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.     

The effects of propofol, isoflurane and sevoflurane on vecuronium infusion rates for surgical muscle relaxation in dogs

OBJECTIVE: To compare the constant rate infusion (CRI) of vecuronium required to maintain a level of neuromuscular blockade adequate for major surgeries, e.g. thoracotomy or laparotomy, in dogs anaesthetized with a CRI of fentanyl and either propofol, isoflurane or sevoflurane. STUDY DESIGN: Prospective, randomized, cross-over study. ANIMALS: Thirteen male beagles (age, 9-22 months; body mass 6.3-11.3 kg). MATERIALS AND METHODS: Dogs were anaesthetized with propofol (24 mg kg(-1) hour(-1) IV CRI; group P), isoflurane (1.3% end-tidal concentration; group I) or sevoflurane (2.3% end-tidal concentration; group S) with fentanyl (5 microg kg(-1) hour(-1) IV, CRI). Sixty to seventy minutes after induction of anaesthesia, vecuronium was administered at a rate of 0.4, 0.3 and 0.2 mg kg(-1) hour(-1) in groups P, I and S respectively. To determine the degree of neuromuscular block, a peripheral nerve was stimulated electrically using the train-of-four (TO4) stimulus pattern. Evoked muscle contractions were evaluated using a neuromuscular monitoring device. Once the TO4 ratio reached 0, the continuous infusion rate was decreased and adjusted to maintain a TO4 count of 1. Continuous infusion was continued for 2 hours. The infusion rate of vecuronium was recorded 20, 40, 60, 80, 100 and 120 minutes after the start of infusion. RESULTS: The mean continuous infusion rates of vecuronium during stable infusion were 0.22 +/- 0.04 (mean +/- SD), 0.10 +/- 0.02 and 0.09 +/- 0.02 mg kg(-1) hour(-1) in groups P, I and S respectively. There were statistically significant differences between the rates in groups P and I and between the rates in groups P and S. Conclusions and clinical relevance In healthy dogs, the recommended maintenance infusion rate of vecuronium is 0.2 mg kg(-1) hour(-1) under CRI propofol-fentanyl anaesthesia and 0.1 mg kg(-1) hour(-1) during CRI fentanyl-isoflurane or sevoflurane anaesthesia.     

Comparison of alfaxalone and propofol on haematological and serum biochemical variables in cats undergoing radiotherapy with sevoflurane maintenance

ObjectiveTo evaluate effects of repeated alfaxalone or propofol administration on haematological and serum biochemical variables in cats undergoing radiotherapy.Study designProspective, block-randomized, clinical trial.AnimalsA group of 39 client-owned cats.MethodsAfter butorphanol (0.2 mg kg^–1) and midazolam (0.1 mg kg^–1) sedation, cats were randomly assigned to receive either alfaxalone or propofol for induction of anaesthesia and sevoflurane maintenance. Cats were anaesthetized daily with the same induction agent for 10–12 days. Complete blood counts, reticulocytes, Heinz body score and serum biochemistry were performed before the first treatment (T1), at T6, T10 and 3 weeks after the final treatment (T21). Cumulative induction agent dose for each cat at each time point was evaluated for an effect on Heinz body score. Data are shown as mean ± standard deviation; p < 0.05.ResultsAt baseline there were no significant differences in signalment or blood variables between groups. A significant decrease in haematocrit of 2.3% ± 0.77 (p = 0.02) between T1-T6 and T1-T10 [mean 4.1% (± 0.78, p < 0.0001)] was detected, with a significant increase in haematocrit of 2.1% ± 0.80 (p = 0.046) between T6-T21 and 4.0% ± 0.8 (p < 0.001) between T10-T21. Heinz body score significantly increased by 1.86 ± 0.616 (p = 0.013) between T1-T10. In the propofol group, reticulocytes increased significantly between T1-T6 [mean 23,090 μL^–1 ± 7670 (p = 0.02)] and T1-T10 [mean 27,440 μL^–1 ± 7990 (p = 0.007)]. Mean cumulative dose at T10 was 19.65 mg kg^–1 ± 5.3 and 43.4 mg kg^–1 ± 14.4 for alfaxalone and propofol, respectively, with no significant effect on Heinz body formation at any time point.Conclusions and Clinical relevanceHaematocrit decreased in both groups with recovery after 3 weeks. Repeated alfaxalone and propofol administration was not associated with marked haematological or serum biochemistry changes.     

A controlled randomized clinical trial to assess postoperative analgesia after thiopental–isoflurane anaesthesia or total intravenous anaesthesia with alfaxalone in dogs

Alfaxalone, a synthetic neuroactive steroid, has been attributed with properties including sedation, anaesthesia and analgesia. The clinical relevance of any analgesic properties of alfaxalone has not been demonstrated. This study was a prospective, blinded, randomized, negative control clinical trial in 65 healthy dogs presented for ovariohysterectomy. Anaesthesia was induced and maintained, for Group 1 (TIVA) dogs (n = 30) with intravenous alfaxalone alone and for Group 2 dogs (n = 35) with thiopental followed by isoflurane in 100% oxygen inhalation. After ovariohysterectomy, quantitative measures of pain or nociception were recorded at 15 min intervals for 4 hr using three independent scoring systems, a composite measure pain scale (CMPS), von Frey threshold testing and measures of fentanyl rescue analgesia. The mean CMPS scores of Group 2 (THIO/ISO) dogs remained higher than Group 1 (TIVA) dogs from 15 to 135 min post‐surgery but this difference was not statistically significant. There were no significant differences between groups in the proportions of dogs requiring rescue fentanyl analgesia, the total fentanyl dose used or the time to first fentanyl dose. The Von Frey threshold testing was found to be unsuitable for measurement of pain in this experimental model. When administered as total intravenous anaesthesia, alfaxalone did not provide analgesia in the postoperative period.     

The use of alfaxalone for premedication,induction and maintenance of anaesthesia in pigs: a pilot study

Objective

The evaluation of alfaxalone as a premedication agent and intravenous anaesthetic in pigs.

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.     

Determination of the Minimum Infusion Rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to a standardised noxious stimulus in goats

ObjectiveTo determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to noxious stimulation.Study DesignProspective, experimental.AnimalsEight healthy goats; four does and four wethers.MethodsAnaesthesia was induced with alfaxalone 3 mg kg⁻¹ intravenously (IV). A continuous IV infusion of alfaxalone, initially at 0.2 mg kg⁻¹ minute⁻¹, was initiated. Following endotracheal intubation the goats breathed spontaneously via a circle breathing circuit delivering supplementary oxygen. The initial infusion rate was maintained for 30 minutes before testing for responses. The stimulus was clamping on the proximal (soft) part of one digit of the hoof with Vulsellum forceps for 60 seconds. In the absence or presence of purposeful movement of the extremities, the infusion rate was reduced or increased by 0.02 mg kg⁻¹ minute⁻¹ and held constant for 30 minutes before claw-clamping again. Alfaxalone MIR was calculated as the mean of the infusion rates that allowed and abolished movement. Cardio-respiratory parameters were measured. Recovery from general anaesthesia was timed and quality scored. Results are presented as median (range).ResultsThe MIR of alfaxalone was 0.16 (0.14–0.18) mg kg⁻¹ minute⁻¹ or 9.6 (8.4–10.8) mg kg⁻¹ hour⁻¹. Induction of and recovery from anaesthesia were excitement-free. Cardio-respiratory changes were minimal, although compared to baseline HR increased, and at 2 minutes post-induction, (prior to oxygen supplementation), PaO₂ decreased significantly from 84 (80–88) to 70 (51–72) mmHg [11.2 (10.7–11.7) to 9.3 (6.8–9.6) kPa]. Sporadic muscle twitches, unrelated to depth of anaesthesia, were observed during the period of general anaesthesia. Time (minutes) to sternal recumbency and standing were 4.0 (3.0–10.0) and 41.5 (25.0–57.0) respectively.Conclusions and Clinical RelevanceAlfaxalone can be used for total intravenous anaesthesia (TIVA) in goats and is associated with minimal adverse effects. Oxygen supplementation is advised, especially when working at higher altitudes.     

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.

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.     

Anaesthetic and cardiorespiratory effects of propofol at 10% for induction and 1% for maintenance of anaesthesia in horses

Reasons for performing study: Studies have demonstrated the clinical usefulness of propofol for anaesthesia in horses but the use of a concentrated solution requires further investigation. Objectives: To determine the anaesthetic and cardiorespiratory responses to a bolus injection of 10% propofol solution in mature horses. Methods: Three randomised crossover experimental trials were completed. Trial 1: 6 horses were selected randomly to receive 10% propofol (2, 4 or 8 mg/kg bwt i.v.). Trial 2: 6 horses received 1.1 mg/kg bwt i.v. xylazine before being assigned at random to receive one of 5 different doses (1–5 mg/kg bwt) of 10% propofol. Trial 3: 6 horses were sedated with xylazine (0.5 mg/kg bwt, i.v.) and assigned randomly to receive 10% propofol (3, 4 or 5 mg/kg bwt, i.v.); anaesthesia was maintained for 60 min using an infusion of 1% propofol (0.2‐0.4 mg/kg bwt/min). Cardiorespiratory data, the quality of anaesthesia, and times for induction, maintenance and recovery from anaesthesia and the number of attempts to stand were recorded. Results: Trial 1 was terminated after 2 horses had received each dose of 10% propofol. The quality of induction, anaesthesia and recovery from anaesthesia was judged to be unsatisfactory. Trial 2: 3 horses administered 1 mg/kg bwt and one administered 2 mg/kg bwt were not considered to be anaesthetised. Horses administered 3–5 mg/kg bwt i.v. propofol were anaesthetised for periods ranging from approximately 10–25 min. The PaO₂ was significantly decreased in horses administered 3–5 mg/kg bwt i.v. propofol. Trial 3: The quality of induction and recovery from anaesthesia were judged to be acceptable in all horses. Heart rate and rhythm, and arterial blood pressure were unchanged or decreased slightly during propofol infusion period. Conclusions: Anaesthesia can be induced with a 10% propofol solution and maintained with a 1% propofol solution in horses administered xylazine as preanaesthetic medication. Hypoventilation and hypoxaemia may occur following administration to mature horses. Potential relevance: Adequate preanaesthetic sedation and oxygen supplementation are required in horses anaesthetised with propofol.     

The effects of diazepam or midazolam on the dose of propofol required to induce anaesthesia in cats

ObjectivesAssess effects of benzodiazepine administration on the propofol dose required to induce anaesthesia in healthy cats, investigate differences between midazolam and diazepam, and determine an optimal benzodiazepine dose for co-induction.Study designProspective, randomised, blinded, placebo-controlled clinical trial.AnimalsNinety client-owned cats (ASA I and II) with a median (interquartile range) body mass of 4.0 (3.4–4.9) kg.MethodsAll cats received 0.01 mg kg⁻¹ acepromazine and 0.2 mg kg⁻¹ methadone intravenously (IV). Fifteen minutes later, sedation was scored on a scale of 1–5, with 5 indicating greatest sedation. Propofol, 2 mg kg⁻¹, administered IV, was followed by either midazolam or diazepam at 0.2, 0.3, 0.4 or 0.5 mg kg⁻¹ or saline 0.1 mL kg⁻¹. Further propofol was administered until endotracheal intubation was possible. Patient signalment, sedation score, propofol dosage and adverse reactions were recorded.ResultsMidazolam and diazepam (all doses) significantly reduced the propofol dose required compared with saline (p < 0.001). There was no difference between midazolam and diazepam in propofol dose reduction (p = 0.488). All individual doses of midazolam reduced propofol requirement compared with saline (0.2 mg kg⁻¹, p = 0.028; 0.3 mg kg⁻¹, p = 0.006; 0.4 mg kg⁻¹, p < 0.001; 0.5 mg kg⁻¹, p = 0.009). Diazepam 0.2 mg kg⁻¹ did not reduce the propofol dose compared with saline (p = 0.087), but the remaining doses did (0.3 mg kg⁻¹, p = 0.001; 0.4 mg kg⁻¹, p = 0.032; 0.5 mg kg⁻¹, p = 0.041). Cats with sedation scores of 3 required less propofol than cats with scores of 2 (p = 0.008). There was no difference between groups in adverse events.Conclusions and clinical relevanceMidazolam (0.2–0.5 mg kg⁻¹) and diazepam (0.3–0.5 mg kg⁻¹) administered IV after 2 mg kg⁻¹ propofol significantly reduced the propofol dose required for tracheal intubation.     

The minimum infusion rate of alfaxalone during its co-administration with lidocaine at three different doses by constant rate infusion in goats

Objective

To determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement in response to standardized stimulation while co-administered with lidocaine at three different doses by constant infusion rate infusion (CRI) in goats.

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

ObjectiveTo describe alfaxalone total intravenous anaesthesia (TIVA) following premedication with buprenorphine and either acepromazine (ACP) or dexmedetomidine (DEX) in bitches undergoing ovariohysterectomy.Study designProspective, randomised, clinical study.AnimalsThirty-eight healthy female dogs.MethodsFollowing 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.ResultsThere 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 relevanceAlfaxalone TIVA is an effective anaesthetic for surgical procedures but, in the protocol of this study, causes respiratory depression at infusion rates required for surgery.     

Dose requirement and cardiopulmonary effects of diluted and undiluted propofol for induction of anaesthesia in dogs

ObjectiveTo compare the dose, cardiopulmonary effects and quality of anaesthetic induction in dogs using propofol (10 mg mL^–1) and diluted propofol (5 mg mL^–1).Study designRandomized, blinded, clinical study.AnimalsA total of 28 client-owned dogs (12 males/16 females).MethodsFollowing intramuscular acepromazine (0.02 mg kg^–1) and methadone (0.2 mg kg^–1), propofol (UP, 10 mg mL^–1) or diluted propofol (DP, 5 mg mL^–1) was administered intravenously (0.2 mL kg^–1 minute^–1) by an anaesthetist unaware of the allocated group to achieve tracheal intubation. Sedation, intubation and induction quality were scored from 0 to 3. Pre- and post-induction pulse rate (PR), respiratory rate (f_R) and systolic (SAP), mean (MAP) and diastolic (DAP) arterial blood pressure were compared. Time to first breath and induction dose were recorded. Data were analysed for normality and Mann–Whitney U or Student t tests were performed where appropriate. Significance was set at p < 0.05. Data are presented as mean ± standard deviation or median (range).ResultsThe propofol dose administered to achieve induction was lower in the DP group (2.62 ± 0.48 mg kg^–1) than in the UP group (3.48 ± 1.17 mg kg^–1) (p = 0.021). No difference was observed in pre- and post-induction PR, SAP, MAP, DAP and f_R between groups. The differences between post-induction and pre-induction values of these variables were also similar between groups. Time to first breath did not differ between groups. Sedation scores were similar between groups. Quality of tracheal intubation was marginally better with UP 0 (0–1) than with DP 1 (0–2) (p = 0.036), but overall quality of induction was similar between groups [UP 0 (0–1) and DP 0 (0–1), p = 0.549].Conclusion and clinical relevanceDiluting propofol reduced the dose to induce anaesthesia without significantly altering the cardiopulmonary variables.