A comparison of epidural buprenorphine with epidural morphine for postoperative analgesia following stifle surgery in dogs

Objective To compare the efficacy of epidural buprenorphine with epidural morphine for post‐operative pain relief in dogs undergoing cranial cruciate ligament rupture repair. Study design A randomized, double blind clinical trial. Animals Twenty client‐owned dogs with cranial cruciate ligament rupture. Methods Dogs were randomly assigned to receive either epidural buprenorphine (4 µg kg^?1) or epidural morphine (0.1 mg kg^?1) in a total volume of 0.2 mL kg^?1. Epidural injections were performed immediately after induction of anesthesia. End‐tidal halothane and CO₂ were recorded every 15 minutes from the time of epidural administration of drug to extubation. A numerical rating pain score system was used by a blinded observer to evaluate analgesia beginning at extubation and continuing at specific intervals for 24 hours after surgery. Heart rate, respiratory rate, and blood pressure were recorded noninvasively at the same times. If pain score indicated moderate discomfort, rescue morphine at 1.0 mg kg^?1 was administered intramuscularly. Results There were no significant differences between groups with respect to pain score, heart rate, respiratory rate, indirect blood pressure, end‐tidal halothane or end‐tidal CO₂ at any time point. Fifty percent of dogs in the buprenorphine group and 50% of dogs in the morphine group required rescue analgesic medication. Time of systemic rescue morphine administration did not differ significantly between the two groups. There were no clinically observable side‐effects from epidural administration of either drug in any of the dogs of this study. Conclusions Epidural buprenorphine is as effective as epidural morphine for the relief of postoperative hindlimb orthopedic pain in dogs. Clinical relevance Buprenorphine appears to be an effective opioid for epidural use in healthy dogs. Buprenorphine may offer certain advantages over morphine for epidural use, such as lower abuse potential and, in some clinics, reduced cost and less wastage of drug.     

A comparison of the haemodynamic effects of epidurally administered medetomidine and xylazine in dogs

Alpha₂ agonists have a significant role in epidural anaesthetic techniques. However, there are few reports regarding epidural administration of these drugs especially in small animals ( Greene et al. 1995; Keegan et al. 1995; Vesal et al. 1996 ). This study compared the haemodynamic effects of xylazine and medetomidine after epidural injection in dogs. Six dogs (four females and two males) weighing 27.5 ± 3.39 kg, aged 5.6 ± 1.42 years were studied on two separate occasions one month apart. Dogs were sedated with 0.5 mg kg^?1 diazepam IM and 0.1 mg kg^?1 acepromazine IM. After 20 minutes, a lumbosacral epidural injection of 0.25 mg kg^?1 xylazine was administered (group X). One month later, following the same sedation, 15 µg kg^?1 medetomidine was administered epidurally (group M). Haemodynamic variables (ECG and indirect blood pressure (Doppler)), respiratory rate and rectal temperature were recorded before (baseline) and then every 5 minutes after the epidural injection, up to 60 minutes. Differences between groups were compared by a paired t‐test. Within group changes were compared to basal values by anova . A p‐value of < 0.05 was considered statistically significant. Both groups showed significant reductions in heart rate (106.3 ± 7.7 beats minute^?1 baseline versus 67.7 ± 7.6 (group M); 91 ± 3.8 baseline versus 52.3 ± 9 (group X)) and mean arterial blood pressure (113.1 ± 12.3 mm Hg baseline versus 87 ± 11 (group M); 118 ± 7 baseline versus 91 ± 14 (group X)). There were no differences between groups in these variables. After epidural injection, first degree atrioventricular block was recorded significantly more often in group X (50% against 33%) but second degree block was significantly more frequent in group M (66% against 33%). Also 50% of dogs in group X and 66% in group M showed sinus arrest. Respiratory rate decreased significantly in both groups following the epidural injection (20.66 ± 0.66 minute^?1 baseline versus 16.33 ± 4.77 (group M); 37.66 ± 0.56 baseline versus 16.33 ± 1.81 group X), but no differences between groups were observed. Rectal temperature decreased significantly in group X (38.16 ± 0.21) with respect to the basal measurement (39.30 ± 0.14 °C). In group M, there was no significant reduction in temperature, however, no statistical difference in rectal temperature was found between groups. This study shows that 0.25 mg kg^?1 xylazine and 15 µg kg^?1 medetomidine produce similar, significant cardiovascular and respiratory changes following lumbosacral epidural administration in dogs.     

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.     

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 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.     

A comparison of epidural analgesia provided by bupivacaine alone,bupivacaine + morphine,or bupivacaine + dexmedetomidine for pelvic orthopedic surgery in dogs

ObjectiveTo compare the analgesic efficacy of bupivacaine, bupivacaine + morphine, or bupivacaine + dexmedetomidine administered epidurally in dogs undergoing pelvic limb orthopedic surgery.Study designProspective, randomized, double blinded clinical trial.AnimalsSixty dogs weighing (mean ± SD) 35 ± 15.7 kg, aged 5 ± 3 years.MethodsDogs were assigned to receive a lumbosacral epidural containing bupivacaine (B) 0.5%, 1 mg kg^?1; B, bupivacaine 0.5%, 1 mg kg^?1 + morphine 1%, 0.1 mg kg^?1; B + M, or bupivacaine 0.5%, 1 mg kg^?1 + dexmedetomidine 0.05%, 4 μg kg^?1; B + D. The anesthetic protocol was standardized. The median expired isoflurane concentration (E′Iso) and requirement for additional induction agent preventing purposeful movement were recorded. Pain was scored using visual analog (VAS) and modified University of Melbourne (UMPS) pain scales. Sedation was assessed using a 0–4 scale. All parameters were recorded preoperatively, and at extubation (t = 0), then at 1, 2, 4, 8, 12, 16, and 20–24 hours. Hydromorphone was administered postoperatively to patients with a VAS ≥ 35 and/or UMPS ≥ 9. Time to first voluntary urination and first motor activity were recorded.ResultsPostoperatively, B + D had a lower UMPS pain score than B at t = 1 hour (p = 0.013), but not compared to B + M. The B + D group had a shorter time to urination (p = 0.0131) and a longer time for return of motor function (p = 0.0068). There were no other differences between the treatments.Conclusion and clinical relevanceEpidurally administered B, B + M, or B + D in dogs all provided acceptable analgesia to manage post–operative orthopedic pelvic limb pain. Epidural administration of B + D is an effective alternative to the analgesia provided by B or B + M, but is associated with increased time to return of motor function. The direct neurotoxic effects of epidural dexmedetomidine have not been fully tested.     

Cardiovascular effects of epidural administration of methadone, ropivacaine 0.75% and their combination in isoflurane anaesthetized dogs

ObjectiveTo compare the cardiovascular effects of four epidural treatments in isoflurane anaesthetised dogs.Study designProspective, randomized. experimental study.AnimalsSix female, neutered Beagle dogs (13.3 ± 1.0 kg), aged 3.6 ± 0.1 years.MethodsAnaesthesia was induced with propofol (8.3 ± 1.1 mg kg^?1) and maintained with isoflurane in a mixture of oxygen and air [inspiratory fraction of oxygen (FiO₂) = 40%], using intermittent positive pressure ventilation. Using a cross-over model, NaCl 0.9% (P); methadone 1% 0.1 mg kg^?1 (M); ropivacaine 0.75% 1.65 mg kg^?1 (R) or methadone 1% 0.1 mg kg^?1 + ropivacaine 0.75% 1.65 mg kg^?1 (RM) in equal volumes (0.23 mL kg^?1) using NaCl 0.9%, was administered epidurally at the level of the lumbosacral space. Treatment P was administered to five dogs only. Cardiovascular and respiratory variables, blood gases, and oesophageal temperature were recorded at T-15 and for 60 minutes after epidural injection (T0).ResultsMean overall heart rate (HR in beats minute^?1) was significantly lower after treatment M (119 ± 16) (p = 0.0019), R (110 ± 18) (p < 0.0001) and RM (109 ± 13) (p < 0.0001), compared to treatment P (135 ± 21). Additionally, a significant difference in HR between treatments RM and M was found (p = 0.04). After both ropivacaine treatments, systemic arterial pressures (sAP) were significantly lower compared to other treatments. No significant overall differences between treatments were present for central venous pressure, cardiac output, stroke volume, systemic vascular resistance, oxygen delivery and arterial oxygen content (CaO₂). Heart rate and sAP significantly increased after treatment P and M compared to baseline (T-15). With all treatments significant reductions from baseline were observed in oesophageal temperature, packed cell volume and CaO₂. A transient unilateral Horner’s syndrome occurred in one dog after treatment R.Conclusions and clinical relevanceClinically important low sAPs were observed after the ropivacaine epidural treatments in isoflurane anaesthetised dogs. Systemic arterial pressures were clinically acceptable when using epidural methadone.     

Glomerular filtration rate after tramadol, parecoxib and pindolol following anaesthesia and analgesia in comparison with morphine in dogs

ObjectiveTo compare the effects of morphine, parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol on nociceptive thresholds in awake animals and their effect on glomerular filtration rate (GFR) in dogs subjected to 30 minutes of anesthesia.AnimalsEight adult mixed breed experimental dogs.Study designRandomized, controlled trial.MethodsDogs received 0.05 mg kg^?1 acepromazine subcutaneously (SC) as anaesthetic pre-medication. Thirty to sixty minutes later, they received either tramadol 3 mg kg^?1 intravenously, (IV), parecoxib (1 mg kg^?1 IV), a combination of tramadol 3 mg kg^?1 (IV), parecoxib 1 mg kg^?1 (IV) and pindolol 5 μg kg^?1 (SC), morphine (0.1 mg kg^?1 (IV) or 0.9% saline (2 mL). Anaesthesia was then induced with IV propofol to effect (2.9 ± 0.8 mg kg^?1) and maintained with halothane in oxygen for 30 minutes. Systolic arterial blood pressure was maintained above 90 mmHg with IV fluids and by adjusting the inspired halothane concentration. Post-treatment nociceptive thresholds to mechanical stimuli, expressed as percent of pre-treatment values, were compared between the treatments to assess the analgesic efficacy of the drugs. Plasma iohexol clearance (ICL), a measure of GFR, was estimated both before and 24 hours after induction of anaesthesia to study the drugs’ effects on renal perfusion. Nociceptive threshold and GFR data were compared using mixed model analysis in sas^®9.1.ResultsBoth tramadol and parecoxib produced similar analgesia, which was less than that of morphine. Their combination with pindolol produced analgesia comparable with morphine. None of the test drugs, either alone or in combination, reduced GFR.ConclusionTramadol and parecoxib (either alone or in combination) can increase nociceptive thresholds in awake dogs and have minimal effects on renal perfusion in normotensive dogs subjected to anaesthesia.     

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.     

Comparison of analgesic efficacy of epidural methadone or ropivacaine/methadone with or without pre‐operative oral tepoxalin in dogs undergoing tuberositas tibiae advancement surgery

ObjectiveTo investigate the clinical efficacy of four analgesia protocols in dogs undergoing tibial tuberosity advancement (TTA).Study designProspective, randomized, blinded study.AnimalsThirty-two client owned dogs undergoing TTA-surgery.MethodsDogs (n= 8 per treatment) received an oral placebo (PM and PRM) or tepoxalin (10 mg kg^?1) tablet (TM and TRM) once daily for 1 week before surgery. Epidural methadone (0.1 mg kg^?1) (PM and TM) or the epidural combination methadone (0.1 mg kg^?1)/ropivacaine 0.75% (1.65 mg kg^?1) (PRM and TRM) was administered after induction of anaesthesia. Intra-operative fentanyl requirements (2 μg kg^?1 IV) and end-tidal isoflurane concentration after 60 minutes of anaesthesia (Fe′ISO₆₀) were recorded. Post-operative analgesia was evaluated hourly from 1 to 8 and at 20 hours post-extubation with a visual analogue scale (VAS) and the University of Melbourne Pain Scale (UMPS). If VAS > 50 and/or UMPS > 10, rescue methadone (0.1 mg kg^?1) was administered IV. Analgesic duration (time from epidural until post-operative rescue analgesia) and time to standing were recorded. Normally distributed variables were analysed with an F-test (α = 0.05) or t-test for pairwise inter-treatment comparisons (Bonferonni adjusted α = 0.0083). Non-normally distributed data were analysed with the Kruskall–Wallis test (α = 0.05 or Bonferonni adjusted α = 0.005 for inter-treatment comparison of post-operative pain scores).ResultsMore intra-operative analgesia interventions were required in PM [2 (0–11)] [median (range)] and TM [2 (1–2)] compared to PRM (0) and TRM (0). Fe′ISO₆₀ was significantly lower in (PRM + TRM) compared to (PM + TM). Analgesic duration was shorter in PM (459 ± 276 minutes) (mean ± SD) and TM (318 ± 152 minutes) compared to TRM (853 ± 288 minutes), but not to PRM (554 ± 234 minutes). Times to standing were longer in the ropivacaine treatments compared to TM.Conclusions and clinical relevanceInclusion of epidural ropivacaine resulted in reduction of Fe′ISO₆₀, avoidance of intra-operative fentanyl administration, a longer duration of post-operative analgesia (in TRM) and a delay in time to standing compared to TM.     

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 clinical effects of epidural levobupivacaine morphine versus bupivacaine morphine in dogs undergoing elective pelvic limb surgery

Objective

To evaluate the efficacy, in terms of the amount of rescue analgesia required, and the clinical usefulness of epidural injection of morphine with bupivacaine or levobupivacaine for elective pelvic limb surgery in dogs during a 24-hour perioperative period.

Sedative effects of hydromorphone or oxymorphone with or without acepromazine in dogs

Hydromorphone is an agonist opioid with potency approximately five times that of morphine and half that of oxymorphone. The purpose of this study was to compare hydromorphone with oxymorphone, with or without acepromazine, for sedation in dogs, and to measure plasma histamine before and after drug administration. Ten dogs received IM hydromorphone (H; 0.2 mg kg^?1), oxymorphone (O; 0.1 mg kg^?1), hydromorphone with acepromazine (H; 0.2 mg kg^?1, A; 0.05 mg kg^?1) or oxymorphone with acepromazine (O; 0.1 mg kg^?1, A; 0.05 mg kg^?1) in a randomized Latin‐square design. Sedation score, heart rate, respiratory rate, blood pressure, and SpO₂ were recorded at baseline and every 5 minutes after drug administration up to 25 minutes. Plasma histamine was measured at baseline and at 25 minutes post‐drug administration. Data were analyzed with repeated measures anova . Mean ± SD body weight was 21.62 ± 1.54 kg. Mean ± SD age was 1.07 ± 0.19 years. Sedation score was significantly greater for OA after 5 minutes than O alone (4.1 ± 3.5 versus 1.9 ± 1.5) and for HA after 15 minutes than H alone (8.6 ± 2.9 versus 5.9 ± 2.5). There was no significant difference in sedation between H and O at any time point. There was no significant difference between groups at any time with respect to heart rate, respiratory rate, blood pressure or SpO₂. Mean ± SD plasma histamine (nM ml^?1) for all groups was 1.72 ± 2.69 at baseline and 1.13 ± 1.18 at 25 minutes. There was no significant change in plasma histamine concentration in any group. Hydromorphone is effective for sedation in dogs and does not cause measurable increase in histamine. Sedation with hydromorphone is enhanced by acepromazine.     

The effects of medetomidine on the action of vecuronium in dogs anaesthetized with halothane and nitrous oxide

ObjectiveTo quantify the effects of medetomidine on the onset and duration of vecuronium-induced neuromuscular blockade in dogs.Study designRandomized, prospective clinical study.AnimalsTwenty-four, healthy, client-owned dogs of different breeds, aged between 6 months and 10 years and weighing between 5.0 and 40.0 kg undergoing elective surgery.MethodsDogs were randomly allocated to two groups. Pre-anaesthetic medication in group M+ was intramuscular acepromazine (ACP) 25 μg kg⁻¹, morphine 0.5 mg kg⁻¹ and medetomidine 5 μg kg⁻¹. Group M− received ACP and morphine only, at the same dose rate. After induction with thiopental, anaesthesia was maintained with halothane in oxygen and nitrous oxide. End-tidal halothane concentration was maintained at 1.1%. Neuromuscular blockade was produced with intravenous vecuronium (50 μg kg⁻¹) and monitored using a train of four stimulus applied at the ulnar nerve. The times taken for loss and reappearance of the four evoked responses (twitches [T]) were recorded. Normal and nonparametric data were analysed with an independent t-test and Mann-Whitney's U-test, respectively.ResultsThe fourth twitch (T4) disappeared at similar times in each group: 107 ± 19; [72–132] (mean ± SD; [range]) seconds in M+ and 98 ± 17 [72–120] seconds in M− dogs. The first twitch (T1) was lost at 116 ± 15; [96–132] seconds in group M+ and 109 ± 19; [72–132] seconds in M−. The fourth twitch returned significantly earlier in M+ dogs: 20.8 ± 3.8 [14–28] minutes compared with 23.8 ± 2.7 [20–27] minutes (p = 0.032). The duration of drug effect (T4 absent) was significantly shorter (p = 0.027) in M+ (18.9 ± 3.7 minutes) compared with M− dogs (22.2 ± 2.9 minutes). The recovery rate (interval between reappearance of T1 and T4) was significantly more rapid (p = 0.0003) in medetomidine recipients (3.0 ± 1.2 versus 5.2 ± 1.3 minutes).Conclusion and clinical relevance Medetomidine 5 μg kg⁻¹ as pre-anaesthetic medication shortened the duration of effect of vecuronium in halothane-anaesthetized dogs and accelerated recovery, but did not affect the onset time. These changes are of limited clinical significance.     

Pharmacokinetics and toxicity of the novel oral demethylating agent zebularine in laboratory and tumor bearing dogs

The purpose of this study was to determine the plasma pharmacokinetics (PK) and toxicity of zebularine, an oral cytidine analog with demethylating activity, in dogs. Plasma zebularine concentrations were determined by HPLC‐MS/MS following an oral zebularine dose of 8 or 4 mg kg^?1. Plasma zebularine clearance was constant. Mean maximum concentration (C_max) was 23 ± 4.8 and 8.6 ± 1.4 µM following 8 and 4 mg kg^?1, respectively. Mean half‐life was 5.7 ± 0.84 and 7.1 ± 2.1 following 8 and 4 mg kg^?1, respectively. A single 8 mg kg^?1 dose was well tolerated. Daily 4 mg kg^?1 treatment in three laboratory dogs resulted in grade 4 neutropenia (n = 3), grade 1 anorexia (n = 2) and grade 1 or 2 dermatologic changes (n = 2). All adverse events resolved with supportive care. A 4 mg kg^?1 dose every 21 days was well tolerated. A follow‐up dose escalation study is in progress with a lower starting dose.     

Cardiovascular effects following epidural injection of romifidine in isoflurane‐anaesthetized dogs

ObjectiveTo investigate the cardiovascular effects of epidural romifidine in isoflurane-anaesthetized dogs.Study designProspective, randomized, blinded experiment.AnimalsA total of six healthy adult female Beagles aged 1.25 ± 0.08 years and weighing 12.46 ± 1.48 (10.25–14.50) kg.MethodsAnaesthesia was induced with propofol (6–9 mg kg^?1) and maintained with 1.8–1.9% end-tidal isoflurane in oxygen. End-tidal CO₂ was kept between 35 and 45 mmHg (4.7–6.0 kPa) using intermittent positive pressure ventilation. Heart rate (HR), arterial blood pressure and cardiac output (CO) were monitored. Cardiac output was determined using a LiDCO monitor and the derived parameters were calculated. After baseline measurements, either 10 μg kg^?1 romifidine or saline (total volume 1 mL 4.5 kg^?1) was injected into the lumbosacral epidural space. Data were recorded for 1 hour after epidural injection. A minimum of 1 week elapsed between treatments.ResultsAfter epidural injection, the overall means (± standard deviation, SD) of HR (95 ± 20 bpm), mean arterial blood pressure (MAP) (81 ± 19 mmHg), CO (1.63 ± 0.66 L minute^?1), cardiac index (CI) (2.97 ± 1.1 L minute^?1 m^?2) and stroke volume index (SI) (1.38 ± 0.21 mL beat^?1 kg^?1) were significantly lower in the romifidine treatment compared with the overall means in the saline treatment [HR (129 ± 24 bpm), MAP (89 ± 17 mmHg), CO (3.35 ± 0.86 L minute^?1), CI (6.17 ± 1.4 L minute^?1 m^?2) and SI (2.21 ± 0.21 mL beat^?1 kg^?1)]. The overall mean of systemic vascular resistance index (SVRI) (7202 ± 2656 dynes seconds cm^?5 m^?2) after epidural romifidine injection was significantly higher than the overall mean of SVRI (3315 ± 1167 dynes seconds cm^?5 m^?2) after epidural saline injection.ConclusionEpidural romifidine in isoflurane-anaesthetized dogs caused significant cardiovascular effects similar to those reportedly produced by systemic romifidine administration.Clinical relevanceSimilar cardiovascular monitoring is required after epidural and systemically administered romifidine. Further studies are required to evaluate the analgesic effects of epidural romifidine.     

Comparison between S(+) ketamine–diazepam and S(+) ketamine–midazolam on anesthetic induction and recovery in dogs

S(+) ketamine, one of the two enantiomers of racemic ketamine, is a phencyclidine derivative that induces amnesia and analgesia. Its activity is related to blockade of NMDA receptors and some opioid action. We compared anesthetic induction and recovery quality with S(+) ketamine in combination with diazepam or midazolam in 10 dogs (ASA 1) admitted for elective surgery. After all clinical examinations, the dogs were separated into two groups (G I and G II). All animals received acepromazine (0.1 mg kg^?1) and fentanyl (5 µg kg^?1) IM, 20 minutes before induction with S(+) ketamine (6 mg kg^?1) and diazepam (0.5 mg kg^?1) IV (G I) or midazolam 0.2 mg kg^?1 (G II) IV. The doses of diazepam and midazolam were chosen according to the literature. All dogs were intubated and then maintained with halothane in oxygen at a vaporizer setting sufficient to maintain surgical anesthesia. Quality of induction, time needed for intubation, heart rate, respiratory rate, SpO₂, time to extubation, and quality of recovery were evaluated. The results were analyzed by Student's t‐test. Smooth induction and recovery were observed in all animals. The time to intubation was 45 ± 20 (GI) and 25 ± 6 seconds (GII), HR was 122 ± 12 (GI) and 125 ± 7 beats minute^?1 (GII), RR was 17 ± 2 (GI) and 21 ± 3 breaths minute^?1 (GII), SpO₂ was 96 ± 2 (GI) and 94 ± 1% (GII), time to extubation was 7 ± 3 (GI) and 4 ± 1 minutes (GII). No statistical differences were found in analyses, although time to intubation was less in GII. The results suggested that both combinations could be used safely for anesthetic induction in healthy dogs.     

Epidural administration of combinations of ropivacaine,morphine and xylazine in bitches undergoing total unilateral mastectomy: a randomized clinical trial

ObjectiveTo investigate the epidural administration of combinations of ropivacaine, morphine and xylazine in bitches undergoing unilateral mastectomy.Study designProspective, randomized, blinded, clinical study.AnimalsA total of 22 bitches scheduled to undergo unilateral mastectomy for mammary tumor excision.MethodsDogs were anesthetized with acepromazine (0.02 mg kg^–1) and morphine (0.3 mg kg^–1) intramuscularly, propofol intravenously (IV) and isoflurane. Prior to the beginning of surgery, dogs were randomly administered one of three epidural treatments: ropivacaine (0.75 mg kg^–1) with morphine (0.1 mg kg^–1) (group RM, n = 7); ropivacaine with xylazine (0.1 mg kg^–1) (group RX, n = 8); or ropivacaine with morphine and xylazine (group RMX, n = 7). Cardiopulmonary variables and the expired concentration of isoflurane (Fe′Iso) were recorded intraoperatively. Meloxicam (0.1 mg kg^–1) was administered IV during skin closure. Postoperative pain scores were evaluated with the Glasgow composite measure pain scale short form for 24 hours, and rescue analgesia with morphine (0.5 mg kg^–1) was administered intramuscularly when pain scores were ≥ 6/24.ResultsFe′Iso was significantly higher in group RM than in groups RX and RMX. Heart rate decreased significantly in groups RX and RMX, but blood pressure remained within acceptable values. The number of dogs administered rescue analgesia within 24 hours was significantly higher in group RX (seven dogs, 87.5%) than in groups RM (one dog, 14.3%; p = 0.01) and RMX (two dogs, 28.6%; p = 0.04). Time to standing was significantly longer in group RX than in group RM.Conclusions and clinical relevanceAll epidural treatments provided adequate antinociception with minimal cardiovascular adverse effects during mastectomy. The inclusion of morphine (groups RM and RMX) provided the best postoperative analgesia. Owing to the undesirable effect of xylazine on ambulation, the combination ropivacaine–morphine appeared to provide greater benefits in bitches undergoing unilateral mastectomy.     

Effects of epidural morphine on gastrointestinal transit in unmedicated horses

ObjectiveTo evaluate the effect of epidural morphine on gastrointestinal (GI) motility in horses.Study designRandomly ordered crossover design.AnimalsSix healthy adult horses weighing 585 ± 48 kg (mean ± SD).MethodsHorses were randomly assigned to receive either 0.2 mg kg^?1 morphine or an equal volume (0.04 mL kg^?1) of saline epidurally (the first inter coccygeal space) with 2 weeks between treatments. The horses were stabled, fed a standardized diet and allowed water ad libitum throughout the duration of the study. Radiopaque spheres were administered by stomach tube. Xylazine 0.2 mg kg^?1 intravenously was administered prior to epidural injection. Heart rate, respiratory rate, GI sounds score and behavior score were recorded before drug administration and after epidural injection at 4, 8, 12, 18, 24 hours and every 12 hours thereafter for 6 days. Feces were weighed, radiographed and the number of spheres counted. Data were analyzed using a mixed effect model.ResultsAt no time did horses exhibit signs of colic or show significant differences between treatments regarding heart rate, respiratory rate, GI sounds score, behavior score, or cumulative number of spheres. The concentration of spheres per kg of feces was significantly lower (p < 0.05) for the morphine group at 18 and 24 hours. Using the centroid of the curves (spheres kg^?1 plotted versus time) the average transit time after saline epidural was 38 hours and after morphine it was 43 hours. The weight of feces hour^?1 was significantly lower (p < 0.05) at only 4 and 8 hours after morphine.Conclusions and clinical relevanceEpidural morphine, at a dose of 0.2 mg kg^?1, temporarily reduced GI motility but did not cause ileus or colic in this small group of healthy unfasted horses. Care should be taken when extrapolating these data to situations in which other factors may also affect GI motility.     

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.