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.     

Postoperative analgesia in dogs receiving epidural morphine plus medetomidine

This investigation was carried out to compare the postoperative analgesia and plasma morphine concentrations in dogs given epidural morphine or epidural morphine combined with medetomidine prior to surgery. Twelve dogs (seven males and five females) with ruptured cranial cruciate ligaments presented to the Washington State University Veterinary Teaching Hospital. Six dogs received an epidural injection of morphine (0.1 mg/kg) and six dogs received epidural morphine (0.1 mg/kg) combined with medetomidine (0.005 mg/kg). Numeric rating scale (NRS) pain scores and cumulative pain scores (CPS) were assigned to 10-min segments of video. Video segments, heart rates and respiratory rates were recorded prior to premedication and at 4, 8, 12, 18 and 24 h after epidural injection. Blood was sampled from the cephalic vein at each of these times and during anesthesia at 0.5, 1, 2 and 3 h after epidural injection. Data were analyzed using either Friedman's test or one-way anova for repeated measures. In the morphine group, significant increases compared with premedication values were detected at 4, 8 and 12 h after epidural injection for NRS and at 4 and 12 h after epidural injection for CPS. In the morphine plus medetomidine group, NRS was significantly higher at 4 and 8 h whereas there were no differences from baseline values for CPS. Plasma morphine concentrations were not significantly different between treatment groups, but were significantly increased compared with preinjection values at 0.5, 1, 12, 18, and 24 h in the morphine plus medetomidine group. Epidurally administered morphine combined with medetomidine was associated with only minor benefits based on subjective pain scoring when compared with morphine alone in these dogs undergoing repair of a ruptured cranial cruciate ligament.     

The post-operative analgesic effects of epidurally administered morphine and transdermal fentanyl patch after ovariohysterectomy in dogs

ObjectiveTo investigate the analgesic and side effects of epidural morphine or a fentanyl patch after ovariohysterectomy in dogs.Study designProspective, randomized clinical study.AnimalsTwenty female mongrel dogs undergoing ovariohysterectomy.MethodsThe dogs were allocated to one of two groups: epidural morphine or transdermal fentanyl patch. Anaesthesia was induced with propofol and maintained with isoflurane. Morphine (0.1 mg kg^?1) was administered epidurally in the epidural morphine group and a transdermal fentanyl patch was applied 24 hours before the operation in the fentanyl patch group.The heart rate, respiratory rate, body temperature, plasma cortisol concentration, and sedation and analgesia scores were recorded during the 24 hour post-operative period. Adverse effects such as vomiting, anorexia, skin reactions, urinary retention, and time to start licking the surgical site were also recorded. p < 0.05 was considered significant. Statistical analyses utilized anova for repeated measures, Friedman tests, Mann-Whitney U-tests and independent sample t-tests as relevant.ResultsPain scores were lower in the epidural group than in the fentanyl group at all post-operative times. The dogs in the epidural morphine group were calm and relaxed, whereas discomfort and vocalization were recorded in the fentanyl patch group. The sedation scores were higher in the fentanyl patch group throughout the 12 hour period. Salivation and anorexia lasted longer in the fentanyl patch group than in the epidural morphine group. Plasma cortisol concentrations were high in the early post-operative period in both groups. The fentanyl patch group had higher cortisol concentrations than the epidural morphine group. Slight erythema was recorded in two dogs when the patches were removed.Conclusion and clinical relevanceEpidurally administered morphine provided better analgesia and caused fewer adverse effects than the fentanyl patch after ovariohysterectomy in dogs.     

Interaction between epidurally administered ketamine and pethidine in dogs

The present study was designed to test the hypothesis that a synergistic interaction could be recorded after epidural administration of ketamine-an N-methyl-D-aspartate (NMDA) antagonist and pethidine--an opioid agonist. Twelve adult mongrel dogs of either sex were randomly divided in three groups A, B and C of four animals each. Ketamine (5%) at 2.5 mg/kg and pethidine (3%) 2 mg/kg were injected at lumbosacral epidural space in animals of groups A and B, respectively. In animals of group C ketamine (2.5 mg/kg) and pethidine (2 mg/kg) were injected. Heart rate increased significantly up to 15 min in group A, whereas in groups B and C, the increase was non-significant for a period of 10 and 45 min, respectively. Respiration increased gradually up to 45-60 min in group A and for 15-20 min in group B. However, in animals of group C respiration fell below the baseline during the first 10-15 min and then returned near the baseline. Rectal temperature decreased only marginally in all the groups. Ketamine alone produced complete analgesia at tail and perineal region for a period of 5-10 min and then moderate analgesia for the next 20-30 min. Analgesia at the flank was moderate to complete between 5 and 15 min. In group B complete analgesia was only moderate at the tail and perineal region up to 30 min. In animals of group C, complete analgesia was observed only at perineal region for a very short period (5 min). Analgesia was not associated with sedation in any of the groups but animals of groups A and C showed signs of motor incoordination. Results of the study suggest rather antagonistic than synergistic interaction between epidurally administered ketamine and pethidine. Further studies are needed to confirm the antagonistic interaction between the two drugs.     

Effects of medetomidine and buprenorphine administered for sedation in dogs

Medetomidine at doses of 10, 20 or 30 microg/kg was administered along with 10 microg/kg buprenorphine intramuscularly to 48 dogs requiring sedation for various diagnostic or therapeutic procedures. The heart rate, respiratory rate and degree of sedation were recorded before and 30 minutes after administration of the drugs. Heart rate fell by a mean of 55 per cent and respiratory rate by a mean of 62 per cent. Mean sedation scores were increased in all groups. Administration of atipamezole at the end of the period of sedation produced rapid recoveries, with a mean time to standing of 12 minutes. Animals that were anaesthetised required much less thiopentone than the 10 mg/kg recommended after premedication with acepromazine maleate.     

Comparison of the hemodynamic effects of halothane alone and halothane combined with epidurally administered morphine for anesthesia in ventilated dogs

The hemodynamic effects of 1.5 minimal alveolar concentration of halothane alone (1.6% end-tidal) and 1.5 minimal alveolar concentration of halothane (1.1% end-tidal concentration) combined with epidurally administered morphine were compared during controlled ventilation in 10 dogs used on 2 occasions and randomly allocated to 2 groups. Arterial blood pressure, cardiac index, stroke volume, left ventricular work, and pulmonary arterial pressure were significantly (P less than 0.05) higher in dogs of the morphine-treated group before administration of morphine. After epidural administration of morphine (0.1 mg/kg of body weight diluted in 0.26 ml of saline solution/kg), hemodynamic changes were not observed, and the aforementioned variables remained significantly (P less than 0.05) higher than values in dogs of the halothane only group. Compared with halothane (1.6%) alone, the reduction in halothane end-tidal concentration (1.1%) associated with epidurally administered morphine is beneficial in maintaining hemodynamic function.     

Isoflurane sparing action of epidurally administered xylazine hydrochloride in anesthetized dogs

OBJECTIVE: To evaluate the influence of epidural administration of xylazine hydrochloride on the minimum alveolar concentration of isoflurane (MAC(ISAO)) and cardiopulmonary system in anesthetized dogs. ANIMALS: 6 clinically normal dogs. PROCEDURE: Dogs were anesthetized with isoflurane in oxygen after randomly being assigned to receive 1 of the following 4 treatments: epidural administration of saline (0.9% NaCl) solution or xylazine at a dose of 0.1, 0.2, or 0.4 mg x kg(-1). Experiments were performed on 5 occasions with at least a 1-week interval between experiments; each dog received all 4 treatments. Following instrumentation, the concentration of isoflurane was maintained constant for 15 minutes at the MAC(ISO) that had been determined for each dog, and data on heart rate, arterial blood pressure, respiratory rate, tidal volume, minute volume, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, and arterial pH were collected. The epidural treatment was administered, and 30 minutes later, data were again collected. From this point on, determination of the MAC(ISO) following epidural treatment (ie, MAC(ISO+EPI)) was initiated. Cardiopulmonary data were collected before each electrical supramaximal stimulus during MAC(ISO+EPI) determinations. RESULTS: The mean (+/-SD) MAC(ISO) was 1.29 +/- 0.04%. The epidural administration of xylazine at doses of 0.1, 0.2, and 0.4 mg x kg(-1) decreased the MAC(ISO), respectively, by 8.4 +/- 2.4%, 21.7 +/- 4.9%, and 33.4 +/- 2.64%. Cardiopulmonary effects were limited. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of xylazine decreases the MAC(ISO) in a dose-dependent manner and is associated with few cardiopulmonary effects in anesthetized dogs.     

Comparison of morphine and carprofen administered alone or in combination for analgesia in dogs undergoing ovariohysterectomy

In this study the analgesic efficacy of the pure agonistic opioid morphine and the cyclo-oxygenase type-2-selective carprofen were compared since there is no previous specific comparative study for these two common analgesics. Forty-five bitches undergoing elective ovariohysterectomy were randomly assigned to one of three groups; receiving morphine 0.4 mg/kg bodyweight pre-operatively and 0.2 mg/kg every 4-6 hours thereafter (Morphine group), receiving a once-off carprofen 4 mg/kg injection (Carprofen group) or receiving both morphine and carprofen (MorphCarp group). The dogs were premedicated with acepromazine 0.01 mg/kg and induced with either thiopentone 5-10 mg/kg or propofol 4-6 mg/kg. General anaesthesia was maintained with halothane in oxygen. The degree of pain was assessed over a 24-hour period under blinded conditions using a pain scale modified from the University of Melbourne pain scale and the Glasgow composite pain tool. Physiological parameters such as respiratory rate, pulse rate and body temperature were also assessed over the same time period. There was no significant difference in pain-scores and thus analgesia offered by the three analgesia protocols at any assessment point across the three groups, but there were differences within groups across time points. Baseline total pain-scores were lower than scores at all post-operative points within all three groups. Both morphine and carprofen provided good analgesia without any obvious adverse effects. This study indicates that at the dosages indicated above, carprofen administered on its own produces analgesia equal to that produced by morphine and that the two drugs administered together do not produce better analgesia than either drug administered on its own.     

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.     

Cardiovascular effects of epidurally administered oxymorphone and an oxymorphone-bupivacaine combination in halothane-anesthetized dogs

OBJECTIVE: To evaluate cardiovascular effects of epidurally administered oxymorphone (OXY) and an OXY-bupivacaine combination (O/B) in halothane-anesthetized dogs. ANIMALS: 6 dogs. PROCEDURE: In a randomized crossover design study, dogs were anesthetized with halothane and given OXY, O/B, and saline solution (SAL). Eucapnia and end-tidal halothane concentration of 1.2% were established. Heart rate (HR), systemic and pulmonary arterial pressures, central venous pressure (CVP), and cardiac output were measured at baseline and 5, 15, 30, 45, 60, and 75 minutes after treatment. At 90 minutes, glycopyrrolate was administered IV, and measurements were repeated at 95 minutes. Cardiac index (CI), stroke volume, stroke index, systemic vascular resistance (SVR), and left ventricular work were calculated. End-tidal halothane concentration was decreased to 0.8% from 17 to 45 minutes and to 0.5% from 47 to 95 minutes for OXY and O/B, whereas for SAL, it was maintained at 1.5 and 1.2%, respectively. Samples were obtained at 0, 2, 5, 15, 30, 45, 60, and 95 minutes for measurement of serum opiate concentration and comparison with values after IM administration of OXY. RESULTS: HR decreased, but CVP and SVR increased in response to OXY and O/B. These changes were reversed after IV administration of glycopyrrolate, resulting in significant increase in CI, compared with that in response to SAL. Serum opiate concentration increased markedly and peaked within 15 minutes after OXY and O/B administration but did not differ from values after IM administration. CONCLUSIONS: Epidural administration of OXY results in rapid systemic uptake and decreased HR. Glycopyrrolate administration improves HR, resulting in improved CI at equipotent halothane concentrations.     

Effects of epidurally administered morphine or buprenorphine on the thermal threshold in cats

Objective: To determine the antinociceptive effects of epidural administration of morphine or buprenorphine in cats by use of a thermal threshold model. ANIMALS: 6 healthy adult cats. PROCEDURES: Baseline thermal threshold was determined in duplicate. Cats were anesthetized with isoflurane in oxygen. Morphine (100 microg/kg diluted with saline [0.9% NaCl] solution to a total volume of 0.3 mL/kg), buprenorphine (12.5 microg/kg diluted with saline solution to a total volume of 0.3 mL/kg), or saline solution (0.3 mL/kg) was administered into the epidural space according to a Latin square design. Thermal threshold was determined at various times up to 24 hours after epidural injection. RESULTS: Epidural administration of saline solution did not affect thermal threshold. Thermal threshold was significantly higher after epidural administration of morphine and buprenorphine, compared with the effect of saline solution, from 1 to 16 hours and 1 to 10 hours, respectively. Maximum (cutout) temperature was reached without the cat reacting in 0, 74, and 11 occasions in the saline solution, morphine, and buprenorphine groups, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of morphine and buprenorphine induced thermal antinociception in cats. At the doses used in this study, the effect of morphine lasted longer and was more intense than that of buprenorphine.     

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.     

Effect of extradurally administered morphine on postoperative analgesia in dogs undergoing surgery for thoracolumbar intervertebral disk extrusion

Objective-To investigate the effect of intraoperative extradural morphine administration on postoperative analgesia in dogs undergoing thoracolumbar spinal surgery to treat disk extrusion. Design-Prospective clinical trial. Animals-26 client-owned dogs undergoing thoracolumbar spinal surgery. Procedures-Animals were randomly allocated to receive morphine (0.1 mg/kg [0.045 mg/lb], extradurally) or no treatment (control group). Following preanesthetic medication with methadone (0.25 mg/kg [0.11 mg/lb], IM), anesthesia was induced with propofol and maintained with isoflurane or sevoflurane in oxygen. Lidocaine and fentanyl were administered during surgery in both groups at fixed rates. In the morphine administration group, morphine was splashed over the dura mater immediately prior to wound closure. Postoperative analgesia was assessed for 48 hours by assessors unaware of group allocation, and methadone was administered as rescue analgesic. Demographic characteristics, urinary output, days of hospitalization, and perioperative use of analgesics were compared via a Mann-Whitney U test. Results-Demographic data were similar between groups. In the morphine administration group, 2 of 13 dogs required postoperative methadone, and in the control group, methadone was administered to 11 of 13 dogs. The total number of doses of methadone administered in the 48 hours after surgery was 28 in the control group and 3 in the morphine administration group. No adverse effects were recorded in any group. Conclusions and Clinical Relevance-Intraoperative extradural morphine administration was effective in reducing postoperative analgesic requirement. Dogs undergoing thoracolumbar spinal surgery benefited from topical administration of preservative-free morphine administered directly on the dura mater as part of analgesic management.     

Anaesthetic and cardiopulmonary effects of intramuscular morphine, medetomidine and ketamine administered to telemetered cats

The quality and duration of anaesthesia, cardiorespiratory effects and recovery characteristics of a morphine, medetomidine, ketamine (MMK) drug combination were determined in cats. Six healthy, adult female cats were administered 0.2 mg/kg morphine sulphate, 60 microg/kg medetomidine hydrochloride, and 5 mg/kg ketamine hydrochloride intramuscularly. Atipamezole was administered intramuscularly at 120 min after MMK administration. Time to lateral recumbency, intubation, extubation and sternal recumbency were recorded. Cardiorespiratory variables and response to a noxious stimulus were recorded before and at 3 min and 10 min increments after drug administration until sternal recumbency. The time to lateral recumbency and intubation were 1.9+/-1.2 and 4.3+/-1.2 min, respectively. Body temperature and haemoglobin saturation with oxygen remained unchanged compared to baseline values throughout anaesthesia. Respiratory rate, tidal volume, minute volume, heart rate, and blood pressure were significantly decreased during anaesthesia compared to baseline values. One cat met criteria for hypotension (systolic blood pressure <90 mmHg). End tidal carbon dioxide increased during anaesthesia compared to baseline values. All but one cat remained non-responsive to noxious stimuli from 3 to 120 min. Time to extubation and sternal recumbency following atipamezole were 2.9+/-1.1 and 4.7+/-1.0 min, respectively. MMK drug combination produced excellent short-term anaesthesia and analgesia with minimal cardiopulmonary depression. Anaesthesia lasted for at least 120 min in all but one cat and was effectively reversed by atipamezole.     

Reversal of medetomidine sedation by atipamezole in dogs

Atipamezole reversed the sedative effect of medetomidine in twelve laboratory beagles. The dogs were sedated with medetomidine doses of 20, 40 and 80 micrograms/kg body wt i.m. Atipamezole was injected (i.m.) 20 min later at dose rates two, four, six and ten times higher (in micrograms/kg) than the preceding medetomidine dose. Placebo treatment was included in the study. The deeply sedated dogs showed signs of arousal in 3-7 min and took their first steps 4-12 min after atipamezole injection. The dose-related reversal effect of atipamezole proved to be optimal with doses which were four, six or ten times higher than the preceding medetomidine dose. Drowsiness was found 0.5-1 h after atipamezole injection in 41% of the cases. No adverse effects nor cases of over-alertness or excitement were found.