A comparison of sedative effects of xylazine alone or combined with levomethadone or ketamine in calves prior to disbudding

ObjectiveTo compare the sedative effects of intramuscular xylazine alone or combined with levomethadone or ketamine in calves before cautery disbudding.Study designRandomized, blinded, clinical trial.AnimalsA total of 28 dairy calves, aged 21 ± 5 days and weighing 61.0 ± 9.3 kg (mean ± standard deviation).MethodsCalves were randomly allocated to three groups: xylazine (0.1 mg kg^–1) and levomethadone (0.05 mg kg^–1; group XL), xylazine (0.1 mg kg^–1) and ketamine (1 mg kg^–1; group XK) and xylazine alone (0.2 mg kg^–1; group X). Local anaesthesia (procaine hydrochloride) and meloxicam were administered subcutaneously 15 minutes after sedation and 15 minutes before disbudding. The calves’ responses to the administration of local anaesthesia and disbudding were recorded. Sedation was assessed at baseline and at intervals up to 240 minutes postsedation. Times of recumbency, first head lift and first standing were recorded. Drug plasma concentrations were measured.ResultsData were obtained from 27 animals. All protocols resulted in sedation sufficient to administer local anaesthesia and to perform disbudding. Sedation scores significantly correlated with drug plasma concentrations (p ≤ 0.002). Times to recumbency did not differ among protocols (2.8 ± 0.3, 3.1 ± 1.1 and 2.1 ± 0.8 minutes for groups XL, XK and X, respectively), whereas interval from drug(s) administration until first head lift was significantly shorter in group XK than X (47.3 ± 14.1, 34.4 ± 5.3 and 62.6 ± 31.9 minutes for groups XL, XK and X, respectively). The area under the time-sedation curve was significantly greater in group X than XK or XL (754 ± 215, 665 ± 118 and 1005 ± 258 minutes for groups XL, XK and X, respectively).Conclusions and clinical relevanceLevomethadone or ketamine with a low dose of xylazine produced short but sufficient sedation for local anaesthesia and disbudding with minimum resistance.     

Comparison of three anaesthetic protocols in Bennett’s wallabies (Macropus rufogriseus)

ObjectiveInvestigate physiological and sedative/anaesthetic effects of xylazine, medetomidine or dexmedetomidine combined with ketamine in free-ranging Bennett's wallabies.Study designProspective clinical trial.AnimalsTwenty-six adult free-ranging Bennett's wallabies.MethodsAnimals were darted intramuscularly with one of three treatments: xylazine and ketamine, 2.0 and 15.0 mg kg^?1, respectively (XK): medetomidine and ketamine 0.1 and 5.0 mg kg^?1 (MK) and dexmedetomidine and ketamine 0.05 and 5.0 mg kg^?1 (DMK). Body weights were estimated. If the animal was still laterally recumbent after 45 minutes of anaesthesia, then an alpha-2 adrenoceptor antagonist, atipamezole, was administered (XK: 0.4 mg kg^?1, MK: 5 mg kg^?1, DMK: 2.5 mg kg^?1). Heart rate (HR) and respiratory rate (f_R) were recorded at 5-minute intervals and temperature at 10-minute intervals. Venous blood was taken 30 minutes after initial injection. Statistical analysis utilized anova. p < 0.05 was considered significant.ResultsAnimals became recumbent rapidly in all groups. XK animals had muscle twitches, responded to external stimuli, and three animals required additional dosing; this was not observed in the MK and DMK groups. HR (mean ± SD beats minute^?1) in XK (81 ± 4) was significantly higher than MK (74 ± 2) and DMK (67 ± 4). There were no differences in f_R, temperature, blood-gas and biochemical values between groups. More animals in MK (9/10) and DMK (5/6) needed antagonism of anaesthesia compared with XK (1/10). There were no adverse effects after anaesthesia.Conclusion and clinical relevanceCardio-respiratory effects were similar in all groups. There were fewer muscle twitches and reactions to external stimuli in MK and DMK. Duration of anaesthesia was shorter in XK; most animals in MK and DMK needed atipamezole to assist recovery. All three treatments provided satisfactory sedation/anaesthesia and are suitable for use in Bennett's wallabies.     

Influence of detomidine and xylazine on spleen dimensions and on splenic response to epinephrine infusion in healthy adult horses

ObjectiveTo compare the changes in splenic length and thickness and in packed cell volume (PCV) following detomidine or xylazine administration and subsequent epinephrine infusion. Hypothesis: Spleen relaxation occurs following xylazine or detomidine administration and interferes with subsequent splenic contractile response to epinephrine.Study designRandomized non‐blinded crossover experimental study.Animals6 healthy adult mares.MethodsThe mares received an intravenous (IV) epinephrine infusion (1 μg kg^?1minute^?1 over 5 minutes) one hour after IV administration of detomidine (0.01 mg kg^?1), xylazine (0.5 mg kg^?1) or no drug (control), with a withdrawal period of at least 7 days between experiments. The splenic length measured in two different axes, the splenic thickness, and the PCV were measured prior to sedation (T0), 30 minutes later, and at 5‐minute intervals from the start of the epinephrine infusion (T1) until T1 + 40 minutes. Changes from base‐line and between treatments were compared using a two‐way anova for repeated measures. Significance was set at p < 0.05.ResultsSplenic length was significantly increased and PCV was significantly decreased after detomidine administration compared to baseline. Epinephrine infusion resulted in a significant decrease in splenic length and thickness, and a significant increase in PCV, irrespective of prior treatment with detomidine or xylazine.ConclusionsDetomidine administration was followed by a sonographically detectable increase of splenic length. Neither detomidine nor xylazine interfered with the ability of the spleen to contract following subsequent administration of an epinephrine infusion given one hour later.Clinical relevancePrevious sedation with alpha‐2 agonists does not preclude the efficiency of epinephrine as a medical treatment of left dorsal displacement of the large colon, but further investigations are required with other drug doses and different time intervals between administrations.     

Cardiopulmonary effects of diazepam/ketamine/isoflurane or xylazine/ketamine/isoflurane in foals undergoing abdominal surgery

The purpose of this study was to evaluate the cardiopulmonary effects of anesthetic induction with diazepam/ketamine or xylazine/ketamine with subsequent maintenance of anesthesia using isoflurane in foals undergoing abdominal surgery. Seventeen foals underwent laparotomy at 7–10 days of age and a laparoscopy 7–10 days later. Foals were randomly assigned to receive xylazine (0.8 mg kg^?1)/ketamine (2 mg kg^?1) (X/K)(n = 9) or diazepam (0.2 mg kg^?1)/ketamine (2 mg kg^?1) (D/K)(n = 8) for induction of anesthesia for both procedures. In all foals, anesthesia was maintained with isoflurane in oxygen with the inspired concentration adjusted to achieve adequate depth of anesthesia as assessed by an individual blinded to the treatments. IPPV was employed throughout using a tidal volume of 10 mL kg^?1 adjusting the frequency to maintain eucapnia (PaCO₂ 35–45 mm Hg, 4.7–6.0 kPa). Cardiopulmonary variables were measured after induction of anesthesia prior to, during, and following surgery. To compare the measured cardiopulmonary variables between the two anesthetic regimes for both surgical procedures, results were analyzed using a three‐way factorial anova for repeated measures (p < 0.05). During anesthesia for laparotomy, mean CI and MAP ranged from 110 to 180 mL kg^?1 minute^?1 and 57–81 mm Hg, respectively, in the D/K foals and 98–171 mL kg^?1 minute^?1 and 50–66 mm Hg in the X/K foals. Overall, CI, HR, SAP, DAP, and MAP were significantly higher in foals in the D/K group versus the X/K group during this anesthetic period. During anesthesia for laparoscopy, mean CI and MBP ranged from 85 to 165 mL kg^?1 minute^?1 and 67–83 mm Hg, respectively, in the D/K group, and 98–171 mL kg^?1 minute^?1 and 48–67 mm Hg in the X/K group. Only HR, SAP, DAP, and MAP were significantly higher in the D/K group versus X/K group during this latter anesthetic period. There were no significant differences between groups during either surgical procedure for end‐tidal isoflurane, PaO₂, PaCO₂, or pH. In conclusion, anesthesia of foals for laparotomy and laparoscopy with diazepam/ketamine/isoflurane is associated with less hemodynamic depression than with xylazine/ketamine/isoflurane.     

Physiologic and blood gas effects of xylazine–ketamine versus xylazine–tiletamine–zolazepam immobilization of white-tailed deer before and after oxygen supplementation: a preliminary study

ObjectiveTo compare oxygenation and ventilation in white-tailed deer (Odocoileus virginianus) anesthetized with two treatments with and without oxygen supplementation.Study designRandomized, blinded, crossover study.AnimalsA total of eight healthy adult white-tailed deer weighing 49–62 kg.MethodsEach deer was anesthetized twice intramuscularly: 1) treatment XK, xylazine (2 mg kg^–1) and ketamine (6 mg kg^–1) and 2) treatment XTZ, xylazine (2 mg kg^–1) and tiletamine–zolazepam (4 mg kg^–1). With the deer in sternal position, arterial and venous blood was collected before and at 30 minutes during administration of oxygen at 1 L minute^–1 through a face mask. PaO₂ and heart rate (HR) were compared using two-way repeated measures anova. pH, PaCO₂ and lactate concentration were analyzed using mixed-effects linear models, p < 0.05.ResultsWhen breathing air, PaO₂ was < 80 mmHg (10.7 kPa) in six and seven deer with XK and XTZ, respectively, and of these, PaO₂ was < 60 mmHg (8.0 kPa) in three and five deer, respectively. With oxygen supplementation, PaO₂ increased to 128 ± 4 and 140 ± 5 mmHg (17.1 ± 0.5 and 18.7 ± 0.7 kPa), mean ± standard error, with XK and XTZ, respectively (p < 0.001). PaO₂ was not significantly different between treatments at either time point. HR decreased during oxygen supplementation in both treatments (p < 0.001). Lactate was significantly lower (p = 0.047) with XTZ than with XK (2.2 ± 0.6 versus 3.5 ± 0.6 mmol L^–1) and decreased (p < 0.001) with oxygen supplementation (4.1 ± 0.6 versus 1.6 ± 0.6 mmol L^–1). PaCO₂ increased in XTZ during oxygen breathing.Conclusions and clinical relevanceTreatments XK and XTZ resulted in hypoxemia, which responded to oxygen supplementation. Both treatments are suitable for immobilization of white-tailed deer under the study circumstances.     

Evaluation of the perioperative stress response from dexmedetomidine infusion alone,with butorphanol bolus or remifentanil infusion compared with ketamine and morphine infusions in isoflurane-anesthetized horses

ObjectiveTo evaluate perioperative stress-related hormones in isoflurane-anesthetized horses administered infusions of dexmedetomidine alone or with butorphanol or remifentanil, compared with ketamine–morphine.Study designRandomized, prospective, nonblinded clinical study.AnimalsA total of 51 horses undergoing elective surgical procedures.MethodsHorses were premedicated with xylazine, anesthesia induced with ketamine–diazepam and maintained with isoflurane and one of four intravenous infusions. Partial intravenous anesthesia (PIVA) was achieved with dexmedetomidine (1.0 μg kg^–1 hour^–1; group D; 12 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and butorphanol bolus (0.05 mg kg^–1; group DB; 13 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and remifentanil (3.0 μg kg^–1 hour^–1; group DR; 13 horses); or ketamine (0.6 mg kg^–1 hour^–1) and morphine (0.15 mg kg^–1, 0.1 mg kg^–1 hour^–1; group KM; 13 horses). Infusions were started postinduction; butorphanol bolus was administered 10 minutes before starting surgery. Blood was collected before drugs were administered (baseline), 10 minutes after ketamine–diazepam, every 30 minutes during surgery and 1 hour after standing. Mean arterial pressure (MAP), pulse rate, end-tidal isoflurane concentration, cortisol, nonesterified fatty acids (NEFA), glucose and insulin concentrations were compared using linear mixed models. Significance was assumed when p < 0.05.ResultsWithin D, cortisol was lower at 120–180 minutes from starting surgery compared with baseline. Cortisol was higher in KM than in D at 60 minutes from starting surgery. Within all groups, glucose was higher postinduction (except DR) and 60 minutes from starting surgery, and insulin was lower during anesthesia and higher after standing compared with baseline. After standing, NEFA were higher in KM than in DB. In KM, MAP increased at 40–60 minutes from starting surgery compared with 30 minutes postinduction.Conclusions and clinical relevanceDexmedetomidine suppressed cortisol release more than dexmedetomidine–opioid and ketamine–morphine infusions. Ketamine–morphine PIVA might increase catecholamine activity.     

A comparison of the effects of two different doses of ketamine used for co-induction of anaesthesia with a target-controlled infusion of propofol in dogs

ObjectiveTo assess the cardiorespiratory and hypnotic-sparing effects of ketamine co-induction with target-controlled infusion of propofol in dogs.Study designProspective, randomized, blinded clinical study.AnimalsNinety healthy dogs (ASA grades I/II). Mean body mass 30.5 ± SD 8.6 kg and mean age 4.2 ± 2.6 years.MethodsAll dogs received pre-anaesthetic medication with acepromazine (0.03 mg kg^?1) and morphine (0.2 mg kg^?1) administered intramuscularly 30 minutes prior to induction of anaesthesia. Heart rate and respiratory rate were recorded prior to pre-medication. Animals were allocated into three different groups: Group 1 (control) received 0.9% NaCl, group 2, 0.25 mg kg^?1 ketamine and group 3, 0.5 mg kg^?1 ketamine, intravenously 1 minute prior to induction of anaesthesia, which was accomplished using a propofol target-controlled infusion system. The target propofol concentration was gradually increased until endotracheal intubation was possible and the target concentration at intubation was recorded. Heart rate, respiratory rate and noninvasive blood pressure were recorded immediately prior to induction, at successful intubation and at 3 and 5 minutes post-intubation. The quality of induction was graded according to the amount of muscle twitching and paddling observed. Data were analysed using a combination of chi-squared tests, Fisher's exact tests, Kruskal–Wallis, and anova with significance assumed at p< 0.05.ResultsThere were no significant differences between groups in the blood propofol targets required to achieve endotracheal intubation, nor with respect to heart rate, noninvasive blood pressure or quality of induction. Compared with the other groups, the incidence of post-induction apnoea was significantly higher in group 3, but despite this dogs in this group had higher respiratory rates overall.Conclusions and clinical relevanceUnder the conditions of this study, ketamine does not seem to be a useful agent for co-induction of anaesthesia with propofol in dogs.     

Medetomidine continuous rate intravenous infusion in horses in which surgical anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine and ketamine

ObjectiveTo evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine.Study designProspective, randomized, blinded clinical trial.AnimalsForty horses undergoing elective surgery.MethodsAfter sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg^?1 initially, then 2 mg kg^?1 hour^?1) and ketamine (2 mg kg^?1 hour^?1), both CRIs reducing to 1.5 mg kg^?1 hour^?1 after 50 minutes. Horses in group MILK received a medetomidine CRI of 3.6 μg kg^?1 hour^?1, reducing after 50 minutes to 2.75 μg kg^?1 hour^?1, and horses in group ILK an equal volume of saline. Mean arterial pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal concentration of isoflurane (FE′ISO) was adjusted as necessary to maintain surgical anaesthesia. Group ILK received medetomidine (3 μg kg^?1) at the end of the procedure. Recovery was evaluated. Differences between groups were analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance was taken as p < 0.05.ResultsFE′ISO required to maintain surgical anaesthesia in group MILK decreased with time, becoming significantly less than that in group ILK by 45 minutes. After 60 minutes, median (IQR) FE′ISO in MILK was 0.65 (0.4–1.0) %, and in ILK was 1 (0.62–1.2) %. Physiological parameters did not differ between groups, but group MILK required less dobutamine to support MAP. Total recovery times were similar and recovery quality good in both groups.Conclusion and clinical relevanceA CRI of medetomidine given to horses which were also receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane necessary to maintain satisfactory anaesthesia for surgery, and reduced the dobutamine required to maintain MAP. No further sedation was required to provide a calm recovery.     

Effects of methadone, alone or in combination with acepromazine or xylazine, on sedation and physiologic values in dogs

ObjectiveTo evaluate the effects of methadone, administered alone or in combination with acepromazine or xylazine, on sedation and on physiologic values in dogs.Study designRandomized cross-over design.AnimalsSix adult healthy mixed-breed dogs weighing 13.5 ± 4.9 kg.MethodsDogs were injected intramuscularly with physiologic saline (Control), or methadone (0.5mg kg⁻¹) or acepromazine (0.1 mg kg⁻¹) or xylazine (1.0 mg kg⁻¹), or acepromazine (0.05 mg kg⁻¹) plus methadone (0.5 mg kg⁻¹) or xylazine (0.5 mg kg⁻¹) plus methadone (0.5 mg kg⁻¹) in a randomized cross-over design, with at least 1-week intervals. Sedation, pulse rate, indirect systolic arterial pressure, respiratory rate (RR), body temperature and pedal withdrawal reflex were evaluated before and at 15-minute intervals for 90 minutes after treatment.ResultsSedation was greater in dogs receiving xylazine alone, xylazine plus methadone and acepromazine plus methadone. Peak sedative effect occurred within 30 minutes of treatment administration. Pulse rate was lower in dogs that received xylazine either alone or with methadone during most of the study. Systolic arterial pressure decreased only in dogs receiving acepromazine alone. When methadone was administered alone, RR was higher than in other treatments during most of the study and a high prevalence of panting was observed. In all treatments body temperature decreased, this effect being more pronounced in dogs receiving methadone alone or in combination with acepromazine. Pedal withdrawal reflex was absent in four dogs receiving methadone plus xylazine but not in any dog in the remaining treatments.Conclusions and clinical relevanceMethadone alone produces mild sedation and a high prevalence of panting. Greater sedation was achieved when methadone was used in combination with acepromazine or xylazine. The combination xylazine–methadone appears to result in better analgesia than xylazine administered alone. Both combinations of methadone/sedative were considered effective for premedication in dogs.     

Comparison of racemic ketamine and S-ketamine as agents for the induction of anaesthesia in goats

ObjectiveTo compare racemic ketamine and S-ketamine as induction agents prior to isoflurane anaesthesia.Study designProspective, blinded, randomized experimental study.AnimalsThirty-one healthy adult goats weighing 39-86 kg.MethodsGoats were premedicated with xylazine (0.1 mg kg^?1) intravenously (IV) given over 5 minutes. Each goat was assigned randomly to one of two treatments for IV anaesthetic induction: group RK (15 goats) racemic ketamine (3 mg kg^?1) and group SK (16 goats) S-ketamine (1.5 mg kg^?1). Time from end-injection to recumbency was measured and quality of anaesthetic induction and condition for endotracheal intubation were scored. Anaesthesia was maintained with isoflurane in oxygen for 90 minutes. Heart rate, invasive arterial blood pressure, oxygen saturation, temperature, end-tidal carbon dioxide and isoflurane were recorded every 5 minutes. Arterial blood samples were taken for analysis every 30 minutes. Recovery time to recurrence of swallowing reflex, to first head movement and to standing were recorded and recovery quality was scored. Two-way repeated measures anova, Mann-Whitney and a Mantel-Cox tests were used for statistical analysis as relevant with a significance level set at p < 0.05.ResultsInduction of anaesthesia was smooth and uneventful in all goats. There was no statistical difference between groups in any measured parameter. Side effects following anaesthetic induction included slight head or limb twitching, moving forward and backward, salivation and nystagmus but were minimal. Endotracheal intubation was achieved in all goats at first or second attempt. Recovery was uneventful on all occasions. All goats were quiet and needed only one or two attempts to stand.Conclusions and clinical relevanceS-ketamine at half the dose rate of racemic ketamine in goats sedated with xylazine and thereafter anaesthetised with isoflurane induces the same clinically measurable effects.     

Plasma histamine concentrations in horses administered sodium penicillin,guaifenesin–xylazine–ketamine and isoflurane with morphine or butorphanol

ObjectiveVarious drugs administered to horses undergoing surgical procedures can release histamine. Histamine concentrations were evaluated in horses prepared for surgery and administered butorphanol or morphine intraoperative infusions.Study designProspective studies with one randomized.AnimalsA total of 44 client-owned horses.MethodsIn one study, anesthesia was induced with xylazine followed by ketamine–diazepam. Anesthesia was maintained with guaifenesin–xylazine–ketamine (GXK) during surgical preparation. For surgery, isoflurane was administered with intravenous (IV) morphine (group M: 0.15 mg kg^–1 and 0.1 mg kg^–1 hour^–1; 15 horses) or butorphanol (group B: 0.05 mg kg^–1 and 0.01 mg kg^–1 hour^–1; 15 horses). Histamine and morphine concentrations were measured using enzyme-linked immunoassay before opioid injection (time 0), and after 1, 2, 5, 30, 60 and 90 minutes. In a subsequent study, plasma histamine concentrations were measured in 14 horses before drug administration (baseline), 15 minutes after IV sodium penicillin and 15 minutes after starting GXK IV infusion. Statistical comparison was performed using anova for repeated measures. Pearson correlation compared morphine and histamine concentrations. Data are presented as mean ± standard deviation. Significance was assumed when p ≤ 0.05.ResultsWith histamine, differences occurred between baseline (3.2 ± 2.4 ng mL^–1) and GXK (5.2 ± 7.1 ng mL^–1) and between baseline and time 0 in group B (11.9 ± 13.4 ng mL^–1) and group M (11.1 ± 12.4 ng mL^–1). No differences occurred between baseline and after penicillin or between groups M and B. Morphine concentrations were higher at 1 minute following injection (8.1 ± 5.1 ng mL^–1) than at 30 minutes (4.9 ± 3.1 ng mL^–1) and 60 minutes (4.0 ± 2.5 ng mL^–1). Histamine correlated with morphine at 2, 30 and 60 minutes.Conclusions and clinical relevanceGXK increased histamine concentration, but concentrations were similar with morphine and butorphanol.     

Effect of sub-anesthetic xylazine and ketamine ('ketamine stun') administered to calves immediately prior to castration

ObjectiveTo describe the pharmacokinetics, cortisol response and behavioral changes associated with administration of sub-anesthetic xylazine and ketamine prior to castration.Study designProspective, randomized experiment.AnimalsTwenty-two male beef calves (260-310 kg).MethodsCalves were randomly assigned to receive the following treatment immediately prior to surgical or simulated castration; 1) uncastrated, placebo-treated control (CONT) (n = 4), 2) Castrated, placebo treated control (CAST) (n = 6), 3) castrated with intravenous xylazine (X) (0.05 mg kg^?1) (n = 6), and 4) castrated with IV xylazine (X) (0.05 mg kg^?1) combined with ketamine (K) (0.1 mg kg^?1) (n = 6). Blood samples collected over 10 hours post-castration were analyzed by LC-MS-MS for drug concentrations and chemiluminescent immunoassay for cortisol determination.ResultsDrug concentrations during the first 60 minutes post-castration fit a one-compartment open model with first-order elimination. The harmonic mean elimination half-lives (± pseudo SD) for X, X with K and K were 12.9 ± 1.2, 11.2 ± 3.1 and 10.6 ± 2.8 minutes, respectively. The proportion of the total area under the effect curve (AUEC) for cortisol during this period was significantly lower in the X group (13 ± 3%; p = 0.006) and the X+K group (14 ± 2%; p = 0.016) compared with the CAST calves (21 ± 2%). However, after 300 minutes the AUEC in the X group was higher than CAST. Significantly more calves demonstrated attitude that was unchanged from pre-manipulation behavior in the CONT (p = 0.021) and X+K treated calves (p = 0.0051) compared with the CAST calves.ConclusionsBehavioral changes and lower serum cortisol concentrations during the first 60 minutes post-castration were associated with quantifiable xylazine and ketamine concentrations.Clinical relevanceLow doses of xylazine and ketamine administered immediately prior to castration may offer a safe, efficacious and cost-effective systemically administered alternative or adjunct to local anesthesia.     

Medetomidine/midazolam/ketamine anaesthesia in ferrets: effects on cardiorespiratory parameters and evaluation of plasma drug concentrations

ObjectiveTo evaluate the cardiorespiratory effects and plasma concentrations of medetomidine-midazolam-ketamine (MMK) combinations administered by intramuscular (IM) or subcutaneous (SC) injection in sable ferrets (Mustela putorius furo).Study designProspective randomized experimental study.AnimalsEighteen adult ferrets: weight median 1.19 (range 0.81–1.60) kg.MethodsAnimals were allocated to one of three groups: group IM07 received 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 7 mg kg^?1 ketamine IM; group IM10 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 10 mg kg^?1 ketamine IM; and group SC10 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 10 mg kg^?1 ketamine SC. Following instrumentation, cardiorespiratory parameters and plasma drug concentrations were measured every 5 minutes (T5–T30) for 30 minutes Ferrets were then euthanased. Data were analysed using anova for repeated measures. p < 0.05 was considered significant.ResultsResults are mean ± SD. Induction of anaesthesia (minutes) in IM07 and IM10 [2 (1)] was significantly faster than in SC10 [5 (2)]. All groups demonstrated the following: results given as groups IM07, IM10 and SC10 respectively. Mean arterial blood pressures (mmHg) were initially high [186 (13); 174 (33) and 174 (9) at T5] but decreased steadily. Pulse rates were initially 202 (20), 213 (17) and 207 (33) beats minute^?1, decreasing with time. PaO₂ (mmHg) was low [54.0 (8), 47.7 (10) and 38.5 (1)] at T5, although in groups IM07 and IM10 it increased over time. Plasma concentrations of all drugs were highest at T5 (36, 794 and 8264 nmol L^?1 for medetomidine, midazolam and ketamine, respectively) and decreased thereafter: for both midazolam and ketamine, concentrations in IM07 and IM10 were higher than SC10.Conclusions and clinical relevanceMMK combinations containing either 7 or 10 mg kg^?1 ketamine and given IM are suitable combinations for anaesthetising ferrets, although the observed degree of hypoxaemia indicates that oxygen administration is vital.     

Influence of ketamine or xylazine supplementation on isoflurane anaesthetized horses‐ a controlled clinical trial

ObjectivesTo determine the influence of ketamine or xylazine constant rate infusions on isoflurane requirements, cardiovascular parameters and quality of anaesthesia in horses undergoing elective surgery.Study designProspective, matched paired clinical trial.AnimalsFifty four adult Warmblood horses.MethodsAfter premedication with acepromazine, xylazine and butorphanol, anaesthesia was induced with ketamine-midazolam and maintained with isoflurane alone (I), isoflurane with either 1 mg kg⁻¹ hour⁻¹ ketamine (IK) or same dose of xylazine (IX). End tidal concentration of isoflurane (Fe’Iso) was adjusted by the same anaesthetist in all horses according to a scoring system. Dobutamine was infused to maintain mean arterial pressure (MAP) =70 mmHg. Arterial blood gases, heart rate (HR), respiratory rate, MAP and cardiac output (lithium dilution) were measured. Groups I and IK received xylazine before recovery. Recovery quality was scored.ResultsMean ± SD averaged Fe’Iso (volume%) was significantly lower in IX (0.95 ± 0.07) and IK (0.97 ± 0.08) than in I (1.16 ± 0.13). In group IX, HR was significantly lower and averaged MAP (90 ± 13 mmHg) significantly higher than in groups I (71 ± 7 mmHg) and IK (76 ± 7 mm Hg). Differences in other cardiopulmonary variables did not reach statistical significance. All horses recovered well with best score in group IX.ConclusionsBoth CRIs of xylazine and of ketamine resulted in pronounced reduction of isoflurane requirements and blood pressure support based on routinely monitored parameters. Cardiac output appeared well maintained in all three protocols, but lithium dilution induced errors mean the results are untrustworthy. The work requires repetition with another mode of measurement of cardiac output.Clinical relevanceAll three protocols provided good clinical anaesthesia with clinically acceptable cardiovascular effects.     

Effects of a low dose infusion of racemic and S-ketamine on the nociceptive withdrawal reflex in standing ponies

ObjectiveTo investigate the effect of plasma concentrations obtained by a low dose constant rate infusion (CRI) of racemic ketamine or S-ketamine on the nociceptive withdrawal reflex (NWR) in standing ponies.Study designProspective, blinded, cross-over study.AnimalsSix healthy 5-year-old Shetland ponies.MethodsPonies received either 0.6 mg kg⁻¹ racemic ketamine (group RS) or 0.3 mg kg⁻¹ S-ketamine (group S) intravenously (IV), followed by a CRI of 20 μg kg⁻¹minute⁻¹ racemic ketamine (group RS) or 10 μg kg⁻¹minute⁻¹ S-ketamine (group S) for 59 minutes. The NWR was evoked by transcutaneous electrical stimulation of a peripheral nerve before drug administration, 15 and 45 minutes after the start of the bolus injection and 15 minutes after the end of the CRI. Electromyographic responses were recorded and analysed. Arterial blood was collected before stimulation and plasma concentrations of ketamine and norketamine were measured enantioselectively using capillary electrophoresis. Ponies were video recorded and monitored to assess drug effects on behaviour, heart rate (HR), mean arterial blood pressure (MAP) and respiratory rate.ResultsThe NWR was significantly depressed in group RS at plasma concentrations between 20 and 25 ng mL⁻¹ of each enantiomer. In group S, no significant NWR depression could be observed; plasma concentrations of S-ketamine (9–15 ng mL⁻¹) were lower, compared to S-ketamine concentrations in group RS, although this difference was not statistically significant. Minor changes in behaviour, HR and MAP only occurred within the first 5–10 minutes after bolus drug administration in both groups.ConclusionAntinociceptive activity in standing ponies, demonstrated as a depression of the NWR, could only be detected after treatment with racemic ketamine. S-ketamine may have lacked this effect as a result of lower plasma concentrations, a more rapid metabolism or a lower potency of S-ketamine in Equidae so further investigation is necessary.     

Effects of intramuscular vatinoxan (MK-467), co-administered with medetomidine and butorphanol,on cardiopulmonary and anaesthetic effects of intravenous ketamine in dogs

ObjectiveTo investigate the impact of intramuscular (IM) co-administration of the peripheral α₂-adrenoceptor agonist vatinoxan (MK-467) with medetomidine and butorphanol prior to intravenous (IV) ketamine on the cardiopulmonary and anaesthetic effects in dogs, followed by atipamezole reversal.Study designRandomized, masked crossover study.AnimalsA total of eight purpose-bred Beagle dogs aged 3 years.MethodsEach dog was instrumented and administered two treatments 2 weeks apart: medetomidine (20 μg kg^–1) and butorphanol (100 μg kg^–1) premedication with vatinoxan (500 μg kg^–1; treatment MVB) or without vatinoxan (treatment MB) IM 20 minutes before IV ketamine (4 mg kg^–1). Atipamezole (100 μg kg^–1) was administered IM 60 minutes after ketamine. Heart rate (HR), mean arterial (MAP) and central venous (CVP) pressures and cardiac output (CO) were measured; cardiac (CI) and systemic vascular resistance (SVRI) indices were calculated before and 10 minutes after MVB or MB, and 10, 25, 40, 55, 70 and 100 minutes after ketamine. Data were analysed with repeated measures analysis of covariance models. A p-value <0.05 was considered statistically significant. Sedation, induction, intubation and recovery scores were assessed.ResultsAt most time points, HR and CI were significantly higher, and SVRI and CVP significantly lower with MVB than with MB. With both treatments, SVRI and MAP decreased after ketamine, whereas HR and CI increased. MAP was significantly lower with MVB than with MB; mild hypotension (57–59 mmHg) was recorded in two dogs with MVB prior to atipamezole administration. Sedation, induction, intubation and recovery scores were not different between treatments, but intolerance to the endotracheal tube was observed earlier with MVB.Conclusions and clinical relevanceHaemodynamic performance was improved by vatinoxan co-administration with medetomidine–butorphanol, before and after ketamine administration. However, vatinoxan was associated with mild hypotension after ketamine with the dose used in this study. Vatinoxan shortened the duration of anaesthesia.     

Effects of medetomidine and xylazine on intraocular pressure and pupil size in healthy Beagle dogs

ObjectiveTo determine the effects of intramuscular (IM) administration of medetomidine and xylazine on intraocular pressure (IOP) and pupil size in normal dogs.Study designProspective, randomized, experimental, crossover trial.AnimalsFive healthy, purpose-bred Beagle dogs.MethodsEach dog was administered 11 IM injections of, respectively: physiological saline; medetomidine at doses of 5, 10, 20, 40 and 80 μg kg⁻¹, and xylazine at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg kg⁻¹. Injections were administered at least 1 week apart. IOP and pupil size were measured at baseline (before treatment) and at 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours post-injection.ResultsA significant decrease in IOP was observed at 6 hours after 80 μg kg⁻¹ medetomidine compared with values at 0.25 and 0.50 hours, although there were no significant changes in IOP from baseline. In dogs treated with 8.0 mg kg⁻¹ xylazine, significant reductions in IOP were observed at 4 and 5 hours compared with that at 0.25 hours after administration. In dogs treated with 5, 10, 20 and 40 μg kg⁻¹ medetomidine and 0.5, 1.0 and 2.0 mg kg⁻¹ xylazine, there were no significant changes in IOP. Pupil size did not change significantly after any of the medetomidine or xylazine treatments compared with the baseline value.Conclusions and clinical relevanceLow or moderate doses of medetomidine or xylazine did not induce significant changes in IOP or pupil size. In contrast, high doses of medetomidine or xylazine induced significant changes up to 8 hours after treatment, but values remained within the normal canine physiological range. The results of this study suggest a lack of significant change in IOP and pupil size in healthy dogs administered low or moderate doses of xylazine or medetomidine.     

Cardiovascular effects of dose escalating of norepinephrine in healthy dogs anesthetized with isoflurane

ObjectiveTo evaluate the systemic cardiovascular effects of dose escalating administration of norepinephrine in healthy dogs anesthetized with isoflurane.Study designExperimental study.AnimalsA total of six adult laboratory Beagle dogs, 10.5 (9.2–12.0) kg [median (range)].MethodsEach dog was anesthetized with isoflurane at an end-tidal concentration of 1.7%, mechanically ventilated and administered a continuous rate infusion of rocuronium (0.5 mg kg^–1 hour^–1). Each dog was administered incremental dose rates of norepinephrine (0.05, 0.125, 0.25, 0.5, 1.0 and 2.0 μg kg^–1 minute^–1), and each dose was infused for 15 minutes. Cardiovascular variables were recorded before administration and at the end of each infusion period.ResultsNorepinephrine infusion increased mean arterial pressure (MAP), cardiac output (CO) and oxygen delivery in a dose-dependent manner. Systemic vascular resistance did not significantly change during the experiment. Stroke volume increased at the lower dose rates and heart rate increased at the higher dose rates. Oxygen consumption and lactate concentrations did not significantly change during infusions.ConclusionsIn dogs anesthetized with isoflurane, norepinephrine increased MAP by increasing the CO. CO increased with a change in stroke volume at lower dose rates of norepinephrine. At higher dosage, heart rate also contributed to an increase in CO. Norepinephrine did not cause excessive vasoconstriction that interfered with the CO during this study.Clinical relevanceNorepinephrine can be useful for treating hypotension in dogs anesthetized with isoflurane.