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.     

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).

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.     

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).

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.     

Evaluation of cardiorespiratory and biochemical effects of ketamine‐propofol and guaifenesin‐ketamine‐xylazine anesthesia in donkeys (Equus asinus)

ObjectivesTo evaluate the cardiorespiratory and biochemical effects of ketamine-propofol (KP) or guaifenesin-ketamine-xylazine (GKX) anesthesia in donkeys.Study designProspective crossover trial.AnimalsEight healthy, standard donkeys, aged 10 ± 5 years and weighing 153 ± 23 kg.MethodsDonkeys were premedicated with 1.0 mg kg^?1 of xylazine (IV) in both treatments. Eight donkeys were administered ketamine (1.5 mg kg^?1) and propofol (0.5 mg kg^?1) for induction, and anesthesia was maintained by constant rate infusion (CRI) of ketamine (0.05 mg kg^?1 minute^?1) and propofol (0.15 mg kg^?1 minute^?1) in the KP treatment. After 10 days, diazepam (0.05 mg kg^?1) and ketamine (2.2 mg kg^?1) were administered for induction, and anesthesia was maintained by a CRI (2.0 mL kg^?1 hour^?1) of ketamine (2.0 mg mL^?1), xylazine (0.5 mg mL^?1) and guaifenesin (50 mg mL^?1) solution. Quality of anesthesia was assessed along with cardiorespiratory and biochemical measurements.ResultsAnesthetic induction took longer in GKX than in KP. The induction was considered good in 7/8 with KP and in 6/8 in GKX. Anesthetic recovery was classified as good in 7/8 animals in both treatments. Xylazine administration decreased heart rate (HR) in both treatments, but in KP the HR increased and was higher than GKX throughout the anesthetic period. Respiratory rate was higher in GKX than in KP. PaO₂ decreased significantly in both groups during the anesthetic period. Glucose concentrations [GLU] increased and rectal temperature and PCV decreased in both treatments. Arterial lactate [LAC] increased at recovery compared with all time points in KP. [GLU] and calcium were higher in GKX than in KP at recovery.Conclusion and clinical relevanceThese protocols induced significant hypoxemia but no other cardiorespiratory or metabolic changes. These protocols could be used to maintain anesthesia in donkeys, however, they were not tested in animals undergoing surgery.     

Effects of sevoflurane,propofol or alfaxalone on neuromuscular blockade produced by a single intravenous bolus of rocuronium in dogs

ObjectiveTo compare the effects of sevoflurane, propofol and alfaxalone on the neuromuscular blockade induced by a single intravenous bolus of rocuronium in dogs.Study designA randomized, prospective, crossover experimental study.AnimalsA total of eight adult Beagle dogs (four female, four male), weighing 8.9–15.3 kg and aged 5–7 years.MethodsThe dogs were anesthetized three times with 1.25× minimum alveolar concentration of sevoflurane (SEVO treatment) and 1.25× minimum infusion rate of propofol (PROP treatment) or alfaxalone (ALFX treatment) at intervals of ≥14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC), a single bolus dose of rocuronium (1 mg kg^–1) was administered intravenously. The times from rocuronium administration to achieving TOF count 0 (onset time), from achieving TOF count 0 to the reappearance of TOF count 4 (clinical blockade period), from 25% to 75% of TOFRC (recovery index) and from achieving TOF count 0 to TOF ratio/TOFRC >0.9 (total neuromuscular blockade duration) were recorded.ResultsThe onset time and recovery index did not differ among the treatments. The median clinical blockade period was longer in the SEVO treatment [27.3 (26.0–30.3) minutes] than in PROP [16.6 (15.4–18.0) minutes; p = 0.002] and ALFX [22.4 (18.6–23.1) minutes; p = 0.017] treatments; and longer in the ALFX treatment than in the PROP treatment (p = 0.020). The mean total neuromuscular blockade duration was longer in the SEVO treatment (43.7 ± 9.9 minutes) than in PROP (25.1 ± 2.7 minutes; p < 0.001) and ALFX (32.5 ± 8.4 minutes; p = 0.036) treatments.Conclusions and clinical relevanceCompared with alfaxalone and propofol, sevoflurane prolonged rocuronium-induced neuromuscular blockade by a significantly greater extent in dogs.     

A comparison of the effect of propofol and alfaxalone on laryngeal motion in nonbrachycephalic and brachycephalic dogs

Objective

To compare the effect of propofol and alfaxalone on laryngeal motion under a light plane of anaesthesia in nonbrachycephalic and brachycephalic dogs anaesthetized for nonemergency procedures.

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.     

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.     

The cardiopulmonary effects of anesthetic induction with isoflurane,ketamine‐diazepam or propofol‐diazepam in the hypovolemic dog

ObjectiveTo evaluate and compare the cardiopulmonary effects of induction of anesthesia with isoflurane (Iso), ketamine–diazepam (KD), or propofol–diazepam (PD) in hypovolemic dogs.Study designProspective randomized cross–over trial.AnimalsSix healthy intact, mixed breed, female dogs weighing 20.7 ± 4.2 kg and aged 22 ± 2 months.MethodsDogs had 30 mL kg^?1 of blood removed at a rate of 1.5 mL kg^?1 minute^?1 under isoflurane anesthesia. Following a 30–minute recovery period, anesthesia was reinduced. Dogs were assigned to one of three treatments: isoflurane via facemask using 0.5% incremental increases in the delivered concentration every 30 seconds, 1.25 mg kg^?1 ketamine and 0.0625 mg kg^?1 diazepam intravenously (IV) with doses repeated every 30 seconds as required, and 2 mg kg^?1 propofol and 0.2 mg kg^?1 diazepam IV followed by 1 mg kg^?1 propofol increments IV every 30 seconds as required. Following endotracheal intubation all dogs received 1.7% end–tidal isoflurane in oxygen. Cardiopulmonary variables were recorded at baseline (before induction) and at 5 or 10 minute intervals following endotracheal intubation.ResultsInduction time was longer in Iso (4.98 ± 0.47 minutes) compared to KD (3.10 ± 0.47 minutes) or PD (3.22 ± 0.45 minutes). To produce anesthesia, KD received 4.9 ± 2.3 mg kg^?1 ketamine and 0.24 ± 0.1 mg kg^?1 diazepam, while PD received 2.2 ± 0.4 mg kg^?1 propofol and 0.2 mg kg^?1 diazepam. End–tidal isoflurane concentration immediately following intubation was 1.7 ± 0.4% in Iso. Arterial blood pressure and heart rate were significantly higher in KD and PD compared to Iso and in KD compared to PD. Arterial carbon dioxide partial pressure was significantly higher in PD compared to KD and Iso immediately after induction.Conclusions and clinical relevanceIn hypovolemic dogs, KD or PD, as used in this study to induce anesthesia, resulted in less hemodynamic depression compared to isoflurane.     

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.     

The bioequivalence of a single intravenous administration of the anesthetic alfaxalone in cyclodextrin versus alfaxalone in cyclodextrin plus preservatives in cats

To demonstrate the bioequivalence of alfaxalone in cyclodextrin (Reference Product) to a formulation of alfaxalone in cyclodextrin also containing the preservatives ethanol, chlorocresol, and benzethonium chloride (Test Product) when administered for the purpose of inducing anesthesia in the cat. Blinded, single‐dose, randomized, two‐period, two‐sequence, cross‐over bioequivalence study with a 7‐day washout period between treatments. Twenty‐four (12 neutered males and 12 intact females), healthy, adult cats weighing 4.1±0.9 kg. Cats were administered 5 mg/kg IV of alfaxalone in the Reference or Test Product using a randomized cross‐over design. One‐milliliter venous blood samples were collected at predetermined time points to 12 hr after drug administration to determine alfaxalone plasma concentration over time. Alfaxalone concentrations were determined by a validated analytical testing method using HPLC‐MS/MS. Plasma profiles of alfaxalone concentration against time were analyzed by noncompartmental analysis. The pivotal variables for bioequivalence were AUC_last and C_max. Equivalence was achieved if the 90% confidence interval for AUC_last and C_max fell into the asymmetric ±20% interval (0.80–1.25). Physiological variables, quality of anesthesia visual analog scale (VAS) scoring and anesthetic event times were recorded. ANOVA or ANCOVA (single time point), RMANOVA or RMANCOVA (multiple time point) was used for normally distributed data. GLIMMIX was used for nonnormally distributed data. VAS scores were analyzed as for blood bioequivalence data. Variables were evaluated for safety and assessed at alpha = 0.10. C_max and AUC_last for Reference and Test Products were statistically bioequivalent. 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 anesthetic event times or VAS scores for quality of anesthesia were different between treatment groups. Neither formulation caused pain upon injection. The Reference and Test Products are pharmaceutically bioequivalent formulations when administered as a single intravenous administration for the purpose of induction of anesthesia in cats.