalic catheter and in a third group, control-propofol (CP), the IV catheter was flushed with an equivalent volume of heparinized saline. Anaesthesia was induced 2 minutes later, with propofol (4 mg kg⁻¹minute⁻¹) administered to effect. After endotracheal intubation anaesthesia was maintained with a standardized anaesthetic protocol. Pulse rate, respiratory rate (RR) and mean arterial pressure (MAP) were recorded before the co-induction agent, before induction, and 0, 2 and 5 minutes after intubation. Apnoea ≥30 seconds was recorded and treated. Sedation after pre-medication, activity after the co-induction agent, quality of anaesthetic induction and endotracheal intubation were scored.ResultsPropofol dose requirement was significantly reduced in FP [2.90 mg kg⁻¹(0.57)] compared to CP [3.51 mg kg⁻¹ (0.74)] and MP [3.58 mg kg⁻¹(0.49)]. Mean pulse rate was higher in MP than in CP or FP (p = 0.003). No statistically significant difference was found between groups in mean RR, MAP or incidence of apnoea. Activity score was significantly higher (i.e. more excited) (p = 0.0001), and quality of induction score was significantly poorer (p = 0.0001) in MP compared to CP or FP. Intubation score was similar in all groups.Conclusions and clinical relevanceFentanyl decreased propofol requirement but did not significantly alter cardiovascular parameters. Midazolam did not reduce propofol requirements and caused excitement in some animals.     

Effects of buprenorphine,butorphanol or tramadol premedication on anaesthetic induction with alfaxalone in common marmosets (Callithrix jacchus)

Objective

To investigate the clinical and physiological effects of intravenous (IV) alfaxalone alone or in combination with buprenorphine, butorphanol or tramadol premedication in marmosets.

Plasma pharmacokinetics and pharmacodynamics of alfaxalone in neonatal foals after an intravenous bolus of alfaxalone following premedication with butorphanol tartrate

ObjectiveTo determine the pharmacokinetics and pharmacodynamics of the neurosteroid anaesthetic, alfaxalone, in neonatal foals after a single intravenous (IV) injection of alfaxalone following premedication with butorphanol tartrate.Study designProspective experimental study.AnimalsFive clinically healthy Australian Stock Horse foals of mean ± SD age of 12 ± 3 days and weighing 67.3 ± 12.4 kg.MethodsFoals were premedicated with butorphanol (0.05 mg kg^?1 IV) and anaesthesia was induced 10 minutes later by IV injection with alfaxalone 3 mg kg^?1. Cardiorespiratory variables (pulse rate, respiratory rate, direct arterial blood pressure, arterial blood gases) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and alfaxalone plasma concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis.ResultsThe harmonic, mean ± SD plasma elimination half life (t½) for alfaxalone was 22.8 ± 5.2 minutes. The observed mean plasma clearance (Cl_p) and volume of distribution (Vd) were 19.9 ± 5.9 mL minute kg^?1 and 0.6 ± 0.2 L kg^?1, respectively. Overall, the quality of the anaesthetic inductions and recoveries was good and most monitored physiological variables were clinically acceptable in all foals, although some foals became hypoxaemic for a short period following recumbency. The mean durations of anaesthesia from induction to first movement and from induction to standing were 18.7 ± 7 and 37.2 ± 4.7 minutes, respectively.ConclusionsThe anaesthetic protocol used provided a predictable and consistent plane of anaesthesia in the five foals studied, with minimal cardiovascular depression. In foals, as in the adult horse, alfaxalone has a short elimination half life.Clinical relevanceAlfaxalone appears to be an adequate anaesthetic induction agent in foals and the pharmacokinetics suggest that, with continuous infusion, it might be suitable to provide more prolonged anaesthesia. Oxygen supplementation is recommended.     

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

ObjectiveTo evaluate the clinical efficacy and cardiorespiratory effects of alfaxalone as an anaesthetic induction agent in dogs with moderate to severe systemic disease.Study designRandomized prospective clinical study.AnimalsForty dogs of physical status ASA III-V referred for various surgical procedures.MethodsDogs 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).ResultsTreatment 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 relevanceInduction 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.     

Effect of alfaxalone infusion on the electroencephalogram of dogs anaesthetized with halothane

ObjectiveTo describe the effects of alfaxalone on the canine electroencephalogram (EEG).Study designExperimental study.AnimalsEight healthy adult Huntaway dogs.MethodsAnaesthesia was induced with propofol and maintained with halothane (0.85-0.95 end-tidal volume %) in oxygen. Animals were ventilated to maintain stable end-tidal CO₂ and halothane concentrations. Following a 30 minute stabilisation period, alfaxalone (0.5 mg kg^?1) was infused intravenously over a 5 minute period. The electroencephalogram was recorded from the beginning of the stabilisation period until 60 minutes following the start of alfaxalone treatment. Data were subjected to fast Fourier transformation, and median frequency, 95% spectral edge frequency and total EEG power were calculated. Two-factorial repeated measures anova (time and EEG channels were factors) was used for statistical analysis (p<0.05).ResultsA shift in the dominant frequency band from beta to delta after alfaxalone treatment and occasional burst suppression were observed. Median frequency decreased significantly below baseline (9.2 ± 1.4 Hz) (mean ± SD) during alfaxalone infusion. The lowest value (4.8 ± 1.2 Hz) was recorded 5 minutes after the start of infusion. Spectral edge frequency also decreased below baseline (26.2 ± 1.5 Hz) and the lowest value (22.6 ± 1.5 Hz) also was detected at 5 minutes after the start of infusion. Total EEG power did not change significantly. In some frequencies EEG power increased soon after the start of alfaxalone infusion, then decreased below baseline later (biphasic pattern).Conclusions and clinical relevanceAlfaxalone induced biphasic changes on EEG and decreased F₅₀ and F₉₅ in halothane anaesthetized dogs.