Kavitha Kongara

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 (0.5mg/kg) or tramadol (3mg/kg) or parecoxib (1mg/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.

Effects of tramadol, morphine or their combination in dogs undergoing ovariohysterectomy on peri-operative electroencephalographic responses and post-operative pain

Abstract AIM: To compare the peri-operative electroencephalogram (EEG) responses and post-operative analgesic efficacy of pre-operative morphine or tramadol with a combination of low-dose pre-operative morphine and post-operative tramadol, in dogs undergoing ovariohysterectomy. METHODS: Dogs undergoing routine ovariohysterectomy were treated with either pre-operative morphine (0.5 mg/kg S/C, n=8), or tramadol (3 mg/kg S/C, n=8), or pre-operative low-dose morphine (0.1 mg/kg S/C) and post-operative tramadol (3 mg/kg I/V, n=8). All dogs received routine pre-anaesthetic medication, and anaesthesia was induced with I/V thiopentone to effect and maintained with halothane in oxygen. Respiratory rate, heart rate, end-tidal halothane tension (EtHal) and end-tidal CO2 tension (EtCO2) were monitored throughout surgery. The EEG was recorded continuously in a three electrode montage. Median frequency (F50), total power (Ptot) and 95% spectral edge frequency (F95) of the EEG power spectra were compared during different 100-second periods of surgery: prior to and during skin incision, ligation of each ovarian pedicle, ligation of uterine body and skin closure. Post-operatively, pain was assessed using the short form of the Glasgow composite measure pain scale (CMPS-SF). RESULTS: There was no difference in F50 or Ptot of the EEG between baseline and noxious surgical events within each treatment group, or between the three groups (p>0.05). The mean F95 was higher during the first three periods of surgery for dogs administered tramadol and low-dose morphine than those that received 0.5 mg/kg morphine (p=0.001). Dogs that received low-dose morphine and tramadol had lower CMPS-SF pain scores after ovariohysterectomy than those that received either tramadol or morphine alone (p=0.001). There was no difference in pain scores between dogs in the latter two groups. CONCLUSION AND CLINICAL RELEVANCE: Tramadol and morphine administered pre-operatively provided an equal degree of post-operative analgesia in dogs after ovariohysterectomy. A combination of pre-operative low-dose morphine and post-operative tramadol produced better post-operative analgesia than either drug administered alone pre-operatively. Administration of analgesics pre- and post-operatively could result in improved post-operative well-being of ovariohysterectomised dogs.

Effects of tramadol or morphine in dogs undergoing castration on intra-operative electroencephalogram responses and post-operative pain

AIM: To compare the effects of pre-operatively administered tramadol with those of morphine on electroencephalographic responses to surgery and post-operative pain in dogs undergoing castration. METHODS: Dogs undergoing castration were treated with either pre-operative morphine (0.5 mg/kg S/C, n = 8) or tramadol (3 mg/kg S/C, n = 8). All dogs also received 0.05 mg/kg acepromazine and 0.04 mg/kg atropine S/C in addition to the test analgesic. Anaesthesia was induced with thiopentone administered I/V to effect and maintained with halothane in oxygen. Respiratory rate, heart rate, end-tidal halothane tension (EtHal) and end-tidal CO2 tension (EtCO2) were monitored throughout surgery. Electroencephalograms (EEG) were recorded continuously using a three electrode montage. Median frequency (F50), total power (Ptot) and 95% spectral edge frequency (F95) derived from EEG power spectra recorded before skin incision (baseline) were compared with those recorded during ligation of the spermatic cords of both testicles. Post-operatively, pain was assessed after 1, 3, 6 and 9 h using the short form of the Glasgow composite measure pain scale (CMPS-SF). RESULTS: Dogs premedicated with tramadol had higher mean F50 (12.2 (SD 0.2) Hz) and lower Ptot (130.39 (SD 12.1) µv2) compared with those premedicated with morphine (11.5 (SD 0.2) Hz and 161.8 (SD 15.1) µv2, respectively; p<0.05) during ligation of testicle 1. There were no differences in EEG responses between the two treatment groups during ligation of testicle 2 (p>0.05). The F95 of the EEG did not differ between the two groups during the ligation of either testicle (p > 0.05). Post-operatively, no significant differences in the CMPS-SF score were found between animals premedicated with tramadol and morphine at any time during the post-operative period. No dog required rescue analgesia. CONCLUSION AND CLINICAL RELEVANCE: Tramadol and morphine administered pre-operatively provided a similar degree of post-operative analgesia in male dogs at the doses tested.

Electroencephalographic evaluation of decapitation of the anaesthetized rat

The objective of this study was to evaluate the changes in electroencephalographic (EEG) power spectrum in response to decapitation of anaesthetized rats, in order to assess the nociception or otherwise of this procedure. Ten young adult male Sprague-Dawley rats were anaesthetized with halothane in oxygen and anaesthesia was maintained at a stable concentration of halothane between 1.20% and 1.25%. The rat’s head and neck were placed through the opening of a small animal guillotine so that the blade of the guillotine was positioned over the atlanto-occipial joint of the rat’s neck. The EEG was recorded in a five-electrode montage, bilaterally. After recording a 15 min baseline the rat was decapitated by swiftly pressing the guillotine blade and the EEG recording was continued until the signal was isoelectric on both channels. Changes in the median frequency (F50), 95% spectral edge frequency (F95) and total power of the EEG (Ptot) were used to investigate the effects of decapitation. During the first 15 s following decapitation, there were significant increases in the F50 and F95, and a decrease in the Ptot compared with baseline values. There was a clear window of time immediately following decapitation where changes in the EEG frequency spectrum were obvious; these changes in the EEG indices of nociception could be attributed as responses generated by the rat’s cerebral cortex following decapitation.

Alteration of Electroencephalographic Responses to Castration in Cats by Administration of Opioids

The aim of this study was to investigate the effect of opioids on electroencephalogram (EEG) indices of nociception in cats undergoing castration. Cats were randomly assigned to receive one of the four treatments (n=8); 0.2 mg/kg morphine, 0.005 mg/ kg fentanyl, 0.01 mg/kg buprenorphine or 0.2 mg/kg butorphanol, administered subcutaneously (SC) at the time of pre-anesthetic medication. Anesthesia was induced with intravenous propofol and maintained with halothane in oxygen. EEG was recorded continuously in a three electrode montage. Median frequency (F50), total power (PTOT) and 95% spectral edge frequency (F95) derived from the EEG power spectra recorded prior to skin incision (baseline) were compared with those recorded during the ligation of the spermatic cords of both testicles. During the ligation of testicle 1, the mean F50 of cats that received buprenorphine and butorphanol was significantly (p0.05). These results indicate that opioid analgesics, acting at different opioid receptors with variable affinity, produce changes in the EEG responses that reflect their anti-nociceptive efficacy. This study demonstrates the usefulness of the EEG as a valid tool for evaluating analgesic efficacy in cats, as shown in other species of animals in previous studies.

Attitudes and perceptions of veterinary paraprofessionals in New Zealand to postoperative pain in dogs and cats

Abstract AIM: To survey the attitudes and perceptions of veterinary paraprofessionals in New Zealand to postoperative pain in dogs and cats. METHODS: In December 2011, veterinary paraprofessionals (VP) from throughout New Zealand were invited to participate in an online survey. Eleven questions, which were divided into five sections, were used to determine demographic information, the respondents’ assessment of pain after commonly performed surgeries in dogs and cats, their opinions on provision of analgesia, who had responsibility for pain monitoring and the use of any formal pain scoring system in the practice. RESULTS: Data from 165 respondents were able to be used, and 162 (98%) respondents to the survey were female. According to the respondents’ estimates, fracture repair in dogs and repair of diaphragmatic hernias in cats had the highest pain score following surgery. Neutering procedures involving dogs were scored higher than for cats (p<0.01). All respondents agreed that animals benefit from perioperative analgesia. The veterinary nurse was reported to be predominantly responsible for monitoring pain in animals postoperatively by 116/165 (70.3%) respondents. Of 165 respondents, 154 (93%) considered that their knowledge of pain and assessment of pain could be enhanced. CONCLUSIONS: This survey reflects the attitudes and perceptions of a sample of VP in New Zealand to postoperative pain in dogs and cats. The results indicate that all respondents believe that surgery results in sufficient pain to warrant analgesic therapy. Routine neutering surgeries were considered to be more painful in dogs than in cats. The current survey also provides information to educators on potential areas of focus, given that 93% of respondents felt that their knowledge of pain and assessment of pain could be enhanced.

Pharmacogenetics of opioid analgesics in dogs

Genetic variation causes interindividual variability in drug absorption, distribution, metabolism and excretion. These pharmacokinetic processes will influence the observed efficacy and toxicity of a drug. Polymorphisms in the genes encoding the metabolizing enzymes, transport proteins and receptors have been linked to the inconsistency in responses to opioid treatment in humans and laboratory animals. Pharmacogenetics is relatively less developed field in veterinary medicine compared to significant advances in knowledge on genetic basis of variation in drug responses and clinical applications in human medicine. This review discusses the opioid drug metabolism and possible genetic polymorphism of metabolizing enzymes in dogs. Polymorphism of genes encoding opioid drug transporter proteins and its effect on opioid response and opioid receptor gene variants are also discussed. Due to the scarcity of studies reported on opioid pharmacogenetics in dogs, relevant studies in humans and rodents have also been discussed to indicate current trends and potential targets for research in dogs.

Robenacoxib in the treatment of pain in cats and dogs: safety, efficacy, and place in therapy

Robenacoxib is a novel nonsteroidal anti-inflammatory drug (NSAID) of coxib class developed for the control of inflammation and pain in dogs and cats. It shows high selectivity for the cyclooxygenase-2 (COX-2) enzyme in rats, cats, and dogs. Robenacoxib is available in both injectable and tablet formulations. This review initially focuses on the preclinical pharmacology of robenacoxib in rats that includes its high affinity for COX-2 enzyme and weaker and rapidly reversible binding for COX-1 enzyme in in vitro and ex vivo models of inflammation and its pharmacokinetics in the blood and inflammatory exudate, selective tissue distribution, and safety. These basic pharmacological profiles highlight the suitability of robenacoxib for use in target species, such as cats and dogs. Since the level of expression and activity of COX enzymes is species specific, COX-2-selective inhibition and the resultant effects of coxibs must be studied in target species. The pharmacological and toxicological profiles of robenacoxib in cats and dogs have been discussed prior to reviewing its clinical efficacy and safety. Large, multicenter field trials conducted in cats and dogs demonstrated the noninferior efficacy and safety of robenacoxib compared with noncoxib NSAIDs used in dogs and cats. These trials investigated the efficacy of robenacoxib against various acute and chronic painful conditions. Robenacoxib produced superior efficacy to placebo and COX-2 preferential inhibitors in postsurgical cats. The tissue-selective anti-inflammatory activity of robenacoxib has been demonstrated in dogs with osteoarthritis. Robenacoxib has also been shown to be safe in healthy dogs and cats receiving antihypertensive drugs and loop diuretics that could cause renal injury. The developmental objective of coxibs, comparable efficacy but superior safety to less selective/nonselective NSAIDs, is well established with robenacoxib in preclinical studies. More studies need to be conducted to fully explore the benefits of robenacoxib in clinical subjects.

Pharmacokinetics of articaine hydrochloride and its metabolite articainic acid after subcutaneous administration in red deer (Cervus elaphus)

AIM: To develop and validate a simple and sensitive method using liquid chromatography-mass spectrometry (LC-MS) for quantification of articaine, and its major metabolite articainic acid, in plasma of red deer (Cervus elaphus), and to investigate the pharmacokinetics of articaine hydrochloride and articainic acid in red deer following S/C administration of articaine hydrochloride as a complete ring block around the antler pedicle. METHODS: The LC-MS method was validated by determining linearity, sensitivity, recovery, carry-over and repeatability. Articaine hydrochloride (40 mg/mL) was administered S/C to six healthy male red deer, at a dose of 1 mL/cm of pedicle circumference, as a complete ring block around the base of each antler. Blood samples were collected at various times over the following 12 hours. Concentrations in plasma of articaine and articainic acid were quantified using the validated LC-MS method. Pharmacokinetic parameters of articaine and articainic acid were estimated using non-compartmental analysis. RESULTS: Calibration curves were linear for both articaine and articainic acid. The limits of quantifications for articaine and articainic acid were 5 and 10 ng/mL, respectively. Extraction recoveries were >72% for articaine and >68% for articainic acid. After S/C administration as a ring block around the base of each antler, mean maximum concentrations in plasma (Cmax) of articaine were 1,013.9 (SD 510.1) ng/mL, detected at 0.17 (SD 0.00) hours, and the Cmax for articainic acid was 762.6 (SD 95.4) ng/mL at 0.50 (SD 0.00) hours. The elimination half-lives of articaine hydrochloride and articainic acid were 1.12 (SD 0.17) and 0.90 (SD 0.07) hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The LC-MS method used for the quantification of articaine and its metabolite articainic acid in the plasma of red deer was simple, accurate and sensitive. Articaine hydrochloride was rapidly absorbed, hydrolysed to its inactive metabolite articainic acid, and eliminated following S/C administration as a ring block in red deer. These favourable pharmacokinetic properties suggest that articaine hydrochloride should be tested for efficacy as a local anaesthetic in red deer for removal of velvet antlers. Further studies to evaluate the safety and residues of articaine hydrochloride and articainic acid are required before articaine can be recommended for use as a local anaesthetic for this purpose.

Toxicity and Pharmacokinetic Studies of Lidocaine and Its Active Metabolite, Monoethylglycinexylidide, in Goat Kids

Simple Summary Disbudding is becoming a routine husbandry procedure in goat farms even though it is a painful procedure without appropriate pain relief. One of the ways to alleviate or minimize the pain associated with disbudding is by using local anesthetics like lidocaine hydrochloride. However, lidocaine hydrochloride has been reported to be toxic in goat kids and there is some data regarding the doses that produce toxicity in goat kids. Therefore, the research team studied the toxicity and pharmacokinetics of lidocaine hydrochloride in goat kids to recommend a safe dose for disbudding. Abstract This study determined the convulsant plasma concentrations and pharmacokinetic parameters following cornual nerve block and compared the results to recommend a safe dose of lidocaine hydrochloride for goat kids. The plasma concentrations of lidocaine and monoethylglycinexylidide (MGX) were quantified using liquid chromatography-mass spectrometry. A total dose of 7 mg/kg body weight (BW) was tolerated and should therefore be safe for local and regional anesthesia in goat kids. The mean plasma concentration and mean total dose that produced convulsions in goat kids were 13.59 ± 2.34 µg/mL and 12.31 ± 1.42 mg/kg BW (mean ± S.D.), respectively. The absorption of lidocaine following subcutaneous administration was rapid with Cmax and Tmax of 2.12 ± 0.81 µg/mL and 0.33 ± 0.11 h, respectively. The elimination half-lives (t½λz) of lidocaine hydrochloride and MGX were 1.71 ± 0.51 h and 3.19 ± 1.21 h, respectively. Injection of 1% lidocaine hydrochloride (0.5 mL/site) was safe and effective in blocking the nerves supplying horn buds in goat kids.