Effects of hydromorphone or oxymorphone, with or without acepromazine, on preanesthetic sedation, physiologic values, and histamine release in dogs

OBJECTIVE: To compare hydromorphone with oxymorphone, with or without acepromazine, for preanesthetic sedation in dogs and assess changes in plasma concentration of histamine after drug administration. DESIGN: Randomized clinical study. ANIMALS: 10 healthy mixed-breed dogs. PROCEDURE: Dogs were treated IM with hydromorphone (group H), oxymorphone (group O), hydromorphone with acepromazine (group H/A), or oxymorphone with acepromazine (group O/A). Sedation score, heart rate, respiratory rate, systolic blood pressure, and oxygen saturation were recorded at baseline immediately after drug administration (T0) and every 5 minutes for 25 minutes (T25). Plasma histamine concentration was measured at baseline and T25. RESULTS: Sedation was similar between groups H and 0 at all times. Sedation was significantly greater for groups H/A and O/A from T10 to T25, compared with other groups. Systolic blood pressure was significantly reduced at T25 in group H/A, compared with group H, and in group O/A, compared with group O. Prevalence of panting at T25 was 50% for groups H and O, compared with 20% for group H/A and 30% for group O/A. By T25, heart rate was significantly lower in all groups. Oxygen saturation was unaffected by treatment. Mean +/- SD plasma histamine concentration was 1.72 +/- 2.69 ng/ml at baseline and 1.13 +/- 1.18 ng/ml at T25. There was no significant change in plasma histamine concentration in any group. CONCLUSIONS AND CLINICAL RELEVANCE: Hydromorphone is comparable to oxymorphone for preanesthetic sedation in dogs. Sedation is enhanced by acepromazine. Neither hydromorphone nor oxymorphone caused an increase in plasma histamine concentration.     

Sedative and cardiorespiratory effects of acepromazine or atropine given before dexmedetomidine in dogs

To test the hypothesis that acepromazine could potentiate the sedative actions and attenuate the pressor response induced by dexmedetomidine, the effects of acepromazine or atropine were compared in six healthy adult dogs treated with this alpha2-agonist. In a randomised block design, the dogs received intravenous doses of either physiological saline, 0.05 mg/kg acepromazine or 0.04 mg/kg atropine, 15 minutes before an intravenous dose of 5 microg/kg dexmedetomidine. The dogs' heart rate was reduced by 50 to 63 per cent from baseline and their mean arterial blood pressure was increased transiently from baseline for 20 minutes after the dexmedetomidine. Atropine prevented the alpha2-agonist-induced bradycardia and increased the severity and duration of the hypertension, but acepromazine did not substantially modify the cardiovascular effects of the alpha2-agonist, except for a slight reduction in the magnitude and duration of its pressor effects. The dexmedetomidine induced moderate to intense sedation in all the treatments, but the dogs' sedation scores did not differ among treatments. The combination of acepromazine with dexmedetomidine had no obvious advantages in comparison with dexmedetomidine alone, but the administration of atropine before dexmedetomidine is contraindicated because of a severe hypertensive response.     

Cystometry in dogs under oxymorphone and acepromazine restraint

Cystometry was performed in 12 dogs under oxymorphone and acepromazine restraint. A detrusor reflex occurred in 10 of 12 dogs (83%). Mean threshold pressure and volume were 31 cm H2O and 22 ml/kg, respectively. Tonus limb II varied inversely with threshold volume. Threshold volume varied directly with body weight; threshold pressure was independent of body weight.     

Cardiopulmonary and behavioral effects of combinations of acepromazine/butorphanol and acepromazine/oxymorphone in dogs.

Cardiopulmonary and behavioral effects of the following tranquilizer-opioid drug combinations were compared in conscious dogs: acepromazine (0.22 mg/kg of body weight, IV) and butorphanol (0.22 mg/kg, IV); acepromazine (0.22 mg/kg, IM) and butorphanol (0.22 mg/kg, IM); and acepromazine (0.22 mg/kg, IV) and oxymorphone (0.22 mg/kg, IV). Marked sedation and lateral recumbency that required minimal or no restraint was achieved with every drug combination. Analgesia was significantly better in dogs receiving oxymorphone than in dogs receiving butorphanol, as evaluated by response to toe pinch. There were no significant differences between the effects of the 3 drug combinations on heart rate, respiratory rate, arterial blood pressure, body temperature, and arterial pH, PCO2, PO2, and bicarbonate concentration. Heart rate, respiratory rate, and systolic arterial pressure decreased significantly over time with all drug combinations. Total recovery time (minutes from the initial injection to standing) was significantly longer in the dogs given acepromazine and oxymorphone.     

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.     

Sedative and analgesic effects of buprenorphine,combined with either acepromazine or dexmedetomidine,for premedication prior to elective surgery in cats and dogs

ObjectiveTo evaluate the sedative and analgesic effects of intramuscular buprenorphine with either dexmedetomidine or acepromazine, administered as premedication to cats and dogs undergoing elective surgery.Study designProspective, randomized, blinded clinical study.AnimalsForty dogs and 48 cats.MethodsAnimals were assigned to one of four groups, according to anaesthetic premedication and induction agent: buprenorphine 20 μg kg^?1 with either dexmedetomidine (dex) 250 μg m^?2 or acepromazine (acp) 0.03 mg kg^?1, followed by alfaxalone (ALF) or propofol (PRO). Meloxicam was administered preoperatively to all animals and anaesthesia was always maintained using isoflurane. Physiological measures and assessments of pain, sedation and mechanical nociceptive threshold (MNT) were made before and after premedication, intraoperatively, and for up to 24 hours after premedication. Data were analyzed with one-way, two-way and mixed between-within subjects anova, Kruskall–Wallis analyses and Chi squared tests. Results were deemed significant if p ≤ 0.05, except where multiple comparisons were performed (p ≤ 0.005).ResultsCats premedicated with dex were more sedated than cats premedicated with acp (p < 0.001) and ALF doses were lower in dex cats (1.2 ± 1.0 mg kg^?1) than acp cats (2.5 ± 1.9 mg kg^?1) (p = 0.041). There were no differences in sedation in dogs however PRO doses were lower in dex dogs (1.5 ± 0.8 mg kg^?1) compared to acp dogs (3.3 ± 1.1 mg kg^?1) (p < 0.001). There were no differences between groups with respect to pain scores or MNT for cats or dogs.ConclusionChoice of dex or acp, when given with buprenorphine, caused minor, clinically detectable, differences in various characteristics of anaesthesia, but not in the level of analgesia.Clinical relevanceA combination of buprenorphine with either acp or dex, followed by either PRO or ALF, and then isoflurane, accompanied by an NSAID, was suitable for anaesthesia in dogs and cats undergoing elective surgery. Choice of sedative agent may influence dose of anaesthetic induction agent.     

Naloxone reversal of oxymorphone effects in dogs

Oxymorphone was administered IV to dogs 4 times at 20-minute intervals (total dosage, 1 mg/kg of body weight, IV) on 2 separate occasions. Minute ventilation, mixed-expired carbon dioxide concentration, arterial and mixed-venous pH and blood gas tensions, arterial, central venous, pulmonary arterial, and pulmonary wedge pressures, and cardiac output were measured. Physiologic dead space, base deficit, oxygen transport, and vascular resistance were calculated before and at 5 minutes after the first dose of oxymorphone (0.4 mg/kg) and at 15 minutes after the first and the 3 subsequent doses of oxymorphone (0.2 mg/kg). During 1 of the 2 experiments in each dog, naloxone was administered 20 minutes after the last dose of oxymorphone; during the alternate experiment, naloxone was not administered. In 5 dogs, naloxone was administered IV in titrated dosages (0.005 mg/kg) at 1-minute intervals until the dogs were able to maintain sternal recumbency, and in the other 5 dogs, naloxone was administered IM as a single dose (0.04 mg/kg). Naloxone (0.01 mg/kg, IV or 0.04 mg/kg, IM) transiently reversed most of the effects of oxymorphone. Within 20 to 40 minutes after IV naloxone administration and within 40 to 70 minutes after IM naloxone administration, most variables returned to the approximate values measured before naloxone administration. The effects of oxymorphone outlasted the effects of naloxone; cardiovascular and pulmonary depression and sedation recurred in all dogs. Four hours and 20 minutes after the last dose of oxymorphone, alertness, responsiveness, and coordination improved in all dogs after IM administration of naloxone. Cardiac arrhythmia, hypertension, or excitement was not observed after naloxone administration.     

Cardiopulmonary effects of medetomidine, oxymorphone, or butorphanol in selegiline-treated dogs

OBJECTIVES: To determine if chronic selegiline HCl administration affects the cardiopulmonary response to medetomidine, oxymorphone, or butorphanol in dogs. STUDY DESIGN: Prospective randomized experimental study. ANIMALS: Twenty-eight adult, random source, hound dogs weighing 21-33 kg. METHODS: Dogs were assigned to the following treatment groups: selegiline + medetomidine (MED; n = 6); placebo + MED (n = 6), selegiline + oxymorphone (OXY; n = 6); placebo + OXY (n = 6); selegiline + butorphanol (BUT; n = 7) or placebo + BUT (n = 6). Nine dogs were treated with two of the three pre-medicants. Dogs were treated with selegiline (1 mg kg(-1) PO, q 24 hours) or placebo for at least 44 days prior to pre-medicant administration. On the day of the experiment, arterial blood for blood gas analysis, blood pressure measurements, ECG, cardiac ultrasound (mM-mode, 2-D, and continuous wave Doppler), and behavioral observations were obtained by blinded observers. An IV injection of MED (750 micro g m(-2)), OXY (0.1 mg kg(-1)) or BUT (0.4 mg kg(-1)) was given. Cardiopulmonary and behavioral data were collected at 1, 2, 5, 15, 30, and 60 minutes after injection. RESULTS: Selegiline did not modify responses to any of the pre-medicant drugs. Medetomidine caused a significant decrease in heart rate (HR), cardiac output (CO), and fractional shortening (FS). Mean arterial pressure (MAP), systemic vascular resistance (SVR), and central venous pressure (CVP) were increased. Level of consciousness and resistance to restraint were both decreased. Oxymorphone did not affect MAP, CO, CVP, or SVR, but RR and PaCO(2) were increased. Level of consciousness and resistance to restraint were decreased. BUT decreased heart rate at 1 and 5 minutes. All other cardiovascular parameters were unchanged. BUT administration was associated with decreased arterial pH and increased PaCO(2). BUT decreased level of consciousness and resistance to restraint. CONCLUSIONS AND CLINICAL RELEVANCE: Although pre-medicants themselves altered cardiopulmonary and behavioral function, selegiline did not affect the response to medetomidine, oxymorphone, or butorphanol in this group of normal dogs.     

Effects of oxymorphone and hydromorphone on the minimum alveolar concentration of isoflurane in dogs

OBJECTIVES: To quantify the change in the minimum alveolar concentration (MAC) of isoflurane (ISO) associated with oxymorphone (OXY) or hydromorphone (HYDRO) in dogs. DESIGN: Randomized crossover study with at least 1 week between assessments. ANIMALS: Six young, healthy, mixed-breed dogs (1-3 years old), weighing 24.7 +/- 4.70 kg. METHODS: Following mask induction, anesthesia was maintained with ISO in 100% O(2) using mechanical ventilation. The dogs received 0.05 mg kg(-1) OXY, 0.1 mg kg(-1) HYDRO, or 1 mL saline (control) IV. Following equilibration (15 minutes) at each percentage ISO tested, a supramaximal electrical stimulus was applied to the toe web and the response was assessed. Two separate MAC determinations were carried out during 4.5 hours of anesthesia, with completion of the evaluations at 1.5-2 and 4-4.5 hours after drug administration. A two-factor anova was used to determine whether there was a time or treatment effect on MAC and a Tukey test compared the drug effects at each time. Significance is reported at p < 0.05. RESULTS: The mean MAC values (+/-SD) were 1.2 +/- 0.18 and 1.2 +/- 0.16% for control, 0.7 +/-0.15 and 1.0 +/- 0.15% for OXY, and 0.6 +/- 0.14 and 0.8 +/- 0.17% for HYDRO. The initial MAC with OXY and the MAC determined at both times with HYDRO were significantly different from the control MAC values. CONCLUSIONS: Both OXY and HYDRO significantly reduced the MAC of ISO in dogs at 2 hours. At approximately 4.5 hours, HYDRO had a significant MAC-sparing effect, whereas OXY did not. CLINICAL RELEVANCE: Although both OXY and HYDRO resulted in a significant reduction in the MAC of ISO at approximately 2 hours, HYDRO may be preferred for procedures of long duration and rarely needs repeated dosing before 4.5 hours.     

Pharmacokinetics of ammonium sulfate gradient loaded liposome‐encapsulated oxymorphone and hydromorphone in healthy dogs

ObjectiveTo evaluate the pharmacokinetics, in dogs, of liposome–encapsulated oxymorphone and hydromorphone made by the ammonium sulfate gradient loading technique (ASG).AnimalsFour healthy purpose–bred Beagles aged 9.5 ± 3.2 months and weighing 13.4 ± 2.3 kg.Study designRandomized cross–over design.MethodsEach dog was given either 4.0 mg kg^?1 of ASG–oxymorphone or 8.0 mg kg^?1 of ASG–hydromorphone SC on separate occasions with a 3–month washout period. Blood was collected at baseline and at serial time points up to 1032 hours (43 days) after injection for determination of serum opioid concentrations. Serum opioid concentrations were measured with HPLC–MS and pharmacokinetic parameters were calculated using commercial software and non–compartmental methods.ResultsSerum concentrations of oxymorphone remained above the limit of quantification for 21 days, while those for hydromorphone remained above the limit of quantification for 29 days. C_max for ASG–oxymorphone was 7.5 ng mL^?1; C_max for ASG–hydromorphone was 5.7 ng mL^?1.Conclusions and clinical relevanceOxymorphone and hydromorphone, when encapsulated into liposomes using the ammonium sulfate gradient loading technique, result in measureable serum concentrations for between 3 to 4 weeks. This formulation may have promise in the convenient use of opioids for clinical treatment of chronically painful conditions in dogs.     

Effect of acepromazine, diazepam, fentanyl-droperidol, and oxymorphone on gastroesophageal sphincter pressure in healthy dogs

Treatment of healthy dogs with 4 commonly used psychotropic or analgesic agents significantly decreased resting gastroesophageal sphincter pressure (GESP). Acepromazine decreased GESP by 35% (P = 0.02); oxymorphone decreased GESP by 38% (P less than 0.005); diazepam decreased GESP by 42% (P = 0.005); and fentanyl-droperidol decreased GESP by 40% (P = 0.03). Therefore, esophageal manometric evaluation of gastroesophageal sphincter function should not be preceded by administration of these drugs.