Comparative analgesia of xylazine, xylazine/morphine, xylazine/butorphanol, and xylazine/nalbuphine in the horse, using dental dolorimetry

Xylazine, morphine, butorphanol, and nalbuphine were evaluated in 5 adult male horses, using dental dolorimetry. Comparisons were made at 30, 60, and 100 minutes after IV drug administration. Peak analgesia and the time to develop peak analgesia also were compared. Xylazine induced a marked increase in the tooth pulp pain threshold measurements as did the xylazine/narcotic combinations. Statistical differences were not detectable between these treatments. Xylazine and xylazine/butorphanol were better analgesics than was butorphanol alone at 30 and 60 minutes. Xylazine resulted in peak analgesia faster than did butorphanol or the combination of xylazine/butorphanol. Additive analgesic effects were not detected with the combined treatments.     

Effect of butorphanol, pentazocine, meperidine, or metoclopramide on intestinal motility in female ponies

Effect of butorphanol, pentazocine, meperidine, and metoclopramide on jejunal and pelvic flexure myoelectric and mechanical activity in 4 female ponies was investigated. The agent to be tested or saline solution was administered IV at the start of a 6-hour recording trial. In the jejunum, duration between activity fronts of regular spiking activity, defined as the length of the migrating myoelectric complex (MMC), was measured. The average duration of the MMC during control trials was 150 +/- 46 minutes. The average duration of the MMC after meperidine, butorphanol, pentazocine, and metoclopramide administration was 295 +/- 70 minutes, 260 +/- 60 minutes, 275 +/- 60 minutes, and 163 +/- 64 minutes, respectively. Meperidine, butorphanol, or pentazocine significantly increased the MMC duration (P less than 0.05), and did not significantly alter the pelvic flexure activity. Seemingly, meperidine, butorphanol, and pentazocine inhibited cyclic myoelectric activity in the jejunum. Metoclopramide had no effect on jejunal or pelvic flexure motility.     

Comparison of lidocaine, xylazine, and xylazine/lidocaine for caudal epidural analgesia in horses.

Caudal epidural analgesia was achieved in 6 adult horses on 3 successive occasions at weekly intervals by injection of lidocaine, xylazine, and a combination of lidocaine/xylazine through indwelling epidural catheters. Analgesia was defined as a lack of response to pinprick and hemostat pressure in the skin of the perineal area. A significant (P < 0.05) difference was not found for time of onset of analgesia between lidocaine (4.3 +/- 0.8 minutes, mean +/- SEM) and the lidocaine/xylazine combination (5.3 +/- 1.3 minutes). Time to onset of analgesia after administration of xylazine was significantly (P < 0.05) longer (32.0 +/- 3.4 minutes) than that for either of the other 2 treatments. Duration of analgesia was significantly (P < 0.05) longer for the combination (329.8 +/- 6.2 minutes) than for either drug used alone (lidocaine, 87.2 +/- 7.5 minutes; xylazine, 204.2 +/- 12.9 minutes). Pulse and respiratory rates were not significantly altered by any of the drugs. Neurologic sequelae were not clinically apparent after administration of the drugs or after chronic epidural catheterization.     

Epidural injection of xylazine for perineal analgesia in horses

Local anesthetics given in the epidural space of a horse may cause hind limb weakness in addition to analgesia. Because alpha 2 agonists given by epidural injection cause sensory blockade without motor effects in human beings and other species, their use in veterinary anesthesia is appealing. This study was designed to examine the effectiveness of xylazine HCl, an alpha 2 agonist commonly used in horses. Xylazine, 0.9% NaCl, and lidocaine were given by epidural injection to horses subjected to perineal electrical stimulation. Administration of xylazine (0.17 mg/kg of body weight, diluted to a 10-ml volume, using 0.9% NaCl) induced approximately 2.5 hours of local analgesia without apparent side effects. Higher doses of xylazine caused mild hind limb ataxia. Administration of lidocaine induced a similar duration of analgesia, with severe hind limb ataxia (100% incidence). We concluded that xylazine given by epidural injection results in safe, effective perineal analgesia in horses.     

Cardiovascular effects of medetomidine, detomidine and xylazine in horses

The cardiovascular effects of medetomidine, detomidine, and xylazine in horses were studied. Fifteen horses, whose right carotid arteries had previously been surgically raised to a subcutaneous position during general anesthesia were used. Five horses each were given the following 8 treatments: an intravenous injection of 4 doses of medetomidine (3, 5, 7.5, and 10 microg/kg), 3 doses of detomidine (10, 20, and 40 microg/kg), and one dose of xylazine (1 mg/kg). Heart rate decreased, but not statistically significant. Atrio-ventricular block was observed following all treatments and prolonged with detomidine. Cardiac index (CI) and stroke volume (SV) were decreased with all treatments. The CI decreased to about 50% of baseline values for 5 min after 7.5 and 10 microg/kg medetomidine and 1 mg/kg xylazine, for 20 min after 20 microg/kg detomidine, and for 50 min after 40 microg/kg detomidine. All treatments produced an initial hypertension within 2 min of drug administration followed by a significant decrease in arterial blood pressure (ABP) in horses administered 3 to 7.5 microg/kg medetomidine and 1 mg/kg xylazine. Hypertension was significantly prolonged in 20 and 40 microg/kg detomidine. The hypotensive phase was not observed in 10 microg/kg medetomidine or detomidine. The changes in ABP were associated with an increase in peripheral vascular resistance. Respiratory rate was decreased for 40 to 120 min in 5, 7.5, and 10 microg/kg medetomidine and detomidine. The partial pressure of arterial oxygen decreased significantly in 10 microg/kg medetomidine and detomidine, while the partial pressure of arterial carbon dioxide did not change significantly. Medetomidine induced dose-dependent cardiovascular depression similar to detomidine. The cardiovascular effects of medetomidine and xylazine were not as prolonged as that of detomidine. KEY WORDS: cardiovascular effect, detomidine, equine, medetomidine, xylazine.     

Cardiovascular effects of xylazine and detomidine in horses

The cardiovascular effects of xylazine and detomidine in horses were studied. Six horses were given each of the following 5 treatments, at 1-week intervals: xylazine, 1.1 mg/kg, IV; xylazine, 2.2 mg/kg, IM; detomidine, 0.01 mg/kg, IV; detomidine, 0.02 mg/kg, IV; and detomidine, 0.04 mg/kg, IM. All treatments resulted in significantly decreased heart rate, increased incidence of atrioventricular block, and decreased cardiac output and cardiac index; cardiac output and cardiac index were lowest following IV administration of 0.02 mg of detomidine/kg. Mean arterial pressure was significantly reduced for various periods with all treatments; however, IV administration of 0.02 mg of detomidine/kg caused hypertension initially. Systemic vascular resistance was increased by all treatments. Indices of ventricular contractility and relaxation, +dP/dt and -dP/dt, were significantly depressed by all treatments. Significant changes were not detected in stroke volume or ejection fraction. The PCV was significantly reduced by all treatments. Respiratory rate was significantly decreased with all treatments, but arterial carbon dioxide tension did not change. Arterial oxygen tension was significantly decreased briefly with the 3 IV treatments only.     

Analgesic effects of butorphanol in horses: dose-response studies

The analgesic effects of butorphanol (0.05, 0.1, 0.2, and 0.4 mg/kg), pentazocine (2.2 mg/kg), and butorphanol vehicle (0.04 ml/kg) were observed in 6 horses. These horses were instrumented to measure response objectively to painful superficial and visceral stimuli. The tested drugs were given IV according to a Latin square design. After preinjection base-line measurements were made, the analgesic effects were observed at 15 and 30 minutes and then at 30-minute intervals until postinjection minute 240. Analgesic effects of butorphanol were dose-related, with durations between 15 and 90 minutes. Duration of analgesia after pentazocine (2.2 mg/kg) was given was between 15 and 30 minutes. When compared with pentazocine, the 0.4 mg/kg dose of butorphanol provided a more intense and longer period of analgesia. A butorphanol dose of 0.2 mg/kg IV appears optimal. On a dose-body weight basis, the potency of butorphanol was 10 to 17 times that of pentazocine. Behavioral side effects were noted with both agents and were dose-related.     

Perineal analgesia and hemodynamic effects of the epidural administration of meperidine or hyperbaric bupivacaine in conscious horses

Epidural administration of bupivacaine and meperidine produces analgesia in several animal species and in humans. A prospective randomized study was conducted in 18 healthy horses to compare the effect of these 2 drugs administered by the epidural route. Animals were divided into 3 treatment groups of 6 animals each. All drugs were injected by the epidural route in all animals between the 1st and 2nd coccygeal vertebrae. Treatment 1 (BUP)--0.06 mg/kg of body weight of 0.5% hyperbaric bupivacaine; treatment 2 (MEP)--0.6 mg/kg of body weight of 5% meperidine; treatment 3 (SS)--0.9% saline solution (control group). Heart rate, arterial pressure, respiratory rate, rectal temperature, analgesia, sedation, and motor-blocking were determined before drug administration (baseline values); at 5, 10, 15, and 30 minutes after drug administration, and then at 30-minute intervals thereafter. Both hyperbaric bupivacaine and meperidine administered epidurally produced complete bilateral perineal analgesia in all horses. The onset of analgesia was 6, s = 2.6 minutes after injection of bupivacaine, as opposed to 9, s = 2 minutes after meperidine. The duration of analgesia was 240, s = 57 minutes for meperidine and 320, s = 30 minutes for bupivacaine. Heart and respiratory rates, arterial pressure, and rectal temperature did not change (P < 0.05) significantly from basal values after the epidural administration of bupivacaine, meperidine, or saline solution. To conclude, both bupivacaine and meperidine induced long-lasting perineal analgesia, with minimal cardiovascular effects. Analgesia was induced faster and lasted longer with bupivacaine.     

Effects of xylazine butorphanol on cecal arterial blood flow, cecal mechanical activity, and systemic hemodynamics in horses

A chronic model with an ultrasonic transit time blood flow probe and strain gauge force transducers implanted on the cecum was used to evaluate cecal mechanical activity and cecal arterial blood flow in 4 conscious adult horses. Intravenous administration of xylazine (1.1 mg/kg of body weight) significantly decreased heart rate and cardiac output, but significantly increased diastolic pulmonary arterial pressure, mean pulmonary arterial pressure, carotid arterial pressure, and central venous pressure. Lateral cecal arterial blood flow after xylazine administration was decreased substantially more than was cardiac output, suggesting that xylazine caused constriction of the cecal vasculature. This effect of xylazine may have resulted from either a direct effect of xylazine on the cecal vasculature or from reflex vasoconstriction attributable to reduced cardiac output. Intravenous administration of butorphanol tartrate (0.1 mg/kg) did not significantly alter the hemodynamic responses to xylazine. Cecal mechanical activity, as measured by the motility index, was decreased for 120 minutes after administration of xylazine and for 150 minutes after administration of xylazine/butorphanol.     

Sedative and cardiopulmonary effects of buprenorphine and xylazine in horses

This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 μg/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX50), or 0.75 mg/kg BW (BX75), all of them by IV. Cardiopulmonary parameters were evaluated for 120 min after the drugs were administered and intestinal motility was observed for 12 h after treatment. Sedation was found to be dose-dependent in all groups receiving buprenorphine and xylazine and it was observed that the heart rate decreased in the first 5 min and increased at the end of the sedation period. Arterial blood gas tension analyses showed minimal alterations during the experiment. Gastrointestinal hypomotility was observed for up to 8 h. The combination of buprenorphine and 0.50 mg/kg BW of xylazine (BX50) provided a 30-minute period of sedation without intense ataxia and maintained cardiopulmonary parameters within acceptable limits for the species.     

Effects of treatment with oxytocin,xylazine butorphanol,guaifenesin, acepromazine,and detomidine on esophageal manometric pressure in conscious horses

OBJECTIVE: To compare effects of oxytocin, acepromazine maleate, xylazine hydrochloride-butorphanol tartrate, guaifenesin, and detomidine hydrochloride on esophageal manometric pressure in horses. ANIMALS: 8 healthy adult horses. PROCEDURE: A nasogastric tube, modified with 3 polyethylene tubes that exited at the postpharyngeal area, thoracic inlet, and distal portion of the esophagus, was fitted for each horse. Amplitude, duration, and rate of propagation of pressure waveforms induced by swallows were measured at 5, 10, 20, 30, and 40 minutes after administration of oxytocin, detomidine, acepromazine, xylazine-butorphanol, guaifenesin, or saline (0.9% NaCI) solution. Number of spontaneous swallows, spontaneous events (contractions that occurred in the absence of a swallow stimulus), and high-pressure events (sustained increases in baseline pressure of > 10 mm Hg) were compared before and after drug adminision. RESULTS: At 5 minutes after administration, detomidine increased waveform amplitude and decreased waveform duration at the thoracic inlet. At 10 minutes after administration, detomidine increased waveform duration at the thoracic inlet. Acepromazine administration increased the number of spontaneous events at the thoracic inlet and distal portion of the esophagus. Acepromazine and detomidine administration increased the number of high-pressure events at the thoracic inlet. Guaifenesin administration increased the number of spontaneous events at the thoracic inlet. Xylazine-butorphanol, detomidine, acepromazine, and guaifenesin administration decreased the number of spontaneous swallows. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine, acepromazine, and a combination of xylazine butorphanol had the greatest effect on esophageal motility when evaluated manometrically. Reduction in spontaneous swallowing and changes in normal, coordinated peristaltic activity are the most clinically relevant effects.     

Cardiorespiratory and metabolic effects of xylazine, detomidine, and a combination of xylazine and acepromazine administered after exercise in horses

OBJECTIVE: To determine sedative, cardiorespiratory and metabolic effects of xylazine hydrochloride, detomidine hydrochloride, and a combination of xylazine and acepromazine administered i.v. at twice the standard doses in Thoroughbred horses recuperating from a brief period of maximal exercise. ANIMALS: 6 adult Thoroughbreds. PROCEDURE: Horses were preconditioned by exercising them on a treadmill to establish a uniform level of fitness. Each horse ran 4 simulated races, with a minimum of 14 days between races. Simulated races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until they were fatigued or for a maximum of 2 minutes. One minute after the end of exercise, horses were treated i.v. with xylazine (2.2 mg/kg of body weight), detomidine (0.04 mg/kg), a combination of xylazine (2.2 mg/kg) and acepromazine (0.04 mg/kg), or saline (0.9% NaCl) solution. Treatments were randomized so that each horse received each treatment once, in random order. Cardiopulmonary indices were measured, and samples of arterial and venous blood were collected immediately before and at specific times for 90 minutes after the end of each race. RESULTS: All sedatives produced effective sedation. The cardiopulmonary depression that was induced was qualitatively similar to that induced by administration of these sedatives to resting horses and was not severe. Sedative administration after exercise prolonged the exercise-induced increase in body temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of xylazine, detomidine, or a combination of xylazine-acepromazine at twice the standard doses produced safe and effective sedation in horses that had just undergone a brief, intense bout of exercise.     

Development of a xylazine constant rate infusion with or without butorphanol for standing sedation of horses

ObjectiveTo elaborate constant rate infusion (CRI) protocols for xylazine (X) and xylazine/butorphanol (XB) which will result in constant sedation and steady xylazine plasma concentrations.Study designBlinded randomized experimental study.AnimalsTen adult research horses.MethodsPart I: After normal height of head above ground (HHAG = 100%) was determined, a loading dose of xylazine (1 mg kg^?1) with butorphanol (XB: 18 μg kg^?1) or saline (X: equal volume) was given slowly intravenously (IV). Immediately afterwards, a CRI of butorphanol (XB: 25 μg kg^?1 hour^?1) or saline (X) was administered for 2 hours. The HHAG was used as a marker of depth of sedation. Sedation was maintained for 2 hours by additional boluses of xylazine (0.3 mg kg^?1) whenever HHAG >50%. The dose of xylazine (mg kg^?1 hour^?1) required to maintain sedation was calculated for both groups. Part II: After the initial loading dose, the calculated xylazine infusion rates were administered in parallel to butorphanol (XB) or saline (X) and sedation evaluated. Xylazine plasma concentrations were measured by HPLC-MS-MS at time points 0, 5, 30, 45, 60, 90, and 120 minutes. Data were analyzed using paired t-test, Wilcoxon signed rank test and a 2-way anova for repeated measures (p < 0.05).ResultsThere was no significant difference in xylazine requirements (X: 0.69, XB: 0.65 mg kg^?1 hour^?1) between groups. With treatment X, a CRI leading to prolonged sedation was developed. With XB, five horses (part I: two, part II: three) fell down and during part II four horses appeared insufficiently sedated. Xylazine plasma concentrations were constant after 45 minutes in both groups.ConclusionXylazine bolus, followed by CRI, provided constant sedation. Additional butorphanol was ineffective in reducing xylazine requirements and increased ataxia and apparent early recovery from sedation in unstimulated horses.Clinical relevanceData were obtained on unstimulated healthy horses and extrapolation to clinical conditions requires caution.     

Comparison of detomidine hydrochloride, xylazine, and xylazine plus morphine in horses: a double blind study

Detomidine (30 mcg/kg), xylazine (1.1 mg/kg) and xylazine/morphine (1.1 mg/kg and 0.75 mg/kg with 300 mg maximum dose) were compared in horses admitted for broncho-alveolar lavage. Horses (n=99) were randomized and clinicians performing the procedure were unaware of the sedation used. Horses were assessed during the procedure and for the next 2 hours. A significant number of xylazine/morphine-sedated horses showed excitement (p<0.05). The frequency of sinus block or arrest and second-degree atrioventricular block was significantly greater with detomidine. Detomidine-sedated horses were significantly more depressed than either xylazine or xylazine/morphine treated animals. Heart rate was significantly greater in horses given xylazine/morphine by 60 min. There was no significant difference between drug treatments related to reactions to the procedure or respiratory rate depression. The study indicated that all three methods are suitable for standing restraint. The more frequent adverse side effects (circling, muscle fasciculations, head pressing) accompanying xylazine/morphine should be considered.     

Effects of butorphanol, flunixin, levorphanol, morphine, and xylazine in ponies

The analgesic and behavioral effects of butorphanol (0.22 mg/kg), flunixin (2.2 mg/kg), levorphanol (0.033 mg/kg), morphine (0.66 mg/kg), and xylazine (2.2 mg/kg), given IM were observed in 8 ponies. These ponies were instrumented to measure response objectively to painful superficial and visceral stimuli. Effects on the cardiopulmonary system and rectal temperature also were evaluated in 6 of these ponies. Observations were conducted before drug injection (base-line values) and after injection at 30, 60, 120, 180, and 240 minutes. Xylazine provided the highest pain threshold for the first 60 minutes and a sedative effect for 105 minutes. The effects for superficial pain and visceral pain persisted 3 hours and 4 hours, respectively. Morphine produced good analgesia for superficial pain (30 minutes), whereas butorphanol provided good effect for visceral pain (4 hours). A slight degree of analgesia for visceral pain was obtained after morphine (1 hour) and levorphanol (4 hours); flunixin did not induce analgesia. Butorphanol, levorphanol, and morphine stimulated motor activity. Behavioral effects did not occur after flunixin was given. Xylazine decreased systolic, diastolic, and mean blood pressures. Marked increases in these pressures, heart rate, and respiratory rate were observed after morphine was given. Changes of central venous pressure, rectal temperature, and blood gas values remained within base-line limits after both drugs were given. Butorphanol increased heart rates for 1 hour; flunixin and levorphanol did not alter any of the above values.     

The effects of xylazine,detomidine, acepromazine and butorphanol on equine solid phase gastric emptying rate

The aim of this study was to measure the effects of specific commonly used sedative protocols on equine solid phase gastric emptying rate, using the 13C-octanoic acid breath test (13C-OABT). The gastric emptying of a standard 13C-labelled test meal was measured once weekly in 8 mature horses over two 4 week treatment periods. Each horse acted as its own control. In treatment Period 1, saline (2 ml i.v.), xylazine (0.5 mg/kg i.v.), detomidine (0.01 mg/kg i.v.) or detomidine/butorphanol combination (0.01/0.02 mg/kg i.v.) was administered in randomised order after ingestion of the test meal. During treatment Period 2, test meal consumption was followed by saline, xylazine (1.0 mg/kg i.v.), or detomidine (0.03 mg/kg i.v.) administration, or preceded by acepromazine (0.05 mg/kg i.m.) in randomised order. The 13C:12C ratio of sequential expiratory breath samples was determined by isotope ratio mass spectrometry, and used to measure the gastric half-emptying time, t 1/2, and duration of the lag phase, t lag, for each of the 64 tests. In treatment Period 1, detomidine/butorphanol prolonged both t 1/2 and t lag with respect to xylazine 0.5 mg/kg and the saline control (P < 0.05). In Period 2, detomidine 0.03 mg/kg delayed each parameter with respect to saline, acepromazine and xylazine 1.0 mg/kg (P < 0.001). Xylazine 1.0 mg/kg also lengthened t lag relative to the saline control (P = 0.0004), but did not cause a significant change in t 1/2. Comparison of treatment periods showed that the inhibitory effect of detomidine on gastric emptying rate was dose related (P<0.05). These findings may have clinical significance for case selection when these agents are used for purposes of sedation and/or analgesia.