Characterisation of tramadol,morphine and tapentadol in an acute pain model in Beagle dogs

ObjectiveTo evaluate the analgesic potential of the centrally acting analgesics tramadol, morphine and the novel analgesic tapentadol in a pre-clinical research model of acute nociceptive pain, the tail-flick model in dogs.Study designProspective part-randomized pre-clinical research trial.AnimalsFifteen male Beagle dogs (HsdCpb:DOBE), aged 12–15 months.MethodsOn different occasions separated by at least 1 week, dogs received intravenous (IV) administrations of tramadol (6.81, 10.0 mg kg^?1), tapentadol (2.15, 4.64, 6.81 mg kg^?1) or morphine (0.464, 0.681, 1.0 mg kg^?1) with subsequent measurement of tail withdrawal latencies from a thermal stimulus (for each treatment n = 5). Blood samples were collected immediately after the pharmacodynamic measurements of tramadol to determine pharmacokinetics and the active metabolite O-demethyltramadol (M1).ResultsTapentadol and morphine induced dose-dependent antinociception with ED50-values of 4.3 mg kg^?1 and 0.71 mg kg^?1, respectively. In contrast, tramadol did not induce antinociception at any dose tested. Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal amounts of the M1 metabolite, which explains the absence of the antinociptive effect of tramadol in this experimental pain model in dogs.Conclusions and clinical relevanceDifferent breeds of dogs might not or only poorly respond to treatment with tramadol due to low metabolism of the drug. Tapentadol and morphine which act directly on μ-opioid receptors without the need for metabolic activation are demonstrated to induce potent antinociception in the experimental model used and should also provide a reliable pain management in the clinical situation. The non-opioid mechanisms of tramadol do not provide antinociception in this experimental setting. This contrasts to many clinical situations described in the literature, where tramadol appears to provide useful analgesia in dogs for post-operative pain relief and in more chronically pain states.     

Intravenous tramadol: effects, nociceptive properties, and pharmacokinetics in horses

ObjectiveTo determine the optimal dose, serum concentrations and analgesic effects of intravenous (IV) tramadol in the horse.Study designTwo-phase blinded, randomized, prospective crossover trial.AnimalsSeven horses (median age 22.5 years and mean weight 565 kg).MethodsHorses were treated every 20 minutes with incremental doses of tramadol HCl (0.1–1.6 mg kg^?1) or with saline. Heart rate, respiratory rate, step frequency, head height, and sweating, trembling, borborygmus and head nodding scores were recorded before and up to 6 hours after treatment. In a second study, hoof withdrawal and skin twitch reflex latencies (HWRL and STRL) to a thermal stimulus were determined 5 and 30 minutes, and 1, 2, 4 and 6 hours after bolus IV tramadol (2.0 mg kg^?1) or vehicle. Blood samples were taken to determine pharmacokinetics.ResultsCompared to saline, tramadol caused no change in heart rate, step frequency or sweating score. Respiratory rate, head height, and head nodding and trembling scores were transiently but significantly increased and borborygmus score was decreased by high doses of tramadol. Following cumulative IV administration of 3.1 mg kg^?1 and bolus IV administration of 2 mg kg^?1, the elimination half-life of tramadol was 1.91 ± 0.33 and 2.1 ± 0.9 hours, respectively. Baseline HWRL and STRL were 4.16 ± 1.0 and 3.06 ± 0.99 seconds, respectively, and were not significantly prolonged by tramadol.Conclusion and clinical relevanceIV tramadol at cumulative doses of up to 3.1 mg kg^?1 produced minimal transient side effects but 2.0 mg kg^?1 did not provide analgesia, as determined by response to a thermal nociceptive stimulus.     

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 tramadol and morphine for pre-medication of dogs undergoing general anesthesia for orthopedic surgery

Tramadol is a centrally acting analgesic with opioid and monoaminergic actions. Its clinical effects have been well characterized in humans, where it has been in use for many years, but little is known for veterinary species. This study evaluated the sedative, emetic, thiopental‐sparing and intraoperative respiratory and hemodynamic effects of tramadol in comparison to morphine for pre‐medication of dogs undergoing orthopedic surgery under halothane anesthesia. Sixteen adult, healthy, mixed breed dogs (8.0 ± 2.6 kg) were studied. Eight dogs were pre‐medicated with tramadol (1.0 mg kg^‐1 IM) and the other eight with morphine (1.0 mg kg^–1 IM). After 20 minutes, anesthesia was induced with thiopental and subsequently maintained with halothane in oxygen using a Bain system, with spontaneous respiration. Degree of sedation and occurrence of emesis were evaluated after pre‐anesthetic medication. Dose of thiopental necessary for tracheal intubation was compared between the two groups. Arterial blood gas analyzes were done before pre‐medication and at 60 minutes of anesthesia. Heart rate and noninvasive arterial blood pressure were recorded before pre‐medication and every 10 minutes during anesthesia. Observer was blinded of the treatment given for each dog. Tramadol produced no visible sedation and no vomiting, while morphine induced a moderate degree of sedation in all dogs and vomiting in 62% of them. Dogs pre‐medicated with tramadol required significantly more thiopental (17 ± 3.8 mg kg^–1) for induction of anesthesia than those pre‐medicated with morphine (12 ± 1.8 mg kg^–1). Pre‐medication with morphine was associated with significantly higher PaCO₂ and lower pH at 60 minutes of anesthesia. The remaining respiratory parameters and the hemodynamic variables were similar between the two groups. In conclusion, dogs pre‐medicated with tramadol at 1 mg kg^–1 IM do not become visibly sedated and require a greater amount of thiopental for induction of anesthesia than pre‐medication with morphine. As intraoperative respiratory function is better preserved with tramadol, it may be useful for pre‐medication of respiratory compromised patients.     

Comparison of analgesia provided by lidocaine, lidocaine-morphine or lidocaine-tramadol delivered epidurally in dogs following orchiectomy

ObjectiveTo evaluate and compare the postoperative analgesia provided by epidural lidocaine, lidocaine/morphine or lidocaine/tramadol in dogs following elective orchiectomy.Study designProspective experimental trial.AnimalsThirty-six mongrel dogs aged 2-8 years old, weighing 6.6-22 kg.MethodsThe dogs received 6.0 mg kg^?1 of lidocaine combined with 1.0 mg kg^?1 of tramadol, 0.1 mg kg^?1 of morphine or 0.01 mL kg^?1 of 0.9% NaCl epidurally. Analgesia was assessed at 4, 8, 12, 18 and 24 hours (T4, T8, T12 and T24) after the offset of lidocaine using a scale composed of physiologic and behavioral parameters. Rescue analgesia with morphine (0.2 mg kg^?1, IM) was performed if the evaluation score exceeded 10 during the postoperative period. The scores over time were analyzed using the Friedman’s two-way analysis of variance and the comparison between groups was made by the Kruskal-Wallis test with statistical significances accepted if p = 0.05.ResultsThere were no differences in the pain scores between the morphine and tramadol groups over time and no rescue analgesia was administered. In the NaCl group, rescue analgesia was needed at T4, T8 and T12. Within this group, the final evaluation times (T18 and T24) had lower pain scores than at T4, T8 and T12.Conclusions and clinical relevanceEpidural lidocaine/tramadol provided an analgesic effect comparable to that of epidural lidocaine/morphine during the first 12 hours after surgical castration without substantial side effects, suggesting that tramadol may be an effective postoperative analgesic in dogs submitted to this surgical procedure.     

Use of a pulsed electromagnetic field for treatment of post-operative pain in dogs: a pilot study

Objective To determine if pulsed electromagnetic field (PEMF) therapy reduces post‐operative pain in dogs following ovariohysterectomy, and to evaluate PEMF interaction with post‐operative morphine analgesia. Study design Randomized controlled clinical trail. Animals Sixteen healthy dogs weighing 18 (10–32) kg [median (range)] and aged 13 (3–36) months. Materials and methods Anesthesia consisted of atropine (0.04 mg kg^?1, SC), acepromazine (0.02 mg kg^?1, SC), fentanyl (0.01 mg kg^?1, SC), thiopental (10–15 mg kg^?1, IV) and halothane in oxygen. Ovariohysterectomies were performed by senior veterinary students. Pain score (numeric rating scale, 0–28), pulse rate, respiratory rate, indirect mean arterial pressure (MAP), and body temperature were evaluated prior to anesthetic premedication, at extubation, 30 minutes after extubation, and then hourly for 6 hours. Following extubation, dogs were randomly divided into four groups: a control group that received 0.9% NaCl, IV, and no PEMF; a magnet group that received 0.9% NaCl, IV, and PEMF; a morphine group that received morphine 0.25 mg kg^?1, IV, and no PEMF; and, a magnet/morphine group that received morphine 0.25 mg kg^?1, IV, and PEMF. A single observer, blinded to treatment, obtained all behavioral observations and physiologic data. Data were analyzed using the Kruskal–Wallis statistical test with a significance of p < 0.05. Results Significant differences in MAP (mm Hg) [median (range)] occurred at 300 minutes [morphine 108 (83–114) and magnet/morphine 90 (83–97) < magnet 135 (113–117)], and at 360 minutes [magnet/morphine 93 (81–100) < control 127 (111–129) and magnet 126 (111–129)]. At 30 minutes the total pain score for the magnet/morphine group [1.5 (0–5)] was significantly less than control [8 (6–13)], but not different from magnet [5.5 (4–7)] or morphine [4.5 (2–9)]. Conclusions and clinical relevance Although no clear benefit was seen in this study, the results suggest that PEMF may augment morphine analgesia following ovariohysterectomy in dogs, and that further study of the analgesic effects of PEMF is warranted.     

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.     

Effects of tramadol alone,in combination with meloxicam or dipyrone,on postoperative pain and the analgesic requirement in dogs undergoing unilateral mastectomy with or without ovariohysterectomy

ObjectiveTo compare the effects of tramadol alone, or in combination with dipyrone or meloxicam, on postoperative pain and analgesia requirement after unilateral mastectomy with or without ovariohysterectomy in dogs.Study designProspective, randomized, clinical study.AnimalsTwenty seven bitches undergoing unilateral mastectomy with or without ovariohysterectomy.MethodsAnesthesia was induced with propofol and maintained with isoflurane and a constant rate infusion of morphine. Before the end of surgery, dogs were randomly assigned to receive intravenous tramadol alone (3 mg kg^?1, group T), combined with dipyrone (30 mg kg^?1, group TD) or meloxicam (0.2 mg kg^?1, group TM). Dogs received additional doses of tramadol (groups T and TM) or tramadol with dipyrone (group TD) at 8 and 16 hours after extubation. Postoperative pain was assessed by a blinded observer before anesthesia (baseline) and at 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours after extubation using a visual analog scale (VAS) and a modified Glasgow scale. Rescue analgesia (morphine, 0.5 mg kg^?1) was administered if the Glasgow pain score was >3.5.ResultsThere were no significant differences among groups in pain scores evaluated by the VAS or the Glasgow scale. In groups T, TD and TM, pain scores were significantly higher than at baseline for 6, 8 and 2 hours, respectively. Rescue analgesia was administered to 3/9, 2/9 and 1/9 dogs in groups T, TD and TM, respectively (p > 0.05) [Correction added on 15 August 2013, after first online publication: ‘T, TM and TD’ was changed to ‘T, TD and TM’.].Conclusions and clinical relevanceUnder the conditions of this study, tramadol alone or in combination with dypyrone or meloxicam provided effective analgesia for 24 hours in most dogs after unilateral mastectomy with or without ovariohysterectomy. Further evaluation of combination therapies is needed in larger groups of dogs.     

Effects of continuous intravenous infusion of morphine and morphine‐tramadol on the minimum alveolar concentration of sevoflurane and electroencephalographic entropy indices in dogs

ObjectiveTo compare the effects of continuous rate infusions (CRIs) of intravenous (IV) morphine and morphine-tramadol on the minimum alveolar concentration (MAC) of sevoflurane, and on electroencephalographic entropy indices in dogs.DesignProspective study.AnimalsEight young, healthy German shepherds, weighing 26.3 ± 3.1 kg (mean ± SD).MethodsAnaesthesia was induced and maintained with sevoflurane. A standard tail-clamp technique was used for MAC determination. Within one anaesthetic period, MAC was first determined during sevoflurane anaesthesia alone (MAC_B); then during morphine infusion (MAC_M), (loading dose 0.5 mg kg⁻¹IM; CRI, 0.2 mg kg⁻¹hour⁻¹⁾ then finally during morphine-tramadol infusion (tramadol loading dose 1.5 mg kg⁻¹IV; CRI, 2.6 mg kg⁻¹ hour⁻¹) (MAC_MT). At each change, periods of 45 minutes were allowed for equilibration. Stated entropy (SE), response entropy (RE), and RE-SE differences were measured five minutes prior to and during tail clamping.ResultsThe MAC_B was 2.1 ± 0.3vol%. The morphine and morphine-tramadol infusions reduced MAC to 1.6 ± 0.3vol% and 1.3 ± 0.3vol%, respectively. MAC was decreased below baseline more during morphine-tramadol than during morphine alone (39 ± 9% versus 25 ± 6%, respectively; p = 0.003). All SE and RE and most RE-SE differences were increased significantly (p < 0.05) over pre-stimulation in all groups when the dogs responded purposefully to noxious stimulation. When no response to noxious stimulation occurred, the entropy indices did not change.Conclusion and clinical relevanceIn dogs, combined morphine-tramadol CRI decreased sevoflurane MAC more than morphine CRI alone. Entropy indices changed during nociceptive responses in anaesthetized animals, suggesting that entropy measurements may be useful in determining anaesthetic depth in dogs.     

Effect of intravenous propofol and remifentanil on heart rate, blood pressure and nociceptive response in acepromazine premedicated dogs

ObjectiveTo investigate the cardiorespiratory, nociceptive and endocrine effects of the combination of propofol and remifentanil, in dogs sedated with acepromazine.Study designProspective randomized, blinded, cross-over experimental trial.AnimalsTwelve healthy adult female cross-breed dogs, mean weight 18.4 ± 2.3 kg.MethodsDogs were sedated with intravenous (IV) acepromazine (0.05 mg kg^?1) followed by induction of anesthesia with IV propofol (5 mg kg^?1). Anesthesia was maintained with IV propofol (0.2 mg kg^?1 minute^?1) and remifentanil, infused as follows: R1, 0.125 μg kg^?1 minute^?1; R2, 0.25 μg kg^?1 minute^?1; and R3, 0.5 μg kg^?1 minute^?1. The same dogs were administered each dose of remifentanil at 1-week intervals. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (f_R), end tidal CO₂ (Pe′CO₂), arterial hemoglobin O₂ saturation, blood gases, and rectal temperature were measured before induction, and 5, 15, 30, 45, 60, 75, 90, and 120 minutes after beginning the infusion. Nociceptive response was investigated by electrical stimulus (50 V, 5 Hz and 10 ms). Blood samples were collected for plasma cortisol measurements. Statistical analysis was performed by anova (p < 0.05).ResultsIn all treatments, HR decreased during anesthesia with increasing doses of remifentanil, and increased significantly immediately after the end of infusion. MAP remained stable during anesthesia (72–98 mmHg). Antinociception was proportional to the remifentanil infusion dose, and was considered satisfactory only with R2 and R3. Plasma cortisol concentration decreased during anesthesia in all treatments. Recovery was smooth and fast in all dogs.Conclusions and clinical relevanceInfusion of 0.25–0.5 μg kg^?1 minute^?1 remifentanil combined with 0.2 mg kg^?1 minute^?1 propofol produced little effect on arterial blood pressure and led to a good recovery. The analgesia produced was sufficient to control the nociceptive response applied by electrical stimulation, suggesting that it may be appropriate for performing surgery.     

The use of pulsed electromagnetic field (PEMF) therapy to provide post-operative analgesia in the dog

Buprenorphine is an effective analgesic when administered epidurally to humans. The purpose of this study was to compare epidural buprenorphine (B; n = 10) with epidural morphine (M; n = 10) for post‐operative analgesia in dogs undergoing cranial cruciate ligament repair. All dogs were premedicated with acepromazine (0.1 mg kg^?1 IM), induced with propofol (4–6 mg kg^?1 IV) and maintained with halothane in oxygen. Dogs were randomly assigned to receive B (0.004 mg kg^?1) or M (0.1 mg kg^?1) in the lumbosacral epidural space in a total volume of 0.2 mL kg^?1. End‐tidal halothane and CO₂ and temperature were recorded every 15 minutes until extubation (t = 0). A numerical rating pain score (SPS) was recorded at t = 0, 1, 2, 4, 6, 10 and 24 hours by a blinded observer. Dogs received rescue morphine (1.0 mg kg^?1 IM) if indicated by SPS and the time of rescue analgesic administration was recorded. Observable side‐effects such as urinary retention, sedation or pruritus were recorded. Data were analyzed with repeated measures anova . Mean ± SD body weight (kg) and age (yrs) for B dogs was 34.2 ± 10.8 and 5.5 ± 2.8; for M dogs these values were 36.6 ± 13.5 and 5.9 ± 3.3. Mean ± SD SPS for B dogs at t = 0, 1, 2, 4, 6, 10 and 24 hours were 1.2 ± 0.75, 3.2 ± 2.0, 4.5 ± 4.3, 4.6 ± 3.4, 4.7 ± 3.0, 5.0 ± 4.9 and 5.1 ± 3.5. For M dogs these values were 1.7 ± 0.5, 2.6 ± 2.0, 3.7 ± 0.75, 4.2 ± 2.2, 4.1 ± 3.0, 3.1 ± 2.1 and 3.9 ± 1.9. There were no significant differences between B and M with respect to SPS, times or frequency of rescue morphine administration, end‐tidal halothane and CO₂, or esophageal temperature. Fifty per cent of dogs in both groups required rescue morphine. Buprenorphine is as effective as morphine for epidural analgesia in healthy dogs undergoing hindlimb orthopedic surgery.     

Effects of dexmedetomidine alone or in combination with opioids on intraocular pressure in healthy Beagle dogs

ObjectiveTo evaluate the effects of dexmedetomidine alone or in combination with different opioids on intraocular pressure (IOP) in dogs.Study designExperimental, prospective, crossover, randomized, blinded study.AnimalsA total of six Beagle dogs (two males and four females) aged 2 years and weighing 15.9 ± 2.9 kg (mean ± standard deviation).MethodsDogs were distributed randomly into seven treatments (n = 6 per treatment) and were administered dexmedetomidine alone (10 μg kg^–1; Dex) or in combination with butorphanol (0.15 mg kg^–1; DexBut), meperidine (5 mg kg^–1; DexMep), methadone (0.5 mg kg^–1; DexMet), morphine (0.5 mg kg^–1; DexMor), nalbuphine (0.5 mg kg^–1; DexNal) or tramadol (5 mg kg^–1; DexTra). All drugs were administered intramuscularly. IOP was measured before drug injection (time 0, baseline) and every 15 minutes thereafter for 120 minutes (T15–T120).ResultsThere were significant reductions in IOP compared with baseline in treatments Dex and DexMep at times T30–T120, and in treatment DexMet at T15–T90. IOP decreased compared with baseline in treatments DexBut, DexNal and DexTra at all evaluation times. No changes in IOP were seen in treatment DexMor. The mean IOP values in treatment DexMet at T105–T120 were higher than those for other treatments.Conclusions and clinical relevanceDexmedetomidine alone or in combination with butorphanol, meperidine, methadone, nalbuphine or tramadol resulted in decreased IOP for 120 minutes in dogs. The magnitude of the reduction was small and lacked clinical significance.     

Modulation of nociceptive withdrawal reflexes evoked by single and repeated nociceptive stimuli in conscious dogs by low-dose acepromazine

ObjectivesTo investigate the modulation of the nociceptive withdrawal reflex (NWR) and temporal summation (TS) by low‐dose acepromazine (ACP) in conscious dogs. To assess the short‐ and long‐term stability of the reflex thresholds.Study designRandomized, blinded, placebo‐controlled cross‐over experimental study.AnimalsEight adult male Beagles.MethodsThe NWR was elicited using single transcutaneous electrical stimulation of the ulnar nerve. Repeated stimuli (10 pulses, 5 Hz) were applied to evoke TS. The responses of the deltoideus muscle were recorded and quantified by surface electromyography and the behavioural reactions were scored. Each dog received 0.01 mg kg^?1 ACP or an equal volume saline intravenously (IV) at 1 week intervals. Measurements were performed before (baseline) and 20, 60 and 100 minutes after drug administration. Sedation was scored before drug administration and then at 10 minutes intervals. Data were analyzed with Friedman repeated measures analysis of variance on ranks and Wilcoxon signed rank tests.ResultsAcepromazine resulted in a mild tranquilization becoming obvious at 20 minutes and peaking 30 minutes after injection. Single (I_t) and repeated stimuli (TS_t) threshold intensities, NWR and TS characteristics and behavioural responses were not affected by the ACP at any time point. Both I_t and TS_t were stable over time.Conclusions and clinical relevanceIn dogs, 0.01 mg kg^?1 ACP IV had no modulatory action on the NWR evoked by single or repeated stimuli, suggesting no antinociceptive activity on phasic nociceptive stimuli. The evidence of the stability of the NWR thresholds supports the use of the model as an objective tool to investigate nociception in conscious dogs. A low dose of ACP administered as the sole drug, can be used to facilitate the recordings in anxious subjects without altering the validity of this model.     

Assessment of cardiac troponin I and C-reactive protein concentrations associated with anesthetic protocols using sevoflurane or a combination of fentanyl, midazolam, and sevoflurane in dogs

ObjectiveTo report serum cardiac troponin I (cTnI) and C-reactive protein (CRP) concentrations in dogs anesthetized for elective surgery using two anesthetic protocols.Study designProspective, randomized clinical study.AnimalsTwenty client-owned dogs presenting for elective ovariohysterectomy or castration.MethodsThe dogs were randomized into two groups. All dogs were premedicated with glycopyrrolate (0.011 mg kg^?1) and hydromorphone (0.1 mg kg^?1) IM approximately 30 minutes prior to induction of anesthesia. Anesthesia in dogs in group 1 was induced with propofol (6 mg kg^?1) IV to effect and in dogs in group 2 with diazepam (0.2 mg kg^?1) IV followed by etomidate (2 mg kg^?1) IV to effect. For maintenance of anesthesia, group 1 received sevoflurane (adjustable vaporizer setting 0.5–4%) and group 2 received a combination of fentanyl (0.8 μg kg^?1 minute^?1) and midazolam (8.0 μg kg^?1 minute^?1) IV plus sevoflurane (adjustable vaporizer setting 0.5–4%) to maintain anesthesia. Serum cTnI and CRP concentrations were measured at baseline and 6, 18, and 24 hours post-anesthetic induction. Biochemical analysis was performed at baseline. Lactate was obtained at baseline and 6 hours post-anesthetic induction. Heart rate and mean arterial blood pressure were measured intra-operatively.ResultsBaseline serum cTnI and CRP concentrations were comparable between groups. A significant difference in serum cTnI or CRP concentrations was not detected post-operatively between groups at any time point. Serum CRP concentrations were significantly increased post-anesthetic induction in both groups, which was attributed to surgical trauma.Conclusions and clinical relevanceThere was no significant difference in serum cTnI and CRP concentrations between anesthetic protocols. Further investigation in a larger number of dogs is necessary to confirm the current findings.     

Evaluation of analgesic and physiologic effects of epidural morphine administered at a thoracic or lumbar level in dogs undergoing thoracotomy

ObjectiveTo evaluate the analgesic and physiological effects of epidural morphine administered at the sixth and seventh lumbar or the fifth and sixth thoracic vertebrae in dogs undergoing thoracotomy.Study designProspective, randomized, blinded trial.AnimalsFourteen mixed-breed dogs, weighing 8.6 ± 1.4 kg.MethodsThe animals received acepromazine (0.1 mg kg^?1) IM and anesthesia was induced with propofol (4 mg kg^?1) IV. The lumbosacral space was punctured and an epidural catheter was inserted up to the region between the sixth and seventh lumbar vertebrae (L, n = 6) or up to the fifth or sixth intercostal space (T, n = 8). The dogs were allowed to recover and after radiographic confirmation of correct catheter position, anesthesia was reinduced with propofol IV and maintained with 1.7% isoflurane. Following stabilization of monitored parameters, animals received morphine (0.1 mg kg^?1) diluted in 0.9% NaCl to a final volume of 0.25 mL kg^?1 via the epidural catheter, and after 40 minutes, thoracotomy was initiated. Heart rate and rhythm, systolic, mean and diastolic arterial pressures, respiratory rate, arterial hemoglobin oxygen saturation, partial pressure of expired CO₂ and body temperature were measured immediately before the epidural administration of morphine (0 minute) and every 10 minutes during the anesthetic period. The Melbourne pain scale and the visual analog scale were used to assess post-operative pain. The evaluation began 3 hours after the epidural administration of morphine and occurred each hour until rescue analgesia.ResultsThere were no important variations in the physiological parameters during the anesthetic period. The post-operative analgesic period differed between the groups, being longer in T (9.9 ± 1.6 hours) compared with L (5.8 ± 0.8 hours).ConclusionsThe use of morphine, at a volume of 0.25 mL kg^?1, administered epidurally over the thoracic vertebrae provided longer lasting analgesia than when deposited over the lumbar vertebrae.Clinical relevanceThe deposition of epidural morphine provided longer lasting analgesia when administered near to the innervation of the injured tissue without increasing side effects.     

A comparison of epidural morphine with low dose bupivacaine versus epidural morphine alone on motor and respiratory function in dogs following splenectomy

ObjectiveTo compare post-operative motor function in dogs that received epidural morphine and low dose bupivacaine versus epidural morphine alone following splenectomy.Study designProspective, randomized study.Animals16 client owned dogs undergoing routine splenectomy.MethodsFollowing splenectomy dogs were randomly allocated into one of two groups. The morphine group (MOR) was administered epidural morphine (0.1 mg kg^?1); the morphine-bupivacaine group (MORB) received epidural morphine (0.1 mg kg^?1) and low dose bupivacaine [0.25 mg kg^?1, (0.167%)]. The adjusted final volume was 0.15 mL kg^?1 in both groups. Motor function and pain assessment were performed at pre-determined times using a simple numerical motor score and the University of Melbourne Pain Scale (UMPS) respectively. An arterial blood gas was performed 2 hours following epidural administration to check for respiratory compromise. If patients scored >7 on the UMPS or were deemed painful by the observer they were administered hydromorphone intravenously and dose and time of rescue analgesia were recorded.ResultsThere were no statistically significant differences in motor scores, pain scores, amount of rescue analgesia administered or PaCO₂ between treatment groups. No dogs demonstrated respiratory depression or profound motor dysfunction at any time point during the study. 9/16 (56%) dogs did not require rescue analgesia during the first 18 hours following splenectomy.Conclusions and clinical relevanceThe combination of low dose bupivacaine (0.25 mg kg^?1) and morphine (0.1 mg kg^?1) when administered epidurally has little effect on post-operative motor function. This combination can be used without concern of motor paralysis in healthy animals.     

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.     

Bispectral monitoring in dogs subjected to ovariohysterectomy and anesthetized with halothane, isoflurane or sevoflurane

ObjectiveTo assess the effect of halothane (H), isoflurane (I) or sevoflurane (S) on the bispectral index (BIS), and the effect of the addition of meperidine in dogs subjected to ovariohysterectomy.Study designProspective, randomized, blinded, clinical trial.AnimalsForty-eight female mixed-breed dogs, with weights varying from 10 to 25 kg.MethodsAll dogs were premedicated with acepromazine (A) (0.1 mg kg^?1 IM) or A and meperidine (M) (3 mg kg^?1 IM) and they were divided into six groups of eight animals (AH, AMH, AI, AMI, AS, and AMS). Fifteen minutes after premedication they were anesthetized with propofol (5 mg kg^?1 IV) and then orotracheally intubated. Anesthesia was maintained with halothane, isoflurane or sevoflurane, respectively. The BIS,

variables were recorded at 15 minutes after administering pre-anesthetic medication (T0); 10 minutes of anesthesia maintenance (T1); right ovarian pedicle ligation (T2); muscle suturing (T3); skin suture (T4) and 10 minutes after terminating the inhalant anesthetic (T5), respectively.ResultsBIS values were decreased at all times when compared to the baseline values in all groups (p < 0.05). In the comparative assessment between groups, the values obtained at T0 and T1 were similar for all groups. At T2, the values in AMH were lower than those obtained in AI, AMI and AS (p < 0.05). At the same time significantly higher values were found for AI when compared to AMS (p < 0.01). There was a correlation between the bispectral index and the expired anesthetic fraction in all groups.Conclusions and clinical relevanceWithin groups given the same inhalant anesthetic the bispectral index was a good indicator for the degree of hypnosis in dogs, indicating a good correlation with the amount of anesthetic and the nociceptive stimulation. BIS was a less reliable indicator of relative anesthetic depth when comparing equipotent end-tidal concentrations between the three inhalants.     

Propofol and fentanyl infusions in dogs of various breeds undergoing surgery

ObjectiveTo report the cardiovascular variables, anaesthetic effects and recovery quality of an anaesthesia technique using variable rate infusion propofol combined with constant rate infusion fentanyl in dogs undergoing elective surgery.Study designProspective clinical trial.AnimalsA total of 27 dogs, aged 2.7 ± 2.65 years and weighing 24 ± 11 kg.MethodsFollowing intramuscular acepromazine (0.03 or 0.05 mg kg^?1) and subcutaneous carprofen (4 mg kg^?1) pre-medication, anaesthesia was induced with propofol (4.0 ± 0.5 mg kg^?1) intravenously (IV). All dogs were ventilated with 100% oxygen to maintain normocapnia. Propofol was infused at 0.4 mg kg^?1 minute^?1 for 20 minutes and then at 0.3 mg kg^?1minute^?1. If mean arterial blood pressure (MAP) decreased below 70 mmHg, propofol infusion was reduced by 0.1 mg kg^?1 minute^?1. Five minutes after induction of anaesthesia, fentanyl was administered (2 μg kg^?1) IV followed by the infusion at 0.5 μg kg^?1 minute^?1 and atropine (40 μg kg^?1) IV. Heart rate, MAP, respiratory rate, tidal volume, end-tidal carbon dioxide, presence of reflexes, movements and recovery times and quality were recorded.ResultsMean anaesthetic duration was 131 ± 38.5 minutes. Mean heart rate peaked 10 minutes after atropine injection and gradually declined, reaching pre-anaesthetic values at 55 minutes. MAP easily was maintained above 70 mmHg. Mean times to return of spontaneous ventilation, extubation, head lift and sternal recumbency were 21 ± 10.1, 33 ± 14.6, 43 ± 19.7 and 65 ± 23.4 minutes, respectively. Recovery was smooth and quiet. The time to sternal recumbency was significantly correlated with the duration of anaesthesia and total dose of propofol; time to extubation was correlated to total dose of propofol.Conclusion and clinical relevancePropofol and fentanyl infusions provided stable cardiovascular function and satisfactory conditions for surgery. Some modifications of infusion rates are required to improve the long-recovery times.     

Assessment of a carbon dioxide laser for the measurement of thermal nociceptive thresholds following intramuscular administration of analgesic drugs in pain‐free female cats

ObjectiveTo assess the potential of a thermal carbon dioxide (CO₂) laser to explore antinociception in pain-free cats.Study designExperimental, prospective, blinded, randomized study.AnimalsSixty healthy adult female cats with a (mean ± standard deviation) weight of 3.3 ± 0.6 kg.MethodsCats were systematically allocated to one of six treatments: saline 0.2 mL per cat; morphine 0.5 mg kg⁻¹; buprenorphine 20 μg kg⁻¹; medetomidine 2 μg kg⁻¹; tramadol 2 mg kg⁻¹, and ketoprofen 2 mg kg⁻¹. Latency to respond to thermal stimulation was assessed at baseline and at intervals of 15–30, 30–45, 45–60, 60–75, 90–105 and 120–135 minutes. Thermal thresholds were assessed using time to respond behaviourally to stimulation with a 500 mW CO₂ laser. Within-treatment differences in response latency were assessed using Friedman’s test. Differences amongst treatments were assessed using independent Kruskal–Wallis tests. Where significant effects were identified, pairwise comparisons were conducted to elucidate the direction of the effect.ResultsCats treated with morphine (X² = 12.90, df = 6, p = 0.045) and tramadol (X² = 20.28, df = 6, p = 0.002) showed significant increases in latency to respond. However, subsequent pairwise comparisons indicated that differences in latencies at specific time-points were significant (p < 0.05) only for tramadol at 60–75 and 90–105 minutes after administration (21.9 and 43.6 seconds, respectively) in comparison with baseline (11.0 seconds). No significant pairwise comparisons were found within the morphine treatment. Injections of saline, ketoprofen, medetomidine or buprenorphine showed no significant effect on latency to respond.Conclusions and clinical relevanceThe CO₂ laser technique may have utility in the assessment of thermal nociceptive thresholds in pain-free cats after analgesic administration and may provide a simpler alternative to existing systems. Further exploration is required to examine its sensitivity and comparative utility.