Comparison of alfaxalone and propofol administered as total intravenous anaesthesia for ovariohysterectomy in dogs

ObjectiveTo compare the anaesthetic and cardiopulmonary effects of alfaxalone with propofol when used for total intravenous anaesthesia (TIVA) during ovariohysterectomy in dogs.Study designA prospective non-blinded randomized clinical study.AnimalsFourteen healthy female crossbred bitches, aged 0.5–5 years and weight 16–42 kg.MethodsDogs were premedicated with acepromazine 0.01 mg kg^?1 and morphine 0.4 mg kg^?1. Anaesthesia was induced and maintained with either propofol or alfaxalone to effect for tracheal intubation followed by an infusion of the same agent. Dogs breathed spontaneously via a ‘circle’ circuit, with oxygen supplementation. Cardiopulmonary parameters (respiratory and heart rates, end-tidal carbon dioxide, tidal volume, and invasive blood pressures) were measured continuously and recorded at intervals related to the surgical procedure. Arterial blood samples were analysed for blood gas values. Quality of induction and recovery, and recovery times were determined. Non-parametric data were tested for significant differences between groups using the Mann–Whitney U-test and repeatedly measured data (normally distributed) for significant differences between and within groups by anova.ResultsBoth propofol and alphaxalone injection and subsequent infusions resulted in smooth, rapid induction and satisfactory maintenance of anaesthesia. Doses for induction (mean ± SD) were 5.8 ± 0.30 and 1.9 ± 0.07 mg kg^?1 and for the CRIs, 0.37 ± 0.09 and 0.11 ± 0.01 mg kg^?1 per minute for propofol and alfaxalone respectively. Median (IQR) recovery times were to sternal 45 (33–69) and 60 (46–61) and to standing 74 (69–76) and 90 (85–107) for propofol and alphaxalone respectively. Recovery quality was good. Cardiopulmonary effects did not differ between groups. Hypoventilation occurred in both groups.Conclusions and clinical relevanceFollowing premedication with acepromazine and morphine, both propofol and alphaxalone produce good quality anaesthesia adequate for ovariohysterectomy. Hypoventilation occurs suggesting a need for ventilatory support during prolonged infusion periods with either anaesthetic agent.     

Induction dose and recovery quality of propofol and alfaxalone with or without midazolam coinduction followed by total intravenous anesthesia in dogs

Objectives

To compare propofol and alfaxalone, with or without midazolam, for induction of anesthesia in fentanyl-sedated dogs, and to assess recovery from total intravenous anesthesia (TIVA).

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.

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.     

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.     

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.     

Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats

AIMS: To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats.

METHODS: Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two–treatment, two-period study. Alfaxalone at a dose of 5?mg/kg was administered either I/V or I/M. Blood samples were collected between 2–480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5–120 minutes after drug administration using a numerical rating scale (from 0–18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded.

RESULTS: The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5–15 minutes after I/V administration and deep sedation (scores 11–15) at 20 and 30 minutes. Deep sedation was observed from 10–45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery.

CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.     

Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy

ObjectiveTo determine the induction doses, then minimum infusion rates of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent, cardiopulmonary effects, recovery characteristics and alfaxalone plasma concentrations in cats undergoing ovariohysterectomy after premedication with butorphanol-acepromazine or butorphanol-medetomidine.Study designProspective randomized blinded clinical study.AnimalsTwenty-eight healthy cats.MethodsCats undergoing ovariohysterectomy were assigned into two groups: together with butorphanol [0.2 mg kg^?1 intramuscularly (IM)], group AA (n = 14) received acepromazine (0.1 mg kg^?1 IM) and group MA (n = 14) medetomidine (20 μg kg^?1 IM). Anaesthesia was induced with alfaxalone to effect [0.2 mg kg^?1 intravenously (IV) every 20 seconds], initially maintained with 8 mg kg^?1 hour^?1 alfaxalone IV and infusion adjusted (±0.5 mg kg^?1 hour^?1) every five minutes according to alterations in heart rate (HR), respiratory rate (f_R), Doppler blood pressure (DBP) and presence of palpebral reflex. Additional alfaxalone boli were administered IV if cats moved/swallowed (0.5 mg kg^?1) or if f_R >40 breaths minute^?1 (0.25 mg kg^?1). Venous blood samples were obtained to determine plasma alfaxalone concentrations. Meloxicam (0.2 mg kg^?1 IV) was administered postoperatively. Data were analysed using linear mixed models, Chi-squared, Fishers exact and t-tests.ResultsAlfaxalone anaesthesia induction dose (mean ± SD), was lower in group MA (1.87 ± 0.5; group AA: 2.57 ± 0.41 mg kg^?1). No cats became apnoeic. Intraoperative bolus requirements and TIVA rates (group AA: 11.62 ± 1.37, group MA: 10.76 ± 0.96 mg kg^?1 hour^?1) did not differ significantly between groups. Plasma concentrations ranged between 0.69 and 10.76 μg mL^?1. In group MA, f_R, end-tidal carbon dioxide, temperature and DBP were significantly higher and HR lower.Conclusion and clinical relevanceAlfaxalone TIVA in cats after medetomidine or acepromazine sedation provided suitable anaesthesia with no need for ventilatory support. After these premedications, the authors recommend initial alfaxalone TIVA rates of 10 mg kg^?1 hour^?1.     

A comparison of cardiopulmonary and anesthetic effects of an induction dose of alfaxalone or propofol in dogs

ObjectiveTo compare the physiological parameters, arterial blood gas values, induction quality, and recovery quality after IV injection of alfaxalone or propofol in dogs.Study designProspective, randomized, blinded crossover.AnimalsEight random-source adult female mixed-breed dogs weighing 18.7 ± 4.5 kg.MethodsDogs were assigned to receive up to 8 mg kg^?1 propofol or 4 mg kg^?1 alfaxalone, administered to effect, at 10% of the calculated dose every 10 seconds. They then received the alternate drug after a 6-day washout. Temperature, pulse rate, respiratory rate, direct blood pressure, and arterial blood gases were measured before induction, immediately post-induction, and at 5-minute intervals until extubation. Quality of induction, recovery, and ataxia were scored by a single blinded investigator. Duration of anesthesia and recovery, and adverse events were recorded.ResultsThe mean doses required for induction were 2.6 ± 0.4 mg kg^?1 alfaxalone and 5.2 ± 0.8 mg kg^?1 propofol. After alfaxalone, temperature, respiration, and pH were significantly lower, and PaCO₂ significantly higher post-induction compared to baseline (p < 0.03). After propofol, pH, PaO₂, and SaO₂ were significantly lower, and PaCO₂, HCO₃, and PA-aO₂ gradient significantly higher post-induction compared to baseline (p < 0.03). Post-induction and 5-minute physiologic and blood gas values were not significantly different between alfaxalone and propofol. Alfaxalone resulted in significantly longer times to achieve sternal recumbency (p = 0.0003) and standing (p = 0.0004) compared to propofol. Subjective scores for induction, recovery, and ataxia were not significantly different between treatments; however, dogs undergoing alfaxalone anesthesia were more likely to have ≥1 adverse event (p = 0.041). There were no serious adverse events in either treatment.Conclusions and clinical relevanceThere were no clinically significant differences in cardiopulmonary effects between propofol and alfaxalone. A single bolus of propofol resulted in shorter recovery times and fewer adverse events than a single bolus of alfaxalone.     

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).

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.

Comparison of the effects of propofol or alfaxalone for anaesthesia induction and maintenance on respiration in cats

ObjectiveTo compare the effects of propofol and alfaxalone on respiration in cats.Study designRandomized, ‘blinded’, prospective clinical trial.AnimalsTwenty cats undergoing ovariohysterectomy.MethodsAfter premedication with medetomidine 0.01 mg kg⁻¹ intramuscularly and meloxicam 0.3 mg kg⁻¹ subcutaneously, the cats were assigned randomly into two groups: group A (n = 10) were administered alfaxalone 5 mg kg⁻¹ minute⁻¹ followed by 10 mg kg⁻¹ hour⁻¹ intravenously (IV) and group P (n = 10) were administered propofol 6 mg kg⁻¹ minute⁻¹ followed by 12 mg kg⁻¹hour⁻¹ IV for induction and maintenance of anaesthesia, respectively. After endotracheal intubation, the tube was connected to a non-rebreathing system delivering 100% oxygen. The anaesthetic maintenance drug rate was adjusted (± 0.5 mg kg⁻¹ hour⁻¹) every 5 minutes according to a scoring sheet based on physiologic variables and clinical signs. If apnoea > 30 seconds, end-tidal carbon dioxide (Pe′CO₂) > 7.3 kPa (55 mmHg) or arterial haemoglobin oxygen saturation (SpO₂) < 90% occurred, manual ventilation was provided. Methadone was administered postoperatively. Data were analyzed using independent-samples t-tests, Fisher's exact test, linear mixed-effects models and binomial test.ResultsManual 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. Pe′CO₂ > 7.3 kPa was recorded in zero versus four and SpO₂ < 90% in zero versus six cats in groups A and P respectively. Induction and maintenance dose rates (mean ± SD) were 11.6 ± 0.3 mg kg⁻¹ and 10.7 ± 0.8 mg kg⁻¹ hour⁻¹ for alfaxalone and 11.7 ± 2.7 mg kg⁻¹ and 12.4 ± 0.5 mg kg⁻¹ hour⁻¹ for propofol.Conclusion and clinical relevanceAlfaxalone 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.     

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%.

Chronotropic effect of propofol or alfaxalone following fentanyl administration in healthy dogs

ObjectiveTo compare the effect of alfaxalone and propofol on heart rate (HR) and blood pressure (BP) after fentanyl administration in healthy dogs.Study designProspective, randomised clinical study.AnimalsFifty healthy client owned dogs (ASA I/II) requiring general anaesthesia for elective magnetic resonance imaging for neurological conditions.MethodsAll dogs received fentanyl 7 μg kg⁻¹ IV and were allocated randomly to receive either alfaxalone (n = 25) or propofol (n = 25) to effect until endotracheal (ET) intubation was possible. Heart rate and oscillometric BP were measured before fentanyl (baseline), after fentanyl (Time F) and after ET intubation (Time GA). Post-induction apnoea were recorded. Data were analysed using Fisher’s exact test, Mann Whitney U test and one-way anova for repeated measures as appropriate; p value <0.05 was considered significant.ResultsDogs receiving propofol showed a greater decrease in HR (-14 beat minute⁻¹, range -47 to 10) compared to alfaxalone (1 beat minute⁻¹, range -33 to 26) (p = 0.0116). Blood pressure decreased over the three time periods with no difference between groups. Incidence of post-induction apnoea was not different between groups.ConclusionFollowing fentanyl administration, anaesthetic induction with propofol resulted in a greater negative chronotropic effect while alfaxalone preserved or increased HR.Clinical relevanceFollowing fentanyl administration, HR decreases more frequently when propofol rather than alfaxalone is used as induction agent. However, given the high individual variability and the small change in predicted HR (-7.7 beats per minute after propofol), the clinical impact arising from choosing propofol or alfaxalone is likely to be small in healthy animals. Further studies in dogs with myocardial disease and altered haemodynamics are warranted.     

Effect of anesthetic induction with propofol,alfaxalone or ketamine on intraocular pressure in cats: a randomized masked clinical investigation

ObjectiveTo compare the effect of propofol, alfaxalone and ketamine on intraocular pressure (IOP) in cats.Study designProspective, masked, randomized clinical trial.AnimalsA total of 43 ophthalmologically normal cats scheduled to undergo general anesthesia for various procedures.MethodsFollowing baseline IOP measurements using applanation tonometry, anesthesia was induced with propofol (n = 15), alfaxalone (n = 14) or ketamine (n = 14) administered intravenously to effect. Then, midazolam (0.3 mg kg^?1) was administered intravenously and endotracheal intubation was performed without application of topical anesthesia. The IOP was measured following each intervention. Data was analyzed using one-way anova and repeated-measures mixed design with post hoc analysis. A p-value <0.05 was considered significant.ResultsMean ± standard error IOP at baseline was not different among groups (propofol, 18 ± 0.6; alfaxalone, 18 ± 0.7; ketamine, 17 ± 0.5 mmHg). Following induction of anesthesia, IOP increased significantly compared with baseline in the propofol (20 ± 0.7 mmHg), but not in the alfaxalone (19 ± 0.8 mmHg) or ketamine (16 ± 0.7 mmHg) groups. Midazolam administration resulted in significant decrease from the previous measurement in the alfaxalone group (16 ± 0.7 mmHg), but not in the propofol group (19 ± 0.7 mmHg) or the ketamine (16 ± 0.8 mmHg) group. A further decrease was measured after intubation in the alfaxalone group (15 ± 0.9 mmHg).Conclusions and clinical relevancePropofol should be used with caution in cats predisposed to perforation or glaucoma, as any increase in IOP should be avoided.     

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

Objective

To compare the effects of alfaxalone and propofol, with and without acepromazine and butorphanol followed by doxapram, on laryngeal motion and quality of laryngeal examination in dogs.