STUDIES USING ALFAXALONE TOTAL INTRAVENOUS ANAESTHESIA IN CATS.
1. Clinical evaluation of alfaxalone to induce and maintain anaesthesia in cats undergoing neutering procedures.
Beths et al. (2013) investigated the use and efficacy of alfaxalone for total intravenous anaesthesia (TIVA) in thirty-four cats presenting for routine neutering procedures. Ten males, twenty-four females and both domestic and those of feral nature were included in the study.
Method: Twenty minutes following premedication with intramuscular medetomidine (0.02mg/kg) and morphine (0.3mg/kg), anaesthesia was induced via intravenous alfaxalone (median dose of 1.7mg/kg, range of 0.7-3.0mg/kg) administered to effect, over approximately 1 minute, until endotracheal intubation was possible. Each patient was then attached to an anaesthetic machine and allowed to breathe 100% oxygen. Anaesthesia was maintained with alfaxalone administered intravenously as a continuous rate infusion (median dose of 0.18mg/kg/min, range of 0.06-0.25mg/kg/min) and the rate altered depending on the patient’s anaesthetic depth. Criteria for inadequate anaesthesia were a sudden increase in indirect arterial blood pressure (DAP; measured via Doppler) of >20%, a sudden increase in heart rate of 10% in the absence of hypovolaemia and somatic responses such as swallowing or movement. In these cats alfaxalone infusion was increased by 0.05mg/kg/min increments every minute until no response to noxious stimulation was observed. Between increments, the surgeon was asked to stop the procedure. A DAP <80 mmHg (hypotension) was treated by increasing fluid therapy (Lactated Ringer’s solution) from 10 to 50ml/kg/hour. In addition, if possible, the alfaxalone infusion rate was decreased by a 0.02mg/kg/min increment every 5 minutes. If hypotension had not resolved after 15 minutes other pharmacological interventions were made.
Results: Once the alfaxalone infusion was stopped the time to first spontaneous movement (TS) was a mean of 27 minutes in male and 49 minutes in female cats (females having a proportionally longer anaesthetic and therefore longer infusion time). TS was greater than 30 minutes in 19 cats, atipamezole administration did not appear to hasten recovery in the 12 cats where this was administered. Apnoea was not observed in any cat although body temperature was found to be significantly lower in the 19 cats that had slower recoveries.
Conclusion: It was found that alfaxalone TIVA in combination with medetomidine and morphine premedication was effective in feral and domestic cats for the performance of neutering surgery; low body temperature might have resulted in longer recoveries in some cats.
2. Studies performed by Pypendop et al. (2018a, b, c) investigated the pharmacokinetics and clinical effects of the preserved formulation of alfaxalone (Alfaxan Multidose, Jurox) in cats. In all three of these studies alfaxalone was used to successfully maintain anaesthesia via intravenous infusion, and in two (Pypendop et al. (2018b, c) anaesthesia was maintained for prolonged periods of time (up to 4 hours in some). It must be noted that the current Alfaxan Multidose licence in the UK states that ‘The veterinary medicinal product has been used safely and effectively in dogs and cats for procedures lasting for up to one hour’ and so the above information should only be taken as assurance for the safety of the preserved formulation of Alfaxan when used in this manner.
3. Comparison of the effects of propofol or alfaxalone for anaesthesia induction and maintenance on respiration in cats.
In a study by Campagna et al. (2014) twenty female cats undergoing ovariohysterectomy were administered either alfaxalone (Group A, n = 10) or propofol (Group P, n = 10) for both induction and maintenance of anaesthesia.
Method: Premedication in all cases comprised of intramuscular medetomidine (0.01mg/kg) and subcutaneous meloxicam (0.3mg/kg). In group A, alfaxalone at 5mg/kg/min was administered for induction followed by 10mg/kg/hr intravenously (IV) for maintenance of anaesthesia. In group P, propofol at 6mg/kg/min was administered for induction followed by 12mg/kg/hr intravenously for maintenance. After induction all cats were connected to a non-rebreathing system delivering 100% oxygen. The anaesthetic maintenance drug rate was adjusted (±0.5 mg/kg/hr) every 5 minutes according to a scoring sheet based on physiologic variables and clinical signs.
Results: Manual ventilation was required in two and eight of the cats in group A and P, respectively (p = 0.02). Two cats in both groups showed apnoea. Induction and maintenance dose rates (mean±SD) were 11.6±0.3 mg/kg and 10.7±0.8 mg/kg/hr for alfaxalone and 11.7±2.7 mg/kg and 12.4±0.5 mg/kg/hour for propofol.
Conclusion: Alfaxalone had less adverse influence on respiration than propofol in cats premedicated with medetomidine. Alfaxalone might be better than propofol for induction and maintenance of anaesthesia when artificial ventilation cannot be provided.
4. Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy.
In this prospective, randomised and ‘blinded’ study by Schwarz et al. (2014) the minimum infusion rate of alfaxalone for total intravenous anaesthesia was assessed in twenty-eight cats undergoing ovariohysterectomy.
Method: Premedication included intramuscular butorphanol (0.2mg/kg) alongside either intramuscular acepromazine (0.1mg/kg, group AA) or intramuscular medetomidine (0.02mg/kg, group MA). Anaesthesia was induced with alfaxalone administered intravenously to effect (0.2mg/kg every 20 seconds) and maintained on an initial intravenous alfaxalone infusion rate of 8mg/kg/hr which was adjusted at 5-minute intervals (±0.5mg/kg/hr) dependent on alterations in heart rate, respiratory rate, doppler blood pressure and the presence of a palpebral reflex. Additional alfaxalone boluses were administered intravenously if cats moved/swallowed (at 0.5 mg/kg) or if respiratory rate increased over 40 breaths per minute (at 0.25 mg/kg). Results: Alfaxalone anaesthesia induction dose (mean±SD), was lower in group MA (1.87±0.5; group AA: 2.57±0.41 mg/kg). No cats became apnoeic. Intraoperative bolus requirements and TIVA rates (group AA: 11.62±1.37, group MA: 10.76±0.96 mg/kg/hr) did not differ significantly between groups.
Conclusion: Alfaxalone TIVA in cats after medetomidine or acepromazine sedation provided suitable anaesthesia with no need for ventilatory support. After these premedicants, the authors recommend initial alfaxalone TIVA rates of 10 mg/kg/hour.
STUDIES USING ALFAXALONE TOTAL INTRAVENOUS ANAESTHESIA IN DOGS.
1. Alfaxalone for total intravenous anaesthesia in dogs undergoing ovariohysterectomy: a comparison of premedication with acepromazine or dexmedetomidine.
Herbert et al. (2012) investigated the use of alfaxalone for total intravenous anaesthesia (TIVA) in dogs undergoing ovariohysterectomy.
Method: Dogs received a premedication of intramuscular buprenorphine (0.02mg/kg) and either acepromazine (0.05mg/kg) or dexmedetomidine (approximately 0.01mg/kg, adjusted for body surface area) followed by induction with alfaxalone dosed to effect. Anaesthetic maintenance was performed with alfaxalone via continuous rate infusion.
Results: Doses for induction and maintenance are presented as mean±SD. Induction was achieved with 1.5±0.57mg/kg and this dose did not differ significantly between group. Alfaxalone infusion rate was significantly lower in the dexmedetomidine group (0.08 [0.06 0.19] mg/kg/min) than those administered acepromazine (0.11 [0.07– 0.33] mg/kg/min). Alfaxalone boluses were given intravenously if required and the total dose of these (1.2 [0-6.3]mg/kg) did not differ between groups. 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 dogs that received dexmedetomidine than those that were administered acepromazine.
Conclusion: 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.
2. Comparison of alfaxalone and propofol administered as total intravenous anaesthesia for ovariohysterectomy in dogs.
In a study by Suarez et al. (2012) fourteen healthy crossbred female dogs presenting for ovariohysterectomy were induced and maintained with either intravenous alfaxalone or propofol via total intravenous anaesthesia (TIVA).
Method: Doses for induction and maintenance are presented as mean±SD. Anaesthesia was induced with either alfaxalone (1.9±0.07mg/kg) or propofol (5.8±0.3 mg/kg) following a premedication of subcutaneous acepromazine (0.01mg/kg) and morphine (0.4mg/kg) administered approximately 30 minutes beforehand. Anaesthesia was then maintained via a continuous rate infusion of alfaxalone (0.11±0.01 mg/kg/min) or propofol (0.37±0.09 mg/kg/min).
Results: Median (interquartile range) recovery times in minutes to sternal were 45 (33–69) and 60 (46–61) and to standing 74 (69– 76) and 90 (85–107) for propofol and alfaxalone respectively. Recovery quality was classed as good. Cardiopulmonary effects did not differ between groups although hypoventilation was observed in both groups.
Conclusion: Following premedication with acepromazine and morphine, both propofol and alfaxalone produce good quality anaesthesia adequate for ovariohysterectomy. Hypoventilation occurs suggesting a need for ventilatory support during prolonged infusion periods with either anaesthetic agent.
3. Comparison of the anesthetic efficacy and cardiopulmonary effects of continuous rate infusions of alfaxalone-2-hydroxypropyl-β-cyclodextrin and propofol in dogs.
In their crossover study, Ambros et al. (2008) compared the anaesthetic efficacy and cardiopulmonary effects of alfaxalone and propofol when delivered via continuous rate infusion (CRI) in dogs.
Method: Six young and clinically healthy dogs were administered intravenous alfaxalone (2mg/kg) or propofol (4mg/kg) for induction following an intravenous premedication of acepromazine (0.02mg/kg) and hydromorphone (0.05mg/kg). Following intubation, anaesthesia was maintained with the same agent (alfaxalone at 0.07 mg/kg/min; propofol at 0.25 mg/kg/min).
Results: Both alfaxalone and propofol produced excellent induction of anaesthesia, maintenance, and recovery. Respiratory depression was evident with both anaesthetics. Mild hemodynamic changes (considered clinically acceptable) were similar for both anaesthetics.
Conclusion: Alfaxalone produced clinically acceptable anesthetic quality and hemodynamic values ideal for use as a CRI. Ventilation may need to be supported if hydromorphone is used at these propofol and alfaxalone-HPCD infusion rates.
1. The bioequivalence of a single intravenous administration of the anesthetic alfaxalone in cyclodextrin versus alfaxalone in cyclodextrin plus preservatives in cats.
In a randomised, two period, cross-over (7-day washout period) study by Pasloske et al. 2018, twenty-four cats (12 male and 12 female) were administered either the unpreserved (Alfaxan, Jurox) or preserved formulation (Alfaxan Multidose, Jurox) of alfaxalone at 5mg/kg (the licenced induction dose for unpremedicated cats; administered intravenously over 60 seconds) in order to assess drug bioequivalence.
Method: Subjective assessment of quality of anaesthetic induction, effectiveness and recovery were performed (via visual analogue scale [VAS] scoring) alongside continuous measurement of select physiological values (i.e. pulse rate, heart rate and rhythm (auscultated), respiratory rate, Sp02, ETC02, mucous membrane colour and rectal temperature). Time to endotracheal tube placement, endotracheal tube removal, head lift, sternal recumbency and unassisted standing were also recorded. Venous blood samples were collected at predetermined time points to 12 hr after drug administration to determine alfaxalone plasma concentration over time.
Results: No physiological variables except for a drug by time interaction for respiratory rate differed between treatment groups, and this difference was not clinically relevant. No anaesthetic event times or VAS scores for quality of anaesthesia were different between treatment groups. Neither formulation caused pain upon injection.
Conclusion: This pharmacokinetic and pharmacodynamic bioequivalence study demonstrates both the unpreserved and preserved formulations of alfaxalone (i.e. Alfaxan and Alfaxan Multidose respectively) are bioequivalent when administered as a single dose of 5 mg/kg body weight in the cat. Therefore, veterinarians and technicians can interchange the formulations without observing any change in induction for anesthetic efficacy or safety.
2. An in vivo study investigating the bioequivalence of Alfaxan® versus alfaxalone plus preservatives as an injectable anesthetic agent in dogs.
In a bioequivalence study (unpublished), similar to the published bioequivalence study performed in cats (see above; Pasloske et al. 2018), twenty-four adult male dogs were anaesthetised with 3mg/kg (licenced induction dose for unpremedicated dogs) of either the unpreserved or preserved formulations of alfaxalone (i.e. Alfaxan and Alfaxan Multidose respectively) administered intravenously over 60 seconds.
Method: Subjective measurements of anaesthetic induction, drug effectiveness and anaesthetic recovery (via visual analogue scale [VAS] scoring) as well as the recording of select physiological values (i.e. pulse rate, heart rate and rhythm, respiratory rate, Sp02, ETC02, mucous membrane colour and rectal temperature) were performed. Time to endotracheal tube placement, endotracheal tube removal, head lift, sternal recumbency and unassisted standing were also recorded. As well as this, venous blood samples being taken were collected at predetermined time points to determine alfaxalone plasma concentration over time.
Results: There was no observed pain upon injection or injection site reactions for either the unpreserved or preserved formulation. All physiological variables observed after the induction of anaesthesia were within clinically acceptable limits for both formulations. Neither formulation scored ‘better’ compared to the other in terms of induction, anaesthetic and recovery quality. Neither formulation demonstrated consistently longer or shorter anaesthetic durations.
Conclusion: Clinical data confirmed that Alfaxan and Alfaxan Multidose are pharmacodynamically similar. For pharmacokinetic data, Alfaxan and Alfaxan Multidose met the bioequivalence criteria.
Please note that there is a large amount of other peer reviewed literature available on this topic. Should you require any further information on this, or for any other technical query, please contact our Customer Services team on 0800 500 3171.
The Jurox User Guide to Achieving the Best Outcome When Using Alfaxan® for the Induction and Maintenance of Anaesthesia is available here
Alfaxan for Maintenance of Anaesthesia: Frequently Asked Questions is available here.
A downloadable Dose Chart for Alfaxan® TIVA by CRI and Intermittent Bolus Administration is available here
Originally published: Thursday, 13th December 2018
Ambros B., Duke-Novakovski T., Pasloske K.S. 2008. Comparison of the anesthetic efficacy and cardiopulmonary effects of continuous rate infusions of alfaxalone-2-hydroxypropyl-β-cyclodextrin and propofol in dogs. American journal of veterinary research. 69(11): 1391-1398.
Beths T., Touzot-JourdeG ., Musk G., Pasloske, K. 2014. Clinical evaluation of alfaxalone to induce and maintain anaesthesia in cats undergoing neutering procedures. Journal of feline medicine and surgery. 16(8): 609-615.
Campagna I., Schwarz A., Keller S., Bettschart‐Wolfensberger R., Mosing M. 2015. Comparison of the effects of propofol or alfaxalone for anaesthesia induction and maintenance on respiration in cats. Veterinary anaesthesia and analgesia. 42(5): 484-492.
Herbert G.L., Bowlt K.L., Ford-Fennah V., Covey-Crump G.L., Murrell, J.C. 2013. Alfaxalone for total intravenous anaesthesia in dogs undergoing ovariohysterectomy: a comparison of premedication with acepromazine or dexmedetomidine. Veterinary anaesthesia and analgesia. 40(2): 124-133.
Pasloske K., Ranasinghe M.G., Sauer S., Hare, J. 2018. The bioequivalence of a single intravenous administration of the anesthetic alfaxalone in cyclodextrin versus alfaxalone in cyclodextrin plus preservatives in cats. Journal of veterinary pharmacology and therapeutics. 41(3): 437-446.
Pypendop B.H., Siao K.T., Ranasinghe M.G., Pasloske K. 2018a. Effective plasma alfaxalone concentration to produce immobility in male neutered cats. Veterinary anaesthesia and analgesia. 45(3): 269-277.
Pypendop B.H., Ranasinghe M.G., Pasloske, K. 2018b. Comparison of two intravenous anesthetic infusion regimens for alfaxalone in cats. Veterinary anaesthesia and analgesia. 45(4): 459-466
Pypendop B.H., Ranasinghe M.G., Pasloske, K. 2018a. Pharmacokinetics of alfaxalone infusions, context-sensitive half-time and recovery times in male neutered cats. Veterinary anaesthesia and analgesia. 45(5): 630-639.
Schwarz A., Kalchofner K., Palm J., Picek S., Hartnack S., Bettschart‐Wolfensberger R. 2014. Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy. Veterinary anaesthesia and analgesia. 41(5): 480-490.
Suarez M.A., Dzikiti B.T., Stegmann F.G., Hartman M. 2012. Comparison of alfaxalone and propofol administered as total intravenous anaesthesia for ovariohysterectomy in dogs. Veterinary Anaesthesia and Analgesia. 39(3): 236-244.
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