Caudal epidural co-administration of methadone and morphine in horses: An evaluation of analgesic properties and effects on locomotor function,mentation and physical examination parameters

Caudal epidural analgesia is a well-established therapeutic modality for pain alleviation in horses. Additionally, epidural analgesia could potentially be a complementary diagnostic tool for confirmation of pain-related conditions in horses presenting with nonspecific signs of poor performance or rideability issues. To use the epidural as a diagnostic tool, the administered medications should provide efficient analgesia without accompanying adverse effects. Therefore, the objectives of the current study were to evaluate the analgesic properties and effects on locomotor function, mentation and physical examination parameters of caudal epidural co-administration of methadone and morphine in horses. Five mares received a caudal epidural injection of 0.1 mg/kg bwt methadone and 0.1 mg/kg bwt morphine diluted to a total volume of 4.4 mL/100 kg. Before and several times thereafter, horses were subjected to mechanical nociceptive threshold evaluation, physical examination, assessment of mentation and locomotor function examination. Horses were assigned ataxia scores (0–4) by a group of inexperienced raters (three senior-year veterinary students) and a group of experienced raters (two board-certified internal medicine specialists) that assessed the locomotor examinations either live or video-based. The epidural co-administration of methadone and morphine resulted in clinically relevant and statistically significant increases of horses’ tolerance to mechanical noxious stimuli at the coccygeal, perineal, sacral, lumbar and thoracic regions. Analgesia was evident after 4.4 h and lasted at least 5 h. Regional differences in the onset of analgesia reflected a cranial spread of the analgesic solution. No horses showed signs of gait disturbances; the overall median ataxia score was 0 at all times; and the average difference in scores between two randomly selected raters for a random horse at a random time point was 0.377 indicating high inter-rater agreement. There were no adverse changes of mentation and physical examination parameters. Observed side effects included signs of decreased frequency of defaecation, generalised sweating, and pruritus.     

Plasma histamine concentrations in horses administered sodium penicillin,guaifenesin–xylazine–ketamine and isoflurane with morphine or butorphanol

ObjectiveVarious drugs administered to horses undergoing surgical procedures can release histamine. Histamine concentrations were evaluated in horses prepared for surgery and administered butorphanol or morphine intraoperative infusions.Study designProspective studies with one randomized.AnimalsA total of 44 client-owned horses.MethodsIn one study, anesthesia was induced with xylazine followed by ketamine–diazepam. Anesthesia was maintained with guaifenesin–xylazine–ketamine (GXK) during surgical preparation. For surgery, isoflurane was administered with intravenous (IV) morphine (group M: 0.15 mg kg^–1 and 0.1 mg kg^–1 hour^–1; 15 horses) or butorphanol (group B: 0.05 mg kg^–1 and 0.01 mg kg^–1 hour^–1; 15 horses). Histamine and morphine concentrations were measured using enzyme-linked immunoassay before opioid injection (time 0), and after 1, 2, 5, 30, 60 and 90 minutes. In a subsequent study, plasma histamine concentrations were measured in 14 horses before drug administration (baseline), 15 minutes after IV sodium penicillin and 15 minutes after starting GXK IV infusion. Statistical comparison was performed using anova for repeated measures. Pearson correlation compared morphine and histamine concentrations. Data are presented as mean ± standard deviation. Significance was assumed when p ≤ 0.05.ResultsWith histamine, differences occurred between baseline (3.2 ± 2.4 ng mL^–1) and GXK (5.2 ± 7.1 ng mL^–1) and between baseline and time 0 in group B (11.9 ± 13.4 ng mL^–1) and group M (11.1 ± 12.4 ng mL^–1). No differences occurred between baseline and after penicillin or between groups M and B. Morphine concentrations were higher at 1 minute following injection (8.1 ± 5.1 ng mL^–1) than at 30 minutes (4.9 ± 3.1 ng mL^–1) and 60 minutes (4.0 ± 2.5 ng mL^–1). Histamine correlated with morphine at 2, 30 and 60 minutes.Conclusions and clinical relevanceGXK increased histamine concentration, but concentrations were similar with morphine and butorphanol.     

Antinociceptive and selected physiological effects of morphine and xylazine on tiletamine‐zolazepam anesthesia in llamas

ObjectiveEvaluate antinociception, anesthesia, and recovery in llamas given tiletamine-zolazepam (TZ) with either morphine, xylazine, morphine and xylazine, or saline.Study designRandomized crossover experimental study.AnimalsSix healthy, adult intact male llamas.MethodsLlamas were given each of four treatments intramuscularly with a 1-week washout: TZ (2 mg kg^?1) combined with either morphine (0.5 mg kg^?1; M), xylazine (0.15 mg kg^?1; X), morphine (0.5 mg kg^?1) and xylazine (0.15mg kg^?1) (MX), or saline (C). Llamas breathed room air during the experiment. Characteristics of anesthesia, recovery, and selected cardiopulmonary variables were recorded. Antinociception was assessed by clamping a claw at 5-minute intervals. Data were analyzed using a mixed-model anova and Tukey-Kramer test, and are expressed as least squares mean ± SEM. Significance was set at p < 0.05.ResultsNo llama in the control group demonstrated antinociception. Antinociception was longest with treatment MX, followed by treatments X and M, respectively. Heart rates in llamas given treatments X and MX were significantly lower than with other treatments. The respiratory rate in llamas given treatment C was greater (p < 0.05) than for all other treatments, however, the respiratory rate was not significantly different among treatments X, M and MX. The PaO₂ for llamas given MX remained <60 mmHg throughout the 20 minute period of blood gas analysis. Mean arterial blood pressure in llamas in treatment MX was less than for treatments M or C.Conclusion and clinical relevanceThe combination of morphine (0.5 mg kg^?1) and xylazine (0.15 mg kg^?1) increased the duration of antinociception compared with xylazine alone, in TZ-anesthetized llamas. Treatments X, M and MX were associated with hypoxemia (PaO₂ < 60 mmHg).     

Alkaloid accumulation in capsules of the selfed and cross-pollinated poppy

In harmony with international regulations the creation of poppy cultivars with high alkaloid content as well as free of alkaloids is in progress. In the course of selection procedures, five poppy cultivars of high chemical diversity, ‘Kheops’, ‘AT, ‘Tebona’, ‘Kék Gemona’ and ‘Przemko’, were selfed and crossed in two successive years (2000‐01). After full ripening, both the biomass production and the alkaloid content of capsules of selfed and crossed plants were determined. When the castrated alkaloid‐free cultivar ‘Przemko’ (accumulating only 0.01 mg/100 g morphine in capsules) was pollinated with cultivars rich in alkaloids, the morphine content of its capsules increased to 0.9‐7.5 mg/100 g‐values. Based on the well‐known biosynthetic background of poppy alkaloids, this can be explained by promotion of (S)‐norcoclaurine synthesis, which seems to be suppressed in alkaloid‐free plants; but tissues of the developing hybrid seeds, which contain a combined gene pool of both alkaloid‐free cultivar and that of the pollen donor plants, release this suppression. The chemical metaxenia also manifested itself in other combinations. In particular, the appearance of narcotine (0.1‐1.1 mg/100 g) in the narcotine‐free cultivars ‘Kheops’, ‘A1’ and ‘Przemko’ can be explained biochemically. If the narcotine‐type plants ‘Kék Gemona’ (accumulating 11.3 mg/g narcotine) were used for pollination, the developing seed tissue, which contains the gene pool of narcotine biosynthesis, might contribute to the suppression of the activity of 1,2‐dehydroreticuline reductase, which leads to the accumulation of narcotine at the cost of morphinanes.     

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.     

Problems associated with perioperative morphine in horses: a retrospective case analysis

Objective To identify the incidence of adverse effects caused by morphine 100–170 µg kg^?1 administration during surgery in horses. Design Retrospective case record analysis (1996–2000). Animals Eighty‐four healthy (ASA 1 or 2) horses, mean age 5.5 ± 3.1 (SD) years (2 months to 16 years), mean weight 524 ± 14 kg (100–950). Methods Physiological data and evidence of complications were collected from the anaesthetic records of all animals anaesthetized with romifidine, ketamine, diazepam and halothane and undergoing laryngeal surgery or orchiectomy at the Royal (Dick) School of Veterinary Studies. Cases were divided into those receiving (group M+; n = 18) and those not receiving morphine (M?; n = 29), and the data compared. Values for heart and respiratory rate and mean arterial pressure were compared at 15‐minute intervals between 30 and 120 minutes after induction using anova for repeated measures. The incidence of intraoperative problems was compared using Fisher's exact test. Recovery scores were compared using Student's unpaired t‐test. The records of a further 37 horses undergoing umbilical herniorrhaphy (n = 5), arthroscopy (n = 29) or tarsal arthrodesis (n = 3) were also studied but not analysed statistically due to disparate treatment distribution. Results There were no significant differences between the M+ and M? groups. The incidence of post‐operative complications such as box‐walking and colic were similar in each group. Conclusions Morphine doses of 100–170 µg kg^?1 do not increase the risk of problems when used to provide perioperative analgesia in horses anaesthetized with romifidine, ketamine, diazepam and halothane. Clinical relevance Morphine provides an acceptable and relatively inexpensive way to provide perioperative analgesia in horses.     

The effects of morphine on the recovery of horses from halothane anaesthesia

OBJECTIVE: To investigate the effects of peri-operative morphine on the quality and duration of recovery from halothane anaesthesia in horses. STUDY DESIGN: Prospective randomized study. ANIMALS: Twenty-two client owned horses, ASA category I or II. METHODS: Horses undergoing elective surgical procedures were divided into two groups and paired according to procedure, body position during surgery, body mass and breed. Group M+ received morphine by intravenous injection (0.15 mg kg(-1)) before induction of anaesthesia and then by infusion (0.1 mg kg(-1) hour(-1)) during anaesthesia. Group M- received the same anaesthetic agents except that morphine was excluded. At the end of surgery, the horses were placed in a recovery box and allowed to recover without assistance. Recoveries were recorded on videotape, beginning when the anaesthetist left the recovery box, and ending when the horse stood up. Recoveries were assessed from digital video recordings by three observers, unaware of treatment. The time to first movement, attempting and attaining sternal recumbency and standing were recorded. The quality of various aspects of the recovery was assessed to produce a total recovery score; high numerical values indicate poor recoveries. The duration of anaesthesia and the total dose of morphine administered were recorded. RESULTS: The mean morphine dose (95% CI) was 147 (135-160) mg [equivalent to 0.27 (0.25-0.29) mg kg(-1)]. The recovery scores (median, 95% CI) for the M- and M+ groups were 25, 19-41 and 20, 14-26, respectively. Total score increased as duration of anaesthesia increased, independent of treatment. Untreated (M-) horses made more attempts to achieve sternal recumbency: mean number of attempts (95% CI) for M- was 4.5 (2.7-6.2) compared with 2.0 (1.4-2.6) (M+). Untreated horses made more attempts to stand (2.1, 1.6-2.6) compared with the morphine recipients (1.3, 1.1-1.5). Time to standing (in minutes) was significantly (p = 0.0146) longer for the untreated (31.3, 24.3-38.3) compared with treated animals (26.6, 20.9-32.3). The interval between the first movement in recovery to the time at standing was significantly (p < 0.001) longer for M- (14.5, 12.1-16.9 minutes) compared with M+ animals (7.4, 5.0-9.8 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Recoveries from anaesthesia in the morphine recipients were characterized by fewer attempts to attain sternal recumbency and standing, and a shorter time from the first recovery movement to the time of standing.