Respiratory Depressant and Skeletal Muscle Relaxant Effects of Low-Dose Pancuronium Bromide in Spontaneously Breathing, Isoflurane-Anesthetized Dogs

Objective—To assess and compare the respiratory depressant and skeletal muscle relaxant effects of two low doses of a nondepolarizing neuromuscular blocker, pancuronium bromide. To determine if a “low dose” of pancuronium bromide can produce selective skeletal muscle relaxation in extraocular muscles sufficient to perform intraocular surgery while sparing or minimizing depression of muscles of ventilation. Study Design—Blinded, randomized crossover, placebo controlled study. Animals—Six healthy, adult mongrel dogs weighing 20.8 ±1.9 kg. Methods—Spontaneously breathing, isoflurane-anesthetized dogs received 0.02 mg/kg pancuronium bromide, intravenously (IV), (high dose [HD]), 0.01 mg/kg pancuronium bromide, IV, (low dose [LD]), or saline placebo IV in a blinded, randomized crossover study. Indices of patient ventilation including tidal volume (Vt), respiratory rate (RR), and minute ventilation (V_E) were recorded throughout the study period. Serial arterial blood gas analyses were performed at timed intervals. Neuromuscular blockade of skeletal muscle was assessed at timed intervals with train-of-four stimulus/response ratios. Eye position scores, based on the degree of ocular rotation from a neutral gaze axis, were assigned by an ophthalmologist who was blinded to the treatment given. Results—Vt and V_E in HD dogs decreased by 82% from baseline after administration of pancuronium bromide. Similarly, Vt and V_E in LD dogs decreased 40% and 55%, respectively. Decreased ventilation in HD dogs corresponded with significant (P< .05) neuromuscular blockade, as indicated by train-of-four ratio less than 75% between 0 and 60 minutes. Eye position scores in HD and LD dogs were suitable for intraocular surgery between 0 and 60 minutes. Eye position scores in five of six control dogs were unsuitable for intraocular surgery at any time period. Conclusions—LD dogs experienced only transient, mild to moderate respiratory depression compared with HD dogs, which experienced prolonged, moderate to severe respiratory depression. Both LD and HD dogs acquired and maintained eye position scores suitable for intraocular surgery between 0 to 60 minutes. A “low dose” of pancuronium bromide, which would provide adequate extraocular muscle relaxation while minimizing ventilatory depression, was not identified. Clinical Relevance—All patients receiving any dose of neuromuscular blocking agents should be closely monitored and receive ventilatory assistance as needed.     

Renal effects of medetomidine in isoflurane-anesthetized dogs with special reference to its diuretic action

Renal effects of the selective alpha(2)-adrenoceptor agonist, medetomidine, were investigated in anesthetized dogs. Animals were administered medetomidine 20 and 40 microg/kg intravenously (IV) and 80 mug/kg intramuscularly (IM) or 1 ml of saline IV. Urine and blood samples were collected before and at 30, 60, 90 and 120 min following medetomidine injection. Mean arterial blood pressure (MABP), renal blood flow (RBF), glomerular filtration rate (GFR), urine volume (U(v)), urine osmolality (U(osm)), free water clearance (C(H2O)), fractional clearance of sodium (F(Na)), plasma osmolality (P(osm)), plasma glucose levels and plasma antidiuretic hormone (ADH) concentrations were measured. The results showed that IV administration of medetomidine initially increased MABP 5-15 min followed by long-lasting decrease. The initial hypertension was not observed after IM administration, which was accompanied by a more profound hypotensive effects. RBF, GFR, U(v), C(H2O) increased after IV injection and decreased after IM. Medetomidine increased FNa and Posm and decreased U(osm). Plasma glucose levels initially increased and subsequently decreased. Plasma ADH concentration was decreased by IV injection but increased by IM administration. Our data imply that: 1) IV administration of medetomidine at dose rates of 20 and 40 microg/kg results in profound diuresis up to 2 hr; 2) Suppression of ADH release from the CNS is one of the mechanisms of medetomidine-induced diuresis although it may not be the principal one.     

Influence of yohimbine and tolazoline on the cardiovascular, respiratory, and sedative effects of xylazine in the horse

To determine the effects of yohimbine and tolazoline on the cardiovascular, respiratory and sedative effects of xylazine, four horses were sedated with xylazine and treated with either yohimbine, tolazoline or saline. Xylazine was administered as an intravenous (i.v.) bolus (1.0 nig/kg) followed by a continuous infusion at the rate of 12 μg/kg/min. Heart rate, respiratory rate, mean arterial pressure, arterial blood gases, and the chin-to-floor distance were recorded throughout the experiment. After 60 min, either yohimbine or tolazoline was administered i.v. in incremental doses until reversal of sedation (defined as the return of the chin-to-floor distance to baseline values) was achieved. A control group in which a saline bolus was administered instead of an antagonist drug was included for comparison.
The average dose of yohimbine administered was 0.12 ± 0.02 (SEM) mg/kg. While the average dose of tolazoline was 7.5 ± 1.1 mg/kg. Both tolazoline and yohimbine antagonized the ventricular bradycardia and A-V conduction disturbances observed with xylazine administration. No change in mean arterial pressure was observed with xylazine or yohimbine administration, but tolazoline caused persistent mild systemic hypertension. There were no clinically significant changes in respiratory rate or arterial blood gas values with administration of either xylazine, yohimbine or tolazoline. The chin-to-floor distance decreased significantly with xylazine administration and increased significantly with administration of either yohimbine or tolazoline. In conclusion, both yohimbine and tolazoline successfully antagonized the cardiovascular and CNS depression associated with xylazine administration.     

Alterations in epinephrine-induced arrhythmogenesis after xylazine and subsequent yohimbine administration in isoflurane-anesthetized dogs

Effects of xylazine (1.1 mg/kg of body weight, IV bolus, plus 1.1 mg/kg/h infusion) and subsequent yohimbine (0.125 mg/kg, IV bolus) administration on the arrhythmogenic dose of epinephrine (ADE) in isoflurane (1.8% end-tidal)-anesthetized dogs were evaluated. The ADE was defined as the total dose of epinephrine that induced greater than or equal to 4 premature ventricular contractions within 15 seconds during a 3-minute infusion period or within 1 minute after the end of infusion. Total ADE values during isoflurane anesthesia, after xylazine administration, and after yohimbine injection were 36.6 +/- 8.45 micrograms/kg, 24.1 +/- 6.10 micrograms/kg, and 45.7 +/- 6.19 micrograms/kg, respectively. Intravenous xylazine administration significantly (P less than 0.05) increased blood pressure and decreased heart rate, whereas yohimbine administration induced a significant (P less than 0.05) decrease in blood pressure. induced a significant (P less than 0.05) decrease in blood pressure. After yohimbine administration, the ADE significantly (P less than 0.05) increased above that after isoflurane plus xylazine administration. After yohimbine administration, blood pressure measured immediately before epinephrine-induced arrhythmia was significantly (P less than 0.05) less than the value recorded during isoflurane plus xylazine anesthesia. Heart rate was unchanged among treatments immediately before epinephrine-induced arrhythmia. Seemingly, yohimbine possessed a protective action against catecholamine-induced arrhythmias in dogs anesthetized with isoflurane and xylazine.     

The influence of atipamezole on the cardiovascular effects of detomidine in horses

The reversal of the cardiovascular effects of the α₂-adrenoceptor agonist detomidine by the α₂-antagonist atipamezole was studied. Nine horses were given detomidine 20 μg/kg iv. On a separate occasion they were given atipamezole 100 μg/kg iv 15 mins after the detomidine injection. Blood gas tensions were measured and clinical signs of sedation were also observed. Bradycardia and the frequency of heart blocks induced by detomidine were reduced after atipamezole and blood pressure decreased. These reversal effects of atipamezole were of short duration (a few minutes) at the dose level tested. Two of the nine horses exhibited premature depolarisations after administration of detomidine, but not after atipamezole injection. PaO₂ decreased and PaCO₂ increased slightly after detomidine injection, but the arterial pH was within reference values or slightly elevated. Administration of atipamezole did not alter these values. Base excess rose after detomidine, and it decreased more quickly towards the baseline level, when the horses were given detomidine alone. No clinical adverse effects were seen from the administration of atipamezole. Atipamezole may be beneficial, if detomidine-induced bradycardia needs to be reversed in horses.     

A comparison of two intramuscular doses of xylazine-ketamine combination and tolazoline reversal in llamas

OBJECTIVE: To evaluate the anesthetic and cardiorespiratory effects of two doses of intramuscular xylazine/ketamine in llamas, and to determine if an intramuscular injection of tolazoline would shorten the anesthesia recovery time. STUDY DESIGN: Prospective randomized study. ANIMALS: Six castrated male llamas. METHODS: Each llama received a low dose (LD) (0.4 mg kg(-1) xylazine and 4 mg kg(-1) ketamine) and high dose (HD) (0.8 mg kg(-1) xylazine and 8 mg kg(-1) ketamine). Time to sedation, duration of lateral recumbency and analgesia, pulse, respiratory rate, hemoglobin oxygen saturation, arterial blood pressure, blood gases, and the electrocardiogram were monitored and recorded during anesthesia. Three llamas in each treatment were randomized to receive intramuscular tolazoline (2 mg kg(-1)) after 30 minutes of lateral recumbency. RESULTS: Onset of sedation, lateral recumbency, and analgesia was rapid with both treatments. The HD was able to provide at least 30 minutes of anesthesia in all six llamas. The LD provided only 30 minutes of anesthesia in two out of six llamas. Respiratory depression and hypoxemia were seen in the HD treatment during the first 10 minutes of lateral recumbency. Two llamas were severely hypoxemic during this period and were given nasal oxygen for five minutes. Heart rate decreased, but there were no significant changes in blood pressure. Tolazoline significantly shortened the duration of recumbency in the HD treatment. CONCLUSIONS: The HD provided more consistent clinical effects in llamas than did the LD. Intramuscular tolazoline shortens the duration of lateral recumbency in llamas anesthetized with this combination. CLINICAL RELEVANCE: Both doses appear to be very effective in providing restraint in llamas. The LD may be used for procedures requiring a short period of anesthesia or restraint. The HD could be used when a longer duration of anesthesia is desired. Supplemental oxygen should be available if using the HD. Tolazoline (IM) shortened the recovery time with this combination in llamas.     

A comparison of two combinations of xylazine-ketamine administered intramuscularly to alpacas and of reversal with tolazoline

ObjectiveTo evaluate the anesthetic and cardiorespiratory effects of two doses of intramuscular (IM) xylazine/ketamine in alpacas, and to determine if tolazoline would reduce the anesthetic recovery time.Study designProspective randomized crossover study.AnimalsSix castrated male alpacas.MethodsEach alpaca received a low dose (LD) (0.8 mg kg⁻¹ xylazine and 8 mg kg⁻¹ ketamine IM) and high dose (HD) (1.2 mg kg⁻¹ xylazine and 12 mg kg⁻¹ ketamine IM) with a minimum of one week between trials. Time to sedation, duration of lateral recumbency and analgesia, pulse rate, respiratory rate, hemoglobin oxygen saturation, arterial blood pressure, blood-gases, and the electrocardiogram were monitored and recorded during anesthesia. With each treatment three alpacas were randomly selected to receive tolazoline (2 mg kg⁻¹ IM) after 30 minutes of lateral recumbency.ResultsOnset of sedation, lateral recumbency and analgesia was rapid with both treatments. The HD was able to provide ≥30 minutes of anesthesia in five of six alpacas. The LD provided ≥30 minutes of anesthesia in three of six alpacas. Respiratory depression and hypoxemia occurred with the HD treatment during the first 10 minutes of lateral recumbency: two animals were severely hypoxemic and received nasal oxygen for 5 minutes. Heart rate decreased, but there were no significant changes in arterial blood pressure. Tolazoline significantly shortened the duration of recumbency with the HD.ConclusionsThe HD provided more consistent clinical effects in alpacas than the LD. Intramuscular tolazoline shortened the duration of lateral recumbency in alpacas anesthetized with the HD combination.Clinical relevanceBoth doses of the combination were effective in providing restraint in alpacas and the duration of restraint was dose dependent. Supplemental oxygen should be available if using the HD and IM administration of tolazoline will shorten the recovery time.     

An investigation of the effects of intratesticular alfaxalone and lidocaine during castration in piglets

Objective

To determine whether intratesticular injection of an alfaxalone–lidocaine combination can induce anesthesia and provide a rapid recovery in piglets undergoing surgical castration.

Antagonistic effects of atipamezole,yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats

This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 2 mg/kg BW xylazine intramuscularly, and saline (as the control); 160 μg/kg BW prazosin; or 40, 160, or 480 μg/kg BW atipamezole or yohimbine intravenously 0.5 h later. Urine and blood samples were collected 10 times over 8 h. Urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine, osmolality, and electrolyte values in both urine and plasma were measured. Both atipamezole and yohimbine antagonized xylazine-induced diuresis, but prazosin did not. The antidiuretic effect of atipamezole was more potent than that of yohimbine but not dose-dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed xylazine-induced decreases in both urine specific gravity and osmolality, and the increase in free water clearance. Glomerular filtration rate, osmolar clearance, and plasma electrolyte concentrations were not significantly altered. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP concentration, although the highest dose of both atipamezole and yohimbine increased plasma AVP concentration initially and temporarily, suggesting that this may in part influence antidiuretic effects of both agents. The diuretic effect of xylazine in cats may be mediated by α₂-adrenoceptors but not α₁-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against xylazine-induced diuresis in clinically normal cats.     

Sedative and physiological effects of brimonidine tartrate ophthalmic solution in healthy cats

Objective

To determine the effects of brimonidine tartrate ophthalmic solution on sedation, heart rate (HR), respiratory frequency (f_R), rectal temperature (RT) and noninvasive mean arterial pressure (MAP) in healthy cats.

Evaluation of neoadjuvant prednisone administration and surgical excision in treatment of cutaneous mast cell tumors in dogs

OBJECTIVE: To determine response rate and reduction in tumor burden and effect of dose on tumor response in dogs treated with neoadjuvant prednisone for cutaneous mast cell tumors (MCTs). DESIGN: Combined prospective clinical study and retrospective case series. ANIMALS: 49 dogs with MCT. PROCEDURES: Medical records were retrospectively reviewed for dogs with primary untreated cutaneous MCT managed with neoadjuvant prednisone administration and surgery. Tumor characteristics and response to treatment were recorded. A subset of dogs assigned to low-dose (LD) treatment with neoadjuvant prednisone (1.0 mg/kg [0.45 mg/lb], PO, q 24 h) or high-dose (HD) treatment (2.2 mg/kg [1.0 mg/lb], PO, q 24 h) was used to determine the effects of dose. RESULTS: The overall objective response rate was 70% for dogs treated with neoadjuvant prednisone; prednisone dose was not significantly associated with response. Prospectively, the median sum maximal diameter (MaxD) reduction was 45.2%, and reduction in tumor volume was 80.6%. In both treatment groups, the mean percentage MaxD reduction and tumor volume reduction were significant. The difference in response between the LD and HD groups was not significant. The LD group had mean MaxD and tumor volume reductions of 35.4% and 52.5%, respectively, compared with mean reductions of 48.8% in MaxD and 78% in tumor volume in the HD group. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with neoadjuvant prednisone appears to be useful for inducing reduction of MCTs and may facilitate resection when adequate surgical margins cannot be confidently attained because of mass location or size or both.     

The cardiovascular effects of dexmedetomidine given by continuous infusion during isoflurane anesthesia in dogs

In a previous study we showed that the MAC of isoflurane was decreased by 18 ± 12% and 59 ± 7% by constant rate infusions of dexmedetomidine at 0.5 and 3 μg kg^–1 hour^–1. The purpose of this study was to document the cardiovascular changes associated with these infusions of dexmedetomidine at 1.3 MAC isoflurane/ dexmedetomidine. Dogs were anesthetized with isoflurane in oxygen given by mask. A cephalic venous catheter, a dorsal pedal arterial catheter and a balloon tipped, Swan–Ganz, pulmonary arterial catheter were placed percutaneously. After instrumentation the dogs were maintained at 1.3 MAC isoflurane for 60 minutes. At this time a set of measurements was made including, heart rate, respiratory rate, core body temperature, pulmonary and systemic arterial blood pressures (SAP, MAP, DAP, CVP, SPAP, MPAP, DPAP and PAOP), cardiac output and arterial and mixed venous blood samples were collected for the measurement of blood gases, pH, hemoglobin concentration, PCV and total protein. Calculated variables included base excess (BE), (HCO₃^?), cardiac index, systemic and pulmonary vascular resistance indices, oxygen delivery, oxygen consumption, oxygen utilization ratio and shunt fraction. After these measurements to dogs were randomly assigned to receive a loading dose of 0.5 or 3 μg kg^–1 of dexmedetomidine given over 6 minutes followed by an infusion of 0.5 (LD) or 3 μg kg^–1 hour^–1 (HD), respectively. The concentration of isoflurane was reduced by the above percentages, respectively, to maintain 1.3 MAC. Full sets of measurements were repeated at 10, 30, 60, 90, 120, 150 and 180 minutes after the start of the loading dose. Measured and calculated variables were compared with baseline using an anova and a post‐hoc Tukey's test. Significance was set at p = 0.05 and results are given as mean ± SD. The initial concentration of isoflurane was 1.73 ± 0.02% and was reduced to 1.41 ± 0.02 and 0.72 ± 0.09% for the LD and HD, respectively. Heart rate decreased with both doses but no other parameter changed significantly with the LD. With the HD there were significant changes in SAP, MAP, DAP, CVP, MPAP, PAOP, CI, SVRI, PCV, DO₂ and shunt fraction. The LD appeared to have minimal effect on the cardiopulmonary values measured, whereas the HD caused typical changes expected with an alpha‐2 agonist.     

Effects of xylazine on airway function in ponies with recurrent airway obstruction.

The effect of IV administration of the alpha 2-adrenoceptor agonist xylazine hydrochloride (0.5 mg/kg of body weight) was examined in ponies with recurrent obstructive pulmonary disease, commonly called heaves. Six ponies with the disease (principals) were studied during clinical remission and during an acute attack of airway obstruction precipitated by stabling and feeding of dusty hay. Six control ponies were also studied. In principal ponies with airway obstruction, xylazine administration significantly (P < 0.05) decreased pulmonary resistance and increased dynamic compliance, but did not affect PaO2 or PaCO2. The alpha 2-antagonist yohimbine blocked the pulmonary effects of xylazine. Administration of saline solution was without effect in both groups of ponies at all periods and xylazine did not have effect in controls or in principals in clinical remission.     

Effects of intravenously administered yohimbine on antinociceptive, cardiorespiratory, and postural changes induced by epidural administration of detomidine hydrochloride solution to healthy mares

OBJECTIVE: To determine effects of i.v. administered yohimbine on perineal analgesia, cardiovascular and respiratory activity, and head and pelvic limb position in healthy mares following epidural administration of detomidine hydrochloride solution. ANIMALS: 8 healthy mares. PROCEDURE: Each mare received detomidine hydrochloride (0.06 mg/kg of body weight), administered in the caudal epidural space, followed 61 minutes later by yohimbine (0.05 mg/kg; test) or sterile saline (0.9% NaCl) solution (control), administered i.v., in a randomized, crossover study design with > or = 2 weeks between treatments. Analgesia was determined by lack of sensory perception to electrical stimulation of perineal dermatomes and needle-prick stimulation of coccygeal to 15th thoracic dermatomes. Arterial pH, PaCO2, PaO2, heart and respiratory rates, rectal temperature, arterial blood pressure, and cardiac output were determined, and mares were observed for sweating and urination. Mean scores obtained for test and control groups were compared. RESULTS: Intravenously administered yohimbine significantly reduced mean scores of detomidine-induced perineal analgesia, head ptosis, changes in pelvic limb position, and sweating and diuresis; antagonized detomidine-induced decreases in heart rate and cardiac output; but did not affect detomidine-induced decrease in respiratory rate. CONCLUSIONS AND CLINICAL RELEVANCE: Most effects of epidurally administered detomidine, except bradypnea, were antagonized by yohimbine, suggesting that detomidine may influence respiratory rate by mechanisms other than stimulation of alpha2-adrenoceptors, or that yohimbine induces respiratory depressant effects. Yohimbine may be an effective alpha2-adrenoceptor antagonist for all but respiratory depression following epidural administration of detomidine to mares.     

Food intake and rumen motility in dwarf goats. Effects of atipamezole on the inhibitory effects induced by detomidine,medetomidine and romifidine

The effects of some ₂-adrenoceptor agonists and of the ₂-adrenoceptor antagonist atipamezole on food intake and ruminal contractions were studied in dwarf goats. Detomidine, 0.2 µg/kg per min for 10 min, failed to modify food intake during either the first or second observation period (0–30 min and 180–210 min after drug infusion, respectively). Given at a higher dose rate (0.4 µg/kg per min for 10 min), the drug inhibited food consumption during the first observation period, but stimulated food intake during the second period. A similar pattern was observed after IV infusion with medetomidine (0.2 µg/kg per min for 10 min), romifidine (0.4 µg/kg per min for 10 min) or xylazine (1 µg/kg per min for 10 min). The ₂-antagonist atipamezole (2 µg/kg per min for 10 min) failed to modify food intake during either the first or second observation period. After treatment with atipamezole, the effects of ₂-agonists on feeding behaviour were completely antagonized.The ₂-agonists administered at similar dose rates to those used in the food intake experiments induced bradycardia, decreases in body temperature and inhibition of ruminal contractions. The inhibition of ruminal contractions induced by romifidine was partly antagonized by atipamezole pre-treatment. These findings demonstrate that the ₂-agonist-induced changes in ruminal contractions do not simply cause changes in feeding behaviour. The drop in body temperature induced by ₂-agonists was prevented by atipamezole pre-treatment, whereas the induced bradycardia was not modified by this ₂-antagonist.Abbreviations IV intravenous - SEM standard error of the mean     

Modulation of formalin‐induced pain‐related behaviour by clonidine and yohimbine in the Speke's hinged tortoise (Kiniskys spekii)

The study was designed to investigate the involvement of noradrenergic and serotonergic receptor systems in the modulation of formalin‐induced pain‐related behaviour in the Speke's hinged tortoise. Intradermal injection of 100 μL of formalin at a dilution of 12.5% caused pain‐related behaviour (hindlimb withdrawal) that lasted for a mean time of 19.28 min (monophasic response). Intrathecal administration of clonidine (α₂‐adrenergic receptor agonist) and yohimbine (α₂‐adrenergic receptor antagonist) at a dose of 40 μg/kg and 37.5 μg/kg or 50 μg/kg, respectively, caused a highly significant reduction in the duration of the formalin‐induced pain‐related behaviour. The effect of clonidine was reversed by intrathecal administration of yohimbine at a dose of 26.7 μg/kg. The effect of yohimbine at a dose of 50 μg/kg was reversed by intrathecal injection of 20 μg/kg of the serotonergic receptor antagonist methysergide maleate. When performing antagonistic reactions, the administration of the antagonist was followed immediately by that of the agonist. The study indicates that for experimental purposes, intrathecal route of drug administration through the atlanto‐occipital joint is effective in tortoises. The data also suggest that testudines have noradrenergic and serotonergic systems that appear to play a role in the modulation of pain in this species.     

Influence of yohimbine and atipamezole on haemodynamics and ECG after lumbosacral subarachnoid administration of medetomidine in goats

Effects of intravenous yohimbine and atipamezole on haemodynamics and electrocardiogram (ECG) were studied after lumbosacral subarachnoid administration of medetomidine in eight goats. All goats received lumbosacral subarachnoid medetomidine at a dosage of 0.01 mg/kg followed by yohimbine (0.25 mg/kg) or atipamezole (0.005 mg/kg) intravenously 45 min after administration of medetomidine, in a randomized crossover design, in right lateral recumbency keeping a gap of 1 week between each trial. Heart rate, respiratory rate, rectal temperature, mean arterial pressure (MAP), mean central venous pressure (MCVP) and ECG were determined. Goats were observed for sedation and urination. All goats showed sedation and depression after medetomidine administration became alert within 2-5 min after reversal. Bradycardia and bradypnoea were the consistent findings after medetomidine injection. Tachycardia and tachypnoea were recorded within 2-5 min after reversal in both groups. A decrease in MAP and an increase in MCVP were seen after medetomidine administration in both groups. Effects of yohimbine and atipamezole on the reversal of MAP and MCVP were more or less the same and statistically non-significant (P > 0.05) in all animals. The ECG changes were non-significant (P > 0.05) in both groups. It is concluded that in the given dose rates both yohimbine (0.25 mg/kg) and atipamezole (0.005 mg/kg) produced equal reversal of the sedation, CNS depression, cardiopulmonary and ECG changes induced by subarachnoid administration of medetomidine in goats indicating that most of the actions of medetomidine were mediated via activation of alpha2-adrenergic receptors.     

Clinical use of yohimbine as an antagonist of xylazine depression of the central nervous system in cats

Antagonizing effects of various doses of yohimbine on a xylazine depression of the cerebroneural system (CNS) were studied in cats. Administration of various doses of yohimbine was investigated with respect to its antagonizing effects on various doses of xylazine. The time of CNS depression induced by commonly recommended doses of xylazine (2-4 mg/kg live weight) was shortened statistically significantly by intramuscular injections of yohimbine at a dose of 3 mg per kg live weight. After this yohimbine dose, the animals recovered consciousness already 10-15 minutes from application, with the complete resumption of reflexes. Preventive administration of the same dose of yohimbine hindered reliably the full development of CNS depression after the two xylazine doses (2 and 4 mg/kg live weight).     

A comparison of two intramuscular doses of xylazine–ketamine combination and tolazoline reversal in llamas

The anesthetic and cardiorespiratory effects of a low dose (LD, 0.4 mg kg^?1 xylazine and 4 mg kg^?1 ketamine) and a high dose (HD, 0.8 mg kg^?1 xylazine and 8 mg kg^?1 ketamine) of IM xylazine–ketamine combination were compared in a randomized cross‐over study using six castrated male llamas. Three llamas in each dosage group (LDT, HDT) were assigned to receive IM tolazoline (2 mg kg^?1) after 30 minutes of recumbency. All IM injections were given in the semitendinosus or semimembranosus muscles. Pulse, respiratory rate, and indirect arterial blood pressure were recorded every 10 minutes, and hemoglobin oxygen saturation was recorded every 5 minutes during lateral recumbency. Samples for arterial blood gas analysis were collected 5 minutes following recumbency and every 30 minutes thereafter. Base‐to‐apex ECG was monitored continuously. Analgesia was evaluated every 5 minutes by both a 30 minutes skin pinch and a needle prick of the toe. Most llamas breathed room air throughout anesthesia. Two llamas that developed severe hypoxemia (SpO₂ < 75%) received 5 minutes of nasal oxygen insufflation, but were maintained on room air for the rest of the anesthetic period. anova for repeated measures and Tukey's test were used to analyze cardiorespiratory data. Fischer's exact test was used to compare the ability of each to provide >30 minutes of lateral recumbency and analgesia. A p‐value < 0.05 was considered significant. Both dosages provided reasonably rapid induction following injection (LD: 10.8 ± 6.3 minutes; HD: 5.0 ± 1.1 minutes; p = 0.07). Duration of lateral recumbency and analgesia were 34.7 ± 6.7 and 27.3 ± 4.6 minutes, respectively, in the LDT llamas. None of the three remaining LD llamas remained in lateral recumbency for longer than 12 minutes. Duration of lateral recumbency and analgesia were 87.3 ± 18.5 and 67.7 ± 16.0 minutes, respectively, for the HD llamas that did not receive tolazoline. The HDT llamas were recumbent for a significantly shorter time (43.3 ± 0.6 minutes; p = 0.05). The ability to provide >30 minutes of recumbency and analgesia was better in the HD group (6/6) than in the LD group (2/6) (p = 0.03). No differences between dosages were seen in pulse rate, respiratory rate, or arterial pressures. No ECG abnormalities were seen. Transient hypoxemia was seen in the first 10 minutes of lateral recumbency in the HD group by both hemoglobin oxygen saturation (84 ± 9.5%) and by blood gas PaO₂ (44.5 ± 5.8 mm Hg). It was concluded that the HD provided more consistent results than the LD, but induced transient hypoxemia. Tolazoline shortened the recovery time in llamas receiving the HD.     

The reversal of xylazine hydrochloride by yohimbine and 4-aminopyridine in goats

Yohimbine, 4-aminopyridine, and a combination of the 2 drugs were studied to assess their potential as antagonists to xylazine in goats. Twenty-four small East African goats were divided randomly into 4 groups of 6 goats each in a placebo-controlled study. They were all treated with intramuscular xylazine at 0.44 mg/kg. At the time of maximum sedation, sterile water was administered intravenously to the control group, 0.15% 4-aminopyridine at 0.4mg/kg to Group 2, 0.1% yohimbine at 0.25 mg/kg to Group 3, and the combination of the 2 drugs at the same dose rates to Group 4. The yohimbine/4-aminopyridine combination was also used to antagonise xylazine at 0.88mg/kg in 6 goats. The heart rate, respiratory rate and rate of ruminal movements, the pedal and palpebral reflexes as well as the reaction to noxious stimuli, the standing time and the total recovery time were established and evaluated to assess the effects of the treatments. The drugs reversed the xylazine-induced decrease in the heart rate, respiratory rate and rate of ruminal movements, and also rapidly restored the reflexes as well as the reaction to noxious stimulation. In addition, they significantly (P < 0.05) decreased the mean standing time. The mean total recovery time was decreased significantly (P < 0.05) by 4-aminopyridine and the yohimbine/4-aminopyridine combination, but non-significantly (P > 0.05) by yohimbine. No relapse in sedation occurred. Overall, the combination of yohimbine and 4-aminopyridine produced better responses than the individual drugs, and may therefore be used for rapid reversal of xylazine-induced sedation in goats. Yohimbine or 4-aminopyridine may also be useful for this purpose but recovery may be prolonged.