Evaluation of the sedative and cardiorespiratory effects of dexmedetomidine,dexmedetomidine-butorphanol,and dexmedetomidine-ketamine in cats

OBJECTIVE: To determine sedative and cardiorespiratory effects of dexmedetomidine alone and in combination with butorphanol or ketamine in cats. DESIGN: Randomized crossover study. ANIMALS: 6 healthy adult cats. PROCEDURES: Cats were given dexmedetomidine alone (10 microg/kg [4.5 mg/lb], IM), a combination of dexmedetomidine (10 microg/kg, IM) and butorphanol (0.2 mg/kg [0.09 mg/lb], IM), or a combination of dexmedetomidine (10 microg/kg, IM) and ketamine (5 mg/kg [2.3 mg/lb], IM). Treatments were administered in random order, with > or = 1 week between treatments. Physiologic variables were assessed before and after drug administration. Time to lateral recumbency, duration of lateral recumbency, time to sternal recumbency, time to recovery from sedation, and subjective evaluation of sedation, muscle relaxation, and auditory response were assessed. RESULTS: Each treatment resulted in adequate sedation; time to lateral recumbency, duration of lateral recumbency, and time to recovery from sedation were similar among treatments. Time to sternal recumbency was significantly greater after administration of dexmedetomidine-ketamine. Heart rate decreased significantly after each treatment; however, the decrease was more pronounced after administration of dexmedetomidine-butorphanol, compared with that following the other treatments. Systolic and diastolic blood pressure measurements decreased significantly from baseline with all treatments; 50 minutes after drug administration, mean blood pressure differed significantly from baseline only when cats received dexmedetomidine and butorphanol. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in cats, administration of dexmedetomidine combined with butorphanol or ketamine resulted in more adequate sedation, without clinically important cardiovascular effects, than was achieved with dexmedetomidine alone.     

Effect of administering dexmedetomidine with or without atropine on cardiac troponin I level in isoflurane-anesthetized dogs

We aimed to determine whether dexmedetomidine administration with or without atropine increases cardiac troponin I (cTnI) level in healthy dogs. We hypothesized that 10 µg/kg dexmedetomidine + atropine increases the cTnI level, whereas 5 µg/kg dexmedetomidine + atropine does not. Eighteen healthy, pet dogs that underwent an orthopedic surgery or ovariohysterectomy were included in this study. The dogs were randomly assigned to atropine (0.02 mg/kg)–dexmedetomidine (10 µg/kg), saline–dexmedetomidine (10 µg/kg), and atropine (0.02 mg/kg)–dexmedetomidine (5 µg/kg) groups. Each dog was premedicated with atropine or saline intramuscularly (IM). After 10 min, they were IM injected with dexmedetomidine (10 or 5 µg/kg)–morphine (0.5 mg/kg)–midazolam (0.2 mg/kg). Following this, anesthesia was induced after 10 min with propofol and maintained with isoflurane in 100% oxygen. The median plasma cTnI level at 6, 12 and 24 hr after premedication was significantly higher than that at baseline. The cTnI level in the atropine–dexmedetomidine (10 µg/kg) group was significantly higher than that in the saline–dexmedetomidine (10 µg/kg) and atropine–dexmedetomidine (5 µg/kg) groups at 6 and 12 hr after premedication. The cTnI level returned to normal within 72 hr after premedication in all groups. The administration of atropine in combination with 10 µg/kg dexmedetomidine increased the cTnI level, indicating subclinical myocardial damage.     

Effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration of sevoflurane in dogs

Sparing effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration (MAC) of sevoflurane were determined in 6 dogs. Anesthesia was induced and maintained with sevoflurane in oxygen, and MAC was determined by use of a tail clamp method. The dogs were administered a subcutaneous injection of carprofen (4 mg/kg) or meloxicam (0.2 mg/kg), or no medication (control) one hour prior to induction of anesthesia. Following the initial determination of MAC, butorphanol (0.3 mg/kg) was administered intramuscularly, and MAC was determined again. The sevoflurane MACs for carprofen alone (2.10 +/- 0.26%) and meloxicam alone (2.06 +/- 0.20%) were significantly less than the control (2.39 +/- 0.26%). The sevoflurane MACs for the combination of carprofen with butorphanol (1.78 +/- 0.20%) and meloxicam with butorphanol (1.66 +/- 0.29%) were also significantly less than the control value after the administration of butorphanol (2.12 +/- 0.28%). The sevoflurane sparing effects of the combinations of carprofen with butorphanol and meloxicam with butorphanol were additive.     

Duration of nonresponse to noxious stimulation after intramuscular administration of butorphanol, medetomidine, or a butorphanol-medetomidine combination during isoflurane administration in dogs

OBJECTIVE: To assess duration of actions of butorphanol, medetomidine, and a butorphanol-medetomidine combination in dogs given subanesthetic doses of isoflurane (ISO). ANIMALS: 6 healthy dogs. PROCEDURE: Minimum alveolar concentration (MAC) values for ISO were determined. for each dog. Subsequently, 4 treatments were administered to each dog (saline [0.9% NaCl] solution, butorphanol [0.2 mg/kg of body weight], medetomidine [5.0 microg/kg], and a combination of butorphanol [0.2 mg/kg] and medetomidine [5.0 microg/kg]). All treatments were administered IM to dogs concurrent with isoflurane; treatment order was determined, using a randomized crossover design. Treatments were given at 7-day intervals. After mask induction with ISO and instrumentation with a rectal temperature probe, end-tidal CO2 and anesthetic gas concentrations were analyzed. End-tidal ISO concentration was reduced to 90% MAC for each dog. A tail clamp was applied 15 minutes later. After a positive response, 1 of the treatments was administered. Response to application of the tail clamp was assessed at 15-minute intervals until a positive response again was detected. RESULTS: Duration of nonresponse after administration of saline solution, butorphanol, medetomidine, and butorphanol-medetomidine (mean +/- SD) was 0.0+/-0.0, 1.5+/-1.5, 2.63+/-0.49, and 5.58+/-2.28 hours, respectively. Medetomidine effects were evident significantly longer than those for saline solution, whereas effects for butorphanol-medetomidine were evident significantly longer than for each agent administered alone. CONCLUSION AND CLINICAL RELEVANCE: During ISO-induced anesthesia, administration of medetomidine, but not butorphanol, provides longer and more consistent analgesia than does saline solution, and the combination of butorphanol-medetomidine appears superior to the use of medetomidine or butorphanol alone.     

Sedative effects of dexmedetomidine,dexmedetomidine–pethidine and dexmedetomidine–butorphanol in cats

The purpose of this study was to assess the clinical effects of dexmedetomidine, both alone and combined with pethidine or butorphanol, in cats. A prospective randomized blind study was performed. Thirty cats were randomly assigned to three groups of 10 animals: D: dexmedetomidine (20 μg/kg IM); DP: dexmedetomidine (10 μg/kg IM) and pethidine (2.5 mg/kg IM); DB: dexmedetomidine (10 μg/kg IM) and butorphanol (0.4 mg/kg IM). Quality of sedation, analgesia, muscle relaxation and the possibility of performing some clinical procedures were compared using a multifactorial scale. Sedation, analgesia and muscle relaxation increased progressively over time and did not differ in the three protocols. The three protocols facilitated the completion of several clinical procedures. The clinical variables studied showed a similar behaviour in the three protocols and remained close to the baseline, except for a drop in heart rate in protocol D. In conclusion, dexmedetomidine, either alone or combined with pethidine or butorphanol, offers suitable sedation, analgesia and relaxation to perform various clinical procedures in cats.     

Effect of orally administered tramadol alone or with an intravenously administered opioid on minimum alveolar concentration of sevoflurane in cats

OBJECTIVE-To compare the effect of oral administration of tramadol alone and with IV administration of butorphanol or hydromorphone on the minimum alveolar concentration (MAC) of sevoflurane in cats. DESIGN-Crossover study. ANIMALS-8 Healthy 3-year-old cats. PROCEDURES-Cats were anesthetized with sevoflurane in 100% oxygen. A standard tail clamp method was used to determine the MAC of sevoflurane following administration of tramadol (8.6 to 11.6 mg/kg [3.6 to 5.3 mg/lb], PO, 5 minutes before induction of anesthesia), butorphanol (0.4 mg/kg [0.18 mg/lb], IV, 30 minutes after induction), hydromorphone (0.1 mg/kg [0.04 mg/lb], IV, 30 minutes after induction), saline (0.9% NaCl) solution (0.05 mL/kg [0.023 mL/lb], IV, 30 minutes after induction), or tramadol with butorphanol or with hydromorphone (same doses and routes of administration). Naloxone (0.02 mg/kg [0.009 mg/lb], IV) was used to reverse the effects of treatments, and MACs were redetermined. RESULTS-Mean +/- SEM MACs for sevoflurane after administration of tramadol (1.48 +/- 0.20%), butorphanol (1.20 +/- 0.16%), hydromorphone (1.76 +/- 0.15%), tramadol and butorphanol (1.48 +/- 0.20%), and tramadol and hydromorphone (1.85 +/- 0.20%) were significantly less than those after administration of saline solution (2.45 +/- 0.22%). Naloxone reversed the reductions in MACs. CONCLUSIONS AND CLINICAL RELEVANCE-Administration of tramadol, butorphanol, or hydromorphone reduced the MAC of sevoflurane in cats, compared with that in cats treated with saline solution. The reductions detected were likely mediated by effects of the drugs on opioid receptors. An additional reduction in MAC was not detected when tramadol was administered with butorphanol or hydromorphone.     

Evaluation of the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication

OBJECTIVE: To compare the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication. ANIMALS: 42 client-owned dogs that underwent elective ovariohysterectomy. PROCEDURE: Each dog was randomly allocated to receive medetomidine and butorphanol tartrate (20 microgram/kg and 0.2 mg/kg, respectively, IM) or acepromazine maleate and butorphanol (0.05 and 0.2 mg/kg, respectively, IM) for preanesthetic medication. Approximately 80 minutes later, anesthesia was induced by administration of propofol and maintained by use of isoflurane in oxygen. Each dog was also given carprofen before surgery and buprenorphine after surgery. Plasma concentrations of epinephrine, norepinephrine, cortisol, and beta-endorphin were measured at various stages during the perioperative period. In addition, cardiovascular and clinical variables were monitored. RESULTS: Concentrations of epinephrine, norepinephrine, and cortisol were significantly lower for dogs administered medetomidine. Concentrations of beta-endorphin did not differ between the 2 groups. Heart rate was significantly lower and mean arterial blood pressure significantly higher in dogs administered medetomidine, compared with values for dogs administered acepromazine. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that for preanesthetic medications, medetomidine may offer some advantages over acepromazine with respect to the ability to decrease perioperative concentrations of stress-related hormones. In particular, the ability to provide stable plasma catecholamine concentrations may help to attenuate perioperative activation of the sympathetic nervous system.     

Sedative and cardiorespiratory effects of medetomidine, medetomidine-butorphanol, and medetomidine-ketamine in dogs

OBJECTIVE: To determine sedative and cardiorespiratory effects of i.m. administration of medetomidine alone and in combination with butorphanol or ketamine in dogs. DESIGN: Randomized, crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs were given medetomidine alone (30 micrograms/kg [13.6 micrograms/lb] of body weight, i.m.), a combination of medetomidine (30 micrograms/kg, i.m.) and butorphanol (0.2 mg/kg [0.09 mg/lb], i.m.), or a combination of medetomidine (30 micrograms/kg, i.m.) and ketamine (3 mg/kg [1.36 mg/lb], i.m.). Treatments were administered in random order with a minimum of 1 week between treatments. Glycopyrrolate was given at the same time. Atipamezole (150 micrograms/kg [68 micrograms/lb], i.m.) was given 40 minutes after administration of medetomidine. RESULTS: All but 1 dog (given medetomidine alone) assumed lateral recumbency within 6 minutes after drug administration. Endotracheal intubation was significantly more difficult when dogs were given medetomidine alone than when given medetomidine and butorphanol. At all evaluation times, percentages of dogs with positive responses to tail clamping or to needle pricks in the cervical region, shoulder region, abdominal region, or hindquarters were not significantly different among drug treatments. The Paco2 was significantly higher and the arterial pH and Pao2 were significantly lower when dogs were given medetomidine and butorphanol or medetomidine and ketamine than when they were given medetomidine alone. Recovery quality following atipamezole administration was unsatisfactory in 1 dog when given medetomidine and ketamine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a combination of medetomidine with butorphanol or ketamine resulted in more reliable and uniform sedation in dogs than did medetomidine alone.     

Effects of preoperative administration of ketoprofen on whole blood platelet aggregation,buccal mucosal bleeding time,and hematologic indices in dogs undergoing elective ovariohysterectomy

OBJECTIVE: To determine effects of preoperative administration of ketoprofen on whole blood platelet aggregation, buccal mucosal bleeding time, and hematologic indices in dogs after elective ovariohysterectomy. DESIGN: Randomized, masked clinical trial. ANIMALS: 22 healthy dogs. PROCEDURE: 60 minutes before induction of anesthesia, 11 dogs were given 0.9% NaCl solution (control), and 11 dogs were given ketoprofen (2 mg/kg [0.9 mg/lb], IM). Thirty minutes before induction of anesthesia, glycopyrrolate (0.01mg/kg [0.005 mg/lb]), acepromazine (0.05 mg/kg [0.02 mg/lb]), and butorphanol (0.2 mg/kg 10.09 mg/lb]) were given IM to all dogs. Anesthesia was induced with thiopental (5 to 10 mg/kg [2.3 to 4.5 mg/lb], IV) and maintained with isoflurane (1 to 3%). Ovariohysterectomy was performed and butorphanol (0.1 mg/kg [0.05 mg/lb], IV) was given 15 minutes before completion of surgery. Blood samples for measurement of variables were collected at intervals before and after surgery. RESULTS: In dogs given ketoprofen, platelet aggregation was decreased 95 +/- 10% and 80 +/- 35% (mean +/- SD) immediately after surgery and 24 hours after surgery, respectively, compared with preoperative values. At both times, mean values in dogs given ketoprofen differed significantly from those in control dogs. Significant differences between groups were not observed for mucosal bleeding time or hematologic indices. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative administration of ketoprofen inhibited platelet aggre gation but did not alter bleeding time. Ketoprofen can be given before surgery to healthy dogs undergoing elective ovariohysterectomy, provided that dogs are screened for potential bleeding problems before surgery and monitored closely after surgery.     

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.     

Effects of intramuscular administration of low doses of medetomidine and medetomidine-butorphanol in middle-aged and old dogs.

OBJECTIVE: To determine effects of low doses of medetomidine administered with and without butorphanol and glycopyrrolate to middle-aged and old dogs. DESIGN: Prospective randomized clinical trial. ANIMALS: 88 healthy dogs > or = 5 years old. PROCEDURE: Dogs were assigned randomly to receive medetomidine (2, 5, or 10 micrograms/kg [0.9, 2.3, or 4.6 micrograms/lb] of body weight, i.m.) alone or with glycopyrrolate (0.01 mg/kg [0.005 mg/lb], s.c.), medetomidine (10 micrograms/kg) and butorphanol (0.2 mg/kg [0.1 mg/lb], i.m.), or medetomidine (10 micrograms/kg), butorphanol (0.2 mg/kg), and glycopyrrolate (0.01 mg/kg). Anesthesia was induced with thiopental sodium and maintained with isoflurane. Degree of sedation and analgesia were determined before and after medetomidine administration. Respiratory rate, heart rate, and mean arterial blood pressure were determined 10 and 30 minutes after medetomidine administration. Adverse effects and amounts of thiopental and isoflurane used were recorded. RESULTS: Sedation increased after medetomidine administration in 79 of 88 dogs, but decreased in 7 dogs that received 2 or 5 micrograms of medetomidine/kg. Mean postsedation analgesia score and amounts of thiopental and isoflurane used were less in dogs that received medetomidine and butorphanol, compared with other groups. Respiratory rate, heart rate, and blood pressure were not different among groups. Significantly more adverse effects developed in dogs that did not receive glycopyrrolate. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of medetomidine (10 micrograms/kg, i.m.) and butorphanol (0.2 mg/kg, i.m.) induced sedation and analgesia and reduced amounts of thiopental and isoflurane required for anesthesia in middle-aged and old dogs. Glycopyrrolate decreased frequency of medetomidine-associated adverse effects.     

Effects of 2.0% end-tidal isoflurane with and without atropine prior to dexmedetomidine administration on cardiovascular variables in dogs

The purpose of this study was to determine the cardiovascular effects of 2.0% end‐tidal isoflurane in dogs administered dexmedetomidine (DEX). Using a randomized crossover design and allowing at least 2 weeks between treatments 12 adult hound dogs of either sex weighing 22 ± 1.7 SD kg were anesthetized by face mask administration of either sevoflurane or isoflurane to facilitate instrumentation prior to administration of treatment drugs. Dogs were intubated and instrumented to enable measurement of heart rate (HR), systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures, mean pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), pulmonary arterial temperature (TEMP), and cardiac output (CO) via thermodilution using 5 mL of 5% dextrose, and recording the average of three replicate measurements. Cardiac index (CI) and systemic (SVR) and pulmonary vascular resistances were calculated. Following completion of instrumentation, dogs were allowed to recover for 40 minutes. After collection of baseline data, dogs were administered one of four treatments at T‐10 minutes prior to injection of DEX (500? g M^–2 IM): 1) saline (SAL); 2) atropine [ATR, 0.02 (n = 6) or 0.04 (n = 6) mg kg^–1 IM]; 3) ISO (2.0% end tidal concentration); or 4) ISO + ATR. Cardiovascular data were collected at T‐20 and T‐5 minutes prior to administration of DEX, and at 5, 10 , 20, 30, 40, and 60 min following DEX. Data were analyzed using anova for repeated measures with post‐hoc differences between means identified using Bonferroni's method (p < 0.05). Differences in ATR dose were not found to be significant and thus results for ATR dose groups were pooled. Administration of SAL (dexmedetomidine alone) was associated with decreases in HR and CO and increases in SAP, MAP, DAP, CVP, and SVR. Administration of ATR was associated with an increase in HR and CO compared with SAL. Administration of ISO was associated with an increase in HR and a decrease in SVR, MAP and CVP compared with SAL. Administration of ISO + ATR was associated with effects similar to that of ISO or ATR alone. We conclude that administration of ISO reduces the increase in SVR associated with administration of DEX and does not adversely affect CO.     

Relationships between a proprietary index, bispectral index, and hemodynamic variables as a means for evaluating depth of anesthesia in dogs anesthetized with sevoflurane

OBJECTIVE: To evaluate relationships among various techniques for monitoring anesthetic depth in sevoflurane-anesthetized dogs undergoing orthopedic surgery. ANIMALS: 10 dogs. PROCEDURE: Dogs were medicated with acepromazine (0.05 mg/kg, IM), buprenorphine (0.01 mg/kg, IM), and atropine (0.04 mg/kg, IM). Anesthesia was induced and maintained with sevoflurane. Cardiovascular and respiratory responses were monitored. Anesthetic depth was monitored by use of the bispectral index (BIS), and a proprietary index was used to monitor activity of the autonomic nervous system. RESULTS: A significant decrease in BIS was seen after induction but concurrent changes were not observed for the other techniques. The proprietary index increased significantly after intubation, but no changes were seen for the other techniques. No significant changes were detected during incision or when higher nociceptive stimuli were applied. We did not identify a correlation between BIS and the proprietary index, the proprietary index and hemodynamic variables, or the BIS and hemodynamic variables during induction and maintenance. A significant increase in the proprietary index and BIS was detected at the time of resumption of reflexes. During anesthetic recovery, a correlation was found between the proprietary index and BIS but not between hemodynamic variables and the other techniques. CONCLUSIONS AND CLINICAL RELEVANCE: A significant increase in the proprietary index, but not the BIS or hemodynamic variables, was detected during intubation. Anesthetic induction with sevoflurane did not prevent the sympathetic stimulus attributable to tracheal intubation. Monitoring of hemodynamic variables does not provide sufficient information to allow clinicians to evaluate stress during anesthetic recovery.     

Yohimbine/flumazenil antagonism of hemodynamic alterations induced by a combination of midazolam, xylazine, and butorphanol in dogs.

Reversal of hemodynamic alterations induced by midazolam maleate (1.0 mg/kg of body weight), xylazine hydrochloride (0.44 mg/kg), and butorphanol tartrate (0.1 mg/kg) with yohimbine (0.1 mg/kg) and flumazenil (0.25 mg/kg) was evaluated in 5 dogs. The dogs were anesthetized with isoflurane for instrumentation. With return to consciousness, baseline values were recorded, and the midazolam/xylazine/butorphanol mixture with glycopyrrolate was administered IV. Hemodynamic data were recorded for 60 minutes, and then a reversal mixture of yohimbine and flumazenil was administered IV. All variables were measured 1 minute from beginning of the reversal injection. Mean arterial pressure, pulmonary arterial pressure, systemic vascular resistance, and right ventricular stroke work index increased significantly (P < 0.05) above baseline at 60 minutes. Cardiac index and central venous pressure significantly decreased below baseline at 60 minutes. After reversal, mean arterial pressure and central venous pressure significantly decreased from baseline, whereas cardiac index, pulmonary arterial pressure, and right ventricular stroke work index increased significantly above baseline. Heart rate, cardiac index, and right ventricular stroke work index increased significantly above the 60-minute value after reversal. Mean arterial pressure and systemic vascular resistance decreased significantly (P < 0.05) below the 60-minute value after reversal. The hemodynamic alterations accompanying midazolam/xylazine/butorphanol sedation-anesthesia may be rapidly reversed with a combination of yohimbine and flumazenil.     

Hemodynamic Effects of Intravenous Midazolam-Xylazine-Butorphanol in Dogs

The hemodynamic effects of a mixture of midazolam (1.0 mg/kg), xylazine (0.44 mg/kg), and butorphanol (0.1 mg/kg) were evaluated in six adult dogs. The dogs were anesthetized with isoflurane for instrumentation. As the dogs returned to consciousness, baseline values were recorded and the midazolam-xylazine-butorphanol mixture and glycopyrrolate (0.01 mg/kg) were administered intravenously (IV). Hemodynamic data were recorded 3, 10, 20, 30, 40, 50, and 60 minutes after injection. Mean arterial pressure (AP), mean pulmonary arterial pressure (PAP), heart rate (HR), rate-pressure product (RPP), mean pulmonary capillary wedge pressure (PCWP), systemic vascular resistance (SVR), and right ventricular stroke work index (RVSWI) were increased significantly above baseline values. Cardiac output (CO), stroke volume (SV), cardiac index (CI), stroke index (SI), mean central venous pressure (CVP), and left ventricular stroke work index (LVSWI) were decreased significantly below baseline values. When administered IV at the dosages used in this study, midazolam-xylazine-butorphanol-glycopyrrolate induced profound acute alterations in several critical hemodynamic variables.     

Serum concentrations and analgesic effects of liposome-encapsulated and standard butorphanol tartrate in parrots

OBJECTIVE: To compare serum concentrations of liposome-encapsulated butorphanol tartrate (LEBT) and standard butorphanol tartrate (STDBT) following SC and IM administration, respectively, and to evaluate analgesic effects of LEBT and STDBT after parenteral administration to Hispaniolan parrots. ANIMALS: 11 adult Hispaniolan parrots. PROCEDURE: The ability of LEBT to prolong the duration of analgesia in an avian species was tested. Blood samples were collected at serial time points after SC administration of LEBT (10 mg/kg or 15 mg/kg) or IM administration of STDBT (5 mg/kg). Serum concentrations of butorphanol tartrate were determined by use of a commercial immunoassay that measured parent drug and metabolites. Analgesic efficacy was evaluated in parrots exposed to electrical and thermal stimuli. Foot withdrawal thresholds were recorded at baseline and at serial time points after LEBT (15 mg/kg), liposome vehicle, STDBT (2 mg/kg), or physiologic saline (0.9% NaCl) solution administration. RESULTS: LEBT had a prolonged in vivo release for up to 5 days. Negligible serum butorphanol and butorphanol metabolite concentrations were obtained at 24 hours after IM administration of STDBT. Analgesic efficacy of LEBT as measured by foot withdrawal threshold to noxious thermal and electrical stimuli persisted for 3 to 5 days following SC administration of LEBT. CONCLUSIONS AND CLINICAL RELEVANCE: SC administration of LEBT provided analgesia and detectable serum butorphanol concentrations in Hispaniolan parrots for up to 5 days. The use of LEBT may allow for substantial improvement in long-term pain relief without subjecting birds to the stress of handling and multiple daily injections.     

Influence of medetomidine on stress-related neurohormonal and metabolic effects caused by butorphanol, fentanyl, and ketamine administration in dogs

OBJECTIVE: To examine stress-related neurohormonal and metabolic effects of butorphanol, fentanyl, and ketamine administration alone and in combination with medetomidine in dogs. ANIMALS: 10 Beagles. PROCEDURE: 5 dogs received either butorphanol (0.1 mg/kg), fentanyl (0.01 mg/kg), or ketamine (10 mg/kg) IM in a crossover design. Another 5 dogs received either medetomidine (0.02 mg/kg) and butorphanol (0.1 mg/kg), medetomidine and fentanyl (0.01 mg/kg), medetomidine and ketamine (10 mg/kg), or medetomidine and saline (0.9% NaCI) solution (0.1 mL/kg) in a similar design. Blood samples were obtained for 6 hours following the treatments. Norepinephrine, epinephrine, cortisol, glucose, insulin, and nonesterified fatty acid concentrations were determined in plasma. RESULTS: Administration of butorphanol, fentanyl, and ketamine caused neurohormonal and metabolic changes similar to stress, including increased plasma epinephrine, cortisol, and glucose concentrations. The hyperglycemic effect of butorphanol was not significant. Ketamine caused increased norepinephrine concentration. Epinephrine concentration was correlated with glucose concentration in the butorphanol and fentanyl groups but not in the ketamine groups, suggesting an important difference between the mechanisms of the hyperglycemic effects of these drugs. Medetomidine prevented most of these effects except for hyperglycemia. Plasma glucose concentrations were lower in the combined sedation groups than in the medetomidine-saline solution group. CONCLUSIONS AND CLINICAL RELEVANCE: Opioids or ketamine used alone may cause changes in stress-related biochemical variables in plasma. Medetomidine prevented or blunted these changes. Combined sedation provided better hormonal and metabolic stability than either component alone. We recommend using medetomidine-butorphanol or medetomidine-ketamine combinations for sedation or anesthesia of systemically healthy dogs.     

A comparison of the analgesic effects of butorphanol with those of meloxicam after elective ovariohysterectomy in dogs

This study was designed to compare the analgesic effects of butorphanol with those of meloxicam following ovariohysterectomy. Fifteen dogs were premedicated with 0.05 mg/kg body weight (BW) of acepromazine by intramuscular (IM) injection, plus 0.2 mg/kg BW of meloxicam by subcutaneous (SC) injection. Fifteen dogs were premedicated with 0.05 mg/kg BW of Acepromazine, IM, plus 0.2 mg/kg BW of butorphanol, IM. Anesthesia was induced with thiopental, and dogs were maintained on halothane. All pain measurements were performed by 1 experienced individual, blinded to treatment. Pain scores and visual analogue scales (VAS) were performed at 2, 3, 4, 6, 8, 12, and 24 hours postpremedication. An analgesiometer was used to determine the pressure required to produce an active avoidance response to pressure applied at the incision line. Pain scores, VAS, and analgesiometer scores were analyzed by using a generalized estimating equations method. A significance level of P < 0.05 was considered significant. Animals that received meloxicam demonstrated significantly lower pain scores and VAS than did animals that received butorphanol in the first 12 hours after surgery. Results of this study suggest that meloxicam will produce better postoperative analgesia than will butorphanol. Mucosal bleeding times were performed on cooperative animals in the study group (11 butorphanol, 13 meloxicam). Bleeding times were performed prior to premedication, 6 hours following premedication, and 24 hours after premedication. The 6- and 24-hour readings were compared with baseline bleeding times by using a paired t-test with a Bonferroni correction (a significance level of P < 0.025). Bleeding times did not change significantly over time.     

Effects of butorphanol and carprofen on the minimal alveolar concentration of isoflurane in dogs

OBJECTIVE: To evaluate the effects of butorphanol and carprofen, alone and in combination, on the minimal alveolar concentration (MAC) of isoflurane in dogs. DESIGN: Randomized complete-block crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURE: Minimal alveolar concentration of isoflurane was determined following administration of carprofen alone, butorphanol alone, carprofen and butorphanol, and neither drug (control). Anesthesia was induced with isoflurane in oxygen, and MAC was determined by use of a tail clamp method. Three hours prior to induction of anesthesia, dogs were fed a small amount of canned food without any drugs (control) or with carprofen (2.2 mg/kg of body weight [1 mg/lb]). Following initial determination of MAC, butorphanol (0.4 mg/kg [0.18 mg/lb], i.v.) was administered, and MAC was determined again. Heart rate, respiratory rate, indirect arterial blood pressure, endtidal partial pressure of CO2, and saturation of hemoglobin with oxygen were recorded at the time MAC was determined. RESULTS: Mean +/- SD MAC of isoflurane following administration of butorphanol alone (1.03 +/- 0.22%) or carprofen and butorphanol (0.90 +/- 0.21%) were significantly less than the control MAC (1.28 +/- 0.14%), but MAC after administration of carprofen alone (1.20 +/- 0.13%) was not significantly different from the control value. The effects of carprofen and butorphanol on the MAC of isoflurane were additive. There were not any significant differences among treatments in regard to cardiorespiratory data. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of butorphanol alone or in combination with carprofen significantly reduces the MAC of isoflurane in dogs; however, the effects of butorphanol and carprofen are additive, not synergistic.     

The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs

Different doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, with or without dexmedetomidine were compared in conscious dogs. Eight animals received either dexmedetomidine (10 μg/kg [D]), MK-467 (250 μg/kg [M250] or dexmedetomidine (10 μg/kg) with increasing doses of MK-467 (250 μg/kg [DM250], 500 μg/kg [DM500] and 750 μg/kg [DM750], respectively). Treatments were given intravenously (i.v.) in a randomized, crossover design with a 14-day washout period. Systemic hemodynamics and arterial blood gas analyses were recorded at baseline and at intervals up to 90 min after drugs administration. Dexmedetomidine alone decreased heart rate, cardiac index and tissue oxygen delivery and increased mean arterial pressure and systemic vascular resistance 5 min after administration. DM250 did not completely prevent these early effects, while DM750 induced a decrease in mean arterial pressure. With DM500, systemic hemodynamics remained stable throughout the observational period. MK-467 alone increased cardiac index and tissue oxygen delivery and had no deleterious adverse effects. No differences in arterial blood gases were observed between treatments that included dexmedetomidine. It was concluded that MK-467 attenuated or prevented dexmedetomidine's systemic hemodynamic effects in a dose-dependent manner when given simultaneously i.v. but had no effect on the pulmonary outcome in conscious dogs. A 50:1 dose ratio (MK-467:dexmedetomidine) induced the least alterations in cardiovascular function.