Wendy Goodwin

Continuous digital hypothermia initiated after the onset of lameness prevents lamellar failure in the oligofructose laminitis model.

REASONS FOR PERFORMING STUDY Prophylactic digital hypothermia reduces the severity of acute laminitis experimentally but there is no evidence for its efficacy as a treatment once lameness has already developed. OBJECTIVES To investigate the therapeutic effects of digital hypothermia, applied after the onset of lameness, in an experimental acute laminitis model. STUDY DESIGN Randomised, controlled (within subject), blinded, experimental trial. METHODS Eight Standardbred horses underwent laminitis induction using the oligofructose model. Once lameness was detected at the walk, one forelimb was continuously cooled (CRYO), with the other forelimb maintained at ambient temperature (NON-RX). Dorsal lamellar sections (proximal, middle and distal) harvested 36 h after the onset of lameness/initiation of cryotherapy were analysed by 2 blinded observers: laminitis pathology was scored (0 [normal] to 4 [severe]) and morphometric analyses performed. RESULTS Median (interquartile range) histological scores were greater (P<0.05) in NON-RX (proximal 2.8 [2.5-4]; middle 3.5 [2-4]; distal 2.5 [2-3.8]) compared with CRYO limbs (proximal 0.5 [0.5-1.4]; middle 1 [0.6-1]; distal 0.75 [0.5-1]). There was complete physical separation of lamellar dermis from epidermis (score of 4) in 4 of the NON-RX feet at one or more section level(s), which was not observed in any CRYO sections. Histomorphometry was thus limited to sections that remained intact; there was a trend of increased total (TELL) and secondary (SELL) epidermal lamellar length and decreased secondary epidermal lamellar width (SELW) in NON-RX limbs compared with CRYO at all 3 levels; differences were significant (P<0.05) for SELL and SELW in the distal sections. CONCLUSIONS Digital hypothermia reduced the severity of lamellar injury and prevented lamellar structural failure (complete dermoepidermal separation) when initiated at the detection of lameness in an acute laminitis model. This study provides the first evidence to support the use of therapeutic digital hypothermia as a treatment for acute laminitis.

The pharmacokinetics and pharmacodynamics of the injectable anaesthetic alfaxalone in the horse

OBJECTIVE 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. STUDY DESIGN Prospective experimental study. ANIMALS Ten (five male and five female), adult, healthy, Standardbred horses. METHODS 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). RESULTS 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. CONCLUSIONS AND CLINICAL RELEVANCE 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.

Plasma pharmacokinetics and pharmacodynamics of alfaxalone in neonatal foals after an intravenous bolus of alfaxalone following premedication with butorphanol tartrate

OBJECTIVE 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. STUDY DESIGN Prospective experimental study. ANIMALS Five clinically healthy Australian Stock Horse foals of mean ± SD age of 12 ± 3 days and weighing 67.3 ± 12.4 kg. METHODS 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. RESULTS 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. CONCLUSIONS 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. CLINICAL RELEVANCE 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.

Alfaxalone and medetomidine intravenous infusion to maintain anaesthesia in colts undergoing field castration

REASONS FOR PERFORMING THE STUDY The 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. HYPOTHESIS Alfaxalone-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. RESULTS Overall, 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 RELEVANCE The 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.

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. 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 horses 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.