Gabapentin as an adjuvant for postoperative pain management in dogs undergoing mastectomy

This study aimed to evaluate the analgesic efficacy of gabapentin as an adjuvant for postoperative pain management in dogs. Twenty dogs undergoing mastectomy were randomized to receive perioperative oral placebo or gabapentin (10 mg/kg). All dogs were premedicated with intramuscular acepromazine (0.03 mg/kg) and morphine (0.3 mg/ kg). Anesthesia was induced with propofol (4 mg/kg) intravenously and maintained with isoflurane. Intravenous meloxicam (0.2 mg/kg) was administered preoperatively. Postoperative analgesia was evaluated for 72 hr. Rescue analgesia was provided with intramuscular morphine (0.5 mg/kg). Dogs in the Placebo group received significantly more morphine doses than the Gabapentin group (P=0.021), despite no significant differences in pain scores. Perioperative gabapentin reduced the postoperative morphine requirements in dogs after mastectomy.     

Effects of continuous intravenous infusion of morphine and morphine‐tramadol on the minimum alveolar concentration of sevoflurane and electroencephalographic entropy indices in dogs

ObjectiveTo compare the effects of continuous rate infusions (CRIs) of intravenous (IV) morphine and morphine-tramadol on the minimum alveolar concentration (MAC) of sevoflurane, and on electroencephalographic entropy indices in dogs.DesignProspective study.AnimalsEight young, healthy German shepherds, weighing 26.3 ± 3.1 kg (mean ± SD).MethodsAnaesthesia was induced and maintained with sevoflurane. A standard tail-clamp technique was used for MAC determination. Within one anaesthetic period, MAC was first determined during sevoflurane anaesthesia alone (MAC_B); then during morphine infusion (MAC_M), (loading dose 0.5 mg kg⁻¹IM; CRI, 0.2 mg kg⁻¹hour⁻¹⁾ then finally during morphine-tramadol infusion (tramadol loading dose 1.5 mg kg⁻¹IV; CRI, 2.6 mg kg⁻¹ hour⁻¹) (MAC_MT). At each change, periods of 45 minutes were allowed for equilibration. Stated entropy (SE), response entropy (RE), and RE-SE differences were measured five minutes prior to and during tail clamping.ResultsThe MAC_B was 2.1 ± 0.3vol%. The morphine and morphine-tramadol infusions reduced MAC to 1.6 ± 0.3vol% and 1.3 ± 0.3vol%, respectively. MAC was decreased below baseline more during morphine-tramadol than during morphine alone (39 ± 9% versus 25 ± 6%, respectively; p = 0.003). All SE and RE and most RE-SE differences were increased significantly (p < 0.05) over pre-stimulation in all groups when the dogs responded purposefully to noxious stimulation. When no response to noxious stimulation occurred, the entropy indices did not change.Conclusion and clinical relevanceIn dogs, combined morphine-tramadol CRI decreased sevoflurane MAC more than morphine CRI alone. Entropy indices changed during nociceptive responses in anaesthetized animals, suggesting that entropy measurements may be useful in determining anaesthetic depth in dogs.     

Evaluation of histamine release during constant rate infusion of morphine in dogs

OBJECTIVE: To evaluate histamine release and selected physiologic variables during constant rate infusion (CRI) of morphine in dogs. ANIMALS: Five healthy, conscious, intact female dogs. MATERIAL AND METHODS: Using a Latin square, repeated-measures design, dogs were randomly assigned to three treatment groups to receive a 4-hour CRI of saline (SAL), or a loading dose of morphine at 0.3 mg kg(-1) (LM), or 0.6 mg kg(-1) (HM), followed by an infusion of 0.17 mg kg(-1) hour(-1) (LM) and 0.34 mg kg(-1) hour(-1) (HM) respectively. Dogs received each of the three treatments at intervals of at least 7 days. Plasma histamine concentration, skin flushing, edema and wheals, heart rate and rhythm and non-invasive arterial blood pressure were measured before the loading dose and at 1, 2, 5, 15, 30, 60, 120, 180 and 240 minutes during the CRI, or at the time of occurrence. RESULTS: The loading dose induced the highest histamine release in the HM group being statistically higher than the SAL group. The histamine release obtained in the LM group after the loading dose did not differ from SAL. During the infusion, plasma histamine levels were numerically higher in the LM group. Besides one dog that developed hypotension for 2 minutes after the loading dose in the HM group and one dog that showed occasional ventricular premature contractions during both morphine infusions, cardiovascular variables were similar among the three treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Both doses of morphine induced variable histamine release with minimal adverse cardiovascular effects in these conscious, healthy dogs. The plasma histamine levels obtained may be associated with significant hemodynamic changes in patients with limited cardiovascular reserve and sympathetic nervous tone.     

Morphine-associated pruritus after single extradural administration in a horse

Pruritus following a single administration of 100 microg kg(-1) of preservative-free morphine sulphate given via an extradural catheter was seen in a 580 kg horse. The catheter was placed in the first intercoccygeal space. Focal irritation, represented by both local alopecia over the left gluteal muscles and serum exudation, occurred 4-8 hours after injection. This was attributed to the extradural morphine administration.     

Evaluation of a local anesthetic delivery system for the postoperative analgesic management of canine total ear canal ablation--a randomized, controlled, double-blinded study

OBJECTIVE: To determine if a constant rate local anesthetic delivery system is more effective than continuous intravenous (IV) morphine infusion for postoperative analgesia. ANIMALS: Twenty client-owned dogs undergoing total ear canal ablation. METHODS: Dogs were randomly assigned to the lidocaine group (LID) or the morphine group (MOR). The LID group received a constant rate infusion of lidocaine locally and a continuous IV infusion of saline, while the MOR group received a constant rate infusion of saline locally and a continuous IV infusion of morphine. The primary investigator evaluated each patient and determined a hospital behavior score, anesthesia recovery score, preoperative pain score, and serial postoperative pain and sedation scores over 38 hours. Pain and sedation observations were videotaped and scored by three additional evaluators. Evaluators were blinded to treatment assignments. RESULTS: There were no significant differences in age, weight, hospital behavior scores or anesthesia recovery scores. The primary investigator's pain scores were not significantly different, but sedation scores were significantly lower for the LID group. Sedation and pain scores by the video evaluators were not significantly different between groups. Kappa agreement between observers was poor, but better agreement was noted between sedation scores than pain scores. Drug-related complications were significantly lower in the LID group (n = 0) compared with the MOR group (n = 5). Wound complications were not significantly different (LID = 4, MOR = 4). Intravenous delivery complications occurred in 12 (60%) patients. Local delivery complications occurred in five (25%) dogs. Delivery complications were not significantly different between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous incisional lidocaine delivery was an equipotent and viable method of providing postoperative analgesia compared with IV morphine. Lidocaine delivery resulted in a trend toward lower pain scores, significantly lower sedation scores, and no dogs requiring analgesic rescue. Wound complications secondary to local infusion were minor and self-limiting. Drug-related complications occurred only in the MOR group.     

类吗啡类拮抗物的抑食活性与拓扑指数的相关性研究

计算了23个新近报道的类吗啡类拮抗物,3,4—二甲基—4(3—羟基笨基)哌淀衍生物的A_m指数,并首次用多元回归分析及神经网络法对这类拮抗物的结构与抑食活性的相关性进行了研究,结果表明,A_m指数能反映这类拮抗物的结构特征,而用神经网络法所得结果优于用多元回归分析所得结果.     

Characterization of the pharmacokinetics,behavioral effects and effects on thermal nociception of morphine 6-glucuronide and morphine 3-glucuronide in horses

ObjectiveTo describe the pharmacokinetics, behavioral and physiologic effects and effects on thermal thresholds of morphine, morphine 6-glucuronide (M6G) and morphine 3-glucuronide (M3G) following administration to horses.Study designRandomized balanced crossover study.AnimalsA total of seven University-owned horses, five mares and two geldings, aged 3–6 years.MethodsHorses were treated with a single intravenous dosage of saline, morphine (0.2 mg kg^–1), M6G (0.01 mg kg^–1) and M3G (0.03 mg kg^–1). Blood was collected prior to (baseline) and at several times post administration. Drug and metabolite concentrations were determined by liquid chromatography–mass spectrometry, and plasma pharmacokinetics were calculated. Behavioral observations and physiologic variables (heart rate, step counts, packed cell volume, total plasma protein and gastrointestinal sounds) were determined at baseline and for up to 6 hours. The effects on thermal nociception were determined and thermal excursion was calculated.ResultsThe volumes of distribution were 4.75–10.5, 0.244–0.295 and 0.215–0.356 L kg^–1 for morphine, M6G and M3G, respectively. Systemic clearances were 26.8–39.6, 3.16–3.88 and 1.46–2.13 mL minute^?1 kg^?1 for morphine, M6G and M3G, respectively. Morphine administration resulted in signs of excitation as evidenced by an increase in step counts and subjective behavioral observations, whereas M6G and M3G, based on the same criteria, appeared to cause sedative-like effects. Significant effects on thermal nociception were observed until 4 hours post morphine administration, 1 hour post M6G administration and at various times post M3G administration.Conclusions and clinical relevanceResults of this study provide additional information regarding the use of morphine in horses. Less locomotor excitation and gastrointestinal adverse effects, compared with morphine, coupled with favorable effects on thermal nociception are encouraging for further study of the pharmacodynamics of both M6G and M3G in horses.     

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.     

Comparative study on the sedative effects of morphine, methadone, butorphanol or tramadol, in combination with acepromazine, in dogs

Objective  To compare the effects of morphine (MOR), methadone (MET), butorphanol (BUT) and tramadol (TRA), in combination with acepromazine, on sedation, cardiorespiratory variables, body temperature and incidence of emesis in dogs.
Study design  Prospective randomized, blinded, experimental trial.
Animals  Six adult mixed-breed male dogs weighing 12.0 ± 4.3 kg.
Methods  Dogs received intravenous administration (IV) of acepromazine (0.05 mg kg⁻¹) and 15 minutes later, one of four opioids was randomly administered IV in a cross-over design, with at least 1-week intervals. Dogs then received MOR 0.5 mg kg⁻¹; MET 0.5 mg kg⁻¹; BUT 0.15 mg kg⁻¹; or TRA 2.0 mg kg⁻¹. Indirect systolic arterial pressure (SAP), heart rate (HR), respiratory rate ( f _R), rectal temperature, pedal withdrawal reflex and sedation were evaluated at regular intervals for 90 minutes.
Results  Acepromazine administration decreased SAP, HR and temperature and produced mild sedation. All opioids further decreased temperature and MOR, BUT and TRA were associated with further decreases in HR. Tramadol decreased SAP whereas BUT decreased f _R compared with values before opioid administration. Retching was observed in five of six dogs and vomiting occurred in one dog in MOR, but not in any dog in the remaining treatments. Sedation scores were greater in MET followed by MOR and BUT. Tramadol was associated with minor changes in sedation produced by acepromazine alone.
Conclusions and clinical relevance  When used with acepromazine, MET appears to provide better sedation than MOR, BUT and TRA. If vomiting is to be avoided, MET, BUT and TRA may be better options than MOR.