Cardiovascular effects of intravenous gadolinium administration to anaesthetized dogs undergoing magnetic resonance imaging

Objective To assess changes in heart rate and arterial blood pressure following intravenous (IV) gadolinium‐based contrast media administration to sevoflurane‐anaesthetized dogs undergoing magnetic resonance imaging (MRI). Study design Prospective clinical study. Animals Fifty client‐owned dogs (31 male, 19 female; aged 6–156 months; weighing 4.2–45.4 kg; ASA 2–3). Methods Heart rate and oscillometric blood pressures (systolic, mean and diastolic) were recorded at 10 minutes, 5 minutes and immediately pre‐administration of IV gadolinium contrast medium (time 0), then at 1, 2, 3, 5 and 10 minutes post‐gadolinium administration. Repeated measures anova was used to compare cardiovascular variables pre and post‐gadolinium administration. Significance was set at p < 0.05. Results There were no significant changes in cardiovascular variables following the IV administration of gadolinium. Conclusions and clinical relevance Administration IV of gadolinium‐based contrast media was not associated with adverse cardiovascular effects in these sevoflurane‐anaesthetized dogs undergoing MRI.     

Influence of a preload of hydroxyethylstarch 6% on the cardiovascular effects of epidural administration of ropivacaine 0.75% in anaesthetized dogs

ObjectiveTo evaluate the cardiovascular effects of a preload of hydroxyethylstarch 6% (HES), preceding an epidural administration of ropivacaine 0.75% in isoflurane anaesthetized dogs.AnimalsSix female, neutered Beagle dogs (mean 13.3 ± SD 1.0 kg; 3.6 ± 0.1 years).Study designRandomized experimental cross-over study (washout of 1 month).MethodsAnaesthesia was induced with propofol and maintained with isoflurane in oxygen/air. All dogs were anaesthetized twice to receive either treatment HESR (continuous rate infusion [CRI] of 7 mL kg^?1 HES started 30 minutes [T-30] prior to epidural administration of ropivacaine 0.75% 1.65 mg kg^?1 at T0) or treatment R (no HES preload and similar dose and timing of epidural ropivacaine administration). Baseline measurements were obtained at T-5. Heart rate (HR), mean (MAP), diastolic (DAP) and systolic (SAP) invasive arterial pressures, cardiac output (Lithium dilution and pulse contour analysis) and derived parameters were recorded every 5 minutes for 60 minutes. Statistical analysis was performed on five dogs, due to the death of one dog.ResultsClinically relevant decreases in MAP (<60 mmHg) were observed for 20 and 40 minutes following epidural administration in treatments HESR and R respectively. Significant decreases in MAP and DAP were present after treatment HESR for up to 20 minutes following epidural administration. No significant within-treatment and overall differences were observed for other cardiovascular parameters. A transient unilateral Horner's syndrome occurred in two dogs (one in each treatment). One dog died after severe hypotension, associated with epidural anaesthesia.Conclusions and clinical relevanceA CRI of 7 mL kg^?1 HES administered over 30 minutes before epidural treatment did not prevent hypotension induced by epidural ropivacaine 0.75%. Epidural administration of ropivacaine 0.75% in isoflurane anaesthetized dogs was associated with a high incidence of adverse effects in this study.     

Influence of general anaesthesia on the intravenous acetaminophen pharmacokinetics in Beagle dogs

ObjectiveTo determine if general anaesthesia influences the intravenous (IV) pharmacokinetics (PK) of acetaminophen in dogs.Study designProspective, crossover, randomized experimental study.AnimalsA group of nine healthy Beagle dogs.MethodsAcetaminophen PK were determined in conscious and anaesthetized dogs on two separate occasions. Blood samples were collected before, and at 5, 10, 15, 30, 45, 60 and 90 minutes and 2, 3, 4, 6, 8, 12 and 24 hours after 20 mg kg^–1 IV acetaminophen administration. Haematocrit, total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, urea and creatinine were determined at baseline and 24 hours after acetaminophen. The anaesthetized group underwent general anaesthesia (90 minutes) for dental cleaning. After the administration of dexmedetomidine (3 μg kg^–1) intramuscularly, anaesthesia was induced with propofol (2–3 mg kg^–1) IV, followed by acetaminophen administration. Anaesthesia was maintained with isoflurane in 50% oxygen (Fe′Iso 1.3–1.5%). Dogs were mechanically ventilated. Plasma concentrations were analysed with high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling. A Wilcoxon test was used to compare PK data between groups, and clinical laboratory values between groups, and before versus 24 hours after acetaminophen administration. Data are presented as median and range (p < 0.05).ResultsA two-compartmental model best described time–concentration profiles of acetaminophen. No significant differences were found for volume of distribution values 1.41 (0.94–3.65) and 1.72 (0.89–2.60) L kg^–1, clearance values 1.52 (0.71–2.30) and 1.60 (0.91–1.78) L kg^–1 hour^–1 or terminal elimination half-life values 2.45 (1.45–8.71) and 3.57 (1.96–6.35) hours between conscious and anaesthetized dogs, respectively. Clinical laboratory variables were within normal range. No adverse effects were recorded.Conclusions and clinical relevanceIV acetaminophen PK in healthy Beagle dogs were unaffected by general anaesthesia under the study conditions. Further studies are necessary to evaluate the PK in different clinical contexts.     

Effects of medetomidine,l‐methadone,and their combination on arterial blood gases in dogs

ObjectiveTo investigate the influence of l–methadone on medetomidine–induced changes in arterial blood gases and clinical sedation in dogs.Study designProspective experimental cross–over study (Latin square design).AnimalsFive 1–year–old purpose bred laboratory beagle dogs of both sexes.MethodsEach dog was treated three times: medetomidine (20 μg kg^?1 IV), l–methadone (0.1 mg kg^?1 IV) and their combination. Arterial blood was collected for blood gas analysis. Heart and respiratory rates were recorded, and clinical sedation and reaction to a painful stimulus were scored before drug administration and at various time points for 30 minutes thereafter.ResultsArterial partial pressure of oxygen decreased slightly after medetomidine administration and further after medetomidine/l–methadone administration (range 55.2–86.7 mmHg, 7.4–11.6 kPa, at 5 minutes). A slight increase was detected in arterial partial pressure of carbon dioxide after administration of l–methadone and medetomidine/l–methadone (42.6 ± 2.9 and 44.7 ± 2.4 mmHg, 5.7 ± 0.4 and 6.0 ± 0.3 kPa, 30 minutes after drug administration, respectively). Arterial pH decreased slightly after administration of l–methadone and medetomidine/l–methadone. Heart and respiratory rates decreased after administration of medetomidine and medetomidine/l–methadone, and no differences were detected between the two treatments. Most dogs panted after administration of l–methadone and there was slight sedation. Medetomidine induced moderate or deep sedation, and all dogs were deeply sedated after administration of medetomidine/l–methadone. Reaction to a noxious stimulus was strong or moderate after administration of methadone, moderate or absent after administration of medetomidine, and absent after administration of medetomidine/l–methadone.Conclusions and clinical relevanceAt the doses used in this study, l–methadone potentiated the sedative and analgesic effects and the decrease in arterial oxygenation induced by medetomidine in dogs, which limits the clinical use of this combination.     

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.     

The effect of buprenorphine on isoflurane minimum alveolar concentration in dogs

ObjectiveTo determine the effect of intravenous (IV) buprenorphine on the isoflurane (ISO) minimum alveolar concentration (ISOMAC) in dogs.Study designRandomized, crossover, design.AnimalsSix healthy, adult (2–3 years old), intact dogs (two males and four females) weighing 7.4–11.0 kg.MethodsEach dog was studied on three occasions, 1 week apart, and baseline ISOMAC (MAC_B) was determined on each occasion. ISOMAC was defined as the mean of the end-tidal ISO concentrations that prevented and allowed purposeful movement in response to a noxious stimulus. After MAC_B determination, dogs were randomly given buprenorphine (BUP) at either 0.01, 0.05 or 0.1 mg kg^?1 IV, and ISOMAC was determined at two time periods after BUP administration. The first post-treatment determination (MAC_T1) was initiated 45 minutes after BUP administration and the second determination (MAC_T2) was initiated 4 hours after BUP administration. MAC values were determined in duplicate and the mean values were used for statistical analysis.ResultsIsoflurane minimum alveolar concentration was decreased at 141 minutes (the time of MAC_T1 determination) by 25%, 35%, and 27% after administration of BUP at 0.01, 0.05, and 0.1 mg kg^?1, respectively (p ≤ 0.05). The MAC reductions were not statistically different among doses. The reductions in ISOMAC at 342 minutes (the time of MAC_T2 determination) ranged from 13 to 16%, and were not statistically different among doses.Conclusions and clinical significanceBuprenorphine at 0.01, 0.05, and 0.1 mg kg^?1 significantly decreased ISOMAC in dogs at 141 minutes but not at 342 minutes. When using BUP for MAC reduction re-dosing may be required for procedures of long duration, and there may be no advantage to using the 0.1 mg kg^?1 dose.     

CASE REPORT: Suspected acute meperidine toxicity in a dog

ObservationsA 22‐month‐old male neutered Coton De Tulear dog was presented for upper gastrointestinal endoscopy under general anesthesia. The anesthetic plan included premedication with intramuscular meperidine (4 mg kg^?1) but meperidine was inadvertently administered at ten‐fold this dose. Within 5 minutes, the dog was unresponsive to external stimulation, and by 10 minutes post‐injection developed generalized signs of central nervous system (CNS) excitement. Initial therapy included inspired oxygen supplementation, and single intravenous (IV) doses of diazepam (0.68 mg kg^?1) and naloxone (0.03 mg kg^?1) to no effect. A second dose of diazepam (0.46 mg kg^?1, IV) abolished most of the signs of CNS excitement. General anesthesia was induced and the endoscopy performed. Time to extubation was initially prolonged, but administering naloxone (final dose 0.1 mg kg^?1, IV) to effect enabled extubation. After naloxone, the dog became agitated, noise sensitive, and had leg and trunk muscle twitches. Diazepam (0.30 mg kg^?1, IV) abolished these signs and the dog became heavily sedated and laterally recumbent. Naloxone administration was continued as a constant rate infusion (0.02 mg kg^?1 hour^?1, IV) until approximately 280 minutes post‐meperidine injection, at which time the dog suddenly sat up. Occasional twitches of the leg and trunk muscles were observed during the night. The dog was discharged the next day appearing clinically normal.ConclusionsGiven that the CNS excitatory effects of normeperidine are not a μ opioid receptor effect, the use of naloxone should be considered carefully when normeperidine excitotoxicity is suspected. Benzodiazepines may be beneficial in ameliorating clinical signs of normeperidine excitotoxicity.     

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.     

Evaluation of xylazine–alfaxalone anesthesia for field castration in donkey foals

ObjectiveTo evaluate the anesthetic and cardiopulmonary effects of xylazine–alfaxalone anesthesia in donkey foals undergoing field castration.Study designProspective clinical study.AnimalsA group of seven standard donkeys aged [median (range)] 12 (10–26) weeks, weighing 47.3 (37.3–68.2) kg.MethodsDonkeys were anesthetized with xylazine (1 mg kg⁻¹) intravenously (IV) followed 3 minutes later by alfaxalone (1 mg kg⁻¹) IV. Additional doses of xylazine (0.5 mg kg⁻¹) and alfaxalone (0.5 mg kg⁻¹) IV were administered as needed to maintain surgical anesthesia. Intranasal oxygen was supplemented at 3 L minute⁻¹. Heart rate (HR), respiratory rate (f_R) and mean arterial pressure (MAP) by oscillometry were recorded before drug administration and every 5 minutes after induction of anesthesia. Peripheral oxygen saturation (SpO₂) was recorded every 5 minutes after induction. Time to recumbency after alfaxalone administration, time to anesthetic re-dose, time to first movement, sternal and standing after last anesthetic dose and surgery time were recorded. Induction and recovery quality were scored (1, very poor; 5, excellent).ResultsMedian (range) induction score was 5 (1–5), and recovery score 4 (1–5). Overall, two donkeys were assigned a score of 1 (excitement) during induction or recovery. HR and MAP during the procedure did not differ from baseline. f_R was decreased at 5 and 10 minutes but was not considered clinically significant. SpO₂ was <90% at one time point in two animals.Conclusions and clinical relevanceXylazine–alfaxalone anesthesia resulted in adequate conditions for castration in 12 week old donkeys. While the majority of inductions and recoveries were good to excellent, significant excitement occurred in two animals and may limit the utility of this protocol for larger donkeys. Hypoxemia occurred despite intranasal oxygen supplementation.     

Comparative evaluation of sedative and clinical effects of dexmedetomidine and xylazine in dromedary calves (Camelus dromedarius)

ObjectiveTo compare the sedative and clinical effects of intravenous (IV) administration of dexmedetomidine and xylazine in dromedary calves.Study designExperimental, crossover, randomized, blinded study.AnimalsA total of seven healthy male dromedary calves aged 14 ± 2 weeks and weighing 95 ± 5.5 kg.MethodsCalves were assigned three IV treatments: treatment XYL, xylazine (0.2 mg kg⁻¹); treatment DEX, dexmedetomidine (5 μg kg⁻¹); and control treatment, normal saline (0.01 mL kg⁻¹). Sedation scores, heart rate (HR), respiratory rate (f_R), rectal temperature (RT) and ruminal motility were recorded before (baseline) and after drug administration. Sedation signs were scored using a 4-point scale. One-way anova and Mann–Whitney U tests were used for data analysis.ResultsCalves in treatments XYL and DEX were sedated at 5–60 minutes. Sedation had waned in XYL calves, but not DEX calves, at 60 minutes (p = 0.037). Sedation was not present in calves of any treatment at 90 minutes. HR decreased from baseline in XYL and DEX at 5–90 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.017). HR was lower in DEX (p = 0.001) and XYL (p = 0.013) than in control treatment at 90 minutes. f_R decreased from baseline in XYL and DEX at 5–60 minutes after drug administration and was lower in DEX than XYL at 5 minutes (p = 0.013). RT was unchanged in any treatment over 120 minutes. Ruminal motility was decreased in XYL at 5, 90 and 120 minutes and absent at 10–60 minutes. Motility was decreased in DEX at 5, 10 and 120 minutes and was absent at 15–90 minutes.Conclusion and clinical relevanceThe duration of sedation from dexmedetomidine (5 μg kg^–1) and xylazine (0.2 mg kg^–1) was similar in dromedary calves.     

The cardiopulmonary effects of a peripheral alpha‐2‐adrenoceptor antagonist,MK‐467, in dogs sedated with a combination of medetomidine and butorphanol

ObjectiveTo compare the cardiopulmonary effects of intravenous (IV) and intramuscular (IM) medetomidine and butorphanol with or without MK-467.Study designProspective, randomized experimental cross-over.AnimalsEight purpose–bred beagles (two females, six males), 3–4 years old and weighing 14.5 ±1.6 kg (mean ± SD).MethodsAll dogs received four different treatments as follows: medetomidine 20 μg kg^?1 and butorphanol tartrate 0.1 mg kg^?1 IV and IM (MB), and MB combined with MK-467,500 μg kg^?1 (MBMK) IV and IM. Heart rate (HR), arterial blood pressures (SAP, MAP, DAP), central venous pressure (CVP), cardiac output, respiratory rate (f_R), rectal temperature (RT) were measured and arterial blood samples were obtained for gas analysis at baseline and at 3, 10, 20, 30, 45 and 60 minutes after drug administration. The cardiac index (CI), systemic vascular resistance index (SVRI) and oxygen delivery index (DO₂I) were calculated. After the follow-up period atipamezole 50 μg kg^?1 IM was given to reverse sedation.ResultsHR, CI and DO₂I were significantly higher with MBMK after both IV and IM administration. Similarly, SAP, MAP, DAP, CVP, SVRI and RT were significantly lower after MBMK than with MB. There were no differences in f_R between treatments, but arterial partial pressure of oxygen decreased transiently after all treatments. Recoveries were uneventful following atipamezole administration after all treatments.Conclusions and clinical relevanceMK-467 attenuated the cardiovascular effects of a medetomidine-butorphanol combination after IV and IM administration.     

Pharmacokinetic‐pharmacodynamic modelling of intravenous buprenorphine in conscious horses

ObjectiveDescribe the pharmacokinetics of buprenorphine and norbuprenorphine in horses and to relate the plasma buprenorphine concentration to the pharmacodynamic effects.Study designSingle phase non-blinded study.AnimalsSix dedicated research horses, aged 3–10 years and weighing 480–515 kg.MethodsThermal and mechanical nociceptive thresholds, heart and respiratory rates and locomotor activity were measured before and 15, 30, 45 &; 60 minutes and 2, 4, 6, 8, 12 &; 24 hours post-administration of 10 μg kg⁻¹ buprenorphine IV. Intestinal motility was measured 1, 6, 12 &; 24 hours after buprenorphine administration. Venous blood samples were obtained before administration of buprenorphine 10 μg kg⁻¹ IV and 1, 2, 4, 6, 10, 15, 30, 45 &; 60 minutes, and 2, 4, 6, 8, 12 &; 24 hours afterwards. Plasma buprenorphine and norbuprenorphine concentrations were measured using a liquid chromatography-tandem mass spectroscopy (LC-MS/MS) assay with solid-phase extraction. A non-compartmental method was used for analysis of the plasma concentration–time data and plasma buprenorphine concentrations were modelled against two dynamic effects (change in thermal threshold and mechanical threshold) using a simple Emax model.ResultsPlasma buprenorphine concentrations were detectable to 480 minutes in all horses and to 720 minutes in two out of six horses. Norbuprenorphine was not detected. Thermal thresholds increased from 15 minutes post-buprenorphine administration until the 8–12 hour time points. The increase in mechanical threshold ranged from 3.5 to 6.0 Newtons (median: 4.4 N); and was associated with plasma buprenorphine concentrations in the range 0.34–2.45 ng mL⁻¹.Conclusions and clinical relevanceThe suitability of the use of buprenorphine for peri-operative analgesia in the horse is supported by the present study.     

Midazolam,as a co‐induction agent,has propofol sparing effects but also decreases systolic blood pressure in healthy dogs

ObjectiveTo evaluate the effects of the co-administration of midazolam on the dose requirement for propofol anesthesia induction, heart rate (HR), systolic arterial pressure (SAP) and the incidence of excitement.Study designProspective, randomized, controlled and blinded clinical study, with owner consent.AnimalsSeventeen healthy, client owned dogs weighing 28 ± 18 kg and aged 4.9 ± 3.9 years old.MethodsDogs were sedated with acepromazine 0.025 mg kg^?1 and morphine 0.25 mg kg^?1 intramuscularly (IM), 30 minutes prior to induction of anesthesia. Patients were randomly allocated to receive midazolam (MP; 0.2 mg kg^?1) or sterile normal saline (CP; 0.04 mL kg^?1) intravenously (IV) over 15 seconds. Propofol was administered IV immediately following test drug and delivered at 3 mg kg^?1 minute^?1 until intubation was possible. Scoring of pre-induction sedation, ease of intubation, quality of induction, and presence or absence of excitement following co-induction agent, was recorded. HR, SAP and respiratory rate (f_R) were obtained immediately prior to, immediately following, and 5 minutes following induction of anesthesia.ResultsThere were no significant differences between groups with regard to weight, age, gender, or sedation. Excitement occurred in 5/9 dogs following midazolam administration, with none noted in the control group. The dose of propofol administered to the midazolam group was significantly less than in the control group. Differences in HR were not significant between groups. SAP was significantly lower in the midazolam group compared with baseline values 5 minutes after its administration. However, values remained clinically acceptable.Conclusions and clinical relevanceThe co-administration of midazolam with propofol decreased the total dose of propofol needed for induction of anesthesia in sedated healthy dogs, caused some excitement and a clinically unimportant decrease in SAP.     

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.     

The effect of autonomic manipulation on heart rate variability in dogs

Beat‐to‐beat variation of heart rate is reflective of autonomic balance and has been used to assess pain and stress in human beings. The purpose of this investigation was to pharmacologically manipulate the autonomic nervous system and to determine the effect of these manipulations on heart rate variability (HRV) in dogs. Four adult male hound dogs (27 ± 1 kg) were used in the investigation. Each dog was given five treatments: Parasympathetic blockade (glycopyrrolate; 0.01 mg kg^–1 IV and 0.01 mg kg^–1 IM), parasympathetic stimulation (phenylephrine; 0.005 mg kg^–1 IV + 0.05 mg kg^–1hour^–1), sympathetic blockade (propranolol; 0.11 mg kg^–1 IV), sympathetic stimulation propranolol; 0.01 μg kg^–1 minute^–1), and saline control. At least 48 hours were allowed between treatments. ECG recordings were obtained using an ambulatory ECG monitor. A 5‐minutes period of continuous recording obtained ~30 minutes after initiation of drug administration was used for data analysis. Changes in HRV were evaluated by time and frequency‐domain analysis. The standard deviation of normal R‐R intervals (SDNN), as well as the standard deviation of successive differences in RR intervals (SDSD) were assessed for each treatment. Low frequency (LFP; 0.05–0.15 Hz), high frequency (HFP; 0.15–0.35 Hz), and total (TP; 0.017–0.5 Hz) spectral power were also determined. The LFP:HFP ratio was also evaluated. A two‐way anova with a Tukey's test was used to detect differences (p < 0.05). Administration of glycopyrrolate or isoproterenol increased HR and decreased SDNN and SDSD below control levels. Phenylephrine or propranolol administration were without effect. LFP was diminished by glycopyrrolate and isoproterenol, but was unaffected by phenylephrine and propranolol. HFP, TP, and LFP:HFP were unaffected by treatment. Both branches of the autonomic nervous system influence SDNN and LFP. SDSD, in contrast, is altered primarily by parasympathetic activity. Thus, it appears that parasympathetic activity modulates HRV in the resting dog, as either withdrawal of parasympathetic influence or accentuated sympathetic activity led to significant changes in these measures of HRV. Conversely, augmentation of parasympathetic activity or withdrawal of sympathetic tone minimally affected HRV.     

Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses

ObjectiveTo evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses.Study designProspective, blinded, randomized cross-over study.AnimalsTen healthy adult horses weighing 527–645 kg and aged 11–21 years old.MethodsElectrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg^?1, romifidine 0.08 mg kg^?1, or xylazine, 1 mg kg^?1, was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation.ResultsThe administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively.Conclusions and clinical relevanceDetomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific.     

Pharmacokinetics of intravenous and oral amitriptyline and its active metabolite nortriptyline in Greyhound dogs

ObjectiveTo evaluate the pharmacokinetics of amitriptyline and its active metabolite nortriptyline after intravenous (IV) and oral amitriptyline administration in healthy dogs.Study designProspective randomized experiment.AnimalsFive healthy Greyhound dogs (three males and two females) aged 2–4 years and weighing 32.5–39.7 kg.MethodsAfter jugular vein catheterization, dogs were administered a single oral or IV dose of amitriptyline (4 mg kg⁻¹). Blood samples were collected at predetermined time points from baseline (0 hours) to 32 hours after administration and plasma concentrations of amitriptyline and nortriptyline were measured by liquid chromatography triple quadrupole mass spectrometry. Non-compartmental pharmacokinetic analyses were performed.ResultsOrally administered amitriptyline was well tolerated, but adverse effects were noted after IV administration. The mean maximum plasma concentration (C_MAX) of amitriptyline was 27.4 ng mL⁻¹ at 1 hour and its mean terminal half-life was 4.33 hours following oral amitriptyline. Bioavailability of oral amitriptyline was 6%. The mean C_MAX of nortriptyline was 14.4 ng mL⁻¹ at 2.05 hours and its mean terminal half-life was 6.20 hours following oral amitriptyline.Conclusions and clinical relevanceAmitriptyline at 4 mg kg⁻¹ administered orally produced low amitriptyline and nortriptyline plasma concentrations. This brings into question whether the currently recommended oral dose of amitriptyline (1–4 mg kg⁻¹) is appropriate in dogs.     

Pharmacokinetic and pharmacodynamic modelling of intravenous,intramuscular and subcutaneous buprenorphine in conscious cats

ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats.Study designRandomized, prospective, blinded, three period crossover experiment.AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg.MethodsBuprenorphine (0.02 mg kg^?1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics.ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t_1/2k_e0 = 47.4 minutes) and receptor binding (k_on = 0.011 mL ng^?1 minute^?1). Persistence of thermal antinociception was due to slow receptor dissociation (t_1/2k_off = 18.2 minutes).Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats.     

Efficacy of maropitant in preventing vomiting in dogs premedicated with hydromorphone

ObjectiveThe goal of this study was to evaluate the effectiveness of maropitant (Cerenia^®) in preventing vomiting after premedication with hydromorphone.Study designRandomized, blinded, prospective clinical study.AnimalsEighteen dogs ASA I/II admitted for elective orthopedic surgical procedures. The dogs were a mixed population of males and females, purebreds and mixed breeds, 1.0–10.2 years of age, weighing 3–49.5 kg.MethodsDogs were admitted to the study if they were greater than 1 year of age, healthy and scheduled to undergo elective orthopedic surgery. Dogs were randomly selected to receive one of two treatments administered by subcutaneous injection. Group M received 1.0 mg kg^?1 of maropitant, Group S received 0.1 mL kg^?1 of saline 1 hour prior to anesthesia premedication. Dogs were premedicated with 0.1 mg kg^?1 of hydromorphone intramuscularly. A blinded observer documented the presence of vomiting, retching and/or signs of nausea for 30 minutes after premedication.ResultsAll dogs in S vomited (6/9), retched (1/9) or displayed signs of nausea (2/9). None (0/9) of the dogs in M vomited, retched or displayed signs of nausea. Dogs in M had significantly fewer incidences of vomiting (p = 0.0090), vomiting and retching (p = 0.0023) and vomiting, retching and nausea (p < 0.0001) when compared to S.Conclusion and clinical relevanceMaropitant prevents vomiting, retching and nausea associated with intramuscular hydromorphone administration in dogs.     

Anesthetic management of an off-pump open-heart surgery in a dog

ObservationsA 9 year-old, 40 kg, female spayed Bouvier des Flandres was anesthetized for surgical removal of an intra-cardiac mass. Pre-anesthetic work-up included thoracic radiographs, which revealed moderate pleural effusion, and cardiac ultrasound, which identified a mass attached to the wall of the right ventricular outflow tract (RVOT). The mass caused dynamic obstruction of the RVOT during systole. The dog was pre-medicated with intravenous (IV) hydromorphone (0.05 mg kg^?1). Following pre-oxygenation, anesthesia was induced with ketamine (3.75 mg kg^?1, IV) and diazepam (0.18 mg kg^?1, IV). Anesthesia was maintained with isoflurane in oxygen, an intravenous constant rate infusion (CRI) of fentanyl (10–30 μg kg^?1 hour^?1) and a CRI of lidocaine (50–200 μg kg^?1 minute^?1). A right lateral thoracotomy was performed. The heart was stopped transiently with a cold cardioplegic solution for 7.83 minutes to allow the removal of the mass through an open-heart procedure. No cardiopulmonary bypass was used. The heart was successfully restarted after cardiopulmonary resuscitation with internal cardiac massage and internal defibrillation. The dog recovered uneventfully from anesthesia without any apparent neurological sequelae. Post-operative analgesia consisted of intercostal nerve blocks with bupivacaine, CRIs of fentanyl (2–5 μg kg^?1 hour^?1) and lidocaine (40 μg kg^?1 minute^?1) and with oral meloxicam (0.1 mg kg^?1). Five days following surgery, the dog was discharged from the hospital. Histopathology and immunohistochemistry of the mass identified an ectopic thyroid carcinoma.ConclusionsThis case showed the feasibility of whole body hypothermia and using a cold cardioplegic solution to induce cardiac arrest for a short open-heart procedure.