Behavioral and Antinociceptive Effects of Alfentanil,Butorphanol, and Flunixin in Horses

To determine the behavioral and antinociceptive effects of narcotic and non-narcotic analgesics administered by intravenous injection in horses, 10 thoroughbred mares weighing between 450 and 550 kg and ranging in age from 8 to 13 years old were analyzed. The effects of alfentanil, butorphanol, flunixin, and saline solution on the general activity of the horses were investigated by measuring spontaneous locomotor activity (SLA) and head height (HH) in two behavior stalls. The antinociceptive effects of alfentanil (0.02 mg kg⁻¹), butorphanol (0.1 mg kg⁻¹), flunixin meglumine (0.5 mg kg⁻¹), and saline were determined by measuring skin twitch reflex latency (STRL) after thermal cutaneous nociceptive stimulation. A paired Student t-test was used to compare SLA and HH between the groups of horses receiving different doses of the same drug at various time points. The Tukey test was used to compare the antinociceptive effect of the treatments. Differences were considered significant when P value was <.05. Horses treated with opioid analgesics demonstrated excitation, as shown by a significant increase in SLA at all doses tested and by neighing and demonstrating attentive attitudes with movement of the ears, stereotypical walking, and ataxia in most of the animals. HH was elevated only in animals treated with alfentanil. Antinociception was observed at 5 and 30 minutes after administration of alfentanil and butorphanol, respectively. Increased SLA was observed at 30 and 90 minutes after administration of alfentanil and butorphanol, respectively. We observed no effect on antinociception in horses given flunixin. In conclusion, this study suggests that alfentanil has a faster onset and a shorter duration than butorphanol; however, both drugs are able to stimulate the central nervous system.     

Antinociceptive Effect of Intravenous Regional Analgesia in Horses Underwent Selected Short-Time Distal Limb Surgeries

The aim of the present study was to establish appropriate doses for both lidocaine hydrochloride (Hcl) and mepivacaine in intravenous regional analgesia (IVRA) and to assess their intraoperative and postoperative analgesic effects in horses with distal limb surgeries. A total of 55 draft horses were included in the present study. Six clinically healthy horses were selected randomly for establishing the doses of lidocaine Hcl and mepivacaine in IVRA in horse limbs. After selection, 32 horses suffered from various distal limb surgical affections were randomly allocated into three groups: thiopental group (n = 6), animals were operated under general anesthesia using thiopental sodium; IVRA-LID group (n = 12), animals were operated under both general anesthesia and IVRA using lidocaine Hcl; and IVRA-MEP group (n = 14), horses were operated under both general anesthesia and IVRA using mepivacaine. Postoperative pain was measured using both Horse Grimace Pain Scale and multifactorial numerical rating composite pain. The results showed that conjunction of IVRA along with thiopental general anesthesia using either lidocaine or mepivacaine significantly decreased the total required doses of thiopental sodium during the operations and significantly increased the duration of postoperative analgesia to 60 and 150 minutes using lidocaine and mepivacaine, respectively. In conclusion, the uses of local IVRA before distal limb surgery improve the depth of general anesthesia and reduced postoperative pain, despite thiopental anesthesia alone. Mepivacaine is superior to lidocaine in IVRA, with a longer duration of action.     

Antinociceptive and Behavioral Effects of Methadone Alone or in Combination with Detomidine in Conscious Horses

The antinociceptive and behavioral effects of methadone (MET) alone or combined with detomidine (DET) were studied in horses. Intravenous treatments were randomly administered in a two-phase crossover study. In phase 1, six horses were treated with saline (control) or 0.2 or 0.5 mg/kg methadone (MET_0.2; MET_0.5, respectively). In phase 2, six horses were treated with 0.01 mg/kg DET alone or with DET combined with 0.2 mg/kg MET (DET/MET_0.2). Thermal nociceptive threshold (TNT) and electrical nociceptive thresholds (ENT) were recorded by using a heat projection lamp and electrodes placed in the coronary band of the thoracic limbs, respectively. Spontaneous locomotor activity (SLA) was studied by movement sensors in the stall (phase 1). Chin-to-floor distance was assessed in phase 2. In phase 1, the TNT increased significantly for 30 minute after MET_0.5 but not after saline or MET_0.2. Hyperesthesia and ataxia were observed in 2 of 6 and 6 of 6 horses after MET_0.2 and MET_0.5, respectively. SLA increased significantly for 120 minutes after MET in a dose-dependent way, but not after placebo. In phase 2, DET and DET/MET_0.2 significantly increased the TNT and ENT above baseline for 15 and 30 minutes, respectively; thresholds were significantly higher with DET/MET_0.2 than with DET at the same times. Chin-to-floor distance decreased significantly from baseline for 30 minutes, and no excitatory behavior was observed in both treatments. Although the higher dose of MET induced short-acting antinociception, the associated adverse effects may contraindicate its clinical use. The lower dose of MET potentiated DET-induced antinociception without adverse effects, which might be useful under clinical circumstances.     

Preemptive Analgesia,Including Morphine,Does Not Affect Recovery Quality and Times in Either Pain-Free Horses or Horses Undergoing Orchiectomy

Recovery quality and times from general anesthesia in horses may be influenced by surgery, analgesia with morphine or combinations of both. Twenty-three adult healthy horses were enrolled in this prospective experimental trial in a clinical setting and were randomly allocated to one of the following groups: anesthesia only (GA; n = 6), preemptive analgesia and anesthesia (GAA; n = 5), anesthesia and castration (GC; n = 6), or preemptive analgesia, anesthesia, castration, and intraoperative local analgesia (GCA; n = 6). All horses were sedated with intramuscular (IM) xylazine (0.5 mg/kg). Anesthesia was induced with intravenous (IV) guaifenesin (100 mg/kg) and thiopental (5 mg/kg) and maintained with isoflurane in oxygen. Animals in groups with preemptive analgesia received IM morphine (0.2 mg/kg) and dipyrone (10 mg/kg) and IV flunixin meglumine (1.0 mg/kg) immediately before sedation. Recoveries from general anesthesia were rope-assisted. Recovery scores (from 8 [excellent recovery] to 70 [worst recovery]) and times were compared between groups, using a one-way analysis of variance followed by a Tukey's test (P < .05). Mean ± standard deviation (SD) and range recovery scores were 22 ± 14 (8–45), 9 ± 2 (8–12), 14 ± 5 (8–22), and 12 ± 1 (10–13) in groups GA, GAA, GC, and GCA, respectively. Mean ± SD times to stand in minutes were 21 ± 10, 18 ± 7, 33 ± 12, and 35 ± 21 in groups GA, GAA, GC and GCA, respectively. No statistically significant differences were found for any of the variables. Neither preoperative administration of analgesics, including morphine, nor castration interfered with the recovery qualities and times in horses undergoing general anesthesia. Preemptive morphine did not worsen anesthetic recovery quality in horses.     

Pharmacokinetics of Tramadol and its Metabolites M1, M2 and M5 in Horses Following Intravenous, Immediate Release (Fasted/Fed) and Sustained Release Single Dose Administration

Tramadol (T) is a centrally acting analgesic structurally related to codeine and morphine. This drug displays a weak affinity for the μ and δ-opioid receptors, and weaker affinity for the κ-subtype; it also interferes with the neuronal release and reuptake of serotonin and noradrenaline in the descending inhibitory pathways. The metabolism of this drug has been investigated in different animals (rats, mice, Syrian hamsters, guinea pigs, rabbits, and dogs) and humans; similar metabolites are produced but in different amounts. The major metabolic pathways involved in phase I metabolite production (M1–M5) are O-demethylation, N-demethylation, and N,N-demethylation. The aim of the current study is to evaluate the pharmacokinetic profile of T in the horse, and its M1, M2, and M5 metabolites after single-dose administration (5 mg/kg body weight [BW]) by intravenous, sustained-release tablets and immediate-release capsules. We also will investigate the potential effects of fasting and feeding on bioavailability of immediate-release capsules. The study design was divided into four randomized phases. Twenty-four gelding Italian trotter race horses were divided into four groups (6 animals each) and administered T intravenously, with T immediate-release capsules in a fasting status, T immediate-release capsules in a feeding status, and T sustained-release in fasting status. Blood samples were collected at different times and analyzed by high-pressure liquid chromatography (HPLC) with fluorimetric detection. The limit of quantification was 5 ng/ml for T, M1, and M2, and 10 ng/ml for M5. A one-compartment model best fit the plasma concentrations of T and M2 after all treatments. Unfortunately, for M1 and M5, it was not always possible to fit plasma curves because of very low and variable concentrations. M2 was the main metabolite produced in the four different treatments and its concentration was higher than the concentration of T after sustained-release administration. Conversely, M1, the main metabolite in humans, and M5 seemed to be only marginally produced in the horse. When T was administered in both fasted and fed states, variations in some pharmacokinetic parameters were not considered clinically significant. We concluded that T could be administered in either a fasted or a fed condition.