Evaluation of intraperitoneal and subcutaneous lidocaine and bupivacaine for analgesia following ovariohysterectomy in the dog

Evaluation of intraperitoneal and subcutaneous lidocaine and bupivacaine for analgesia following ovariohysterectomy in the dog

Veterinary Anaesthesia and Analgesia, 2003, 30, 99^119 MEETING ABSTRACTS Proceedings of the American College of Veterinary Anesthesiologists 27th An...

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Veterinary Anaesthesia and Analgesia, 2003, 30, 99^119

MEETING ABSTRACTS

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, Florida, 10^11 October 2002

SMALL ANIMALS Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs AValverde, S Cantwell, J Herna¤ndez, C Brotherson University of Florida, Gainesville, FL, USA

Opioids used in the pre-operative period may frequently induce vomiting. Acepromazine is commonly combined with opioids as a pre-anesthetic drug, and has antiemetic properties. The purpose of this study was to evaluate the antiemetic properties of acepromazine in dogs receiving opioids as a pre-anesthetic. One hundred and sixteen dogs (ASA I or II), 58 males and 58 females; purebreds and mixed breeds; 3 months13.4 years of age; weighing 1.8^57.7 kg admitted for elective surgical procedures, were randomly assigned to one of the three groups. All groups received acepromazine (0.05 mg kg1 IM). Group I (n ¼ 40) received acepromazine 15 minutes prior to opioid administration. Group II (n ¼ 38) received acepromazine in combination with the opioid. Group III (n ¼ 38) received acepromazine 15 minutes after opioid administration. One of the three di¡erent opioids was administered IM to each dog: morphine at 0.5 mg kg1, hydromorphone at 0.1 mg kg1, or oxymorphone at 0.075 mg kg1. Statistical analysis included a w2-test for the incidence of vomiting and a Kruskal^Wallis nonparametric test for the sedation comparison between groups. The dogs receiving acepromazine before the opioid (Group I) had signi¢cantly lower incidence of vomiting (18%) than those in Groups II (45%) and III (55%). The degree of sedation assessed 15 minutes after administration of the last drug (s) in each group was signi¢cantly lower in the dogs receiving the combination of acepromazine and opioid (Group II) than in those receiving opioid as the ¢rst drug (Group III). Time to vomiting was less than 8 minutes in all groups.

In conclusion, acepromazine administered 15 minutes before opioid reduces the incidence of vomiting induced by opioids. Comparative cardiovascular, analgesic, and sedative effects of medetomidine, medetomidine–hydromorphone, and medetomidine–butorphanol in dogs WC Kuo, RD Keegan Washington State University, Pullman,WA, USA

The purpose of this study was to determine the cardiovascular, analgesic, and sedative e¡ects of IV medetomidine (M,20 mg kg1), medetomidine^hydromorphone (MH, 20 mg kg1 0.1 mg kg1), and medetomidine^butorphanol (MB, 20 mg kg1 0.2 mg kg1) in dogs. Using a randomized cross-over design and allowing 1 week between treatments, six healthy, mixedbreed dogs (¢ve males and one female) weighing 20  3 kg, were induced to anesthesia by face-mask administration of 2.9% ET sevo£urane to facilitate instrumentation prior to administration of the treatment combinations. Dogs were intubated and instrumented to enable measurement of heart rate (HR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (PAP), pulmonary arterial occlusion pressure (PAOP), central venous pressure (CVP), pulmonary arterial temperature (TEMP), and cardiac output via thermodilution using 5 mL of 5% dextrose, and recording the average of the three replicate measurements. Cardiac index (CI) and systemic (SVR) and pulmonary vascular resistances were calculated. After instrumentation was completed, administration of sevo£urane was discontinued, and the dogs were allowed to recover for 30 minutes prior to administration of the treatment drugs. After collection of the baseline samples for blood gas analysis and recording the baseline cardiovascular variables, the test agents were administered 99

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

IVover10 seconds and the CV variables recorded at 5, 10,15, 30, 45, and 60 minutes post-injection. In addition, arterial blood was sampled for blood gas analysis at 15 and 45 minutes following injection. Intensity and duration of analgesia (assessed by toe-pinch response using a hemostat) and level of sedation were evaluated at the above time points and at 75 and 90 minutes post-injection. Data were analyzed using ANOVA for repeated measures with posthoc di¡erences between means identi¢ed using Bonferroni’s method (p < 0.05). Administration of M, MH, or MB was associated with increases in SAP, MAP, DAP, PAP, PAOP, CVP, SVR, and TEMP and with decreases in HR and CI. No di¡erences in CV variables between treatment groups were identi¢ed at any time. PaO2 increased over time in all groups and was signi¢cantly higher when MH was compared with M. At 45 minutes, PaO2 tended to decrease over time and was signi¢cantly lower when MH and MB were compared with M at 15 minutes. Analgesia scores for MH and MB were signi¢cantly higher compared with M through 45 minutes, while analgesia scores for MH were signi¢cantly higher compared with M through 90 minutes. Sedation scores were higher for MH and MB compared with M throughout 90 minutes. Durations of lateral recumbency were 108  10.8, 172  15.5, and 145  9.9 minutes for M, MH, and MB, respectively. We conclude that MH and MB are associated with improved analgesia and sedation and have similar CVe¡ects when compared with M. Evaluation of the side-effects and thermal antinociceptive effects of intravenous hydromorphone in cats K Wegner, SA Robertson University of Florida, Gainesville, FL, USA

Hydromorphone (H) may be an e¡ective analgesic agent in cats, but fear of negative behavioral sidee¡ects associated with opioids is cited as a reason for avoiding this class of analgesics in cats. This study was designed to assess onset and duration of antinociception using an established feline thermal threshold model in cats, given an accepted clinical dose of 0.1 mg kg1 of H. In addition, cats were observed for changes in behavior and other side-e¡ects. Six adult cats from an established colony (four spayed females and two castrated males, 4.7^7.0 kg) received 0.1 mg kg1 H IV following establishment of baseline thermal threshold (TT) values. TT was tested at 15 minutes 100

post-injection, then at every 30^60 minutes for 12 hours. Side-e¡ects and behavior changes were recorded for 12 hours. Changes in TT over time were analyzed using a one-way ANOVA; a p-value <0.05 was considered signi¢cant. TT increased from a pre-treatment value of (mean  SD) 40.9  1.65 8C to instrument cutout (55.5 8C) within 30 minutes for 5/6 cats. Mean TT was signi¢cantly elevated above baseline from 15 to 450 minutes after treatment. There was a signi¢cant increase in skin temperature from 15 to 300 minutes with peak increase of 1.55 8C at 135 minutes. Sidee¡ects included mydriasis (6/6) and nausea (4/6), characterized by licking, foaming, and gagging. Mydriasis occurred within 10^30 seconds of injection and persisted for 5^7 hours. Nausea was noted within 2 minutes of injection and persisted for 30^ 90 minutes; no vomiting occurred. Commonly observed behavioral changes included ventral tail curl (6/6 cats, onset 5^45 minutes, duration 4^ 5 hours) and euphoria (5/6 cats, onset <6 minutes for 4/6, duration1^6 hours).2/6 cats were profoundly sedate. Three cats showed signs of dysphoria with or without increased motor activity with variable onset and duration. Dysphoric behavior included staring, pacing, vocalizing, and sudden movements. 3/6 cats exhibited both euphoria and dysphoria at di¡erent times during the study. At no time were cats di⁄cult to restrain or work with. Return to baseline behavior occurred 7^8.5 hours post-injection. Mydriasis did not correlate closely with antinociception. Signs of sedation and euphoria corresponded with onset of antinociception, but not duration. Tail curl signs correlated with antinociception. In this model, H proved to be a rapid acting, potent, analgesic with a long (7.5 hours) duration of action. The most common behavioral changes noted were ventral tail curl, euphoria, and sedation. Mydriasis and nausea were noted as side-e¡ects.

The effect of four anesthetic protocols on the spleen in dogs DV Wilson, RE Carpenter, AT Evans Michigan State University, East Lansing, MI, USA

Splenic enlargement following administration of barbiturates has been well described in dogs; other agents have not been investigated. This study aimed to compare the e¡ects of four anesthetic protocols on splenic size. Twenty-four fasted Beagle dogs scheduled for laparotomy were allocated to one of the four groups. # Association of Veterinary Anaesthetists, 2003, 30, 99^119

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

Group 1: acepromazine and butorphanol followed by induction with thiopental; Group 2: acepromazine and butorphanol followed by induction with propofol; Group 3: medetomidine and butorphanol followed by induction with propofol; Group 4: medetomidine and butorphanol followed by induction with ketamine and diazepam. Anesthesia was maintained with halothane in oxygen, intravenous £uids were administered. Splenic length, width and height were measured once when the abdomen was opened and again just prior to closure. Spleens were also traced, the image was digitized, and the area was calculated. PCV and total solids were measured before and after pre-medication, after induction, and each time the spleen was measured. Data were analyzed using a Repeated Measures ANOVA with splenic variables indexed by body surface area and dose of induction agent as a covariate. Area and width of the spleens were less in the dogs of Groups 2 and 3 than in those of the other groups. Splenic area and length did not change signi¢cantly during surgery. Dosage of propofol was not signi¢cantly di¡erent between Groups 2 and 3. Baseline PCV was not signi¢cantly di¡erent among groups and decreased signi¢cantly in all dogs, but at di¡erent times. In Groups 1 and 2, the decrease occurred after pre-medication, in Group 3 at induction, and in Group 4 during surgery. A signi¢cant decrease in TS occurred in all groups during surgery. We concluded that the use of propofol resulted in smaller spleen size during surgery than that following the use of thiopental. Multiple factors in£uenced the PCV.

Comparison between S(þ) ketamine– diazepam and S(þ) ketamine–midazolam on anesthetic induction and recovery in dogs FB Riviera, JS Pires University of Passo Fundo, Passo Fundo, RS, Brazil

S(þ) ketamine, one of the two enantiomers of racemic ketamine, is a phencyclidine derivative that induces amnesia and analgesia. Its activity is related to blockade of NMDA receptors and some opioid action. We compared anesthetic induction and recovery quality with S(þ) ketamine in combination with diazepam or midazolam in 10 dogs (ASA 1) admitted for elective surgery. After all clinical examinations, the dogs were separated into two groups (G I and G II). All animals received acepromazine (0.1 mg kg1) and fentanyl (5 mg kg1) IM, 20 minutes before # Association of Veterinary Anaesthetists, 2003, 30, 99^119

induction with S(þ) ketamine (6 mg kg1) and diazepam (0.5 mg kg1) IV (G I) or midazolam 0.2 mg kg1 (G II) IV. The doses of diazepam and midazolam were chosen according to the literature. All dogs were intubated and then maintained with halothane in oxygen at a vaporizer setting su⁄cient to maintain surgical anesthesia. Quality of induction, time needed for intubation, heart rate, respiratory rate, SpO2, time to extubation, and quality of recovery were evaluated. The results were analyzed by Student’s t-test. Smooth induction and recovery were observed in all animals. The time to intubation was 45  20 (GI) and 25  6 seconds (GII), HR was 122  12 (GI) and 125  7 beats minute1 (GII), RR was 17  2 (GI) and 21  3 breaths minute1 (GII), SpO2 was 96  2 (GI) and 94  1% (GII), time to extubation was 7  3 (GI) and 4  1 minutes (GII). No statistical di¡erences were found in analyses, although time to intubation was less in GII. The results suggested that both combinations could be used safely for anesthetic induction in healthy dogs.

Comparison of two injectable anesthetic regimes in feral cats at a large-volume spay clinic AM Cistola, FJ Golder, JK Levy, AM Waas, SA Robertson University of Florida, Gainesville, FL, USA

Same-day mass sterilization of feral cats requires rapid onset, short-duration anesthesia. The purpose of this study was to compare our current anesthetic protocol, Telazol^ketamine^xylazine (TKX) with medetomidine^ketamine^buprenorphine (MKB). Feral female cats received either IM TKX (n ¼ 68; 0.25 mL cat1; tiletamine 12.5 mg, zolazepam 12.5 mg, K 20 mg, and X 5 mg per 0.25 mL) or MKB (n ¼ 17; M 40 mg kg1, K 15 mg kg1, and B 10 mg kg1). Intervals measured included time from injection to recumbency, time to surgery, duration of surgery, and time from reversal of anesthesia (TKX: yohimbine 0.50 mg cat1 IV; MKB: atipamezole 0.50 mg cat1 IM) to sternal recumbency. Following instrumentation (Vet/Ox 4403 and Vet/BP Plus 6500), physiological measurements were recorded at 5-minute intervals, and included rectal temperature, heart rate (HR), respiratory rate (RR), SpO2 (lingual or rectal probes), and indirect mean arterial blood pressure (MAP) (oscillometric method). Nonparametric means were compared using Mann^Whitney U-tests. Parametric means were compared using a 101

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

two-factorial ANOVA with Bonferroni’s t-tests. The alpha-priori signi¢cance level was p < 0.05. Values were mean  SD. Body weight (TKX:2.9  0.5 kg, MKB:2.7  0.7 kg), time to recumbency (TKX: 4  1 minutes, MKB: 3  1 minutes), time to surgery (TKX: 28  7 minutes, MKB: 28  5 minutes), and duration of surgery (TKX: 11 7 minutes, MKB: 8  5 minutes) did not di¡er between groups. In contrast, MKB cats required less time from reversal to sternal recumbency (TKX: 68  41 minutes, MKB: 7  2 minutes) and were recumbent for shorter duration (TKX: 114  39 minutes, MKB: 53  6 minutes). Temperature decreased during the study in both groups, but overall temperature was higher in MKB cats (38.0  0.95 8C) than in TKX cats (37.5  0.95 8C). RR, HR, and SpO2 did not change during the study in either group. However, overall HR and RR were higher in TKX cats (RR: 18  8 breaths minute1, HR: 153  30 beats minute1) compared to MKB cats (RR: 15  7 breaths minute1, HR: 128  19 beats minute1). In contrast, overall SpO2 was lower in the TKX group (90  6%) compared to the MKB group (94  4%). MAP was also lower in the TKX group (112  29 mm Hg) compared to that in the MKB group (122  20 mm Hg). However, MAP increased in the TKX group during surgery compared to pre-surgical values, but did not change in the MKB group. The results of this study suggested that MKB might be more suitable as an anesthetic for the purpose of mass sterilization of feral female cats.

Echocardiographic evaluation of dogs receiving 1:1 thiopental/propofol in a clinical setting AT Evans, LK Anderson, J Hauptman Michigan State University, East Lansing, MI, USA

The purpose of this study was to compare the echocardiographic Doppler blood pressure and heart rate e¡ects of 1:1 thiopental/propofol with thiopental and propofol, when used as anesthesia-induction agents. Seven healthy dogs (six Beagles and one Pembroke Welsh Corgi), ranging in age from 1 to 9 years and weighing14.2  2.4 kg (mean  SD), were used during the study. In a cross-over study design with a minimum drug interval of 3 days, each dog received propofol, thiopental, or a mixture of propofol^thiopental IV until each dog received all the three anesthetic agents. An initial dose (propofol 4.9  0.8 mg kg1; thiopental 12.9  2.4 mg kg1; propofol^ thiopental 2.3  0.3 mg kg1 (P)5.7  0.8 mg kg1 102

(T)) of each anesthetic agent was titrated IV until intubation was accomplished. Echocardiographic Doppler blood pressure and heart rate variables were recorded prior to anesthesia and at 1, 5, and 10 minutes after induction of anesthesia. ANOVA and the Bonferroni’s t-test were used to evaluate the groups for di¡erences. Alpha was <0.05. There was no signi¢cant e¡ect of treatment on systolic or diastolic ventricular wall thickness, septal thickness, left atrial diameter, or systolic left ventricular diameter. There was a tendency for diastolic left ventricular diameter to decrease over time. There was a tendency for heart rate to increase with a signi¢cant di¡erence at the 10-minute time period between propofol (109  26 beats minute1) and thiopental (129  23 beats minute1). At the10-minute recording period, heart rate following the propofol/thiopental mixture (110  34 beats minute1) was closer to that following propofol than to that following thiopental.With all induction agents, indirect blood pressure tended to decrease over time (p ¼ 0.005); however, there was no di¡erence between the groups. The changes observed were not considered to be of clinical signi¢cance. The propofol/thiopental mixture produces similar changes in echocardiographic variables when compared to propofol or thiopental, and could be substituted for propofol for induction of anesthesia in dogs.

Cardiovascular effects of propofol alone and in combination with ketamine for total intravenous anesthesia in healthy cats JE Ilkiw, PJ Pascoe University of California-Davis, Davis, CA, USA

This study was designed to compare the cardiovascular e¡ects of equipotent maintenance of anesthetic doses (determined in a previous study) of propofol and propofol/ketamine, administered with and without noxious stimulation. Six healthy adult cats were anesthetized with propofol (loading dose 6.6 mg kg1, infusion 0.22 mg kg1 minute1), and instrumented to allow determination of blood gas and acid^base balance and measurement of blood pressures and cardiac output. The propofol infusion was continued for a further 60 minutes after which measurements were taken prior to and during application of a noxious stimulus. The propofol infusion was decreased to 0.14 mg kg1 minute1, and ketamine (loading dose 2 mg kg1, infusion 23 mg kg minute1) was administered. After a further 60 minutes, measurements were # Association of Veterinary Anaesthetists, 2003, 30, 99^119

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

again taken prior to and during application of a noxious stimulus. The data were analyzed, using several Repeated Measures ANOVA (¢rst, ketamine/propofol and noxious stimulation were each treated as within-subject factors; secondly, the levels of these two factors were combined into a single within-subject factor). Mean arterial pressure, CVP, PAOP, SI, CI, SVRI, PVRI, oxygen delivery index, oxygen consumption index, oxygen utilization ratio, PvO2, pHa, PaCO2, bicarbonate concentration, and BD values collected during propofol administration were not changed by addition of ketamine and reduction of propofol concentration or by application of a noxious stimulus under propofol alone. Application of a noxious stimulus under propofol alone did, however, signi¢cantly increase HR and PaO2, and these responses were not blunted by the addition of ketamine. Compared with propofol, administration of ketamine and reduction of propofol concentration signi¢cantly increased PAP and venous admixture, and signi¢cantly decreased PaO2. Although application of a noxious stimulus to cats under propofol alone did not signi¢cantly change CVP, SI, CI, PVRI, oxygen delivery index, and oxygen consumption index, signi¢cant di¡erences were found in these variables between propofol and propofol/ketamine. In conclusion, propofol alone provided cardiopulmonary stability; addition of ketamine did not improve hemodynamics but did decrease oxygenation.

Effect of pre-medication on gastroduodenoscopy in isoflurane-anesthetized cats AA Smith, LP Posner, RE Goldstein, JW Ludders, HN Erb, KW Simpson, RD Gleed Cornell University, Ithaca, NY, USA

The pre-medicant chosen may in£uence the ease with which gastroduodenoscopy (GD) is performed. The purpose of this study was to evaluate the relative ease of GD in cats under ketamine and iso£urane anesthesia after IM injection of hydromorphone (H, 0.1 mg kg1), hydromorphone plus glycopyrrolate (HG, 0.1 mg kg1 (H), 0.01 mg kg1 (G)), medetomidine (M, 0.03 mg kg1), or butorphanol (B, 0.4 mg kg1). Eight cats were assigned randomly to receive each treatment in a cross-over design with at least 7 days between treatments. Twenty minutes after pre-medication, medetomidine produced greater (p ¼ 0.001) # Association of Veterinary Anaesthetists, 2003, 30, 99^119

sedation than the other treatments when assessed, using a subjective ordinal scale. The cats were injected with ketamine (10 mg kg1 IM), orotracheally intubated, connected to a pediatric circle breathing system, and allowed to spontaneously breathe iso£urane in oxygen. Once end-tidal iso£urane concentration was stable at 1.4% for 15 minutes, endoscopy was started. A single endoscopist (REG), who was unaware of the treatment used, performed all endoscopies. The endoscopist scored the di⁄culty of endoscopy subjectively (0^3). The signi¢cance of differences between treatments was evaluated using Friedman’s test. Time for entering the stomach was 9.4 (4.7^15.9) (median (minimum^maximum)), 6.6 (5.2^11.7), 8.4 (6.3^16.5), and 7.7 (5.1^14.7) seconds and for entering the duodenum from the stomach was 20.5 (13.8^ 40.9), 18.2 (10.3^39.8), 20.2 (16.2^119.5), and 22.2 (11.8^83.8) seconds for H, HG, M, and B treatments, respectively. There were no signi¢cant di¡erences in the time for, or di⁄culty of, endoscopy. We conclude that any of these drugs can be used satisfactorily at the doses and combinations tested to pre-medicate cats prior to general anesthesia for GD.

Comparison of sevoflurane and isoflurane anesthetic index in unpremedicated dogs DS Galloway, JCH Ko, RE Mandsager, HF Reaugh, ME Payton, E Portillo Oklahoma State University, Stillwater, OK, USA

Anesthetic respiratory e¡ects of sevo£urane (SEVO) were compared with iso£urane (ISO) in unpremedicated dogs. Minimum alveolar concentration (MAC), apneic concentration (AC), and anesthetic index (AI) of SEVO and ISO were determined in eight 1-year-old healthy dogs, weighing 19  3 kg (mean  SEM) in a randomized complete block multiple cross-over design. Dogs were mask-induced with either SEVO or ISO in100% oxygen. Following endotracheal intubation, dogs were instrumented, mechanically ventilated, and MAC was determined using a tail-clamp method. Next, spontaneous ventilation was re-established, and anesthetic concentration was increased to determine the AC. Throughout the anesthetic event, heart rate (HR), systolic blood pressure (SAP), mean blood pressure (MAP), diastolic blood pressure (DAP), respiratory rate (RR), end-tidal carbon dioxide (PE0 CO2), and oxyhemoglobin saturation (SpO2) were recorded at 3-minute intervals. Following AC determination, AI was calculated as AC/MAC, and dogs 103

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

were allowed to recover. Each dog was anesthetized four times (twice with ISO and SEVO each) at 1-week intervals. All data were analyzed using the two-way ANOVA. Multiple comparisons were performed between ISO and SEVO treatments. Statistical signi¢cance was set at p < 0.05. Signi¢cant di¡erences were noted between agents for MAC (SEVO, 2.13  0.10%; ISO, 1.38  0.14%; p < 0.0001), AC (SEVO, 7.34  0.13%; ISO, 3.60  0.13%; p < 0.0001), and AI (SEVO, 3.46  0.22; ISO, 2.63  0.14; p ¼ 0.0002). Physiologic parameters were compared between SEVO and ISO at 1MAC, 2MAC, 3MAC, and AC. No di¡erences were noted between SEVO and ISO treatments for cardiovascular parameters (HR, SAP, MAP, DAP). Signi¢cant di¡erences were noted, favoring SEVO, for all respiratory parameters (RR, PE0 CO2, SpO2) at increasing MAC multiples. Additionally, regression analysis was conducted for physiologic variable data points. Analysis of PE0 CO 2 data points demonstrated a signi¢cant slope di¡erence of 6.47  1.02 (BSEVO  BISO; p < 0.0001; r2 ¼ 0.6042) favoring SEVO.While expected dose-related ventilatory depression was noted for both agents, all the respiratory parameters for SEVO demonstrated less respiratory depression than ISO at equipotent doses. These results indicated that SEVO caused less dose-dependent ventilatory depression than ISO, having a signi¢cantly higher AI and causing less detrimental change in pulmonary parameters at increasing levels of MAC.

Effect of intravenous lidocaine on isoflurane MAC in dogs AValverde,y,TJ Doherty,z, J Herna¤ndezy,W Daviesy yUniversity of Florida, Gainesville, FL, USA zUniversity ofTennessee, Knoxville,TN, USA

Lidocaine decreases minimum alveolar concentration (MAC) of inhalational anesthetics. This study determined the in£uence of a low dose, 50 mg kg1 minute1 (LDI) and high dose, 200 mg kg1 minute1 (HDI) constant rate infusion of lidocaine on the MAC of iso£urane (I) in dogs. Ten mongrel dogs were anesthetized with I in oxygen and mechanically ventilated. End-tidal anesthetic (FE0 A) and CO2 (PE0 CO2) concentrations were monitored at the endotracheal tube adaptor with an infrared gas analyzer calibrated before each experiment with a standardized calibration gas mixture designed for the analyzer. PE0 CO2 and body temperature were maintained within normal limits. Noxious 104

stimuli included clamping the hindlimb paw (HC) and electrical current (50 Vat 50 cycles second1 for 10 milliseconds pulse1) applied subcutaneously to the forelimb (FE) at the level of the ulna. After an initial equilibration period of at least 40 minutes at an FE0 A of 1.7%, the FE0 A was decreased to a value close to the estimated MAC for dogs. MAC was de¢ned as the FE0 A mid-way between the value permitting and preventing purposeful movement. Following baseline MAC, a loading dose of 2 mg kg1 of lidocaine IV was administered over 3 minutes followed by the LDI, and MAC determinations for the combination started after 30 minutes of infusion. Once determined, the lidocaine infusion was stopped for 30 minutes and the dog maintained at the ETC that prevented movement without the lidocaine. Following this period, a second loading dose of lidocaine was given (2 mg kg1) over 3 minutes followed by the HDI, and the MAC determination procedure repeated after 30 minutes of infusion. Data were analyzed using an ANOVA for repeated measures. MAC of I was 1.34  0.035% (mean  SEM) for both the FE and HC stimuli. The LDI signi¢cantly decreased MAC to 1.09  0.043% (18.7% reduction) and HDI to 0.76  0.030% (43.3% reduction). In conclusion, lidocaine infusions decreased the MAC of iso£urane in a dose-dependent manner.

Measurement of cardiac output by transesophageal Doppler ultrasonography in anesthetized dogs: comparison with thermodilution T Lazic, DH Riedesel, RB Evans Iowa State University, Ames, Iowa, IA, USA

Thermodilution (TD) is the standard method for cardiac output (CO) monitoring in human medicine. Although called the ‘gold standard’, TD is related to numerous complications and data misinterpretations. Recently, a noninvasive, continuous, ultrasound-based technique for CO measurement has been developed (Hemosonic 100, Arrow Intl). This study compared transesophageal Doppler ultrasonography (TED) for measuring CO with TD in anesthetized dogs. In this study, ten dogs were used to simultaneously measure CO by TED and TD. All dogs were pre-medicated with acepromazine at 0.1 mg kg1 IM, induced with thiopental at 10 mg kg1 IV, and maintained on iso£urane at end-tidal concentrations of 1.3%. Baseline and four di¡erent levels of CO were used for comparison. Low CO levels were induced by caudal vena # Association of Veterinary Anaesthetists, 2003, 30, 99^119

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

cava occlusion. High CO levels were induced by the constant IV infusion of dopamine, dobutamine, or norepinephrine. Each level of CO allowed one comparison between TED and TD. Forty-nine paired comparisons of CO were determined ranging from 0.73 to10.9 L minute1. Simple linear regression was used to determine the correlation between the two techniques. Correlation coe⁄cient (r2) was 0.53. Bland and Altman statistical method was used for assessing agreement between the two methods. The di¡erence between the TD and TED when all data were included was 0.82 (bias)  1.63 L minute1 (mean  SD). At low CO levels (baseline and caudal vena cava occlusion), the correlation coe⁄cient was 0.77, bias was 0.35  0.64 L minute1. At high CO levels (dopamine, dobutamine, or norepinephrine), the correlation coe⁄cient was 0.39. It was concluded that TED was not a reliable monitoring method in determining CO when positive inotropes were used. TED might have importance in situations of low CO values; however, further investigation is warranted.

Inhalant anesthetic requirement in cats is animal-dependent LS Barter, JE Ilkiw, EP Ste¡ey, BH Pypendop, A Imai, JA Bolich University of California-Davis, Davis, CA, USA

Minimum alveolar concentration (MAC) of an inhalant is an indicator of its anesthetic potency. Individuals vary in their sensitivity to anesthetic agents as demonstrated by di¡erent individual MAC values.We hypothesized that individual animal sensitivity would be maintained with di¡erent inhalant anesthetics. As part of separate studies, six female DSH cats, aged 24  2.5 (mean  SD) months and weighing 3.5  0.3 kg, were studied similarly on three separate occasions over a 12-month period to determine the MAC of iso£urane (ISO), sevo£urane (SEVO), and des£urane (DES), respectively. In each study, chamber induction was followed by orotracheal intubation, and anesthesiawas maintained via a nonrebreathing circuit. ECG, pulse oximetry, Doppler systolic blood pressure, end-tidal gases, and esophageal temperature were monitored. End-tidal gases were handsampled from a catheter whose tip lay level with the distal end of the ET tube. Gases were analyzed by Raman spectrometry and, for each agent, the analyzer was calibrated with at least three gas standards. MAC was determined in triplicate using standard # Association of Veterinary Anaesthetists, 2003, 30, 99^119

tail-clamp technique. Data were analyzed by twoway ANOVA followed byTukey’s test and signi¢cant differences were found. Average MACs (%) for ISO, SEVO, and DES were 1.90  0.18, 3.41 0.65, and 10.27  1.06, respectively. Body temperatures, Doppler systolic blood pressure, and SpO2 were recorded at the time of MAC determinations for ISO, SEVO, and DES were 38.3  0.3, 38.6  0.1, 38.3  0.35 8C; 71  8, 75  16, 88  12 mm Hg; 99  1, 99  1, 99  1%, respectively. Both the anesthetic agent and the individual cat had signi¢cant e¡ects on MAC (p ¼ 0.0001 and 0.0185, respectively). MAC varied between individuals and cats were consistent in their order of sensitivity to inhalant anesthetics across the three agents. Within this group of cats, the relationship of individual MAC to the group MAC for each of the three inhalant agents was maintained. This suggests that any individual may be consistently more or less sensitive to a variety of inhalant agents.

Hemodynamic effects of sevoflurane in spontaneously breathing cats BH Pypendop, JE Ilkiw, JA Bolich University of California-Davis, Davis, CA, USA

Sevo£urane has recently been introduced in feline anesthesia. However, its cardiovascular e¡ects have not, to our knowledge, been reported in this species. Six healthy cats, aged 1.81 0.31 years (mean  SEM) and weighing 3.47  0.11 kg, were studied. Anesthesia was induced and maintained with sevo£urane in oxygen. Body temperature was maintained between 38.5 and 39.55 8C. After instrumentation, end-tidal sevo£urane concentration was randomly set at1.25,1.5, and1.75 times the individual minimum alveolar concentration (MAC), determined in a previous study, according to a Latin Square Design. Thirty minutes of stabilization was allowed after each change of concentration. ECG and heart rate, systemic and pulmonary arterial pressures, central venous pressure (CVP), and core body temperature were continuously monitored and recorded. Inspired and end-tidal oxygen, carbon dioxide, and sevo£urane concentrations were measured using a Raman spectrometer, calibrated every 80 minutes with three calibration gases of known sevo£urane concentration (1, 2, and 5%). Moreover, at selected times, pulmonary artery occlusion pressure and cardiac output (thermodilution) were measured, and arterial and mixed venous blood samples were collected for pH and blood gas analysis, hemoglobin 105

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

concentration, hemoglobin oxygen saturation, packed cell volume (PCV) and total protein determination, and lactate concentration measurement. Cardiac index (CI), stroke index (SI), systemic and pulmonary vascular resistance indices, rate-pressure product, left and right ventricular stroke work indices (LVSWI and RVSWI, respectively), arterial and mixed venous oxygen contents, oxygen delivery, oxygen consumption, and oxygen utilization ratio were calculated. Data were analyzed by a Repeated Measure Latin Square Design followed by a Tukey’s test for 2 2 comparisons. Arterial pH signi¢cantly decreased from 7.40  0.05 to 7.29  0.07 with the administration of increasing concentrations of sevo£urane. Similarly, LVSWI decreased from 3.72  0.60 to 2.60  0.46 g m2. Mean arterial pressure, PaO2, mixed venous pH, CI, SI, and oxygen delivery tended to decrease dose-dependently, whereas CVP, PaCO2, PVCO2, PCV, and arterial and mixed venous hemoglobin concentrations tended to increase dose-dependently with the administration of sevo£urane. However, these trends did not reach statistical significance, possibly because of the limited number of animals studied. Sevo£urane seemed to induce dose-dependent cardiovascular depression in cats.

Quantitative characteristics of anesthetic induction with and recovery from isoflurane and sevoflurane in cats A Imai, EP Ste¡ey, JE Ilkiw, BH Pypendop University of California-Davis, Davis, CA, USA

Iso£urane (ISO) is the most commonly administered feline inhalant anesthetic in North America. A newer agent, sevo£urane (SEVO), may provide faster induction and recovery from anesthesia based on its physical characteristics. Accordingly, we compared some induction and recovery characteristics of ISO and SEVO in healthy cats. Six female DSH cats (17.9  9.0 (mean  SD) months, 3.7  0.3 kg) received four randomly assigned treatments: ISO for 1 hour (IS), SEVO for 1 hour (SS), ISO for 5 hours (IL), and SEVO for 5 hours (SL). Anesthesia was induced in a chamber into which ISO or SEVO was delivered at 2.7 times the individual’s MAC (determined previously) in 6 L minute1 O2. Measured (Rascal II, Ohmeda) anesthetic concentration was reported after correction using a multiple gas, standard-de¢ned calibration curve. For induction, time (seconds) from 106

introduction of inhalant to onset of incoordinated movement (IM), recumbency with movement (RM), recumbency without movement, loss of pedal re£ex (PD), and intubation (ET) were recorded. Following intubation, anesthesia was maintained for the required time at 1.25 times the individual’s MAC. For recovery, time (seconds) from discontinuation of the inhalant (with continuation of O2) to ¢rst movement, extubation (EXT), start of incoordinated movement, head-lift, sternal recumbency (SR), crawl, stand/ walk with incoordination, and jump without incoordination were recorded. Esophageal normothermia was maintained. Data were analyzed by paired t-test (induction) or One-way Repeated Measures ANOVA followed, when appropriate, by Tukey’s test (recovery). p < 0.05 was regarded as signi¢cant. For induction, IM was not signi¢cantly di¡erent between ISO and SEVO (118  28 seconds vs. 104  28 seconds). All other induction times were signi¢cantly shorter with SEVO vs. ISO, e.g. RM (181  31 seconds vs. 213  31 seconds), PD (426  68 seconds vs. 504  70 seconds), and ET (434  66 seconds vs. 515  69 seconds). For recovery, there were no di¡erences between ISO and SEVO for any stage of recovery, e.g. EXT (IS 588  163 seconds vs. SS 425  109 seconds), SR (IS 735  215 seconds vs. SS 655  337 seconds), and IL (710  658 seconds vs. SL 807  465 seconds). We concluded that quantitative recovery characteristics did not depend on whether cats are anesthetized with equipotent amounts of SEVO or ISO, but some induction end-points were reached more quickly with SEVO.

Validation of the MAC technique in dogs and rabbits AValverde, J Herna¤ndez,W Davies University of Florida, Gainesville, FL, USA

Minimum alveolar concentrations (MAC) are determined using one of the di¡erent noxious stimuli (clamping, electrical stimulation, or surgical incision), based on a study conducted in the 1960s with three dogs. This study compares di¡erent noxious stimuli applied in a randomized order in dogs (n ¼ 10) anesthetized with iso£urane (I) and halothane (H), and in rabbits (n ¼ 10) anesthetized with I. Anesthesia was induced with the anesthetic in oxygen and maintained with mechanical ventilation. End-tidal anesthetic (FE0 A) and CO2 (PE0 CO2) concentrations were monitored with a calibrated infrared gas analyzer. PE0 CO2 and body temperature were # Association of Veterinary Anaesthetists, 2003, 30, 99^119

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

maintained within normal limits. Noxious stimuli included skin incision on the lateral chest (SI), clamping of the tail (TC), fore- (FC) and hindlimb paw (HC), and electrical current (50 V at 50 cycles second for 10 msecond pulses) applied to the fore- (FE) and hindlimb (HE), and oral mucosa (OE) (except rabbits). SI was applied ¢rst and only for the ¢rst two consecutive measurements using the up^down method for sequential sampling of quantal-response data. After an initial equilibration period of at least 20 minutes at an FE0 A of 1.4% (H) or 1.7% (I), the FE0 A was decreased in the ¢rst animal to 0.85% of H (dog) or 1% of I (dog and rabbit) and maintained for at least 20 minutes before the noxious stimuli. If the animal responded or did not respond, the stimuli were then tested at an FE0 A 0.1% higher or lower, respectively. The new FE0 A was kept constant for at least 20 minutes and the noxious stimuli repeated until purposeful movement ceased or returned, respectively. MAC was de¢ned as the FE0 A mid-way between the value permitting and preventing purposeful movement. Data were analyzed using an ANOVA. MAC for I in dogs was 1.27  0.047 (mean  SEM) for TC, FC, and HC; 1.36  0.035 for OE; 1.35  0.040 for FE and HE; and 0.99 for SI. MAC for H in dogs was 0.97  0.028 for TC; 0.96  0.032 for FC and HC; 1.04  0.033 for OE, FE, and HE; and 0.73 for SI. MAC for I in rabbits was 2.08  0.021 for TC, FC, and HC; 2.04  0.023 for FE and HE; and 0.90 for SI. MAC for SI was signi¢cantly lower than the other methods. In conclusion, electrical current and clamping resulted in similar MAC values. Effect of 0.1, 0.2, 0.4, and 0.8 mg kg1 of intravenous butorphanol on thermal antinociception in cats SA Robertson,y, BDX Lascellesz, PM Taylor‰ yUniversity of Florida, Gainesville, FL, USA zNorth Carolina State University, Raleigh, NC, USA ‰University of Cambridge, Cambridge, UK

Many cats do not receive analgesics for treatment of perioperative pain, but when they do, the opioid agonist^antagonist butorphanol (B) is widely used. B is reported to provide long-lasting visceral analgesia, but its somatic actions are not well documented. This study aimed to assess B by using a thermal threshold (TT) model. Six cats (four spayed females, two castrated males, 4.4^6.9 kg) participated in the study. The day before each study, the lateral thorax of each of the cats was shaved and a cephalic catheter was placed. TT was measured using a thermal threshold testing device # Association of Veterinary Anaesthetists, 2003, 30, 99^119

speci¢cally developed for cats. A heater element and temperature sensor housed in a small probe was held against the cat’s thorax with an elastic band and pressure bladder to assure consistent contact. Skin temperature was recorded before each test, then the heater was activated. When the cat responded by £inching, turning, or jumping, the stimulus was terminated and the threshold temperature recorded. A cut-out temperature was set at 55.5 8C. Three baseline measurements were recorded before IV injections of 0.1, 0.2, 0.4, or 0.8 mg kg1 of B. Each cat received all doses in a randomized order at least 1 week apart, and the investigator was blinded to the treatments. TT was measured at every 15 minutes for 6 hours. Data were analyzed using a three-factor ANOVA, and the critical mean di¡erence was calculated. Pre-treatment threshold was 40.8  2.25 8C in all cats. There was a signi¢cant increase in threshold in all groups from15 to 90 minutes, but no dose-related di¡erences were observed. Peak threshold achieved was 48.35 8C, 60 minutes after 0.4 mg kg1 of B was injected. Mydriasis was present in all cats after treatment, and many exhibited dysphoric behavior. In this model, B had a short duration of action and no dose^response relationship. Compared to other opioids tested under similar conditions, the intensity of the e¡ect of B was small and of shorter duration. Thermal antinociceptive pharmacodynamics of 0.1 mg kg1 hydromorphone administered intramuscularly in cats and effect of concurrent butorphanol administration BDX Lascellesy, SA Robertsonz, PM Taylor‰, J Hauptmanô yNorth Carolina State University, Raleigh, NC, USA zUniversity of Florida, Gainesville, FL, USA ‰University of Cambridge, Cambridge, UK ô Michigan State University, East Lansing, MI, USA

Hydromorphone (HY) has not been objectively assessed as an analgesic in cats. It has been suggested that butorphanol (B) can have a synergistic action with pure m-agonists. The aim of this study was to assess the antinociceptive activity of a single dose of HY, and to examine the e¡ect of concurrent B administration on the thermal threshold (TT). Thermal thresholds were measured following IM administration of HY, B, a combination of B and HY (HY-B), or saline (S). Six cats (four spayed females, two castrated males, 4.75^6.8 kg) were used. Each cat received HY (0.1 mg kg1), B (0.4 mg kg1), HY (0.1 mg kg1), and B (0.4 mg kg1) (HY-B), or S (0.05 mL kg1) in a randomized, blinded, cross-over 107

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

study design. Each cat received each treatment, with at least 12 days interval between the treatments. All injections were IM randomized to left or right quadriceps using a 24 SWG needle.Twenty-four hours prior to each study, the thorax of each of the cats was shaved. On the day of the study, TT was measured using a thorax-mounted thermal threshold-testing device speci¢cally developed for cats. Skin temperature was recorded before each test and then the heater was activated. When the cat responded by £inching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. Three baseline thresholds were recorded over 1 hour before IM injection of test drug. Thermal threshold cut-o¡ was 55.5 8C. TT was measured at 5 and 15 minutes, every 15 to 360 minutes, every 30 minutes to 8 hours, every hour to 12 hours, and at 24 hours post-injection. Threshold data were analyzed using an ANOVA with a repeat factor of time. Behavioral adverse e¡ects (dysphoria) were associated with B administration, but not with HYor HYB administration (these produced calm euphoria). The control group was stable over time (p ¼ 0.22) (mean threshold 40.15 8C). Overall, there was no period e¡ect, no signi¢cant e¡ect of administering B, but a signi¢cant e¡ect (raised TT) of administering HY or HY-B. If the mean value of one of the experimental groups di¡ered from the control group (40.075 8C) by more than 2.355 8C (>42.425 8C), that mean was signi¢cantly di¡erent from control at p < 0.05 (Bonferroni’s t-tests). This occurred between 15 and 165 minutes for B, from 15 to 345 minutes for HY, and between15 and 540 minutes for HY-B. In this model, HYprovided up to 5.75 hours of antinociception at 0.1 mg kg1, and concurrent administration of butorphanol (0.4 mg kg1) decreased the intensity of antinociception over the ¢rst 2 hours, but extended the duration of signi¢cant antinociception to about 9 hours. Comparison of the pharmacokinetics and thermal antinociceptive pharmacodynamics of 20 lg kg1 buprenorphine administered sublingually or intravenously in cats BDX Lascellesy, SA Robertson,z, PM Taylor‰, J Hauptmanô yNorth Carolina State University, Raleigh, NC, USA zUniversity of Florida, Gainesville, FL, USA ‰University of Cambridge, Cambridge, UK ôMichigan State University, East Lansing, MI, USA

Little is known about the analgesic action of buprenorphine (BUP) in cats. Relative to man, the cat has 108

a more alkaline oral pH, which may make this an e¡ective route for administering BUP in this species. This study aimed to assess and compare the pharmacokinetics and pharmacodynamics of sublingual (SL) and IVadministration of BUP. Thermal threshold (TT) was measured and blood samples were collected following IV or S-L administration (20 mg kg1) of the injectable formulation. Six cats (¢ve spayed females, one castrated male, 4.1^6.6 kg) were used. Each cat received both treatments in a randomized cross-over study design with 1 month between experiments. Twenty-four hours prior to each study, the lateral thorax of each of the cats was shaved, cephalic and jugular catheters placed, and oral pH measured. On the day of the study, TT was measured using a ‘thorax-mounted’ thermal threshold-testing device speci¢cally developed for cats. The cats were free to move around. Skin temperature was recorded before each test, then the heater activated. When the cat responded by £inching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. The thermal threshold cut-o¡ point was 55.5 8C. Three baseline thresholds were recorded before treatment with S-L or IV (via cephalic catheter) BUP (20 mg kg1). Blood was withdrawn (jugular) at 1, 2, 4, 6,10,15, 30, 45, 60 minutes and at 2, 4, 6, 8, 12, and 24 hours post-administration. TT was measured every 30 minutes6 hours, 1^12 hours, and at 24 hours post-administration. Plasma was immediately separated, stored at 20.5 8C, and assayed within 4 months using a commercially available 125I radioimmunoassay. Threshold data were analyzed using ANOVA with a repeat factor of time. No adverse e¡ects were noted. Pupils were dilated for up to 9 hours post-BUP. Behavioral changes were calm euphoria. Measured oral pH was 9 in each cat. Pre-treatment mean threshold (SD) was 41.2  0.9 8C in the S-L group and 40.8  0.85 8C in the IV group. There were no signi¢cant di¡erences between the groups with respect to thresholds over time (p ¼ 0.72). Thresholds were signi¢cantly increased from 30 to 360 minutes in both the groups (>44.615 8C). Peak plasma BUP (Cmax) was lower (11  6.7 ng mL1 vs. 92.9  107.9 ng mL1) and occurred later (Tmax) (30 minutes vs. 1 minute) after S-L compared to IVadministration, respectively. BUP (20 mg kg1)-administered S-L or IV provided antinociception between 30 and 360 minutes after administration. Plasma levels did not correspond to TT. # Association of Veterinary Anaesthetists, 2003, 30, 99^119

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

Effect of low-dose ketamine on thermal thresholds in cats SA Robertson,y, BDX Lascellesz, PM Taylor‰ yUniversity of Florida, Gainesville, FL, USA zNorth Carolina State University, Raleigh, NC, USA ‰University of Cambridge, Cambridge, UK

The role of ketamine (K) in pain management is controversial. It is reported to provide visceral analgesia in cats. This study aimed to assess its somatic actions using a thermal threshold (TT) model. Six cats (four spayed females, two castrated males, 4.3^7.2 kg) participated in the study. The day before each study, the thorax of each of the cats was shaved and a cephalic catheter was placed.TT was measured using a device speci¢cally developed for cats. A heater element and temperature sensor housed in a small probe were held against the thorax of the cats with an elastic band and pressure bladder to assure consistent contact. The skin temperature was recorded before each test, then the heater was activated.When the cat responded by £inching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. Treatments were 2 mg kg1 of K (10 mg mL1), or 0.2 mL kg1 of saline (S) IV, given in a randomized cross-over design with at least 1 week between treatments. The investigator was blinded to the treatment. TT was measured thrice before treatment (baseline threshold) at 15 minutes, then every 30 minutes for 8 hours and once at 24 hours after injection. Data were analyzed using a four-factor ANOVA. Cats were sedated for 45 minutes following K treatment. There was no di¡erence in baseline TT between treatments (K ¼ 41.9  1.7 8C, S ¼ 41.0  1.45 8C), and no change in TT at any time in the S group. TT increased signi¢cantly at 15 and 30 minutes after K, then decreased below baseline values between 210 and 390 minutes, with a nadir of 38.8   1.05 8C at 390 minutes. During this time period, cats exhibited normal activity, but responses to thermal stimuli were exaggerated. This study suggested that K caused a delayed onset hyperalgesia in cats. Evaluation of intraperitoneal and subcutaneous lidocaine and bupivacaine for analgesia following ovariohysterectomy in the dog RE Carpenter, DV Wilson, AT Evans Michigan State University, East Lansing, MI, USA

Many dogs in private practice undergo ovariohysterectomy (OHE) without analgesics. The purpose of # Association of Veterinary Anaesthetists, 2003, 30, 99^119

this study was to determine if intraperitoneal (IP) and subcutaneous (SQ) lidocaine or bupivacaine provide analgesia following OHE. Thirty dogs presenting to the Veterinary Teaching Hospital for elective OHE were included in the study. All dogs were pre-medicated with acepromazine and butorphanol IM, induced with thiopental, and maintained with iso£urane. Dogs were randomly assigned to three groups: 10 received 8.8 mg kg1 2% lidocaine with epinephrine IP (LID), 10 received 2.2 mg kg1 0.75% bupivacaine IP (BUP), and 10 received 0.9% saline IP (SAL) upon completion of OHE. All IP doses were standardized to 0.88 mL kg1 with saline. An additional 2 mL of the assigned solution was placed SC as a splash block prior to incisional closure. Dogs were scored at 0.5, 1, 2, 3, 6, 8, and 18 hours post-extubation by one observer blinded to treatment status. Dogs were evaluated using a visual analogue scale (VAS) for pain and sedation, and a scoring system that included physiologic and behavioral variables. Dogs were given supplemental analgesia with 0.22 mg kg1 butorphanol  acepromazine if their VAS (pain) score was >50. Parametric variables were analyzed using Student’s ttest or Repeated Measures ANOVA as appropriate. Nonparametric variables were analyzed by w2-test. There were no signi¢cant di¡erences in age, weight, incision length, surgery time, anesthesia time, or total thiopental dose between groups. Peak pain scores for all groups occurred at 0.5 hour and returned to baseline by 18 hours. Dogs in the BUP group had signi¢cantly lower pain scores at 0.5 hour than did dogs in the SAL group. Seven out of 10 dogs in the SAL group, 4 out of 10 dogs in the LID group, and 2 out of10 dogs in the BUP group were given supplemental analgesia. No adverse side-e¡ects were observed. Our ¢ndings supported the use of IP and SC bupivacaine for post-operative analgesia following OHE in the dog.

Analgesic effect of pre-operative etodolac and butorphanol administration in dogs undergoing ovariohysterectomy T Inoue, JCH Ko, RE Mandsager, ME Payton, DS Galloway, DN Lange Oklahoma State University, Stillwater, OK, USA

The analgesic, bleeding, and renal e¡ects of dogs pre-medicated with etodolac with and without butorphanol were evaluated. 109

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

Twenty-four 1-year-old healthy dogs, weighing 19  3 kg (mean  SD) were randomly assigned to four treatment groups (n ¼ 6): control (C), etodolac (E), butorphanol (B), and etodolac with butorphanol (EB). Etodolac (12^14 mg kg1 PO) was given 1 hour before propofol induction and iso£urane maintenance anesthesia. Butorphanol (0.4 mg kg1 IV) was given immediately following endotracheal intubation. Control dogs received only propofol (8 mg kg1 to e¡ect) and iso£urane anesthesia. All dogs were mechanically ventilated to maintain PE0 CO2 between 35 and 45 mm Hg (4.7^6.0 kPa). Lactated Ringer’s solution was given at 10 mL kg1 hour1 during anesthesia. Plasma cortisol concentrations were assessed 1 day prior to surgery (baseline), immediately prior to anesthesia induction, and every 30 minutes until 5 hours following extubation, and 1 day after surgery. Total duration of anesthesia was 50 minutes and total surgery duration was 30 minutes. Iso£urane concentration area under the curve (AUC) over time during the anesthesia was compared among treatment groups. Buccal mucosal bleeding time (BMBT) was assessed 1 day before E administration and during surgery. Urine GGT to urine creatinine ratio, BUN, and plasma creatinine were taken daily from 1 day before to 3 days after surgery. Behavioral pain scores (numerical rating scale) were assessed by two observers blinded to the treatment during the 5-hour recovery period at 30 minute intervals until 3 hours, and again at 5 hours after extubation. All data were analyzed using ANOVA. Multiple comparisons were performed if the ANOVA was signi¢cant. Alpha value was set at 0.05. Plasma cortisol concentrations signi¢cantly increased from time of extubation in all the treatment groups. They did not return to the baseline until 5, 2.5, 1.5, and 1.5 hours after extubation in the C, B, E, and EB groups, respectively. Iso£urane AUC was not signi¢cantly di¡erent among treatment groups. Dogs treated with EB had signi¢cantly less behavioral pain than all other groups throughout the 5-hour recovery period. No signi¢cant di¡erence was found between treatment groups or within treatment groups over time in BMBT, or any renal variables. This study demonstrated that (i) pre-operative administration of E provides profound analgesia during the post-operative period without renal or bleeding side-e¡ects in dogs undergoing OHE; and (ii) a combination of butorphanol^etodolac provides the best analgesic e¡ect during the post-operative period based on the behavioral pain score.

110

Comparison of carprofen and butorphanol as post-surgical analgesics in cats MM Al-Gizawiy, EP Robinson University of Minnesota, St Paul, MN, USA

Post-operative pain management bya single subcutaneous (SC) injection of carprofen has been found to be e¡ective in cats and dogs. This clinical study compared the analgesic properties of injectable carprofen and butorphanol in 71 healthy cats (0.5^5 years, mean weight 3.24  0.61 kg) undergoing ovariohysterectomy. Cats were randomly assigned to three groups: Group C received carprofen 4 mg kg1 SC at intubation and sterile saline 0.08 mL kg1 SC at extubation; Group B received sterile saline 0.08 mL kg1 SC at intubation and butorphanol 0.4 mg kg1 SC at extubation; Group S received sterile saline 0.08 mL kg1 SC at intubation and extubation. All cats were pre-medicated with atropine (0.04 mg kg1 SC), acepromazine (0.02 mg kg1 SC), ketamine (5 mg kg1 SC), and induced IV with ketamine (5 mg kg1) and diazepam (0.25 mg kg1). Serum biochemistry values were taken at 24 and 48 hours post-surgically and compared to a pre-surgical baseline. Behavioral data were collected by a blinded investigator prior to surgery (baseline) and 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours post-surgery; the data were compiled into composite pain scores on a scale from 0 to 21 and complemented by visual analogue scores (VAS). Scoring was based on changes in behavior, posture, vocalization, and response to interactive stimulation. Cats with pain scores >12 were considered to be moderately painful, received meperidine (4 mg kg1 IM), and were excluded from further statistical analyses. Sixty of 71 cats completed the study. Anesthetic time was 88.5  21.8 minutes (mean  SD). Meperidine was given to one cat in C, three in B, and ¢ve in S. There were no signi¢cant di¡erences in biochemistry values. There were no signi¢cant di¡erences in pain scores between C and B at any time period; B and C pain scores were signi¢cantly lower than S at 1, 2, 12, 16, and 20 hours post-operatively, and C lower than S at 3 and 8 hours post-surgery. Pain scores decreased over the 24-hour study in all groups; the greatest decrease in each group was between 4 and 8 hours post-operatively. In this study, carprofen provided post-surgical analgesia comparable to butorphanol.

# Association of Veterinary Anaesthetists, 2003, 30, 99^119

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

The evaluation of analgesia provided by epidural ketamine in dogs with chemically induced synovitis SM Hamilton, RV Broadstone, SA Johnston Virginia^Maryland Regional College of Veterinary Medicine, Blacksburg,VA, USA

Ketamine, a noncompetitive NMDA receptor antagonist, has been shown to provide analgesia in some species. To target the NMDA receptor speci¢cally and to potentially minimize some untoward sidee¡ects, ketamine had been used epidurally.The objective of this study was to determine the analgesic e¡ect of epidurally administered ketamine in dogs with chemically induced synovitis. Sixteen healthy dogs were used. Dogs were anesthetized with propofol (4 mg kg1 IV). Synovitis was induced by injecting 1 mL of sodium urate crystal solution (10 mg mL1) into the right sti£e. Dogs were allowed to recover and the synovitis was allowed to develop for 12 hours. The dogs were then anesthetized again using propofol (4 mg kg1 IV). Lumbosacral epidural injections were performed with each dog receiving either 2 mg kg1 of ketamine (20 mg mL1) or an equal volume of placebo (sterile water containing not more than 0.1 mg mL1 benzethonium chloride). Analgesia was assessed at baseline and then at 12, 14, 16, 18, 20, and 24 hours after induction of synovitis. Ground reaction forces (peak vertical force and impulse area) and overall pain were measured using a force platform and a pain scoring system (numerical rating scale). Analysis of the data by Repeated Measures ANOVA showed that the dogs developed a signi¢cant lameness between the baseline and 12 hours. However, no signi¢cant di¡erence in ground reaction forces or total pain score was demonstrated between the treatment and control groups at any other time. In conclusion, ketamine administered epidurally at a dose of 2 mg kg1 did not provide signi¢cant analgesia in dogs with chemically induced synovitis. Comparison of opioid and alpha-2 adrenergic receptor location and density in the horse and dog using radioligand binding PW Hellyer, L Bai, J Supon, C Quail, AE Wagner, KR Mama, KR Magnusson Colorado State University, Fort Collins, CO, USA

As a result of the observed behavioral di¡erences between dogs and horses in response to opioid and a-2 adrenergic agonists, we tested the hypothesis that the distribution, density, and subtype of opiate and a-2 adrenergic receptors within the central # Association of Veterinary Anaesthetists, 2003, 30, 99^119

nervous system (CNS) are signi¢cantly di¡erent between the horse and the dog. Brain tissue was obtained following euthanasia as a secondary use of tissue from three dogs (3 years of age) at 126 days post-surgery and from three horses (2^5 years of age) at 72 days post-surgery. Animals were opioid- and a-2 agonist-free at the time of euthanasia. The brains were removed, sectioned coronally into 1 cm slabs, frozen in methylbutane cooled by liquid nitrogen, and stored at 70.5 8C. Receptor autoradiography was performed using established techniques. [3H]DAMGO, [3H]U-69593, and [3H]RX821002 were used for m-opiate, k-opiate, and a-2 adrenergic binding assays, respectively. Binding densities (fmol mg1 protein binding) were not a¡ected by di¡erences in brain size. Species di¡erences were analyzed separately for each major brain region by Repeated Measures ANOVA for subregions followed by Fisher’s protected LSD. p < 0.05 was considered signi¢cant. Only signi¢cant di¡erences were reported. There was higher binding of m-opiate receptors in the frontal cortex, left somatosensory cortex, colliculus (mid-brain), and granule cell layer of the cerebellum of the horse than that of the dog. There was higher binding to k-opiate receptors in the frontal cortex of the dogs compared to the horses, whereas binding to k-opiate receptors in the cerebellum was higher in horses. Binding to a-2 adrenergic receptors in the mid-brain was signi¢cantly higher in the dog than the horse. There was higher binding in the dorsomedial and dorsolateral periaqueductal grey matter of the dog as compared to the horse. These results suggest a neuroanatomical basis for the di¡erences in opioid and a-2 adrenergic pharmacodynamics observed between horses and dogs.

HORSES Cardiorespiratory effects of a cardioselective muscarinic antagonist in anesthetized horses FJ Teixeira Neto,WN McDonell,W Black, S Durongphongtorn University of Guelph, Guelph, ON, Canada

Treatment of bradycardia in horses has been historically ignored because of the motility depressant e¡ects of nonselective antimuscarinics. This study evaluated the cardiopulmonary e¡ects of a cardioselective (M2) muscarinic antagonist, methoctramine (MET), in anesthetized horses. In a previous in vitro study, we determined that supraphysiological doses of MET were necessary to inhibit acetylcholine111

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

induced longitudinal jejunal smooth muscle contractions in this species. Six adult horses were allocated to two treatments in a randomized complete block design. Anesthesia was induced with xylazine/ketamine, and maintained with halothane (1% end-tidal) and a constant infusion of xylazine (1 mg kg1 hour1) under mechanical ventilation. Invasive hemodynamic variables were monitored at baseline (approximately 45 minutes after induction) and for 120 minutes after MET or saline (control) had been injected. MET was titrated at 10-minute intervals (10 mg kg1 IV) until the heart rate (HR) increased at least 30% above the baseline, or a maximum cumulative dose of 30 mg kg1 had been injected. A person blinded to the treatment evaluated recovery scores and monitored intestinal auscultation until 24 hours after the end of anesthesia using previously published methods. Cardiovascular parameters were analyzed by ANOVA followed by a Dunnet’s test, and nonparametrical data were analyzed by a Mann^Whitney U-test (p < 0.05). Values were mean  SEM unless otherwise stated. MET signi¢cantly increased HR from baseline to 120 minutes post-injection (from 29  1 to 36  2 beats minute1 at 20 minutes). Thermodilution cardiac output (CO) and mean arterial pressure (MAP) were increased from baseline to 75 minutes post-MET injection (from 13.9  0.8 to 19.4  2.0 L minute1 for CO at 20 minutes, and from 82  3 to 103  5 mm Hg for MAP at 20 minutes). Recovery characteristics and bowel auscultation scores did not di¡er among the groups. The return to at least 75% of the maximum auscultation score occurred at 10 (8^18) hours [median (range)] for controls and at 9 (8^12) hours for MET. It was concluded that MET increased HR and improved hemodynamic function during halothane/xylazine anesthesia with no apparent e¡ect on return to full-bowel motility, as assessed by auscultation. Accordingly, M2 muscarinic antagonists might be represented as a safer alternative to treat intraoperative bradycardia in horse.

An ethogram of post-anesthetic recovery behaviors in horses: comparison of pre- and post-anesthetic behaviors LM Seibert,V Parthasarathy, CM Trim, SL Crowell-Davis University of Georgia, Athens, GA, USA

Pain management is an important post-operative concern. Pain scales may rely on the observer’s subjective assessment of the level of discomfort and may 112

not correlate with physiologic or pharmacologic measures of pain. The purpose of this study was to develop an objective measure of behavior in healthy pain-free horses recovering from anesthesia that could be used for comparison with the behavior of horses recovering from a surgical procedure. Focal sampling with videotape and observation was done on ¢ve healthy horses before anesthesia to establish baselines. Behavioral measures included head turns, tail swishes, eyelid aperture/size, ear position, angle of neck, weight shifts, and ambulation. Physiologic measures included heart rate, respiratory rate, and temperature. The horses were anesthetized for 2 hours with iso£urane, and in the recovery stall, data were collected continuously on videotape from the time of extubation to standing. Focal sampling of 15 minutes was repeated at 1, 2, 4, and 24 hours after the horses returned to their stalls. Video data were analyzed using the Noldus Observer Video Analysis System. A wide variation in behavior was observed between horses in the recovery stall. Observations at 1, 2, and 4 hours revealed change from the up/forward ear position to the down ear position, and a decrease in weight bearing of the hind limb from a baseline of 11^12 minutes out of 15 minutes to 7^ 9 minutes with an increase in toe pointing. Time spent standing was similar to baseline of 93.8%, and the neck angle was not changed from baseline of 173.58.Values had returned to baseline at 24 hours. Changes in behavior were induced by anesthesia alone and must be taken into consideration when evaluating analgesic treatments.

Endotracheal intubation in horses: a study of two cuff inflation pressures, correlation with liquid aspiration, and tracheal wall damage G Touzot-Jourde, NL Stedman, CM Trim University of Georgia, Athens, GA, USA

Nine adult horses were anesthetized for a nonsurvival abdominal adhesion study. Horses were randomly assigned into two groups to receive endotracheal tube cu¡ pressures of either 80 cm H2O (Group P80) or 120 cm H2O (Group P120). After intubation (Bivona 30 mm ID), anesthesia was maintained with iso£urane. Horses were ventilated 10 times per minute with a suitable inspiratory pressure to maintain PE0 CO2 in the 35^40 mm Hg (4.7^6.0 kPa) range. Cu¡ pressure was continuously monitored with a pressure transducer (TruWave, Baxter) calibrated to the atmospheric pressure and maintained at a constant # Association of Veterinary Anaesthetists, 2003, 30, 99^119

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

pressure. Twenty-¢ve millilitres of methylene blue dye in saline were instilled proximal to the cu¡ over 5 minutes. The horses were euthanized 123  23 minutes later (mean  SD). Immediately, the trachea was opened distal to the tip of the endotracheal tube, and the mucosa was observed for evidence of dye leaking past the cu¡. The cervical trachea was resected and the lumen exposed by a ventral longitudinal incision. Biopsies (1^2 rings) were obtained at mid-cu¡ level and distal to the tip of the endotracheal tube, and placed in formalin for later histologic examinations (H&E stain). Methylene blue stain was not observed distal to the endotracheal tube cu¡ in any horse.Visual examination of the tracheal mucosa revealed hyperemic or hemorrhagic lesions at the level of cu¡ contact both ventrally and dorsally. Histologic changes included epithelium damage, submucosal neutrophil in¢ltrates, and acute submucosal hemorrhages. P80 horses had none or focal to multifocal lesions on the ventral and dorsal aspects of the rings. P120 horses had multifocal to di¡use lesions on all aspects (dorsal, ventral, and lateral). We concluded that the endotracheal tube cu¡ produced a seal su⁄cient to prevent leakage at both pressures. Tracheal damages on gross and microscopic examinations were more severe and occurred more frequently at the higher cu¡ pressure.

Cardiopulmonary effects of diazepam/ ketamine/isoflurane or xylazine/ketamine/ isoflurane in foals undergoing abdominal surgery C Kerr, L Boure¤, S Pearce, C Martin,WN McDonell University of Guelph, Guelph, Ontario, Canada

The purpose of this study was to evaluate the cardiopulmonary e¡ects of anesthetic induction with diazepam/ketamine or xylazine/ketamine with subsequent maintenance of anesthesia using iso£urane in foals undergoing abdominal surgery. Seventeen foals underwent laparotomy at 7^ 10 days of age and a laparoscopy 7^10 days later. Foals were randomly assigned to receive xylazine (0.8 mg kg1)/ketamine (2 mg kg1) (X/K)(n ¼ 9) or diazepam (0.2 mg kg1)/ketamine (2 mg kg1) (D/ K)(n ¼ 8) for induction of anesthesia for both procedures. In all foals, anesthesia was maintained with iso£urane in oxygen with the inspired concentration adjusted to achieve adequate depth of anesthesia as assessed by an individual blinded to the treatments. IPPV was employed throughout using a tidal volume # Association of Veterinary Anaesthetists, 2003, 30, 99^119

of 10 mL kg1 adjusting the frequency to maintain eucapnia (PaCO2 35^45 mm Hg, 4.7^6.0 kPa). Cardiopulmonary variables were measured after induction of anesthesia prior to, during, and following surgery. To compare the measured cardiopulmonary variables between the two anesthetic regimes for both surgical procedures, results were analyzed using a three-way factorial ANOVA for repeated measures (p < 0.05). During anesthesia for laparotomy, mean CI and MAP ranged from 110 to 180 mL kg1 minute1 and 57^81 mm Hg, respectively, in the D/K foals and 98^171 mL kg1 minute1 and 50^66 mm Hg in the X/K foals. Overall, CI, HR, SAP, DAP, and MAP were signi¢cantly higher in foals in the D/K group versus the X/K group during this anesthetic period. During anesthesia for laparoscopy, mean CI and MBP ranged from 85 to165 mL kg1 minute1 and 67^83 mm Hg, respectively, in the D/K group, and 98^171 mL kg1 minute1 and 48^67 mm Hg in the X/K group. Only HR, SAP, DAP, and MAP were signi¢cantly higher in the D/K group versus X/K group during this latter anesthetic period. There were no signi¢cant di¡erences between groups during either surgical procedure for end-tidal iso£urane, PaO2, PaCO2, or pH. In conclusion, anesthesia of foals for laparotomy and laparoscopy with diazepam/ketamine/iso£urane is associated with less hemodynamic depression than with xylazine/ketamine/iso£urane.

A comparison of anesthetic risk factors and outcomes in light and draft horses CB Rileyy, DH Riedesel,z, IR Dohooy, CL Hat¢eldy, S Clinchy yUniversity of Prince Edward Island, Charlottetown, PEI, Canada zIowa State University, Ames, IA, USA

As a result of anatomic and physiologic di¡erences, draft breeds may be at greater risk of developing anesthetic complications. The aim of the study was to evaluate and compare anesthetic management of draft (DR) and light (LT) horses. A case-matched retrospective study of 371 clinical case records of DR (124 cases) and LT (247 cases) horses presented for general anesthesia between 1991 and 1998 was performed. Data were tabulated and comparisons were made using Student’s t-test (signi¢cance p < 0.05). Prior to induction, there were signi¢cant di¡erences in mean body weight, rectal temperature, PCV, RBC, and serum TP concentration between DR and 113

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

LT breeds. There were di¡erences in mean doses of pre-operative butorphanol (LT 21 mg kg1; DR 17 mg kg1), induction guaifenesin (LT 99 mg kg1; DR 88 mg kg1), and intraoperative ketamine (LT 0.35 mg kg1; DR 0.56 mg kg1) required. There were no signi¢cant di¡erences in the mean doses of preoperative xylazine, detomidine, or induction barbiturate administered.The mean, average, and maximum concentrations of inspired halothane were signi¢cantly higher for DR than for LT horses. Draft horses received 33% less intraoperative IV £uids (8.2 mL kg1 hour1) than LT horses. Mean anesthetic duration, time to extubation, and standing recovery were not signi¢cantly di¡erent. Induction complications were not reported for either group. Rates of occurrence of intraoperative bradycardia, hypercarbia, hypoxemia, and metabolic acidosis (SBE, TCO2, and bicarbonate concentration) did not di¡er signi¢cantly. Average MAP was greater in DR horses, but neither the degree nor the mean duration of hypotension di¡ered between DR and LT horses. Mean PaO2 was signi¢cantly lower in DR (246 mm Hg, 32.8 kPa) than in LT (305 mm Hg, 40.7 kPa) breeds. Draft horses were at greater relative risk of hypoventilation than LT horses. The greater MAP and requirement for halothane and intraoperative ketamine may indicate problems in achieving and maintaining a surgical plane of anesthesia. Draft horses may be at a greater risk of ventilation^perfusion mismatching.

Assessment of the Hemocue-b for measuring hemoglobin in horse blood H Chevalier, LP Posner, JW Ludders, HN Erb, RD Gleed Cornell University, Ithaca, NY, USA

Our purpose was to assess the accuracy and precision of a point of care hemoglobinometer (HemoCueB hemoglobin photometer) for measuring hemoglobin concentration in horse blood. Samples of jugular venous blood from 12 healthy adult horses were collected in EDTA. In order to test the device over a wide range of values, each sample was divided into nine aliquots, and autologous plasma was added or removed from the aliquots to produce blood with PCV values that approximated 5, 10,20,30,40,50,60,70, and 80%, respectively.The aliquots were rocked to ensure mixing of plasma and cells. Then hemoglobin by HemoCue-B (HbHQ) and hemoglobin by the cyanmethemoglobin method (HbCY) were measured on each aliquot. The PCV of each aliquot was also measured and this value was 114

used for subsequent analyses. To test repeatability, hemoglobin was measured twice by the HemoCue-B on approximately 40% samples. Samples with HbHQ >25.4 g dL1 required dilution prior to analysis. HbCY ranged from 1.6 to 33.4 g dL1. After regression, HbCY ¼ 0.16 þ 1.04 HbHQ (n ¼ 101; r2 ¼ 99.6%). By inspection of a modi¢ed Bland-Altman plot, HbHQ values <16 g dL1 closely approximated HbCY; however, at greater values, HbHQ underestimated HbCY by as much as 3.2 g dL1. The di¡erence between repeated measurements with the HemoCue-B was 0.02  0.16 g dL1 (mean  SD; n ¼ 10) and nonsigni¢cant. After regression, PCV ¼ 0.76 þ 2.78 HbHQ (n ¼ 101; r2 ¼ 99.4%). We conclude that HemoCue-B can be used to measure hemoglobin concentration in horse blood, and that it is accurate when hemoglobin is <16 g dL1. PCV can be estimated by multiplying HbHQ by 2.8 and then subtracting 0.8.

LLAMAS A comparison of two intramuscular doses of xylazine–ketamine combination and tolazoline reversal in llamas WR DuBois,TM Prado, JCH Ko, RE Mandsager, GL Morgan Oklahoma State University, Stillwater, OK, USA

The anesthetic and cardiorespiratory e¡ects of a low dose (LD, 0.4 mg kg1 xylazine and 4 mg kg1 ketamine) and a high dose (HD, 0.8 mg kg1 xylazine and 8 mg kg1 ketamine) of IM xylazine^ketamine combination were compared in a randomized cross-over study using six castrated male llamas. Three llamas in each dosage group (LDT, HDT) were assigned to receive IM tolazoline (2 mg kg1) after 30 minutes of recumbency. All IM injections were given in the semitendinosus or semimembranosus muscles. Pulse, respiratory rate, and indirect arterial blood pressure were recorded every 10 minutes, and hemoglobin oxygen saturation was recorded every 5 minutes during lateral recumbency. Samples for arterial blood gas analysis were collected 5 minutes following recumbencyand every 30 minutes thereafter. Base-to-apex ECG was monitored continuously. Analgesia was evaluated every 5 minutes by both a 30 minutes skin pinch and a needle prick of the toe. Most llamas breathed room air throughout anesthesia. Two llamas that developed severe hypoxemia (SpO2 < 75%) received 5 minutes of nasal oxygen insu¥ation, but were maintained # Association of Veterinary Anaesthetists, 2003, 30, 99^119

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

on room air for the rest of the anesthetic period. ANOVA for repeated measures and Tukey’s test were used to analyze cardiorespiratory data. Fischer’s exact test was used to compare the ability of each to provide >30 minutes of lateral recumbency and analgesia. A p-value < 0.05 was considered signi¢cant. Both dosages provided reasonably rapid induction following injection (LD: 10.8  6.3 minutes; HD: 5.0  1.1 minutes; p ¼ 0.07). Duration of lateral recumbency and analgesia were 34.7  6.7 and 27.3  4.6 minutes, respectively, in the LDT llamas. None of the three remaining LD llamas remained in lateral recumbency for longer than 12 minutes. Duration of lateral recumbency and analgesia were 87.3  18.5 and 67.7  16.0 minutes, respectively, for the HD llamas that did not receive tolazoline. The HDT llamas were recumbent for a signi¢cantly shorter time (43.3  0.6 minutes; p ¼ 0.05). The ability to provide >30 minutes of recumbency and analgesia was better in the HD group (6/6) than in the LD group (2/6) (p ¼ 0.03). No di¡erences between dosages were seen in pulse rate, respiratory rate, or arterial pressures. No ECG abnormalities were seen. Transient hypoxemia was seen in the ¢rst10 minutes of lateral recumbency in the HD group by both hemoglobin oxygen saturation (84  9.5%) and by blood gas PaO2 (44.5  5.8 mm Hg). It was concluded that the HD provided more consistent results than the LD, but induced transient hypoxemia. Tolazoline shortened the recovery time in llamas receiving the HD.

LABORATORY ANIMALS Urethane anesthesia in adult female rats: preliminary observations FJ Golder, SA Robertson, AValverde DC Bolser University of Florida, Gainesville, FL, USA

Urethane is widely used as a rodent anesthetic in the laboratory setting, and is characterized as producing long-lasting anesthesia. The purpose of this study was to evaluate the quality of anesthesia provided by a single dose of urethane based on the response to a noxious stimulus. If the quality of anesthesia was insu⁄cient to prevent gross purposeful movement (GPM), iso£urane was also administered until no response to noxious stimulation occurred. Five adult Harlan Sprague Dawley rats (6 months of age, 250^300 g) were given urethane (1.4 g kg1 IP) and evaluated for 120 minutes post-injection. If # Association of Veterinary Anaesthetists, 2003, 30, 99^119

the rats became laterally recumbent by 20 minutes post-injection, a large hemostat was positioned around the tail and the response to tail clamping was assessed. If no GPM occurred, an additional 20 minutes was allowed to elapse. If the rats were not laterally recumbent or GPM was present, they were placed in a chamber and iso£urane in oxygen was administered. Inspired iso£urane concentrations (ISO) were measured using a S/5 anesthetic gas analyzer (Datex-Ohmeda Division, Helsinki, Finland) calibrated before each experiment with a standardized calibration gas mixture (DOT-34 NRC 300/375 M1014, Datex-Ohmeda Division, Helsinki, Finland). A period of 20 minutes was allowed for equilibration to inspired ISO. The tail-clamp stimulus was then re-applied and the animal’s response recorded. If GPM was absent, ISO was lowered by 10^20% and an additional 20 minute interval elapsed. In contrast, if GPM was present, ISO was increased by 10^20%. This procedure was repeated until the ISO required to prevent GPM was determined in duplicate. The position within the estrus cycle in£uenced pain thresholds in the rats. As such, a vaginal smear was prepared from each rat and the position in the estrus cycle was determined based on vaginal cytology. Rats were euthanatized at the end of the study period. All values were mean  SD. Four rats became recumbent after urethane injection (time to recumbency: 45  17 seconds). Of these, two rats (one estrus, one metestrus) did not require iso£urane supplementation for the duration of the study. The three remaining rats (two metestrus, one estrus) required iso£urane supplementation. The mean ISO required to prevent GPM was 0.26  0.16%. Position within the estrus cycle did not appear to a¡ect the animal’s response to urethane. These results indicate that urethane anesthesia is not long lasting in all rats and provides variable quality of anesthesia. This is of particular concern in the laboratory setting where muscle relaxants are often administered to rats shortly after urethane injection.

Liposome-encapsulated oxymorphone prevents hyperalgesia for 7 days in a rat model of neuropathic pain LJ Smith, L Krugner-Higby, M Clark, AWendland,TD Heath University ofWisconsin, Madison,WI, USA

A delayed-release formulation of liposome-encapsulated oxymorphone (LEO) was produced using a 115

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

novel dehydration^rehydration technique. Preparations were standardized spectrophotometrically against a known concentration of the drug. The purpose of this study was to test the analgesic properties of LEO in a rat model of neuropathic pain. Sprague^Dawley rats were divided into control (non-neuropathic) and test (neuropathic) groups. Control and test groups were administered one SC injection of (i) vehicle liposomes (negative control treatment); (ii) liposome-encapsulated morphine, 2.8 mg kg1 (positive control treatment); or (iii) LEO, 1.2 mg kg1. All treatments were administered after baseline thermal withdrawal latencies (TWL) were determined (9.2  0.39 seconds (mean  SEM)). Test groups then underwent sciatic ligation to induce neuropathic pain. TWL were determined in all six groups (n ¼ 8) daily for 1 week. In a separate group of age-matched rats, blood (0.3 mL from the jugular vein) and urine (1^2 mL via metabolism cages) were collected daily for 7 days after administration of LEO (1.2 mg kg1). TWL did not change in the control rats given liposome-encapsulated sucrose or morphine. There was a small increase (p ¼ 0.04) in TWL in control rats given LEO, likely as a result of the relatively higher dose of oxymorphone compared with morphine based on receptor a⁄nity. TWL in test rats given blank liposomes decreased signi¢cantly (p < 0.001) by day 4 (7.1 0.5 seconds), with a maximal decrease by day 7 (5.1 0.36 seconds), indicating development of full hyperalgesia. In contrast, rats given liposome-encapsulated morphine or oxymorphone had no change in TWL at day 4, indicating that these preparations prevented hyperalgesia after a single injection. This treatment e¡ect persisted through day 7. Serum concentrations of oxymorphone after a single injection of LEO peaked at 4 hours (6.8  0.82 ng mL1) and were detectable through day 4 (0.98  0.003 ng mL1), while urine concentrations of drug were detectable through day 7. This result suggests that oxymorphone metabolites might have been responsible for the protracted analgesic response. The encapsulation e⁄ciency of oxymorphone using this novel technique was approximately 96%. In conclusion, liposome encapsulation of oxymorphone proved to be an e⁄cient mechanism to provide a delayed-release formulation of this opioid. This single dose of subcutaneously administered liposomeencapsulated oxymorphone was e¡ective in preventing hyperalgesia for 7 days in this animal model of neuropathic pain. 116

Liposome-encapsulated oxymorphone provides prolonged relief of post-surgical visceral pain in rats LJ Smith, L Krugner-Higby, M Clark, D Ney, E Dahly University ofWisconsin, Madison,WI, USA

A delayed-release formulation of liposome-encapsulated oxymorphone was produced using a novel dehydration^rehydration technique. The purpose of this study was to (i) compare the analgesic properties of this preparation with those of repeated injections of standard oxymorphone in rats with post-operative visceral pain and (ii) determine whether liposomeencapsulated oxymorphone di¡ered from standard oxymorphone in duration of the e¡ect. Visceral pain was elicited in approximately 300 g Sprague^Dawley rats by intestinal resection performed under iso£urane anesthesia. Rats were monitored with pulse oximetry; mean anesthesia time (35  10 minutes) did not di¡er between the groups. Rats were randomly divided into two groups: Group 1 received 1.2 mg kg1 liposome-encapsulated oxymorphone SC once at skin closure and 0.2 mL of saline SC every 4 hours; Group 2 received 0.2 mL liposome-encapsulated sucrose SC once at skin closure and 0.3 mg kg1 standard oxymorphone SC every 4 hours. In both groups, a behavioral ethogram for pain score (grooming, porphyrin staining, body position) was recorded every 4 hours for 48 hours after surgery. Observers were blinded to the treatment. Body weight, food consumption, and urine output were recorded daily for 7 days after anesthetic recovery. Data were analyzed using ANOVA, with signi¢cance at p < 0.05. Based on the behavioral pain score, a single injection of liposome-encapsulated oxymorphone was as e¡ective for relief of post-surgical visceral pain in rats as multiple (every 4 hours) injections of standard oxymorphone administered over a 48 hour period (p ¼ 0.18). In rats, given one dose of liposome-encapsulated oxymorphone, the mean body weight change from day 0 to day 7 was þ9.4 g, whereas rats given multiple injections of standard oxymorphone had a mean body weight change of 3.6 g over this time (p < 0.01). Mean daily food consumption was signi¢cantly less in rats given multiple injections of standard oxymorphone (p < 0.05). There was no di¡erence between groups in urine production. In conclusion, a single dose of liposome-encapsulated oxymorphone was e¡ective in treating visceral pain in rats. Rats treated with liposome-encapsulated oxymorphone had improved recovery, based # Association of Veterinary Anaesthetists, 2003, 30, 99^119

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

on body weight changes and food consumption, compared with rats treated with multiple doses of standard oxymorphone. Liposome-encapsulated oxymorphone o¡ered advantages including provision of e¡ective analgesia, prolonged dosing intervals, and minimal handling stress.

Use of a laryngeal mask airway in rabbits during isoflurane anesthesia L Bateman, JW Ludders, RD Gleed, HN Erb Cornell University, Ithaca, NY, USA

The purpose of this study was to ¢nd out if an LMA (#1 LMA-Classic) would provide a better airway than a face mask in spontaneously breathing anesthetized rabbits, and to test if it could be used for mechanically controlled ventilation. Sixteen rabbits (4.1 0.8 kg, mean  SD) were assigned randomly to three treatment groups; face mask with spontaneous ventilation (FM-SV; n ¼ 5), LMA with spontaneous ventilation (LMA-SV; n ¼ 5), and LMA with controlled ventilation (LMA-CV; n ¼ 6). Rabbits were anesthetized in dorsal recumbency using a circle circuit at constant ET iso£urane (2.3%, Datex airway gas monitor) and constant rectal temperature (38.85 8C) for 2 hours. PaCO2, PaO2, minute volume, tidal volume (Wright’s respirometer), and PECO2 were measured at 15 minute intervals. Two individuals in the FM-SV group had PaCO2 >100 mm Hg (>13.3 kPa). One rabbit in the FM-SV had PaO2 <80 mm Hg (<10.7 kPa). All FM-SV rabbits showed signs of airway obstruction and two were withdrawn from the study at 45 and 90 minutes, respectively, because of cyanosis. Tidal volume could not be measured in the FM-SV group. No signs of airway obstructions were observed in either of the LMA groups. Four rabbits in the LMACV group developed gastric tympany, and one of these re£uxed after 110 minutes. The signi¢cance of di¡erences between the two spontaneously breathing groups and between the two LMA groups were measured using Wilcoxon’s rank sum test (with signi¢cance assumed at p < 0.05). There were no statistical di¡erences between FM-SV and LMASV in any variable tested. PaCO2 and PE0 CO2 were less in the LMA-CV group than in the LMA-SV group, while PaO2, tidal volume, and minute volume were all more. We conclude that biologically, the LMA provides a better airway than the face mask during spontaneous breathing and that it can be used for IPPV, # Association of Veterinary Anaesthetists, 2003, 30, 99^119

but that gastric tympany is likely to occur during IPPV.

Effectiveness of passive gas-scavenging canisters attached to isoflurane anesthesia systems under standard-use conditions in a laboratory animal facility JC Smith, J Hernandez, B Bolon Amgen Inc.,Thousand Oaks, CA, USA

Chronic exposure to trace levels of waste anesthetic gases has been linked to higher incidences of neurologic and reproductive dysfunction, hepatic and renal toxicity, and neoplasia in health care professionals. We have shown that low levels of iso£urane emissions are likely in conventional laboratory animal treatment rooms during the use of standard anesthesia delivery systems equipped with activated charcoal canisters for passive gas scavenging. In the present study, we surveyed the e¡ectiveness of canisters (attached to well-maintained precision iso£urane vaporizers) in current use throughout our AAALAC-accredited laboratory animal facility. Canisters (Omnicon f/air) had been weighed prior to use and then attached to dual-loop systems (face mask and induction box circuits) from 1 week to 6 months of service. Iso£urane emissions were measured using a pre-calibrated, portable infrared spectrophotometer by attaching each canister to the face-mask circuit, occluding the face mask and closing the stopcock to the induction circuit, and running the system at uniform iso£urane concentration (2%) and oxygen £ow rate (1 L minute1). Samples were taken in animal procedure rooms (size range, 45^80 m3) in which the air turnover rate ranged between 20 and 30 nonrecirculating changes per hour. Nine of the 60 canisters (15%) in current use were found to have exceeded the manufacturer’s recommended use-life (de¢ned as a weight increase of 50 g). Of these nine, seven canisters did not scavenge iso£urane at all (indicated by emissions greatly exceeding 100 ppm). Iso£urane was not detected in the operator’s breathing zone under normal use conditions (i.e. gas directed to both circuits at once). Of the 51 canisters that had not exceeded their rated use-life, 12 (23.5%) exhausted iso£urane at >2 ppm. Our data show that (i) the potential for exposure to waste iso£urane emissions will depend on the con¢guration of the delivery system and that (ii) enhanced 117

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

attention to canister surveillance may be warranted even in well-run facilities.

GOATS The effect of medetomidine and its antagonism with atipamezole on stress-related hormones, metabolites, physiologic responses, sedation, and analgesia in goats GL Carroll, SM Harts¢eld,TM Champney, SC Geller, EA Martinez, EL Haley Texas A & M University, College Station,TX, USA

Six 3-year-old goats (three males and three females) weighing 60.0  18 kg (mean  SD) were used to investigate the e¡ect of medetomidine (MED; 20 mg kg1 IV) and its antagonism with atipamezole (ATI;100 mg kg1 IV) on physiologic responses (heart rate (HR; beats minute1), respiratory rate (RR; breaths minute1), electrocardiogram (ECG), rectal temperature (T; 8C), blood pressure (oscillometric; mm Hg), sedation (SED), posture (REC), analgesia (ALG), and stress-related hormonal and metabolic responses (epinephrine and norepinephrine (high performance liquid chromatography with electrochemical detection), cortisol (COR; mg dL1; radioimmunoassay), glucose (GLU; mg mL1; enzymatic colorimetric assay), and free fatty acids (modi¢ed enzymatic colorimetric assay)); each goat received ATI or SAL in random order separated by 1 week. Jugular catheters were placed for drug administration and blood sampling (10^12 mL sample1) using a lidocaine skin block (20 mg) 2 hours prior to beginning of each trial; during this trial, goats breathed room air. Physiologic parameters were measured, SED, REC, and ALG were scored, and blood samples were collected from jugular catheters at baseline (time ¼ 30 minutes), 5 minutes post-MED administration (time ¼ 25 minutes), 25 minute postMED administration and immediately prior to antagonism (time ¼ 0 minute), and at 5, 30, 60, and 120 minutes after administering ATI or SAL. ALG was tested by clamping the withers and metacarpus with hoof testers ¢tted with a force transducer to measure applied isometric force (lb) (a technique used previously in goats to evaluate analgesia). Continuous variables were analyzed by Repeated Measures analysis of variance (ANOVA); categorical data were analyzed using a Friedman Repeated Measures ANOVA on ranks. A p-value of <0.05 was considered signi¢cant. If a signi¢cant di¡erence was found, a 118

Dunnett’s pair-wise comparison of means was conducted. Di¡erences between ATI and SAL were examined at 5, 30, 60, and 120 minutes using a paired ttest with a Bonferroni correction. Administration of MED resulted in a decrease in T (38.7  0.3 to 34.5  0.4 8C), HR (78  19 to 55  9), and RR (31 12 to 14  5) over time; an increase in mean arterial blood pressure (90  19 to 132  23), COR (0.254  0.125 to 4.327  1.233), and GLU (82.0  13.2 to 255.9  38.9); and changes in SED (alert to marked sedation), REC (standing to recumbent), and ALG (metacarpus ¼ 5  2 to 14  0; withers ¼ 3  2 to 14  0). GLU was 62^70% higher at 60 and 120 minutes and COR was 336% higher after SAL than after ATI at 120 minutes; at 30, 60, and 120 minutes, T was 4^10% higher after ATI than SAL. There were no other signi¢cant di¡erences. REC, SED, and ALG were antagonized after ATI. ATI did not antagonize the e¡ect of MED on HR, RR, or MAP, but stabilized Tand antagonized the increase in GLU and COR.

ANESTHESIA EDUCATION Web-based, interactive simulation of an anesthesia machine S Lampotang, EB Liem, D Lizdas, S Cantwell JH Modell, University of Florida, Gainesville, FL, USA

Gases are transparent and the piping layout in anesthesia machines is not obvious, making it hard to understand anesthesia machine function, potential failure modes, and recovery from faults. We experimented with an approach that simpli¢ed the layout of the anesthesia machine piping by removing extraneous details and making gases not only visible, but also color-coded. More than 15 anesthesia machine controls were represented by icons that a user can adjust byclicking on the icon with a pointing device and subsequently observing the e¡ect of his/ her intervention on anesthesia machine function in real time.We simulated two anesthesia machine failures and also supported non-English languages and non-US gas color codes. Further, we initiated an experiment in Web philanthropy by deliberately choosing to make the educational module accessible without charge and selected the Web as the preferred medium for dissemination of the Virtual Anesthesia # Association of Veterinary Anaesthetists, 2003, 30, 99^119

Proceedings of the American College of Veterinary Anesthesiologists 27th Annual Meeting, Orlando, October 2002

Machine (VAM) viewable at http://www.anest.u£.edu/vam. Originally designed for use in human anesthesiology, a signi¢cant percentage (about 30%) of the 54 000 international visitors, as tracked byan independent third-partyWeb tra⁄c monitoring

# Association of Veterinary Anaesthetists, 2003, 30, 99^119

service, for the period 9/00^5/02, were from the veterinary ¢eld.VAM is being used as part of the curriculum in veterinary programs in the US and overseas and has been well received by the global anesthesia community (human and veterinary).

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