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.     

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.     

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.     

Effects of ketamine or midazolam continuous rate infusions on alfaxalone total intravenous anaesthesia requirements and recovery quality in healthy dogs: a randomized clinical trial

ObjectiveTo determine the alfaxalone dose reduction during total intravenous anaesthesia (TIVA) when combined with ketamine or midazolam constant rate infusions and to assess recovery quality in healthy dogs.Study designProspective, blinded clinical study.AnimalsA group of 33 healthy, client-owned dogs subjected to dental procedures.MethodsAfter premedication with intramuscular acepromazine 0.05 mg kg^-1 and methadone 0.3 mg kg^-1, anaesthetic induction started with intravenous alfaxalone 0.5 mg kg^-1 followed by either lactated Ringer’s solution (0.04 mL kg^-1, group A), ketamine (2 mg kg^-1, group AK) or midazolam (0.2 mg kg^-1, group AM) and completed with alfaxalone until endotracheal intubation was achieved. Anaesthesia was maintained with alfaxalone (6 mg kg^-1 hour^-1), adjusted (±20%) every 5 minutes to maintain a suitable level of anaesthesia. Ketamine (0.6 mg kg^-1 hour^-1) or midazolam (0.4 mg kg^-1 hour^-1) were employed for anaesthetic maintenance in groups AK and AM, respectively. Physiological variables were monitored during anaesthesia. Times from alfaxalone discontinuation to extubation, sternal recumbency and standing position were calculated. Recovery quality and incidence of adverse events were recorded. Groups were compared using parametric analysis of variance and nonparametric (Kruskal-Wallis, Chi-square, Fisher’s exact) tests as appropriate, p < 0.05.ResultsMidazolam significantly reduced alfaxalone induction and maintenance doses (46%; p = 0.034 and 32%, p = 0.012, respectively), whereas ketamine only reduced the alfaxalone induction dose (30%; p = 0.010). Recovery quality was unacceptable in nine dogs in group A, three dogs in group AK and three dogs in group AM.Conclusions and clinical relevanceMidazolam, but not ketamine, reduced the alfaxalone infusion rate, and both co-adjuvant drugs reduced the alfaxalone induction dose. Alfaxalone TIVA allowed anaesthetic maintenance for dental procedures in dogs, but the quality of anaesthetic recovery remained unacceptable irrespective of its combination with ketamine or midazolam.     

Attitudes and concerns of French veterinarians towards pain and analgesia in dogs and cats

OBJECTIVE: To compare the attitudes of French veterinarians to pain, and their provision of analgesia to animals, with that reported from other countries. STUDY DESIGN: Epidemiological study. METHODS: In June 1999, 379 French veterinarians were surveyed to ascertain their views on pain evaluation and control in dogs and cats, and their use of analgesics in daily practice. Survey results are expressed as a percentage of responses. RESULTS: The questionnaire was returned by 189 veterinarians (49.9%). The response rate was influenced by age (younger veterinarians were more likely to respond) but not gender. A majority (99.5%) expressed moderate to extreme concern over pain in their patients. Pain evaluation was based on the animal's attitude (88.3% dogs, 82.5% cats), interaction with the caregiver, response to palpation of the painful area (66.5% dogs, 62.7% cats) and inappetence (29.3% dogs, 46.3% cats, p < 0.001). Only 14.3% of respondents considered their knowledge of pain recognition to be inadequate. Many (58.8%) considered their methods of pain quantification and control (47% dogs, 59% cats) to be inadequate. Difficulties in recognizing pain (58.3%), a lack of knowledge in the appropriate use of analgesics (41.7%) and fear of drug side effects (30%) were used to explain inadequate provision of analgesia. Only 16.1 and 8.1% used opioids in dogs and cats, respectively. This low level of use resulted from the imposition of French narcotic legislation (79.9%) and lack of knowledge of opioid pharmacology (73.7%). Nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids were the most commonly used analgesics in both species (100% (dogs) and 96.7% (cats)). The most popular NSAID used in France was tolfenamic acid, followed by meloxicam (dogs), ketoprofen, nimesulide (cats) and carprofen (dogs). The type of surgery performed influenced the use of analgesics, from 17.2% for castration to 83.7% for orthopaedic procedures. Nonsurgical conditions believed to warrant analgesia included osteoarthritis (97.8%), trauma (97.3%) and bone neoplasia (93.4%). Female veterinarians were more likely than males to evaluate pain and provide analgesia. CONCLUSION: French practitioners demonstrate a level of interest in analgesia, which appears to be at least equivalent to that reported from English-speaking countries. The signs used to indicate the presence of pain do not, in general, appear to differ. Excessive confidence in their ability to recognize pain (despite a general ignorance of the subject), the minor role of animal health technicians in pain management and misconceptions about analgesics (mainly opioids) are French pecularities.     

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.     

Alfaxalone for total intravenous anaesthesia in horses

Objective

To determine the suitability of alfaxalone total intravenous (IV) anaesthesia in horses and concurrently evaluate infusion rates, cardiovascular effects, pharmacokinetics and the quality of the anaesthetic recovery period.

Partial intravenous anaesthesia in the horse: a review of intravenous agents used to supplement equine inhalation anaesthesia. Part 1: lidocaine and ketamine

ObjectiveTo review the literature with regard to the use of different intravenous agents as supplements to inhalational anaesthesia in horses. These drugs include lidocaine, ketamine, opioids and α₂-agonists. The Part 1 of this review will focus in the use of lidocaine and ketamine.Databases usedPubmed &; Web of Science. Search terms: horse, inhalant anaesthesia, balanced anaesthesia, partial intravenous anaesthesia, lidocaine, ketamine.ConclusionsDifferent drugs and their combinations can be administered systemically in anaesthetized horses, with the aim of reducing the amount of the volatile agent whilst improving the recovery qualities and providing a multimodal analgesic approach. However, full studies as to whether these techniques improve cardiopulmonary status are not always available and potential disadvantages should also be considered.     

Effects of vatinoxan in dogs premedicated with medetomidine and butorphanol followed by sevoflurane anaesthesia: a randomized clinical study

ObjectiveTo investigate effects of vatinoxan in dogs, when administered as intravenous (IV) premedication with medetomidine and butorphanol before anaesthesia for surgical castration.Study designA randomized, controlled, blinded, clinical trial.AnimalsA total of 28 client-owned dogs.MethodsDogs were premedicated with medetomidine (0.125 mg m^?2) and butorphanol (0.2 mg kg^?1) (group MB; n = 14), or medetomidine (0.25 mg m^?2), butorphanol (0.2 mg kg^?1) and vatinoxan (5 mg m^?2) (group MB-VATI; n = 14). Anaesthesia was induced 15 minutes later with propofol and maintained with sevoflurane in oxygen (targeting 1.3%). Before surgical incision, lidocaine (2 mg kg^?1) was injected intratesticularly. At the end of the procedure, meloxicam (0.2 mg kg^?1) was administered IV. The level of sedation, the qualities of induction, intubation and recovery, and Glasgow Composite Pain Scale short form (GCPS-SF) were assessed. Heart rate (HR), respiratory rate (f_R), mean arterial pressure (MAP), end-tidal concentration of sevoflurane (Fe′Sevo) and carbon dioxide (Pe′CO₂) were recorded. Blood samples were collected at 10 and 30 minutes after premedication for plasma medetomidine and butorphanol concentrations.ResultsAt the beginning of surgery, HR was 61 ± 16 and 93 ± 23 beats minute^?1 (p = 0.001), and MAP was 78 ± 7 and 56 ± 7 mmHg (p = 0.001) in MB and MB-VATI groups, respectively. No differences were detected in f_R, Pe′CO₂, Fe′Sevo, the level of sedation, the qualities of induction, intubation and recovery, or in GCPS-SF. Plasma medetomidine concentrations were higher in group MB-VATI than in MB at 10 minutes (p = 0.002) and 30 minutes (p = 0.0001). Plasma butorphanol concentrations were not different between groups.Conclusions and clinical relevanceIn group MB, HR was significantly lower than in group MB-VATI. Hypotension detected in group MB-VATI during sevoflurane anaesthesia was clinically the most significant difference between groups.     

The risk of passive regurgitation during general anaesthesia in a population of referred dogs in the UK

Objective To evaluate the risk of passive regurgitation during anaesthesia, and to identify major factors associated with this in dogs attending the Queen Mother Hospital for Animals (QMHA), the Royal Veterinary College. Study design A case‐control study nested within the cohort of dogs undergoing anaesthesia with inhalation agents. Animal population All dogs undergoing general anaesthesia at the referral hospital between October 2006 and September 2008 (4271 cases). Methods All dogs anaesthetized at the QMHA during the study period were included. Regurgitating cases were defined as dogs for which reflux material was observed at the external nares or in the mouth, either during anaesthesia or before return to normal consciousness immediately after general anaesthesia. The risk of regurgitation was estimated and risk factors for regurgitation were evaluated with multivariable logistic regression (p < 0.05). Results The overall risk of regurgitation was 0.96% (41 cases out of 4271 anaesthetics, 95% confidence interval [95% CI] 0.67–1.25%). Exclusion of animals where pre‐existing disease was considered a contributing factor to regurgitation (n = 14) resulted in a risk of passive regurgitation of 0.63% (27 cases of 4257 anaesthetics, 95% CI 0.40–0.87%). In the multivariable logistic regression model, procedure and patient weight were significantly associated with regurgitation. Dogs undergoing orthopaedic surgery were 26.7 times more likely to regurgitate compared to dogs undergoing only diagnostic procedures. Dogs weighing more than 40 kg were approximately five times more likely to regurgitate than those weighing <20 kg. Conclusions and clinical relevance This study highlights the rare but important occurrence of perioperative regurgitation and identifies that dogs undergoing orthopaedic procedures, and those weighing more than 40 kg, are particularly at risk. Further work is required to evaluate the reasons for these observations.     

The incidence of spontaneous movements (myoclonus) in dogs undergoing total intravenous anaesthesia with propofol

ObjectiveTo evaluate the incidence of myoclonus (involuntary movements during anaesthesia, unrelated to inadequate hypnosis or analgesia, and of sufficient severity to require treatment) in dogs anaesthetized with a TIVA of propofol with or without the use of fentanyl.Study designRetrospective clinical study.AnimalsDogs, undergoing general anaesthesia for clinical procedures between January 2012 and January 2013 and subject to TIVA with propofol.MethodsA retrospective analysis reviewed the medical and anaesthetic records. Animals with existing or potential neurological or neuromuscular pathology in the anamnesis or upon clinical examination and cases with incomplete clinical records were excluded. Myoclonus was considered as involuntary muscle contractions which did not cease following a bolus administration of propofol or fentanyl and, due to their intensity and duration, made continuation of the procedure impracticable without other drug administration. Tremors, paddling or muscle spasms, explicable as insufficient hypnosis or analgesia, and transient excitatory phenomena only present during the awakening phase, were not considered as myoclonus.ResultsOut of a total of 492 dogs undergoing anaesthesia, six mixed breed dogs (1.2%), one male and five females, American Society of Anaesthesiologists (ASA) physical status I, median (range) weight 20.5 (7–37) kg and age 1.5 (1–5) years had myoclonus according to the aforementioned definition. In all subjects, myoclonus appeared within 20 minutes after induction of anaesthesia, and mainly involved the limb muscles. All subjects appeared to be in an adequate plane of anaesthesia before and during myoclonus.Conclusions and clinical relevanceThis study shows that 1.2% of dogs, undergoing TIVA with propofol with or without fentanyl administration, developed myoclonus, which required to be, and were treated successfully pharmacologically. The cause of this phenomenon is yet to be determined.     

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.

Plasma pharmacokinetics of alfaxalone in dogs after an intravenous bolus of Alfaxan-CD RTU

OBJECTIVE: To determine the pharmacokinetic parameters of alfaxalone in dogs after the intravenous (IV) administration of clinical and supra-clinical doses of a 2-hydroxypropyl-beta-cyclodextrin (HPCD) alfaxalone formulation (Alfaxan-CD RTU). EXPERIMENTAL DESIGN: Prospective two-period crossover design. Animals Eight (four male and four female) young adult healthy Beagle dogs. Methods The steroid anaesthetic alfaxalone was administered IV at two doses in a crossover design (2 and 10 mg kg(-1)) with a washout period of 21 days. Blood samples were collected before and up to 8 hours after dosing. Plasma concentrations of alfaxalone were assayed using a liquid chromatograph/mass selective detector technique and analyzed to estimate the main pharmacokinetic parameters by noncompartmental analysis. Results were expressed as mean +/- SD. RESULTS: The mean duration of anaesthesia from endotracheal intubation to extubation was 6.4 +/- 2.9 and 26.2 +/- 7.5 minutes, for the 2 and 10 mg kg(-1) doses, respectively. The plasma clearance of alfaxalone for the 2 and 10 mg kg(-1) doses differed statistically at 59.4 +/- 12.9 and 52.9 +/- 12.8 mL kg(-1) minute(-1), respectively (p = 0.008) but this difference was deemed clinically unimportant; the harmonic mean plasma terminal half-lives (t(1/2)) were 24.0 +/- 1.9 and 37.4 +/- 1.6 minutes respectively. The volume of distribution was between 2 and 3 L kg(-1) and did not differ between the two doses. No sex effect was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone, as an HPCD formulation (Alfaxan-CD RTU) administered in the dog provides rapid and smooth induction of anaesthesia, satisfactory conditions for endotracheal intubation and a short duration of anaesthesia. There was no clinically significant modification of the pharmacokinetic parameters between sexes and between the clinical (2 mg kg(-1)) and supra-clinical (10 mg kg(-1)) doses.     

Serum biochemical indicators of hepatobiliary function in dogs following prolonged anaesthesia with sevoflurane or isoflurane

Objective To investigate the changes in serum enzymes considered as biochemical indicators of hepatobiliary function in dogs following 5 hours of anaesthesia with isoflurane (ISO) or sevoflurane (SEVO). Study design Experimental randomized crossover study, with intervals of at least 15 days between successive treatments. Animals Eight healthy adult mongrel dogs, four male, four female, weight 13.6–21.6 kg. Methods Treatments consisted of anaesthesia with ISO or SEVO at 1 or 1.5 minimum alveolar concentration (MAC) delivered in oxygen. MAC was taken as 1.39% for ISO and 2.36% for SEVO. Anaesthesia was induced by mask then, after endotracheal intubation, maintained according to the treatment protocol using a small animal circle system. Cardiopulmonary monitoring was carried out. Venous blood samples, obtained by needle puncture, were taken at 24 hours and 2, 7 and 14 days post anaesthesia. Serum concentrations of total protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, (LDH), alkaline phosphatase (ALP), gamma‐glutamyltransferese and total bilirubin were measured. Changes with time and with treatment were compared by Friedman analysis, Wilcoxon Signed test and Kruskal‐Wallis test as relevant. p‐ value < 0.05 was considered significant. Results Compared to base‐line values, at 24 hours post‐anaesthesia there were significant increases in AST, ALT, ALP and LDH following one or more of the treatments, but by 2 days residual changes were not significant. At 24 hours, AST for treatment 1.5 MAC ISO was higher than 1 MAC ISO (p < 0.002), and LDH higher for 1.5 MAC SEVO than 1 MAC SEVO. Conclusion and clinical relevance Both ISO and SEVO, at concentrations used for clinical anaesthesia, produce transient moderate effects on some hepatobiliary enzyme concentrations in dogs.