Effects of methadone, alone or in combination with acepromazine or xylazine, on sedation and physiologic values in dogs

ObjectiveTo evaluate the effects of methadone, administered alone or in combination with acepromazine or xylazine, on sedation and on physiologic values in dogs.Study designRandomized cross-over design.AnimalsSix adult healthy mixed-breed dogs weighing 13.5 ± 4.9 kg.MethodsDogs were injected intramuscularly with physiologic saline (Control), or methadone (0.5mg kg⁻¹) or acepromazine (0.1 mg kg⁻¹) or xylazine (1.0 mg kg⁻¹), or acepromazine (0.05 mg kg⁻¹) plus methadone (0.5 mg kg⁻¹) or xylazine (0.5 mg kg⁻¹) plus methadone (0.5 mg kg⁻¹) in a randomized cross-over design, with at least 1-week intervals. Sedation, pulse rate, indirect systolic arterial pressure, respiratory rate (RR), body temperature and pedal withdrawal reflex were evaluated before and at 15-minute intervals for 90 minutes after treatment.ResultsSedation was greater in dogs receiving xylazine alone, xylazine plus methadone and acepromazine plus methadone. Peak sedative effect occurred within 30 minutes of treatment administration. Pulse rate was lower in dogs that received xylazine either alone or with methadone during most of the study. Systolic arterial pressure decreased only in dogs receiving acepromazine alone. When methadone was administered alone, RR was higher than in other treatments during most of the study and a high prevalence of panting was observed. In all treatments body temperature decreased, this effect being more pronounced in dogs receiving methadone alone or in combination with acepromazine. Pedal withdrawal reflex was absent in four dogs receiving methadone plus xylazine but not in any dog in the remaining treatments.Conclusions and clinical relevanceMethadone alone produces mild sedation and a high prevalence of panting. Greater sedation was achieved when methadone was used in combination with acepromazine or xylazine. The combination xylazine–methadone appears to result in better analgesia than xylazine administered alone. Both combinations of methadone/sedative were considered effective for premedication 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.     

Analgesic efficacy of preoperative administration of meloxicam or butorphanol in onychectomized cats

OBJECTIVE: To determine analgesic efficacy and adverse effects of preemptive administration of meloxicam or butorphanol in cats undergoing onychectomy or onychectomy and neutering. DESIGN: Randomized controlled study. ANIMALS: 64 female and 74 male cats that were 4 to 192 months old and weighed 1.09 to 705 kg (2.4 to 15.5 lb). PROCEDURE: Cats received meloxicam (0.3 mg/kg [0.14 mg/lb], s.c.) or butorphanol (0.4 mg/kg [0.18 mg/lb], s.c.) 15 minutes after premedication and prior to anesthesia. A single blinded observer measured physiologic variables, assigned analgesia and lameness scores, and withdrew blood samples for each cat at baseline and throughout the 24 hours after surgery. Rescue analgesia (butorphanol, 0.4 mg/kg, i.v. or s.c.) or administration of acepromazine (0.025 to 0.05 mg/kg [0.011 to 0.023 mg/lb], i.v.) was allowed. RESULTS: Meloxicam-treated cats were less lame and had lower pain scores. Cortisol concentration was higher at extubation and lower at 1, 5, and 12 hours in the meloxicam-treated cats. Fewer meloxicam-treated cats required rescue analgesia at 3, 5, 12, and 24 hours after extubation. General impression scores were excellent or good in 75% of meloxicam-treated cats and 44% of butorphanol-treated cats. There was no treatment effect on buccal bleeding time; PCV and BUN concentration decreased in both groups, and glucose concentration decreased in meloxicam-treated cats. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative administration of meloxicam improved analgesia for 24 hours without clinically relevant adverse effects in cats that underwent onychectomy or onychectomy and neutering and provided safe, extended analgesia, compared with butorphanol.     

Comparison of intraperitoneal ropivacaine and ropivacaine–dexmedetomidine for postoperative analgesia in cats undergoing ovariohysterectomy

ObjectiveTo investigate the intraperitoneal (IP) administration of ropivacaine or ropivacaine–dexmedetomidine for postoperative analgesia in cats undergoing ovariohysterectomy.Study designProspective, randomized, blinded, positively controlled clinical study.AnimalsA total of 45 client-owned cats were enrolled.MethodsThe cats were administered intramuscular (IM) meperidine (6 mg kg⁻¹) and acepromazine (0.05 mg kg⁻¹). Anesthesia was induced with propofol and maintained with isoflurane. Meloxicam (0.2 mg kg⁻¹) was administered subcutaneously in all cats after intubation. After the abdominal incision, the cats were administered one of three treatments (15 cats in each treatment): IP instillation of 0.9% saline solution (group Control), 0.25% ropivacaine (1 mg kg⁻¹, group ROP) or ropivacaine and dexmedetomidine (4 μg kg⁻¹, group ROP–DEX). During anesthesia, heart rate (HR), electrocardiography, noninvasive systolic arterial pressure (SAP) and respiratory variables were monitored. Sedation and pain were assessed preoperatively and at various time points up to 24 hours after extubation using sedation scoring, an interactive visual analog scale, the UNESP-Botucatu multidimensional composite pain scale (MCPS) and mechanical nociceptive thresholds (MNT; von Frey anesthesiometer). Rescue analgesia (morphine, 0.1 mg kg⁻¹) IM was administered if the MCPS ≥6. Data were analyzed using the chi-square test, Tukey test, Kruskal–Wallis test and Friedman test (p < 0.05).ResultsHR was significantly lower in ROP–DEX compared with Control (p = 0.002). The pain scores, MNT, sedation scores and the postoperative rescue analgesia did not differ statistically among groups.Conclusions and clinical relevanceAs part of a multimodal pain therapy, IP ropivacaine–dexmedetomidine was associated with decreased HR intraoperatively; however, SAP remained within normal limits. Using the stated anesthetic protocol, neither IP ropivacaine nor ropivacaine–dexmedetomidine significantly improved analgesia compared with IP saline in cats undergoing ovariohysterectomy.     

Effects of intravenous acepromazine and butorphanol on propofol dosage for induction of anesthesia in healthy Beagle dogs

ObjectiveTo determine the effects of intravenous (IV) premedication with acepromazine, butorphanol or their combination, on the propofol anesthetic induction dosage in dogs.Study designProspective, blinded, Latin square design.AnimalsA total of three male and three female, healthy Beagle dogs, aged 3.79 ± 0.02 years, weighing 10.6 ± 1.1 kg, mean ± standard deviation.MethodsEach dog was assigned to one of six IV treatments weekly: 0.9% saline (treatment SAL), low-dose acepromazine (0.02 mg kg^–1; treatment LDA), high-dose acepromazine (0.04 mg kg^–1; treatment HDA), low-dose butorphanol (0.2 mg kg^–1; treatment LDB), high-dose butorphanol (0.4 mg kg^–1; treatment HDB); and a combination of acepromazine (0.02 mg kg^–1) with butorphanol (0.2 mg kg^–1; treatment ABC). Physiologic variables and sedation scores were collected at baseline and 10 minutes after premedication. Then propofol was administered at 1 mg kg^–1 IV over 15 seconds, followed by boluses (0.5 mg kg^–1 over 5 seconds) every 15 seconds until intubation. Propofol dose, physiologic variables, recovery time, recovery score and adverse effects were monitored and recorded. Data were analyzed using mixed-effects anova (p < 0.05).ResultsPropofol dosage was lower in all treatments than in treatment SAL (4.4 ± 0.5 mg kg^–1); the largest decrease was recorded in treatment ABC (1.7 ± 0.3 mg kg^–1). Post induction mean arterial pressures (MAPs) were lower than baseline values of treatments LDA, HDA and ABC. Apnea and hypotension (MAP < 60 mmHg) developed in some dogs in all treatments with the greatest incidence of hypotension in treatment ABC (4/6 dogs).Conclusions and clinical relevanceAlthough the largest decrease in propofol dosage required for intubation was after IV premedication with acepromazine and butorphanol, hypotension and apnea still occurred.     

Evaluation of nalbuphine,butorphanol and morphine in dogs during ovariohysterectomy and on early postoperative pain

ObjectiveTo evaluate the effects of nalbuphine, butorphanol and morphine combined with acepromazine on intraoperative and early postoperative pain management in dogs anesthetized for ovariohysterectomy.Study designProspective, randomized blinded clinical study.AnimalsA total of 48 healthy female dogs of different breeds, aged 1–6 years, weighing (mean ± standard deviation) 14.5 ± 4.8 kg.MethodsDogs were randomly assigned into four groups to be intravenously administered nalbuphine (0.5 mg kg^–1; group N0.5), nalbuphine (1.0 mg kg^–1; group N1.0), butorphanol (0.4 mg kg^–1; group B0.4) or morphine (0.2 mg kg^–1; group M0.2) combined with acepromazine (0.02 mg kg^–1) prior to propofol and isoflurane for anesthesia. Heart rate (HR), respiratory rate, systolic arterial pressure and rectal temperature (RT) were recorded at time points during anesthesia. A dynamic interactive visual analog scale applied in three phases (DIVAS I, II and III) and the modified Glasgow composite measure pain scale were used to assess pain before premedication and 1, 2, 3, 4, 5 and 6 hours after extubation. Administration of rescue analgesia was recorded.ResultsAt the left ovarian pedicle ligation, HR was higher in N1.0 than in B0.4 (p = 0.020). RT decreased significantly by the end of surgery in N0.5 (p = 0.043) and B0.4 (p = 0.010). Rescue analgesia was administered postoperatively over 6 hours to eight, seven, nine and 10 dogs in N0.5, N1.0, B0.4 and M0.2, respectively (p = 0.57). DIVAS II was higher in B0.4 than in N1.0 at 2 and 3 hours (p = 0.038 and p = 0.002, respectively) and N0.5 at 3 hours (p = 0.003).Conclusions and clinical relevanceAt the doses used, all premedication protocols provided insufficient intraoperative analgesia, with minimal clinical differences between groups. No premedication provided satisfactory analgesia in the first 6 hours postoperatively.     

Comparison of the effects of methadone and butorphanol combined with acepromazine for canine gastroduodenoscopy

ObjectiveTo evaluate the feasibility of gastroduodenoscopy in dogs premedicated with acepromazine in combination with butorphanol or methadone.Study designProspective, randomized, double-blinded clinical trial.AnimalsA group of 40 client-owned dogs.MethodsDogs were randomly allocated to one of two groups and give intramuscular acepromazine 0.02 mg kg^–1 combined with either butorphanol 0.3 mg kg^–1 (group ACEBUT) or methadone 0.2 mg kg^–1 (group ACEMET). General anaesthesia was induced with propofol and ketamine and maintained with sevoflurane (2.3%) in oxygen. Cardiopulmonary variables were recorded at 5 minute intervals during anaesthesia. Feasibility of the entire gastroduodenoscopy was evaluated with a visual analogue scale (VAS) from 0 (best) to 100 (worst) (primary outcome of the study). Lower oesophageal sphincter dilatation and duodenal intubation were scored. Pylorus diameter was measured with standard endoscopic inflatable balloons. Overall cardiovascular stability was assessed during anaesthesia, using a VAS (0-100), as was the presence of fluid in the oesophagus, regurgitation, need for mechanical ventilation, and intraoperative and postoperative rescue analgesia (secondary outcomes of the study). Differences between treatments were analysed with Mann–Whitney U, Student t test, Fisher exact test or mixed model analysis of variance as appropriate. Subsequently, feasibility VAS of the gastroduodenoscopy was assessed for noninferiority between groups. The noninferiority margin was set as –10.ResultsAll gastroduodenoscopies were successfully completed in both groups using an endoscope tip diameter of 12.8 mm in all but one dog. Feasibility of gastroduodenoscopy was evaluated as 2.9 ± 5.6 in group ACEBUT and 5.1 ± 5.8 in group ACEMET. No significant differences between groups were detected in any measured or assessed variables, and noninferiority was confirmed.Conclusion and clinical relevanceIn our study population, the effects of methadone and butorphanol when combined with acepromazine were comparable.     

Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy

ObjectiveTo determine the induction doses, then minimum infusion rates of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent, cardiopulmonary effects, recovery characteristics and alfaxalone plasma concentrations in cats undergoing ovariohysterectomy after premedication with butorphanol-acepromazine or butorphanol-medetomidine.Study designProspective randomized blinded clinical study.AnimalsTwenty-eight healthy cats.MethodsCats undergoing ovariohysterectomy were assigned into two groups: together with butorphanol [0.2 mg kg^?1 intramuscularly (IM)], group AA (n = 14) received acepromazine (0.1 mg kg^?1 IM) and group MA (n = 14) medetomidine (20 μg kg^?1 IM). Anaesthesia was induced with alfaxalone to effect [0.2 mg kg^?1 intravenously (IV) every 20 seconds], initially maintained with 8 mg kg^?1 hour^?1 alfaxalone IV and infusion adjusted (±0.5 mg kg^?1 hour^?1) every five minutes according to alterations in heart rate (HR), respiratory rate (f_R), Doppler blood pressure (DBP) and presence of palpebral reflex. Additional alfaxalone boli were administered IV if cats moved/swallowed (0.5 mg kg^?1) or if f_R >40 breaths minute^?1 (0.25 mg kg^?1). Venous blood samples were obtained to determine plasma alfaxalone concentrations. Meloxicam (0.2 mg kg^?1 IV) was administered postoperatively. Data were analysed using linear mixed models, Chi-squared, Fishers exact and t-tests.ResultsAlfaxalone anaesthesia induction dose (mean ± SD), was lower in group MA (1.87 ± 0.5; group AA: 2.57 ± 0.41 mg kg^?1). No cats became apnoeic. Intraoperative bolus requirements and TIVA rates (group AA: 11.62 ± 1.37, group MA: 10.76 ± 0.96 mg kg^?1 hour^?1) did not differ significantly between groups. Plasma concentrations ranged between 0.69 and 10.76 μg mL^?1. In group MA, f_R, end-tidal carbon dioxide, temperature and DBP were significantly higher and HR lower.Conclusion and clinical relevanceAlfaxalone TIVA in cats after medetomidine or acepromazine sedation provided suitable anaesthesia with no need for ventilatory support. After these premedications, the authors recommend initial alfaxalone TIVA rates of 10 mg kg^?1 hour^?1.     

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.     

Effect of intraperitoneal or incisional bupivacaine on pain and the analgesic requirement after ovariohysterectomy in dogs

ObjectiveTo compare the effect of intraperitoneal (IP) or incisional (INC) bupivacaine on pain and the analgesic requirement after ovariohysterectomy in dogs.Study designProspective, randomized clinical study.AnimalsThirty female dogs undergoing ovariohysterectomy (OHE).MethodsDogs admitted for elective OHE were anesthetized with acepromazine, butorphanol, thiopental and halothane. Animals were randomly assigned to one of three groups (n = 10 per group). The treatments consisted of preincisional infiltration with saline solution (NaCl 0.9%) or bupivacaine with epinephrine and/or IP administration of the same solutions, as follows: INC and IP 0.9% NaCl (control group); INC 0.9% NaCl and IP bupivacaine (5 mg kg^?1, IP group); INC bupivacaine (1 mg kg^?1) and IP 0.9% NaCl (INC group). Postoperative pain was evaluated by a blinded observer for 24 hours after extubation by means of a visual analog scale (VAS) and a numeric rating scale (NRS). Rescue analgesia (morphine, 0.5 mg kg^?1, IM) was administered if the VAS was >5/10 or the NRS >10/29.ResultsAt 1 hour after anesthesia, VAS pain scores were [medians (interquartile range)]: 6.4 (3.1–7.9), 0.3 (0.0–2.6) and 0.0 (0.0–7.0) in control, IP and INC groups, respectively. VAS pain scores were lower in the IP compared to the control group. Over the first 24 hours, rescue analgesia was administered to 7/10, 5/10 and 3/10 dogs of the control, INC and IP groups, respectively. Total number of dogs given rescue analgesia over the first 24 hours did not differ significantly among groups.Conclusions and clinical relevanceIntraperitoneal bupivacaine resulted in lower pain scores during the first hour of the postoperative period and there was a trend towards a decreased need for rescue analgesia after OHE in dogs.     

A study to evaluate buprenorphine at 40 μg kg(-1) compared to 20 μg kg(-1) as a post-operative analgesic in the dog

ObjectiveComparison of the analgesic effect of buprenorphine at 20 or 40 μg kg^?1.Study designAn investigator ‘blinded’, randomised study.AnimalsTwenty six dogs presented for ovariohysterectomy.MethodsDogs were premedicated intramuscularly with acepromazine 0.03 mg kg^?1 and buprenorphine at either 20 (B20, n = 12) or 40 μg kg^?1 (B40, n= 14) followed by anaesthetic induction with propofol and maintenance with isoflurane. During anaesthesia non invasive blood pressure, heart rate, respiratory rate, blood oxygen saturation, inspired and expired volatile agent, end-tidal carbon dioxide and ECG were recorded. Pain and sedation were assessed using interactive VAS scores; mechanical nociceptive thresholds were measured at the wound and hindlimb - all were assessed before and up to 22 hours after administration. Carprofen was used for rescue analgesia.ResultsThere were no significant differences between the two groups for any of the parameters examined. Rescue analgesia was required around 5 hours after administration of buprenorphine in a significant number of animals. Sedation was good preoperatively and scores decreased over time postoperatively. Hock thresholds did not change over time; wound thresholds decreased significantly compared to the baseline value from 3 hours onwards.ConclusionsAdministration of buprenorphine at either 20 or 40 μg kg^?1 IM with acepromazine provided good pre-operative sedation. Cardiovascular and respiratory values remained within clinically acceptable limits during anaesthesia. There was no evidence that increasing dose increased adverse events that may be associated with opioid administration (e.g. bradycardia and respiratory depression).Clinical relevanceIncreasing the dose of buprenorphine from 20 to 40 μg kg^?1 did not provide any benefits with respect to analgesia after ovariohysterectomy as assessed using the VAS scoring system.     

Comparison of carprofen and butorphanol as post-surgical analgesics in cats

Post‐operative pain management by a single subcutaneous (SC) injection of carprofen has been found to be effective in cats and dogs. This clinical study compared the analgesic properties of injectable carprofen and butorphanol in 71 healthy cats (0.5–5 years, mean weight 3.24 ± 0.61 kg) undergoing ovariohysterectomy. Cats were randomly assigned to three groups: Group C received carprofen 4 mg kg^?1 SC at intubation and sterile saline 0.08 mL kg^?1 SC at extubation; Group B received sterile saline 0.08 mL kg^?1 SC at intubation and butorphanol 0.4 mg kg^?1 SC at extubation; Group S received sterile saline 0.08 mL kg^?1 SC at intubation and extubation. All cats were pre‐medicated with atropine (0.04 mg kg^?1 SC), acepromazine (0.02 mg kg^?1 SC), ketamine (5 mg kg^?1 SC), and induced IV with ketamine (5 mg kg^?1) and diazepam (0.25 mg kg^?1). Serum biochemistry values were taken at 24 and 48 hours post‐surgically and compared to a pre‐surgical baseline. Behavioral data were collected by a blinded investigator prior to surgery (baseline) and 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours post‐surgery; the data were compiled into composite pain scores on a scale from 0 to 21 and complemented by visual analogue scores (VAS). Scoring was based on changes in behavior, posture, vocalization, and response to interactive stimulation. Cats with pain scores >12 were considered to be moderately painful, received meperidine (4 mg kg^?1 IM), and were excluded from further statistical analyses. Sixty of 71 cats completed the study. Anesthetic time was 88.5 ± 21.8 minutes (mean ± SD). Meperidine was given to one cat in C, three in B, and five in S. There were no significant differences in biochemistry values. There were no significant differences in pain scores between C and B at any time period; B and C pain scores were significantly lower than S at 1, 2, 12, 16, and 20 hours post‐operatively, and C lower than S at 3 and 8 hours post‐surgery. Pain scores decreased over the 24‐hour study in all groups; the greatest decrease in each group was between 4 and 8 hours post‐operatively. In this study, carprofen provided post‐surgical analgesia comparable to butorphanol.     

Cyclooxygenases 1 and 2 inhibition and analgesic efficacy of dipyrone at different doses or meloxicam in cats after ovariohysterectomy

ObjectiveTo evaluate the cyclooxygenases (COX) inhibition, adverse effects and analgesic efficacy of dipyrone or meloxicam in cats undergoing elective ovariohysterectomy.Study designProspective, blinded, randomized, clinical study.AnimalsA total of 30 healthy young cats.MethodsThe cats were randomly assigned to three postoperative groups: D25 (dipyrone 25 mg kg^?1 every 24 hours), D12.5 (dipyrone 12.5 mg kg^?1 every 12 hours) and M (meloxicam 0.1 mg kg^?1 every 24 hours). In the first 24 hours, the drugs were administered intravenously (IV), and then orally for 6 (dipyrone) or 3 days (meloxicam). Prostanoids thromboxane B₂ and prostaglandin E₂ concentrations served as indicators of COX activity and, with physiological variables and pain and sedation scores, were measured for 24 hours after first analgesic administration. Rescue analgesia (tramadol, 2 mg kg^?1 IV) was provided if Glasgow feline composite measure pain scale (CMPS-Feline) ≥5. Laboratory tests included symmetric dimethylarginine and adverse effects were evaluated regularly up to 7 and 10 days after surgery, respectively. Parametric and nonparametric data were analyzed with two-way anova and Kruskal-Wallis tests, respectively (p < 0.05).ResultsIn the first half hour after analgesic administration, COX-1 activity was close to zero and remained significantly lower than before drug administration for 24 hours in all groups. The inhibition of COX-2 activity was significant for 30 minutes in all groups and up to 4 hours in group M. No alterations in laboratory tests or significant adverse effects were observed. Pain scores and need for rescue analgesia did not differ statistically among groups.ConclusionsDipyrone at both doses and meloxicam provided a nonselective inhibition of COX-1 and -2 activities and effective analgesia without causing significant adverse effects or laboratory tests alterations.Clinical relevanceDipyrone at both doses provides equally effective analgesia without causing adverse effects in cats undergoing ovariohysterectomy.     

Electrocardiographic evaluation of the degree of sedation and the isolated use of methadone in healthy dogs

ObjectiveThe present study aimed to investigate the influence of methadone on cardiorespiratory parameters, electrocardiogram and clinical sedation in dogs. Further possible side effects are reported.Study designProspective experimental cross-over study.DogsEight, 1–4-year-old, various breeds of dogs of both genders weighing 9–36 kg.MethodsEach dog was treated three times: methadone 0.3 mg kg^?1 (M0.3), 0.5 mg kg^?1 (M0.5) and 1.0 mg kg^?1 (M1.0) intramuscularly. Respiratory rate, heart rate and arterial blood pressure were recorded as well as electrocardiographic evaluation of lead II. Clinical sedation in each treatment received a score (0–3) after drug administration and at 30 minute intervals until scores and measurements returned to baseline values.ResultsA significant decrease in heart rate was seen with each dose of methadone and bradycardia (HR<60 bpm) was noted in a few dogs at each dose. A clinically significant arrhythmia occurred in one dog at 1 mg kg^?1 that required reversal with butorphanol. There was no significant difference in SAP, MAP and DAP between treatments. Some side effects such as salivation, defecation, vocalization and panting, after administration of methadone were observed. There were no differences in mean values of heart rate, P-wave and QRS complex duration and QT interval between treatments.Conclusion and clinical relevanceMethadone administration was associated with panting and a decrease in heart rate at all doses tested in this study. The cardiac rhythm should be monitored carefully in dogs when methadone is administered on its own, especially at higher doses.     

Sedative, cardiovascular, haematologic and biochemical effects of four different drug combinations administered intramuscularly in cats

ObjectiveTo compare effects of four drug combinations on sedation, echocardiographic, haematologic and biochemical variables and recovery in cats.Study designExperimental randomized ‘blinded’ cross-over study.AnimalsSix healthy cats.Materials and MethodsTreatments were administered intramuscularly: midazolam 0.4 mg kg^?1 and butorphanol 0.4 mg kg^?1 (MB); midazolam 0.4 mg kg^?1, butorphanol 0.4 mg kg^?1 and ketamine 3 mg kg^?1 (MBK); midazolam 0.4 mg kg^?1, butorphanol 0.4 mg kg^?1 and dexmedetomidine 5 μg kg^?1 (MBD); ketamine 3 mg kg^?1 and dexmedetomidine 5 μg kg^?1(KD). Sedation was evaluated at time-points over 10 minutes post injection. Echocardiography, systolic arterial blood pressure (SAP) measurement and blood sampling were performed at baseline and from 10 minutes after treatment. Quality of recovery was scored. Data were analysed by anova for repeated measures. p < 0.05 was considered significant.ResultsThe lowest sedation score was obtained by MB, (median 10.5 [7; 20]), highest by KD (36.5 [32; 38]). Quality of recovery was best with KD (0.5 [0; 2]), and worst with MB (7.5 [4; 11]). Relative to baseline measurements, treatments decreased SAP by 17%, 25%, 13%, 5% in MB, MBK, MBD and KD, respectively. Heart rate decreased (p < 0.05) after MBD (44%) and KD (34%). All treatments decreased stroke volume by 24%, 21%, 24%, 36%, and cardiac output by 23%, 34%, 54%, 53% in MB, MBK, MBD and KD, respectively. Packed cell volume was decreased (p < 0.05) by 20%, 31%, 29% in MBK, MBD and KD, respectively. Plasma glucose was increased after MBD (31%) and KD (52%) and lactate concentration was decreased (p < 0.05) after MBK (58%), MBD (72%) and KD (65%).Conclusions and clinical relevanceThe MB combination did not produce sedation in healthy cats. Treatment MBK led to acceptable sedation and minimal cardiovascular changes. Both treatments with dexmedetomidine produced excellent sedation and recovery but induced more cardiovascular depression and haematologic changes.     

A preliminary investigation comparing pre-operative morphine and buprenorphine for postoperative analgesia and sedation in cats

Objective To compare the postoperative analgesic and sedative properties of buprenorphine and morphine in cats. Study Design Prospective, randomized, blinded study. Animals Thirty‐two domestic cats undergoing surgery. Methods Cats received pre‐anaesthetic medication with acepromazine (0.05 mg kg^?1) given intramuscularly and were randomly allocated to group M and given morphine (0.1 mg kg^?1) intramuscularly (IM) or to group B and given buprenorphine (0.01 mg kg^?1) IM. Anaesthesia was induced with propofol and maintained with halothane in oxygen and nitrous oxide. Pain and sedation scores using visual analogue scales, and heart and respiratory rates, were measured immediately before, and 30, 60, 120, 180, 300 and 420 minutes after anaesthesia. Results Pain scores were significantly lower at 60, 120 and 180 minutes after anaesthesia in group B. Group B also had higher heart rates at 30 minutes. There were no other statistically significant differences between the groups. Clinical relevance Buprenorphine (0.01 mg kg^?1) appeared to provide better postoperative analgesia than morphine (0.1 mg kg^?1) and may also have a longer duration of action.     

Clinical pharmacology of methadone in dogs

ObjectiveTo investigate the pharmacokinetics and effects of methadone on behaviour and plasma concentrations of cortisol and vasopressin in healthy dogs.Study designRandomized, cross-over, experimental trial.AnimalsNine adult dogs (beagle and beagle cross breeds), four males and five females.MethodsMethadone hydrochloride, 0.4 mg kg^?1, was administered intravenously (IV) and subcutaneously (SC) with a crossover design. Drug and hormone analyses in plasma were performed using Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry and radioimmunoassay respectively. Behavioural data were collected using a standardized protocol.ResultsAfter IV administration, the plasma concentration of methadone at 10 minutes was 82.1 ± 9.2 ng mL^?1 (mean ± SD), the terminal half-life was 3.9 ± 1.0 hours, the volume of distribution 9.2 ± 3.3 L kg^?1 and plasma clearance 27.9 ± 7.6 mL minute^?1 kg^?1. After SC administration, time to maximal plasma concentration was 1.26 ± 1.04 hours and maximal plasma concentration of methadone was 23.9 ± 14.4 ng mL^?1, the terminal half-life was 10.7 ± 4.3 hours and bioavailability was 79 ± 22%. Concentrations of both cortisol and vasopressin were increased for an hour following IV methadone. The observed behavioural effects of methadone were decreased licking and swallowing and an increase in whining after SC administration. The latter finding is notable as it can be misinterpreted as pain when methadone is used as an analgesic.Conclusion and clinical relevanceWhen methadone was administered by the SC route, the half-life was longer, but the individual variation in plasma concentrations was greater compared with IV administration. Increased frequency of whining occurred after administration of methadone and may be a drug effect and not a sign of pain. Cortisol and vasopressin concentrations in plasma may not be suitable for evaluating analgesia after methadone treatment.     

The disposition and behavioral effects of methadone in Greyhounds

ObjectiveTo determine the behavioral effects and pharmacokinetics of methadone in healthy Greyhounds.Study designProspective experimental study.AnimalsThree male and three female healthy Greyhounds.MethodsMethadone hydrochloride, 0.5 mg kg⁻¹ IV (equivalent to 0.45 mg kg⁻¹ methadone base), was administered as an IV bolus. Trained observers subjectively assessed the behavioral effects of methadone. Blood samples were obtained at predetermined time points and plasma methadone concentrations were measured by liquid chromatography with tandem mass spectrometry. Pharmacokinetic variables were estimated with computer software.ResultsMethadone was well tolerated by the dogs with panting and defecation observed as adverse effects. Mild sedation was present, but no vomiting, excitement, or dysphoria was observed. The elimination half-life, volume of distribution, and plasma clearance were 1.53 ± 0.18 hours, 7.79 ± 1.87 L kg⁻¹, and 56.04 ± 9.36 mL minute⁻¹ kg⁻¹, respectively.Conclusions and clinical relevanceMethadone was well tolerated by Greyhounds. The volume of distribution was larger than expected, with resultant lower plasma concentrations than expected. Higher doses may need to be administered to Greyhounds in comparison with non-Greyhound dogs in order to achieve similar plasma drug concentrations. A dosage of 1–1.5 mg kg⁻¹ every 3–4 hours is suggested for future studies of analgesic efficacy of methadone in Greyhounds.