No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Alfaxalone for maintenance of anaesthesia in ponies undergoing field castration: continuous infusion compared with intravenous boluses
Abstract
Objective:
To compare alfaxalone as continuous intravenous (IV) infusion with intermittent IV injections for maintenance of anaesthesia in ponies undergoing castration.
Study design:
Prospective, randomized, 'blinded' clinical study.
Animals:
A group of 33 entire male Welsh ponies undergoing field castration.
Methods:
After preanaesthetic medication with IV detomidine (10 μg kg(-1)) and butorphanol (0.05 mg kg(-1)), anaesthesia was induced with IV diazepam (0.05 mg kg(-1)) followed by alfaxalone (1 mg kg(-1)). After random allocation, anaesthesia was maintained with either IV alfaxalone 2 mg kg(-1) hour(-1) (group A; n = 16) or saline administered at equal volume (group S; n = 17). When necessary, additional alfaxalone (0.2 mg kg(-1)) was administered IV. Ponies were breathing room air. Using simple descriptive scales, surgical conditions and anaesthesia recovery were scored. Total amount of alfaxalone, ponies requiring additional alfaxalone and time to administration, time from induction to end of infusion and end of infusion to standing were noted. Indirect arterial blood pressure, pulse and respiratory rates, end-expiratory carbon dioxide partial pressure and arterial haemoglobin oxygen saturation were recorded every 5 minutes. Data were analysed using Student t, Mann-Whitney U and chi-square tests, where appropriate (p < 0.05).
Results:
Total amount of alfaxalone administered after induction of anaesthesia (0.75 ± 0.27 versus 0.17 ± 0.23 mg kg(-1); p < 0.0001) and time to standing (14.8 ± 4 versus 11.6 ± 4 minutes; p = 0.044) were higher in group A compared to group S. Ponies requiring additional alfaxalone boluses [four (group A) versus seven (group S)] and other measured variables were similar between groups; five ponies required oxygen supplementation [three (group A) versus two (group S)].
Conclusion and clinical relevance:
Continuous IV infusion and intermittent administration of alfaxalone provided similar anaesthesia quality and surgical conditions in ponies undergoing field castration. Less alfaxalone is required when used intermittently.
... As with ketamine, the combination with other drugs and the resulting reduction in total dose of propofol and alfaxalone is advantageous for the recovery phase. Excitation during the early recovery phase has been reported after TIVA based on propofol [195,204] and alfaxalone [174,212]; however, alpha2-adrenergic agonists were not used during recovery in the aforementioned studies. Finally, recovery from TIVA with barbiturates and tiletamine/zolazepam is often prolonged and rough, making its use not recommended for TIVA in horses [159,178,180]. ...
Recovery remains the most dangerous phase of general anaesthesia in horses. The objective of this publication was to perform a structured literature review including levels of evidence (LoE) of each study with the keywords “recovery anaesthesia horse”, entered at once, in the search browsers PubMed and Web of Science. The two authors independently evaluated each candidate article. A final list with 444 articles was obtained on 5 April 2021, classified as: 41 “narrative reviews/expert opinions”, 16 “retrospective outcome studies”, 5 “surveys”, 59 “premedication/sedation and induction drugs”, 27 “maintenance with inhalant agents”, 55 “maintenance with total intravenous anaesthesia (TIVA)”, 3 “TIVA versus inhalants”, 56 “maintenance with partial intravenous anaesthesia (PIVA)”, 27 “other drugs used during maintenance”, 18 “drugs before/during recovery”, 18 “recovery systems”, 21 “respiratory system in recovery”, 41 “other factors”, 51 “case series/reports” and 6 “systems to score recoveries”. Of them, 167 were LoE 1, 36 LoE 2, 33 LoE 3, 110 LoE 4, 90 LoE 5 and 8 could not be classified based on the available abstract. This review can be used as an up-to-date compilation of the literature about recovery after general anaesthesia in adult horses that tried to minimise the bias inherent to narrative reviews.
... 40 Since its reformulation, alfaxalone has gained increasing popularity in veterinary medicine as an induction agent, a sedative, and a component of intravenous general anesthesia in a variety of species. 3,4,8,9,11,17,20,30,33,37,40 Recently, 2 publications have evaluated alfaxalone as an anesthetic in mice. One of these studies 34 demonstrated that alfaxalone, in combination with the α 2 -adrenergic agonist xylazine, could be administered intraperitoneally to safely induce a surgical plane of anesthesia in mice. ...
Since its recent reformulation, alfaxalone has gained popularity as an injectable veterinary anesthetic, including promising studies demonstrating the use of alfaxalone-xylazine for anesthesia in mice. Here we sought to expand these studies by testing additional dose ranges, elaborating on physiologic monitoring, testing sex- and strain-associated differences, and evaluating efficacy during actual surgical conditions. C57BL/6J mice showed significant sex-associated differences in anesthetic sensitivity, with males requiring higher doses of alfaxalone (80-120 mg/kg IP alfaxalone with 10 mg/kg IP xylazine) than females (40-80 mg/kg IP alfaxalone with 10 mg/kg IP xylazine) to achieve a surgical plane of anesthesia. In addition, female outbred CD1 mice were less sensitive to alfaxalone than female inbred C57BL/6J mice. When used during actual surgery, alfaxalone-xylazine administered intraperitoneally provided adequate anesthesia for a model of orthopedic surgery, whereas the same anesthetic regimen during laparotomy resulted in unacceptably high mortality; survival during laparotomy increased when drugs were administered subcutaneously. These results indicate that alfaxalone-xylazine may be a viable option for injectable surgical anesthesia in mice, although strain- and sex-associated differences and alternative routes of administration should be considered when optimizing the anesthetic regimen for specific experimental conditions.
... Alfaxalone infusions have been used alone or with various combinations of other infused drugs such as medetomidine, guaifenesin and butorphanol to maintain anaesthesia in horses and ponies undergoing castration for up to 60 minutes Ohmura et al. 2016;Aoki et al. 2017;Deutsch et al. 2017). These studies concluded that alfaxalone, when used alone or combined with other drugs, was suitable for short-term anaesthetic maintenance in horses and ponies; however, there is no information regarding the use of alfaxalone as the sole agent to maintain anaesthesia for periods longer than 60 minutes. ...
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. Study design: Prospective, experimental study. Animals: Eight Standardbred horses. Methods: Horses were premedicated with IV acepromazine (0.03 mg kg–1) and xylazine (1 mg kg–1) and anaesthesia was induced with guaifenesin (35 mg kg–1) and alfaxalone (1 mg kg–1). Anaesthesia was maintained for 180 minutes using an IV infusion of alfaxalone at a rate determined by a horse's response to a supramaximal electrical noxious stimulus. Venous blood samples were regularly collected to determine alfaxalone plasma concentrations and for pharmacokinetic analysis. Cardiopulmonary variables were monitored and the quality of the anaesthetic recovery period scored. Results: The median (range) alfaxalone infusion rate was 3.1 (2.4–4.3) mg kg–1 hour–1. The mean ± standard deviation plasma elimination half-life, plasma clearance and volume of distribution for alfaxalone were 41 minutes, 25 ± 6.3 mL minute–1 kg–1 and 1.6 ± 0.5 L kg–1, respectively. During anaesthesia, mean arterial blood pressure was maintained above 70 mmHg in all horses. Cardiac index reached a minimum value (68% of baseline values) immediately after induction of anaesthesia and was maintained between 74% and 90% of baseline values for the remainder of the anaesthetic protocol. Following the cessation of the alfaxalone infusion, six of eight horses exhibited muscle tremors and paddling. All horses stood without incident on the first or second attempt with a median recovery score of 4.5 (good to excellent). Conclusions and clinical relevance: Anaesthesia in horses can be maintained with an infusion of alfaxalone at approximately 3 mg kg–1 hour–1. The alfaxalone infusion rates used resulted in minimal haemodynamic changes and good recovery quality. Mean alfaxalone plasma concentration was stable over the infusion period and clearance rates were similar to previously published single-dose alfaxalone studies in horses. © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia
Background:
The recovery phase after equine general anaesthesia (GA) is a time of considerable risk and therefore has been the subject of extensive research over the last 20 years. Various pharmacological interventions have been developed and studied with the objective of improving recovery quality and reducing anaesthetic-related mortality and morbidity. Nevertheless, some controversy remains regarding the influence of anaesthetic protocol choice on recovery quality from GA and its implications for recovery-related mortality and morbidity. A systematic review of the literature investigating the influence of anaesthetic protocol choice on recovery quality is currently lacking.
Objectives:
To perform a detailed evaluation of the equine veterinary literature investigating the effect of anaesthetic protocol choice on equine recovery quality utilising the GRADE framework.
Study design:
A systematic evaluation of the equine veterinary literature was performed using the GRADE framework.
Methods:
A literature search was performed and studies were assessed for eligibility by both authors utilising PRISMA guidelines. Studies meeting inclusion criteria were evaluated by both authors, categorically summarised and the quality of evidence for each sub-topic was assessed using the GRADE framework.
Results:
A total of 124 studies were identified which directly assessed the impact of anaesthetic protocol choice on recovery quality after GA in horses. Evaluation of the available evidence indicated that certain partial intravenous anaesthesia (PIVA) agents, cessation of intravenous lidocaine 30 minutes prior to recovery and provision of adequate analgesia improves recovery quality.
Main limitations:
The validity of the results of some studies may have been compromised by missing data and small sample sizes.
Conclusions:
There is evidence to indicate that certain PIVA agents, cessation of intravenous lidocaine 30 minutes prior to recovery and provision of adequate analgesia improves recovery quality.
Objective
To evaluate the anesthetic and cardiopulmonary effects of xylazine–alfaxalone anesthesia in donkey foals undergoing field castration.
Study design
Prospective clinical study.
Animals
A group of seven standard donkeys aged [median (range)] 12 (10–26) weeks, weighing 47.3 (37.3–68.2) kg.
Methods
Donkeys were anesthetized with xylazine (1 mg kg⁻¹) intravenously (IV) followed 3 minutes later by alfaxalone (1 mg kg⁻¹) IV. Additional doses of xylazine (0.5 mg kg⁻¹) and alfaxalone (0.5 mg kg⁻¹) IV were administered as needed to maintain surgical anesthesia. Intranasal oxygen was supplemented at 3 L minute⁻¹. Heart rate (HR), respiratory rate (fR), and mean arterial pressure (MAP) by oscillometry were recorded before drug administration and every 5 minutes after induction of anesthesia. Peripheral oxygen saturation (SpO2) was recorded every 5 minutes after induction. Time to recumbency after alfaxalone administration, time to anesthetic re-dose, time to first movement, sternal and standing after last anesthetic dose, and surgery time were recorded. Induction and recovery quality were scored (1, very poor; 5, excellent).
Results
Median (range) induction score was 5 (1–5), and recovery score 4 (1–5). Two donkeys were assigned a score of 1 (excitement) during induction or recovery. HR and MAP during the procedure did not differ from baseline. fR was decreased at 5 and 10 minutes but was not considered clinically significant. SpO2 was < 90% at one time point in two animals.
Conclusions
and clinical relevance Xylazine–alfaxalone anesthesia resulted in adequate conditions for castration in 12 week old donkeys. While the majority of inductions and recoveries were good to excellent, significant excitement occurred in two animals and may limit the utility of this protocol for larger donkeys. Hypoxemia occurred despite intranasal oxygen supplementation.
To investigate the clinical pharmacokinetics and pharmacodynamics of intravenous alfaxalone in young Thoroughbred horses, seven Thoroughbred horses were randomly anaesthetised twice with either 1 or 2 mg/kg of intravenous alfaxalone after premedication with medetomidine (6 µg/kg intravenous) and midazolam (20 µg/kg intravenous). Blood samples were collected at predetermined time points up to two hours after administration. Plasma alfaxalone concentrations were quantified by a liquid chromatography tandem-mass spectrometry method and analysed by non-compartmental pharmacokinetic analysis. Induction and recovery qualities were good to excellent for both doses. Recovery time for the 2 mg/kg (median 90 minutes) was significantly longer than that for the 1 mg/kg (median 50 minutes). Respiratory rate for the 2 mg/kg was significantly lower than that for the 1 mg/kg, resulting in hypoxaemia. The median (range) elimination half-life, total clearance and volume of distribution were 58.2 (42.3–70.7) minutes, 11.6 (10.3–14.5) ml/minute/kg and 0.8 (0.7–0.9) l/kg for the 1 mg/kg and 59.8 (47.5–68.0) minutes, 14.7 (12.1–16.0) ml/minute/kg and 0.9 (0.9–1.2) l/kg for the 2 mg/kg, respectively. Alfaxalone is rapidly eliminated from the plasma in young Thoroughbred horses. Respiratory depression should be especially noted when alfaxalone is used in clinical practice.
Objective
To evaluate effects of anesthesia induced with alfaxalone and maintained with alfaxalone, dexmedetomidine and remifentanil infusions in foals.
Study design
Prospective, experimental study.
Animals
A group of six healthy foals [median (range) 11 (8–33) days] undergoing abdominal surgery.
Methods
Intravenous (IV) dexmedetomidine (3–7 μg kg⁻¹) provided sedation for insertion of a pulmonary artery catheter. IV anesthesia was induced with alfaxalone (2 mg kg⁻¹) and maintained with alfaxalone (6 mg kg⁻¹ hour⁻¹), dexmedetomidine (1 μg kg⁻¹ hour⁻¹) and remifentanil (3 μg kg⁻¹ hour⁻¹). Foals were endotracheally intubated and lungs were mechanically ventilated with oxygen. Cardiac output (thermodilution), heart rate and systemic arterial pressure were measured. Arterial and mixed venous blood was analyzed for PO2 and PCO2, and glucose, lactate and electrolyte concentrations. Anesthetic depth was subjectively assessed. Systemic vascular resistance (SVR), oxygen utilization and intrapulmonary shunt were calculated. Preinduction (PB) or 10 minutes postinduction (+10B) data were used as baselines with one-way analysis of variance for repeated measures. Data are mean ± standard deviation; significance was p ≤ 0.05.
Results
Duration of anesthesia was 129 ± 22 minutes. One foal was administered additional alfaxalone (0.5 mg kg⁻¹) following induction. Cardiac index decreased to 107 ± 31 and 87 ± 21 mL kg⁻¹ minute⁻¹ at 60 and 80 minutes, respectively, compared with PB (157 ± 33 mL kg⁻¹ minute⁻¹). SVR increased to 1223 ± 166 dynes second⁻¹ cm⁻⁵ at 80 minutes compared with +10B (704 ± 247 dynes second⁻¹ cm⁻⁵). Mean arterial pressures were 63–128 mmHg. Time from stopping infusions to standing was 46–106 minutes. All foals were hypothermic (<36 °C) and three foals were administered atipamezole (0.05 mg kg⁻¹) intramuscularly during recovery.
Conclusion
and clinical relevance Combined alfaxalone–dexmedetomidine–remifentanil provided suitable anesthesia to permit laparotomy in foals. At the doses evaluated, prolonged recovery may occur.
Objective
To compare the effects of propofol and alfaxalone on respiration in cats.Study designRandomized, ‘blinded’, prospective clinical trial.AnimalsTwenty cats undergoing ovariohysterectomy.Methods
After 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.
This study looked at the use and efficacy of alfaxalone for total intravenous anaesthesia (TIVA) in cats. Following intramuscular medetomidine (20 μg/kg) and morphine (0.3 mg/kg) premedication, anaesthesia was induced and maintained with intravenous alfaxalone. Patients were breathing 100% oxygen. Heart rate (HR), respiratory rate (RR), end tidal carbon dioxide, oxygen saturation of haemoglobin and indirect arterial blood pressure via Doppler (DAP) were recorded every 5 mins. Thirty-four cats (10 males and 24 females), between the age of 6 and 18 months, and weighing between 1.8 and 5.3 kg, and undergoing neutering procedures were included in this study. The results are presented as median (min., max.) values. The time to first spontaneous movement (TS) was >30 mins in 19 cats, of which 12 received atipamezole for reversal of the effects of medetomidine. The TS was 53 (43, 130) mins in these 12 cats and 50 (40, 72) mins in the other seven cats. The body temperature in those 19 cats was significantly lower than the other cats (P = 0.05). The alfaxalone induction dose and maintenance infusion rate were1.7 (0.7, 3.0) mg/kg and 0.18 (0.06, 0.25) mg/kg/min, respectively. The HR, RR and DAP were 145 (68, 235) beats/min, 17 (5, 40) breaths/min and 110 (58, 210) mmHg, respectively. Apnoea was not observed in any cat. In conclusion, alfaxalone TIVA in combination with medetomidine and morphine premedication was effective in feral and domestic cats for the performance of neutering surgery; low body temperature might have resulted in longer recoveries in some cats.
To compare the analgesic efficacy of administration of butorphanol tartrate, phenylbutazone, or both drugs in combination in colts undergoing routine castration.
Randomized controlled clinical trial.
36 client-owned colts.
Horses received treatment with butorphanol alone (0.05 mg/kg [0.023 mg/lb], IM, prior to surgery and then q 4 h for 24 hours), phenylbutazone alone (4.4 mg/kg [2.0 mg/lb], IV, prior to surgery and then 2.2 mg/kg [1.0 mg/lb], PO, q 12 h for 3 days), or butorphanol and phenylbutazone at the aforementioned dosages (12 horses/group). For single-drug-treated horses, appropriate placebos were administered to balance treatment protocols among groups. All horses were anesthetized, and lidocaine hydrochloride was injected into each testis. Physical and physiological variables, plasma cortisol concentration, body weight, and water consumption were assessed before and at intervals after surgery, and induction of and recovery from anesthesia were subjectively characterized. Observers assessed signs of pain by use of a visual analogue scale and a numerical rating scale.
Significant changes in gastrointestinal sounds, fecal output, and plasma cortisol concentrations were evident in each treatment group over time, compared with preoperative values. At any time point, assessed variables and signs of pain did not differ significantly among groups, although the duration of recumbency after surgery was longest for the butorphanol-phenylbutazone-treated horses.
With intratesticular injections of lidocaine, administration of butorphanol to anesthetized young horses undergoing routine castration had the same apparent analgesic effect as phenylbutazone treatment. Combined butorphanolphenylbutazone treatment was not apparently superior to either drug used alone.
The cardiovascular effects of medetomidine, detomidine, and xylazine in horses were studied. Fifteen horses, whose right carotid arteries had previously been surgically raised to a subcutaneous position during general anesthesia were used. Five horses each were given the following 8 treatments: an intravenous injection of 4 doses of medetomidine (3, 5, 7.5, and 10 microg/kg), 3 doses of detomidine (10, 20, and 40 microg/kg), and one dose of xylazine (1 mg/kg). Heart rate decreased, but not statistically significant. Atrio-ventricular block was observed following all treatments and prolonged with detomidine. Cardiac index (CI) and stroke volume (SV) were decreased with all treatments. The CI decreased to about 50% of baseline values for 5 min after 7.5 and 10 microg/kg medetomidine and 1 mg/kg xylazine, for 20 min after 20 microg/kg detomidine, and for 50 min after 40 microg/kg detomidine. All treatments produced an initial hypertension within 2 min of drug administration followed by a significant decrease in arterial blood pressure (ABP) in horses administered 3 to 7.5 microg/kg medetomidine and 1 mg/kg xylazine. Hypertension was significantly prolonged in 20 and 40 microg/kg detomidine. The hypotensive phase was not observed in 10 microg/kg medetomidine or detomidine. The changes in ABP were associated with an increase in peripheral vascular resistance. Respiratory rate was decreased for 40 to 120 min in 5, 7.5, and 10 microg/kg medetomidine and detomidine. The partial pressure of arterial oxygen decreased significantly in 10 microg/kg medetomidine and detomidine, while the partial pressure of arterial carbon dioxide did not change significantly. Medetomidine induced dose-dependent cardiovascular depression similar to detomidine. The cardiovascular effects of medetomidine and xylazine were not as prolonged as that of detomidine.
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. Study design: Prospective, experimental study. Animals: Eight Standardbred horses. Methods: Horses were premedicated with IV acepromazine (0.03 mg kg–1) and xylazine (1 mg kg–1) and anaesthesia was induced with guaifenesin (35 mg kg–1) and alfaxalone (1 mg kg–1). Anaesthesia was maintained for 180 minutes using an IV infusion of alfaxalone at a rate determined by a horse's response to a supramaximal electrical noxious stimulus. Venous blood samples were regularly collected to determine alfaxalone plasma concentrations and for pharmacokinetic analysis. Cardiopulmonary variables were monitored and the quality of the anaesthetic recovery period scored. Results: The median (range) alfaxalone infusion rate was 3.1 (2.4–4.3) mg kg–1 hour–1. The mean ± standard deviation plasma elimination half-life, plasma clearance and volume of distribution for alfaxalone were 41 minutes, 25 ± 6.3 mL minute–1 kg–1 and 1.6 ± 0.5 L kg–1, respectively. During anaesthesia, mean arterial blood pressure was maintained above 70 mmHg in all horses. Cardiac index reached a minimum value (68% of baseline values) immediately after induction of anaesthesia and was maintained between 74% and 90% of baseline values for the remainder of the anaesthetic protocol. Following the cessation of the alfaxalone infusion, six of eight horses exhibited muscle tremors and paddling. All horses stood without incident on the first or second attempt with a median recovery score of 4.5 (good to excellent). Conclusions and clinical relevance: Anaesthesia in horses can be maintained with an infusion of alfaxalone at approximately 3 mg kg–1 hour–1. The alfaxalone infusion rates used resulted in minimal haemodynamic changes and good recovery quality. Mean alfaxalone plasma concentration was stable over the infusion period and clearance rates were similar to previously published single-dose alfaxalone studies in horses. © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia
Reasons for performing study:
There is limited information on clinical use of the new injectable anaesthetic agent alfaxalone in Thoroughbred horses.
Objectives:
To compare anaesthetic induction and recovery characteristics and cardiopulmonary responses between alfaxalone, ketamine and thiopental in Thoroughbred horses premedicated with medetomidine and midazolam.
Study design:
Randomised blinded experimental cross-over study.
Methods:
Six Thoroughbred horses were anaesthetised 3 times with alfaxalone 1 mg/kg bwt, ketamine 2.5 mg/kg bwt or thiopental 4 mg/kg bwt after premedication with medetomidine 6 μg/kg bwt and midazolam 20 μg/kg bwt. Qualities of anaesthetic induction and recovery were scored on a scale of 1 (poor) to 5 (excellent). Induction time and recovery time were recorded. Cardiopulmonary values (heart rate, respiratory rate, arterial blood pressures, and arterial blood gases) were recorded throughout anaesthesia. Data were analysed with nonparametric methods.
Results:
The anaesthetic induction (P = 0.2) and recovery (P = 0.1) quality scores (median, range) were not different amongst protocols and were 4.0, 3-5; 5.0, 4-5; 4.5, 3-5; and 4.5, 3-5; 3.5, 2-5; 4.0, 2-5 for alfaxalone, ketamine and thiopental, respectively. Induction time for ketamine (67, 53-89 s) was significantly longer than that for alfaxalone (49, 40-51 s, P = 0.01) and thiopental (48, 43-50 s, P = 0.01). Time to standing for alfaxalone (44, 40-63 min, P = 0.01) and thiopental (39, 30-58 min, P = 0.01) was significantly longer than that for ketamine (25, 18-26 min). Cardiovascular values were maintained within the clinically acceptable level throughout anaesthesia. Respiratory rate significantly decreased during anaesthesia for all 3 drugs; however, spontaneous breathing did not disappear, and PaCO2 values were maintained at approximately 50 mmHg.
Conclusions:
All 3 drugs showed similar effects in relation to anaesthetic induction and recovery qualities and cardiopulmonary responses. However, alfaxalone and thiopental prolonged recovery time compared with ketamine.
Reasons for performing the studyThe use of alfaxalone and medetomidine administered as an i.v. infusion to maintain anaesthesia has not previously been reported in the horse. Objectives
To investigate the use of alfaxalone in hydroxpropyl-beta-cyclodextrin (Alfaxan) and medetomidine infusion as a field anaesthetic for short-term surgical procedures in the horse. HypothesisAlfaxalone–medetomidine anaesthesia is suitable for short-term field anaesthesia in horses. Methods
Eleven healthy colts underwent 45 min of anaesthesia with an i.v. infusion of alfaxalone (2 mg/kg bwt/h) and medetomidine (5 μg/kg bwt/h) for routine field castration. Horses were premedicated with i.v. acepromazine (0.03 mg/kg bwt), medetomidine (7 μg/kg bwt) and guaiphenesin (35 mg/kg bwt) before i.v. induction with alfaxalone (1 mg/kg bwt). Colts were intubated with an endotracheal tube and 100% oxygen insufflated at 10 l/min. The physiological variables monitored included pulse rate, respiratory rate, direct arterial blood pressure, arterial blood gases and the quality of the inductions and recoveries were scored. ResultsOverall, the anaesthetic period and surgical conditions were acceptable and the quality of the anaesthetic inductions and recoveries was good to excellent. All colts stood on their first attempt (mean ± s.d.) 37 ± 13.5 min after the infusion was stopped. During anaesthesia, cardiopulmonary data, presented as range of mean values at each time point were: heart rate: 45–47 beats/min; mean blood pressure: 104–112 mmHg; respiratory rate: 8 breaths/min; PaO2: 117–172 mmHg; PaCO2: 50–56 mmHg and pH 7.34–7.37. Conclusions and potential relevanceThe co-administration of alfaxalone and medetomidine as an i.v. infusion after anaesthetic induction with alfaxalone was suitable for short-term field anaesthesia in the horse.
Objective
To determine the minimum infusion rate (MIR) of propofol required to prevent purposeful movement in response to a standardized stimulus in goats.
Study design
Prospective, experimental study.
Animals
Eight healthy goats (four does, four wethers).
Methods
Anaesthesia was induced with 4 mg kg⁻¹ propofol intravenously (IV). A continuous IV infusion of propofol at 0.6 mg kg⁻¹ minute⁻¹ was initiated immediately to maintain anaesthesia. Following endotracheal intubation, goats breathed spontaneously via a circle breathing system delivering supplementary oxygen. The initial propofol infusion rate was maintained for 30 minutes before responses to noxious stimulation provided by clamping the proximal part of the claw with a Vulsellum forceps for 60 seconds were tested. In the presence or absence of purposeful movements of the extremities, the infusion rate was increased or reduced by 0.1 mg kg⁻¹ minute⁻¹ and held constant for 30 minutes before claw clamping was repeated. The propofol MIR for each goat was calculated as the mean of the infusion rates that allowed and abolished movement. Basic cardiopulmonary parameters were monitored, recorded and tested for statistical significance using Wilcoxon's signed rank test with Bonferroni adjustment for multiple testing. The quality of recovery from anaesthesia was assessed and scored.
Results
The median MIR of propofol was 0.45 mg kg⁻¹ minute⁻¹ (range: 0.45–0.55 mg kg⁻¹ minute⁻¹). Induction and recovery were free of adverse behaviour. No statistically significant cardiopulmonary changes in comparison with baseline were observed, but clinically relevant hypoxaemia at 2 minutes after induction of anaesthesia was consistently observed. Chewing during anaesthesia was observed in three goats. Median times to extubation and standing were 3 minutes (range: 2–6 minutes) and 10 minutes (range: 7–21 minutes), respectively.
Conclusions and clinical relevance
Propofol induction and maintenance of general anaesthesia minimally compromise cardiopulmonary function when oxygen is supplemented in goats.
Objective:
To compare the cardiopulmonary effects of continuous rate infusions (CRIs) of alfaxalone-2-hydroxypropyl-beta-cyclodextrin (HPCD) and propofol in healthy dogs.
Animals:
6 young adult medium-sized healthy crossbred dogs.
Procedures:
A crossover design was used with a washout period of 6 days between anesthetic treatments. Each dog was sedated with acepromazine (0.02 mg/kg, IV) and hydromorphone (0.05 mg/kg, IV). Anesthesia was induced with propofol (4 mg/kg) or alfaxalone-HPCD (2 mg/kg). After endotracheal intubation, anesthesia was maintained with the same agent (propofol, 0.25 mg/kg/min; alfaxalone-HPCD, 0.07 mg/kg/min) for 120 minutes. Dogs spontaneously breathed 100% oxygen. Measurements included end-tidal partial pressure of carbon dioxide, heart and respiratory rates, mean arterial blood pressure, thermodilution-derived cardiac output, and body temperature. Paired arterial and mixed venous blood samples were collected for determination of blood pH, PaCO(2), and PaO(2). Data were recorded prior to induction; 5, 15, 30, 60, 90, and 120 minutes after induction of anesthesia; and 20 minutes after stopping the CRI, when feasible. Stroke volume and systemic vascular resistance were calculated. Quality of anesthetic induction and recovery and interval to recovery were recorded.
Results:
Both propofol and alfaxalone-HPCD produced excellent induction of anesthesia, maintenance, and recovery. Respiratory depression was evident with both anesthetics. Clinically acceptable, mild hemodynamic changes were similar for both anesthetics.
Conclusions and clinical relevance:
Alfaxalone-HPCD produced clinically acceptable anesthetic quality and hemodynamic values ideal for use as a CRI. Ventilation may need to be supported if hydromorphone is used at these propofol and alfaxalone-HPCD infusion rates.
Alfaxalone in a 2-hydroxypropyl-β-cyclodextrin (HPCD) formulation is an intravenous (IV) hypnotic agent characterised by the stability of cardiorespiratory effects after a single-bolus administration. The objective of this study was to investigate the cardiovascular, respiratory, and acid-base effects of alfaxalone-HPCD administered during a continuous rate infusion in six Ripollesa sheep. After instrumentation, a 2mg/kg IV bolus of alfaxalone followed by a continuous infusion of 10mg/kg/h was administered to the sheep. Heart rate, arterial blood pressure, respiratory rate and arterial blood gases were recorded. Occasional side effects and time to standing were also noted. No significant changes were observed in arterial blood pressure, but during the infusion and the initial stages of recovery, a significant increase in heart rate occurred during the last 120min of the study. Significant respiratory depression was detected during the infusion period and the first 15min of recovery. This study showed that a constant rate infusion alfaxalone in un-premedicated sheep produced clinically acceptable haemodynamic results and a mild respiratory depression that may require intermittent positive pressure ventilation.
Objective To compare anaesthesia induced with either alfaxalone or ketamine in horses following premedication with xylazine and guaifenesin.
Study design Randomized blinded cross-over experimental study.
Animals Six adult horses, five Standardbreds and one Thoroughbred; two mares and four geldings.
Methods Each horse received, on separate occasions, induction of anaesthesia with either ketamine 2.2 mg kg−1 or alfaxalone 1 mg kg−1. Premedication was with xylazine 0.5 mg kg−1 and guaifenesin 35 mg kg−1. Incidence of tremors/shaking after induction, recovery and ataxia on recovery were scored. Time to recovery was recorded. Partial pressure of arterial blood oxygen (PaO2) and carbon dioxide (PaO2), arterial blood pressures, heart rate (HR) and respiratory rates were recorded before premedication and at intervals during anaesthesia. Data were analyzed using Wilcoxon matched pairs signed rank test and are expressed as median (range).
Results There was no difference in the quality of recovery or in ataxia scores. Horses receiving alfaxalone exhibited a higher incidence of tremors/shaking on induction compared with those receiving ketamine (five and one of six horses respectively). Horses recovered to standing similarly [28 (24–47) minutes for alfaxalone; 22 (18–35) for ketamine] but took longer to recover adequately to return to the paddock after alfaxalone [44 (38–67) minutes] compared with ketamine [35 (30–47)]. There was no statistical difference between treatments in effect on HR, PaO2 or PaCO2 although for both regimens, PaO2 decreased with respect to before premedication values. There was no difference between treatments in effect on blood pressure.
Conclusions and clinical relevance Both alfaxalone and ketamine were effective at inducing anaesthesia, although at induction there were more muscle tremors after alfaxalone. As there were no differences between treatments in relation to cardiopulmonary responses or quality of recovery, and only minor differences in recovery times, both agents appear suitable for this purpose following the premedication regimen used in this study.
Objective To describe alfaxalone total intravenous anaesthesia (TIVA) following premedication with buprenorphine and either acepromazine (ACP) or dexmedetomidine (DEX) in bitches undergoing ovariohysterectomy.
Study design Prospective, randomised, clinical study.
Animals Thirty-eight healthy female dogs.
Methods Following 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.
Results There 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 relevance Alfaxalone TIVA is an effective anaesthetic for surgical procedures but, in the protocol of this study, causes respiratory depression at infusion rates required for surgery.
The analgesic potency of butorphanol 25 μg/kg bodyweight (BW) and levomethadone 100 μg/kg BW, administered together with detomidine 10 μg/kg BW, was measured in twelve Warmblood horses in a randomized, blinded cross-over study. Detomidine with saline 10 ml 0.9 % was used as placebo. The nociceptive threshold was determined using a constant current and a pneumatic pressure model for somatic pain. Detomidine alone and in combination with butorphanol or levomethadone caused a significant temporary increase (P < 0.05) of the nociceptive threshold with a maximum effect within 15 min and a return to baseline levels within 90 min. Butorphanol and levomethadone increased the nociceptive threshold and prolonged the duration of anti-nociception significantly from 15 to 75 min (P < 0.05) after drug administration compared with detomidine alone to both test methods. No significant difference between butorphanol and levomethadone was registered. It is concluded that the addition of butorphanol or levomethadone to detomidine increases the nociceptive threshold to somatic pain and prolongs the analgesic effect of detomidine in the horse.
Objective To evaluate the induction and maintenance of anaesthesia using alfaxalone following pre-anaesthetic medication with romifidine and butorphanol in ponies undergoing castration in the field.
Study design Prospective clinical study.
Animals Seventeen male ponies weighing 169 ± 29 kg.
Methods The ponies were sedated with romifidine and butorphanol intravenously (IV). Induction time was recorded following administration of alfaxalone 1 mg kg−1 and diazepam 0.02 mg kg−1 IV. If movement during surgery occurred, alfaxalone 0.2 mg kg−1 was administered IV. The quality of anaesthetic induction, and recovery were scored on a subjective scale of 1 (good) to 5 (poor). The number of attempts to attain sternal recumbency and standing, quality of recovery and times from induction to end of surgery, first head lift, sternal recumbency and standing were recorded.
Results Induction quality was good [median score (range) 1 (1–3)] with a mean ± SD time of 29 ± 6 seconds taken to achieve lateral recumbency. Ten ponies required incremental doses of alfaxalone during surgery. Mean times to the end of surgery, first head lift, sternal recumbency and standing were 26 ± 9 minutes, 31 ± 9 minutes, 33 ± 9 minutes and 34 ± 9 minutes respectively. The number of attempts to attain sternal recumbency was 1(1–1) and to attain standing was 1(1–2). Quality of recovery was good, with a recovery score of 1(1–2).
Conclusions and clinical relevance Alfaxalone provided smooth induction and recovery characteristics and was considered suitable for maintenance of anaesthesia for castration in ponies.
To determine the pharmacokinetics and pharmacodynamics of the neurosteroid anaesthetic, alfaxalone, in neonatal foals after a single intravenous (IV) injection of alfaxalone following premedication with butorphanol tartrate.
Prospective experimental study.
Five clinically healthy Australian Stock Horse foals of mean ± SD age of 12 ± 3 days and weighing 67.3 ± 12.4 kg.
Foals were premedicated with butorphanol (0.05 mg kg(-1) IV) and anaesthesia was induced 10 minutes later by IV injection with alfaxalone 3 mg kg(-1) . Cardiorespiratory variables (pulse rate, respiratory rate, direct arterial blood pressure, arterial blood gases) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and alfaxalone plasma concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis.
The harmonic, mean ± SD plasma elimination half life (t½) for alfaxalone was 22.8 ± 5.2 minutes. The observed mean plasma clearance (Cl(p) ) and volume of distribution (Vd) were 19.9 ± 5.9 mL minute kg(-1) and 0.6 ± 0.2 L kg(-1) , respectively. Overall, the quality of the anaesthetic inductions and recoveries was good and most monitored physiological variables were clinically acceptable in all foals, although some foals became hypoxaemic for a short period following recumbency. The mean durations of anaesthesia from induction to first movement and from induction to standing were 18.7 ± 7 and 37.2 ± 4.7 minutes, respectively.
The anaesthetic protocol used provided a predictable and consistent plane of anaesthesia in the five foals studied, with minimal cardiovascular depression. In foals, as in the adult horse, alfaxalone has a short elimination half life.
Alfaxalone appears to be an adequate anaesthetic induction agent in foals and the pharmacokinetics suggest that, with continuous infusion, it might be suitable to provide more prolonged anaesthesia. Oxygen supplementation is recommended.
Romifidine HCl (romifidine) is an α2-agonist commonly used in horses. This study was undertaken to investigate the pharmacokinetics (PK) of romifidine following intravenous (i.v.) administration and describe the relationship between PK parameters and simultaneously recorded pharmacodynamic (PD) parameters. Romifidine (80μg/kg) was administered by i.v. infusion over 2min to six adult Thoroughbred horses, and plasma samples were collected and analyzed using liquid chromatography-mass spectrometry. Limit of quantification was <0.1ng/mL. PD parameters and arterial blood gases were measured for 300min following romifidine administration. Statistical PD data analysis included mixed-effect modeling. After i.v. administration of romifidine, the plasma concentration-vs.-time curve was best described by a two-compartmental model. Terminal elimination half-life (t1/2β) was 138.2 (104.6-171.0)min and volumes for central (Vc) and peripheral (V2) compartments were 1.89 (0.93-2.39) and 2.57 (1.71-4.19)L/kg, respectively. Maximum plasma concentration (Cmax) was 51.9±13.1ng/mL measured at 4min following commencement of drug administration. Systemic clearance (Cl) was 32.4 (25.5-38.4) mL·min/kg. Romifidine caused a significant reduction in heart rate and cardiac index and an increase in mean arterial pressure (P<0.05). Sedation score and head height values were significantly different from the baseline values for 120min (P<0.05). The decline in cardiovascular and sedative effects correlated with the decline in plasma romifidine concentration (P<0.05). In conclusion, a highly sensitive analytical technique for the detection of romifidine in equine plasma allowed detailed description of its PK profile. The drug produces long-lasting sedation in horses that corresponds with the long terminal elimination half-life of the drug.
To compare the anaesthetic and cardiopulmonary effects of alfaxalone with propofol when used for total intravenous anaesthesia (TIVA) during ovariohysterectomy in dogs.
A prospective non-blinded randomized clinical study.
Fourteen healthy female crossbred bitches, aged 0.5-5 years and weight 16-42 kg.
Dogs 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.
Both 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.
Following 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.
To compare the cardiorespiratory effects and quality of induction of and recovery from anaesthesia following etomidate or alphaxalone-HPCD IV.
Randomized 'blinded' cross-over study. Twenty-four hours was allowed between phases.
Eight healthy adult Beagles (four male, four female).
Dogs were anaesthetized with sevoflurane for instrumentation, then allowed to awake. They then received etomidate (treatment E) or alphaxalone-HPCD (treatment A) intravenously to effect. Heart rate (HR), body temperature, invasive arterial pressures (AP), systemic vascular resistance index (SVRI), stroke volume index, cardiac index (CI), contractility, respiratory rate, central venous pressure, and capnometry were obtained before anaesthetic induction (baseline), 30 seconds and 1 minute after induction, after intubation, one minute after intubation, and for every 5 minutes afterwards until the dog began to swallow and the trachea was extubated. Arterial bloods were taken for analyses before induction, after intubation and every 10 minutes thereafter. The dogs breathed room air. The quality of induction of and recovery from anaesthesia were scored categorically. Statistical analyses used anova for repeated measures, paired t-tests or Wilcoxon signed rank-test as relevant. Significance was set at p < 0.05.
The induction doses required were (mean ± SD) 2.91 ± 0.41 mg kg(-1) and 4.15 ± 0.7 mg kg(-1) for treatment E and A respectively. No significant changes in cardiovascular parameters were observed with treatment E. Treatment A resulted in statistically significant increases in HR and CI and reductions of APs and SVRI. Time to extubation was longer with treatment A (25 ± 7 minutes) than with treatment E (17 ± 4 minutes). Dogs became hypoxic with both treatments. The quality of induction and recovery were excellent with treatment A, but significantly less satisfactory with treatment E (recovery score, treatment E median 1, range 0-2; treatment A median 0, range 0-1).
Alphaxalone-HPCD caused significant tachycardia and increase in CI, and statistically (but not clinically) significant decreases in APs and SVRI. Etomidate caused no statistically significant cardiovascular changes. Quality of recovery was better with alfaxalone-HPCD. Both agents caused short-lived hypoxia, and oxygen supplementation is advisable.
Objectives To document the equine perioperative mortality rate and to highlight any factor associated with an increased risk of death up to 7 days after anaesthesia.
Study design A prospective observational epidemiological multicentre study.
Methods Data were recorded from all equidae undergoing general anaesthesia in 62 clinics. Power calculations indicated that 45 000 cases were required to detect the significance of important variables. Details of each horse, operation, anaesthetic agents and clinic personnel were recorded. Outcome at 7 days was recorded as: alive, put to sleep (PTS) or dead. Data were analysed by a standard multilevel logistic regression approach, considering the effects of clustering at the level of clinic.
Results Data were collected from 41 824 cases over 6 years. A total of 39 025 (93.3%) were alive on day 7 and 785 were dead giving an overall death rate of 1.9% (95% CI: 1.8–2.0) and 2014 (4.8%) were PTS. About 5846 horses undergoing emergency abdominal surgeries (‘colics’) were excluded from subsequent analyses. A total of 35 107 ‘noncolic’ horses were alive at 7 days and 328 dead giving a death rate for noncolics of 0.9% (95% CI: 0.8–1.0). Five hundred and forty-three (1.5%) noncolic horses classified PTS were excluded from further analyses. There were 109 (33%) deaths from cardiac arrest or post-operative cardiovascular collapse, with 107 (32%) from fractures and myopathies. Fracture repair, out of hours surgery, and age below 1 month was associated with increased risk of dying whereas the use of acepromazine and intravenous anaesthetic agent maintenance of anaesthesia was associated with reduced risk.
Conclusions A number of potential contributors to the high risk of anaesthetic-related mortality have been identified. Further investigation of the underlying mechanism for their apparent harmful effects and development of alternative techniques is merited.
To determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin.
Prospective experimental study.
Ten (five male and five female), adult, healthy, Standardbred horses.
Horses were premedicated with acepromazine (0.03 mg kg(-1) IV). Twenty minutes later they received xylazine (1 mg kg(-1) IV), then after 5 minutes, guaiphenesin (35 mg kg(-1) IV) followed immediately by IV induction of anaesthesia with alfaxalone (1 mg kg(-1) ). Cardiorespiratory variables (pulse rate, respiratory rate, pulse oximetry) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and plasma concentrations of alfaxalone were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. The quality of anaesthetic induction and recovery was scored on a scale of 1-5 (1 very poor, 5 excellent).
The median (range) induction and recovery scores were 4 (3-5) (good: horse slowly and moderately gently attained recumbency with minimal or no rigidity or paddling) and 4 (1-5) (good: horse stood on first attempt with some knuckling and ataxia) respectively. The monitored cardiopulmonary variables were within the range expected for clinical equine anaesthesia. The mean ± SD durations of anaesthesia from induction to sternal recumbency and from induction to standing were 42.7 ± 8.4 and 47 ± 9.6 minutes, respectively. The mean ± SD plasma elimination half life (t(1/2) ), plasma clearance (Clp) and volume of distribution (V(d) ) for alfaxalone were 33.4 minutes, 37.1 ± 11.1 mL minute(-1) kg(-1) and 1.6 ± 0.4 L kg(-1) , respectively.
Alfaxalone, in a 2-hydroxypropyl-beta-cyclodextrin formulation, provides anaesthesia with a short duration of recumbency that is characterised by a smooth induction and satisfactory recovery in the horse. As in other species, alfaxalone is rapidly cleared from the plasma in the horse.
The aim of this randomised, observer-blinded, crossover study was to compare the effects of six treatments, administered intravenously to six horses: saline and saline (S/S); detomidine and saline (D/S); detomidine and 5 µg/kg buprenorphine (D/B5); detomidine and 7.5 µg/kg buprenorphine (D/B7.5); detomidine and 10 µg/kg buprenorphine (D/B10); and detomidine and 25 µg/kg butorphanol (D/BUT). The detomidine dose was 10 µg/kg for all treatments in which it was included. Sedation was subjectively assessed and recorded on a visual analogue scale. Peak sedation, duration of sedation and the area under the curve (AUC) for sedation scores were investigated using a univariate general linear model with post-hoc Tukey tests (P<0.05). Peak sedation and duration of sedation were statistically significantly different between treatments (P<0.001). No sedation was apparent after administration of S/S. The AUC was significantly different between treatments (P=0.010), with S/S being significantly different from D/S, D/BUT, D/B5 and D/B7.5, but not D/B10 (P=0.051).
To compare alfaxalone with ketamine for total intravenous anaesthesia in ponies undergoing castration.
Prospective, randomised, blinded clinical study.
Forty-two, 12-month-old Welsh Mountain ponies.
Ponies were assigned randomly to receive ketamine or alfaxalone. After administration of romifidine 100 μg kg(-1) and butorphanol 50 μg kg(-1) intravenously (IV), sedation and response to tactile stimulation were scored. If sedation was insufficient, romifidine 30 μg kg(-1) was administered IV. Anaesthesia was induced with ketamine 2.2 mg kg(-1) or alfaxalone 1 mg kg(-1) , both in combination with diazepam 20 μg kg(-1) IV. Time from end of injection to lateral recumbency was recorded. Simple descriptive scores were used to score quality of induction, surgical conditions and recovery. Ketamine 0.5 mg kg(-1) or alfaxalone 0.2 mg kg(-1) were administered if movement was observed. Times to first head lift, sternal recumbency and standing, and number of attempts needed were recorded. All scores were performed by the same observer, unaware of treatment. Normally distributed data were compared using t-test and non-normally distributed data with Mann-Whitney test. Level of significance was set at p<0.05.
Three ponies needed additional sedation. Mean induction times were 30 ± 6 and 18 ± 4 seconds following ketamine and alfaxalone respectively (p<0.0001). Additional doses were required by four ponies given ketamine and seven given alfaxalone. Sedation, induction and surgical scores were similar for both groups. Recovery scores (scale of 1-4 with 1 best) differed statistically between groups [ketamine group, median 1 (1-2); alfaxalone group 1.5 (1-4) (p=0.04)]. No differences in anaesthesia time or times taken from end of surgery to head lift, sternal recumbency and standing were detected.
Induction times following alfaxalone were shorter than following ketamine. Both anaesthetic agents provided acceptable quality of anaesthesia for castration.
Thesis (Ph. D.)--University of London, 1999.
To evaluate the effects of local anaesthesia with lidocaine for castration of horses under intravenous anaesthesia.
Prospective, randomized, blinded clinical trial.
Fifteen equidae, scheduled to undergo castration under total intravenous anaesthesia, were randomly distributed in two groups. One group received lidocaine injections (group L: two ponies, four horses, two donkeys) and the other received saline (group S: two ponies, three horses, two donkeys).
Behaviour, heart rate (HR) and respiratory rate (f(R)) were evaluated prior to anaesthesia. Body mass was measured using an electronic scale and testicular volumes were estimated. The animals were anaesthetized with acepromazine intramuscularly and romifidine intravenously followed 10 minutes later by ketamine. Following romifidine administration lidocaine or saline was administered subcutaneously along the incision line and by intratesticular and intrafunicular injection. Based on clinical observations (movement, f(R), and cranial nerve reflexes) incremental intravenous doses of ketamine and romifidine were administered. HR, f(R), oscillometric mean arterial blood pressure (MAP), duration of surgery, movement and additional doses were recorded. Surgical conditions were assessed using a visual analogue scale (VAS) and a simple descriptive scale (SDS). Recovery was assessed by two assistants, unaware of treatment, acting separately using a VAS and a SDS. Group means were compared using Mann-Whitney and Wilcoxon tests and the Kruskal-Wallis signed rank test for matched pairs used to compare groups at different points (p < 0.05).
The number (median, range) of incremental doses (4 [1-5] compared to 1.5 [1-4]) and movements (1 [1-5] compared to 0 [0-1]) were higher (p = 0.01 for both) in the control group than in the lidocaine group. Groups were similar for other recorded variables.
These results show the effectiveness of lidocaine used as a local anaesthetic adjunct to intravenous anaesthesia in horses undergoing castration.
Objective-To compare the cardiopulmonary effects of continuous rate infusions (CRIs) of alfaxalone-2-hydroxypropyl-beta-cyclodextrin (HPCD) and propofol in healthy dogs. Animals-6 young adult medium-sized healthy crossbred dogs. Procedures-A crossover design was used with a washout period of 6 days between anesthetic treatments. Each dog was sedated with acepromazine (0.02 mg/kg, IV) and hydromorphone (0.05 mg/kg, IV). Anesthesia was induced with propofol (4 mg/kg) or alfaxalone-HPCD (2 mg/kg). After endotracheal intubation, anesthesia was maintained with the same agent (propofol, 0.25 mg/kg/min; alfaxalone-HPCD, 0.07 mg/kg/min) for 120 minutes. Dogs spontaneously breathed 100% oxygen. Measurements included end-tidal partial pressure of carbon dioxide, heart and respiratory rates, mean arterial blood pressure, thermodilution-derived cardiac output, and body temperature. Paired arterial and mixed venous blood samples were collected for determination of blood pH, PaCO(2), and PaO(2). Data were recorded prior to induction; 5, 15, 30, 60, 90, and 120 minutes after induction of anesthesia; and 20 minutes after stopping the CRI, when feasible. Stroke volume and systemic vascular resistance were calculated. Quality of anesthetic induction and recovery and interval to recovery were recorded. Results-Both propofol and alfaxalone-HPCD produced excellent induction of anesthesia, maintenance, and recovery. Respiratory depression was evident with both anesthetics. Clinically acceptable, mild hemodynamic changes were similar for both anesthetics. Conclusions and Clinical Relevance-Alfaxalone-HPCD produced clinically acceptable anesthetic quality and hemodynamic values ideal for use as a CRI. Ventilation may need to be supported if hydromorphone is used at these propofol and alfaxalone-HPCD infusion rates. (Am J Vet Res 2008;69:1391-1398).
The cardiovascular effects of xylazine and detomidine in horses were studied. Six horses were given each of the following 5 treatments, at 1-week intervals: xylazine, 1.1 mg/kg, IV; xylazine, 2.2 mg/kg, IM; detomidine, 0.01 mg/kg, IV; detomidine, 0.02 mg/kg, IV; and detomidine, 0.04 mg/kg, IM. All treatments resulted in significantly decreased heart rate, increased incidence of atrioventricular block, and decreased cardiac output and cardiac index; cardiac output and cardiac index were lowest following IV administration of 0.02 mg of detomidine/kg. Mean arterial pressure was significantly reduced for various periods with all treatments; however, IV administration of 0.02 mg of detomidine/kg caused hypertension initially. Systemic vascular resistance was increased by all treatments. Indices of ventricular contractility and relaxation, +dP/dt and -dP/dt, were significantly depressed by all treatments. Significant changes were not detected in stroke volume or ejection fraction. The PCV was significantly reduced by all treatments. Respiratory rate was significantly decreased with all treatments, but arterial carbon dioxide tension did not change. Arterial oxygen tension was significantly decreased briefly with the 3 IV treatments only.
Ventilation-perfusion relationships were studied by the multiple inert gas elimination technique in seven horses while they were conscious and during inhalation anaesthesia with halothane. A generally good match between ventilation and perfusion was found in the conscious, standing horse. During anaesthesia a huge shunt developed, ie perfusion of completely unventilated lung regions, both in dorsal and left lateral recumbency and whether the horse was breathing spontaneously or mechanically ventilated. The shunt was significantly greater and the arterial oxygen tension (PaO2) significantly lower in dorsal than in left lateral recumbency. Little or no perfusion of low VA/Q regions was observed during anaesthesia, whether ventilation was spontaneous or mechanical. Positive end-expiratory pressure (PEEP) did not significantly improve PaO2 or reduce the shunt. Selective mechanical ventilation of dependent lung regions with PEEP reduced the shunt markedly, an effect that was not achieved by conventional mechanical ventilation with general PEEP. The findings seem compatible with alveolar collapse during anaesthesia, causing shunt, whereas the absence of clearly low VA/Q regions questions the role of airway closure as the major disturbance of gas exchange.
To examine the clinical suitability of medetomidine-propofol infusions for total intravenous anaesthesia in horses.
Fifty client-owned horses of mixed breed, age [mean +/- SD (range)] 6.6 +/- 4.4 (0.04-18) years, mass 478 +/- 168.3 (80-700) kg presented for a range of operations requiring general anaesthesia.
Pre-anaesthetic medication was intravenous (IV) medetomidine 7 mug kg(-1). Anaesthesia was induced with IV ketamine (2 mg kg(-1)) and diazepam (0.02 mg kg(-1)). After endotracheal intubation, O2 was delivered (FiO2 > 0.85). Positive pressure ventilation was initiated if breath-holding in excess of 1 minute occurred. Anaesthesia was maintained with a constant rate medetomidine infusion (3.5 microg kg(-1) hour(-1)) and propofol infused IV to effect (initial dose 0.1 mg kg(-1) minute(-1)). Heart (HR) respiratory (fr) and propofol administration rates, and systemic arterial blood pressures were recorded at 5-minute intervals. Arterial blood gas (O2 and CO2) tensions and pH values were recorded every 15 minutes. Ten minutes after ending medetomidine-propofol infusion, medetomidine (2 microg kg(-1); IV) was given. Cardiopulmonary data were analysed using descriptive statistical techniques.
Thirty-three orthopaedic, seven integumentary and 10 elective abdominal operations were performed. Cardiopulmonary data, presented as range of mean individual (and absolute individual minimum and maximum values) were: HR: 28.0-39.2 (16-88) beats minute(-1); mean arterial blood pressure: 74.0-132.5 (42-189) mmHg; PaO2: 22.1-42.9 (4.9-67.8) kPa; [166-322 (37-508) mmHg], PaCO2: 6.7-8.1 (4.2-11.8) kPa [50-61 (32-88) mmHg] and pH 7.35-7.39 (7.15-7.48). Positive pressure ventilation was required in 23 horses. In three horses, HR values below 20 beats minute(-1) were treated with 20 microg kg(-1) atropine (IV). Mean propofol infusion rates were 98-108 microg kg(-1) minute(-1). During anaesthesia, movement occurring in 14 horses was controlled with thiopental. Duration of anaesthesia was 111.6 +/- 41.4 (46-225) minutes. Recovery in all horses was uneventful and completed within 42.2 +/- 19.8 (12-98) minutes.
Medetomidine-propofol infusion produces adequate conditions for a range of surgical procedures. Cardiovascular function was adequate, as no pressor agents were required. Positive pressure ventilation was required in 23 horses.