Cardiopulmonary effects of butorphanol tartrate in 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.     

Serum concentrations across time after subcutaneous administration of liposome-encapsulated or standard oxymorphone in Rhesus macaques

Our lab has developed a slow‐release liposomal formulation of oxymorphone (LEOx). The purpose of this study was to compare serum concentrations of oxymorphone after administration of LEOx and standard oxymorphone (STDOx) to healthy female rhesus macaques. At baseline, 1 mL of blood was drawn from the femoral vein with the animal in a restraint cage. Primates were divided into two groups: (i) LEOx 1.0 mg kg^–1(n = 4); 2) STDOx 0.1 mg kg^–1(n = 4). Unloaded liposomal vehicle (0.5 mL) was used as a control (n = 2). All treatments were given subcutaneously in a shaved area proximal to the right ileal wing. Femoral venous blood was drawn and serum concentrations of drug were measured at 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, and 120 hours. Serum concentrations were measured with ELISA. Serum concentrations were compared between groups and within groups across time with anova . Drug was not detected at any time point in the control group. While sedation was not objectively measured, no animal appeared overly sedate after either treatment. All animals willingly accepted treats and did not appear nauseated or somnolent. Serum concentrations of drug were not significantly different between the two treatment groups from 0 to 2 hours. From 4 hours through 72 hours, however, serum concentrations were significantly higher (p < 0.05) in the animals that received LEOx. By 12 hours, serum concentrations of drug fell below the limit of detection (1.5 ng mL^–1) in animals that received STOx. In animals that received LEOx, serum concentrations at 72 hours were comparable to those measured at 4 hours in animals that received STOx. These results suggest that subcutaneous administration of liposomal oxymorphone yields extended serum levels of drug. These results also suggest that liposomal oxymorphone may provide therapeutic (i.e. analgesic) serum concentrations of drug for 2–3 days after a single subcutaneous administration. Further studies are warranted to assess analgesic efficacy and pharmacokinetics of lipsomal oxymorphone in primates.     

Serum chlortetracycline concentrations in parrots fed medicated seed diets

Various seed diets containing chlortetracycline were fed to large and small parrots to evaluate serum chlortetracycline concentrations. The substitution of dehulled sunflower seed for whole sunflower in the seed mix may have resulted in higher chlortetracycline concentrations in cockatoos and parrots. The serum chlortetracycline concentration achieved for all diets was less than the goal of 1 μg/mL, but the concentrations attained may be useful for therapy.     

Pharmacokinetics of butorphanol tartrate in rabbits.

The pharmacokinetic properties of butorphanol tartrate were determined in 7 rabbits after IV and SC injection (0.5 mg/kg of body weight). A 2-compartment model (biexponential) best represented the concentration vs time curve after IV injection. The half-life was calculated to be 1.64 hours via IV administration, whereas SC injection resulted in an elimination half-life of 3.16 hours.     

Sedative effects and serum concentrations across time after subcutaneous administration of liposome-encapsulated or standard oxymorphone in healthy dogs

Our lab has developed a slow‐release liposomal formulation of oxymorphone (LEOx). The purpose of this study was to compare sedative effects and serum concentrations of oxymorphone after administration of LEOx and standard oxymorphone (STDOx) to dogs. At baseline, 1 mL of blood was drawn from the cephalic vein and sedation score was recorded. Dogs were divided into four groups (n = 6): (i) LEOx 1.0 mg kg^–1; (ii) LEOx 0.5 mg kg^–1; (iii) STDOx 0.1 mg kg^–1; (iv) STDOx 0.05 mg kg^–1. Unloaded liposomal vehicle (0.5 mL) was used as a control (n = 2). All treatments were given subcutaneously between the scapulae. Sedation score and serum concentration of drug were recorded at 0.5, 1, 2, 4, 8, 12, 16, 24 hours and daily for 5 days. Serum concentrations were measured with ELISA. At all time points, drug was not detected and sedation score was 0 in the control group. Sedation score for group 1 was significantly higher (p < 0.05) at 1 hour than for groups 2,3, and 4. There was no difference in sedation score between treatment groups at any other time. Serum concentrations of drug were significantly higher (p < 0.05) for group 1 at all time points measured after baseline. In groups 2, 3, and 4, serum concentrations of drug fell below the limit of detection (1.5 ng mL^–1) by 24 hours. Serum concentrations after 0.1 mg kg^–1of STDOx were 11.1 ± 3.6 ng mL^–1at 4 hours, which is the recommended time for redosing and presumably reflects the lower end of a therapeutic serum concentration. Serum concentrations were comparable after 1.0 mg kg^–1 of LEOx (10.5 ± 2.4 ng mL^–1) 48 hours after administration. These results suggest that liposomal oxymorphone may provide therapeutic serum concentrations of drug for 2 days after a single subcutaneous administration without undue sedation or other deleterious effects in healthy dogs. Further studies are warranted to assess analgesic efficacy and pharmacokinetics of lipsomal oxymorphone in dogs.     

Cardiopulmonary effects of butorphanol tartrate intravenously administered for placement of duodenal cannulae in isoflurane-anesthetized yearling steers

Cardiopulmonary effects of IV administered butorphanol tartrate (BUT) were assessed in 7 yearling steers medicated with atropine and anesthetized with guaifenesin, thiamylal sodium, and isoflurane in O2 for surgical placement of duodenal cannulae. Heart rate, respiratory rate, arterial blood pressures, pHa, PaCO2, PaO2, arterial [HCO3-], esophageal temperature, and end-tidal isoflurane concentrations were measured before and after IV administration of BUT (10 mg). Mean respiratory rate increased significantly (P less than 0.05) only at 45 and 60 minutes after BUT administration. Mean respiratory rate was 26 +/- 6.3 breaths/min before BUT administration and 46 +/- 12.1 breaths/min 60 minutes after BUT administration. Arterial blood pressures were increased significantly (P less than 0.05) at all times, except 5 minutes after BUT administration. The mean value for mean arterial pressure was 76 +/- 9.6 mm of Hg before BUT injection and 117 +/- 12.6 mm of Hg 60 minutes after BUT injection. Mean values for pHa and arterial [HCO3-] were significantly (P less than 0.05) higher at 60 minutes after BUT administration (baseline, pH = 7.25 +/- 0.04 and [HCO3-] = 29.9 +/- 3.5 mEq/L; 60 minutes after BUT, pH = 7.28 +/- 0.03 and [HCO3-] = 33.0 +/- 1.8 mEq/L). Although some statistically significant changes were recorded, IV administration of BUT to these steers did not have a marked effect on the cardiopulmonary variables measured.     

Experimental pharmacodynamics and analgesic efficacy of liposome-encapsulated hydromorphone in dogs

The purpose of this study was to determine the experimental side effects of liposome-encapsulated hydromorphone (LE-Hydro) in beagles and to evaluate LE-Hydro analgesia in dogs undergoing ovariohysterectomies (OVH). Beagles were injected subcutaneously with 1-3 mg/kg LE-Hydro or 0.1 mg/kg hydromorphone. Dogs were evaluated for sedation, temperature, respiratory rate, and heart rate. OVH dogs were injected with 2 mg/kg LE-Hydro subcutaneously or 0.2 mg/kg morphine and 0.05 mg/kg acepromazine intramuscularly. Side effects of LE-Hydro were within clinically acceptable limits. The analgesic efficacy was superior in dogs administered LE-Hydro at 12 hr postsurgically. LE-Hydro provided adequate, durable analgesia in dogs undergoing OVH.     

Post-operative analgesic effects of butorphanol or firocoxib administered to dogs undergoing elective ovariohysterectomy

ObjectiveTo compare the post-operative analgesic effects of butorphanol or firocoxib in dogs undergoing ovariohysterectomy.Study designProspective, randomized, blinded, clinical trial.AnimalsTwenty-five dogs >1 year of age.MethodsDogs received acepromazine intramuscularly (IM), 0.05 mg kg^?1 and either butorphanol IM, 0.2 mg kg^?1 (BG, n = 12) or firocoxib orally (PO), 5 mg kg^?1 (FG, n = 13), approximately 30 minutes before induction of anesthesia with propofol. Anesthesia was maintained with isoflurane. Ovariohysterectomy was performed by the same surgeon. Pain scores using the dynamic and interactive visual analog scale (DIVAS) were performed before and at 1, 2, 3, 4, 6, 8 and 20 hours after the end of surgery by one observer, blinded to the treatment. Rescue analgesia was provided with morphine (0.5 mg kg^?1) IM and firocoxib, 5 mg kg^?1 (BG only) PO if DIVAS > 50. Groups were compared using paired t-tests and Fisher’s exact test (p < 0.05). Data are presented as mean ± SD.ResultsThe BG required significantly less propofol (BG: 2.6 ± 0.59 mg kg^?1; FG: 5.39 ± 0.7 mg kg^?1) (p < 0.05) but the anesthesia time was longer (BG: 14 ± 6, FG: 10 ± 4 minutes). There were no differences for body weight (BG: 7.9 ± 5.0, FG: 11.5 ± 4.6 kg), sedation scores, and surgery and extubation times (BG: 10 ± 2, 8 ± 5 minutes; FG: 9 ± 3, 8 ± 4 minutes, respectively) (p > 0.05). The FG had significantly lower pain scores than the BG at 1, 2 and 3 hours following surgery (p < 0.05). Rescue analgesia was administered to 11/12 (92%) and 2/13 (15%) dogs in the BG and FG, respectively (p < 0.05).Conclusion and clinical relevanceFirocoxib produced better post-operative analgesia than butorphanol. Firocoxib may be used as part of a multimodal analgesia protocol but may not be effective as a sole analgesic.     

Analgesic effects of butorphanol and buprenorphine in conscious African grey parrots (Psittacus erithacus erithacus and Psittacus erithacus timneh)

OBJECTIVE: To evaluate effects of butorphanol tartrate and buprenorphine hydrochloride on withdrawal threshold to a noxious stimulus in conscious African grey parrots. ANIMALS: 29 African grey parrots (Psittacus erithacus erithacus and Psittacus erithacus timneh). PROCEDURE: Birds were fitted with an electrode on the medial metatarsal region of the right leg, placed into a test box, and allowed to acclimate. An electrical stimulus (range, 0.0 to 1.46 mA) was delivered to each bird's foot through an aluminum perch. A withdrawal response was recorded when the bird lifted its foot from the perch or vigorously flinched its wings. Baseline threshold to a noxious electrical stimulus was determined. Birds then were randomly assigned to receive an i.m. injection of saline (0.9% NaCl) solution, butorphanol (1.0 mg/kg of body weight), or buprenorphine (0.1 mg/kg), and threshold values were determined again. RESULTS: Butorphanol significantly increased threshold value, but saline solution or buprenorphine did not significantly change threshold values. CONCLUSIONS AND CLINICAL RELEVANCE: Butorphanol had an analgesic effect, significantly increasing the threshold to electrical stimuli in African grey parrots. Buprenorphine at the dosage used did not change the threshold to electrical stimulus. Butorphanol provided an analgesic response in half of the birds tested. Butorphanol would be expected to provide analgesia to African grey parrots in a clinical setting.     

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.     

Evaluation of the sedative,analgesic, clinicophysiological and haematological effects of intravenous detomidine,detomidine‐butorphanol,romifidine and romifidine‐butorphanol in standing donkeys

The aim of this investigation was to determine and evaluate the sedative, analgesic, clinicophysiological and haematological effects of intravenous (i.v.) injection of detomidine, detomidine‐butorphanol, romifidine and romifidine‐butorphanol. Six standing donkeys were used. Each donkey received 4 i.v. treatments and the order of treatment was randomised with a one‐week interval between each treatment. We found that i.v. injection of a combination of detomidine‐butorphanol or romifidine‐butorphanol produced potent neuroleptanalgesic effects thus providing better, safe and effective sedation with complete analgesia in standing donkeys compared with injection of detomidine or romifidine alone. The changes and reduction in pulse rate were within acceptable limits. The changes in clinicophysiological, haematological and biochemical values were mild and transient in these clinically healthy donkeys.     

Serum concentrations of ionized calcium, vitamin D3, and parathyroid hormone in captive thick-billed parrots (Rhynchopsitta pachyrhyncha).

Serum collected from 68 thick-billed parrots (Rhynchopsitta pachyrhyncha) from 15 institutions was analyzed for ionized Ca (iCa), total Ca (tCa), P, total protein (TP), albumin (Alb), parathyroid hormone (PTH), and vitamin D3. Values were not distributed normally; 95% frequency intervals were as follows: iCa (0.82-1.3 mmol/L), tCa (1.37-2.09 mmol/L,), P (0.35-1.75 mmol/L), TP (21-39 g/L), Alb (9-13 g/L), PTH (0-65.68 pmol/L), and vitamin D3 (5.2-51 nmol/L). Sixty percent (+/-7.5%) of tCa was ionized. Female thick-billed parrots had significantly higher mean iCa (1.11 mmol/L, n = 22) than male thick-billed parrots (1.05 mmol/L, n = 32). tCa and iCa values in thick-billed parrots were lower than the reported values for other psittacine species. A significant positive linear relationship existed between Alb-TP and iCa-tCa ratios. A significant inverse linear relationship was also identified between the tCa-P ratio and PTH. These findings are consistent with known domestic avian Ca physiology.     

Comparative cardiovascular, analgesic, and sedative effects of medetomidine, medetomidine–hydromorphone, and medetomidine–butorphanol in dogs

The purpose of this study was to determine the cardiovascular, analgesic, and sedative effects of IV medetomidine (M, 20 µg kg^?1), medetomidine–hydromorphone (MH, 20 µg kg^?1 ? 0.1 mg kg^?1), and medetomidine–butorphanol (MB, 20 µg kg^?1 ? 0.2 mg kg^?1) in dogs. Using a randomized cross‐over design and allowing 1 week between treatments, six healthy, mixed‐breed dogs (five males and one female) weighing 20 ± 3 kg, were induced to anesthesia by face‐mask administration of 2.9% ET sevoflurane to facilitate instrumentation prior to administration of the treatment combinations. Dogs were intubated and instrumented to enable measurement of heart rate (HR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (PAP), pulmonary arterial occlusion pressure (PAOP), central venous pressure (CVP), pulmonary arterial temperature (TEMP), and cardiac output via thermodilution using 5 mL of 5% dextrose, and recording the average of the three replicate measurements. Cardiac index (CI) and systemic (SVR) and pulmonary vascular resistances were calculated. After instrumentation was completed, administration of sevoflurane was discontinued, and the dogs were allowed to recover for 30 minutes prior to administration of the treatment drugs. After collection of the baseline samples for blood gas analysis and recording the baseline cardiovascular variables, the test agents were administered IV over 10 seconds and the CV variables recorded at 5, 10, 15, 30, 45, and 60 minutes post‐injection. In addition, arterial blood was sampled for blood gas analysis at 15 and 45 minutes following injection. Intensity and duration of analgesia (assessed by toe‐pinch response using a hemostat) and level of sedation were evaluated at the above time points and at 75 and 90 minutes post‐injection. Data were analyzed using anova for repeated measures with posthoc differences between means identified using Bonferroni's method (p < 0.05). Administration of M, MH, or MB was associated with increases in SAP, MAP, DAP, PAP, PAOP, CVP, SVR, and TEMP and with decreases in HR and CI. No differences in CV variables between treatment groups were identified at any time. PaO₂ increased over time in all groups and was significantly higher when MH was compared with M. At 45 minutes, PaO₂ tended to decrease over time and was significantly lower when MH and MB were compared with M at 15 minutes. Analgesia scores for MH and MB were significantly higher compared with M through 45 minutes, while analgesia scores for MH were significantly higher compared with M through 90 minutes. Sedation scores were higher for MH and MB compared with M throughout 90 minutes. Durations of lateral recumbency were 108 ± 10.8, 172 ± 15.5, and 145 ± 9.9 minutes for M, MH, and MB, respectively. We conclude that MH and MB are associated with improved analgesia and sedation and have similar CV effects when compared with M.     

Hemodynamic effects of butorphanol in desflurane-anesthetized dogs

ObjectiveTo evaluate the effects of butorphanol on cardiopulmonary parameters in dogs anesthetized with desflurane and breathing spontaneously.Study designProspective, randomized experimental trial.AnimalsTwenty dogs weighing 12 ± 3 kg.MethodsAnimals were distributed into two groups: a control group (CG) and butorphanol group (BG). Propofol was used for induction and anesthesia was maintained with desflurane (10%). Forty minutes after induction, the dogs in the CG received sodium chloride 0.9% (0.05 mL kg^?1 IM), and dogs in the BG received butorphanol (0.4 mg kg^?1 IM). The first measurements of body temperature (BT), heart rate (HR), arterial pressures (AP), cardiac output (CO), cardiac index (CI), central venous pressure (CVP), stroke volume index (SVI), pulmonary arterial occlusion pressure (PAOP), mean pulmonary arterial pressure (mPAP), left ventricular stroke work (LVSW), systemic (SVR) and pulmonary (PVR) vascular resistances, respiratory rate (f_R), and arterial oxygen (PaO₂) and carbon dioxide (PaCO₂) partial pressures were taken immediately before the administration of butorphanol or sodium chloride solution (T0) and then at 15-minute intervals (T15–T75).ResultsIn the BG, HR, AP, mPAP and SVR decreased significantly from T15 to T75 compared to baseline. f_R was lower at T30 than at T0 in the BG. AP and f_R were significantly lower than in the CG from T15 to T75. PVR was lower in the BG than in the CG at T30, while PaCO₂ was higher compared with T0 from T30 to T75 in the BG and significantly higher than in the CG at T30 to T75.Conclusions and clinical relevanceAt the studied dose, butorphanol caused hypotension and decreased ventilation during desflurane anesthesia in dogs. The hypotension (from 86 ± 10 to 64 ± 10 mmHg) is clinically relevant, despite the maintenance of cardiac index.