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THE AMERICAN COLLEGE OF VETERINARY ANESTHESIOLOGISTS |
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WM Norman,* MH Court,* DJ Greenblatt. University of Florida, Gainesville, FL and Tufts University, Boston, MA.
Diazepam is used for seizure control and sedation in foals. To permit effective, safe dosing, we evaluated the changes in its disposition in 6 foals at 4, 21, 42 and 84 days of age. Significant differences between age groups were determined by ANOVA (p < 0.05). After a dose of 0.25 mg/kg IV, the disposition was best described as a two-compartment model. Clearance (Cl) and free Cl (mean) at 4 days (5.06 ml/kg/min and 51 ml/kg/min) were significantly less than at 21 (8.64 ml/kg/min and 87 ml/kg/min), 42 (7.31 ml/kg/min and 83 ml/kg/min) and 84 days (8.41 ml/kg/min and 100 ml/kg/min). Volume of distribution (Vd ) and unbound Vd at 4 days (1.57 L/kg and 16.0 L/kg) were significantly less than at 21 (2.66 L/kg and 26.8 L/kg), 42 (3.00 L/kg and 33.9 L/kg) and 84 days (2.5 L/kg and 30.2 L/kg). Peak desmethyldiazepam (DMDZ) concentrations at 4 days (22.7 ng/ml) were significantly lower than at 21 (36 ng/ml), 42 (38.3 ng/ml) and 84 days (34.6 ng/ml). The area under the DMDZ concentration-time curve was lower at 4 days (25.4/ml/min) than at 21 (41.4 µg/g/ml/min) and 42 days (42.6 µg/g/ml/min). Significant changes in free fraction were not observed. The data indicate that factors likely to affect the disposition of diazepam in foals such as body composition and hepatic enzyme activity,evolve rapidly for the first 21 days of life. For diazepam, this evolution affects both Cl and Vd such that the terminal half-life remains unchanged. However, Cl determines whether accumulation of diazepam will occur with repeated doses and care should be taken when administering repeated doses to foals less than 21 days old.
JE Ilkiw ,PJ Pascoe,* LD Fisher. University of Califomia, Davis, CA.
This study was undertaken in cats to determine whether administration of opioids under inhalant anesthesia induced less cardiovascular depression than an equivalent level of inhalant anesthetic alone. Six healthy, spayed cats weighing 4.4 ± 0.9 kg were selected for study.Anesthesiawas induced and maintained with isoflurane and oxygen. Cats were instrumented with a cephalic venous catheter for administration of alfentanil and a balanced electrolyte solution, a femoral arterial catheter for measurement of arterial blood pressure (MAP) and collection of blood for blood-gas and acid-base measurement, and a balloon-tipped, thermodilution catheter for measurement of cardiac output (CO), pulmonary arterial pressure (MPAP), pulmonary arterial occlusion pressure (PAOP), central venous pressure (CVP) and collection of blood for mixed venous blood-gas and acid-base measurements. Using each cat's previously determined isoflurane MAC value, anesthesia was maintained at an end-tidal isoflurane concentration of 1.3 MAC for 60 minutes and measurements taken and samples collected. A large hemostat was applied to the tail for 5 minutes and measurements and collections repeated with the stimulus present. Alfentanil was delivered to an estimated plasma alfentanil concentration of 500 ng/mL; a value found in a previous study to induce maximal isoflurane MAC reduction of 35%. At the same time, the end-tidal isoflurane concentration was decreased by 35%. After 1 hour, measurements were taken and samples collected, the stimulus reapplied for 5 minutes and measurements and collections repeated with the stimulus present. Results were analyzed using a repeated measures ANOVA with two within factors (presence/absence of stimulus and presence/absence of alfentanil). Administration of alfentanil and reduction of isoflurane concentration significantly increased HR, MAP, MPAP, CI, PvO2, PaCO2, PvCO2, BD and significantly decreased pHa and pHv. Application of a noxious stimulus significantly increased HR, CI, PaO2, pHa and pHv and decreased HCO3-, PaCO2 and PvCO2. Alfentanil administration blunted the CI, PaO2, PaCO2 and pHa responses but did not change the HR, PvCO2, pHv and HCO3- responses.
RJ Gmez-Villamandos, JM Santisteban, I Ruiz, JM Dominguez, I Avila, JM Salleras. University of Crdoba, Spain.
The clinical effectiveness of romifidine in the horse was evaluated. Romifidine was administered intravenously at a mean dose of 69.02 ± 18.82 µg/g/kg (range from 20 to 120 µg/kg) to a total of 394 horses, 262 males and 132 females. Mean age was 6.21 ± 3.98 years (range from 1 day to 26 years). The reasons for sedation were prior to general anesthesia (n = 167), minor surgery (n = 93), radiography (n = 61), endoscopy (n = l9), and other procedures - translocation, ultrasonography, handling(n= 54). The following variables were recorded: onset of action (n = 227), degree of sedation (n = 227), duration of sedation (n = 227), adverse effects (n = 227), need for additional restraint (n = 189) and quality of induction of anesthesia (n = 167). Within 2 minutes of injection external signs of sedation were observed. Response to sedation was dose-dependent ranging from slight ataxia at lower doses to moderate ataxia at higher doses. Duration of sedation, 69.45 ± 29.47 minutes, was also dose-dependent and ranged from 15 to 180 minutes. Adverse effects observed were: hyperesthesia (n = 21, 9.3%), copious urination (n = 20, 8.8%), transitory total penile prolapse (n = 11, 4.8%), severe sweating (n = 13, 5.7%), ptyalism (n = 2, 0.9%) and death (n = 1, 0.4%) in a two month old colt in extremely bad condition. Induction of anesthesia was smooth without severe muscular rigidity or excitation in 95.2% of cases. Sedative effects of romifidine in the horse are similar to those reported with the use of other alpha-2 adrenergic agonists. Despite the death of one colt, romifidine was valid for sedation for several diagnostic and therapeutic procedures in the standing horse and for premedication prior to anesthesia.
AL Golden, Kennesaw State University, Kennesaw, GA. JM Bright, GB Daniel, D Fefee, D Schmidt, RC Harvey.* University of Tennessee, Knoxville, TN.
The purpose of this study was to assess the cardiovascular effects of the alpha2 adrenergic receptor agonist, medetomidine (MED) in healthy cats. Cats (n = 11) were anesthetized with isoflurane, and surgically instrumented with aortic, left ventricular, and right atrial catheters for measurement of aortic pressure, left ventricular pressure and right atrial pressure (RAP), respectively. For data collection, end-tidal isoflurane was reduced to 2%, and end tidal CO2 was maintained at 35-40 mmHg with positive pressure ventilation. Following measurement of baseline data, cats were injected with MED (l0 µg/g/kg IM), and data were collected continuously for 75 minutes.
Medetomidine promoted a significant (p = 0.0001) increase in mean arterial pressure (MAP) of 56 ± 21 mmHg (mean ± SD). The maximal change in MAP occurred 17.8 ± 7 minutes after MED injection. Left ventricular peak systolic pressure (LVPSP) increased by 61 ± 27 mmHg (p = 0.0001). Left ventricular end diastolic pressure (LVEDP) increased significantly (p = 0.001) by 10 ± 5 mmHg. RAP increased by 3.7 ± 1.4 mmHg (p = 0.0004). Heart rate decreased significantly (p = 0.01) by 26 ± 27 bpm. Seventy-five minutes post-injection, MAP and LVPSP had returned to baseline levels, but LVEDP (p = 0.01) and RAP (p = 0.03) remained significantly elevated and heart rate remained significantly (p = 0.005) depressed. These results indicate that a low dosage of MED (l0 µg/kg IM) promotes severe vasoconstriction in isoflurane anesthetized cats.
TJ Doherty,* M Provenza, DL Frazier. University of Tennessee, Knoxville,TN.
This study evaluated the effect of premedication on gastric emptying in ponies. Gastric emptying was evaluated using the acetaminophen (AP) method. AP is poorly absorbed from the stomach but is rapidly absorbed from the small intestine. Serial evaluation of serum AP concentrations has been used to evaluate gastric emptying in ponies. Six healthy ponies were used in the study. Each pony was used on five occasions with a minimum of 7 days between studies.
Following a 24 hr fast, the ponies were given either 1 mg/kg xylazine (X), 0.05 mg/kg acepromazine (A), 0.05 mg/kg butorphanol (B), 0.005 mg/kg glycopyrrolate (G) or saline (S), IV. AP was given by stomach tube 15 min later. Venous blood was collected for AP analysis 15, 30, 45, 60, 75, 90, 105 and 120 min later. For each treatment, the time (Tmax) to reach maximum serum concentration (Cmax) and AUC for AP were determined. Data were analyzed using a Curve Stripping Program (R Strip) and Pair-wise t test. The results (mean ± SD) are presented below.
In the control group (S) the mean values for Cmax, Tmax, and AUC were 3.4 mg/dl, 31 min, and 494 mg/ml/hr, respectively. Tmax was increased singificantly (p < 0.05) by X (85 min), A (49 min) B (56 min), and G (66 min). Cmax was decreased by X (2.9 mg/dl) and G (2.5 mg/dl). AUC was decreased significantly by A (399 mg/ml/hr). The results indicate that anesthetic premedicants adversely affect gastric function in ponies.
PJ Pascoe,* JE Ilkiw, LD Fisher. University of California, Davis, CA.
This study was undertaken to define the response of cats to a variety of stimuli with increasing continuous infusions of propofol or propofol with ketamine. Six spayed female cats were used in the study. They were 3.6 ± 0.1 years old and weighed 4.8 ± 0.8 kg. Food was withheld for 12 hours, the cat was weighed and a catheter was placed in a cephalic vein. Propofol was administered at 5 mg/kg/min until the cat lost its righting reflex and had a sluggish withdrawal to toe pinch. The propofol infusion was decreased to 0.1-0.25 mg/kg/min and an arterial catheter was placed in a femoral artery using a cut down technique. The arterial catheter was attached to a pressure transducer and then the propofol infusion was decreased to the lowest dose possible to allow the collection of data (0.05 - 0.1 mg/kg/min). After 30 minutes at this infusion rate the following tests were carried out in sequence: medial canthus palpebral response (MC), eye lash palpebral response (EL), pharyngeal swallow reflex (S), response to laryngoscopy (L), toe pinch for 15 secs (TP), suprarmaximal tetanic stimulus to ulnar nerve for 10 secs (T), and tail clamp for 1 minute (TC). The response to each test was recorded as positive or negative. The infusion rate was increased by 0.05 mg/kg/min and the above tests repeated after 15 minutes at this new infusion rate. The doses were increased until all tests were negative on two consecutive infusion rates. This experiment was repeated twice in each cat with the addition of ketamine as a constant infusion. Ketamine was started after the placement of the arterial line and was given as a 2 mg/kg (low dose - LD) or 4 mg/kg (high dose - HD) loading dose given over 5 minutes followed by a 23 µg/g/kg/min (LD) or 46 µg/g/kg/min (HD) infusion. With ketamine infusions the propofol doses were increased in 0.025 mg/kg/min increments. Data were analyzed using a logistic regression technique to calculate the minimum infusion rate for a response in 50% of the cats for each stimulus (ED50).
The minimum infusion rates (mg/kg/min) for the ED50 with propofol alone, LD and HD were 0.28, 0.16, 0.15 for MC, 0.25, 0.14, 0.14 for EL, 0.14, 0.03, 0.09 for S, 0.16, 0.l0, 0.08 for L, 0.22, 0.14, 0.13 for TP. 0.11, 0.02, 0.02 for T and 0.15, 0.11, 0.09 for TC, respectively.
PM Taylor, JJ Kirby, DJ Shrimpton, CB Johnson. University of Cambridge, Cambridge, UK.
Sixteen pony colts (mean 183 kg) were premedicated with acepromazine (0.03 mg/kg) before induction of anesthesia with detomidine (20 µg/g/kg) and ketamine (2 mg/kg). Ponies were randomly allocated to receive halothane (1.2% ET) (HAL) or IV infusion of detomidine (40 µg/g/ml), guaifenesin (100 mg/ml) and ketamine (4.0 mg/ml) (TIVA) to maintain anesthesia, with oxygen supplementation. Infusion was 0.8 ml/kg/min for 60 mins then 0.6 ml/kg/min. HR, RR, ECG, mean arterial BP (MABP), cardiac index (CI), blood gases, ETCO2/halothane, and plasma cortisol, ketamine and guaifenesin were measured. Systemic vascular resistance (SVR) was calculated. Surgical castration took place between 45 and 75 minutes. Anesthesia lasted 90 mins. Parametric data were analysed using ANOVA and considered significant when p < 0.05. HR and ECG did not change. MABP with TIVA (mean 110-131 mmHg) was significantly higher than with HAL (mean 64-97 mmHg). MABP with HAL increased from pre-surgery (64 ± 6 mmHg) to mid-surgery (80 ± 5 mmHg) but did not change with TIVA. At 30 mins CI was similar in both groups (TIVA 60 ± 3, HAL 53 ± 7 ml/kg/min), but with HAL it decreased during surgery (to 34 ± 11 ml/kg/min) and remained low, where it increased slightly with TIVA, becoming significantly higher than with HAL at 60 and 90 mins. SVR increased with HAL during surgery but did not change with TIVA. RR and pH were lower and PaCO2 and PaO2 were higher during HAL than TIVA. Plasma cortisol decreased in both groups until 40 mins (121 ± 57 ng/ml to 58 ± 33 ng/ml) then increased with HAL only during surgery to 162 ± 60 ng/ml. Ketamine concentration reached a plateau (1.29-1.78 µg/g/ml) between 20 and 90 mins and guaifenesin concentration increased until 60 mins then reached a plateau until 90 mins (99-101 µg/g/ml). This study demonstrates that during HAL the increase in blood pressure associated with surgical stimulus is accompanied by an undesirable fall in CI. In contrast, during TIVA, surgical stimulus appears to increase CI, and is likely to lead to better tissue perfusion than HAL. Surgical stimulus appeared to stimulate adrenocortical activity during HAL. Absence of this response during TIVA may result from pituitary depression, analgesic effects of TIVA or better perfusion.
LA Wetmore,* MM Glowaski, S Schlesinger, E Harkness, B Walsh, A Moore, AZ Karas. Tufts University, N. Grafton, MA.
Veterinary patients requiring radiation therapy (RT) present unique anesthetic problems. Anesthetic agents used must provide immobilization for the duration of radiation exposure yet have minimal residual sedation to facilitate these patients eating, drinking and grooming between daily treatments. Of the many anesthetic techniques in use today, propofol is widely held to meet most of these criteria. This study investigated subjective and objective effects of propofol and a 50:50 (v) mixture of ketamine-midazolam (KM) administered to cats receiving either daily or alternate day RT. Twelve cats (mean age = 9.5 yrs) presenting for RT " chemotherapy were entered into the study and randomly assigned to one of two treatment groups. Blood samples (1 ml) were collected at the end of alternate day treatments for determination of packed cell volume (PCV), total protein (TP), methemoglobin (MetHb) and Heinz body counts (HB). Subjective evaluations were made of each cat's attitude, and hydration and nutritional states. Cats receiving daily propofol showed elevations in MetHb by the second measurement period (approximately day 3) and they remained elevated for the duration of therapy. HB also increased over baseline and PCV decreased below baseline by the fifth measurement period (approximately day 10). These parameters remained abnormal for the duration of therapy. There was no change in TP over the course of the therapy. Results of subjective evaluations suggested that study cats receiving propofol appeared less sedate several hours after treatment, and returned to eating, drinking and grooming more quickly than those receiving KM. We conclude that propofol induced HB formation and abnormalities in hemoglobin are well tolerated by most cats undergoing RT. The brief duration of action of this drug makes it a preferable induction technique to KM for cats receiving daily RT.
NS Matthews,*,1 SM Hartsfield,*,1 B Hague,1 CE Short,*,2 GL Carroll.*,1 1Texas A & M University, College Station, TX and 2Cornell University, Ithaca, NY.
Propofol (PRO) anesthesia was evaluated in 12 horses (7 males, 5 females; weight = 423 " 81 kg) for surgery to create intestinal adhesions. About 20 min post-detomidine (DET: 15 µg/g/kg IV), PRO (2 mg/kg) was given IV over 1-2 min. Restraint included a swing gate with horses' halters secured to a wall. Post-induction, horses were intubated, oxygen was insufflated at 15 L/min, hoisted onto a padded table, and started on PRO (0.2 mg/kg/min) IV. PRO was delivered as needed to maintain surgical anesthesia. Systolic (SAP), mean (MAP), diastolic (DAP) blood pressures, heart rate (HR), respiratory rate (RR) and hemoglobin saturation were monitored; arterial pH and blood gases were analyzed every 15 min and recoveries were evaluated. Mean time to recumbency after PRO was 24 ± 22 sec. Most inductions were acceptable with restraint. Some horses showed muscle rigidity and trembling during induction and paddling after recumbency. Anesthesia was maintained for 61 ± 19 min. with an average infusion of PRO of 0.18 mg/kg/min. MAP increased from 88 ± 10 mm Hg (presurgery) to 121 ± 31 mm Hg at 60 min. SAP and DAP increased; HR was unchanged and RR decreased. Hypoventilation occurred: PaCO2 returned toward baseline by 60 min. Hypoxemia occurred: mean PaO2 was 42, 60, 64, and 57 mm Hg at 15, 30, 45, and 60 min respectively. Mean times to sternal and standing were 54 ± 31 min and 67 ± 29 min, respectively. The number of attempts to stand was 2.4 ± 2.4. DET-PRO provided satisfactory anesthesia for abdominal surgery but PRO for induction should be administered slowly. Supplemental O2 and ventilatory support should be available. Recoveries from DET-PRO anesthesia were smooth and safe.
RD Keegan,*,1 SA Greene,*,1 MP Moore,1 CE Short.*,2 1Washington State University, Pullman, WA and 2Cornell University, Ithaca, NY.
Quantitative electroencephalographic data (QEEG) were obtained from 6 healthy dogs anesthetized with 2.0% end-tidal isoflurane and administered medetomidine (MED, 30 µg/g/kg IV) and atipamezole (ATI, 0.15 mg/kg IV). Arterial blood pressure, end-tidal ISO and CO2, ECG, esophagealtemperatureand arterial blood gases (ABG) were measured. The EEG was recorded using a 21 electrode, linked ear montage and stored on optical disk for analysis at a later time. The cardiovascular (CV) and arterial blood gas (ABG) data collected during the 3 periods were compared using one way AOV (p < 0.05), followed by LSD when significant differences were detected. Values for absolute power (AP) of EEG were determined for B, L, and 1 frequencies. The AP data at each electrode site from the 3 periods were compared using the Wilcoxon Signed Rank Test (p < 0.05). Administration of MED was associated with significant decreases in heart rate and significant increases in SAP, MAP, and DAP. ATI was successful in antagonizing CV changes induced by MED. Administration of MED was associated with an increase in AP in the L bandwidth. Subsequent administration of ATI was associated with a widespread decrease in AP within the L bandwidthandanincreaseinAPat5 electrodesiteswithinthe bandwidth. The AP values recorded prior to administration of MED were not different from those recorded after administration of ATI except in the bandwidth at 1 electrode site. ATI was successful in antagonizing QEEG changes induced by MED in ISO anesthetized dogs.
DC Rankin, SA Greene,* RD Keegan,* AB Weil, WM Bayly. Washington State University, Pullman, WA.
Two injectable anesthetic induction protocols followed by 90 minutes of isoflurane anesthesia were evaluated in horses immediately following strenuous exercise. Anesthesia was induced using either detomidine (DET, 40 µg/g/kg IV) or medetomidine (MED, 15 µg/g/kg IV) followed 5 minutes later with Telazol7( tiletamine and zolazepam, 1 mg/kg IV) in 6 Thoroughbred horses. Detomidine and Telazol7 following sham exercise (standing on treadmill) served as the control. Cardiac output (via thermodilution), heart rate, systolic, mean and diastolic blood pressures, blood gases, serum lactate and plasma potassium concentrations were measured before and after exercise and during the anesthetic period. Results were analyzed with ANOVA (p < 0.05) for repeated measures. Post hoc comparisons of means were made with the Bonferroni test (p < 0.05). Significant deviations from baseline values for PaCO2, serum [lactate], plasma [K+], HR, and temperature were associated with the exercise period. During anesthesia mean values for stroke index, HR, pH, plasma [K+], PaCO2, PaO2 and end tidal [isoflurane] were not significantly different among the three groups. Serum [lactate], SAP, MAP, DAP were significantly different from controls but no difference was noted between MED and DET. Mean values for cardiac index were significantly decreased from control values only in the DET group. Inductions and recoveries were smooth in all groups. Detomidine or medetomidine followed by Telazol @7 appears to be an effective, easily administered IV anesthetic protocol in strenuously exercised horses.
LW Hall,* University of Cambridge, Cambridge, UK; E Lagerweij, University of Utrecht, Utrecht, The Netherlands; AM Nolan, University of Glasgow, Glasgow, UK; JW Sear, University of Oxford, Oxford, UK.
Medetomidine, an extremely potent and selective I2-adrenoceptor agonist, greatly reduces the quantity of propofol needed to produce general anaesthesia. To investigate medetomidine=s effects on dogs, anesthesia with an infusion of propofol was administered to 6 adult Beagle dogs on two separate occasions. The dogs received either no premedication or medetomidine at 20 µg/g/kg IM 15 min before induction of anaesthesia with propofol given at 7 mg/kg/min. After endotracheal intubation the infusion rate was maintained for 120 minutes at 0.4 mg/kg/min in the unpremedicated, and 0.2 mg/kg/min in the premedicated dogs. After induction of anesthesia, a Swan Ganz catheter was inserted via the right jugular vein. Blood propofol concentrations were measured by HPLC with fluorescence detection and kinetic variables calculated using non-compartmental moment analysis. The induction dose of propofol was 7.00 ± 0.55 mg/kg (mean ± SEM) in the unpremedicated compared with 3.09 ± 0.25 mg/kg in the premedicated dogs. There were differences in systemic clearance and mean residence time (MRTiv); 47.5 ± 6.2 ml/kg/min vs 29.0 ± 4.4) ml/kg/min (unpremedicated vs premedicated) and 132.3 ± 5.2 min vs 152.4 ± 3.1 min (p < 0.02 and p < 0.001 respectively). Cardiorespiratory effects were similar in the two groups although heart rate was lower in the premedicated dogs. Venous admixture was high (20 - 45 %) but similar in the two groups.
SA Greene,* DC Rankin, RD Keegan,* WM Bayly, RK Schneider. Washington State University, Pullman, WA.
Injectable anesthesia for transporting horses immediately following racetrack exercise was evaluated. Six Thoroughbred horses weighing 440-636 kg (mean 511.8 kg) were ridden one mile at a gallop on a dirt racetrack. Anesthesia was induced by administration of medetomidine (15 µg/g/kg IV) 2-5 minutes post-exercise, followed by Telazol7 (1 mg/kg IV) 5 minutes later. Heart rate (HR), rectal temperature (Temp), plasma lactate concentration (L), and arterial blood gases were measured before and immediately after exercise. Anesthetized horsesweretransportedto the WSU Teaching Hospital using an equine ambulance. Upon arrival, the horses were removed from the ambulance and placed in a padded equine recovery stall. The time to run 1 mile (T1), time from induction to placement in the recovery stall (T2), and time from placement in the recovery stall to standing (T3) were recorded. Physiologic variables were compared using a paired T-test with probability set at p < 0.05. Mean values for HR, Temp, and L were significantly increased and mean values for arterial pH, PaCO2, plasma bicarbonate concentration, and base excess were significantly decreased after exercise. Mean values for T1, T2, and T3 were 2.06, 14.7, and 65.2 minutes, respectively. Induction and recovery were smooth for each horse. The results suggest that these horses were strenuously exercised and subsequently effectively anesthetized with medetomidine/Telazol allowing safe transportation from the racetrack to the veterinary hospital.
BLH Kraus, MH Court,* DJ Greenblatt. Tufts University, North Grafton, MA.
Clearance of propofol in Greyhounds has been found to be less than half that of mixed breed dogs and is markedly decreased by pretreatment with chloramphenicol. The purpose of this research was to develop an in vitro assay system to study potential gender and breed differences in oxidative metabolism of propofol in the dog and to identify cytochrome P450 (CYP) isoforms responsible for this activity. Liver microsomes were prepared from 4 non-greyhound males (NGM), 4 non-greyhound females (NGF) and 4 Greyhound males (GM). Using these microsomes and a NADPH regeneration system, the in vitro formation of 4OH-propofol (the major metabolite of propofol in the dog) was measured by HPLC with fluorescence detection. Derived enzyme kinetic parameters included Vmax (enzyme amount) and Km (enzyme affinity). Vmax values were significantly higher (by 2-3 fold) in NGM compared with NGF and GM. Significant differences in Km values were not observed. Chemical inhibitors of specific CYP isozymes including furafylline, coumarin, chloramphenicol, sulphaphenazole, quinine, diethyldithiocarbamate and troleandomycin were used to inhibit formation of 4OH-propofol. IC50 values indicated potent inhibition by chloramphenicol (3-44 FM) and diethyldithiocarbamate (7-18FM) in all groups of dogs suggesting involvement of CYP2B and possibly CYP2E. NGF and GM microsomes were also inhibited by quinine which is a CYP2D inhibitor. These data suggest that gender and breed differences in the pharmacokinetics of propofol may result from differences in the relative amount of CYP responsible for the oxidative metabolism of this drug in the dog. In addition, clinically important drug-drug interactions may result from inhibition of these CYP isoforms.
AB Weil, RD Keegan,* SA Greene.* Washington State University, Pullman, WA.
The objective of this study was to determine if a low dose of atropine is associated with decreased requirement for cardiovascular support therapy in horses given detomidine prior to maintenance of general anesthesia with halothane. Detomidine (20 µg/g/kg IM) was administered to 30 horses. Ten horses received atropine (0.006 mg/kg IV) one hour after detomidine administration, ten horses received atropine (0.012 mg/kg IM) at the time of detomidine administration, and ten horses served as a control group. All horses were induced with guaifenesin, diazepam, and ketamine and maintained with halothane. Heart rates were measured and recorded prior to premedication and at fixed intervals throughout anesthesia. The dobutamine infusion rate necessary to maintain mean arterial blood pressure between 70 and 80 mmHg was recorded for each horse. Systemic blood pressures, end-tidal halothane, end-tidal CO2, and blood gas tensions were measured at fixed intervals. All data except dobutamine infusion rate were statistically analyzed using ANOVA (p < 0.05) for repeated measures. The LSD test for pair-wise multiple comparisons of treatment means was applied when significant differences were detected. Dobutamine infusion rates were analyzed using the nonparametric Mann-Whitney procedure (p < 0.05). Mean values for heart rate were higher among horses receiving atropine compared to control horses. Horses that received atropine IV had higher systemic arterial blood pressures and required a lower dobutamine infusion rate than the other groups. Administration of a low dose of atropine intravenously prior to induction of general anesthesia may be beneficial to horses that have received detomidine for premedication.
LW Hall,* University of Cambridge, Cambridge, UK. PK Peshin, Haryana Agricultural University, Hisar, India.
Hospitalization of dogs after anesthesia is costly and often inconvenient for owners so that "day case" anesthesia and surgery is becoming increasingly common. This study investigated the potential of 4 different anesthetic techniques to provide satisfactory anesthesia with short recovery profiles in animals not being subjected to major surgery. Anesthesia was maintained with the 4 different techniques in each of 12 dogs of ASA grades I or II undergoing 4 treatment sessions of mega-voltage x-ray therapy at weekly intervals. After induction of anesthesia with minimal doses of propofol (mean ± SD, 6.0 ± 0.19 mg/kg) they received either (i) continuous propofol intravenous infusion together with nitrous oxide/oxygen by inhalation, or (ii) halothane in nitrous oxide/oxygen, or (iii) enflurane in nitrous oxide/oxygen or (iv) isoflurane in nitrous oxide/oxygen. Anesthesia was always satisfactory but stable anesthesia was achieved more easily when enflurane was used. Recovery to a safe level of consciousness was taken to be return of swallowing reflexes and/or retraction of the tongue or chewing movements of the jaws; after halothane it occurred 4 ± 1 min; after enflurane 2 ± 1 min; after isoflurane 5 ± 1 min and after propofol 4 ± 1 min, from the end of anesthesia. Times to walking were 10 to 23 min for halothane, 7 to 19 min for enflurane, 10 to 20 min for isoflurane and 7 to 27 min for propofol. This study suggested that both the differences in recovery times from the 4 techniques and in the incidence of undesirable effects are of little clinical significance in short duration canine anesthesia unassociated with surgical stimulation.
M Burger. Veterinrmedizinische, Universitt Wien, Austria.
The aim of the study was to investigate the breath- and breathing-patterns of horses undergoing surgery during general anesthesia in lateral (n = 17) and dorsal (n = 15) recumbency.
Flow-tracings were recorded continuously by proximal spirometry (photoelectric Ventury-Vane-Volume7-transducer, Mijnardt, Netherlands) during the first hour of anesthesia (premedication: detomidine, 10 µg/g/kg; induction: guaifenesin, 100 mg/kg; thiopentone, 4 mg/kg; maintenance: halothane/O2). An adequate surgical plane of anesthesia was maintained (ETHal 1.0-1.7 vol%). Inspiratory and expiratory time (Ti, Te), I:E-ratio, mean and peak inspiratory and expiratory flow (MIF, PIF, MEF, PEF), tidal volume (VT), f, minute-ventilation (MV) and end-tidal CO2 (ETCO2) were analyzed on-line with a computer based monitoring system (WFSA 7, Hellige-Biosys, Austria).
The basic shape of inspiration was Arectangular whereas the expiration was Atriangular. Various combinations of mono-, bi-, polyphasic inspiratory and expiratory flow patterns, double-breaths, breaths with pre-inspiratory expiration,inspirationswith a cyclic isolated end-inspiratory peak and Cheyne-Stokes breathing were observed. Ataxic breathing was seen in the post-induction phase. Polyphasic breaths decreased and monophasic breaths increased with time. MIF, PIF, MEF, PEF, f, and MV increased with time. Ti and I:E decreased with time. Te and VT showed no significant changes. The most pronounced influence of ETHAL was seen on MIF (decrease / Vol% ETHAL: lateral recumbency, 44%; dorsal recumbency, 48%),Ti (increase / Vol% ETHAL: lateral recumbency, 57%; dorsal recumbency, 79%) and MV ( decrease 44% in lateral recumbency; 47% in dorsal recumbency).
Horses show substantial changes in breathing strategy during anesthesia. Altered central-neuronal signal processing may cause disintegration of respiratory drive, rhythmogenesis and pattern-formation. Continuous proximal spirometry was demonstrated to be not only a useful method for ventilatory monitoring, but also for estimating anesthetic depth by displaying the characteristic changes in breath- and breathing-patterns.
KR Branson,*,1 JE Quandt,*,2 EA Martinez,*,3 GL Carroll,*,3 CM Trim,*,2 JR Dodam,*,1 SM Hartsfield,*,3 NS Matthews,*,3 A Mackenthun,4 MH Beleau.4 1University of Missouri, Columbia, MO; 2University of Georgia, Athens, GA; 3Texas A&M University, College Station, TX; and 4Abbott Laboratories, Abbott Park, IL.
We evaluated sevoflurane (SEV) as the maintenance inhalant anesthetic agent in 196 dogs (ASA I-III) at 3 sites, using 6 premedicant-induction combinations: 1) oxymorphone-thiopental, 2) oxymorphone/acetylpromazine-thiopental, 3) xylazine/butorphanol-thiopental, 4) opioid - propofol, 5) optional - SEV, and 6) optional - optional. Protocol selection was at the discretion of the attending anesthesiologist. The quality of induction, maintenance and recovery was subjectively rated as excellent, good, fair, or poor. When SEV was used as the induction agent (group 5), the induction quality was excellent or good in 90% of the animals and fair or poor in 10%. In all groups combined, the inductions were rated good or excellent in 95% and fair or poor in 5% of the cases. The quality of maintenance was worst in group 3 (75% good or excellent) and best in groups 2 and 5 (90% good or excellent). The quality of recovery was worst in group 1 (87% good or excellent) and best in group 2 ( 100% good or excellent). The time (mean ± 1 SD) from extubation to sternal recumbency ranged from 4.7 ± 8.1 minutes in group 5 to 15.1 ± 22.4 minutes in group 1. The most commonly reported undesirable side effects (as defined by the attending anesthesiologist) during maintenance and recovery were hypotension (71 dogs; most common in groups 4 and 5), tachypnea (43 dogs; most common in groups 2-4), and apnea (20 dogs; most common in group 4). No severe anesthetic related adverse events were reported. We conclude that SEV provides adequate anesthesia in dogs without unexpected side effects.
M Tomasic.* University of Pennsylvania, Kennett Square, PA.When alveolar hypoxia induces systemic hypoxemia, chemoreceptor-mediated autonomic reflexes are likely to be activated. However autonomic nervous system modulatory effects on hypoxia induced pulmonary vasoconstriction remain unclear. This study examined the effect of hypoxia on the contractile response of small equine pulmonary arterial vascular rings to norepinephrine. Isolated equine pulmonary arterial rings 1 mm O.D. were suspended in 10 ml organ baths in Earle's balanced salt solution at 37EC, and initially aerated with a normoxic gas mixture (18%O2/5%CO2/balance N2). Hypoxic conditions were imposed by switching the aerating gas mixture to one containing 2%O2/5%CO2/balanceN2. Isometric developed tensions were recorded during response to cumulative addition of norepinephrine to the bath solution. Initial cumulative dose responses were obtained under normoxic conditions in 7 rings and under hypoxic conditions in 5 rings. The order of exposure to hypoxia had no apparent effect on the results. Data from individual rings were fit to a sigmoidal function using the Boltzman equation. The EC50 for norepinephrine was 1.4 ± 0.5 FM (mean ± SEM) under normoxic conditions. The mean shift in the EC50 under hypoxic conditions was negligible at -0.1 ± 0.3 FM (mean ± SEM). In contrast, at any given norepinephrine concentration, developed tensions were relatively decreased during hypoxia. When these rings were exposed to a maximally contracting dose (200 FM) of norepinephrine, the maximum developed tensions during hypoxia were significantly reduced (p < 0.001), with peak forces during hypoxia only 68 ± 4% (mean ± SEM) those developed duringnormoxia. These results suggest the pressor response to sympathetic contractile stimulation of the pulmonary vasculature may be significantly attenuated during hypoxia.
K Torske, DH Dyson.* University of Guelph, Guelph, Ontario, Canada.
The influence of epidural oxymorphone/bupivacaine (O/B), epidural bupivacaine alone (B) and IV oxymorphone (O) on end-tidal halothane concentration required to maintain a stable surgical plane of anesthesia was assessed in 24 otherwise healthy dogs scheduled for hindlimb orthopedic surgery. The dogs received acepromazine (0.02 mg/kg)/meperidine (5.0 mg/kg) IM for premedication; thiopental IV to effect for induction and were maintained with halothane. The dogs were randomly assigned to receive: O/B - epidural oxymorphone (0.1 mg/kg) diluted in 0.75% bupivacaine to a total volume of 1ml/5kg + saline IV pre- and post-operatively; B - epidural 0.5% bupivacaine (1ml/5kg) + saline IV preoperatively + 0.05 mg/kg oxymorphone post-operatively; O - epidural saline (1ml/5kg) + 0.05 mg/kg oxymorphone IV pre- and post-operatively. Measurements were recorded prior to test drug administration and every 15 minutes thereafter by a person blinded to the treatment and included HR, RR, temperature, direct arterial BP, end-tidal CO2, end-tidal halothane concentration and arterial blood gases. At 15 minutes after the start of surgery, end-tidal halothane concentrations were decreased by 0.2% increments every 5-10 minutes until the dog was determined to be as light as possible while still remaining in a stable plane suitable for surgery (avoiding mean BP>100 mmHg; rapid, irregular respiration; spontaneous swallowing or blinking; and movement). Data were analyzed using ANOVA with p < 0.05 considered significant.
The end-tidal halothane concentration (mean ± SD) required was 0.48 ± 0.2%, with O/B, 0.54 ± 0 .2% with B, and 0.70 ± 0.2% with O. Respiratory depression (change in PCO2 from baseline) was significantly less at 15 and 60 min in the dogs given B (-4, -7 mmHg) compared to O/B (+13, +6 mmHg) and O (+15, +9 mmHg). HR was also significantly higher at 15 and 30 min with B. Post-operative analgesic requirements were significantly less over the next 24 hr in dogs given O/B(1/8 requiring further analgesia vs 8/8 with O and 7/8 dogs with B).
The primary benefits with O/B appear to be related to post-operative analgesia, although there may be a slight (although not significant) halothane sparing effect.
CM Trim,* MH Barton, JE Quandt.* University of Georgia, Athens, GA.
There is evidence that up to 40% of horses with colic are endotoxemic and that survival is inversely related to endotoxemia. Furthermore, acute deterioration of cardiovascular function in horses during colic surgery may be related to development or worsening of endotoxemia during surgery. In this study, arterial blood samples were collected before the surgical incision and at 30-minute intervals from 20 anesthetized horses with colic. Nine healthy horses anesthetized for elective surgery served as controls. Plasma was tested for endotoxin using the Limulus Amoebocyte Lysate assay. Endotoxin was detected in 10 horses with colic; 6 before the surgical incision, with an increase in plasma concentration of endotoxin in one horse during surgery, and 4 during surgery after correction of colon volvulus (3 horses) or exposure of holes in the colon of another horse. Seven of the 10 endotoxemic horses required treatment with either dobutamine or ephedrine to improve cardiovascular function. In contrast, 4 of the 10 horses negative for endotoxin during anesthesia required similar treatments. Two of the endotoxemic horses were euthanatized during surgery; the remainder of the endotoxemic horses were discharged alive from the hospital. These results suggest that some horses with colic are endotoxemic during anesthesia, that endotoxin may be released into the general circulation after surgical manipulation of compromised intestine, and that endotoxemic horses often require pharmacologic intervention to improve cardiovascular function.
AE Wagner,* JS Gaynor,* CI Dunlop,* S Allen, W Demme. Colorado State University, Fort Collins, Colorado.
Because monitoring of ventilation is especially critical during thoracotomy procedures which require intermittent positive pressure ventilation (IPPV), capnometry is frequently used as a noninvasive estimate of arterial PCO2 (PaCO2). The purpose of this study was to determine if the difference between arterial and end-tidal CO2 (a-ETCO2) increases in association with thoracotomy.
Eighteen dogs (mean weight, 19 kg; range, 7.5 to 43 kg) undergoing clinical thoracotomy procedures were studied. Procedures included 9 lung lobectomies; 2 mediastinal mass resections; 1 heart base tumor; 4 patent ductus arteriosus ligations; and 2 persistent right aortic arch resections. The sampling port of the calibrated capnometer was attached at the junction of the endotracheal tube and the circle breathing system. An arterial blood gas sample was drawn, and ETCO2 and esophageal temperature recorded simultaneously at the following times: after induction of anesthesia (dog breathing spontaneously), 5 minutes prior to surgical incision (dog on IPPV), 5 minutes after chest opened (IPPV), 30 minutes after chest opened (IPPV), 1 hour after chest opened (IPPV), and after the chest was closed and evacuated (dog breathing spontaneously). All PaCO2 values were corrected to the dog's actual esophageal temperature. The ETCO2 was subtracted from the temperature-corrected PaCO2 to obtain the a-ETCO2 difference for each period. The Wilcoxon signed-rank test was used to compare a-ETCO2 differences at the different periods (p < 0.05).
In 10 dogs, the a-ETCO2 difference decreased from induction (spontaneous breathing) to 5 minutes pre-surgery (IPPV), while in 6 dogs, it increased; these changes were not significant. Two dogs were unable to breathe spontaneously and were not included at the first sampling period. Seventeen of 18 dogs evidenced an increase in a-ETCO2 difference between 5 minutes pre-surgery (IPPV) and 5 minutes after the chest was opened (IPPV), which was significant (p = 0.0029). The amount of increase was extremely variable, ranging from 0.7 mm Hg to 33.2 mm Hg (mean, 5.2 mm Hg).
Capnometry is not a reliable indicator of adequacy of ventilation during thoracotomy in dogs, as ETCO2 may differ greatly from PaCO2.
NS Matthews,*,1 D Mercer,1 MH Beleau,2 SM Hartsfield.*,1 1Texas A & M University, College Station, TX and 2Abbott Laboratories, N. Chicago, IL.
Recoveries from 90 min of isoflurane (ISO), sevoflurane (SEVO), and sevoflurane with xylazine (0.1 mg/kg given IV when vaporizer was turned off) (SEVOXYL) anesthesia were compared in 9 Arabian horses. The 3 mares, 3 stallions and 3 geldings ranged in age from 4 to 20 yrs and weighed 409 ± 28 kg. Anesthesia was induced with xylazine (1.1 mg/kg IV), diazepam (0.03 mg/kg IV) and ketamine (2.2 mg/kg IV). Horses were intubated and maintained at 1.2 MAC ISO or SEVO: each horse received all treatments in random order. Recoveries were unassistedandvideotaped. Timetoextubation (TE), first movement (TFM), sternal (TTS), standing (TTST) and the number of attempts to stand (ATS) were recorded. Recoveries were scored on a 1 to 6 score system (1 = best) by the investigators (I), and by 3 blinded reviewers. Blinded evaluators (BE) also evaluated the degree of ataxia (AS) at 10 min after the horse stood.
TE, TFM, TTS, and TTST were 4.1 ± 1.7, 6.8 ± 1.9, 12.6 ± 4.6, and 16.7 ± 7 min with ISO; 3.4 ± 0.83, 6.6 ± 3.1, 10.3 ± 3.1 and 13.9 ± 4.3 min with SEVO; and 4.0 ± 1.2, 9.1 ± 3.3, 13.8 ± 6.5 and 17.8 ± 6.7 min with SEVOXYL. Horses required 3.7, 2.1, and 1.9 ATS with ISO, SEVO, and SEVOXYL, respectively. The mean recovery score for ISO was 2.7 from I and 2.6 from BE. For SEVO, recovery score was 1.6 from I and 2.2 from BE, while SEVOXYL was scored as 1.7 by I and 2.0 from BE. Recovery scores from SEVO and SEVOXYL were significantly lower than from ISO and standing time approached significance (p = 0.0515). Ataxia after standing was significantly less after SEVO than after ISO and SEVOXYL.
Recoveries varied widely from horse to horse, but were slightly shorter with SEVO and of better quality than those from ISO.
SL Cantwell, T Duke,* D Walker, P Walsh, AM Remedios, JG Ferguson. University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
The purpose of this study was to evaluate the cardiopulmonary effects of one-lung ventilation (OLV) as compared to routine two-lung ventilation (TLV) in dogs. OLV will facilitate thoracic surgeries such as bronchopleural fistula repair and thoracoscopy. Fourteen healthy dogs (average weight of 23 kg) were anesthetized with acepromazine (0.05 mg/kg) and morphine (0.6 mg/kg) IM, thiopental (10 mg/kg IV) and maintained with halothane (1.5 times MAC) in 100% O2. All dogs were paralyzed with vecuronium (0.05 mg/kg IV) every 20 minutes, and ventilated at a tidal volume of 10 ml/kg. The rate was adjusted to maintain ETCO2 at 40 ± 2 mmHg. Once instrumentation was completed, rate and tidal volume were not changed and the dogs were monitored for 60 minutes. The left bronchus of seven randomly chosen dogs was obstructed fibre-optically with a bronchial blocker, and the lung was allowed to deflate. Blood gases were drawn at 0, 5, 10, 15, 20, 40, and 60 minutes. Hemodynamic parameters were measured every 10 minutes. For each variable, ANOVA for repeated measures was used to detect significant differences (p < 0.05) between mean scores of each group. HR, MAP, and PaCO2 increased significantly with OLV compared to TLV. (Range of means ± SE in OLV vs TLV: HR (bpm) 71 ± 3 to 80 ± 5 vs 54 ± 2 to 57 ± 3, MAP (mmHg) 65 ± 2 to 71 ± 3 vs 58 ± 2 to 62 ± 2, and PaCO2 (mmHg) 43 ± 2 to 49 ± 2 vs 40 ± 2 to 43 ± 3). PaO2 decreased significantly (189 ± 27 to 229 ± 28 vs 312 ± 15 to 348 ± 26 mmHg). SVR also decreased significantly. There was no significant change in ETCO2, CI, PAP, PVR, shunt fraction or oxygen extraction. One-lung ventilation with 100% O2 did not cause hypoxia although ETCO2 was not reflective of PaCO2 level. This study suggests that OLV in a closed thorax appears to be a safe procedure in healthy medium-sized dogs.
GM Johnston, PM Taylor, MA McGee, MA Holmes, JLN Wood. University of Cambridge, Cambridge, UK; Institute of Public Health, Cambridge; The Animal Health Trust, Newmarket, UK.
This paper reports data from a cohort study (CEPEF-2) of equine death within seven days of general anaesthesia collected from 34,788 general anesthetics in 125 clinics. Clinics were required to keep a diary of all general anaesthetics including outcome (dead as a result of fatal complications or alive) at seven days. Risk factors relating to patient, operation, premedication and induction agent have been identified previously. This paper reports preliminary comparison of maintenance with isoflurane and halothane. 29,083 patients received either halothane (n = 28,255 of which 548 died) or isoflurane (n = 828 of which 23 died). The odds ratio (OR) for all patients receiving halothane compared to isoflurane dying (mortality rate = 1.96%) is 0.69 (95% CI: 0.45 to 1.08, p = 0.09). 25,501 patients which were not colic or obstetrics patients (non-C&O) received either halothane (n = 24,881 of which 226 died) or isoflurane (n = 620 of which 8 died). OR for non-C&O patients receiving halothane compared to isoflurane dying (mortality rate = 0.91%) is 0.7 (95% CI: 0.33 to 1.54, p = 0.32). 3,532 patients which underwent C&O surgery received either halothane (n = 3,374 of which 322 died) or isoflurane (n = 208 of which 15 died). OR for C&O patients receiving halothane compared to isoflurane dying (mortality rate = 9.41%) is 1.36 (95% CI: 0.77 to 2.42, p = 0.26). These figures are not consistent with the reported beneficial effects of isoflurane compared to halothane demonstrated under experimental conditions. This is perhaps due to a significant amount of confounding (e.g. clinicians selecting isoflurane for the higher risk patients) which is impossible to exclude in an observational study (CEPEF-1 & 2). The effects of halothane and isoflurane on perioperative complications need to be identified using a randomised controlled trial whose study design eliminates the effects of confounding. This would identify the true relative benefits of isoflurane and halothane in clinical practice. CEPEF-3, starting October 1996 is designed for this purpose.
EA Martinez,* AA Wooldridge, DR Mercer, MR Slater, SM Hartsfield.* Texas A&M University, College Station, TX.
Six dogs, anesthetized with isoflurane (ISO), were used to determine the cardiovascular and neuromuscular effects of rocuronium bromide (ROC) or placebo (PLAC). Each dog served as its own control with a minimum of 7 days between studies. PaCO2 was maintained near 40 mm of Hg with controlled ventilation. The following cardiovascular variables were determined: heart rate (HR), direct systolic, diastolic, and mean arterial blood pressure (SAP, DAP, MAP), cardiac index (CI), stroke volume (SV), pulmonary artery pressure (PAP), pulmonary wedge pressure (PWP), systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR). Neuromuscular blockade was assessed using the train-of-four technique. After baseline values were recorded, the dogs randomly received either ROC (0.18 mg/kg IV) or PLAC. All variables were determined at 2, 5, 10, 15, 20, 25, and 30 min after ROC or PLAC. Edrophonium (EDRO), 0.5 mg/kg IV, or PLAC was then given and variables determined at 32, 35, 40, and 45 min after ROC or PLAC. An analysis of variance for repeated measures was used to test statistical significance of the effect of ROC, EDRO, or PLAC on cardiovascular variables. Statistical significance was set at p < 0.05. ROC caused a significant decrease in MAP, DAP, and increase in SAP. EDRO caused a significant decrease in HR, CI, PVR, and significant increase in PWP. Mean ± (SD) values for onset, duration, maximal depression of first twitch (T1), and recovery time (25-75% T1) following ROC was 1.8 ± 0.9 min, 12.7 ± 5.3 min, 97.5 ± 6.1%, and 3.8 ± 1.3 min, respectively. We conclude that although some changes seen were statistically significant, it is our opinion that these changes were not great enough to be of clinical significance.
RT Skarda,* WW Muir.* The Ohio State University, Columbus, Ohio.
Selective caudal analgesia in standing mares is desirable for diagnostic, obstetric, and surgical procedures performed in the anal and perineal region, and has been induced by epidural or subarachnoid administration of detomidine. This study determined the antagonistic effects of atipamezole (A) administered at higher doses than previously used (0.1 vs 0.04 mg/kg, IV) on subarachnoidally administered detomidine-induced perineal analgesia, head ptosis, position of pelvic limbs, HR, RR, arterial BP, blood pHa, PaO2, PaCO2, PCV, TS concentrations, and rectal T in 10 healthy mares (480 ± 33 kg, mean "SD). Each mare received 0.9% NaCl administered into the midsacral (S2 to S3) subarachnoid space (negative control); detomidine at 0.03 mg/kg into the S2 to S3 subarachnoid space, followed with atipamezole at 0.1 mg/kg IV at 60 minutes (test); and detomidine at 0.03 mg/kg into the S2 to S3 subarachnoid space, followed with 0.9% NaCl IV at 60 minutes (S-D, control) in a randomized, blinded, 3-way cross-over design study with 2 weeks between treatments. Analgesia was determined by lack of sensory perception to electrical stimulation at the perineal dermatome and no response to needle prick stimulation extending from coccyx to T15 dermatome. Two-way ANOVA with repeated measures was used to detect significant (p < 0.05) differences between mean scores of perineal analgesia, head ptosis, pelvic limb position, urination, and cardiorespiratory variables before and during a 3-hour testing period. Perineal analgesia was induced in 9.0 ± 4.6 minutes and lasted 130 ± 26 minutes after S-D administration with headptosis,changes in pelvic limb position, bradycardia, bradypnoea, and frequent urination without significantly affecting pHa, PaO2, PaCO2, and rectal T. Atipamezole effectively reversed S-D induced analgesia, head ptosis, and pelvic limb position score within 3.8 ± 1.5 minutes, partially reversed bradycardia, and did not affect respiration after administration. The results indicate that the effects of S-D were mediated via activation of I2-adrenoceptors and characterize atipamezole as a potent antagonist at central and peripheral I2-adrenoceptors with a rapid onset.
TM Dyke, JAE Hubbell,* KW Hinchcliff, RA Sams. The Ohio State University, Columbus, OH.
The effects of exercise on pharmacokinetics of drugs administered during the immediate post-race period have not been studied, despite the use of sedative, analgesic and anesthetics agents to facilitate diagnosis and management of acute injury during this period. To model exercise-induced changes in the pharmacokinetics of drugs with high hepatic clearance, this study investigated the effects of acute treadmill exercise on the pharmacokinetics of bromosulphthalein (BSP) administered to horses in the immediate post-exercise period. Our hypothesis was that exercise would lead to decreased hepatic clearance of BSP.
Six healthy, fit Thoroughbred horses, underwent 3 treadmill trials in a randomized cross-over experimental design, I) standing for 40 mins; II) a simulated race (at speeds predicted to require 120% VO2 max for 90-120 sec after a 12 min warm-up) then 30 mins walking at 2 m/s; and III) a simulated race then 30 mins of standing. Horses stayed on the treadmill for drug administration and blood collection. BSP (5 mg/kg) was administered 60 sec after completion of maximal exercise by intravenous infusion over 40-50 sec. Blood samples were collected every 2 min for 30 min for spectrophotometric analysis of plasma BSP concentrations. Pharmacokinetic parameters were analyzed by Friedman repeated measures analysis of variance on ranks and post-hoc Student-Newman-Keuls tests.
Median plasma clearances decreased from 14.2 (I) to 8.4 (II) mL/min/kg (p = 0.006). Median steady state volumes of distribution decreased from 47.6 to 42.7 (II) mL/kg (p = 0.01). Median mean residence times increased from 3.4 (I) to 4.8 (II) min (p = 0.009). No significant differences were detected between parameters during Trial II and III. Pharmacokinetics of BSP are dramatically altered in the immediate post-exercise period, indicating that decreased liver blood flow and decreased plasma volume persist. Drugs highly extracted by the liver and with limited volumes of distribution may be similarly affected.
GL Carroll,* G Flores-Foxworth, K Bretzlaff, M Westhusin, L Nuti, SM Hartsfield,* R Hambleton. Texas A&M University, College Station TX.
We evaluated tiletamine-zolazepam (TZ; 5.5 mg/kg IV) and TZ (5.5 mg/kg IV)-butorphanol (0.1 mg/kg IV)(TZB) for laparotomy in 9 female goats (37.9 ± 4.6 kg). Each goat recevied each treatment (TX). Induction was ranked. Arterial blood pressures (AP), heart rate (HR), respiratory rate (RR), SpO2, ECG and temperature (T) were recorded (q 5 min); arterial samples were taken (q 30 min). Muscle relaxation, anesthesiaqualityandeye signs were scaled and recorded (q 15 min). Anesthesia time, recovery score, attempts to stand and analgesia score were recorded. At baseline, 1 and 2 hr postextubation (PE), plasma cortisol was measured; at extubation (E) and at 1 and 2 hr PE, HR, RR, and T were measured. Inductions were smooth (TZ = 21± 6 sec; TZB = 17 "5 sec). Additional TZ was administered by bolus (0.5-1 mg/kg IV) to maintain acceptable anesthesia; averaged over time, 0.1 " 0.02 mg/kg/min IV was needed. Regurgitation occurred (5 goats; TZ-3, TZB-2). Some required O2 (TZ-2; TZB-1) and IPPV (TZ-1). Ranges for HCO3 - and BE were 21.6-21.9 mEq/L and -3.11 to -3.24 mEq/L (TZ) and 22.6-23.5 mEq/L and -1 to -2.16 mEq/L (TZB). Mean AP was 114-125 (TZ) and 109-125 mm Hg (TZB). Mean HR was 81-109 (TZ), 82-103 (TZB) beats/min; mean T, 37.7-39.2 (TZ), 37.5-39.2EC (TZB). ANOVA showed TX differences (P < 0.05) for HCO3 - and BE, but not for TX or time for RR, pHa, PaO2, PaCO2, SpO2, or SaO2. There were time effects: HR increased after induction; T decreased over time; AP increased after the goats were inclined in the cradle. HR and C increased with time, 1 hr PE. Muscle relaxation was good; anesthesia quality and eye signs were variable. Anesthesia lasted 108 ± 20 (TZ) and 100 ± 12 (TZB) min. From E to standing, 82 &177; 45 (TZ) and 95 ± 54 (TZB) min elapsed. Recoveries and analgesia were good; median attempts to stand = 2. Anesthesia for caprine laparotomy was satisfactory.
DH Dyson,* G Maxie, D Schnurr. University of Guelph, Guelph, Ontario, Canada.
During 1993, 65 small animal veterinary practices participated in a prospective study to document the incidence and categories of anesthetic related morbidity and mortality. Veterinarians recorded the details on their patients and the anesthetic drugs and management practices used during a 6 month period. All unexpected occurrences up to 24 hr after anesthesia were noted. A total of 8,702 cats and 8,087 dogs were considered.
Drug use and management details in cats and dogs, respectively as a % of cases, were as follows: acepromazine (65, 68), butorphanol (37, 37), atropine (59, 44), meperidine (28, 19), glycopyrrolate (10, 9), ketamine/diazepam (11, 26), xylazine/ketamine (7, < 0.2), ketamine alone or with other drugs (29, 0), thiobarbiturates (23, 52), mask inhalant (27, 11), halothane (28, 38), isoflurane (27, 36), methoxyflurane (0, 4), injectable maintenance (45, 22), intubation (42, 77), laryngeal spray (24, 12), technician present (83, 86), apnea monitor (23, 35), heart rate monitor (65, 66), postoperative analgesia (21, 16), non-steroidal anti-inflamatories (4, < 1).
The incidence of anesthetic related complications was (1.3%, 2.1%) and death (0.1%, 0.11%) in cats and dogs, respectively. The logistic regression models developed showed odds ratios as follows: feline complications - ASA 3, 4, 5 (5.3), diazepam (4.1), intubation (1.7), butorphanol (0.45), ketamine (0.17); feline arrest - ASA 3, 4, 5 (21.6), technician present (0.19); canine complications - xylazine (91.5), heart rate monitoring (3.2), ASA 3,4,5 (2.5), isoflurane (2.4), butorphanol (0.35), technician present (0.26), acepromazine (0.24), ketamine (0.21), mask induction (0.2); canine arrest - xylazine (43.6), ASA 3, 4, 5 (7.1).
In conclusion, xylazine use in dogs and anesthesia of cases with ASA 3, 4, or 5 classification appear to obviously impact risk. The other factors identified need to be considered with respect to the limitation that judicious drug use by practitioners exists as a significant confounder in this type of research.
T Duke,* CM Egger, JG Ferguson, M Frketic. University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
The cardiopulmonary effects of using propofol as an infusion for anesthesia in llamas was investigated. Five adult llamas of weight 135 ± 17.7 kg (mean " SD) were instrumented under halothane anesthesia and rested for 48 hours. Before induction with propofol (2 mg/kg IV) a pulmonary artery balloon catheter was placed and baseline measurements taken. After induction, llamas were randomized to receive either propofol infusion 0.2 mg/kg/min (Group 1, n = 5), or 0.4 mg/kg/min (Group 2, n = 5), for 60 minutes, while breathing room air. Llamas were recovered, rested for 48 hours, and crossed over to receive the alternate infusion rate. Direct mean systemic arterial (MAP), mean pulmonary arterial (MPAP), pulmonary arterial wedge (PAWP) and central venous pressures (CVP); heart rate (HR), respiratory rate, and cardiac output were taken at pre-induction and at 3, 10, 20, 30, 40, 50 and 60 minutes postinduction. PaO2, PaCO2 and arterial pH analysis were performed pre-induction and at 3, 10, 20, 40 and 60 minutes postinduction. Systemic and pulmonary vascular resistances, cardiac and stroke index (SI), plasma bicarbonate and base excess were calculated.
Statistically significant differences (p < 0.05) from pre-induction were observed: PaCO2 and heart rate increased in both groups (3 - 60 minutes); PaO2, arterial pH, MPAP, CVP and SI decreased in both groups (3 - 60 minutes). MAP decreased in Group 2 (30 - 60 minutes), PAWP decreased in Group 1 (20 - 40 minutes), and in Group 2 (3 - 60 minutes). All values were within physiologically acceptable limits. Average times to sternal recumbency were 7 minutes (Group 1, n = 2) and 13 minutes (Group 2, n = 3). Standing was achieved in an average of 11 minutes (Group 1) and 22 minutes (Group 2). The infusion rate of 0.2 mg/kg/min was considered too low to maintain a subjectively evaluated suitable depth of anesthesia, but 0.4 mg/kg/min considered sufficient for non-invasive procedures, with minimal cardiopulmonary depression.
RE Meyer,* JS Hahn, S Shan, RD Braun, SA Snyder, JM Taube, ET Ong, GL Rosner, RK Dodge, J Bonaventura, C Bonaventura, J DeAngelo, MW Dewhirst. NC State University, Raleigh NC and Duke University Medical Center, Durham NC.
Side effects of cell-free hemoglobin include vasoconstriction and reduced blood flow due to nitric oxide (NO) quenching. We examined the microvascular effects of a-a uncrosslinked human hemoglobin A (CFHB) in the R3230Ac mammary adenocarcinoma. In female Fischer 344 rats with 1-cm diameter tumors implanted in the lateral quadriceps, 0.1 g/kg and 0.2 g/kg CFHB, administered IV at a constant volume of 0.00425 ml/kg body weight and infused at 0.7 ml/min, decreased both central tumor and peripheral tumor laser doppler flow (LDF) by 20% (p < 0.05). In contrast, 0.2 g/kg CFHB increased normal muscle LDF by 50% (p < 0.05). Tumor PO2 decreased 24%, from 14.3 mmHg (at baseline) to 10.8 mmHg at 10 min following 0.2 g/kg CFHB infusion (p = 0.02). CFHB increased MAP 5-10% (p < 0.01) while HR concurrently decreased by 9-19% (p < 0.05). Neither equal volumes of albumin nor lactated Ringer's solution had a significant elevating effect on MAP, tumor blood flow, or muscle blood flow, indicating that intravascular volume expansion, rate of administration, and oncotic pressure of the infused CFHB were not significant contributing factors. Using intravital microscopy, 0.2 g/kg CFHB rapidly reduced arteriolar diameter 10% (p = 0.037), which remained stable for 60 min of observation (p = 0.005). We conclude that CFHB selectively reduces tumor blood flow for at least 60 min through vasoconstriction of tumor feeding arterioles, while tumor PO2 is decreased for at least 10 min. Vascular NO quenching may provide an alternative to NO synthase inhibition to achieve the goal of selective tumor hypoxia.
JCH Ko,* TG Heaton-Jones. University of Florida, Gainesville, Florida.
Ten, one-year-old, intact male ferrets, weighing 1.7 kg ± 0.3 kg, were used in a crossover study to determine the anesthetic effects of medetomidine (80 µg/g/kg, M), medetomidine (80 µg/g/kg)-butorphanol (0.1 mg/kg, MB), medetomidine (80 µg/g/kg)-ketamine (5 mg/kg, MK), and medetomidine (80 µg/g/kg)-butorphanol (0.1 mg/kg)-ketamine (5 mg/kg, MBK). All drugs were given as a single IM injection. Data were analyzed with ANOVA for significant differences at p #0.05. All ferrets assumed lateral recumbency within 4 minutes following IM injection. Time from IM injection to the achievement of endotracheal intubation was significantly longer in the MB group (19.2 ± 10.2 vs MBK: 7.5 ± 2.7, MK: 9.2 ± 5.8 min). None of the M treated ferrets could be intubated. Intubation duration was significantly shorter in the MK group (45.8 ± 28.8 vs MB: 80.8 ± 10.2 and MBK: 92.5 ± 2.7 min). Duration of toe pinch analgesia was significantly shorter in the M (10.8 ± 8.0) and MK (48.3 ± 31.5) groups compared to the MB (90.8 ± 4.9) and MBK groups (93.3 ± 4.1 min). All ferrets remained in lateral recumbency for 100 minutes until atipamezole (400 µg/g/kg IM) was administered. Time from atipamezole injection to complete mobilization was # 10 minutes for each treatment group. The induction quality with each drug and recovery following atipamezole injection were smooth. Cardiorespiratory data were similar in all four treatment groups. In conclusion, 1) all four combinations were suitable for chemical restraint in ferrets, 2) the addition of B to M significantly increased analgesia as evaluated by toe, skin and tail pinches, and 3) the addition of K to MB facilitated endotracheal intubation.
JE Quandt,* C Greenacre. University of Georgia, Athens, GA.
Sevoflurane is a new halogenated anesthetic agent. Its low blood:gas partition coefficient results in rapid induction and recovery. This may lead to improved induction and recovery when used in psittacine birds. The parameters of mask induction, intubation, and recovery were evaluated in ten psittacine birds anesthetized with sevoflurane compared to isoflurane. Each bird was anesthetized with both agents with a minimum of four weeks between treatments. Each bird was masked with delivered concentration of each agent increased in a step-wise manner until intubation was possible. After intubation the birds were maintained on a non-rebreathing circuit for 20 minutes. The birds were allowed to recover unassisted in a box or cage. Extubation was performed when the birds began vocalizing and demonstrated awareness of the endotracheal tube. The times to intubation, extubation, sternal, and standing were noted. A subjective assessment of induction and recovery was made. Both agents gave an excellent quality of induction and allowed for easy intubation. There was no difference in time to intubation, extubation, or sternal between the two agents. The time to standing was significantly shorter with sevoflurane (p < 0.05). Birds recovering from sevoflurane had a better quality of recovery when compared to isoflurane. These birds became alert sooner and were not ataxic. Sevoflurane is a suitable inhalant agent for induction and recovery in psittacine birds.
JL Cornick-Seahorn,* JA Smith,* SK Mikota, R Aguilar. Louisiana State University, Baton Rouge, LA.
The objectives of this study were: 1) to record hemodynamic and respiratory data from bongos, a species of antelope, during xylazine-carfentanil (X-C) anesthesia; and 2) to evaluate the usefulness of noninvasive monitoring techniques by comparison with standard invasive techniques. Nine bongos (178 ± 39 kg) were anesthetized for embryo collection (4) or for diagnostic evaluation (5) with X (10 mg)-C (1.5-2.75 mg) IM. Monitoring included continuous lead II ECG, arterial blood pressure (invasive, noninvasive or both), mainstream capnometry (ETCO2), pulseoximetry, temperature (rectal or nasopharyngeal) and blood gas analyses. Duration of anesthesia ranged from 20-60 minutes. Intranasal oxygen (2-4 L/min) was administered for procedures over 20 minutes. Data were recorded every 5 minutes. Arterial blood was collected 25 minutes (9) and 60 minutes (4) after IM injection.
Temperature was stable during the anesthetic period with a mean increase of 0.6EC. Heart rate was stable with a range of 55-80 beats/minute. One animal demonstrated a marked sinus arrhythmia but no other arrhythmias were noted. Respiratory rate ranged from 8-28 breaths/minute. Only 3 animals had rates greater than 20 breaths/minute. Arterial blood pressure was high (invasive MAP = 162 "25 mm Hg at 30 minutes postinjection) and increased over time. There was poor correlation between invasive and noninvasive arterial blood pressure values with noninvasive values being consistently lower. Ventilation was well maintained with PaCO2 values ranging from 41-55 mm Hg. There was poor correlation between PaCO2 and ETCO2 . Hypoxia developed but normal PaO2 values could be maintained with supplemental oxygen. There was poor correlation between SaO2 and PaO2.. Inductions and recoveries were smooth. Mean time to standing following IV injection of naltrexone was 1 minute and 45 seconds ± 30 seconds.
JS Gaynor,* J Wimsatt, C Mallinckrodt, D Biggins. Colorado State University, Fort Collins, CO.
Siberian polecats (Mustela eversmanni) serve as investigational surrogates for black-footed ferrets (Mustela nigripes). This abundant, non-endangered species is used to help improve techniques in husbandry, veterinary care, and reproduction with the ultimate goal of refining captive propagation of the black-footed ferret. Twenty-four captive 8 month old, wild polecats from 12 litters were used for this study. After being caught in small wire traps, traps containing ferrets were placed in a clear plastic anesthesia induction chamber. Anesthesia was rapidly induced in the same induction chamber with either 7% sevoflurane or 5% isoflurane in 5 L/minute oxygen. Time to loss of righting reflex was recorded. Upon removal from the chamber, polecats breathed either 5% sevoflurane or 3% isoflurane, respectively, in 0.5 L/min of oxygen through a non-rebreathing circuit and tight fitting mask. An ultrasonic Doppler crystal and a blood pressure cuff were applied to the proximal aspect of the tail. Vaporizer setting adjusted to maintain a light plane of anesthesia and to permit the subcutaneous insertion of an identifying microchip and drawing of blood from the jugular vein. Heart rate, respiratory rate, Doppler systolic blood pressure, and body temperature were monitored every 2 minutes. Prior to removal of the mask, jugular venous blood was sampled for blood gas analysis. Time to resumption of righting reflex was recorded as a standard of recovery from anesthesia. Data were analyzed using least squares analysis of variance. Data were considered significantly different when p < 0.05 . Time to loss of righting reflex (mean ± SEM) with sevoflurane was 1.9 ± 0.1 minutes compared to 2.6 ± 0.1 minutes for isoflurane. Systolic arterial pressure was higher with sevoflurane, 83 ± 2 mmHg, compared to 66 ± 2 mmHg with isoflurane, while heart rate was 191 ± 3 beats/minute with sevoflurane compared to 204 ± 3 beats/minute for isoflurane. There were no differences in respiratory rate, jugular venous pH, PCO2, HCO3-, BE, or recovery of righting reflex. Sevoflurane induces anesthesia more rapidly and maintains blood pressure better than isoflurane. Inhaled sevoflurane should be an appropriate anesthetic for black-footed ferrets in laboratory and field conditions.
JCH Ko,* JM Harrison, CH Maldelach. University of Florida, Gainesville, FL.
Eight 1.5-year-old, male ferrets weighing 1.6 ± 0.3 kg, were used to compare indirect cardiopulmonary data obtained from pulse oximetry, capnometry, and systolic blood pressure, to direct cardiopulmonary data from carotid artery. Simple linear regression was used to evaluate relationships between direct and indirect measurements. Results of the study showed that pulse rate obtained from pulse oximeter accurately predicted the pulse rate (range, 75-220 bpm) obtained from carotid arterial pulsation. Systolic pressure (50-240 mmHg) obtained from carotid artery was estimated by adding 17 mmHg to blood pressure obtained from tail with a pressure cuff, Doppler ultrasonographic unit and sphygmomanometer. Oxyhemoglobin saturation obtained from tail more precisely predicted the HbO2 sat % than SpO2 from a paw and required a correction equation [Direct=51.6 + 0.5 (tail SpO2)] to predict the direct values (range:50-100%). Carbon dioxide concentration (CO2) obtained from carina via endotracheal tube and side stream capnography was a better predictor of PaCO2 (range, 25-95 mmHg) than the CO2 obtained from the nose via main stream capnography. It was concluded that, although certain correcting equations were needed, these non-invasive methods of cardiopulmonary monitoring predicted values obtained from direct, invasive techniques. Furthermore, objective comparison of various anesthetic combinations in the ferret can be done based on data obtained from these non-invasive cardiopulmonary monitoring methods.
RA Johnson, SM Johnson, GS Mitchell. University of Wisconsin, Madison, WI.
Systemic dopamine (DA) administration is often used clinically to produce complex cardiovascular responses by activating peripheraldopaminergicandadrenergic receptors. An unwanted side effect of DA administration is ventilatory depression caused by actions on peripheral arterial chemoreceptors. Chemoafferent neurons from these peripheral chemoreceptors contain DA and project to central cardiorespiratory nuclei in the medulla, suggesting that DA also modulates respiration via actions in the central nervous system. Because little is known concerning the central medullary actions of dopamine on respiration, we determined whether DA alters respiratory motor activity in an isolated in vitro brainstem preparation from an adult vertebrate.
Adult turtles (Chrysemys picta) were anesthetized with halothane and cardioperfused with iced HEPES-bicarbonate buffer bubbled with a 95% O2 :5% CO2 mixture (pH~7.45). The isolated medulla between spinal segment C1 and optic lobes was placed in a chamber and superfused with buffer (22oC). Respiratory motor discharge was recorded from hypoglossal nerve roots; this discharge occurred with a frequency of 0.52 "0.32 episodes/min (mean ± SD).
The discharge frequency increased progressively with increasing DA concentrations (10-200 FM), reaching a maximum of 1.72 ± 0.60 episodes/min (ED50 ~ 25FM; n=6). The DA-induced frequency increase was attenuated by 54% with the D2-dopaminergic antagonist, eticlopride (20 FM; n=6; p < 0.05), but not with the D1-dopaminergic antagonist, R(+)-SCH-23390 (10 FM; n=6). Prazosin (I-adrenergic antagonist; 250 nM; n=6) abolished the DA-induced frequency increase. Norepinephrine (10-200 FM; n=4) and phenylephrine (I-adrenergic agonist; 1-200 FM; n=6) increased respiratory frequency to maximum values of 1.04 ± 0.64 and 0.92 ± 0.40 episodes/min, respectively. We conclude that in addition to its better known actions at the peripheral chemoreceptors, DA may play an important role in modulating respiration by acting at central dopaminergic and I-adrenergic receptors.
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