Jan E. Ilkiw

The effects of intravenous gabapentin administration on the minimum alveolar concentration of isoflurane in cats.

Lidocaine decreases the minimum alveolar concentration (MAC) of inhaled anesthetics and has been used clinically to reduce the requirements for other anesthetic drugs. In this study we examined the effects of lidocaine on isoflurane MAC in cats. Six cats were studied. In Experiment 1, the MAC of isoflurane was determined. An IV bolus of lidocaine 2 mg/kg was then administrated and venous plasma lidocaine concentrations were measured to determine pharmacokinetic values. In Experiment 2, lidocaine was administered to achieve target plasma concentrations between 1 and 11 &mgr;g/mL and the MAC of isoflurane was determined at each lidocaine plasma concentration. Actual lidocaine plasma concentrations were 1.06 ± 0.12, 2.83 ± 0.39, 4.93 ± 0.64, 6.86 ± 0.97, 8.86 ± 2.10, and 9.84 ± 1.34 &mgr;g/mL for the target concentrations of 1, 3, 5, 7, 9, and 11 &mgr;g/mL, respectively. The MAC of isoflurane in this study was 2.21% ± 0.17%, 2.14% ± 0.14%, 1.88% ± 0.18%, 1.66% ± 0.16%, 1.47% ± 0.13%, 1.33% ± 0.23%, and 1.06% ± 0.19% at lidocaine target plasma concentrations of 0, 1, 3, 5, 7, 9, and 11 &mgr;g/mL, respectively. Lidocaine, at target plasma concentrations of 1, 3, 5, 7, 9, and 11 &mgr;g/mL, linearly decreased isoflurane MAC by −6% to 6%, 7% to 28%, 19% to 35%, 28% to 45%, 29% to 53%, and 44% to 59%, respectively. We conclude that lidocaine decreases the MAC of isoflurane.

Effects of tramadol hydrochloride on the thermal threshold in cats

OBJECTIVE-To determine the thermal antinociceptive effect of oral administration of tramadol hydrochloride at doses between 0.5 and 4 mg/kg in cats. ANIMALS-6 healthy adult domestic shorthair cats. PROCEDURES-Baseline (before drug administration; time 0) thermal threshold was determined by applying a thermal probe to the thorax of each cat. Tramadol (0.5, 1, 2, 3, or 4 mg/kg) or a placebo was then administered orally in accordance with a Latin square design. Thermal threshold was determined by an observer who was unaware of treatment at various times until thermal threshold returned to baseline values or 6 hours had elapsed. Plasma tramadol and O-desmethyl-tramadol concentrations were measured prior to drug administration and at 1-hour intervals thereafter. Effect-concentration data were fitted to effect maximum models. RESULTS-Highest plasma tramadol and O-desmethyl-tramadol concentrations increased with increasing tramadol dose. Significant effects of dose and time on thermal threshold were detected. Thermal threshold was significantly higher than the baseline value at 80 and 120 minutes for the 0.5 mg/kg dose, at 80 and from 120 to 360 minutes for the 2 mg/kg dose, from 40 to 360 minutes for the 3 mg/kg dose, and from 60 to 360 minutes for the 4 mg/kg dose. CONCLUSIONS AND CLINICAL RELEVANCE-Tramadol induced thermal antinociception in cats. Doses of 2 to 4 mg/kg appeared necessary for induction of significant and sustained analgesic effects. Simulations predicted that 4 mg/kg every 6 hours would maintain analgesia close to the maximum effect of tramadol.

Hemodynamic effects of dexmedetomidine in isoflurane-anesthetized cats

OBJECTIVE To characterize the hemodynamic effects of dexmedetomidine in isoflurane-anesthetized cats. STUDY DESIGN Prospective experimental study. ANIMALS Six healthy adult female cats weighing 4.6 ± 0.8 kg. METHODS Dexmedetomidine was administered intravenously using target-controlled infusions to maintain nine plasma concentrations between 0 and 20 ng mL(-1) in isoflurane-anesthetized cats. The isoflurane concentration was adjusted for each dexmedetomidine concentration to maintain the equivalent of 1.25 times the minimum alveolar concentration, based on a previous study. Heart rate, systemic and pulmonary arterial pressures, central venous pressure, pulmonary artery occlusion pressure, body temperature, and cardiac output were measured at each target plasma dexmedetomidine concentration. Additional variables were calculated. Arterial and mixed-venous blood samples were collected for blood gas, pH, and (on arterial blood only) electrolyte, glucose and lactate analysis. Plasma dexmedetomidine concentration was determined for each target. Pharmacodynamic models were fitted to the data. RESULTS Heart rate, arterial pH, arterial bicarbonate concentration, mixed-venous PO(2) , mixed-venous pH, mixed-venous hemoglobin oxygen saturation, cardiac index, stroke index, and venous admixture decreased following dexmedetomidine administration. Arterial blood pressure, central venous pressure, pulmonary arterial pressure, pulmonary arterial occlusion pressure, packed cell volume, PaO(2) , PaCO(2) , arterial hemoglobin concentration, mixed-venous PCO(2) , mixed-venous hemoglobin concentration, ionized calcium concentration, glucose concentration, rate-pressure product, systemic and pulmonary vascular resistance indices, left ventricular stroke work index, arterial oxygen concentration, and oxygen extraction increased following dexmedetomidine administration. Most variables changed in a dexmedetomidine concentration-dependent manner. CONCLUSION AND CLINICAL RELEVANCE The use of dexmedetomidine as an anesthetic adjunct is expected to produce greater negative hemodynamic effects than a higher, equipotent concentration of isoflurane alone.

EFFECT OF NON-ADRENAL ILLNESS, ANAESTHESIA AND SURGERY ON PLASMA CORTISOL CONCENTRATIONS IN DOGS

Basal plasma cortisol concentrations in 25 dogs with non-adrenal illness were two to three times higher than in 25 normal dogs (158 +/- 25 nmol litre-1 compared with 65 +/- 22; mean +/- SD). In addition, plasma cortisol concentrations were measured in 12 animals undergoing major abdominal, thoracic or orthopaedic surgery and compared to a group of six anaesthetised dogs. Anaesthesia alone failed to significantly alter plasma cortisol levels, however, all forms of surgery produced a significant increase in plasma cortisol concentration which returned to normal 24 hours after completion of surgery.

Pharmacokinetics of gabapentin in cats

OBJECTIVE To determine the pharmacokinetics of gabapentin in cats after IV and oral administration. ANIMALS 6 healthy female adult domestic shorthair cats. PROCEDURES Gabapentin was administered IV (4 mg/kg) or orally (10 mg/kg) in a crossover randomized design. Blood samples were obtained immediately before gabapentin administration and at various times up to 960 minutes after IV administration or up to 1,440 minutes after oral administration. Blood samples were immediately transferred to tubes that contained EDTA and were centrifuged at 4 degrees C. Plasma was harvested and stored at -20 degrees C until analysis. Plasma concentrations of gabapentin were determined by use of liquid chromatography-mass spectrometry. Gabapentin concentration-time data were fit to compartment models. RESULTS A 3-compartment model with elimination from the central compartment best described the disposition of gabapentin administered IV to cats, but a 1-compartment model best described the disposition of gabapentin administered orally to cats. After IV administration, the mean +/- SEM apparent volume of the central compartment, apparent volume of distribution at steady state, and clearance and the harmonic mean +/- jackknife pseudo-SD for terminal half-life were 90.4 +/- 11.3 mL/kg, 650 +/- 14 mL/kg, 3 +/- 0.2 mL/min/kg, and 170 +/- 21 minutes, respectively. Mean +/- SD systemic availability and harmonic mean +/- jackknife pseudo-SD terminal half-life after oral administration were 88.7 +/- 11.1% and 177 +/- 25 minutes, respectively. CONCLUSIONS AND CLINICAL RELEVANCE The disposition of gabapentin in cats was characterized by a small volume of distribution and a low clearance.

Thermal antinociceptive effect of orally administered gabapentin in healthy cats

OBJECTIVE To determine the thermal antinociceptive effect of various single doses of gabapentin administered orally in cats. ANIMALS 6 healthy adult domestic shorthair cats. PROCEDURES Baseline skin temperature and baseline thermal threshold were determined via application of a thermal probe to the thorax of each cat prior to oral administration (in random order) of an empty capsule (placebo) or a capsule containing 5, 10, or 30 mg of gabapentin/kg (4 experiments/cat). After each treatment, thermal threshold was determined at intervals during an 8-hour period. Plasma gabapentin concentration was measured prior to and at 1-hour intervals after drug administration. Dose and time effects were analyzed by use of a repeated-measures ANOVA. RESULTS Peak plasma gabapentin concentration increased with increasing gabapentin dose. After administration of the 5, 10, and 30 mg/kg doses, median interval until the greatest gabapentin concentration was detected was 60, 120, and 90 minutes, respectively (interval ranges were 60 to 120 minutes, 60 to 120 minutes, and 60 to 180 minutes, respectively). In the experiments involving administration of the placebo or increasing doses of gabapentin, mean+/-SD baseline skin temperature and thermal threshold were 36.8+/-1.21 degrees C and 45.8+/-4.4 degrees C, 36.9+/-1.1 degrees C and 43.1+/-2.4 degrees C, 37.0+/-0.7 degrees C and 44.0+/-1.5 degrees C, and 36.1+/-1.7 degrees C and 43.3+/-3.3 degrees C, respectively. There was no significant effect of treatment on thermal threshold. CONCLUSIONS AND CLINICAL RELEVANCE At the doses evaluated, orally administered gabapentin did not affect the thermal threshold in healthy cats and therefore did not appear to provide thermal antinociception.

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.

ELECTROCARDIOGRAPHY, HEART SCORE AND HAEMATOLOGY OF HORSES COMPETING IN AN ENDURANCE RIDE

Thirty-one horses competing in a 100 kilometre endurance ride had electrocardiograms recorded before and after the ride from which the heart score of each horse was calculated. Blood was also taken to determine the packed cell volume (PCV) and total plasma protein (TPP) before the ride, after 60 kilometres (mid-ride) and at completion of the ride. Statistical analysis of the heart scores showed that a faster group of horses had significantly higher heart scores than either a slower group or those eliminated due to inadequate recovery of heart rate. No horses developed electrocardiogram abnormalities as a result of the ride. Analysis of the results of PCV and TPP showed that horses became dehydrated during the ride. The faster group of horses had significantly higher PCV values and heart rates at both the mid-ride and end of ride sampling times. However, the TPP values indicated no significant differences in the amount of dehydration between the 2 groups.

Fluid balance, glomerular filtration rate, and urine output in dogs anesthetized for an orthopedic surgical procedure

OBJECTIVE To determine fluid retention, glomerular filtration rate, and urine output in dogs anesthetized for a surgical orthopedic procedure. ANIMALS 23 dogs treated with a tibial plateau leveling osteotomy. PROCEDURES 12 dogs were used as a control group. Cardiac output was measured in 5 dogs, and 6 dogs received carprofen for at least 14 days. Dogs received oxymorphone, atropine, propofol, and isoflurane for anesthesia (duration, 4 hours). Urine and blood samples were obtained for analysis every 30 minutes. Lactated Ringers solution was administered at 10 mL/kg/h. Urine output was measured and glomerular filtration rate was estimated. Fluid retention was measured by use of body weight, fluid balance, and bioimpedance spectroscopy. RESULTS No difference was found among control, cardiac output, or carprofen groups, so data were combined. Median urine output and glomerular filtration rate were 0.46 mL/kg/h and 1.84 mL/kg/min. Dogs retained a large amount of fluids during anesthesia, as indicated by increased body weight, positive fluid balance, increased total body water volume, and increased extracellular fluid volume. The PCV, total protein concentration, and esophageal temperature decreased in a linear manner. CONCLUSIONS AND CLINICAL RELEVANCE Dogs anesthetized for a tibial plateau leveling osteotomy retained a large amount of fluids, had low urinary output, and had decreased PCV, total protein concentration, and esophageal temperature. Evaluation of urine output alone in anesthetized dogs may not be an adequate indicator of fluid balance.

Other Potentially Useful New Injectable Anesthetic Agents

Ultrashort barbiturates are not ideal injectable anesthetic agents, and new agents continue to be released as investigators pursue the goal of finding a more ideal agent. Of the new injectable agents discussed, propofol seems to be the most promising drug. Propofol should find a place in veterinary practice as an outpatient anesthetic agent because it has a rapid, smooth, and complete recovery even after repeated or continuous administration. Midazolam does not induce anesthesia in healthy, small animals and, as such, can only be used in combination with other injectable agents, such as ketamine or the thiobarbiturates. In our practice, Telazol has found a place in the anesthetic management of feral cats and aggressive dogs, where it is used for heavy sedation or to induce anesthesia. The role of flumazenil, as a reversal agent, in veterinary practice remains to be determined; however, the role in small domestic animals is unlikely to be significant.