Effects of 2 different infusion rates of medetomidine on sedation score,cardiopulmonary parameters,and serum levels of medetomidine in healthy dogs

The effects of 2 different continuous rate infusions (CRIs) of medetomidine over an 8-hour period on sedation score, selected cardiopulmonary parameters, and serum levels of medetomidine were evaluated in 6 healthy, conscious dogs using a crossover study design. The treatment groups were: CONTROL = saline bolus followed by saline CRI; MED1 = 2 μg/kg body weight (BW) medetomidine loading dose followed by 1 μg/kg BW per hour CRI; and MED2 = 4 μg/kg BW medetomidine loading dose followed by 2 μg/kg BW per hour CRI. Sedation score (SS), heart rate (HR), respiratory rate (RR), temperature (TEMP), systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP), arterial and mixed venous blood gas analyses, lactate, and plasma levels of medetomidine were evaluated at baseline, at various intervals during the infusion, and 2 h after terminating the infusion. Statistical analysis involved a repeated measures linear model. Both infusion rates of medetomidine-induced dose-dependent increases in SS and dose-dependent decreases in HR, SAP, MAP, and DAP were measured. Respiratory rate (RR), TEMP, central venous pH, central venous oxygen tension, and oxygen extraction ratio also decreased significantly in the MED2 group at certain time points. Arterial oxygen and carbon dioxide tensions were not significantly affected by either infusion rate. In healthy dogs, both infusion rates of medetomidine-induced clinically relevant sedative effects, accompanied by typical alpha₂ agonist-induced hemodynamic effects, which plateaued during the infusion and subsequently returned to baseline. While additional studies in unhealthy animals are required, the results presented here suggest that medetomidine infusions at the doses studied may be useful in canine patients requiring sedation for extended periods.     

Evaluation of a constant rate infusion of lidocaine for balanced anesthesia in dogs undergoing surgery

This study assessed the intraoperative analgesic effects of intravenous lidocaine administered by a constant rate infusion (CRI) in surgical canine patients. A prospective, blinded, randomized study was designed with 2 treatment groups: A (lidocaine) and B (placebo), involving 41 dogs. All patients were premedicated with acepromazine and buprenorphine, induced with propofol and midazolam; anesthesia was maintained with isoflurane in oxygen. Group A received 2 mg/kg IV lidocaine immediately after induction, followed within 5 min by a CRI at 50 μg/kg/min. Group B received an equivalent volume of saline instead of lidocaine. Changes in heart rate and blood pressure during maintenance were treated by increasing CRI. Fentanyl was used as a supplemental analgesic when intraoperative nociceptive response was not controlled with the maximum dose of lidocaine infusion. There was a significantly lower use of supplemental intraoperative analgesia in the lidocaine than in the placebo group. Group B dogs had almost twice as high a risk of intraoperative nociceptive response as group A dogs.     

Lamprey GnRH‐III Releases Luteinizing Hormone but not Follicle Stimulating Hormone in Pigs

The effect of exogenous administration of lamprey GnRH‐III (IGnRH‐III) on gonadotropin secretion was evaluated in pigs. Six crossbred barrows (82.4 ± 3.5 kg body weight) were assigned randomly to a replicated 3 × 3 Latin square design to evaluate the effect of 0.1, 1.0 or 10.0 μg/kg body weight of exogenous IGnRH‐III on LH and FSH secretion. To facilitate blood collection and infusion of IGnRH‐III, barrows were catheterized in the jugular vein 1 day before initiation of experiments. Blood samples were taken at 10‐min intervals for 6 h, starting 2 h before treatments were applied. Relative concentrations of LH and FSH were calculated by obtaining the ratio of the average concentration of each hormone 2 h after infusion divided by the average concentration during the 2 h before infusion. Relative concentrations of FSH after IGnRH‐III infusion did not influence mean concentration of FSH at any of the doses; yet 10.0 μg/kg body weight had a significant effect on LH secretion (p < 0.01). Relative concentrations of LH averaged 1.2, 1.0 and 3.0 ng/ml (for doses of 0.1, 1.0 and 10.0 μg/kg body weight of IGnRH‐III respectively). Only a dose of 10 μg/kg body weight elicited a significant LH increase that was associated with exogenous IGnRH‐III infusion. We conclude that IGnRH‐III is a weak GnRH agonist and at high doses, IGnRH‐III has the ability to release LH but not FSH in barrows.     

Postoperative analgesic effects of either a constant rate infusion of fentanyl,lidocaine, ketamine,dexmedetomidine, or the combination lidocaine‐ketamine‐dexmedetomidine after ovariohysterectomy in dogs

ObjectiveTo evaluate the postoperative analgesic effects of a constant rate infusion (CRI) of either fentanyl (FENT), lidocaine (LIDO), ketamine (KET), dexmedetomidine (DEX), or the combination lidocaine-ketamine-dexmedetomidine (LKD) in dogs.Study designRandomized, prospective, blinded, clinical study.AnimalsFifty-four dogs.MethodsAnesthesia was induced with propofol and maintained with isoflurane. Treatments were intravenous (IV) administration of a bolus at start of anesthesia, followed by an IV CRI until the end of anesthesia, then a CRI at a decreased dose for a further 4 hours: CONTROL/BUT (butorphanol 0.4 mg kg⁻¹, infusion rate of saline 0.9% 2 mLkg⁻¹ hour⁻¹); FENT (5 μg kg⁻¹, 10 μg kg⁻¹hour⁻¹, then 2.5 μg kg⁻¹ hour⁻¹); KET (1 mgkg⁻¹, 40 μg kg⁻¹ minute⁻¹, then 10 μg kg⁻¹minute⁻¹); LIDO (2 mg kg⁻¹, 100 μg kg⁻¹ minute⁻¹, then 25 μg kg⁻¹ minute⁻¹); DEX (1 μgkg⁻¹, 3 μg kg⁻¹ hour⁻¹, then 1 μg kg⁻¹ hour⁻¹); or a combination of LKD at the aforementioned doses. Postoperative analgesia was evaluated using the Glasgow composite pain scale, University of Melbourne pain scale, and numerical rating scale. Rescue analgesia was morphine and carprofen. Data were analyzed using Friedman or Kruskal–Wallis test with appropriate post-hoc testing (p < 0.05).ResultsAnimals requiring rescue analgesia included CONTROL/BUT (n = 8), KET (n = 3), DEX (n = 2), and LIDO (n = 2); significantly higher in CONTROL/BUT than other groups. No dogs in LKD and FENT groups received rescue analgesia. CONTROL/BUT pain scores were significantly higher at 1 hour than FENT, DEX and LKD, but not than KET or LIDO. Fentanyl and LKD sedation scores were higher than CONTROL/BUT at 1 hour.Conclusions and clinical relevanceLKD and FENT resulted in adequate postoperative analgesia. LIDO, CONTROL/BUT, KET and DEX may not be effective for treatment of postoperative pain in dogs undergoing ovariohysterectomy.     

Effects of constant rate infusions of dexmedetomidine,remifentanil and their combination on minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effects of constant rate infusions (CRIs) of dexmedetomidine and remifentanil alone and their combination on minimum alveolar concentration (MAC) of sevoflurane in dogs.Study designRandomized crossover experimental study.AnimalsA total of six (three males, three females) healthy, adult neutered Beagle dogs weighing 12.6 ± 1.4 kg.MethodsAnesthesia was induced with sevoflurane in oxygen until endotracheal intubation was possible and anesthesia maintained with sevoflurane using positive-pressure ventilation. Each dog was anesthetized five times and was administered each of the following treatments: saline (1 mL kg^–1 hour^–1) or dexmedetomidine at 0.1, 0.5, 1.0 or 5.0 μg kg^–1 loading dose intravenously over 10 minutes followed by CRI at 0.1, 0.5, 1.0 or 5.0 μg kg^–1 hour^–1, respectively. Following 60 minutes of CRI, sevoflurane MAC was determined in duplicate using an electrical stimulus (50 V, 50 Hz, 10 ms). Then, CRI of successively increasing doses of remifentanil (0.15, 0.60 and 2.40 μg kg^–1 minute^–1) was added to each treatment. MAC was also determined after 30 minutes equilibration at each remifentanil dose. Isobolographic analysis determined interaction from the predicted doses required for a 50% MAC reduction (ED₅₀) with remifentanil, dexmedetomidine and remifentanil combined with dexmedetomidine, with the exception of dexmedetomidine 5.0 μg kg^–1 hour^–1, obtained using log-linear regression analysis.ResultsThe sevoflurane MAC decreased dose-dependently with increasing infusion rates of dexmedetomidine and remifentanil. Remifentanil ED₅₀ values were lower when combined with dexmedetomidine than those obtained during saline–remifentanil. Synergistic interactions between dexmedetomidine and remifentanil for MAC reduction occurred with dexmedetomidine at 0.5 and 1.0 μg kg^–1 hour^–1.Conclusions and clinical relevanceCombined CRIs of dexmedetomidine and remifentanil synergistically resulted in sevoflurane MAC reduction. The combination of dexmedetomidine and remifentanil effectively reduced the requirement of sevoflurane during anesthesia in dogs.     

Opioid-sparing effect of a medetomidine constant rate infusion during thoraco-lumbar hemilaminectomy in dogs administered a ketamine infusion

ObjectiveTo evaluate the perioperative opioid-sparing effect of a medetomidine (MED) infusion compared to a saline (SAL) infusion in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery.Study designRandomized, partially blinded, clinical study.AnimalsA total of 44 client-owned adult dogs.MethodsAll dogs were administered a 1 μg kg^–1 MED loading dose, followed by a 1.7 μg kg^–1 hour^–1 constant rate infusion (CRI) intravenously or equivalent volumes of SAL. Infusions were started 10–15 minutes before surgical incision and continued throughout the surgical procedure. All dogs were administered a standardized anaesthetic and analgesic protocol (including a ketamine CRI). Multiparametric monitoring, including invasive arterial blood pressure, was performed. A trained investigator, unaware of the treatment, performed pain scores for 4 hours postoperatively. Rescue analgesia consisted of fentanyl administered intraoperatively and methadone postoperatively. Data were tested for normality and analysed with Fisher’s exact test, Mann–Whitney U-test, analysis of variance and Kaplan–Meier survival analysis. Data are shown as median (interquartile range) and p-value was set at < 0.05.ResultsThe total dose of fentanyl was significantly lower with MED 0 (0–0.8) μg kg^–1 hour^–1 compared to SAL 3 (1.8–5.3) μg kg^–1 hour^–1 (p = 0.004). In the MED group, one dog compared to 12 dogs in the SAL group required a fentanyl CRI (p = 0.001). There were no statistically significant differences between groups regarding the total dose of methadone administered.Conclusions and clinical relevanceThe addition of a low-dose medetomidine CRI to the anaesthetic protocol decreased the need for a fentanyl CRI in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery during administration of a ketamine CRI.     

Sedative, analgesic, and cardiovascular effects of levomedetomidine alone and in combination with dexmedetomidine in dogs

OBJECTIVE: To determine whether a high dose of levomedetomidine had any pharmacologic activity or would antagonize the sedative and analgesic effects of dexmedetomidine in dogs. ANIMALS: 6 healthy Beagles. PROCEDURE: Each dog received the following treatments on separate days: a low dose of levomedetomidine (10 microg/kg), IV, as a bolus, followed by continuous infusion at a dose of 25 microg/kg/h; a high dose of levomedetomidine (80 microg/kg), IV, as a bolus, followed by continuous infusion at a dose of 200 microg/kg/h; and a dose of isotonic saline (0.9% NaCl) solution, IV, as a bolus, followed by continuous infusion (control). For all 3 treatments, the infusion was continued for 120 minutes. After 60 minutes, a single dose of dexmedetomidine (10 microg/kg) was administered IV. Sedation and analgesia were scored subjectively, and heart rate, blood pressure, respiratory rate, arterial blood gas partial pressures, and rectal temperatures were monitored. RESULTS: Administration of levomedetomidine did not cause any behavioral changes. However, administration of the higher dose of levomedetomidine enhanced the bradycardia and reduced the sedative and analgesic effects associated with administration of dexmedetomidine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of dexmedetomidine alone may have some cardiovascular benefits over administration of medetomidine, which contains both dexmedetomidine and levomedetomidine. Further studies are needed to confirm the clinical importance of the effects of levomedetomidine in dogs.     

Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs

The clinical effects and pharmacokinetics of medetomidine (MED) and its enanti-omers, dexmedetomidine (DEX) and levomedetomidine (LEVO) were compared in a group of six beagle dogs. The dogs received intravenously (i.v.) a bolus of MED (40 microg/kg), DEX (20 and 10 microg/kg), LEVO (20 and 10 microg/kg), and saline placebo in a blinded, randomized block study in six separate sessions. Sedation and analgesia were scored subjectively, and the dogs were monitored for heart rate, ECG lead II, direct blood pressure, respiratory rate, arterial blood gases, and rectal body temperature. Blood samples for drug analysis were taken. Peak sedative and analgesic effects were observed at mean (+/- SD) plasma levels of 18.5 +/- 4.7 ng/mL for MED40, 14.0 +/- 4.5 ng/mL for DEX20, and 5.5 +/- 1.3 ng/mL for DEX10. The overall level of sedation and cardiorespiratory effects did not differ between MED40, DEX20 and DEX10 during the first hour, apparently due to a ceiling effect. However, the analgesic effect of DEX20 lasted longer than the effect of the corresponding dose of racemic medetomidine, suggesting greater potency for dexmedetomidine in dogs. Levomedetomidine had no effect on cardio-vascular parameters and caused no apparent sedation or analgesia. The pharmacokinetics of dexmedetomidine and racemic medetomidine were similar, but clearance of levomedetomidine was more rapid (4.07 +/- 0.69 L/h/kg for LEVO20 and 3.52 +/- 1.03 for LEVO10) than of the other drugs (1.26 +/- 0.44 L/h/kg for MED40, 1.24 +/- 0.48 for DEX20, and 0.97 +/- 0.33 for DEX10).     

Furosemide continuous rate infusion diluted with 5% dextrose in water or hypertonic saline in normal adult dogs: a pilot study

Objective

The goal of this study was to investigate the short-term safety and diuretic efficacy of furosemide constant rate infusion (CRI) diluted with 5% dextrose in water (D5W) compared to dilution with 2.4% hypertonic saline in healthy dogs.

Plasma and serum concentrations of cytarabine administered via continuous intravenous infusion to dogs with meningoencephalomyelitis of unknown etiology

The objective of this study was to evaluate the plasma and serum concentrations of cytarabine (CA) administered via constant rate infusion (CRI) in dogs with meningoencephalomyelitis of unknown etiology (MUE). Nineteen client‐owned dogs received a CRI of CA at a dose of 25 mg/m²/h for 8 h as treatment for MUE. Dogs were divided into four groups, those receiving CA alone and those receiving CA in conjunction with other drugs. Blood samples were collected at 0, 1, 8, and 12 h after initiating the CRI. Plasma (n = 13) and serum (n = 11) cytarabine concentrations were measured by high‐pressure liquid chromatography. The mean peak concentration (C_MAX) and area under the curve (AUC) after CRI administration were 1.70 ± 0.66 μg/mL and 11.39 ± 3.37 h·μg/mL, respectively, for dogs receiving cytarabine alone, 2.36 ± 0.35 μg/mL and 16.91 + 3.60 h·μg/mL for dogs administered cytarabine and concurrently on other drugs. Mean concentrations for all dogs were above 1.0 μg/mL at both the 1‐ and 8‐h time points. The steady‐state achieved with cytarabine CRI produces a consistent and prolonged exposure in plasma and serum, which is likely to produce equilibrium between blood and the central nervous system in dogs with a clinical diagnosis of MUE. Other medications commonly used to treat MUE do not appear to alter CA concentrations in serum and plasma.     

Dexmedetomidine low dose followed by constant rate infusion and antagonism by atipamezole in isoflurane-anesthetized cats: an echocardiographic study

Objective

To investigate the effects of a low dose of dexmedetomidine (DEX) followed by constant rate infusion (CRI) and reversal with atipamezole on systolic and diastolic functions in isoflurane-anesthetized healthy cats.

Comparison of continuous infusion with intermittent bolus administration of cefotaxime on blood and cavity fluid drug concentrations in neonatal foals

Hewson, J., Johnson, R., Arroyo, L. G., Diaz‐Mendez, A., Ruiz‐López, J. A., Gu, Y., del Castillo, J. R. E. Comparison of continuous infusion with intermittent bolus administration of cefotaxime on blood and cavity fluid drug concentrations in neonatal foals. J. vet. Pharmacol. Therap.  36 , 68–77. Healthy neonatal foals were treated with cefotaxime by bolus (40 mg/kg IV q6h for 12 doses; n = 10) or by infusion (loading dose of 40 mg/kg IV followed by continuous infusion of a total daily dose of 160 mg/kg per 24 h for 3 days; n = 5). Population pharmacokinetics was determined, and concentrations in cavity fluids were measured at steady state (72 h). Highest measured serum drug concentration in the bolus group was 88.09 μg/mL and minimum drug concentration (C_min) was 0.78 μg/mL at 6‐h postadministration (immediately before each next dose), whereas infusion resulted in a steady‐state concentration of 16.10 μg/mL in the infusion group. Mean cefotaxime concentration in joint fluid at 72 h was higher (P = 0.051) in the infusion group (5.02 μg/mL) compared to the bolus group (0.78 μg/mL). Drug concentration in CSF at 72 h was not different between groups (P = 0.243) and was substantially lower than serum concentrations in either group. Insufficient data on pulmonary epithelial lining fluid were available to compare the methods of administration for cefotaxime in this cavity fluid. Results support continuous drug infusion over bolus dosing in the treatment for neonatal foal septicemia to optimize time that cefotaxime concentration exceeds the minimum inhibitory concentration of common equine pathogens.     

Effects of 2 different medetomidine infusion rates on selected neurohormonal and metabolic parameters in dogs

The effects of 2 different 8-hour continuous rate infusions (CRIs) of medetomidine on epinephrine, norepinephrine, cortisol, glucose, and insulin levels were investigated in 6 healthy dogs. Each dog received both treatments and a control as follows: MED1 = 2 μg/kg bodyweight (BW) loading dose followed by 1 μg/kg BW per hour CRI; MED2 = 4 μg/kg BW loading dose followed by 2 μg/kg BW per hour CRI; and CONTROL = saline bolus followed by a saline CRI. Both infusion rates of medetomidine decreased norepinephrine levels throughout the infusion compared to CONTROL. While norepinephrine levels tended to be lower with the MED2 treatment compared to the MED1, this difference was not significant. No differences in epinephrine, cortisol, glucose, or insulin were documented among any of the treatments at any time point. At the low doses used in this study, both CRIs of medetomidine decreased norepinephrine levels over the 8-hour infusion period, while no effects were observed on epinephrine, cortisol, glucose, and insulin.     

Cardiopulmonary and isoflurane‐sparing effects of epidural or intravenous infusion of dexmedetomidine in cats undergoing surgery with epidural lidocaine

ObjectiveTo compare the cardiorespiratory, anesthetic-sparing effects and quality of anesthetic recovery after epidural and constant rate intravenous (IV) infusion of dexmedetomidine (DEX) in cats given a low dose of epidural lidocaine under propofol-isoflurane anesthesia and submitted to elective ovariohysterectomy.Study designRandomized, blinded clinical trial.AnimalsTwenty-one adult female cats (mean body weight: 3.1 ± 0.4 kg).MethodsCats received DEX (4 μg kg^?1, IM). Fifteen minutes later, anesthesia was induced with propofol and maintained with isoflurane. Cats were divided into three groups. In GI cats received epidural lidocaine (1 mg kg^?1, n = 7), in GII cats were given epidural lidocaine (1 mg kg^?1) + DEX (4 μg kg^?1, n = 7), and in GIII cats were given epidural lidocaine (1 mg kg^?1) + IV constant rate infusion (CRI) of DEX (0.25 μg kg^?1 minute^?1, n = 7). Variables evaluated included heart rate (HR), respiratory rate (f_R), systemic arterial pressures, rectal temperature (RT), end-tidal CO₂, end-tidal isoflurane concentration (e′ISO), arterial blood gases, and muscle tone. Anesthetic recovery was compared among groups by evaluation of times to recovery, HR, f_R, RT, and degree of analgesia. A paired t-test was used to evaluate pre-medication variables and blood gases within groups. anova was used to compare parametric data, whereas Friedman test was used to compare muscle relaxation.ResultsEpidural and CRI of DEX reduced HR during anesthesia maintenance. Mean ± SD e′ISO ranged from 0.86 ± 0.28% to 1.91 ± 0.63% in GI, from 0.70 ± 0.12% to 0.97 ± 0.20% in GII, and from 0.69 ± 0.12% to 1.17 ± 0.25% in GIII. Cats in GII and GIII had longer recovery periods than in GI.Conclusions and clinical relevanceEpidural and CRI of DEX significantly decreased isoflurane consumption and resulted in recovery of better quality and longer duration, despite bradycardia, without changes in systemic blood pressure.     

Furosemide continuous rate infusion in the horse: evaluation of enhanced efficacy and reduced side effects

Continuous rate infusion (CRI) of furosemide in humans is considered superior to intermittent administration (IA). This study examined whether furosemide CRI, compared with IA, would increase diuretic efficacy with decreased fluid and electrolyte fluctuations and activation of the renin-angiotensin-aldosterone system (RAAS) in the horse. Five mares were used in a crossover-design study. During a 24-hour period, each horse received a total of 3 mg/kg furosemide by either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1 mg/kg IV q8h). There was not a statistically significant difference in urine volume over 24 hours between methods; however, urine volume was significantly greater after CRI compared with IA during the first 8 hours ([median 25th percentile, 75th percentile]: 9.6 L [8.9, 14.4] for CRI versus 5.9 L [5.3, 6.0] for IA). CRI produced a more uniform urine flow, decreased fluctuations in plasma volume, and suppressed renal concentrating ability throughout the infusion period. Potassium, Ca, and Cl excretion was greater during CRI than IA (1,133 mmol [1.110, 1,229] versus 764 mmol [709, 904], 102.7 mmol [96.0, 117.2] versus 73.3 mmol [65.0, 73.5], and 1,776 mmol [1,657, 2.378] versus 1,596 mmol [1,457, 1,767], respectively). Elimination half-lives of furosemide were 1.35 and 0.47 hours for CRI and IA, respectively. The area under the excretion rate curve was 1,285.7 and 184.2 mL x mg/mL for CRI and IA, respectively. Furosemide CRI (0.12 mg/kg/h) for 8 hours, preceded by a loading dose (0.12 mg/kg), is recommended when profound diuresis is needed acutely in horses.     

Behavioral and Cardiopulmonary Effects of a Constant Rate Infusion of Remifentanil–Xylazine for Sedation in Horses

Xylazine and remifentanil in constant rate infusion (CRI) could be used for sedation in horses without adverse effects. The objective was to evaluate behavioral and cardiopulmonary effects of an intravenous (IV) infusion of xylazine and remifentanil for sedation in horses. Xylazine (0.8 mg/kg IV) followed after 3 minutes by a CRI of xylazine and remifentanil (0.65 mg/kg/h and 6 μg/kg/h, respectively) was administered in 10 healthy horses for 60 minutes. Sedation, ataxia, and cardiopulmonary, hematological, and blood gases variables were evaluated. Heart rate decreased significantly during the first 25 minutes after CRI of xylazine and remifentanil, whereas the respiratory rate showed a significant decrease at 20 minutes and remained significantly low until the endpoint. There were no statistically significant fluctuations in blood arterial pressure, blood pH, partial pressure of arterial carbon dioxide, lactate, creatinine, calcium, chlorine, and sodium, compared with baseline values. Blood partial pressure of arterial oxygen and bicarbonate values were significantly higher compared with baseline values, whereas potassium decreased. Sedation and ataxia developed immediately after the administration of xylazine in all horses. All horses recovered successfully within 10 minutes after interruption of the CRI of xylazine and remifentanil, with no ataxia. No adverse effects were observed. The use of a combination of xylazine and remifentanil as sedation protocol has no adverse effects at the described dosage.     

A COMPARISON OF THE SEDATIVE EFFECTS OF MEDETOMIDINE AND XYLAZINE IN THE HORSE.

The sedative effects in horses of the new α₂-agonist medetomidine were compared with those of xylazine. Four ponies and one horse were treated on separate occasions with two doses of medetomidine (5 mμ/kg bodyweight and 10 μg/kg bodyweight) and with one dose of xylazine (1 μg/kg bodyweight) given by intravenous injection. Medetomidine at 10 μg/kg was similar to 1 mg/kg xylazine in sedative effect but produced greater and more prolonged ataxia. Ataxia was so severe following 10 μg/kg of medetomidine that one animal fell over during the study. Medetomidine (5 μg/kg) produced less sedation but a similar degree of ataxia to 1 mg/kg xylazine.     

Equine Endometrial Tissue Concentration of Fluconazole Following Oral Administration

The objective of this study was to determine the plasma and endometrial tissue concentrations of orally administered fluconazole and to determine if these tissue levels surpassed the minimum inhibitory concentration (MIC) for Candida spp. organisms in the reproductive tract of the mare. Mares from study 1 (n = 9) were administered a single oral loading dose of 14 mg/kg fluconazole. Plasma and endometrial tissue samples were collected before fluconazole administration and for 24 hours after the loading dose. Study 2 mares (n = 3), a subset of study 1, were administered the loading dose, followed by maintenance doses of 5 mg/kg every 24 hours for 6 days. Plasma and biopsy samples were collected for 48 hours after the last maintenance dose. High pressure liquid chromatography-tandem mass spectrometry was used to determine the concentration of fluconazole in all samples. The mean plasma and endometrial fluconazole levels 24 hours after the loading dose were 9.53 ± 0.824 μg/mL (mean ± standard deviation) and 11.3 ± 2.38 μg/g, respectively. Fluconazole levels in plasma and endometrial tissue 24 hours after the last maintenance dose were 7.82 ± 1.81 μg/mL and 7.23 ± 3.86 μg/g, respectively. Oral fluconazole administered as a 14-mg/kg loading dose and a 5-mg/kg maintenance dose every 24 hours will result in endometrial tissue levels near the accepted MIC values for most Candida spp. and surpass the MIC for Candida albicans in the reproductive tract of the mare. Consequently, this dosage regimen could be considered for the treatment of infectious endometritis caused by susceptible fungal organisms of Candida spp. in the mare.     

Influence of Cholinergic Blockade on the Development of Epinephrine-Induced Ventricular Arrhythmias in Halothane- and Isoflurane-Anesthetized Dogs

The arrhythmogenic effects of anesthetic drugs are assessed using the arrhythmogenic dose of epinephrine (ADE) model. The purpose of this study was to determine the influence of cholinergic blockade (CB) produced by glycopyrrolate (G) on ADE in 1.5 minimum alveolar concentration (MAC) halothane (H)- and isoflurane (I)-anesthetized dogs. Eight dogs (weighing between 12.5 and 21.5 kg) were randomly assigned to four treatment groups (H, HG, I, and IG) and each treatment was replicated three times. Anesthesia was induced and maintained with H (1.31%, end-tidal [ET]) or I (1.95%, ET) in oxygen. Ventilation was controlled (carbon dioxide [PCO₂] 35 to 40 mmHg, ET). G was administered 10 minutes before ADE determination at a dose of 22 μg/kg (11 μg/kg, intravenous [IV] and 11 μg/kg, intramuscular [IM]). The ADE was determined by IV infusion of epinephrine at sequentially increasing rates of 1.0, 2.5, and 5.0 μg/kg/min; and defined as the total dose of epinephrine producing at least four ectopic ventricular contractions (EVCs) within 15 seconds during a 3-minute infusion and up to 1 minute after the end of the infusion. Total dose was calculated as the product of infusion rate and time to arrhythmia. Data were analyzed using a randomized complete block analysis of variance. When significant (P < .05) F values were found a least significant difference test was used to compare group means. Values are reported as means ± standard error. The ADE (μg/kg) for H, HG, I, and IG were 1.53 ± 0.08, 3.37 ± 0.46, 1.61 ± 0.21, and > 15.00, respectively. Heart rates (HRs) (beats/min) and systolic pressures (mmHg) at the time of arrhythmia formation for H, HG, I, and IG were (60.3 ±4.0 and 142.0 ± 7.6), (213.0 ± 13.1 and 239.2 ± 7.1), (62.9 ± 4.5 and 151.9 ± 6.3), and (226.3 ± 6.1 and 323.5 ± 3.4), respectively. The H and I ADE were not different. The HG ADE was significantly less than the IG ADE. The H and I ADE were significantly less than the HG and IG ADE. We conclude the following from the results of this study of epinephrine infusion in halothane- and isoflurane-anesthetized dogs: (1) two distinct mechanisms are responsible for the development of arrhythmias, (2) CB produced by G significantly increases ADE but is associated with higher rate pressure products (RPP) and myocardial work, and (3) ADE methodology could be improved by determining ADE with and without CB.     

Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs

ObjectiveTo compare postoperative analgesia provided by a constant rate infusion (CRI) of dexmedetomidine (DMED) to that of a well-established positive control [morphine (MOR)] in critically ill dogs. The sedative, cardiorespiratory effects and clinical safety of a 24-hour DMED CRI were also evaluated.Study designProspective, randomised, blinded, positive-controlled parallel-group clinical study.AnimalsForty hospitalised, client-owned dogs requiring post-operative pain management after invasive surgery.MethodsAfter surgery, a loading dose of either DMED (25 μg m^?2) or MOR (2500 μg m^?2) followed by a 24-hour CRI of DMED (25 μg m^?2 hour^?1) or MOR (2500 μg m^?2 hour^?1) was administered. Pain was measured using the Short Form of the Glasgow Composite Measure Pain Scale, sedation and physiological variables were scored at regular intervals. Animals considered to be painful received rescue analgesia and were allocated to a post-rescue protocol; animals which were unresponsive to rescue analgesia were removed from the study. Data were analysed with anova, two-sample t-tests or Chi-square tests. Time to intervention was analysed with Kaplan–Meier methodology.ResultsForty dogs were enrolled. Twenty dogs (9 DMED and 11 MOR) did not require rescue analgesia. Eleven DMED and eight MOR dogs were allocated to the post-rescue protocol and seven of these removed from the study. Significant differences in pain scores between groups were not observed during the first 12 hours, however, DMED dogs were less (p = 0.009) painful during the last 12 hours. Sedation score over the entire 24-hour study was not significantly different between groups.Conclusion / Clinical RelevanceDexmedetomidine CRI was equally effective as MOR CRI at providing postoperative analgesia and no clinically significant adverse reactions were noted. This study shows the potential of DMED to contribute to a balanced postoperative analgesia regimen in dogs.