Selected Aspects of the Clinical Pharmacology of Visceral Analgesics and Gut Motility Modifying Drugs in the Horse

Comparison of the visceral analgesic effects of xylazine, morphine, butorphanol, pentazocine, meperidine, dipyrone, and flunixin in a cecal distention model of colic pain indicated that xylazine produces the most relief from abdominal discomfort. Repeated administration of xylazine may reduce visceral pain so effectively that the seriousness of abdominal disease is obscured. Xylazine decreased propulsive motility in the jejunum and pelvic flexure of healthy ponies. Morphine and butorphanol also gave relief from visceral pain in the cecal distention model. Morphine may inhibit colonic, and butophanol jejunal, motility. Whether xylazine or opiate mediated decreases in gut motility cause clinically important slowing of ingesta transit is controversial and requires further investigation. The development of behavioral changes (i.e., apprehension and pawing) in horses given opiate therapy may limit the use of these drugs. Combinations of xylazine and morphine or butorphanol produce excellent, safe, visceral analgesia and sedation without untoward behavioral effects. Although flunixin fails to demonstrate good visceral analgesic effects in the cecal distention model, this drug produces analgesia in some cases of colic by blocking prostaglandin mediated induction of pain. Improvement of propulsive gut motility in patients with ileus may follow administration of neostigmine (which is particularly effective when the large bowel is hypomotile), naloxone (which experimentally stimulates propulsive colonic motility), and metoclopramide (which stimulates stomach and proximal small intestinal motility).     

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.     

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.     

Visceral analgesia: effects of xylazine, butorphanol, meperidine, and pentazocine in horses

The visceral analgesic, cardiorespiratory, and behavioral effects induced by xylazine, butorphanol, meperidine, and pentazocine were determined in 9 adult horses with colic. Colic was produced by inflating a balloon in the horses' cecum. Heart rate, respiratory rate, mean arterial blood pressure, and cardiac output increased after cecal balloon inflation. Xylazine and butorphanol decreased the hemodynamic response to cecal balloon inflation. Meperidine and pentazocine had minimal effects on the cardiorespiratory changes induced by cecal balloon inflation. Xylazine produced the most pronounced visceral analgesia. The duration of visceral analgesia was longest with xylazine (approx 90 minutes) followed by butorphanol (approx 60 min) and then by meperidine and pentazocine (approx 30 to 35 min). Accurate assessment of the effects of visceral analgesics is dependent upon the use of objective tests to evaluate pain.     

A comparison of ketorolac with flunixin, butorphanol, and oxymorphone in controlling postoperative pain in dogs.

Ketorolac tromethamine, a nonsteroidal anti-inflammatory analgesic, was compared with flunixin and butorphanol for its analgesic efficacy and potential side effects after laparotomy or shoulder arthrotomy in dogs. Sixty-four dogs were randomly assigned to receive butorphanol 0.4 mg/kg body weight (BW) (n = 21), flunixin 1.0 mg/kg BW (n = 21), or ketorolac 0.5 mg/kg BW (n = 22), in a double blind fashion. The analgesic efficacy was rated from 1 to 4 (1 = inadequate, 4 = excellent) for each dog. The average scores after laparotomy were ketorolac, 3.4; flunixin, 2.7; and butorphanol, 1.6. After shoulder arthrotomy, the average scores were ketorolac, 3.5; flunixin, 3.0; and butorphanol, 1.4 (5/11 dogs). As butorphanol was unable to control pain after shoulder arthrotomy, oxymorphone, 0.05 mg/kg BW, replaced butorphanol in a subsequent group of dogs and had a score of 2.0 (6/11 dogs). Serum alanine aminotransferase and creatinine were significantly elevated above baseline at 24 hours postoperatively in dogs receiving flunixin. One dog in each group developed melena or hematochezia. One dog receiving ketorolac had histological evidence of gastric ulceration. We concluded that ketorolac is a good analgesic for postoperative pain in dogs.     

Comparison of Intra-articular and Epidural Morphine for Analgesia Following Stifle Arthrotomy in Dogs

We prospectively studied 18 dogs that presented for exploratory stifle arthrotomy, with or without meniscectomy, and lateral extracapsular stabilization as a result of cranial cruciate ligament rupture. Dogs were premedicated with acepromazine, induced with thiopental, and maintained with halothane in oxygen. Preoperatively, dogs were assigned to one of three groups. Group 1 (n = 6) received intra-articular morphine (0.1 mg/kg diluted in 1 mL/10 kg body weight of saline) and epidural saline (1 mL/5 kg body weight saline plus the volume of saline representing 0.1 mg/kg of morphine). Group 2 (n = 6) received intra-articular saline (1 mL/10 kg body weight of saline plus the volume of saline representing 0.1 mg/kg of morphine) and epidural saline (1 mL/5 kg body weight saline plus the volume of saline representing 0.1 mg/kg of morphine). Group 3 (n = 6) received intra-articular saline (1 mL/10 kg body weight of saline plus the volume of saline representing 0.1 mg/kg of morphine) and epidural morphine (0.1 mg/kg of morphine diluted in 1 mL/5 kg body weight saline). The efficacy of each analgesia regimen was evaluated for 6 hours postoperatively with a pain score based on subjective and objective variables. Serum Cortisol and blood glucose concentrations were measured. Butorphanol was used to provide analgesia as needed based on a predetermined maximum pain score. Supplemental analgesics were required postoperatively every 2 to 3 hours for 6 hours in all dogs that did not initially receive analgesics (group 2). Pain scores were significantly lower in dogs administered morphine intra-articularly (group 1) and epidurally (group 3) at 30 minutes and 30, 120, and 360 minutes, respectively, compared with dogs that did not initially receive analgesics (group 2). One dog in group 1 and one dog in group 3 required supplemental analgesia with butorphanol. There was no difference between analgesia produced by intra-articular morphine compared with that of epidural morphine. Side effects after intra-articular or epidural morphine were not observed. Intra-articular administration of morphine can produce effective analgesia in dogs comparable with that produced by epidural administration of morphine.     

Dose response to butorphanol administered subcutaneously to increase visceral nociceptive threshold in dogs.

Butorphanol (0.025, 0.05, 0.1, 0.2, 0.4, and 0.8 mg/kg of body weight, and placebo) was given SC to 8 healthy unmedicated dogs to determine its efficacy for visceral analgesia, using a colonic balloon for minimal threshold nociceptor stimulation. Degree of sedation; systolic, diastolic, and mean arterial pressure; and pulse rate were recorded. The highest 3 dosages, 0.2, 0.4, and 0.8 mg/kg, were found to be most effective, with 0.8 mg/kg the only dosage that was significantly different from control responses at the 45-minute interval. Duration of analgesia ranged from 23 to 53 minutes for all 6 dosages and dosing durations were not significantly different from one another. Blood pressures did not change, but pulse rate was significantly decreased by 0.8 mg of butorphanol/kg. We concluded that butorphanol is an effective visceral analgesic of relatively short duration in the dog.     

Analgesic effect of butorphanol in ponies following castration

Reasons for performing study: In the UK butorphanol has a marketing authorisation for administration to horses for sedation in combination with detomidine, and at a higher dose (0.1 mg/kg bwt), for the alleviation of pain. There is only a limited number of clinical studies designed to examine the analgesic effects of butorphanol administration following surgery. Objective: To investigate the effect of premedication with butorphanol on post operative pain following castration under general anaesthesia in ponies. Hypothesis: Ponies receiving butorphanol would experience less pain after castration than ponies that did not receive butorphanol. Methods: A randomised, observer blinded clinical study in which 20 ponies received butorphanol and detomidine (Group B) or detomidine alone (Group C). Anaesthesia was induced with ketamine and diazepam and open castration performed. Pain was assessed by one individual using a dynamic interactive visual analogue scale (DIVAS) 100 mm in length (0 = no pain, 100 mm the maximum possible pain for that procedure). ‘Rescue’ analgesia was administered when DIVAS >50 mm and was butorphanol i.v. On the second occasion DIVAS was >50 mm, flunixin was administered i.v. Data from the DIVAS were analysed using a Mann Whitney Test. Results: Only one animal did not require rescue analgesia after surgery (Group C). DIVAS were not significantly different between groups (P = 0.063). Conclusions and potential relevance: Castration is sufficiently painful that administration of a single preoperative dose of butorphanol does not provide adequate post operative analgesia.     

Combined use of detomidine with opiates in the horse

The effects of administration of one of four opiates (pethidine 1 mg/kg bodyweight (bwt), morphine 0.1 mg/kg bwt, methadone 0.1 mg/kg bwt, and butorphanol 0.05 mg/kg bwt) given intravenously to horses and ponies already sedated with detomidine (10 micrograms/kg bwt) were investigated. Behavioural, cardiovascular and respiratory effects of the combinations were compared with those occurring with detomidine alone. Addition of the opiate increased the apparent sedation and decreased the response of the animal to external stimuli. At doses used, butorphanol produced the most reliable response. Side effects seen were increased ataxia (greatest following methadone and butorphanol) and excitement (usually muzzle tremors and muscle twitching). Following pethidine, generalised excitement was sometimes seen. Marked cardiovascular changes occurred in the first few minutes after morphine or pethidine injection, but within 5 mins cardiovascular changes were minimal. Following morphine or pethidine there was a significant increase in arterial carbon dioxide tension. Fourteen clinical cases were successfully sedated using detomidine/butorphanol combinations.     

A Preliminary Comparison of Lidocaine and Xylazine as Epidural Analgesics in Ponies

Xylazine (0.35 mg/kg) or lidocaine (0.35 mg/kg) was injected into the epidural space of six ponies to compare their effectiveness as epidural analgesics. Each pony received both treatments at 1 week intervals with the order of treatments randomized. Xylazine produced analgesia of significantly longer duration (247 +/- 58 minutes) than that produced by an equal dose of lidocaine (135 +/- 22 minutes). Mild transient ataxia of no clinical significance developed in all ponies with both treatments. Spinal cords were removed from two ponies and examined histologically. No discernible pathologic changes were noted.     

A comparison of the postoperative analgesic and sedative effects of flimixin and pap aver etum in the dog

Twenty-nine dogs undergoing a variety of surgical procedures were assigned randomly to one of two groups. All animals were premedicated with acepromazine (0–05 mg/kg) intramuscularly. Induction of anaesthesia was achieved with thiopentone sodium, or propofol in the case of sight hounds, and maintained with halothane in an oxygen/nitrous oxide mixture using a non-rebreathing circuit. Dogs in group 1 were given flunixin (1 mg/kg made up to 5 ml with 0–9 per cent saline) slowly intravenously 10 minutes before the halothane was switched off. Group 2 dogs received papaveretum (0–2 mg/kg made up to 5 ml with saline] administered as before. Using a visual analogue scale, the dogs were scored for sedation and for pain by trained theatre staff who were unaware of the analgesic used. Scoring was at 15, 30, 60, 120 , 240 and 360 minutes after analgesic administration. Seven dogs were withdrawn from the trial (three from the papaveretum group and four from the group which received flunixin) because analgesia was deemed unsatisfactory and these animals were given pethidine (3 mg/kg intramuscularly) which produced adequate analgesia within 15 minutes in all cases. Clinically, flunixin proved to be as effective a postoperative analgesic as papaveretum for up to six hours and was associated with less sedation, Pain scores were significantly different at two and four hours with flunixin providing more analgesia than papaveretum and at the four hour time point, flunixin was associated with significantly less sedation than papaveretum. From this study it was concluded that flunixin has a place in the treatment of acute post surgical pain, either alone or in combination with opioid analgesics where pain is refractory to treatment with clinical doses of opioids alone.     

Objective tests of analgesic drugs in ponies

An equine model, subjected to three kinds of pain (superficial, deep, and visceral) was used to test effects of analgesic drugs. Two groups of ponies were used. In the first group of six ponies, six drugs (fentanyl, meperidine, methadone, oxymorphone, pentazocine, and xylazine) were given according to a Latin square experimental design, and tests were made at 30-minute intervals for 4 hours. Mean values (control) for the three kinds of pain were obtained before and after the tests and were compared with the mean values (drugs) obtained over 2- and 4-hour intervals (four and eight measurements per interval, respectively). Xylazine was significantly more effective in obtunding deep pain (P less than 0.05) at 2- and 4-hour intervals than were the other drugs. Significant differences were not found between values for controls and values for drugs tested for relief of superficial and visceral pain at 2- and 4-hour intervals. In the second group of four ponies, the drug (xylazine) determined most effective in group 1 ponies was given alone or in combination with the next most effective drugs (fentanyl, meperidine, and oxymorphone). Data were obtained in the same manner as for the first group. Mean values were calculated for 2- and 4-hour intervals, and the variance was analyzed. Xylazine and fentanyl combined had the best 2- and 4-hour performance for the relief of visceral pain in the second group (P less than 0.1). Neither xylazine nor a combination of drugs differed markedly from control values for 2- and 4-hour intervals for relief of superficial and deep pain.     

Analgesic efficacy of butorphanol and morphine in bearded dragons and corn snakes

OBJECTIVE: To test the hypothesis that administration of butorphanol or morphine induces antinociception in bearded dragons and corn snakes. DESIGN: Prospective crossover study. ANIMALS: 12 juvenile and adult bearded dragons and 13 corn snakes. PROCEDURES: Infrared heat stimuli were applied to the plantar surface of bearded dragon hind limbs or the ventral surface of corn snake tails. Thermal withdrawal latencies (TWDLs) were measured before (baseline) and after SC administration of physiologic saline (0.9% NaCl) solution (equivalent volume to opioid volumes), butorphanol tartrate (2 or 20 mg/kg [0.91 or 9.1 mg/lb]), or morphine sulfate (1, 5, 10, 20, or 40 mg/kg [0.45, 2.27, 4.5, 9.1, or 18.2 mg/lb]). RESULTS: For bearded dragons, butorphanol (2 or 20 mg/kg) did not alter hind limb TWDLs at 2 to 24 hours after administration. However, at 8 hours after administration, morphine (10 and 20 mg/kg) significantly increased hind limb TWDLs from baseline values (mean +/- SEM maximum increase, 2.7+/-0.4 seconds and 2.8+/-0.9 seconds, respectively). For corn snakes, butorphanol (20 mg/kg) significantly increased tail TWDLs at 8 hours after administration (maximum increase from baseline value, 3.0+/-0.8 seconds); the low dose had no effect. Morphine injections did not increase tail TWDLs at 2 to 24 hours after administration. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with doses used in most mammalian species, high doses of morphine (but not butorphanol) induced analgesia in bearded dragons, whereas high doses of butorphanol (but not morphine) induced analgesia in corn snakes.     

Pharmacokinetics and pharmacodynamics of butorphanol in llamas after intravenous and intramuscular administration.

OBJECTIVE: To evaluate disposition of butorphanol after i.v. and i.m. administration, effects on physiologic variables, and analgesic efficacy after i.m. administration in llamas. DESIGN: Nonrandomized crossover study. ANIMALS: 6 healthy adult male llamas. PROCEDURE: Butorphanol (0.1 mg/kg [0.045 mg/lb] of body weight) was administered i.m. first and i.v. 1 month later. Blood samples were collected intermittently for 24 hours after administration. Plasma butorphanol versus time curves were subjected to pharmacokinetic analysis. Two months later, butorphanol (0.1 mg/kg) was administered i.m., and physiologic variables and analgesia were assessed. RESULTS: Extrapolated peak plasma concentrations after i.v. and i.m. administration were 94.8 +/- 53.1 and 34.3 +/- 11.6 ng/ml, respectively. Volume of distribution at steady state after i.v. administration was 0.822 +/- 0.329 L/kg per minute and systemic clearance was 0.050 +/- 0.014 L/kg per minute. Slope of the elimination phase was significantly different, and elimination half-life was significantly shorter after i.v. (15.9 +/- 9.1 minutes) versus i.m. (66.8 +/- 13.5 minutes) administration. Bioavailability was 110 +/- 49% after i.m. administration. Heart rate decreased and rectal temperature increased. Somatic analgesia was increased for various periods. Two llamas became transiently sedated, and 2 became transiently excited after butorphanol administration. CONCLUSIONS AND CLINICAL RELEVANCE: Although i.v. administration of butorphanol results in a short half-life that may limit its analgesic usefulness, the elimination half-life of butorphanol administered i.m. is likely to be clinically useful. The relationship among plasma butorphanol concentration, time, and analgesia differed with the somatic analgesia model; clinically useful analgesia may occur at lower plasma concentrations than those reported here.     

Antinociceptive effects of hydromorphone, butorphanol, or the combination in cats

The goal of this study was to assess the antinociceptive activity of a single dose of hydromorphone or butorphanol and to examine the effect of their coadministration on thermal thresholds in cats. Thermal thresholds were measured after IM administration of hydromorphone (0.1 mg/kg), butorphanol (0.4 mg/kg), a combination of butorphanol and hydromorphone (0.4 and 0.1 mg/kg), or saline to each of 6 cats in a randomized, blinded, crossover study design. There were at least 12 days between treatments. Thermal thresholds were measured by a thorax-mounted thermal threshold-testing device specifically developed for cats. Thermal thresholds were measured before treatment, at varying intervals to 12 hours, and at 24 hours after treatments. Data were analyzed by an analysis of variance with a repeat factor of time. Dysphoria was associated with butorphanol administration but not with hydromorphone or hydromorphone-butorphanol combined administration. Vomiting was seen with hydromorphone but not with butorphanol or hydromorphone-butorphanol combined. The control treatment group was stable over time (P = .22; mean threshold, 40.1 degrees C). Thresholds were significantly (P < .05) higher than the control treatment between 15 and 165 minutes for butorphanol, between 15 and 345 minutes for hydromorphone, and between 15 and 540 minutes for hydromorphone-butorphanol combined. The addition of butorphanol to hydromorphone decreased the intensity of antinociception during the 1st 2 hours but extended the duration of observable antinociception from 5.75 to 9 hours. The present study suggests that the combination of butorphanol and a pure OP3 (mu) receptor agonist clinically does not produce increased analgesia and indeed may result in decreased analgesia.     

Effects of xylazine and/or butorphanol or neostigmine on myoelectric activity of the cecum and right ventral colon in female ponies

Effects of xylazine HCl (0.5 mg/kg of body weight, IV) and/or butorphanol tartrate (0.04 mg/kg, IV) or neostigmine methylsulfate (0.022 mg/kg, IV) on myoelectric activity of the cecum and right ventral colon were studied in 4 conscious female ponies. Eight bipolar Ag/AgCl electrodes were sequentially placed on the seromuscular layer of the cecum (6 electrodes) and right ventral colon (2 electrodes). Recordings began 30 minutes before and continued for 90 minutes after drug administration. Each drug or drug combination was studied on 2 occasions in each pony. Two major patterns of coordinated spike bursts were identified. A series of coordinated spike bursts began at the cecal base and was conducted to the cecal apex (pattern I). A series of coordinated spike bursts began at the cecal apex, traversed the cecum, cecocolic orifice, and right ventral colon and was termed a progressive pattern (pattern II). Xylazine administration caused a significant decrease in patterns I and II for 20 minutes (P less than 0.05). Butorphanol tartrate administration caused a significant decrease in the progressive pattern for 10 minutes (P less than 0.05) without affecting the orally directed pattern. Administration of the combination of xylazine/butorphanol significantly decreased the frequency of pattern I for 40 minutes (P less than 0.05) and pattern II for 30 minutes (P less than 0.05). Neostigmine administration caused a significant increase in the frequency of pattern II for 30 minutes (P less than 0.05) without affecting pattern I (P greater than 0.05). Changes in conduction velocity of pattern I or II or the duration of spiking activity were not significantly different because of any treatment.     

Effect of acepromazine, butorphanol, or N-butylscopolammonium bromide on visceral and somatic nociception and duodenal motility in conscious horses

OBJECTIVE: To evaluate effects of butorphanol, acepromazine, and N-butylscopolammonium bromide (NBB) on visceral and somatic nociception and duodenal motility in conscious, healthy horses. ANIMALS: 6 adult horses. PROCEDURES: Visceral nociception was evaluated by use of colorectal distention (CRD) and duodenal distention (DD) threshold. Somatic nociception was evaluated via thermal threshold (TT). Nose-to-ground height, heart rate, and respiratory rate were also measured. Each horse received each treatment in randomized order; investigators were not aware of treatments. Butorphanol was administered IV as a bolus (18 microg/kg) followed by constant rate infusion at 13 microg/kg/h for 2 hours, whereas acepromazine (0.04 mg/kg), NBB (0.3 mg/kg), and saline (0.9% NaCl) solution (2 mL) were administered IV as a bolus followed by constant rate infusion with saline solution (10 mL/h) for 2 hours. Variables were measured before and for 3 hours after treatment. Data were analyzed by use of a 3-factor ANOVA followed by a Bonferroni t test for multiple comparisons. RESULTS: Nose-to-ground height decreased after acepromazine. Respiratory rate decreased after acepromazine and increased after butorphanol. Heart rate increased briefly after NBB. Some horses had an increase in TT after butorphanol and acepromazine, but there was not a significant treatment effect over time. Drug effect on DD or motility was not evident. The CRD threshold increased significantly at 5, 65, 155, and 185 minutes after acepromazine and from 5 to 65 minutes after NBB. CONCLUSIONS AND CLINICAL RELEVANCE: Each drug caused predictable changes in sedation and vital signs, but consistent anti-nociceptive effects were not evident.     

Comparison of electroacupuncture and butorphanol on respiratory and cardiovascular effects and rectal pain threshold after controlled rectal distention in mares

OBJECTIVE: To compare effects of electroacupuncture and butorphanol on hemodynamic and respiratory variables and rectal analgesia in mares after controlled rectal distention. ANIMALS: 8 healthy mares. PROCEDURE: Each horse received saline (0.9% NaCl) solution (0.01 mL/kg, IV; control treatment), butorphanol tartrate (0.1 mg/kg, IV), or 2 hours of electroacupuncture (EA) at acupoints Bladder 21, 25, and 27 on both sides of the vertebral column, Bai hui, and Stomach 36 (right side only). Order of treatments in each mare was randomized. At least 7 days elapsed between treatments. A balloon was inserted in the rectum of each mare, and controlled distention of the balloon (pressures of < or = 220 mm Hg) was used to measure nociceptive rectal pain threshold. Rectal temperature and cardiovascular and respiratory variables were measured before (baseline) and 5,15, 30, 60, 90, and 120 minutes after onset of each treatment. RESULTS: Butorphanol produced greater increases in rectal pain threshold, compared with EA (mean +/- SD, 214 +/- 24 vs 174 +/- 35 mm Hg of balloon pressure). Electroacupuncture produced minimal cardiovascular and respiratory changes. Although clinically not important, butorphanol produced moderate significant increases in heart and respiratory rates, arterial blood pressure, and rectal temperature and decreases in arterial oxygen tension. Arterial pH, carbon dioxide tension, bicarbonate concentrations, base excess, Hct, and concentration of total solids were not significantly different from baseline values after EA, butorphanol, and control treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Electroacupuncture and butorphanol (0.1 mg/kg, IV) may provide useful rectal analgesia in horses.     

Equine endotoxemia: cardiovascular, eicosanoid, hematologic, blood chemical, and plasma enzyme alterations

Ponies with electromagnetic blood flow transducers implanted around the main pulmonary and left main coronary arteries, were used to evaluate effects of chronic sublethal endotoxin on cardiac output (CO), stroke volume, and left coronary blood flow (LCBF). Plasma thromboxane (TX), as indicated by TXB2, prostacyclin as indicated by 6-keto-prostaglandin (PG) F1 alpha, and hematologic and blood chemical values also were evaluated. Over 24 hours, 2 groups of ponies were given progressively increasing IV and intraperitoneal doses of Escherichia coli lipopolysaccharide (LPS) at 0, 6, 12, and 18 hours. Group 1 was not treated and group 2 was treated with flunixin meglumine, before each LPS insult. Initial LPS inoculation in group 1 led to 10-fold increases in TXB2 and 6-keto-PGF1 alpha values by 30 and 90 minutes, respectively. These eicosanoid values returned to base line by 6 hours after each insult. Although repeated LPS injections stimulated recurring high plasma concentrations of 6-keto-PGF1 alpha, TXB2 production became less with each successive LPS insult. Cardiac output decreased to 55% to 60% of base-line values in association with increased 6-keto-PGF1 alpha values. Left coronary blood flow could not be evaluated accurately. Severe lactic acidosis developed in group 1. Group-2 ponies remained clinically normal, indicating protection of cardiovascular function and peripheral perfusion with flunixin meglumine. Seemingly, flunixin meglumine helped to maintain acceptable cardiovascular function and tissue perfusion during endotoxemia. Flunixin meglumine given to healthy ponies had no effect on cardiovascular function.(ABSTRACT TRUNCATED AT 250 WORDS)