Browning AP, Collins JA. (2005)
Sedation of horses with romifidine and butorphanol.
Vet Rec 134, 90-91.
Combinations of romifidine and butorphanol were used to sedate 55 horses for a variety of surgical, therapeutic and diagnostic procedures. Eighteen of the horses were given the drugs separately, romifidine first followed by butorphanol four minutes later, and 37 were given the drugs together. The levels of sedation and ataxia were assessed and graded, and there were no statistically significant differences between the two methods of administration. The side effects were typical of the alpha-2 agonists, including bradycardia, heart block and some sweating. Box-walking was observed in one horse. The procedure attempted was successfully completed in 54 of the horses, and the combination of drugs was judged to be a safe and effective sedative for horses.
Budsberg SC, Cross AR, Quandt JE, Pablo LS, Runk AR. (2002)
Evaluation of intravenous adinistration of meloxicam for perioperative pain management following stifle joint surgery in dogs.
Am J Vet Res 63, 1557-1563.
OBJECTIVE: To compare preoperative administration of meloxicam and butorphanol to perioperative administration of butorphanol alone for control of postoperative signs of pain in dogs.
ANIMALS: 40 client-owned dogs scheduled for surgical repair of a cranial cruciate ligament rupture.
PROCEDURE: Group-1 dogs received butorphanol (0.2 mg/kg, IV) and meloxicam (0.2 mg/kg, IV) just prior to surgery. Group-2 dogs received butorphanol just prior to surgery (0.2 mg/kg, IV) and at incision closure (0.1 mg/kg, IV). Pain assessment began 1 to 2 hours before surgery and from extubation until 24 hours after surgery by obtaining the following measurements: the visual analog scale (VAS) score, cumulative pain score (CPS), adjusted cumulative pain score, modified cumulative pain score, and the adjusted modified cumulative pain score (AMCPS). Serum cortisol concentration was measured between 12 to 24 and between 1 to 2 hours prior to surgery, and at 30 minutes, and 1, 2, 4, 8, 18, and 24 hours after extubation.
RESULTS: No significant differences between treatment groups were observed in CPS or VAS score. At 8, 9, 10, and 11 hours after extubation, meloxicam-butorphanol-treated dogs had a significantly lower AMCPS, compared with butorphanol-alone-treated dogs. Total serum cortisol concentration (area under the curve) during the measurement period was significantly lower in meloxicam-butorphanol-treated dogs, compared with butorphanol-alone treated dogs.
CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative single dose administration of meloxicam-butorphanol is equivalent to or slightly better than the administration of 2 perioperative doses of butorphanol for the control of postoperative signs of pain in dogs.
OBJECTIVE: The effect of sedation on gastric emptying was evaluated in six ponies by monitoring serum concentrations of acetaminophen (AP) after intragastric administration.
EXPERIMENTAL DESIGN: Prospective randomized experimental study. ANIMALS: Six adult ponies, 135 to 275 kg.
METHODS: Fifteen minutes after the intravenous administration of xylazine (1 mg/kg), butorphanol (0.05 mg/kg), acepromazine (0.05 mg/kg) or saline, ponies were given AP (20 mg/kg in 350 mL water) by stomach tube. Blood for AP analysis was collected at baseline and 15, 30, 45, 75, 90, 105, and 120 minutes after AP administration. The time (Tmax) to reach peak serum concentration (Cmax), and the area under the AP serum concentration versus time curve (AUC) were determined for each treatment group.
RESULTS: Tmax was 31 mins in the control group, and this increased significantly (P<.05) after sedation. Cmax decreased (P<.05) after xylazine administration, and AUC decreased (P<.05) after acepromazine. CONCLUSIONS: This study indicated that sedation has a significant effect on the gastric emptying rate of a liquid in ponies.
Suitable analgesia should be effective enough to prevent self-mutilation and allow appropriate therepy, but not so profound as to mask the need for surgical intervetion. In clinical trials, butorphanol has met these criteria.
OBJECTIVE: To describe a technique for laparoscopic bilateral ovariectomy in standing mares and report the outcome of 22 clinical cases.
STUDY DESIGN: Prospective study.
ANIMALS OR SAMPLE POPULATION: A total of 22 mares between 4 and 23 years of age, weighing between 360 and 600 kg.
METHODS: Mares with normal ovaries, as determined by palpation per rectum, were restrained in standing stocks and sedated with detomidine (0.01 to 0.02 mg/kg intravenously [i.v.]) and butorphanol (0.01 to 0.02 mg/kg i.v.). The laparoscope and instrument insertion sites were infiltrated with 2% lidocaine before incision. One laparoscope portal and two instrument portals were located in each paralumbar fossa. Ovariectomy was accomplished by intracorporeal dissection and ligation of the ovarian pedicles. The two instrument portals in each flank were ultimately connected resulting in a 4 to 5 cm laparotomy to facilitate ovarian removal.
RESULTS: No major operative or postoperative complications occurred. Minor complications included incomplete hemostasis of an ovarian pedicle with a single ligature (three mares), transient inappetence, pyrexia and incisional infection. Owner satisfaction and cosmetic results were considered excellent.
CONCLUSIONS: Standing laparoscopic ovariectomy appears to eliminate many of the potential complications associated with traditional surgical methods for ovariectomy and avoids the risk of general anesthesia.
CLINICAL RELEVANCE: This technique requires minimal laparoscopic instrumentation and will provide surgeons with an alternative approach for bilateral ovariectomy in mares.
Houghton KJ, Rech RH, Sawyer DC, Durham RA, Adams T, Langham MA, Striler EL. (1999)
Dose-response of intravenous butorphanol to increase visceral nociceptive threshold in dogs.
Proc Soc Exp Biol Med 197, 290-296.
This study was designed to determine the effective analgesic dose of butorphanol administered intravenously to obtund visceral nociception, as well as to determine duration of this effect. Additionally, cardiovascular changes and sedative effects were defined.
Eight healthy dogs were each given five doses of butorphanol (0.025, 0.05, 0.1, 0.2, and 0.4 mg/kg) plus a sterile water placebo intravenously in a randomized blinded format. Antinociception was assessed using an inflatable Silastic balloon inserted into the colon. Blood pressures and pulse rates were measured with a noninvasive monitor.
The greatest efficacy and longest duration of antinociception were produced by 0.4 mg/kg of butorphanol, with a duration of 38 +/- 9 min. Arterial blood pressure and pulse rate did not vary at antinociceptive doses. Mild sedation was observed at all doses, which generally lasted longer than the antinociceptive effects.
These data suggest that butorphanol can be given alone intravenously to provide visceral antinociception lasting 30-45 min without significant side effects.
Inoue T, Ko JC, Mandsager RE, Payton ME, Galloway DS, Lange DN. (2006)
Efficacy and safety of preoperative etodolac and butorphanol administration in dogs undergoing ovariohysterectomy.
J Am Anim Hosp Assoc 42, 178-188.
Eighteen dogs undergoing ovariohysterectomy were premedicated with etodolac, butorphanol, or their combination. Various parameters, such as blood pressure, isoflurane requirements, behavioral pain scores, plasma cortisol concentration, plasma glucose concentration, and mucosal bleeding time, were assessed. The integrated plasma cortisol values were significantly lower in the etodolac and etodolac with butorphanol groups. Dogs receiving etodolac and butorphanol had the lowest behavioral pain scores from extubation until the end of monitoring. Isoflurane concentration over time (area under the curve), buccal mucosal bleeding time, and indices of renal function were not significantly different among the treatment groups.
Jochle W, Moore JN, Brown J, Baker GJ, Lowe JE, Fubini S, Reeves MJ, Watkins JP, White NA. (1985)
Comparison of detomidine, butorphanol, flunixin meglumine and xylazine in clinical cases of equine colic.
Equine Vet J 7, Suppl (Equine Colic), 111- 116.
Detomidine hydrochloride, butorphanol tartrate, flunixin meglumine and xylazine hydrochloride were evaluated in a blind multi-centre clinical trial in 152 horses with abdominal pain. The drugs were administered as follows: detomidine 20 or 40 micrograms/kg bodyweight (bwt); butorphanol 0.1 mg/kg bwt; flunixin meglumine 1.0 mg/kg bwt; xylazine hydrochloride 0.5 mg/kg bwt. Each centre compared responses to the two doses of detomidine with those to one of the other analgesics. The drugs were administered intravenously (i.v.) after clinical assessment of the degree of sweating, kicking, pawing, head and body movement, attitude, lip curling, stretching to urinate, pulse rate, respiratory rate and rectal temperature. Similar assessments were repeated at 15 min intervals for at least 1 h. The investigators ranked the response to treatment from ‘not satisfactory’ to ‘highly satisfactory’. Significant differences in sweating, kicking, pawing, head and body movement, attitude, pulse rate and respiratory rate were noted between the horses receiving butorphanol and either dose of detomidine. The investigators’ subjective evaluation of the analgesic and sedative effects of either dose of detomidine were significantly better than for butorphanol. Analgesia was rated as highly satisfactory or satisfactory in 93.3 per cent and 6.7 per cent of the horses receiving 40 micrograms/kg bwt of detomidine, 73.3 per cent and 26.7 per cent of the horses receiving 20 micrograms/kg bwt of detomidine, and none of the horses receiving butorphanol. There were no differences in the incidence of side effects with the two compounds. Significant differences were noted in kicking, pawing, head and body movement and attitude between the horses receiving flunixin meglumine and either dose of detomidine. Flunixin meglumine provided significantly less analgesia than either dose of detomidine. Analgesia was rated as highly satisfactory or satisfactory in 73.7 per cent and 21.0 per cent of the horses receiving 40 micrograms/kg bwt of detomidine, 42.9 per cent and 21.4 per cent of the horses receiving 20 micrograms/kg bwt of detomidine, and 6.3 per cent and 37.5 per cent of the horses receiving xylazine. Sedation was considered to be at least satisfactory in 84.2 per cent of the horses receiving 40 micrograms/kg of detomidine, 71.5 per cent of the horses receiving 20 micrograms/kg of detomidine and 53.3 per cent of the horses receiving xylazine.
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.
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).
OBJECTIVE: To report a technique for laparoscopic ablation of the renosplenic space in standing horses.
STUDY DESIGN: Development of a technique to perform laparoscopic renosplenic space ablation in standing horses.
ANIMALS: Five healthy horses, aged 3 to 13 years, weighing 380 to 520 kg.
METHODS: Horses were restrained in standing stocks and sedated with detomidine (0.01 mg/kg intravenously [IV]) and butorphanol (0.01 mg/kg IV). Portal sites in the left paralumbar fossa were infiltrated with 2% mepivacaine. A laparoscopic portal was placed between the 17th and the 18th ribs. Two instrument portals were located caudal to the 18th rib. Closure of the renosplenic space was accomplished by apposing the dorsomedial splenic capsule to the dorsal portion of the renosplenic ligament with 1 polyglactin 910 in a continuous pattern. All horses had repeat laparoscopy 3 weeks after initial surgery.
RESULTS: Laparoscopic closure of the renosplenic space required 35 minutes (range, 20-65 minutes) and was successful without intraoperative or postoperative complications. On laparoscopic re-examination at 3 weeks, there was smooth connecting fibrous-like tissue between the dorsal splenic capsule and the dorsal portion of the renosplenic ligament.
CONCLUSIONS: Laparoscopic closure of the renosplenic space can be efficiently and safely performed in standing horses.
CLINICAL RELEVANCE: Laparoscopic-assisted closure of the renosplenic space can be performed in standing horses and may be useful in preventing recurrent incarceration of viscera in this space.
Mathews KA, Pettifer G, Foster R, McDonell W. (2001)
Safety and efficacy of preoperative administration of meloxicam, compared with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery.
Am J Vet Res 62, 882-888.
OBJECTIVE: To compare the safety and efficacy of preoperative administration of meloxicam with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery.
ANIMALS: 36 dogs undergoing laparotomy, splenectomy, or cystotomy.
PROCEDURE: Dogs were randomly assigned to 1 of 3 groups. In the first part of the study, dogs were given a single dose of meloxicam, ketoprofen, or a placebo, and buccal mucosal bleeding times were measured. In the second part of the study, dogs were given meloxicam, ketoprofen, or butorphanol prior to surgery. Dogs in the butorphanol group received a second dose immediately after surgery. Pain scores (1 to 10) were assigned hourly for 20 hours after surgery and used to determine an overall efficacy score for each dog. Dogs with a pain score > or =3 were given oxymorphone for pain. Dogs were euthanatized 8 days after surgery, and gross and histologic examinations of the liver, kidneys, and gastrointestinal tract were conducted.
RESULTS: Overall efficacy was rated as good or excellent in 9 of the 12 dogs that received meloxicam, compared with 9 of the 12 dogs that received ketoprofen and only 1 of the 12 dogs that received butorphanol. No clinically important hematologic, biochemical, or pathologic abnormalities were detected
CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that preoperative administration of meloxicam is a safe and effective method of controlling postoperative pain for 20 hours in dogs undergoing abdominal surgery; the analgesic effects of meloxicam were comparable to those of ketoprofen and superior to those of butorphanol.
Six healthy six to eight-month-old horses were surgically prepared with Ag bipolar electrodes sutured to the gastric antrum and duodenum. Leads from the electrodes were exteriorised through a stab incision in the flank. During experimental sessions the horses were lightly restrained in stocks and electrode leads were connected to a physiograph to record antroduodenal myoelectrical activity. Intravenous (i.v.) injection of 0.05 mg/kg bodyweight (bwt) of the opioid agonist/antagonist, butorphanol was followed within 2 to 3 mins by a normal appearing period of repetitive spike activity, or phase III, of the migrating motor complex (MMC) on the duodenum. This was followed by a period of no spike activity, or phase I, of the MMC and then resumption of intermittent spike activity, or phase II, of normal duration. Pre-treatment with 15 micrograms/kg bwt of the non-selective opioid antagonist, naloxone, or with 1 mg/kg bwt of the alpha 2-adrenergic antagonist, tolazoline, did not block the myoelectrical response to butorphanol. It was concluded that a dose of butorphanol that has effective analgesic effects in a colicky horse resets the antroduodenal MMC without causing undesirable effects on antroduodenal motility. This particular effect of butorphanol might not be mediated by either a2-adrenergic or opioid receptors, although the latter question needs further investigation.
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.
Butorphanol, a new, totally synthetic morphinan, which is chemically related to naloxone, has been demonstrated to have both analgesic and narcotic antagonist properties. In rodent antiwrithing analgesic tests, butorphanol was 4 to 30 times more potent than morphine and dl-pentazocine, respectively. As an antagonist, butorphanol was about equivalent to nalorphine and 30 times more potent than dl-pentazocine. On the basis of the naloxone-induced mouse jumping test and the lack of substitution in withdrawn morphine-dependent mice, it is estimated that the potential for physical dependence of butorphanol will be less than that of dl-pentazocine but greater than that of nalorphine and dl-cyclazocine. Animal data also show that agonistic actions of butorphanol, such as respiratory depression and miosis, reach ceiling effects which are lower than those seen with morphine with an increase in dosage. Thus, butorphanol differed from morphine which exhibited agonist effects in a dose-related manner. Butorphanol showed weak to moderate central depressant properties at doses which were considerably higher (greater than 100 X) than those producing analgesia. Minimal cardiovascular and respiratory effects were seen with butorphanol in conscious dogs.
The effects of butorphanol given (IV) at dose levels of 0.1 and 0.4 mg/kg were evaluated in conscious dogs, n = 5 for each dose. Mild sedation occurred, though it was greater in dogs given the larger dose. Two dogs in each group panted, but PaCO2 was not significantly changed. Small, but significant, decreases in arterial blood pressure, heart rate, and PaO2 occurred (P less than 0.05). Base excess developed a negative trend. The PCV and total protein decreased slightly in dogs given the smaller dose, but were unchanged with the larger dose. Plasma glucose remained within acceptable limits.
Yamashita K, Tsubakishita S, Futaok S, Ueda I, Hamaguchi H, Seno T, Katoh S, Izumisawa Y, Kotani T, Muir WW. (2000)
Cardiovascular effects of medetomidine, detomidine and xylazine in horses.
J Vet Med Sci.62, 1025-1032.
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.