Administration Of Medetomidine Research Articles

Comparison of the effects of xylazine bolus versus medetomidine constant rate infusion on cardiopulmonary function and depth of anesthesia in horses anesthetized with isoflurane

To compare the effects of xylazine bolus versus medetomidine constant rate infusion (MCRI) on cardiopulmonary function and depth of anesthesia in dorsally recumbent, spontaneously breathing, isoflurane-anesthetized horses. Prospective, randomized crossover study. 10 healthy adult Standardbreds. Horses were premedicated with xylazine or medetomidine IV. Anesthesia was induced with diazepam and ketamine and maintained with isoflurane for 150 minutes. For the xylazine treatment, end-tidal isoflurane concentration was maintained at 1.7%, and xylazine (0.2 mg/kg [0.09 mg/lb], IV) was administered as a bolus at the end of anesthesia. For the MCRI treatment, end-tidal isoflurane concentration was maintained at 1.4%, and medetomidine (0.005 mg/kg/h [0.0023 mg/lb/h], IV) was infused throughout anesthesia. Physiologic data (ie, heart rate, respiratory rate, rectal temperature, bispectral index, and electromyographic values) were compared between treatments with xylazine bolus versus MCRI. Heart rate was lower, but mean arterial blood pressure was higher from 20 to 40 minutes with MCRI treatment, compared with conventional treatment with xylazine. Respiratory rate and rectal temperature were greater with MCRI treatment. Bispectral index was lower with MCRI treatment from 80 to 150 minutes, and electromyographic values were lower with MCRI treatment from 30 to 150 minutes. In isoflurane-anesthetized horses, premedication with medetomidine followed by administration of medetomidine as a constant rate infusion resulted in decreased heart rate, higher arterial blood pressure from 20 through 40 minutes after induction of anesthesia, and better preserved body temperature, compared with conventional treatment with xylazine. Greater depth of anesthesia and muscle relaxation were seen with MCRI treatment, despite the lower isoflurane concentration.

Medetomidine immobilisation and atipamezole reversal in large estuarine crocodiles (Crocodylus porosus) using metabolically scaled dosages

Restraint of large estuarine crocodiles is potentially dangerous. Neuromuscular blockers and other immobilising drugs have been used with variable results. Medetomidine has been reported as a reliable, repeatable and reversible immobilisation agent in small estuarine crocodilians. Two wild and two farmed male animals, between 3.05 and 4.6 m long, were hand-injected into a triceps muscle with a metabolically scaled medetomidine dosage. Immobilisation occurred within 30 min. At the conclusion of the procedures, 70 min after medetomidine administration, three animals were injected with atipamezole IM into the opposite triceps muscle at a dosage based on body surface area. Reversal occurred within 5 min. The fourth animal was intubated prior to reversal of medetomidine and maintained on isoflurane anaesthesia for a gastrotomy. All animals were monitored closely post recovery and then regularly for at least 1 week. Medetomidine at a metabolically scaled dosage delivered IM into the forelimb was effective for immobilising large estuarine crocodiles for at least 40 min. Atipamezole administered at a dosage calculated as a function of surface area effectively reversed this immobilisation.

Pharmacokinetics and pharmacodynamics of intravenous medetomidine in the horse

ObjectiveTo describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse. Study designProspective experimental trial. AnimalsEight, mature healthy horses age 11.7 ± 4.6 (mean ± SD) years, weighing 557 ± 54 kg. MethodsMedetomidine (10 μg kg−1) was administered IV. Blood was sampled at fixed time points from before drug administration to 48 hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0 minutes to 24 hours post administration. An algometer was also used to measure threshold responses to noxious stimuli. Medetomidine concentrations were determined by liquid chromatography-Mass Spectrometry and used for calculation of pharmacokinetic parameters using noncompartmental and compartmental analysis. ResultsPharmacokinetic analysis estimated that medetomidine peaked (8.86 ± 3.87 ng mL−1) at 6.4 ± 2.7 minutes following administration and was last detected at 165 ± 77 minutes post administration. Medetomidine had a clearance of 39.6 ± 14.6 mL kg−1 minute−1 and a volume of distribution of 1854 ± 565 mL kg−1. The elimination half-life was 29.1 ± 12.5 minutes. Glucose concentration reached a maximum of 176 ± 46 mg dL−1 approximately 1 hour post administration. Decreased heart rate, respiratory rate, borborygmi, packed cell volume, and total protein concentration were observed following administration. Horses lowered their heads from 107 ± 12 to 20 ± 10 cm within 10 minutes of drug administration and gradually returned to normal. Horse mobility decreased after drug administration. An increased mechanical threshold was present from 10 to 45 minutes and horses were less responsive to sound.Conclusion and clinical relevance Behavioral and physiological effects following intravenous administration positively correlate with pharmacokinetic profiles from plasma medetomidine concentrations. Glucose concentration gradually transiently increased following medetomidine administration. The analgesic effect of the drug appeared to have a very short duration.

Medetomidine, an .ALPHA.2-Adrenergic Agonist, Activates Cardiac Vagal Nerve Through Modulation of Baroreflex Control

Although α(2)-adrenergic agonists have been reported to induce a vagal-dominant condition through suppression of sympathetic nerve activity, there is little direct evidence that they directly increase cardiac vagal nerve activity. Using a cardiac microdialysis technique, we investigated the effects of medetomidine, an α(2)-adrenergic agonist, on norepinephrine (NE) and acetylcholine (ACh) release from cardiac nerve endings. A microdialysis probe was implanted into the right atrial wall near the sinoatrial node in anesthetized rabbits and perfused with Ringer's solution containing eserine. Dialysate NE and ACh concentrations were measured using high-performance liquid chromatography. Both 10 and 100µg/kg of intravenous medetomidine significantly decreased mean blood pressure (BP) and the dialysate NE concentration, but only 100µg/kg of medetomidine enhanced ACh release. Combined administration of medetomidine and phenylephrine maintained mean BP at baseline level, and augmented the medetomidine-induced ACh release. When we varied the mean BP using intravenous administration of phenylephrine, treatment with medetomidine significantly steepened the slope of the regression line between mean BP and log ACh concentration. Medetomidine increased ACh release from cardiac vagal nerve endings and augmented baroreflex control of vagal nerve activity.

Subeffective doses of nitroparacetamol (NCX-701) enhance the antinociceptive activity of the α2-adrenoceptor agonist medetomidine

The α2-adrenergic system is involved in pain processing and inflammation-induced sensitization. α2-adrenoceptor agonists induce analgesia, and this effect is greater when administered in combination with other analgesics. In the present study, we assessed a possible enhancement of antinociception combining the α2-adrenoceptor agonist medetomidine with subeffective doses of NCX701 (nitroparacetamol). The effects of the drugs were studied in spinal cord neuronal responses from adult male Wistar rats with carrageenan-induced inflammation, using the recording of single motor unit technique. The experiments showed that the i.v. administration of medetomidine and NCX701 induced a more potent and effective antinociceptive effect than medetomidine when given alone (ID50: 0.47±0.1 vs. 1.1±0.1μg/kg) or in the presence of paracetamol, in naturally-evoked nociceptive responses. In addition, the duration of antinociception was significantly longer (P<0.001, 100min after administration). The use of low doses of NCX701 and α2-adrenoceptor agonists might open new perspectives in the treatment of inflammatory pain.

Efficacy of tricaine methanesulphonate, clove oil and medetomidine-ketamine and their side effects on the physiology of sturgeon hybrid Acipenser naccarii × Acipenser baerii

Three anaesthetic agents were tested in sturgeon hybrid Acipenser naccarii female × Acipenser baerii male: clove oil at 100 mg L−1 (CLO); tricaine methanesulfonate at 150 mg L−1 (MS-222); combined medetomidine and ketamine hydrochloride (MK) administered by intravenous injection at 0.04 mg kg−1 + 4 mg kg−1, respectively. Efficacy of the anaesthetics was evaluated as well as physiological effects on blood gas status, acid-base balance and stress response by measuring blood PCO2, PO2, pH, , haematocrit and serum cortisol, glucose, NEFA, lactate, Na+, K+, Cl− concentration. Anaesthetic dosages were safe and effective in order to rapidly anaesthetize the sturgeons: induction time was significantly shorter with MS-222 (3.2 min) compared with CLO (4.7 min) and MK (5.4 min). Recovery time was significantly longer in MK anaesthetized fish (16 min) in comparison with CLO (5.8 min) and MS-222 (3.8 min). Anaesthesia induced blood hypercapnia, respiratory acidosis and stress response, with differences among anaesthetics. Blood PCO2 and cortisol levels were significantly higher in MS-222 (11 mmHg; 97.0 ng ml−1) and CLO (9.6 mmHg; 65.3 ng ml−1) anaesthetized groups compared to MK (7.8 mmHg; 39.6 ng ml−1) and control (7.0 mmHg; 10 ng ml−1). Overall results indicated that anaesthesia with MS-222 produced a greater physiological impact in sturgeons compared to the other anaesthetics. The effects were slightly attenuated in fish anaesthetized with clove oil, indicating that the use of this chemical was better than MS-222 in reducing handling stress. MK anaesthesia affected physiological parameters to a lesser extent. Intravascular administration of medetomidine at a dose of 0.04 mg kg−1 in combination with ketamine at a dose of 4 mg kg−1 proved to be a safe and effective anaesthetic protocol in this hybrid sturgeon, suitable for experimental studies and diagnostic procedures related to broodstock management and artificial reproduction.

Cardiac troponin I concentrations following medetomidine–butorphanol sedation in dogs

ObjectiveTo evaluate the effect of medetomidine–butorphanol sedation on serum cardiac troponin I (cTnI) concentration, a marker of myocardial ischemia and injury, in healthy dogs undergoing pre–surgical radiographs for orthopedic procedures. Study designProspective clinical study. AnimalsTwenty client–owned dogs with no history of cardiac disease. MethodsDogs were evaluated for pre–existing cardiac disease with electrocardiogram (ECG), noninvasive blood pressure and echocardiogram. Sedation was achieved using a combination of medetomidine (10 μg kg−1) and butorphanol (0.2 mg kg−1) intravenously. Blood pressure, heart rate and ECG were serially recorded throughout the duration of sedation. Serum cTnI concentration was measured at baseline and 6, 18, and 24–hours post–sedation. ResultsFollowing administration of medetomidine and butorphanol, all dogs were adequately sedated for radiographs and had a decreased heart rate and increased diastolic blood pressure. Arrhythmias associated with increased parasympathetic tone occurred, including a sinus arrhythmia further characterized as a sinus bigeminy in 17 of the dogs. Serum cTnI was undetectable at all time points in all but three dogs. Two of the three dogs had a detectable concentration of cTnI at all time points measured, including prior to sedation. Only one of the two dogs had a cTnI concentration above the normal reference interval. The dogs that exhibited detectable cTnI had no significant difference in signalment, heart rate, blood pressure, or lactate concentration as compared to those with undetectable cTnI. Conclusions and clinical relevanceSedation with medetomidine and butorphanol had predictable cardiovascular effects including bradycardia, an increase in arterial blood pressure, and arrhythmias in apparently healthy dogs requiring radiographs for orthopedic injuries, but did not induce significant increases in serum cTnI concentration following the drug doses used in this study.

The hemodynamic effects of medetomidine continuous rate infusions in the dog

ObjectiveTo characterize the hemodynamic effects of continuous rate infusions (CRI) of medetomidine administered at doses ranging from 0 to 3 μg kg−1 hour−1. Study designProspective, blinded, randomized experimental trial. AnimalsSix adult purpose-bred mongrel dogs. MethodsAnesthesia was induced with sevoflurane for placement of arterial and venous catheters. Dogs recovered from anesthesia after which baseline hemodynamic measurements were obtained via lithium dilution cardiac output (CO) determination, with subsequent measurements via pulse power analysis to provide continuous CO determinations. Medetomidine, 1, 2, or 3 μg kg−1 hour−1 or a volume equivalent placebo, was administered via CRI for 60 minutes. Systolic, mean, and diastolic arterial pressure, heart rate (HR), CO and stroke volume were measured and stroke index (SI), cardiac index (CI), total peripheral resistance (TPR), and total peripheral resistance index (TPRI) were calculated at 3, 7, 10, 20, 30, 45, 60, 90, and 120 minutes from the start of the infusion. ResultsIncrease in dose decreased SI by 25%, 19%, and 30%, HR by 33%, 57%, and 60%, CI by 50%, 65%, 70% and increased TPRI by 109%, 235%, and 222% from baseline to the 60-minute measurement for the 1, 2, and 3 μg kg−1 hour−1 doses, respectively. HR, TPRI, and CI all showed significant differences over the duration of the study from the placebo treatment. ConclusionsMedetomidine CRI produces clinically relevant changes in CO, TPR, and HR. The demonstrated decrease in CO is largely because of bradycardia and the degree of cardiovascular depression appears to be dose-dependent. These findings are consistent with previously described hemodynamic changes with single bolus administration of medetomidine. Clinical relevanceLow-dose medetomidine CRIs produce clinically relevant hemodynamic depression at doses as low as 1 μg kg−1 hour−1 and should be used cautiously in dogs.

Comparison of cardiovascular function and quality of recovery in isoflurane‐anaesthetised horses administered a constant rate infusion of lidocaine or lidocaine and medetomidine during elective surgery

The effects of lidocaine combined with medetomidine or lidocaine alone on cardiovascular function during anaesthesia and their effects on recovery have not been thoroughly investigated in isoflurane-anaesthetised horses. To determine the effects of an intraoperative i.v. constant rate infusion of lidocaine combined with medetomidine (Group 1) or lidocaine (Group 2) alone on cardiovascular function and on the quality of recovery in 12 isoflurane-anaesthetised horses undergoing arthroscopy. The combination would depress cardiovascular function but improve the quality of recovery when compared to lidocaine alone in isoflurane-anaesthetised horses. Lidocaine (2 mg/kg bwt i.v. bolus followed by 50 microg/kg bwt/min i.v.) or lidocaine (same dose) and medetomidine (5 microg/kg bwt/h i.v.) was started 30 min after induction of anaesthesia. Lidocaine administration was discontinued 30 min before the end of surgery in both groups, whereas medetomidine administration was continued until the end of surgery. Cardiovascular function and quality of recovery were assessed. Horses in Group 1 had longer recoveries, which were of better quality due to better strength and overall attitude during the recovery phase than those in Group 2. Arterial blood pressure was significantly higher in Group 1 than in Group 2 and this effect was associated with medetomidine. No significant differences in cardiac output, arterial blood gases, electrolytes and acid-base status were detected between the 2 groups. The combination of an intraoperative constant rate infusion of lidocaine and medetomidine did not adversely affect cardiovascular function in isoflurane-anaesthetised horses and improved the quality of recovery when compared to an intraoperative infusion of lidocaine alone.

In vitro evaluation of fresh sperm quality in tomcats: A comparison of two collection techniques

The collection of semen from tomcats by urethral catheterization (CT) after medetomidine administration offers a novel and easy approach to obtain good quality sperm for in vitro fertilization. This study was designed to compare the sperm quality parameters and in vitro fertilizing capacity of CT spermatozoa with those of spermatozoa retrieved after epididymal slicing (EP). Semen was collected in seventeen adult cats by urethral catheterization, after which the cat was orchiectomized. Motility, morphology, plasma membrane integrity, acrosomal status, and in vitro fertilizing capacity of both fresh CT and EP samples were evaluated. The results showed that both total and progressive motility, as well as the percentage of normal spermatozoa, were higher for EP sperm than for CT sperm (P<0.01). Epididymal sperm had a lower percentage of spermatozoa with an intact acrosome (P<0.01), while CT sperm contained more spermatozoa with tail abnormalities (P<0.01). Other morphological parameters, as well as plasma membrane integrity, did not differ (P>0.05) between CT and EP sperm. Nevertheless, no difference (P>0.05) in in vitro fertilizing capacity between spermatozoa collected by means of the two different methods was found. In conclusion, semen collection by means of urethral catheterization after medetomidine administration yields fertilization results similar to epididymal slicing, despite the fact that several sperm variables were different. Since this novel catheterization technique is repeatable, is easy to perform and facilitates semen preparation protocols, it may be preferable for routine IVF experiments with fresh spermatozoa.

High field BOLD response to forepaw stimulation in the mouse

We have established a robust protocol for longitudinal fMRI in mice at high field MRI using a medetomidine anesthesia. Electrical forepaw stimulation in anesthetized animals is widely used to produce BOLD contrast in the primary somatosensory cortex. To preserve neuronal activity, most fMRI experiments used α-chloralose to produce sedation, but severe side effects make this procedure unsuitable for survival experiments. As advantageous alternative, the α2-adrenergic receptor agonist medetomidine has been applied successfully to permit longitudinal fMRI studies in rats. With the advent of transgenic technology, mouse models have become increasingly attractive raising the demand for implementation of a suitable fMRI protocol for mice. Therefore, we investigated the use of medetomidine for repetitive fMRI experiments in C57BL/6 mice. We evaluated the optimal medetomidine dose for subcutaneous application. Somatosensory evoked potentials (SSEPs) in the contralateral somatosensory cortex were recorded to assess brain activity under medetominidine following forepaw stimulation. Repetitive administration of medetomidine, the requirement for longitudinal brain activation studies, was well tolerated. Using the forepaw stimulation paradigm, we observed BOLD contrast in the contralateral somatosensory cortex in ∼50% of the performed scans using gradient echo-echo planar imaging (GE-EPI). However, imaging the small mouse brain at high field strength is challenging and we observed strong susceptibility artifacts in GE-EPI images in the cortex. We have developed an agar gel cap for successful compensation of these artifacts as prerequisite for successful mouse fMRI at 11.7T. The established protocol will be suitable for brain activation studies in transgenic animals and for studies of functional deficit and recovery after brain injury in mice.

Alfaxalone induction dose following administration of medetomidine and butorphanol in the dog

ObjectiveTo determine in dogs the effects of medetomidine and butorphanol, alone and in combination, on the induction dose of alfaxalone and to describe the induction and intubation conditions. Study designProspective, randomized, blinded clinical trial. AnimalsEighty-five client-owned dogs (ASA 1 or 2). MethodsSubjects were block randomized to treatment group according to temperament. The treatment groups were: medetomidine 4 μg kg−1 (M), butorphanol 0.1 mg kg−1 (B), or a combination of both (MB), all administered intramuscularly. After 30 minutes, a sedation score was assigned, and alfaxalone 0.5 mg kg−1 was administered intravenously over 60 seconds by an observer who was unaware of treatment group. Tracheal intubation conditions were assessed and, if tracheal intubation was not possible after 20 seconds, further boluses of 0.2 mg kg−1 were given every 20 seconds until intubation was achieved. Induction dose and adverse events (sneezing, twitching, paddling, excitement, apnoea and cyanosis) were recorded; induction quality and intubation conditions were scored and recorded. ResultsThe mean dose of alfaxalone required for induction was similar for groups M and B: 1.2 ± 0.4 mg kg−1. The mean dose requirement for group MB (0.8 ± 0.3 mg kg−1) was lower than groups M and B (p < 0.0001). Induction dose was not influenced by temperament or level of sedation. Induction and intubation scores did not differ between treatment groups. Adverse events were noted in 16 dogs; there was no association with treatment group, temperament or level of sedation. Conclusions and clinical relevanceMedetomidine and butorphanol administered in combination reduce the anaesthetic induction dose of alfaxalone compared to either agent alone. This difference should be taken into account when using this combination of drugs in a clinical setting.

268 IN VITRO EVALUATION OF FRESH SPERM QUALITY IN TOMCATS: A COMPARISON OF COLLECTION TECHNIQUES

Semen can be collected from tomcats by urethral catheterization (CT) after medetomidine administration, offering a novel approach to obtain sperm for in vitro fertilization. This study was designed to determine motion characteristics of CT sperm samples by means of computer-assisted sperm analysis (CASA) and to compare sperm quality parameters and in vitro fertilizing capacity of CT spermatozoa with those of spermatozoa retrieved after epididymal slicing (EP). Semen was collected in 17 adult cats by urethral catheterization as reported by Zambelli et al. (2008 Theriogenology 69, 485-490), after which the cat was orchidectomized. Motility (subjective and objective by means of CASA), morphology [eosin/nigrosin (E/N)], plasma membrane integrity (E/N and SYBR14-PI staining), and acrosomal status (FITC-PSA staining) of fresh CT and EP samples were evaluated and compared between both methods with a paired t-test or the Wilcoxon Rank test, dependent on normality of the data. In vitro maturation (24 h), fertilization (18 h), and culture (6h) of grade I to III oocytes were carried out as described by Pope et al. (2009 Theriogenology 71, 864-871). Twenty-four hours after in vitro insemination, fertilization rates were assessed for group 1 (CT; n = 148) and group 2 (EP; n = 159) presumptive zygotes. The distribution of presumptive zygotes between CT and EP over the different developmental stages was compared using Pearson chi-square test. Results showed that total and progressive motility as well as the percentage of normal spermatozoa were higher for EP sperm compared with CT sperm (P &lt; 0.01). Epididymal sperm had a lower percentage of spermatozoa with an intact acrosome (P &lt; 0.01), whereas CT sperm contained more spermatozoa with tail abnormalities (P &lt; 0.01). Other sperm parameters did not differ (P &gt; 0.05) between collection techniques. In group 1, 84% of in vitro-matured oocytes (metaphase II) were penetrated (40.2% cleaved, 24.4% with 2 pronuclei, 12.2% with &gt;2 pronuclei, 7.3% with expanded sperm head), whereas in group 2, penetration rate was 88.5% (42.7% cleaved, 21.8% with 2 pronuclei, 16.7% with &gt;2 pronuclei, 7.3% with expanded sperm head). No difference (P &gt; 0.05) in in vitro fertilizing capacity between spermatozoa collected by means of the 2 methods was found. In conclusion, semen collection by means of CT yields fertilization results similar to epididymal slicing, despite the fact that several sperm variables were different. Because CT is repeatable and easy to perform and does not require a trained male/queen in heat, it may be preferable for routine IVF experiments with fresh spermatozoa. The first author is a research fellow of the Fund for Scientific Research-Flanders (Belgium).

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.

The effect of the novel alpha–2–adrenoceptor agonist naphthylmedetomidine on pulse rate, arterial blood pressure and sedation in rabbits

ObjectiveThe aim of this study was to investigate the effect of a novel alpha–2–adrenoceptor (α2–AR) agonist, naphthylmedetomidine, on cardiorespiratory function and sedation in rabbits in comparison with medetomidine. Study designProspective, randomized, experimental trial. AnimalsForty–two chinchilla rabbits of both sexes, weighing 2.5–4.5 kg. MethodsThe rabbits received 350 μg kg−1 naphthylmedetomidine (n = 21) or medetomidine (n = 21) intramuscularly according to a randomization scheme. Arterial blood pressure (AP), oxygen saturation of haemoglobin (SpO2), pulse rate (PR) and righting reflex were monitored for 20 minutes after injection. ResultsBoth drugs significantly decreased PR. The effect of medetomidine was significantly greater than that of naphthylmedetomidine and was evident within 1 minute. The decrease in PR after naphthylmedetomidine administration first appeared after 4 minutes. Medetomidine decreased the SpO2 after 3 minutes but there was no effect after naphthylmedetomidine. Medetomidine decreased the mean, systolic and diastolic AP within 5 minutes of administration but naphthylmedetomidine had no effect. The mean time to loss of righting reflex was 185 and 714 seconds after the administration of medetomidine and naphthylmedetomidine respectively. Conclusions and clinical relevanceThese results provide the first description of the effects of naphthylmedetomidine on cardiovascular and psychomotor functions in rabbits. Further work is required to reveal the anaesthetic sparing, analgesic or sedative effect of partial naphthylmedetomidine.

The use of lingual venous blood to determine the acid–base and blood–gas status of dogs under anesthesia

ObjectiveTo assess the suitability of lingual venous blood (LBG) as an alternative to arterial blood (ABG) samples in determining acid–base balance and blood–gas status in dogs anesthetized for elective procedures and with medetomidine and isoflurane administration under experimental conditions. Study designProspective, randomized clinical and experimental study. AnimalsClinical population of 18 ASA I/II dogs for elective surgery and five healthy Beagles (3 females and 2 males) for the experimental study. MethodsBlood sampling was simultaneously performed at dorsal pedal arterial and lingual venous sites, generating paired data. Two paired samples were collected from each dog in the clinical part and four from each dog in the experimental part (two during isoflurane anesthesia and two during isoflurane plus medetomidine). A modified Bland and Altman method was used to examine data from the clinical part and the experimental data were subjected to a paired sign's test following transformation where appropriate. ResultsThe pH of LBG overestimated ABG, with limits of agreement of (−0.01, 0.02). The partial pressure of carbon dioxide (PCO2) of LBG overestimated ABG by 0.6 mmHg [0.1 kPa], with limits of agreement of (−3.5, 4.6) mmHg [−0.5, 0.6 kPa]. The partial pressure of oxygen (PO2) of LBG underestimated ABG by 86.3 mmHg [−11.5 kPa], with limits of agreement of (−199.8, 27.3) mmHg [−26.6, 3.6 kPa]. During medetomidine administration values for PO2 (p = 0.03) and lactate (p = 0.03) were lower for LBG when compared with ABG. The LBG value of PO2 was lower (p = 0.03) during medetomidine and isoflurane administration versus isoflurane alone. Conclusions and clinical relevanceThe pH and PCO2 of LBG samples provide clinically acceptable substitutes of ABG samples in the dog population studied. The wider limits of agreement for PO2 render it less reliable as a substitute for ABG. The difference in PO2 identified between LBG and ABG during medetomidine administration may not preclude the use of LBG as substitutes for ABG samples.

Effect of bupivacaine on epidural analgesia produced by xylazine or medetomidine in buffaloes (Bubalus bubalis)

ObjectiveTo evaluate and compare the effect of epidural bupivacaine on analgesia produced by epidural xylazine or medetomidine in buffaloes. Study designProspective, blinded study. AnimalsTen male buffalo calves (6-8 months of age; body weight 70-90 kg) were used on two occasions to conduct a total of 20 investigations. MethodsCaudal extradural analgesia was produced in four buffalo calves each by the injection of either xylazine (0.05 mg kg−1), medetomidine (15 μg kg−1) or 0.5% bupivacaine (0.125 mg kg−1), or combinations of xylazine and bupivacaine (0.05 and 0.125 mg kg−1), or medetomidine and bupivacaine (15 μg kg−1 and 0.125 mg kg−1) at the first intercoccygeal extradural space. Analgesia was tested using deep pinprick stimuli. ResultsExtradural administration of xylazine or medetomidine resulted in complete analgesia of the tail, perineum, inguinal region and the upper parts of the hind limbs, which was faster in onset and longer in duration in the medetomidine group than in the xylazine group. Addition of bupivacaine increased the intensity of the analgesia produced by xylazine, but not that produced by medetomidine. All the drugs caused mild to moderate ataxia, but signs of sedation were apparent only in animals which received xylazine or medetomidine. The extradural injections of all the drugs caused significant decrease in heart rate (p = 0.024), respiratory rate (p = 0.026) and rectal temperature (p = 0.036) from the respective baseline values, but the differences between the groups were not significant. ConclusionsMedetomidine produced a longer duration of analgesia than that produced by xylazine. Bupivacaine prolonged the analgesia produced by xylazine, but the analgesia produced by the combination of medetomidine and bupivacaine was not superior to that produced by medetomidine alone. Clinical relevanceBupivacaine may be used to prolong the extradural analgesia produced by xylazine, but not that produced by medetomidine in buffaloes.

The effects of medetomidine hydrochloride on the electroretinogram of normal dogs

To determine the effects of a standardized intravenous dose of an alpha-2 agonist (Domitor, Orion Pharma, distributed by Pfizer Animal Health, Exton, PA) on the electroretinogram (ERG) response in normal dogs. Twenty-five normal dogs were used to collect ERG responses including a- and b-wave implicit times (IT) and amplitudes (AMP) before and after administration of medetomidine. Dogs were dark adapted for 20 min and ERGs were obtained using the HMsERG (RetVetCorp Inc., Columbia, MO). The QuickRetCheck protocol (Narfström) was employed to provide the following flash intensities: 10 mcd s/m(2), 3 cd s/m(2), and 10 cd s/m(2). ERGs were repeated after 375 microg/m(2) of medetomidine intravenously. Statistical analysis of the difference between the responses before and after medetomidine at all flash intensities was performed using a mixed effects model for anova. The P value for the effect of medetomidine on each of the ERG responses was < 0.01. The estimates of the effect of medetomidine were (+)1.35 ms, (-)23 microV, (+)3.16 ms, and (-)47 microV for the a-wave IT, a-wave AMP, b-wave IT, and the b-wave AMP, respectively. Medetomidine significantly prolongs the implicit time and lowers the amplitude response of both the a- and b-waves in normal dogs at all flash intensities examined. Clinically, however, medetomidine only minimally affects the retinal responses and is a viable choice for use in dog ERGs.

Effects of a peripheral α2 adrenergic-receptor antagonist on the hemodynamic changes induced by medetomidine administration in conscious dogs

To evaluate the effects of administration of a peripheral alpha(2)-adrenergic receptor antagonist (L-659,066), with and without concurrent administration of glycopyrrolate, on cardiopulmonary effects of medetomidine administration in dogs. 6 healthy adult dogs. Dogs received saline (0.9% NaCl) solution (saline group), L-659,066 (group L), or L-659,066 with glycopyrrolate (group LG). These pretreatments were followed 10 minutes later by administration of medetomidine in a randomized crossover study. Hemodynamic measurements and arterial and mixed-venous blood samples for blood gas analysis were obtained prior to pretreatment, 5 minutes after pretreatment, and after medetomidine administration at intervals up to 60 minutes. After pretreatment in the L and LG groups, heart rate, cardiac index, and partial pressure of oxygen in mixed-venous blood (PvO2) values were higher than those in the saline group. After medetomidine administration, heart rate, cardiac index, and PvO2 were higher and systemic vascular resistance, mean arterial blood pressure, and central venous pressure were lower in the L and LG groups than in the saline group. When the L and LG groups were compared, heart rate was greater at 5 minutes after medetomidine administration, mean arterial blood pressure was greater at 5 and 15 minutes after medetomidine administration, and central venous pressure was lower during the 60-minute period after medetomidine administration in the LG group. Administration of L-659,066 prior to administration of medetomidine reduced medetomidine-induced cardiovascular changes in healthy dogs. No advantage was detected with concurrent administration of L-659,066 and glycopyrrolate.

Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves

To assess the sedative and cardiopulmonary effects of medetomidine and xylazine and their reversal with atipamezole in calves. 25 calves. A 2-phase (7-day interval) study was performed. Sedative characteristics (phase I) and cardiopulmonary effects (phase II) of medetomidine hydrochloride and xylazine hydrochloride administration followed by atipamezole hydrochloride administration were evaluated. In both phases, calves were randomly allocated to receive 1 of 4 treatments IV: medetomidine (0.03 mg/kg) followed by atipamezole (0.1 mg/kg; n = 6), xylazine (0.3 mg/kg) followed by atipamezole (0.04 mg/kg; 7), medetomidine (0.03 mg/kg) followed by saline (0.9% NaCl; 6) solution (10 mL), and xylazine (0.3 mg/kg) followed by saline solution (10 mL; 6). Atipamezole or saline solution was administered 20 minutes after the first injection. Cardiopulmonary variables were recorded at intervals for 35 minutes after medetomidine or xylazine administration. At the doses evaluated, xylazine and medetomidine induced a similar degree of sedation in calves; however, the duration of medetomidine-associated sedation was longer. Compared with pretreatment values, heart rate, cardiac index, and PaO(2) decreased, whereas central venous pressure, PaCO(2), and pulmonary artery pressures increased with medetomidine or xylazine. Systemic arterial blood pressures and vascular resistance increased with medetomidine and decreased with xylazine. Atipamezole reversed the sedative and most of the cardiopulmonary effects of both drugs. At these doses, xylazine and medetomidine induced similar degrees of sedation and cardiopulmonary depression in calves, although medetomidine administration resulted in increases in systemic arterial blood pressures. Atipamezole effectively reversed medetomidine- and xylazine-associated sedative and cardiopulmonary effects in calves.