Efficacy of tolfenamic acid and meloxicam in the control of postoperative pain following ovariohysterectomy in the cat

Objective The hypothesis was that Visual Analog Scale (VAS) scores would be lower, and mechanical wound thresholds (MWT) higher, in cats receiving tolfenamic acid compared to those receiving placebo in the postoperative period following elective ovariohysterectomy. Animals Sixty‐nine client‐owned cats. Methods A prospective, randomized, blinded and placebo‐controlled study was performed in cats which underwent ovariohysterectomy following preoperative tolfenamic acid, meloxicam, or placebo. A second dose of the same analgesic was administered 24 hours postoperatively. Assessments were made 1‐hour before induction and 1, 2, 4, 6, 22, and 25 hours postoperatively. Pain was assessed by a blinded observer using Numerical Rating (NRS) and VAS scales. The MWT were measured using a force‐measuring device. Group comparison was performed by using one‐way anova and chi‐squared test for qualitative and quantitative data, respectively, and a mixed model for repeated measurements (p < 0.05). Results Sixty‐five cats were included in the study. There were no differences between groups at baseline. There was a treatment effect on the NRS scores at 6, 22 and 25 hours. The meloxicam group was less painful than controls at 6 and 22 hours; both treatment groups were less painful than controls at 25 hours. There were no differences between groups in VAS for pain or sedation. The number of animals receiving rescue analgesia did not differ between groups. There was a treatment effect on MWT; thresholds in both treatment groups were significantly higher than that observed in controls at all time points. Conclusions Preoperative tolfenamic acid or meloxicam reduced wound sensitivity following ovariohysterectomy in the cat. Clinical relevance Tolfenamic acid and meloxicam administered preoperatively provided a similar analgesic effect in the postoperative period lasting 24 hours. Mechanical thresholds may be a better way of evaluating postoperative analgesia provided by nonsteroidal anti‐inflammatory drugs in cats.     

Effects of tramadol,morphine or their combination in dogs undergoing ovariohysterectomy on peri-operative electroencephalographic responses and post-operative pain

Abstract

AIM: To compare the peri-operative electroencephalogram (EEG) responses and post-operative analgesic efficacy of pre-operative morphine or tramadol with a combination of low-dose pre-operative morphine and post-operative tramadol, in dogs undergoing ovariohysterectomy.

METHODS: Dogs undergoing routine ovariohysterectomy were treated with either pre-operative morphine (0.5 mg/kg S/C, n=8), or tramadol (3 mg/kg S/C, n=8), or pre-operative low-dose morphine (0.1 mg/kg S/C) and post-operative tramadol (3 mg/kg I/V, n=8). All dogs received routine pre-anaesthetic medication, and anaesthesia was induced with I/V thiopentone to effect and maintained with halothane in oxygen. Respiratory rate, heart rate, end-tidal halothane tension (EtHal) and end-tidal CO₂ tension (EtCO₂) were monitored throughout surgery. The EEG was recorded continuously in a three electrode montage. Median frequency (F50), total power (Ptot) and 95% spectral edge frequency (F95) of the EEG power spectra were compared during different 100-second periods of surgery: prior to and during skin incision, ligation of each ovarian pedicle, ligation of uterine body and skin closure. Post-operatively, pain was assessed using the short form of the Glasgow composite measure pain scale (CMPS-SF).

RESULTS: There was no difference in F50 or Ptot of the EEG between baseline and noxious surgical events within each treatment group, or between the three groups (p>0.05). The mean F95 was higher during the first three periods of surgery for dogs administered tramadol and low-dose morphine than those that received 0.5 mg/kg morphine (p=0.001). Dogs that received low-dose morphine and tramadol had lower CMPS-SF pain scores after ovariohysterectomy than those that received either tramadol or morphine alone (p=0.001). There was no difference in pain scores between dogs in the latter two groups.

CONCLUSION AND CLINICAL RELEVANCE: Tramadol and morphine administered pre-operatively provided an equal degree of post-operative analgesia in dogs after ovariohysterectomy. A combination of pre-operative low-dose morphine and post-operative tramadol produced better post-operative analgesia than either drug administered alone pre-operatively. Administration of analgesics pre- and post-operatively could result in improved post-operative well-being of ovariohysterectomised dogs.     

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.     

A comparison of preoperative tramadol and morphine for the control of early postoperative pain in canine ovariohysterectomy

Objective To compare morphine with tramadol for the management of early postoperative pain following ovariohysterectomy after pyometra in dogs. Study design Prospective randomized blinded clinical trial. Animals Thirty female dogs, 2–14 years old. Methods Animals were randomly divided into two equal groups. Group 1 received 0.2 mg kg^?1 of morphine IV and group 2 received 2 mg kg^?1 of tramadol IV after the induction of anesthesia. The dogs were premedicated with acepromazine, and anesthesia was induced with intravenous midazolam and ketamine. Isoflurane was used for the maintenance of anesthesia. The variables measured were: analgesia; sedation; cardiac and respiratory rates; arterial blood pressure; end‐tidal isoflurane and carbon dioxide (Pe ′CO₂); oxyhemoglobin saturation (SpO₂); plasma catecholamines; serum cortisol and glucose concentrations; pH and blood gases. The animals were monitored for 6 hours after the administration of the analgesic agent. Results There were no differences between the two groups with regard to analgesia, sedation, SpO₂, pH and blood gases, cardiovascular variables, glucose, catecholamine and cortisol concentrations. Forty minutes postopioid administration, the end‐tidal isoflurane concentration was significantly lower in the morphine‐treated group as compared to the tramadol group. At 30 minutes following opioid injection, Pe ′CO₂ was significantly higher in the morphine group than in the tramadol group. Two dogs in the tramadol group and one in the morphine group were given morphine postoperatively because of increasing pain scores. Conclusion and clinical relevance Morphine and tramadol, administered preemptively can be used safely in dogs to control early pain after ovariohysterectomy without significant adverse effects.     

Comparison of postoperative effects between lidocaine infusion,meloxicam, and their combination in dogs undergoing ovariohysterectomy

ObjectiveTo compare the postoperative analgesic effects of intravenous (IV) lidocaine, meloxicam, and their combination in dogs undergoing ovariohysterectomy.Study designProspective, randomized, double‐blind, controlled clinical trial.AnimalsTwenty‐seven dogs aged (mean ± SD) 16.1 ± 7.5 months and weighing 22.4 ± 17.9 kg scheduled for ovariohysterectomy.MethodsAnaesthesia was induced with propofol and maintained with isoflurane. Dogs (n = 9 in each group) were allocated to receive just prior to and during surgery one of the following regimens: M group, 0.2 mg kg^?1 IV meloxicam then a continuous rate infusion (CRI) of lactated Ringer's at 10 mL kg^?1 hour^?1; L group, a bolus of lidocaine (1 mg kg^?1 IV) then a CRI of lidocaine at 0.025 mg kg^?1 minute^?1; and M + L group, both the above meloxicam and lidocaine treatments. Pain and sedation were scored, and venous samples taken for serum cortisol and glucose measurement before and at intervals for 12 hours after anaesthesia. Pain scores were assessed using a multi‐parameter subjective scoring scale (cumulative scale 0–21) by three observers. The protocol stated that dogs with a total score exceeding 9 or a sub‐score above 3 in any one category would receive rescue analgesia. Sedation was scored on a scale of 0–4.ResultsThere were no significant differences in subjective pain scores, serum cortisol, and glucose concentrations between the three groups. The highest pain score at any time was 5, and no dog required rescue analgesia. None of the three regimens caused any observable side effects during or after anaesthesia. At 1 and 2 hours after extubation dogs in group L were significantly more sedated than in the other two groups.Conclusions and Clinical relevanceThis study suggests that, with the scoring system used, IV lidocaine and meloxicam provide similar and adequate post‐operative analgesia in healthy dogs undergoing ovariohysterectomy.     

Pharmacokinetics and analgesic efficacy of intranasal administration of tramadol in dogs after ovariohysterectomy

ObjectiveTo assess analgesic efficacy and the pharmacokinetics of intranasal (IN) tramadol in dogs following ovariohysterectomy.Study designRandomized, blinded clinical study.AnimalsA total of 30 bitches undergoing elective ovariohysterectomy.MethodsDogs were randomly assigned to one of three experimental groups (10 dogs per group): IN tramadol 4 mg kg^–1 (group T-IN), intravenous (IV) tramadol 4 mg kg^–1 (group T-IV) and IV methadone 0.2 mg kg^–1 (group M). Drugs were administered at extubation. At established time points (before surgery and up to 8 hours after drug administration) analgesia was assessed using the Italian version of the Glasgow Composite Measure Pain Scale Short Form and physiological variables were recorded. To determine the pharmacokinetics of IN tramadol, blood samples were collected at predetermined time points. Shapiro–Wilk test was used to assess whether data were normally distributed and consequently parametric or non parametric tests were applied. A p value < 0.05 was considered significant.ResultsNo significant intergroup differences were observed in the dogs that were administered rescue analgesia and time of its administration. Excluding dogs that were administered rescue analgesia, no significant intergroup differences emerged in pain scores and physiological variables, except for a lower rectal temperature in group M compared with the tramadol groups. After IN administration, tramadol was rapidly absorbed into the systemic circulation, reaching its maximum concentration (range 74.74–200.29 ng mL^–1) within 30–60 minutes, it then decreased rapidly and was detectable in plasma for up to 2 hours after treatment in all dogs.Conclusions and clinical relevanceIN tramadol administration appears to be as effective as IV tramadol and methadone treatments in pain management of dogs after elective ovariohysterectomy. Given its low concentrations and short detection time in plasma after the IN route, systemic tramadol action appears unlikely.     

Cardiorespiratory,sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone,morphine or tramadol in dogs

ObjectiveTo evaluate the cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone, morphine or tramadol in dogs.Study designExperimental, blinded, randomized, crossover study.AnimalsSix mixed breed dogs (two males and four females) weighing 10 ± 4 kg.MethodsThe animals were randomly divided into four treatments: D (10 μg kg^?1 of dexmedetomidine), DM (dexmedetomidine 10 μg kg^?1 and methadone 0.5 mg kg^?1); DMO (dexmedetomidine 10 μg kg^?1 and morphine 0.5 mg kg^?1), and DT (dexmedetomidine 10 μg kg^?1 and tramadol 2 mg kg^?1). The combinations were administered intramuscularly in all treatments. The variables evaluated were heart rate (HR), respiratory rate (f_R), rectal temperature (RT), systolic arterial pressure (SAP), sedation scale and pedal withdrawal reflex. These variables were measured at T0 (immediately before the administration of the protocol) and every 15 minutes thereafter until T105.ResultsA decrease in HR and f_R occurred in all the treatments compared with T0, but no significant difference was observed between the treatments. The RT decreased from T45 onward in all the treatments. The SAP did not show a difference between the treatments, but in the DT treatment, the SAP was lower at T30 and T45 compared with T0. The D treatment had lower scores of sedation at T15 to T75 compared with the other treatments, and the DMO and DM treatments showed higher scores at T60 and T75 compared with DT.Conclusions and clinical relevanceThe treatments with morphine and methadone added to the dexmedetomidine showed higher sedation scores than the control treatment and the treatment with tramadol added to the dexmedetomidine showed no relevant differences in any of the variables evaluated in the study.     

Comparison of the postoperative analgesic effects of cimicoxib,buprenorphine and their combination in healthy dogs undergoing ovariohysterectomy

Objective

To determine the noninferior postoperative analgesic efficacy of cimicoxib compared to buprenorphine following elective ovariohysterectomy in healthy bitches.

Analgesic effects of epidurally administered levogyral ketamine alone or in combination with morphine on intraoperative and postoperative pain in dogs undergoing ovariohysterectomy

OBJECTIVE: To evaluate the analgesic and adverse effects of epidurally administered levogyral (S[+]) ketamine alone or in combination with morphine on intraoperative and postoperative pain in dogs undergoing ovariohysterectomy. ANIMALS: 30 dogs scheduled for ovariohysterectomy. PROCEDURE: Dogs were randomly allocated to 1 of 3 groups. Dogs in group 1 received S(+) ketamine (1 mg/kg), dogs in group 2 received S(+) ketamine (0.5 mg/kg) and morphine (0.05 mg/kg), and dogs in group 3 received S(+) ketamine (1 mg/kg) and morphine (0.025 mg/kg). The skin was incised 15 minutes after epidural administration of analgesics. Heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), oxygen saturation as measured by pulse oximetry, and arterial blood gases were obtained before anesthesia, 15 minutes after epidural administration of analgesics, 15 and 30 minutes after initiation of surgery, and at the end of surgery. During the intraoperative period, an increase of > or =20% in baseline values for HR, RR, and SBP was considered a sign of intraoperative pain. Signs of pain and adverse effects were assessed at 2, 4, and 8 hours postoperatively. RESULTS: There were no significant differences in intraoperative or postoperative measurements among the 3 groups. No dogs had intraoperative signs of pain. Mean postoperative pain assessment scores were <3.5 in all 3 groups. Salivation was the most frequent adverse effect in dogs in groups 1 and 3, and sedation occurred more frequently in dogs in groups 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE: All 3 analgesic regimens provided good respiratory and cardiovascular stability intraoperatively and adequate postoperative analgesia with minimal adverse effects.     

Effect of tepoxalin on renal function and hepatic enzymes in dogs exposed to hypotension with isoflurane

ObjectiveTo evaluate the possible renal and hepatic toxicity of tepoxalin in dogs exposed to hypotension during isoflurane anesthesia.Study designProspective, randomized experimental study.AnimalsTwenty adult mixed-breed dogs, weighing 18.8 ± 2.8 kg.MethodsThe animals received 10 mg kg^?1 tepoxalin orally 2 hours before the anesthetic procedure (PRE; n = 6), or 30 minutes after anesthesia (POST; n = 6), along with a control group (CON; n = 8), which were only anesthetized. The PRE and POST groups also received the same dose of tepoxalin for 5 days post-procedure. All dogs were anesthetized with propofol and maintained with isoflurane and the end-tidal isoflurane (Fe’Iso) was increased until mean arterial pressure decreased to 50–60 mmHg. These pressures were maintained for 60 minutes. Heart rate, arterial pressures and Fe’Iso were recorded at 0, 10 and every 10 minutes up to 60 minutes of hypotension. Blood gases, pH, electrolytes and bleeding time were analyzed before and at 30 and 60 minutes of hypotension. Renal and hepatic changes were quantified by serum and urinary biochemistry and creatinine clearance.ResultsSerum concentrations of alanine amino transferase (ALT), alkaline phosphatase (ALP) and σ-glutamyl transferase (GGT), blood urea nitrogen (BUN) and creatinine (Cr), and urinary output, urinary Cr, Cr clearance, and GGT:Cr ratio remained stable throughout the evaluations. During the anesthetic procedure there were no important variations in the physiological parameters. No side effects were observed in any of the groups.Conclusions and clinical relevanceTepoxalin did not cause significant effects on renal function or cause hepatic injury in healthy dogs exposed to hypotension with isoflurane, when administered pre- or postanesthetic and continued for five consecutive days.     

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.     

Anaesthetic,analgesic and cardiorespiratory effects of intramuscular medetomidine‐ketamine combination alone or with morphine or tramadol for orchiectomy in cats

ObjectivesTo compare the anaesthetic, analgesic and cardiorespiratory effects of intramuscular (IM) medetomidine and ketamine administered alone or combined with morphine or tramadol, for orchiectomy in cats.Study designRandomised, blinded, prospective clinical study.AnimalsThirty client-owned cats.Materials and methodsCats (n = 10 in each group) received a combination of medetomidine (60 μgkg^?1) and ketamine (10 mg kg^?1) alone (MedK); combined with morphine (0.2 mg kg^?1) (MedKM), or combined with tramadol (2 mg kg^?1) (MedKT) IM. Time of induction, surgical and recovery events were recorded, and physiological parameters measured and recorded. Analgesia was evaluated with a visual analogue scale, a composite scoring system and the von Frey mechanical threshold device, every hour from three to eight hours post-drug administration injection. Data were analyzed with a linear mixed model, Kruskal–Wallis or Chi-square tests (p < 0.05).ResultsMedian (IQR) induction and recovery times (minutes) were not significantly (p = 0.125) different between groups: 5.6 (2.7–8.0), 7.4 (5.1–9.6) and 8.0 (5.8–14.9) for induction and 128.5 (95.1–142.8), 166.4 (123.1–210.0) and 142.9 (123.4–180.2) for recovery, with MedK, MedKT and MedKM, respectively. Two cats (MedKM) required alfaxalone for endotracheal intubation. In all groups, three or four cats required additional isoflurane for surgery. Arterial oxygen tension overall (mean ± SD: 66 ± 2 mmHg) was low. Surgery resulted in increased systolic arterial blood pressure (p < 0.001), haemoglobin saturation (p < 0.001), respiratory (p = 0.003) and heart rates (p = 0.002). Pain scores did not differ significantly between groups. Von Frey responses decreased over time; changes over time varied by treatment (p < 0.001), MedK returning to baseline values more rapidly than MedKM and MedKT. No cat required rescue analgesics.Conclusion and clinical relevanceAll three protocols can provide adequate anaesthesia and analgesia for orchiectomy in cats. However, rescue intervention to maintain surgical anaesthesia may be required in some cats. Oxygen supplementation is advised.     

Dose range finding study for the efficacy of meloxicam administered prior to sodium urate-induced synovitis in cats

ObjectiveTo determine the lowest efficacious dose of oral meloxicam for relieving pain in cats with a sodium urate (SU)-induced acute inflammatory synovitis.Study designRandomized, blinded, controlled, and four-way crossover study.AnimalsEight surgically neutered cats (four males, four females) paired according to sex.MethodsEach pair of cats was treated with 0 (placebo), 0.025, 0.05, or 0.075 mg kg^?1 oral meloxicam once daily for 4 days prior to injection, into alternating stifles, of 1 mL of 20 mg mL^?1 SU crystals, beginning with the right stifle. Each cat received each of the four treatments, separated by at least 21 days. Analgesic efficacy was evaluated based on objective (e.g., pressure mat data total force, contact pressure, and contact area) and subjective (e.g., scores for Analgesia Scale [AS], Lameness Scale [LS], and Visual Analog Scale [VAS]) outcome measures for pain assessment. All outcome measures were recorded before and during 30 hours after SU injection. The pre-defined primary outcome measure was the area under the response–time curve (AUC_0–30 hours) of the total force of the injected limb. Data were analyzed by analysis of variance. A sequential test procedure was applied and the test sequence stopped in case of a nonsignificant result.ResultsMeloxicam at doses of 0.05 and 0.075 mg kg^?1 day^?1 PO was significantly different from placebo for the pre-defined primary outcome measure (i.e., AUC_0–30 hours of total force). All tested meloxicam doses were lower than placebo for the subjective outcome measures (i.e., AUC_0–30 hours of AS, LS, and VAS).Conclusions and clinical relevanceThe lowest efficacious dose of meloxicam for relieving pain in cats with an SU-induced synovitis was 0.05 mg kg^?1 day^?1 PO according to the pre-defined primary outcome measure. However, lower doses may also be effective as seen in the subjective outcome measures.     

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.     

The effects of ketoconazole and cimetidine on the pharmacokinetics of oral tramadol in greyhound dogs

Tramadol is administered to dogs for analgesia but has variability in its extent of absorption, which may hinder its efficacy. Additionally, the active opioid metabolite (M1) occurs in low concentrations. The purpose of this study was to determine if administration of oral tramadol with suspected metabolism inhibitors (ketoconazole, cimetidine) would lead to improved bioavailability of tramadol and M1. Six healthy Greyhounds were included. They were administered tramadol orally and intravenously, M1 intravenously, oral tramadol with oral ketoconazole and oral tramadol with oral cimetidine. Oral tramadol bioavailability was low (2.6%). Ketoconazole and cimetidine significantly increased tramadol bioavailability to 18.2% and 20.3%, respectively. The mean maximum plasma concentration of tramadol alone was 22.9 ng/ml, and increased to 109.9 and 143.2 ng/ml with ketoconazole and cimetidine, respectively. However, measured tramadol plasma concentrations were below the minimum concentration considered effective in humans (228 μg/ml). In all treatment groups, measured M1 concentrations (<7 μg/ml) were below concentrations associated with efficacy in humans. To conclude, tramadol and M1 concentrations were low and variable in dogs after oral dosing of tramadol, even in combination with cimetidine or ketoconazole, but effective concentrations in dogs have not been defined.     

Comparative study on the sedative effects of morphine, methadone, butorphanol or tramadol, in combination with acepromazine, in dogs

Objective  To compare the effects of morphine (MOR), methadone (MET), butorphanol (BUT) and tramadol (TRA), in combination with acepromazine, on sedation, cardiorespiratory variables, body temperature and incidence of emesis in dogs.
Study design  Prospective randomized, blinded, experimental trial.
Animals  Six adult mixed-breed male dogs weighing 12.0 ± 4.3 kg.
Methods  Dogs received intravenous administration (IV) of acepromazine (0.05 mg kg⁻¹) and 15 minutes later, one of four opioids was randomly administered IV in a cross-over design, with at least 1-week intervals. Dogs then received MOR 0.5 mg kg⁻¹; MET 0.5 mg kg⁻¹; BUT 0.15 mg kg⁻¹; or TRA 2.0 mg kg⁻¹. Indirect systolic arterial pressure (SAP), heart rate (HR), respiratory rate ( f _R), rectal temperature, pedal withdrawal reflex and sedation were evaluated at regular intervals for 90 minutes.
Results  Acepromazine administration decreased SAP, HR and temperature and produced mild sedation. All opioids further decreased temperature and MOR, BUT and TRA were associated with further decreases in HR. Tramadol decreased SAP whereas BUT decreased f _R compared with values before opioid administration. Retching was observed in five of six dogs and vomiting occurred in one dog in MOR, but not in any dog in the remaining treatments. Sedation scores were greater in MET followed by MOR and BUT. Tramadol was associated with minor changes in sedation produced by acepromazine alone.
Conclusions and clinical relevance  When used with acepromazine, MET appears to provide better sedation than MOR, BUT and TRA. If vomiting is to be avoided, MET, BUT and TRA may be better options than MOR.