Marlis L. Rezende

Plasma concentrations and behavioral, antinociceptive, and physiologic effects of methadone after intravenous and oral transmucosal administration in cats

OBJECTIVE To determine plasma concentrations and behavioral, antinociceptive, and physiologic effects of methadone administered via IV and oral transmucosal (OTM) routes in cats. ANIMALS 8 healthy adult cats. PROCEDURES Methadone was administered via IV (0.3 mg/kg) and OTM (0.6 mg/kg) routes to each cat in a balanced crossover design. On the days of drug administration, jugular catheters were placed in all cats under anesthesia; a cephalic catheter was also placed in cats that received methadone IV. Baseline measurements were obtained ≥ 90 minutes after extubation, and methadone was administered via the predetermined route. Heart and respiratory rates were measured; sedation, behavior, and antinociception were evaluated, and blood samples were collected for methadone concentration analysis at predetermined intervals for 24 hours after methadone administration. Data were summarized and evaluated statistically. RESULTS Plasma concentrations of methadone were detected rapidly after administration via either route. Peak concentration was detected 2 hours after OTM administration and 10 minutes after IV administration. Mean ± SD peak concentration was lower after OTM administration (81.2 ± 14.5 ng/mL) than after IV administration (112.9 ± 28.5 ng/mL). Sedation was greater and lasted longer after OTM administration. Antinociceptive effects were detected 10 minutes after administration in both groups; these persisted ≥ 2 hours after IV administration and ≥ 4 hours after OTM administration. CONCLUSIONS AND CLINICAL RELEVANCE Despite lower mean peak plasma concentrations, duration of antinociceptive effects of methadone was longer after OTM administration than after IV administration. Methadone administered via either route may be useful for perioperative pain management in cats.

Effects of intravenous administration of lidocaine on the minimum alveolar concentration of sevoflurane in horses

OBJECTIVE To determine effects of a continuous rate infusion of lidocaine on the minimum alveolar concentration (MAC) of sevoflurane in horses. ANIMALS 8 healthy adult horses. PROCEDURES Horses were anesthetized via IV administration of xylazine, ketamine, and diazepam; anesthesia was maintained with sevoflurane in oxygen. Approximately 1 hour after induction, sevoflurane MAC determination was initiated via standard techniques. Following sevoflurane MAC determination, lidocaine was administered as a bolus (1.3 mg/kg, IV, over 15 minutes), followed by constant rate infusion at 50 μg/kg/min. Determination of MAC for the lidocaine-sevoflurane combination was started 30 minutes after lidocaine infusion was initiated. Arterial blood samples were collected after the lidocaine bolus, at 30-minute intervals, and at the end of the infusion for measurement of plasma lidocaine concentrations. RESULTS IV administration of lidocaine decreased mean ± SD sevoflurane MAC from 2.42 ± 0.24% to 1.78 ± 0.38% (mean MAC reduction, 26.7 ± 12%). Plasma lidocaine concentrations were 2,589 ± 811 ng/mL at the end of the bolus; 2,065 ± 441 ng/mL, 2,243 ± 699 ng/mL, 2,168 ± 339 ng/mL, and 2,254 ± 215 ng/mL at 30, 60, 90, and 120 minutes of infusion, respectively; and 2,206 ± 329 ng/mL at the end of the infusion. Plasma concentrations did not differ significantly among time points. CONCLUSIONS AND CLINICAL RELEVANCE Lidocaine could be useful for providing a more balanced anesthetic technique in horses. A detailed cardiovascular study on the effects of IV infusion of lidocaine during anesthesia with sevoflurane is required before this combination can be recommended.

Comparison of the cardiovascular effects of equipotent anesthetic doses of sevoflurane alone and sevoflurane plus an intravenous infusion of lidocaine in horses

OBJECTIVE To compare cardiovascular effects of sevoflurane alone and sevoflurane plus an IV infusion of lidocaine in horses. Animals-8 adult horses. PROCEDURES Each horse was anesthetized twice via IV administration of xylazine, diazepam, and ketamine. During 1 anesthetic episode, anesthesia was maintained by administration of sevoflurane in oxygen at 1.0 and 1.5 times the minimum alveolar concentration (MAC). During the other episode, anesthesia was maintained at the same MAC multiples via a reduced concentration of sevoflurane plus an IV infusion of lidocaine. Heart rate, arterial blood pressures, blood gas analyses, and cardiac output were measured during mechanical (controlled) ventilation at both 1.0 and 1.5 MAC for each anesthetic protocol and during spontaneous ventilation at 1 of the 2 MAC multiples. RESULTS Cardiorespiratory variables did not differ significantly between anesthetic protocols. Blood pressures were highest at 1.0 MAC during spontaneous ventilation and lowest at 1.5 MAC during controlled ventilation for either anesthetic protocol. Cardiac output was significantly higher during 1.0 MAC than during 1.5 MAC for sevoflurane plus lidocaine but was not affected by anesthetic protocol or mode of ventilation. Clinically important hypotension was detected at 1.5 MAC for both anesthetic protocols. CONCLUSIONS AND CLINICAL RELEVANCE Lidocaine infusion did not alter cardiorespiratory variables during anesthesia in horses, provided anesthetic depth was maintained constant. The IV administration of lidocaine to anesthetized nonstimulated horses should be used for reasons other than to improve cardiovascular performance. Severe hypotension can be expected in nonstimulated horses at 1.5 MAC sevoflurane, regardless of whether lidocaine is administered.

Pharmacokinetics and tolerance of transdermal fentanyl administration in foals

OBJECTIVE To characterize the pharmacokinetics of fentanyl and the tolerance of foals to the drug following a single application of a commercially available transdermal system (TS). STUDY DESIGN Prospective experimental study. ANIMALS Six (two male, four female) foals aged 4-8 days, weighing 56-74 kg. METHODS After placement of a jugular sampling catheter, one fentanyl TS (FTS) containing 10.2 mg fentanyl, released at 100 microg hour(-1), was applied for 72 hours. Blood samples were withdrawn over the course of 90 hours for fentanyl plasma analysis. Before and after the study, weight, complete blood count and blood chemistry values were obtained. During the study, tolerance and safety were monitored by physical examination and assessment of behavior. RESULTS Fentanyl was detected as early as 20 minutes after FTS placement. Peak plasma concentrations were variable (0.1-28.7 ng mL(-1)), were reached after 14.3 +/- 7.6 hours (mean +/- SD), and returned to baseline concentrations 12 hours after FTS removal. All foals satisfactorily tolerated the FTS application and no significant adverse effects were observed. Rectal temperature increased above 38.5 degrees C (max. 39.0 degrees C) in all foals, although this did not correlate with fentanyl plasma concentrations. Results of hematological and biochemical analyses were within reference ranges. CONCLUSION AND CLINICAL RELEVANCE Our data show that 100 microg hour(-1) fentanyl administered by an FTS results in time-related but variable plasma concentrations in foals. The FTS was easy to apply and was well tolerated.

Evaluation of cardiovascular, respiratory and biochemical effects, and anesthetic induction and recovery behavior in horses anesthetized with a 5% micellar microemulsion propofol formulation.

OBJECTIVE To characterize cardiovascular, respiratory and biochemical effects and recovery behavior associated with a 3-hour continuous infusion of a micellar microemulsion propofol formulation in horses. STUDY DESIGN Prospective experimental trial. ANIMALS Six healthy adult horses, 9 +/- 2 years old and weighing 557 +/- 14 kg. METHODS All horses received xylazine (1 mg kg(-1), IV) 5 minutes prior to anesthetic induction. Each horse was anesthetized on two occasions with a 5% micellar microemulsion propofol formulation (2 mg kg(-1), IV); first as a single bolus (phase I) and then as a 3-hour continuous infusion (phase II). Propofol pharmacokinetics were obtained from phase I and used to determine the starting infusion rates in phase II. Anesthetic induction and recovery characteristics were quantitatively and qualitatively assessed. Cardiovascular, respiratory and biochemical parameters were monitored during anesthesia and recovery. RESULTS Induction quality varied, ranging from good to poor. Standing and overall recovery quality scores were consistently excellent in phase I but more variability was observed among horses in phase II. Heart rate (HR) and mean arterial pressure (MAP) were adequately maintained but marked hypoventilation developed. There were only minimal changes in blood biochemical analytes following anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE The micellar microemulsion propofol formulation, administered as a 3-hour continuous infusion, showed similar results compared to those previously described with a commercially available propofol preparation. However, based on present findings, use of propofol as a primary anesthetic in horses for prolonged periods of anesthesia requires further study to determine the limits of safety and clinical applicability.

Evaluation of transesophageal echo-Doppler ultrasonography for the measurement of aortic blood flow in anesthetized cats

OBJECTIVE To evaluate the use of a transesophageal echo-Doppler ultrasonography (TED) technique for measurement of aortic blood flow (ABF) in relation to cardiac output (CO) measured by use of a thermodilution technique in anesthetized cats. ANIMALS 6 adult cats (mean +/- SD body weight, 5 +/- 0.7 kg). PROCEDURES Anesthesia was induced and maintained in cats by administration of isoflurane. A thermodilution catheter was placed in a pulmonary artery. The TED probe was positioned in the esophagus in the region where the aorta and esophagus are almost parallel. Five baseline values for ABF and CO were concurrently recorded. Cats were randomly assigned to a high or low CO state (increase or decrease in CO by at least 25% from baseline, respectively). Baseline conditions were restored, and the other CO state was induced, after which baseline conditions were again restored. For each CO state, ABF and CO were measured 5 times at 5-minute intervals. Correlation and agreement between the techniques were determined by use of the Pearson product-moment correlation and Bland-Altman method. RESULTS CO ranged from 0.16 to 0.75 L/min and ABF from 0.05 to 0.48 L/min. Overall data analysis revealed a high correlation (r = 0.884) between techniques but poor agreement (limits of agreement, -0.277 to 0.028 L/min). During the low CO state, correlation between techniques was low (r = 0.413). CONCLUSIONS AND CLINICAL RELEVANCE TED did not accurately measure CO. However, it allowed evaluation of CO patterns and may be useful clinically in anesthetized cats.

Comparison of the analgesic efficacy of oral ABT-116 administration with that of transmucosal buprenorphine administration in dogs

OBJECTIVE To evaluate the analgesic efficacy of ABT-116, a transient receptor potential cation channel vanilloid subfamily V member 1 antagonist, and compare it with that of buprenorphine by measurement of mechanical and thermal nociceptive thresholds in dogs. ANIMALS Six 7- to 8-month-old dogs (3 males and 3 females). PROCEDURES In a crossover study design, all dogs received ABT-116 (30 mg/kg, PO) and buprenorphine (0.03 mg/kg, orotransmucosally), with each treatment separated by 1 week. Physiologic variables were recorded prior to and 1, 6, and 24 hours after drug administration. Thermal (thoracic) and mechanical (dorsolateral aspect of the radius [proximal] and dorsopalmar aspect of the forefoot [distal]) nociceptive thresholds were assessed prior to (baseline) and 15 minutes and 1, 2, 4, 6, 12, 18, and 24 hours after treatment. RESULTS Buprenorphine administration resulted in higher overall thermal and proximal mechanical nociceptive thresholds, compared with ABT-116. Distal mechanical nociceptive thresholds after treatment were higher than baseline values for both treatments, but the magnitude of change was greater for buprenorphine at 1 hour after administration. Whereas HR and RR sporadically differed from baseline values after ABT-116 administration, rectal temperature increased from a baseline value of 39 ± 0.2°C (mean ± SD) to a peak of 40.6 ± 0.2°C at 6 hours. CONCLUSIONS AND CLINICAL RELEVANCE In dogs without inflammation or nerve injury, PO administration of ABT-116 did not consistently result in an increase in nociceptive thresholds. However, clinically relevant increases in rectal temperature were identified after ABT-116 administration.

Efficacy of Manual Ventilation Techniques During Cardiopulmonary Resuscitation in Dogs

The efficacy of ventilation of dogs during cardiopulmonary resuscitation (CPR) with a tight fitting face mask or mouth-to-nose rescue breathing has not been evaluated. Twenty-four purpose bred research dogs: Dogs were randomized to be ventilated by cuffed orotracheal tube, tight fitting face mask, mouth-to-nose breathing or compressions only during CPR (n = 6 in all groups). Orotracheal tube and face mask ventilation was performed on room air. Chest compressions were performed during the experimental procedure. Arterial blood gases were performed prior to euthanasia (baseline), at 3 min and at 6 min of CPR. PaO2 and PaCO2 were compared for each time point and each group. There was no difference in PaO2 or PaCO2 between groups at baseline. At 6 min all groups had a significantly higher PaCO2 (P ≤ 0.005) and the facemask and compression only groups had a significantly lower PaO2 (P < 0.02) when compared to the orotracheal tube group. There was no difference between the PaO2 of the mouth-to-nose group compared to the orotracheal tube group at 3 or 6 min. Gastric distension, regurgitation, gas leakage around the mouth, and ineffective breaths were all noted in both the face mask and mouth-to-nose group. The results of this study supports that orotracheal intubation is the preferred technique for ventilation during CPR in dogs. When orotracheal intubation is not possible, face mask ventilation or mouth-to-nose ventilation would be reasonable alternatives. When oxygen supplementation is available, face mask ventilation is likely to be superior. Appropriate training for both face mask and mouth-to-nose ventilation techniques is recommended.