Evaluation of the analgesic effects of epidurally administered morphine, alfentanil, butorphanol, tramadol, and U50488H in horses

OBJECTIVE: To evaluate and compare effects of epidurally administered morphine, alfentanil, butorphanol, tramadol, and U50488H on avoidance threshold to noxious electrical stimulation over the dermatomes of the perineal, sacral, lumbar, and thoracic regions in horses. ANIMALS: 5 healthy adult horses. PROCEDURE: Using a Latin square complete repeated-measures design, horses were randomly assigned to receive 1 of 6 treatments (morphine, alfentanil, butorphanol, tramadol, U50488H, or sterile water) at intervals of at least 7 days. Agents were injected epidurally at the first intercoccygeal epidural space, and electrical stimulation was applied at repeated intervals for 24 hours to the dermatomes of the perineal, sacral, lumbar, and thoracic regions. Avoidance threshold to electrical stimulation was recorded. RESULTS: Administration of butorphanol, U50488H, and sterile water did not induce change in avoidance threshold. Alfentanil increased avoidance threshold during the first 4 hours, but not significantly. Tramadol and morphine significantly increased threshold and analgesic effects. Complete analgesia (avoidance threshold, >40 V) in the perineal and sacral areas was achieved 30 minutes after tramadol injection, compared with 6 hours after morphine injection. Duration of complete analgesia was 4 hours and 5 hours after tramadol and morphine injections, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of tramadol and morphine induces long-lasting analgesia in healthy adult horses. Epidural administration of opioids may provide long-lasting analgesia in horses without excitation of the CNS.     

Electroencephalographic responses of tramadol, parecoxib and morphine to acute noxious electrical stimulation in anaesthetised dogs

This study compared the efficacy of different classes of analgesics in preventing the changes in electroencephalographic (EEG) indices of nociception in anaesthetised dogs, subjected to a standard electrical stimulus. In a crossover study, eight dogs received morphine (0.5 mg/kg) or tramadol (3 mg/kg) or parecoxib (1 mg/kg) or 0.9% saline subcutaneously (SC) at the time of pre-anaesthetic medication. After induction with intravenous propofol, anaesthesia was maintained with halothane at a stable concentration between 0.85% and 0.95%. EEG was recorded in a three electrode montage, using SC needle electrodes, before and after electrical stimulation of dogs during anaesthesia. Post-stimulation median frequency (a reliable indicator of nociception) of the EEG increased significantly in tramadol, parecoxib and saline groups compared to that of morphine. Total EEG power decreased in all treatment groups following stimulation. These results indicate that the changes in EEG responses to noxious stimulation can be used for evaluating anti-nociceptive efficacy of analgesics.     

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.     

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.     

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

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

Cardiopulmonary and analgesic effects of caudal epidurally administered ropivacaine in cattle

ObjectiveTo assess cardiopulmonary and analgesic effects after administration of ropivacaine into the caudal epidural space of cattle.Study designProspective, single-dose trial.AnimalsEight healthy mixed breed cows aged 8 ± 5 years and weighing 507 ± 112 kg.MethodsCaudal epidural anesthesia was produced in cows with 0.75% ropivacaine (0.11 mg kg^?1). Onset time, duration and cranial spread of analgesia were recorded. Heart rate (HR), respiratory rate (f_R), rectal temperature (RT), and mean arterial blood pressure (MAP) were measured prior to epidural administration (T₀) and at 15, 30, 60, 120, 180 and 240 minutes after epidural administration (T₁₅, T₃₀, T₆₀, T₁₂₀, T₁₈₀ and T₂₄₀). Arterial blood acid-base balance (pH, standard bicarbonate and base excess), gas tension (PaO₂, PaCO₂, SaO₂) and electrolytes (Na⁺, K⁺, iCa²⁺,Cl^?) were recorded at T₀, T₃₀, T₆₀, T₁₂₀, T₁₈₀ and T_240. Ataxia was evaluated at T₀, T₃₀, T₆₀, T₁₂₀, T₁₈₀ and T₂₄₀ and at 1 hour intervals thereafter until analgesia was no longer present in each animal.ResultsEpidurally administered ropivacaine induced variable analgesia extending bilaterally from the coccyx to S3. Time to onset of analgesia and mean duration in the perineal area were 15 ± 4 and 359 ± 90 minutes, respectively. Respiratory rate and RT increased from T₁₂₀ to T₂₄₀ when compared to the value at T₀. Ionized calcium and chloride concentrations increased at T₁₈₀ and T₂₄₀ when compared to T₀. The other variables were not significantly different from baseline values (p> 0.05). Four animals were mildly ataxic.Conclusion and clinical relevanceRopivacaine (0.75%, 0.11 mg kg^?1) can be administered by caudal epidural injection to produce prolonged bilateral perineal analgesia with minimal ataxia and cardiopulmonary changes in standing cattle.     

Antinociceptive effects of tramadol and acepromazine in cats

Effects of tramadol and acepromazine on pressure and thermal thresholds were examined in eight cats. After baseline measurements, subcutaneous (SC) tramadol 1 mg/kg, acepromazine 0.1 mg/kg, tramadol 1 mg/kg with acepromazine 0.1 mg/kg, or saline 0.3 ml were given. Serial measurements were made for 24 h. Mean thermal thresholds did not change significantly [analysis of variance (ANOVA)] from baseline. The maximum thermal threshold increase above baseline was 2.8+/-2.8 degrees C at 6 h (P>0.05) after tramadol; it was above the 95% confidence interval (CI) at 0.75, 3 and 6 h. Pressure thresholds increased above baseline from 0.25 to 2 h after acepromazine (P<0.05) and from 0.5 to 3 h after the combination (P<0.05), with a maximum increase of 132+/-156 mmHg 0.25 h after acepromazine and 197+/-129 mmHg 0.5 h after the combination. Pressure thresholds were above the 95% CI from 0.25 to 2 h after acepromazine and from 0.5 to 3 h after the combination. SC tramadol at 1 mg/kg in cats had limited effect on thermal and pressure nociception, but this was enhanced by acepromazine. Acepromazine alone had pressure antinociceptive effects.     

Comparison of behavioral effects of morphine and fentanyl in dogs and cats

Behavioral effects induced by intravenous administration of morphine at 0.3, 0.6, 1.2, and 2.4 μg/kg and fentanyl at 5, 10, 20, and 40 μg/kg were evaluated in dogs and cats. In dogs, fentanyl and morphine depressed activity and level of consciousness in a dose- dependant manner. In cats, higher doses of fentanyl stimulated activity temporarily, but excitement, so-called "opioid mania," was not observed. Morphine induced distinctive behavioral changes characterized by sitting with fixed staring, and "opioid mania" was not observed in cats.     

Preliminary investigations into the analgesic effects of topical ocular 1% morphine solution in dogs and cats

ObjectiveTo perform preliminary evaluations into the ocular analgesic effect of topical 1% morphine in a clinical setting and to determine onset, duration and complications.Study designProspective, randomised, blinded clinical study.AnimalsTwenty six dogs and seventeen cats, all client‐owned.MethodsDogs and cats with corneal ulceration requiring medical treatment or corneal conditions requiring surgery were included and randomly assigned to receive one drop of topical morphine (group M) or base solution (group B). Recordings were made prior to application and at 5, 10, 20, 30, 40, 50 and 60 minutes, then 2, 3, 4, 5 and 6 hours. Corneal aesthesiometry, blink rates and scores for blepharospasm (BLEPH), conjunctival hyperaemia (CH) and lacrimation (LAC) were recorded. Statistical analyses used anova,t‐tests and Mann–Whitney U tests as relevant.ResultsNo significant effect of treatment group on any recordings was found at any time point in either dogs or cats. Adverse effects of increased BLEPH, CH or blink rate were observed in six animals (three cats from group M and three dogs from group B), occurring within 5 minutes of drop application and lasting for between 10 minutes and 6 hours.Conclusions and clinical relevanceTopical ocular morphine showed no measurable analgesic effect against corneal pain in dogs and cats.     

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.     

Sedative and analgesic effects of intravenous xylazine and tramadol on horses

This study was performed to evaluate the sedative and analgesic effects of xylazine (X) and tramadol (T) intravenously (IV) administered to horses. Six thoroughbred saddle horses each received X (1.0 mg/kg), T (2.0 mg/kg), and a combination of XT (1.0 and 2.0 mg/kg, respectively) IV. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), indirect arterial pressure (IAP), capillary refill time (CRT), sedation, and analgesia (using electrical stimulation and pinprick) were measured before and after drug administration. HR and RR significantly decreased from basal values with X and XT treatments, and significantly increased with T treatment (p < 0.05). RT and IAP also significantly increased with T treatment (p < 0.05). CRT did not change significantly with any treatments. The onset of sedation and analgesia were approximately 5 min after both X and XT treatments; however, the XT combination produced a longer duration of sedation and analgesia than X alone. Two horses in the XT treatment group displayed excited transient behavior within 5 min of drug administration. The results suggest that the XT combination is useful for sedation and analgesia in horses. However, careful monitoring for excited behavior shortly after administration is recommended.     

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.     

Sedative, analgesic and cardiorespiratory effects of romifidine in cats

OBJECTIVE: To evaluate the sedative, analgesic, and cardiorespiratory effects of intramascular (IM) romifidine in cats. STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: Ten healthy adult cats. METHODS: Romifidine (100, 200, and 400 microg kg(-1)) or xylazine (1 mg kg(-1)) was given IM in a cross-over study design. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), hemoglobin saturation, oscillometric arterial pressure, and scores for sedation, muscle relaxation, position, auditory response, and analgesia were determined before and after drug administration. Time to recumbency, duration of recumbency, and time to recover from sedation were determined. Subjective evaluation and cardiorespiratory variables were recorded before and at regular intervals for 60 minutes after drug administration. RESULTS: Bradycardia developed in all cats that were given romifidine or xylazine. No other significant differences in physiologic parameters were observed from baseline values or between treatments. Increasing the dose of romifidine did not result in increased sedation or muscle relaxation. Cats given xylazine showed higher sedation and muscle relaxation scores over time. Analgesia scores were significantly higher after administration of romifidine (400 microg kg(-1)) and xylazine (1 mg kg(-1)) than after romifidine at 100 or 200 microg kg(-1). Duration of lateral recumbency was not significantly different between treatments; however, cats took longer to recover after administration of 400 micro g kg(-1) romifidine. CONCLUSIONS AND CLINICAL RELEVANCE: Bradycardia is the most important adverse effect after IM administration of romifidine at doses ranging from 100 to 400 microg kg(-1) or 1 mg kg(-1) of xylazine in cats. The sedative effects of romifidine at 200 microg kg(-1) are comparable to those of 1 mg kg(-1) of xylazine, although muscle relaxation and analgesia were significantly less with romifidine than with xylazine.     

Effects of remifentanil infusion regimens on cardiovascular function and responses to noxious stimulation in propofol-anesthetized cats

OBJECTIVE: To evaluate the effects of 2 remifentanil infusion regimens on cardiovascular function and responses to nociceptive stimulation in propofol-anesthetized cats. ANIMALS: 8 adult cats. PROCEDURES: On 2 occasions, cats received acepromazine followed by propofol (6 mg/kg then 0.3 mg/kg/min, i.v.) and a constant rate infusion (CRI) of remifentanil (0.2 or 0.3 microg/kg/ min, i.v.) for 90 minutes and underwent mechanical ventilation (phase I). After recording physiologic variables, an electrical stimulus (50 V; 50 Hz; 10 milliseconds) was applied to a forelimb to assess motor responses to nociceptive stimulation. After an interval (> or = 10 days), the same cats were anesthetized via administration of acepromazine and a similar infusion regimen of propofol; the remifentanil infusion rate adjustments that were required to inhibit cardiovascular responses to ovariohysterectomy were recorded (phase II). RESULTS: In phase I, heart rate and arterial pressure did not differ between remifentanil-treated groups. From 30 to 90 minutes, cats receiving 0.3 microg of remifentanil/kg/min had no response to noxious stimulation. Purposeful movement was detected more frequently in cats receiving 0.2 microg of remifentanil/kg/min. In phase II, the highest dosage (mean +/- SEM) of remifentanil that prevented cardiovascular responses was 0.23 +/- 0.01 microg/kg/min. For all experiments, mean time from infusion cessation until standing ranged from 115 to 140 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Although the lower infusion rate of remifentanil allowed ovariohysterectomy to be performed, a CRI of 0.3 microg/kg/min was necessary to prevent motor response to electrical stimulation in propofol-anesthetized cats. Recovery from anesthesia was prolonged with this technique.     

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.