Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies

ObjectiveTo evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies.Study designProspective single-group interventional study.AnimalsA group of six healthy adult research ponies (four mares, two geldings).MethodsPonies were sedated with intravenous (IV) detomidine (0.02 mg kg^–1) and butorphanol (0.01 mg kg^–1) for an unrelated study. Additional IV detomidine (0.004 mg kg^–1) was administered 85 minutes later, followed by induction of anaesthesia using IV diazepam (0.05 mg kg^–1) and ketamine (2.2 mg kg^–1). Anaesthesia was maintained with isoflurane in oxygen. Baseline readings were taken after 15 minutes of stable isoflurane anaesthesia. l-Methadone (0.25 mg kg^–1) with fenpipramide (0.0125 mg kg^–1) was then administered IV. Selected cardiorespiratory variables were recorded every 10 minutes and compared to baseline using the Wilcoxon signed-rank test. Adverse events were recorded. Arterial plasma samples for analysis of plasma concentrations and pharmacokinetics of l-methadone were collected throughout anaesthesia at predetermined time points. Data are shown as mean ± standard deviation or median and interquartile range (p < 0.05).ResultsPlasma concentrations of l-methadone showed a rapid initial distribution phase followed by a slower elimination phase which is best described with a two-compartment model. The terminal half-life was 44.3 ± 18.0 minutes, volume of distribution 0.43 ± 0.12 L kg^–1 and plasma clearance 7.77 ± 1.98 mL minute^–1 kg^–1. Mean arterial blood pressure increased from 85 (±16) at baseline to 100 (±26) 10 minutes after l-methadone/fenpipramide administration (p = 0.031). Heart rate remained constant. In two ponies fasciculations occurred at different time points after l-methadone administration.Conclusions and clinical relevanceAdministration of a l-methadone/fenpipramide combination to isoflurane anaesthetized ponies led to a transient increase in blood pressure without concurrent increases in heart rate. Pharmacokinetics of l-methadone were similar to those reported for conscious horses administered racemic methadone.     

Intravenous anaesthesia using detomidine, ketamine and guaiphenesin for laparotomy in pregnant pony mares

Objective To characterize intravenous anaesthesia with detomidine, ketamine and guaiphenesin in pregnant ponies. Animals Twelve pony mares, at 260–320 days gestation undergoing abdominal surgery to implant fetal and maternal vascular catheters. Materials and methods Pre‐anaesthetic medication with intravenous (IV) acepromazine (30 µg kg^?1), butorphanol (20 µg kg^?1) and detomidine (10 µg kg^?1) preceded induction of anaesthesia with detomidine (10 µg kg^?1) and ketamine (2 mg kg^?1) IV Maternal arterial blood pressure was measured directly throughout anaesthesia and arterial blood samples were taken at 20‐minute intervals for measurement of blood gases and plasma concentrations of cortisol, glucose and lactate. Anaesthesia was maintained with an IV infusion of detomidine (0.04 mg mL^?1), ketamine (4 mg mL^?1) and guaiphenesin (100 mg mL^?1) (DKG) for 140 minutes. Oxygen was supplied by intermittent positive pressure ventilation (IPPV) adjusted to maintain PaCO₂ between 5.0 and 6.0 kPa (38 and 45 mm Hg), while PaO₂ was kept close to 20.0 kPa (150 mm Hg) by adding nitrous oxide. Simultaneous fetal and maternal blood samples were withdrawn at 90 minutes. Recovery quality was assessed. Results DKG was infused at 0.67 ± 0.17 mL kg^?1 hour^?1 for 1 hour then reduced, reaching 0.28 ± 0.14 mL kg^?1 hour^?1 at 140 minutes. Arterial blood gas values and pH remained within intended limits. During anaesthesia there was no change in heart rate, but arterial blood pressure decreased by 10%. Plasma glucose and lactate increased (10‐fold and 2‐fold, respectively) and cortisol decreased by 50% during anaesthesia. Fetal umbilical venous pH, PO₂ and PCO₂ were 7.34 ± 0.06, 5.8 ± 0.9 kPa (44 ± 7 mm Hg) and 6.7 ± 0.8 kPa (50 ± 6 mm Hg); and fetal arterial pH, PO₂ and PCO₂ were 7.29 ± 0.06, 4.0 ± 0.7 kPa (30 ± 5 mm Hg) and 7.8 ± 1.7 kPa (59 ± 13 mm Hg), respectively. Surgical conditions were good but four ponies required a single additional dose of ketamine. Ponies took 60 ± 28 minutes to stand and recovery was good. Conclusions and clinical relevance Anaesthesia produced with DKG was smooth while cardiovascular function in mare and fetus was well preserved. This indicates that DKG infusion is suitable for maintenance of anaesthesia in pregnant equidae.     

Evaluation of intramuscular anesthetic protocols in healthy domestic horses

ObjectiveTo assess anesthetic induction, recovery quality and cardiopulmonary variables after intramuscular (IM) injection of three drug combinations for immobilization of horses.Study designRandomized, blinded, three-way crossover prospective design.AnimalsA total of eight healthy adult horses weighing 470–575 kg.MethodsHorses were administered three treatments IM separated by ≥1 week. Combinations were tiletamine–zolazepam (1.2 mg kg⁻¹), ketamine (1 mg kg⁻¹) and detomidine (0.04 mg kg⁻¹) (treatment TKD); ketamine (3 mg kg⁻¹) and detomidine (0.04 mg kg⁻¹) (treatment KD); and tiletamine–zolazepam (2.4 mg kg⁻¹) and detomidine (0.04 mg kg⁻¹) (treatment TD). Parametric data were analyzed using mixed model linear regression. Nonparametric data were compared using Skillings–Mack test. A p value <0.05 was considered statistically significant.ResultsAll horses in treatment TD became recumbent. In treatments KD and TKD, one horse remained standing. PaO₂ 15 minutes after recumbency was significantly lower in treatments TD (p < 0.0005) and TKD (p = 0.001) than in treatment KD. Times to first movement (25 ± 15 minutes) and sternal recumbency (55 ± 11 minutes) in treatment KD were faster than in treatments TD (57 ± 17 and 76 ± 19 minutes; p < 0.0005, p = 0.001) and TKD (45 ± 18 and 73 ± 31 minutes; p = 0.005, p = 0.021). There were no differences in induction quality, muscle relaxation score, number of attempts to stand or recovery quality.Conclusions and clinical relevanceIn domestic horses, IM injections of tiletamine–zolazepam–detomidine resulted in more reliable recumbency with a longer duration when compared with ketamine–detomidine and tiletamine–zolazepam–ketamine–detomidine. Recoveries were comparable among protocols.     

Effect of different inspired fractions of oxygen on F-shunt and arterial partial pressure of oxygen in isoflurane-anaesthetized and mechanically ventilated Shetland ponies

ObjectiveTo determine the effect of fraction of inspired oxygen (FiO₂) on intrapulmonary shunt fraction as measured by F-shunt in ponies during isoflurane anaesthesia.Study designProspective, randomized clinical study.AnimalsA group of 23 adult Shetland ponies undergoing a total of 32 anaesthetic procedures.MethodsPonies were premedicated intravenously (IV) with detomidine (0.01 mg kg^–1) and either morphine (0.1 mg kg^–1) or butorphanol (0.02 mg kg^–1). Anaesthesia was induced with ketamine (2.2 mg kg^–1) and midazolam (0.07 mg kg^–1) administered IV. Ponies were randomly allocated to maintenance of anaesthesia with isoflurane in oxygen (group TH; FiO₂ = 0.95) or a mixture of oxygen and medical air (group TL; FiO₂ = 0.65); all ponies were given a constant rate of infusion of detomidine. Animals were mechanically ventilated to maintain PaCO₂ between 40 and 50 mmHg. Arterial blood gas analysis was performed every 30 minutes. The F-shunt equation was calculated for each time point T0, T30, T60 and T90. Data were analysed using linear mixed model analysis and presented as mean ± standard deviation (p < 0.05).ResultsPaO₂ was greater in group TH than in group TL (TH: 406 ± 90, 438 ± 83, 441 ± 69 and 464 ± 53 mmHg versus TL: 202 ± 90, 186 ± 84, 172 ± 85 and 191 ± 98 mmHg at T0, T30, T60 and T90, respectively; p < 0.0001). In TH, F-shunt was < TL. Significant differences were found at T60 (TH: 13.2% ± 4.3 versus TL: 19.4% ± 8.3; p = 0.016) and T90 (TH: 11.7% ± 3.5 versus TL: 18.6% ± 9.5; p = 0.036).Conclusions and clinical relevanceOur findings do not support a beneficial effect of using a reduced FiO₂ to improve oxygenation in anaesthetized and mechanically ventilated Shetland ponies.     

The influence of body mass and thoracic dimensions on arterial oxygenation in anaesthetized horses and ponies

ObjectiveTo examine the relationship between body mass and thoracic dimensions on arterial oxygen tensions (PaO₂) in anaesthetized horses and ponies positioned in dorsal recumbency.Study designProspective clinical study.AnimalsThirty six client-owned horses and ponies, mean [±SD (range)] age 8.1 ± 4.8 (1.5–20) years and mean body mass 467 ± 115 (203–656) kg.MethodsBefore general anaesthesia, food and water were withheld for 12 and 1 hours respectively. Body mass (kg), height at the withers (H), thoracic circumference (C), thoracic depth (length between dorsal spinous process and sternum; D), thoracic width (between point of shoulders; W), and thoracic diagonal length (point of shoulder to last rib; L) were measured. Pre-anaesthetic medication was with intravenous (IV) romifidine (0.1 mg kg⁻¹). Anaesthesia was induced with an IV ketamine (2.2 mg kg⁻¹) and diazepam (0.05 mg kg⁻¹) combination and maintained with halothane in 1:1 oxygen:nitrous oxide (N₂O) mixture. Animals were positioned in dorsal recumbency and allowed to breathe spontaneously. Nitrous oxide was discontinued after 10 minutes, and arterial blood samples obtained and analysed for gas tensions at 15, 30 and 60 minutes after connection to the anaesthetic breathing circuit. Data were analysed using anova and Pearson's correlation co-efficient.ResultsThe height per unit body mass (H kg⁻¹) and thoracic circumference per unit body mass (C kg⁻¹) correlated strongly (r = 0.85, p < 0.001 and r = 0.82, p < 0.001 respectively) with arterial oxygen tensions (PaO₂) at 15 minutes.ConclusionsThere is a strong positive correlation between H kg⁻¹ and C kg⁻¹ and PaO₂ after 15 minutes of anaesthesia in halothane-anaesthetized horses positioned in dorsal recumbency.Clinical relevanceReadily obtained linear measurements (height and thoracic circumference) and body mass may be used to predict the ability of horses to oxygenate during anaesthesia.     

Propofol anaesthesia for surgery in late gestation pony mares

Objective To characterize propofol anaesthesia in pregnant ponies. Animals Fourteen pony mares, at 256 ± 49 days gestation, undergoing abdominal surgery to implant fetal and maternal vascular catheters. Materials and methods Pre‐anaesthetic medication with intravenous (IV) acepromazine (20 µg kg^?1), butorphanol (20 µg kg^?1) and detomidine (10 µg kg^?1) was given 30 minutes before induction of anaesthesia with detomidine (10 µg kg^?1) and ketamine (2 mg kg^?1) IV Maternal arterial blood pressure was recorded (facial artery) throughout anaesthesia. Arterial blood gas values and plasma concentrations of glucose, lactate, cortisol and propofol were measured at 20‐minute intervals. Anaesthesia was maintained with propofol infused initially at 200 µg kg^?1 minute^?1, and at 130–180 µg kg^?1 minute^?1 after 60 minutes, ventilation was controlled with oxygen and nitrous oxide to maintain PaCO₂ between 5.0 and 6.0 kPa (37.6 and 45.1 mm Hg) and PaO₂ between 13.3 and 20.0 kPa (100 and 150.4 mm Hg). During anaesthesia flunixin (1 mg kg^?1), procaine penicillin (6 IU) and butorphanol 80 µg kg^?1 were given. Lactated Ringer's solution was infused at 10 mL kg^?1 hour^?1. Simultaneous fetal and maternal blood samples were withdrawn at 85–95 minutes. Recovery from anaesthesia was assisted. Results Arterial blood gas values remained within intended limits. Plasma propofol levels stabilized after 20 minutes (range 3.5–9.1 µg kg^?1); disposition estimates were clearance 6.13 ± 1.51 L minute^?1 (mean ± SD) and volume of distribution 117.1 ± 38.9 L (mean ± SD). Plasma cortisol increased from 193 ± 43 nmol L^?1 before anaesthesia to 421 ± 96 nmol L^?1 60 minutes after anaesthesia. Surgical conditions were excellent. Fetal umbilical venous pH, PO₂ and PCO₂ were 7.35 ± 0.04, 6.5 ± 0.5 kPa (49 ± 4 mm Hg) and 6.9 ± 0.5 kPa (52 ± 4 mm Hg); fetal arterial pH, PO₂ and PCO₂ were 7.29 ± 0.06, 3.3 ± 0.8 kPa (25 ± 6 mm Hg) and 8.7 ± 0.9 kPa (65 ± 7 mm Hg), respectively. Recovery to standing occurred at 46 ± 17 minutes, and was generally smooth. Ponies regained normal behaviour patterns immediately. Conclusions and clinical relevance Propofol anaesthesia was smooth with satisfactory cardiovascular function in both mare and fetus; we believe this to be a suitable anaesthetic technique for pregnant ponies.     

Clinical evaluation of ketamine and lidocaine intravenous infusions to reduce isoflurane requirements in horses under general anaesthesia

ObjectiveTo compare isoflurane alone or in combination with systemic ketamine and lidocaine for general anaesthesia in horses.Study designProspective, randomized, blinded clinical trial.AnimalsForty horses (ASA I-III) undergoing elective surgery.MethodsHorses were assigned to receive isoflurane anaesthesia alone (ISO) or with ketamine and lidocaine (LKI). After receiving romifidine, diazepam, and ketamine, the isoflurane end-tidal concentration was set at 1.3% and subsequently adjusted by the anaesthetist (unaware of treatments) to maintain a light plane of surgical anaesthesia. Animals in the LKI group received lidocaine (1.5 mg kg⁻¹ over 10 minutes, followed by 40 μg kg⁻¹ minute⁻¹) and ketamine (60 μg kg⁻¹ minute⁻¹), both reduced to 65% of the initial dose after 50 minutes, and stopped 15 minutes before the end of anaesthesia. Standard clinical cardiovascular and respiratory parameters were monitored. Recovery quality was scored from one (very good) to five (very poor). Differences between ISO and LKI groups were analysed with a two-sample t-test for parametric data or a Fischer's exact test for proportions (p < 0.05 for significance). Results are mean ± SD.ResultsHeart rate was lower (p = 0.001) for LKI (29 ± 4) than for ISO (34 ± 6). End-tidal concentrations of isoflurane (ISO: 1.57% ± 0.22; LKI: 0.97% ± 0.33), the number of horses requiring thiopental (ISO: 10; LKI: 2) or dobutamine (ISO:8; LKI:3), and dobutamine infusion rates (ISO:0.26 ± 0.09; LKI:0.18 ± 0.06 μg kg⁻¹ minute⁻¹) were significantly lower in LKI compared to the ISO group (p < 0.001). No other significant differences were found, including recovery scores.Conclusions and clinical relevanceThese results support the use of lidocaine and ketamine to improve anaesthetic and cardiovascular stability during isoflurane anaesthesia lasting up to 2 hours in mechanically ventilated horses, with comparable quality of recovery.     

Sedative effects and pharmacokinetics of detomidine when administered intravenously and intravaginally as a gel in alpacas

ObjectivesTo evaluate the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to alpacas in comparison with intravenously (IV) administered detomidine.Study designRandomized, crossover, blinded experiment.AnimalsA group of six healthy adult female Huacaya alpacas (70.3 ± 7.9 kg).MethodsAlpacas were studied on two occasions separated by ≥5 days. Treatments were IV detomidine hydrochloride (70 μg kg⁻¹; treatment DET–IV) or detomidine gel (200 μg kg⁻¹; treatment DET–VAG) administered intravaginally. Sedation and heart rate (HR) were evaluated at intervals for 240 minutes. Venous blood was collected at intervals for 360 minutes after treatment for analysis of detomidine, carboxydetomidine and hydroxydetomidine using liquid chromatography–tandem mass spectrometry. Measured variables were compared between treatments and over time using mixed model analysis. Data are presented as the mean ± standard error of the mean, and a p value of <0.05 was considered significant.ResultsOnset of sedation was faster in treatment DET–IV (1.6 ± 0.2 minutes) than in treatment DET–VAG (13.0 ± 2.5 minutes). Time to maximum sedation was shorter in treatment DET–IV (8.3 ± 1.3 minutes) than in treatment DET–VAG (25 ± 4 minutes). Duration of sedation was not different between treatments. There was a significant linear relationship between sedation score and plasma detomidine concentration. HR was less than baseline for 60 and 125 minutes for treatments DET–IV and DET–VAG, respectively. The maximal decrease in HR occurred at 15 minutes for both treatments. The mean maximum plasma concentration of detomidine, time to maximum concentration and bioavailability for treatment DET–VAG were 39.6 ng mL⁻¹, 19.9 minutes and 20%, respectively.Conclusions and clinical relevanceDetomidine administration at the doses studied resulted in moderate sedation when administered IV or intravaginally to alpacas.     

A clinical study on the effect in horses during medetomidine-isoflurane anaesthesia, of butorphanol constant rate infusion on isoflurane requirements, on cardiopulmonary function and on recovery characteristics

ObjectiveTo test if the addition of butorphanol by constant rate infusion (CRI) to medetomidine–isoflurane anaesthesia reduced isoflurane requirements, and influenced cardiopulmonary function and/or recovery characteristics.Study designProspective blinded randomised clinical trial.Animals61 horses undergoing elective surgery.MethodsHorses were sedated with intravenous (IV) medetomidine (7 μg kg^?1); anaesthesia was induced with IV ketamine (2.2 mg kg^?1) and diazepam (0.02 mg kg^?1) and maintained with isoflurane and a CRI of medetomidine (3.5 μg kg^?1 hour^?1). Group MB (n = 31) received butorphanol CRI (25 μg kg^?1 IV bolus then 25 μg kg^?1 hour^?1); Group M (n = 30) an equal volume of saline. Artificial ventilation maintained end-tidal CO₂ in the normal range. Horses received lactated Ringer’s solution 5 mL kg^?1 hour^?1, dobutamine <1.25 μg kg^?1 minute^?1 and colloids if required. Inspired and exhaled gases, heart rate and mean arterial blood pressure (MAP) were monitored continuously; pH and arterial blood gases were measured every 30 minutes. Recovery was timed and scored. Data were analyzed using two way repeated measures anova, independent t-tests or Mann–Whitney Rank Sum test (p < 0.05).ResultsThere was no difference between groups with respect to anaesthesia duration, end-tidal isoflurane (MB: mean 1.06 ± SD 0.11, M: 1.05 ± 0.1%), MAP (MB: 88 ± 9, M: 87 ± 7 mmHg), heart rate (MB: 33 ± 6, M: 35 ± 8 beats minute^?1), pH, PaO₂ (MB: 19.2 ± 6.6, M: 18.2 ± 6.6 kPa) or PaCO_2. Recovery times and quality did not differ between groups, but the time to extubation was significantly longer in group MB (26.9 ± 10.9 minutes) than in group M (20.4 ± 9.4 minutes).Conclusion and clinical relevanceButorphanol CRI at the dose used does not decrease isoflurane requirements in horses anaesthetised with medetomidine–isoflurane and has no influence on cardiopulmonary function or recovery.     

S‐ketamine versus racemic ketamine in dogs: their relative potency as induction agents

ObjectiveTo determine the potency ratio between S-ketamine and racemic ketamine as inductive agents for achieving tracheal intubation in dogs.Study designProspective, randomized, ‘blinded’, clinical trial conducted in two consecutive phases.Animals112 client-owned dogs (ASA I or II).MethodsAll animals were premedicated with intramuscular acepromazine (0.02 mg kg⁻¹) and methadone (0.2 mg kg⁻¹). In phase 1, midazolam (0.2 mg kg⁻¹) with either 3 mg kg⁻¹ of racemic ketamine (group K) or 1.5 mg kg⁻¹ of S-ketamine (group S) was administered IV, for induction of anaesthesia and intubation. Up to two additional doses of racemic (1.5 mg kg⁻¹) or S-ketamine (0.75 mg kg⁻¹) were administered if required. In phase 2, midazolam (0.2 mg kg⁻¹) with 1 mg kg⁻¹ of either racemic ketamine (group K) or S-ketamine (group S) was injected and followed by a continuous infusion (1 mg kg minute⁻¹) of each respective drug. Differences between groups were statistically analyzed via t-test, Fisher exact test and ANOVA for repeated measures.ResultsDemographics and quality and duration of premedication, induction and intubation were comparable among groups. During phase 1 it was possible to achieve tracheal intubation after a single dose in more dogs in group K (n = 25) than in group S (n = 16) (p = 0.046). A dose of 3 mg kg⁻¹ S-ketamine allowed tracheal intubation in the same number of dogs as 4.5 mg kg⁻¹ of racemic ketamine. The estimated potency ratio was 1.5:1. During phase 2, the total dose (mean ± SD) of S-ketamine (4.02 ±1.56 mg kg⁻¹) and racemic ketamine (4.01 ± 1.42) required for tracheal intubation was similar.Conclusion and clinical relevanceRacemic and S-ketamine provide a similar quality of anaesthetic induction and intubation. S-ketamine is not twice as potent as racemic ketamine and, if infused, the potency ratio is 1:1.     

Sublingual administration of detomidine to calves prior to disbudding: a comparison with the intravenous route

ObjectiveTo study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously (IV) administered detomidine.Study designRandomised, prospective clinical study.AnimalsTwenty dairy calves aged 12.4 ± 4.4days (mean ± SD), weight 50.5 ± 9.0 kg.MethodsDetomidine at 80 μg kg^?1 was administered to ten calves sublingually (GEL) and at 30 μg kg^?1 to ten control calves IV (V. jugularis). Meloxicam (0.5 mg kg^?1) and local anaesthetic (lidocaine 3 mg kg^?1) were administered before heat cauterization of horn buds. Heart rate (HR), body temperature and clinical sedation were monitored over 240 minutes. Blood was collected from the V. cephalica during the same period for drug concentration analysis. Pharmacokinetic variables were calculated from the plasma detomidine concentration-time data using non-compartmental methods. Statistical analyses compared routes of administration by Student’s t-test and linear mixed models as relevant.ResultsThe maximum plasma detomidine concentration after GEL was 2.1 ± 1.2 ng mL^?1 (mean ±SD) and the time of maximum concentration was 66.0 ± 36.9 minutes. The bioavailability of detomidine was approximately 34% with GEL. Similar sedation scores were reached in both groups after administration of detomidine, but maximal sedation was reached earlier in the IV group (10 minutes) than in the GEL group (40 minutes). HR was lower after IV than GEL from 5 to 10 minutes after administration. All animals were adequately sedated, and we were able to administer local anaesthetic without resistance to all of the calves before disbudding.Conclusions and clinical relevanceOromucosally administered detomidine is an effective sedative agent for calves prior to disbudding.     

Effects of dobutamine on cardiovascular function and respiratory gas exchange after enoximone in isoflurane-anaesthetized ponies

ObjectiveTo evaluate the combined effects of enoximone and dobutamine on the cardiovascular system and respiratory gas exchange in isoflurane-anaesthetized ponies.Study designProspective, randomized, experimental study.AnimalsSix ponies (286 ± 52 kg), aged 5.0 ± 1.6 years.MethodsAfter sedation (romifidine 80 μg kg⁻¹), anaesthesia was induced with midazolam (0.06 mg kg⁻¹) and ketamine (2.2 mg kg⁻¹) and maintained with isoflurane in oxygen. The ponies were ventilated to maintain eucapnia. After 90 minutes (=T0), enoximone alone (0.5 mg kg⁻¹) (E) or enoximone, followed by a constant rate infusion of dobutamine (0.5 μg kg⁻¹ minute⁻¹) (ED) for 120 minutes, was administered. Each pony received both treatments in a crossover trial, with at least 2 weeks between treatments. Heart rate (HR), cardiac output (CO), stroke volume (SV), right atrial (RAP), systolic (SAP), diastolic (DAP) and mean arterial pressure (MAP), blood gases, systemic vascular resistance (SVR), oxygen delivery (D⌽O₂) and several respiratory gas exchange variables were measured before treatment and until T120. Statistical analysis was based on a mixed model with treatment, time and their interaction as fixed categorical effects, pony as random effect, comparing treatments globally (α = 0.05) and at specific timepoints (Bonferroni-adjusted α = 0.00625).ResultsCompared to enoximone alone, ED treatment produced an increase in HR, CO, SV, RAP, SAP, DAP, MAP, packed cell volume (PCV) and D⌽O₂. The difference was significant from T60 to T120 (except at T80) for HR, throughout the observational period for CO, SAP, MAP, PCV and D⌽O₂, from T40 to T120 for DAP, at T10,T60,T80 and T120 for SV and at T10 and T20 for RAP. Overall decreases occurred in SVR and dead space ventilation (V_D/V_T). V_D/V_T was lower at T20 and from T80 to T120. Venous oxygen saturation was increased from T60 onwards.Conclusions and clinical relevanceThe results suggest that enoximone and dobutamine have additive cardiovascular effects and reduce V_D/V_T in isoflurane-anaesthetized ponies.     

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

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

Detomidine and the combination of detomidine and MK‐467, a peripheral alpha‐2 adrenoceptor antagonist,as premedication in horses anaesthetized with isoflurane

ObjectiveTo investigate MK-467 as part of premedication in horses anaesthetized with isoflurane.Study designExperimental, crossover study with a 14 day wash-out period.AnimalsSeven healthy horses.MethodsThe horses received either detomidine (20 μg kg⁻¹ IV) and butorphanol (20 μg kg⁻¹ IV) alone (DET) or with MK-467 (200 μg kg⁻¹ IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg⁻¹) and midazolam (0.06 mg kg⁻¹) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO₂) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index (CI), systemic vascular resistance (SVR), ratio of arterial oxygen tension to inspired oxygen (P_aO₂/FiO₂) and tissue oxygen delivery (DO₂) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p < 0.05.ResultsThe induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+MK, while SVR was higher with DET. Arterial oxygen tension and P_aO₂/FiO₂ (40 minutes after induction), DO₂ and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+MK. Plasma detomidine concentrations were reduced in the group receiving MK-467. After DET+MK, the area under the plasma concentration time curve of butorphanol was smaller.Conclusions and clinical relevanceMK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP.     

Chemical restraint of African mole‐rats (Fukomys sp.) with a combination of ketamine and xylazine

ObjectiveTo establish an accurate anaesthetic dose for chemical restraint of African mole-rats using ketamine and xylazine.Study designProspective nonrandomized laboratory study.AnimalsSixteen adult Ansell’s mole-rats (Fukomys anselli) and eight giant mole-rats (F. mechowii).MethodsFukomys anselli of different ages, sexes and reproductive status were systematically anaesthetized starting with an intramuscular injection of ketamine (2.5 mg kg⁻¹) and increasing the doses in steps of 0.5 mg kg⁻¹ until loss of the righting reflex (LRR) was observed. Xylazine was added to a constant dose of ketamine, starting at 0.5 mg kg⁻¹ that was increased by 0.5 mg kg⁻¹ in further trials. Once an effective combination was established and evaluated in F. anselli, it was also tested in F. mechowii. Heart and respiratory rates and rectal temperatures were measured during anaesthesia. anova for repeated measures and Student’s t-test were used to compare means.ResultsChemical restraint was accomplished at a dose of 6 mg kg⁻¹ ketamine combined with 2.5 mg kg⁻¹ xylazine. LRR lasted on average mean 56 ± SD 19 minutes (F. anselli) and 140 ± 41 minutes (F. mechowii). Loss of pedal withdrawal reflex (LPR) lasted for 20 ± 15 minutes (F. anselli) and for 29 ± 2 minutes (F. mechowii), respectively. All animals recovered satisfactorily. Heart and respiratory rates were stable during anaesthesia, but rectal temperature fell significantly in F. mechowii after losing the righting reflex (LRR) from T1 (32.6 ± 0.6 °C) to T3 (30.4 ± 0.9 °C).Conclusions and Clinical relevanceAfrican mole-rats (Bathyergidae) live in closed burrow systems under particular conditions (hypercapnia, hypoxia, stable temperature, humidity, darkness) and show several physiological adaptations. Injectable anaesthetics in the dose rates used in other rodents are not appropriate for use in these subterranean species. Here, a reliable protocol for chemical restraint is provided.     

Anti‐nociceptive and sedative effects of romifidine,tramadol and their combination administered intravenously slowly in ponies

ObjectiveTo evaluate the anti-nociceptive and sedative effects of slow intravenous (IV) injection of tramadol, romifidine, or a combination of both drugs in ponies.Study designWithin-subject blinded.AnimalsTwenty ponies (seven male, 13 female, weighing mean ± SD 268.0 ± 128 kg).MethodsOn separate occasions, each pony received one of the following three treatments IV; romifidine 50 μg kg⁻ (R) tramadol 3 mg kg⁻¹ given over 15 minutes (T) or tramadol 3 mg kg⁻¹followed by romifidine 50 μg kg⁻¹ (RT). Physiologic parameters and caecal borborygmi (CB) were measured and sedation and response to electrical stimulation of the coronary band assessed before and up to 120 minutes following drugs administration. Results were analyzed using the Friedman’s test and 2 way anova as relevant.ResultsWhen compared to baseline, heart (HR, beats minute⁻¹) and respiratory rates (f_R, breaths minute⁻¹) increased with treatment T (highest mean ± SD, HR 43 ± 1; f_R 33 ± 2) and decreased with R (lowest HR 29 ± 1 and f_R 10 ± 4) and RT (lowest HR 32 ± 1 and f_R 9 ± 3). There were no changes in other measured physiological variables. The height of head from the ground was lower following treatments R and TR than T. There was slight ataxia with all three treatments. No excitatory behavioural effects were observed. The response to electrical stimulation was reduced for a prolonged period relative to baseline following all three treatments, the effect being significantly greatest with treatment RT.ConclusionTramadol combined with romifidine at the stated doses proved an effective sedative and anti-nociceptive combination in ponies, with no unacceptable behavioural or physiologic side effects.Clinical relevanceSlow controlled administration of tramadol should reduce the occurrence of adverse behavioural side effects.     

The effect of three anaesthetic protocols on the stress response in cane toads (Rhinella marina)

ObjectiveThree anaesthetics (MS222, clove oil and a mixture of ketamine/diazepam) were administered to cane toads to determine their effect on the hypothalamic-pituitary-adrenal (HPA) axis. Time to induction and recovery and any adverse events were also evaluated.Study designProspective randomized experimental trial.AnimalsThirty adult male cane toads (Rhinella marina) with body mass ranging between 130 and 250 g were captured from the field.MethodsThree groups of 10 toads were anaesthetized with ketamine (200 mg kg^?1) and diazepam (0.2 mg kg^?1) by intramuscular injection, MS222 (3 g L^?1) or clove-oil (0.3 mL L^?1) both by immersion. Blood samples were collected to determine plasma corticosterone concentrations. Induction and recovery time were recorded in each treatment. After full recovery animals were euthanized and a complete post-mortem examination was performed.ResultsSignificant differences were found in the activation of the HPA axis and in the times of induction and recovery between treatments (p < 0.001). Animals anaesthetized with clove-oil had the highest levels of corticosterone in plasma (42.5 ± 21.6 ng mL^?1). No differences were found between ketamine/diazepam (15.0 ± 13.3 ng mL^?1) and MS222 (22.0 ± 13.6 ng mL^?1) groups. The mean ± SD induction (minutes) and recovery (hours) times respectively were; ketamine/diazepam 66.5 ± 11 and 8 ± 3, clove oil 39 ± 12 and 7.6 ± 3, and MS222 42.5 ± 11 and 1.5 ± 0.5. Clove oil exposure had 30% mortality. Death followed a period of respiratory distress with changes consistent with non-cardiogenic oedema observed at post-mortem examination.Conclusions and Clinical relevanceBased on shorter induction and recovery times and minimal activation of HPA, MS222 is the anaesthetic of choice in cane toads. If it is not possible to use immersion methods of anaesthesia, ketamine/diazepam can be used but induction and recovery times are prolonged. Clove oil had unacceptable mortality in this study and should be used with extreme caution.