VM Lukasik, WM Nogami, SE Morgan. University of Arizona, Tucson, AZ.
This study was undertaken to determine desflurane MAC in adult sheep and to
evaluate its cardiovascular effects at 1.0, 1.5, and 2.0 MAC. Anesthesia was
induced with 18% desflurane in 10 L/minute of O2 delivered by mask in six
healthy (determined by physical exam and preanesthetic hematology and serum
chemistry panel) non-pregnant ewes between 1 and 8 years of age and weighing
between 46 and 98 kg. Ewes were intubated within 7 minutes, placed in left
lateral recumbency, and ventilated to maintain end-tidal CO2 at 33-36 mm Hg.
Body temperature was maintained at 39° C throughout the investigation. The
right auricular artery was catheterized and systolic (SP), diastolic (DP), and
mean arterial pressure (MAP) were monitored. To determine MAC, end-tidal (ET)
anesthetic concentration was allowed to equilibrate 15 minutes prior to
application of a 10 inch hemostat to the coronary band of the right, rear,
lateral dewclaw until the ratchet locked, leaving it in place for 60 seconds.
MAC was determined to be the ET desflurane concentration midway between that
which allowed purposeful movement and that which did not. After completion of
the MAC study, changes in heart rate (HR), SP, DP, and MAP were determined at
1.0, 1.5, and 2.0 MAC. ET desflurane concentration was allowed to equilibrate
15 minutes prior to data collection. Data were analyzed with Friedman
nonparametric repeated measures test with p < 0.01 considered significant.
Data are expressed as the median and range.
Induction was rapid and smooth with recumbency occurring in less than 5
minutes. Regurgitation, struggling, or excess salivation did not occur.
Desflurane MAC in sheep was 9.5% (range, 8.4 to 11.1). HR was not altered by
increasing desflurane concentration, but a significant (p < 0.005) decrease in
median MAP from 101 (range: 90-111) at 1.0 MAC to 64 (47-79) mm Hg occurred at
2.0 MAC. Recovery from anesthesia was rapid and smooth. All ewes stood within
5 minutes of discontinuing anesthesia. Desflurane is an acceptable anesthetic
in sheep, but increasing anesthetic concentration above 1.5 MAC may cause
significant hypotension.
PHARMACOKINETICS OF FENTANYL IN ISOFLURANE- ANESTHETIZED MONKEYS.
CR Valverde, KR Mama,* C Kollias-Baker, EP Steffey,* D Baggot. University of California - Davis, Davis, CA.
Laboratory studies evaluating benefits of continuous fentanyl (FEN) infusion as part of an improved anesthetic management plan for monkeys necessitates knowledge of FEN pharmacokinetics. Accordingly, pharmacokinetic information was derived from six male Rhesus macaques (11.75 ± 1.88 kg [mean ± SD], 10.7 ± 3.0 yrs) anesthetized only with isoflurane (ISO) in O2 and given 8 µg/kg FEN IV. Anesthetic and respiratory gases were continuously sampled from the distal end of the endotracheal tube and analyzed with a calibrated Datex® analyzer. The ECG was monitored continuously. A femoral arterial catheter permitted measurement of mean blood pressure (MAP), and sampling for pH, blood gas, and fentanyl concentration analyses. End-tidal ISO concentration was maintained at 1.2 % [0.8 MAC (rhesus)], and esophageal temperature at 37 ± 1% C. Ventilation was mechanically assisted and PaCO2 ranged from 29.2 ± 3 to 34.6 ± 4.4 mm Hg. Arterial pH and PaO2 ranged from 7.46 ± 0.04 to 7.51 ± 0.05 units and 412.6 ± 105.3 to 482.9 ± 71.2 mm Hg, respectively. Heart rate (HR) and MAP decreased transiently following FEN administration; HR from 123 ± 11.5 to 102 ± 12 beats/minute and MAP from 77 ± 12 to 41 ± 9 mm Hg. Maximal decreases were observed 15 minutes after FEN administration. Non-compartmental methods based on statistical moment theory were used to analyze the plasma drug concentration-time data obtained in each (individual) animal. The Cl_, Vd(area), Vd(ss), MRT, and t1/2 were 32.5 ± 2.4 ml/kg/min, 9.04 ± 1.9 L/kg, 7.0 ± 1.2 L/kg, 218.5 ± 35.5 minutes, and 192 ± 33.5 minutes, respectively. These distribution and clearance data are similar to those reported in the dog and provide information necessary for determination of FEN infusion dose in isoflurane anesthetized Rhesus monkeys.
STRESS-RELATED HORMONAL, METABOLIC, AND BEHAVIORAL RESPONSES TO RESTRAINT AND INTRAVENOUS BUTORPHANOL IN CONDITIONED GOATS.
GL Carroll,* SM Hartsfield,* TM Champney, JA Newman. Texas A & M University, College Station TX.
The purpose of this study was to determine if goats could be conditioned to restraint as measured by physiologic responses, behavior, and stress-related hormonal and metabolic responses (epinephrine [Epi], norepinephrine [NEpi], cortisol [Cort], glucose [Glu], and free fatty acids [FFA]), and to determine if IV butorphanol altered these responses. Each of 12 goats had a catheter inserted into a jugular vein through a lidocaine skin block 1 hour before collecting baseline data. Heart rate (HR), respiratory rate (RR), response to cutaneous stimulation (CS; an indicator of responsiveness) and a behavioral score (SB) were recorded at baseline and q15 minutes for 2 hours. Blood samples were collected from the catheter and temperature (T) was recorded at baseline and q30 minutes for 2 hours. The goats were administered B (0.1 mg/kg, IV) or isovolumetric saline (S) immediately after baseline measurements. Each goat received each treatment (TX). ANOVA showed TX differences (P < 0.05) for RR and Glu and time effects for FFA; TX and time interactions were found for RR, HR, and T. No significant differences were found for Epi, NEpi, or Cort. Wilcoxon signed rank test showed TX differences for CS at 75 minutes and for SB at 15, 30, 45, 60, and 75 minutes. RR ranged from 33-47 (B) and 30-39 (S) breaths/minute, with RR being higher in B than S at 60 minutes; HR ranged from 113-133 (B) and 112-124 (S) beats/minute; in B, HR at 75 minutes was higher than at baseline. T ranged from 39.4-39.7% C (B) and 39.6-39.7% C (S); in B, T was higher at 30 minutes than at 120 minutes. Glu was always lower in B (72-79 mg/dl) than in S (77-85 mg/dl), but did not appear clinically important. FFA were high initially and decreased over time in both TX groups: B (167-59 µEq/L) and S (115-67 µq/L). Behaviorally, the goats were more active and responsive after B than S. Restraint in conditioned goats does not impact on HR, RR, T, Epi, NEpi, Cort, Glu, CS, or SB. B may increase HR and RR, while decreasing T. The clinical impact of the physiologic changes is probably minor, but may impact on interpretation of analgesic efficacy. If stress-related hormonal and metabolic responses are used to evaluate analgesia, B should not impact on these variables. The increase in FFA in both TX groups probably reflects the response to catheterization. B alters behavior in non-painful conditioned goats.
SEVOFLURANE ANESTHESIA IN DESERT TORTOISES (Xerobates agassizi).
JS Gaynor,* MB Rooney, G Levine, E MacDonald, J Wimsatt. Colorado State University, Fort Collins, CO.
The use of inhalant anesthetics in chelonians has become recognized as a
highly effective method of anesthesia for various procedures. This study
investigated the effects of sevoflurane on induction, recovery, ventricular
pressures, heart rate, ventricular pH and blood gas values, and
electrolytes.
Tortoises were orotracheally intubated while awake and ventilated manually
with 5%inspired sevoflurane in oxygen until flaccid head and limbs were
observed as well as loss of righting reflex. Data were collected prior to
anesthesia and at 2.50% and 3.75% expired sevoflurane. Sevoflurane
concentrations were measured with a quartz crystal anesthetic analyzer. Blood
pressure measurement and blood sampling were achieved by placing a 25 ga needle
through a previously placed plastron port into the heart. Blood samples were
immediately withdrawn from the ventricle. The needle was then connected via
saline filled tubing to a pressure transducer zeroed at the level of the heart.
Data were analyzed with a mixed model, least squares analysis of variance for
repeated measures with unequally spaced treatment intervals. Data were
considered significant when P < 0.05. Data are represented as mean ±
SEM.
Induction time was 2.55 ± 0.55 minutes. Recovery time was 27.58
± 7.55 minutes. Awake systolic, diastolic and mean ventricular pressures
were 28 ± 3 mm Hg, 22 ± 2 mm Hg and 24 ± 2 mm Hg,
respectively. Sevoflurane (2.5% expired) significantly decreased systolic (14
± 3 mm Hg), diastolic (12 ± 1 mm Hg), and mean (13 ± 1 mm Hg)
ventricular pressures. Ventricular pressures did not decrease further with
increasing depth of anesthesia. Heart rate (32 ± 4 beats/minute) did not
change significantly with sevoflurane. Ventricular PO2 increased from baseline
with sevoflurane/O2 administration from 54 ± 17 mm Hg at baseline to 100
± 17 mm Hg and 112 ± 17 mm Hg at 2.5% and 3.75% expired sevoflurane
respectively. Ventricular PCO2 decreased from baseline with sevoflurane/O2
administration and positive pressure ventilation from 44 ± 3 mm Hg at
baseline to 33 ± 3 mm Hg and 24 ± 3 mm Hg at 2.5% and 3.75% expired
sevoflurane respectively. Sevoflurane did not change Na+, K+, or iCa++.
Sevoflurane provides effective anesthesia with rapid induction and recovery.
MINIMUM ALVEOLAR CONCENTRATION AND CARDIOVASCULAR EFFECTS OF SEVOFLURANE IN SHEEP.
VM Lukasik, WM Nogami, SE Morgan. University of Arizona, Tucson, AZ.
This investigation was undertaken to determine sevoflurane MAC in adult
sheep and to evaluate the cardiovascular effects of sevoflurane at 1.0, 1.5,
and 2.0 MAC. Anesthesia was induced with 8% sevoflurane in 10 L/minute of O2
delivered by mask to six healthy (determined by physical exam and preanesthetic
hematology and serum chemistry panel) non-pregnant ewes between 1 and 8 years
of age and weighing between 50 and 86 kg. Ewes were intubated within 8
minutes, placed in left lateral recumbency, and ventilated to maintain
end-tidal CO2 at 33-36 mm Hg. Body temperature was maintained at 39% C. The
auricular artery was catheterized and systolic (SP), diastolic (DP), and mean
arterial pressure (MAP) were monitored. To determine MAC, end-tidal (ET)
sevoflurane concentration was allowed to equilibrate 15 minutes prior to
application of a 10 inch hemostat to the coronary band of the right, rear,
lateral dewclaw until the ratchet locked, leaving it in place for 60 seconds.
MAC was determined to be the ET desflurane concentration midway between that
which allowed purposeful movement and that which did not. After completion of
the MAC study, changes in heart rate (HR), SP, DP, and MAP were determined at
1.0, 1.5, and 2.0 MAC. Data were analyzed with Friedman nonparametric repeated
measures test with p < 0.01 considered significant. Data are expressed as the
median and range.
Induction and recovery were smooth and uneventful and all ewes stood within
7 minutes after anesthesia was discontinued. Sevoflurane MAC in sheep is 3.3%
(range, 3.0 to 3.8). HR was not altered by increasing sevoflurane
concentration but a significant decrease (p < 0.002) in median MAP from 98
(range, 91-111) at 1.0 MAC to 61 (58-74) mm Hg at 2.0 MAC occurred.
Sevoflurane is an acceptable inhalant anesthetic in sheep but increasing
anesthetic concentration above 1.5 MAC may cause significant hypotension.
SEVOFLURANE OUTPUT FROM ENFLURANE SPECIFIC VAPORIZERS.
SA Greene* and RD Keegan.* Washington State University, Pullman, WA.
Enflurane and sevoflurane (SEVO) have similar values for vapor pressure. The purpose of this study was to determine whether use of SEVO in an enflurane-specific vaporizer results in vaporizer output similar to that indicated by the vaporizer dial. In this study, SEVO was delivered using either a calibrated Drager Vapor 19.1® enflurane vaporizer or a calibrated Cyprane Enfluratec® vaporizer. Both a calibrated Hewlett Packard (HP) anesthetic gas agent monitor and a calibrated Rascal II® (RS) monitor were used to measure SEVO. Oxygen flow rates of 0.5, 1, 2, 4, and 8 L/minute were studied at vaporizer dial settings of 0.5, 1, 2, 3, 4, 5, and (for the Vapor 19.1®) 6 and 7 %. At each oxygen flow rate, the vaporizer dial setting was set and SEVO output was recorded at 0.5, 1, 2, 3, 4, 5, and 10 minutes after beginning oxygen flow. The averages of measurements taken up and down the dial settings at each oxygen flow rate were used for analyses. Linear regression lines were constructed for data using SEVO concentration plotted against the enflurane dial setting. Regression analysis for the Vapor 19.1® vaporizer yielded these equations: SEVOmeas = -0.04 + (0.91 x dial) @ 0.5 L/minute and SEVOmeas = 0.30 + (0.69 x dial) @ 8 L/minute and the Enfluratec® vaporizer yielded these equations: SEVOmeas = -0.13 + (0.97 x dial) @ 0.5 L/minute and SEVOmeas = 0.10 + (0.70 x dial) @ 8 L/minute. Equations for flow rates of 1, 2, and 4 L/minute were similar to those obtained for 0.5 L/minute. Vaporizer output was most variable at an oxygen flow rate of 8 L/minute. We conclude that these enflurane-specific vaporizers delivered SEVO concentrations that are similar to the expected output as indicated by the vaporizer dial and are reasonably accurate for clinical use when using flow rates of 4 L/minute or less.
A COMPARISON OF TRANSDERMAL FENTANYL AND ORAL PHENYLBUTAZONE FOR POSTOPERATIVE ANALGESIA IN SHEEP.
G Dowd, JS Gaynor,* M Alvis, M Salman, AS Turner. Colorado State University, Fort Collins, CO.
Sheep are increasingly used as animals for comparative orthopedic research. Intravenous fentanyl and oral phenylbutazone have been shown to provide analgesia for variable amounts of time. The effects of transdermal fentanyl have not been investigated in sheep. The purpose of this study was to compare the effects of transdermal fentanyl and oral phenylbutazone for the treatment of postoperative orthopedic pain. Twelve sheep were randomly assigned to receive either transdermal fentanyl (TF) or oral phenylbutazone (P). Based on pilot studies, sheep in the TF group received 3 transdermal fentanyl patches (50 µg/hr) 24 hours prior to surgery. Sheep in the P group received phenylbutazone (2 mg/kg) intravenously immediately prior to surgical incision and orally BID for 72 hours. All sheep had abdominal wraps to blind the 18 evaluators to treatment. All sheep received diazepam-ketamine intravenously, followed by halothane in oxygen. Sheep underwent unilateral stifle surgery. Blood samples were collected preoperatively and at 24, 48, and 72 hours postoperatively to determine plasma cortisol and fentanyl levels. Sheep were evaluated 24, 48, and 72 hours postoperatively for comfort (0-4), movement (0-4), flock behavior (0-3), feeding behavior (0-3), and respiratory rate (0-3) based on specific criteria and scoring systems, and for pain on a visual analog scale (0-10). Lower values indicated normal behavior or no pain, respectively. Data were analyzed with a one-way ANOVA for repeated measures. Data were considered significant when P < 0.05. Sheep in the TF group had plasma levels consistent with analgesia in other species. Sheep in the TF group had significantly more normal scores for movement (1.03 vs 1.16) and flock behavior (0.13 vs 0.37) and significantly lower plasma cortisol levels compared to the P group. There were no other differences between groups. Transdermal fentanyl appears to provide equivalent if not better analgesia than oral phenylbutazone for postoperative orthopedic pain using the criteria in this study.
COMPARISON OF THERMODILUTION CARDIAC OUTPUT MEASUREMENTS WITH CARDIAC OUTPUT MEASUREMENTS OBTAINED USING TRANSIT-TIME ULTRASONIC FLOW PROBES IN DOGS.
RD Keegan,* RL Tucker, SA Greene,* AH Tobias, C Peng. Washington State University, Pullman, WA.
To compare the accuracy of two temperature ranges of thermodilution (TD) thermal indicators, cardiac output (CO) was determined in 6 healthy dogs (23 - 39 kg) during halothane (HAL) anesthesia. Anesthesia was induced by administration of halothane in 50% N20 and O2. The electrocardiogram (ECG), pulmonary blood temperature and end-tidal HAL and CO2 tensions were measured. Ventilation was controlled to maintain normocapnia. TD CO was measured with the use of a 110 cm balloon-tipped TD catheter (Swan-Ganz) that was inserted percutaneously via a catheter introducer into the right jugular vein. The catheter was advanced to the level of the pulmonary artery with the aid of fluoroscopy and securely fixed in position. Ultrasonic flow probe CO was measured with the use of a 16-20 mm transit-time ultrasonic flow probe placed around the ascending aortic root. Placement of the flow probe was facilitated by a median sternotomy incision. TD CO measurement was made using 5 ml of 5% dextrose in 2 temperature ranges (20-24% C and 0-5% C) as the thermal indicator. CO for each dog was varied by using dobutamine infusion and/or changing inspired HAL concentration. TD cardiac output values obtained over a range of cardiac outputs from each indicator temperature range were compared to those obtained simultaneously from the same dogs using the ultrasonic transit-time volume flow meter. Multiple linear regression was used to evaluate relationships between room temperature or iced dextrose indicators and the ultrasound flow probe. TD CO measurements made with room temperature or iced indicator had adjusted R2 values of 0.963 and 0.974 respectively, throughout the range of cardiac outputs studied. We conclude that TD CO determination using 5 ml of either room temperature or iced dextrose as the thermal indicator accurately predicts CO values measured by an aortic ultrasonic flow probe.
MINIMUM ALVEOLAR CONCENTRATION AND CARDIOVASCULAR EFFECTS OF SEVOFLURANE IN THE PREGNANT EWE AND LAMB FETUS.
VM Lukasik, WM Nogami, SE Morgan, KR Reed. University of Arizona, Tucson, AZ.
This investigation was undertaken to determine sevoflurane MAC in pregnant
ewes and to evaluate the maternal and fetal cardiovascular effects of
increasing sevoflurane concentrations. After a 7 day conditioning period, four
healthy (determined by physical exam and preanesthetic hematology and serum
chemistry panel) pregnant ewes, weighing between 37-39 kg at 127 days
gestation, were instrumented with a maternal jugular catheter, an ultrasonic
flow probe placed around the uterine artery supplying the horn occupied by the
fetus, and a fetal femoral arterial catheter. A 5 day recovery was allowed
prior to the investigation. On the day of the investigation, anesthesia was
induced in the ewes with sevoflurane in O2 delivered by mask. Ewes were
intubated, placed in left lateral recumbency, and ventilated to maintain
end-tidal CO2 at 35-37 mm Hg. Body temperature was maintained at 38% C during
the investigation. The auricular artery was catheterized and systolic (SP),
diastolic (DP), and mean arterial pressure (MAP) were monitored. To determine
MAC, end-tidal (ET) anesthetic concentration was allowed to equilibrate 15
minutes prior to application of a 10 inch hemostat to the coronary band of the
right, rear, lateral dewclaw until the ratchet locked, leaving it in place for
60 seconds. MAC was determined to be the ET desflurane concentration midway
between that which allowed purposeful movement and that which did not. After
completion of the MAC investigation, changes in maternal and fetal heart rate
(HR), MAP, arterial blood gas (ABG), and uterine blood flow (UBF) were
determined at 1.0, 1.5, and 2.0 MAC. Data are expressed as the median and
range.
Sevoflurane MAC in pregnant ewes was 2.2% (range, 2.1 to 2.2), a decrease of
33% from non-pregnant ewes (MAC 3.3%). Increasing ET sevoflurane concentration
decreased median maternal HR from 104 (101-120) at 1.0 MAC to 83 (76-101)
beats/minute at 2.0 MAC, median MAP from 96 (87-99) at 1.0 MAC to 60 (47-67) mm
Hg at 2.0 MAC, and median UBF from 274 (248-312) at 1.0 MAC to 173 (140-204)
ml/minute at 2.0 MAC. Median fetal HR decreased from 152 (123-170) at 1.0 MAC
to 131 (116-143) beats/minute at 2.0 MAC. Fetal MAP was not affected.
Maternal ABG was not affected, but median fetal PaCO2 increased from 50 (47-54)
at 1.0 MAC to 59 (57-61) mm Hg at 2.0 MAC and median PaO2 decreased from 23
(21-25) at 1.0 MAC to 17 (13-21) mm Hg at 2.0 MAC. Sevoflurane may be an
acceptable inhalant anesthetic for general anesthesia during pregnancy but
increasing anesthetic concentration above 1.5 MAC may cause fetal compromise.
PRE-ANESTHETIC LABORATORY TESTING - A SURVEY OF CLIENT COMPLIANCE RATE AND INCIDENCE OF ABNORMAL TEST RESULTS: PRELIMINARY RESULTS.
JA Smith*,+ and NS Matthews.*,** +Louisiana State University, Baton Rouge, LA; and **Texas A & M University, College Station, TX.
This study was undertaken with three primary objectives: (1) to determine client compliance rate regarding pre-anesthetic laboratory testing; (2) to determine the incidence of laboratory test abnormalities in different age and risk category animals; and (3) to survey anesthetic practices of the participating clinics (data not included). Twenty private veterinary practices in eighteen states were randomly selected from a list of clinics known to have in-house laboratory testing equipment. Each participating clinic was asked to record information on the next fifty consecutive dogs and cats requiring anesthesia for any reason. Each clinic was sent a package of fifty client consent forms and patient data forms, and instructed to complete one for each animal. Data recorded included signalment, presenting signs, reason for anesthesia and pre-operative physical exam results. Complete blood count and serum chemistry profile, including electrolytes, were performed on all animals regardless of consent. If the owner did not consent to pre-operative examination, then they were asked for permission to collect blood from their pet while in the hospital. Results were collected within a six-week period, and an honorarium was paid to each clinic upon receipt of the completed data packages. Nineteen clinics returned their packages, and, of those, only one clinic failed to obtain all fifty. A total of 913 observations (625 dogs; 288 cats) were recorded. Client compliance (consent for pre-operative laboratory examination) averaged 70%, with cost being the most common reason for declining. Abnormal results in 11% of cases prompted an alteration in anesthetic approach. Surgery was postponed in 33% of these. Pre-anesthetic laboratory testing is well accepted by clients and may identify an underlying disease process causing a change in anesthetic management or further diagnostic evaluation.
CARDIOPULMONARY AND BEHAVIORAL EFFECTS OF MIDAZOLAM HCl AND REVERSAL WITH FLUMAZENIL IN PONY FOALS.
JL Cornick-Seahorn* and TL Seahorn. Louisiana State University, Baton Rouge, LA.
An advantage of benzodiazepine administration is minimal cardiopulmonary depression. Unfortunately, diazepam alone produces minimal tranquilization and may, in fact, promote restlessness in adult horses. Minimal cardiopulmonary depression is a desirable quality for a sedative used for chemical restraint or as a premedication for general anesthesia in foals. Seven pony foals (2 - 12 weeks old) were anesthetized with isoflurane for arterial catheter placement and allowed to recover for 30 minutes prior to recording baseline values for HR, RR, arterial SAP, DAP and MAP (ABP) and blood gas analysis. Following midazolam administration (0.44 mg/kg IV), HR, RR and ABP were recorded every 5 minutes for 15 minutes and blood gas analysis was performed at 15 minutes. Flumazenil (0.01 mg/kg IV) was administered 15 minutes after midazolam administration and HR, RR and ABP were recorded 5 minutes after injection. Data was evaluated using nonparametric analysis (Friedman's test). Experiment-wise error was set at Alpha = 0.05. Heart rate and ABP increased significantly following midazolam administration. RR showed an inconsistent change, increasing in some foals (n = 4) and decreasing in others (n = 3). Blood gas values did not change significantly following midazolam administration. Clinical effects included weakness, periods of lethargy from which the foals could be easily aroused, hyperreactivity to touch, and nystagmus. All foals became difficult to restrain by 15 minutes thus the monitoring period was limited to this time frame. No significant changes in HR or ABP occurred at 5 minutes after flumazenil administration but RR did increase in 5 foals. Lethargy or weakness did not persist after flumazenil administration. This study suggests that 1) midazolam administration produces a modest increase in HR and ABP and an inconsistent effect on RR in pony foals; 2) reversal of midazolam with flumazenil in pony foals produces no adverse effect; and 3) midazolam alone is not effective for chemical restraint in pony foals.
RISK FACTOR ANALYSIS OF NEONATAL MORTALITY AFTER CESAREAN SECTION IN A NORTH AMERICAN DOG POPULATION.
PF Moon,*,+ HN Erb,+ JW Ludders,*,+ RD Gleed,*,+ PJ Pascoe.*,** +Cornell University, Ithaca, NY; and **University of California, Davis, CA.
A prospective study (109 private and institutional practices) assessed perioperative risk factors for neonatal mortality in 808 litters requiring cesarean surgery for delivery of at least 1 puppy. Risk factors were based on 2 outcomes: percentage of all puppies delivered by cesarean section that were alive at surgery (pupbirth), and the percentage that were alive at 2 hrs (pup2hr). Due to skewedness of the data, non-parametric statistics were used: Wilcoxon's rank-sum test evaluated yes/no factors, the Kruskal-Wallis test evaluated factors with greater than two levels of categories, and Spearman's rank correlation evaluated ordinal or continuous factors. For preliminary analysis, 2-sided alpha = 10% was chosen and risk-factors were tested without adjusting for other variables. For pupbirth, the following factors were associated with a higher puppy mortality: emergency surgery, brachycephalic or mesaticephalic maternal head type, large litter size, deformed puppies present in the litter, treatment of the dam with antibiotics, and the use of xylazine, ketamine or methoxyflurane. For pup2hr, the following factors were associated with a higher puppy mortality: brachycephalic maternal head type, dam was a bulldog, longer overall surgery and anesthesia time as well as longer time to deliver the first puppy; deformed puppies in the litter, and non-vigorous puppies at birth (vigorous = spontaneously breathing, moving or vocalizing). No anesthetic drugs were associated with a higher puppy mortality at pup2hr.
THE INFLUENCE OF BUTORPHANOL ON THE HALOTHANE SPARING EFFECT OF XYLAZINE.
RC Bennett and EP Steffey.* University of California - Davis, Davis, CA.
Xylazine (XYL) has been shown to cause consistent, dose-related decrease in isoflurane MAC in horses. The aim of this study was to confirm that XYL decreased halothane (HALO) MAC and to determine if butorphanol (BUT) increased the XYL induced HALO sparing effect. Four unpremedicated, fasted horses [2-6 years, weight 495 ± 32 (mean ± SD) kg] were anesthetized three times, (a minimum of 10 days apart) using HALO in oxygen. After determining HALO MAC in triplicate in each horse, on each study day, horses were given one of three randomly assigned intravenous treatments: 0.5 mg/kg XYL plus either saline, 0.03 mg/kg BUT or 0.06 mg/kg BUT. MAC was then redetermined at least four times over the following 2-3 hours. XYL plus saline decreased HALO MAC by 24.2 ± 2.4% at 40.0 ± 10.1 minutes following injection. HALO MAC then returned to control values over the subsequent three hours. Low dose BUT did not produce any further reduction in HALO MAC compared to results using XYL alone. High dose BUT produced a 11.1 ± 19.4% increase in HALO MAC at 80.0 ± 5.9 minutes in contrast to a MAC reduction of 11.6 ± 8.0% at 72.0 ± 2.9 minutes using XYL alone. Butorphanol does not increase the MAC sparing effect of XYL in horses and may even decrease it at higher dose rates.
EFFECTS OF MEDETOMIDINE ON RENAL TUBULAR FUNCTION IN DOGS.
SA Burton, KA Lemke,* SL Ihle, AL MacKenzie. University of Prince Edward Island, Charlottetown, PEI, Canada.
Alpha-2 agonists increase urine production in several species. The purpose of the study reported here was to determine the effects of medetomidine administration on renal tubular function in dogs. Six healthy, adult Beagles were assigned at random to each of three treatments. At least three weeks were allowed to elapse between trials in the same dog. Serum and urine osmolality, urine specific gravity, urine volume, urine pH, and fractional clearances of sodium, chloride, potassium and glucose were determined 20, 40, 60, 120, 180, 240, 300, 360, 420 and 480 minutes after intravenous administration of 0.9% saline solution or medetomidine (10 or 20 µg/kg IV). Data from each sampling time were analyzed using 1-way repeated measures ANOVA. Serum osmolality increased after medetomidine administration and was significantly (P < 0.05) higher than respective saline values at 60, 120, 180, 240 and 300 minutes. Urine osmolality and specific gravity decreased after medetomidine administration, and were lower than respective saline values at 60, 120, 180 and 240 minutes. Urine volume increased after medetomidine administration, and was higher than respective saline values at 120 and 180 minutes. Urine pH decreased after medetomidine administration, and was lower than respective saline values at 60, 120 and 180 minutes. Fractional clearance of sodium did not change after medetomidine administration. Fractional clearances of chloride and potassium increased after medetomidine administration, and were higher than respective saline values at 300, 360 and 420 minutes. Fractional clearance of glucose increased after medetomidine administration, and was higher than the respective saline value at 120 minutes. Medetomidine given intravenously at dosages of 10 and 20 µg/kg alters renal tubular function for up to 8 hours in normal dogs.
CARDIOPULMONARY EFFECTS OF LOW-DOSE MEDETOMIDINE AND XYLAZINE IN ENDOTOXIN-CHALLENGED HORSES.
JL Cornick-Seahorn,* E Bueno, R Moore, and TL Seahorn. Louisiana State University, Baton Rouge, LA.
Alpha-2 agonists, most commonly xylazine, are used at relatively low dosages as premedication to general anesthesia and to control pain associated with gastrointestinal crises. Cardiopulmonary data on xylazine in horses has most commonly been reported for high-dose administration. Studies on medetomidine in horses have established an equipotent dose in relation to xylazine and cardiopulmonary effects of medetomidine have been reported in ponies but not in horses. This study investigated the acute cardiopulmonary effects of low-dose xylazine and an approximate equipotent dose of medetomidine, both administered IV to mature female horses previously challenged with E. coli endotoxin 055:B5 LPS. Ten healthy adult mares of a variety of breeds were instrumented for measurement of HR, RR, arterial SAP, DAP and MAP (ABP), pulmonary arterial SAP, DAP and MAP (PABP), cardiac output (CO), and core body temperature. Endotoxin (35 ng/kg) was administered 24 hours prior to drug administration. Following recording of the above baseline values and arterial blood gas analysis, horses were given either medetomidine: 4 µg/kg IV (Group 1; n = 5) or xylazine: 0.4 mg/kg IV (Group 2; n = 5). All measurements were recorded every 5 minutes, except for body temperature and blood gas analyses which were performed every 15 minutes, for a total of 60 minutes. Additionally, sedation and ataxia scores were assigned at baseline and every 5 minutes of the monitoring period. All data was analyzed using nonparametric analysis (Friedman's test). Experimentwise error was set at Alpha = 0.05. A significant decrease occurred for both groups in RR, ABP, PABP, and CO over time but there was no statistically significant difference between groups. The decrease in PABP and CO was transient with return to baseline values by 10-15 minutes after drug injection. The decrease in ABP persisted throughout the monitoring period for both groups. Despite the significant decrease in RR, blood gas values did not change over time. Ataxia and sedation scores were similar for both groups with all horses resuming eating by 10 to 30 minutes after drug injection. This study suggests that equipotent low-doses of medetomidine and xylazine produce similar cardiopulmonary changes of the same duration in endotoxin-challenged adult horses.
PHARMACOKINETICS OF INTRAVENOUS MIVACURIUM IN HALOTHANE-ANESTHETIZED DOGS.
LJ Smith,*,+ WS Schwark,+ DR Cook,** PF Moon,*,+ HN Erb,+ AL Looney.+ +Cornell University, Ithaca, NY; and **University of Pittsburgh, Pittsburgh, PA.
Mivacurium (MIV) is a non-depolarizing muscle relaxant commercially available as a racemic mix of 2 predominant isomers. In humans MIV has a small Vd, a short t1/2_, and rapid clearance. MIV is metabolized by plasma cholinesterase. The purpose of this study was to describe the pharmacokinetics of MIV after IV administration in dogs. Seven healthy dogs were anesthetized with thiopental (12 mg/kg) and maintained with halothane in oxygen. Dogs were mechanically ventilated to an end-tidal CO2 of 35-40 mm Hg. MIV was administered at 0.05 mg/kg IV by rapid bolus. Arterial blood was collected for determination of plasma MIV concentration at 0, 3, 5, 10, 15, 30, 60, 90, 120, and 180 minutes after MIV administration. Blood was collected into EDTA tubes containing 0.25% echothiophate (a potent cholinesterase inhibitor) to prevent in vitro metabolism of MIV. MIV concentration was determined using reversed phase HPLC with atracurium as the internal standard. Pharmacokinetic parameters were determined using PharmK® software. Data are expressed as mean ± SD. Mean end-tidal halothane concentration was 0.9 ± 0.3%. For the trans-trans isomer Vd (L/kg) was 0.18 ± 0.024, t1/2_ (minutes) was 10.4 and clearance (ml/min/kg) was 12 ± 2. For the cis-trans isomer these values were 0.31 ± 0.05, 14.3, and 15 ± 2. In humans, Vd, t1/2_, and clearance for the trans-trans isomer are 0.21 ± 0.08, 2.3 (range 1.6 - 8.1), and 57 ± 18. In humans, these values for the cis-trans isomer are 0.28 ± 0.14, 2.0 (range 1.3 - 4.4), and 106 ± 36. There is a much longer t1/2_ and slower clearance of MIV in dogs compared with that in humans, although Vd does not differ significantly between these two species.
COMPARISON OF XYLAZINE OR DIAZEPAM AND BUTORPHANOL FOLLOWED BY KETAMINE AND DIAZEPAM FOR INDUCTION OF ANESTHESIA IN FOALS UNDERGOING PERIOSTEAL STRIPPING.
SA Robertson,*,+ SJ Holcombe,+ J Colon,** S Ahlschwede.** +Michigan State University, East Lansing, MI; and **Rood & Riddle Equine Hospital, Lexington, KY.
The purpose of this study was to compare xylazine [X] or butorphanol [B] plus diazepam [D] followed by D/ketamine and isoflurane in foals scheduled for periosteal stripping. Foals were randomly assigned to receive 0.1 mg/kg B and 0.1 mg/kg D IV [group A, n = 6] or 0.8 mg/kg X IV [group B, n = 10]. Five minutes later all foals received D [0.1 mg/kg] and ketamine [2 mg/kg] IV, were intubated and maintained with isoflurane. Mean preparation and surgery times were 17 and 10 minutes respectively. Respiratory rate [RR], heart rate [HR] and rectal temperature [T] were recorded before and after sedation [S] and at 2, 5, 10, 15 and 20 minutes post induction [PI]. Direct arterial blood pressure [MAP] was recorded at 2, 5, 10, 15 and 20 minutes PI. Quality of induction, recovery and muscle relaxation were scored on a scale of 1 to 3 [1, excellent; 3, poor]. Time to induction [TI] and recovery were recorded. RR, HR, T and MAP data were analyzed using a 2 way ANOVA for repeated measures. Other comparisons between the groups were analyzed using an unpaired t-test. There was no significant difference [mean ± SD] in age [A: 32 ± 14, B: 43 ± 15 days] or weight [A: 90 ± 14, B: 109 ± 21 kg] between the groups. TI was 23 ± 9 and 27 ± 10 seconds in group A and B respectively. HR did not change in group B and was increased after S and at 2 and 20 minutes PI in group A. HR was significantly higher in group A foals after S until the end of the study. RR decreased significantly [50%] and remained low in both groups after induction. T did not change over time in group A and rose at 2 and 5 minutes PI in group B. T was not significantly different between groups. MAP was well maintained in all foals during anesthesia [MAP > 65 mm Hg] with no difference between groups. There was no difference in time to sternal recumbency [A: 16 ± 7, B: 17 ± 10 minutes] or standing [A: 22 ± 9, B: 25 ± 11 minutes] between groups after isoflurane was discontinued. Induction score was 1 for both groups. Recovery score was 1.5 and 1.3 for group A and B respectively. Muscle relaxation was scored as 1.5 in groups A and 1 in group B. In healthy foals X or B + D are acceptable premedicant agents when followed by D/K and isoflurane. X appears to offer superior muscle relaxation.
MECHANISM FOR THE DIFFERENTIAL ONSET AND OFFSET OF ROCURONIUM AND MIVACURIUM BLOCKADE.
C Ibebunjo and F Donati. Royal Victoria Hospital and McGill University, Montreal, Canada.
Onset and offset of neuromuscular blockade are governed by circulatory factors, drug potency, rate of plasma drug clearance, and rate of drug access to and from the synaptic cleft. We investigated the influence of drug access to the synaptic cleft on onset and offset after bypassing circulatory and clearance factors by intra-arterial (i.a.) injection of rocuronium (ROC) or mivacurium (MIV). In cats anesthetized with pentobarbital, the femoral artery and vein in one hind leg were cannulated for monitoring blood pressure and injecting fluids and anesthetic agents. The other hind leg had the femoral artery cannulated for i.a. injections, and the sciatic nerve stimulated at 0.1 Hz (during onset) or at 2 Hz for 2 seconds every 12 seconds (during recovery) while recording the evoked EMG in the tibialis and soleus muscles. The masseter muscle was also monitored to estimate systemic drug levels. The evoked EMG before injection of MIV or ROC was taken as baseline (control) response. After obtaining stable baseline records, a dose of ROC or MIV (n = 7 - 8 each) that produced ~ 90 ± 5% blockade in the tibialis muscle was injected i.a. over 10 seconds. Maximum blockade (%), time from injection to maximum blockade (onset time), time for recovery of the first of the train-of-four responses (T1), time 50% of baseline (RecT50), and time for recovery of T1 from 25 to 75% of baseline (recovery index, RI) were compared between muscles and drugs. In the tibialis muscle, a dose of ROC and MIV that produced 98 ± 0.6% (mean ± SEM) vs 92 ± 2% block had onset times of 0.5 ± 0.1 vs 2.2 ± 0.4 minutes, RecT50 of 3.7 ± 0.6 vs 8.0 ± 1.5 minutes, and RI of l.5 ± 0.2 vs 3.4 ± 0.3 minutes, respectively. In the soleus muscle, maximum blockade after ROC and MIV was 96.3 ± 1.3% vs 83.5 ± 4.2%, onset time was 0.8 ± 0.2 vs 3.5 ± 0.4 minutes, RecT50 was 5.0 ± 0.8 vs 9.6 ± 1.5 minutes, and RI was 2.3 ± 0.3 and 4.8 ± 0.7 minutes, respectively. In each muscle, maximum blockade was greater, while onset time, RecT50 and RI were shorter after ROC than MIV (P < 0.05). For each drug, onset time, RecT50 and RI tended to be shorter in the tibialis than in the soleus muscle (P > 0.05). These results indicate that the rate of drug diffusion between the plasma and post-synaptic acetylcholine receptors differs among drugs and muscles, probably reflecting differences in drug potency and the ultra-structure of peri-junctional tissues, respectively. This might explain, at least partially, differences in onset and offset of blockade among nondepolarizing neuromuscular blockers and muscles.
PROPOFOL VERSUS KETAMINE FOR TOTAL INTRAVENOUS ANESTHESIA IN THE HORSE.
KR Mama,* PJ Pascoe,* EP Steffey,* C Kollias-Baker. University of California - Davis, Davis, CA.
Six horses (13.6 ± 2.8 yrs, 534 ± 37 kg [mean ± SD]) were
anesthetized 3 times under laboratory conditions to characterize physiologic
(presented elsewhere) and behavioral responses associated with a 1 hour period
of total intravenous anesthesia (TIVA). Each horse was premedicated with
xylazine (X, 0.75 mg/kg) and anesthesia induced 5 minutes later with 10%
guaifenesin (75 mg/kg) and either ketamine (K, 2 mg/kg) or propofol (P, 2
mg/kg) all IV. After anesthetic induction each horse received an infusion of X
(35 µg/kg/min) and either K (90 µg/kg/min) or one of two doses of P (LP, 0.15
mg/kg/min, and HP, 0.25 mg/kg/min). Infusion drug was linked to induction
drug. Treatment order was determined by a series of Latin Squares. Quality of
anesthetic induction was assessed independently by three investigators (KRM,
PJP, and EPS). All horses breathed O2 from a large animal breathing circuit
(FIO2 > 95 %). Arterial blood was collected for determination of X, K and P
concentrations before anesthesia and at 20, 40 and 60 minutes following start
of the infusion. A noxious electrical stimulus was applied to oral membranes
after each sample and any purposeful movement recorded. After the final set of
measurements was obtained, drug infusions were discontinued and the horses
allowed to recover unassisted. Nature of recovery was independently assessed by
two investigators (EPS, PJP or KRM). Times to sternal recumbency and standing
were recorded.
Induction and recovery quality were good to excellent in all horses. Mean
plasma X concentrations were similar for all groups (1.1 ± 0.1 µg/ml
[mean ± SD]). Mean P concentrations were 4.5 ± 0.74 µg/ml in the
LP group and 6.6 ± 0.82 µg/ml in the HP group. Ketamine concentration
averaged 2.2 ± 0.48 µg/ml. No purposeful responses were observed in
the HP group. Four horses responded at all time points in the K group; one
responded in the LP group. Mean times to sternal recumbency and standing were
36 ± 12 and 42 ± 13, 74 ± 31 and 80 ± 33, 75 ± 15
and 91 ± 36 minutes in the K, LP and HP groups, respectively. None of
the TIVA techniques studied here were flawless from a clinical perspective but
results encourage further study.
ONSET AND DURATION OF ACTION AND HEMODYNAMIC EFFECTS OF MIVACURIUM IN HALOTHANE-ANESTHETIZED DOGS.
LJ Smith,* PF Moon,* HN Erb. Cornell University, Ithaca, NY.
Mivacurium (MIV) is a non-depolarizing muscle relaxant with duration of action in humans of 21 minutes at dosages of 0.10 mg/kg. MIV is metabolized by plasma cholinesterase. The purpose of this study was to define onset time and duration of MIV and its hemodynamic properties in dogs. Seven healthy dogs were anesthetized with thiopental (12 mg/kg) and maintained with halothane. Dogs were mechanically ventilated to an end-tidal CO2 of 35-40 mm Hg. HR, direct BP, core temperature and pH were monitored throughout each trial. Blood was collected for determination of plasma cholinesterase activity prior to administration of MIV. Neuromuscular function was assessed with a supramaximal square wave pulse applied to the ulnar nerve at 2 Hz (train-of-four) delivered every 10 seconds. MIV was administered by bolus at 3 dosages (0.01, 0.02, and 0.05 mg/kg IV) in a randomized block. Hemodynamic data and onset and duration times were analyzed with repeated-measures ANOVA. All data are expressed as mean ± standard deviation. Mean end-tidal halothane concentration was 0.9 ± 0.3%. All dogs had normal plasma cholinesterase activity. There was no difference between groups in HR, MAP, SAP, DAP, temperature, pH, or end-tidal [halothane]. There was no change at any time in HR, MAP, SAP, or DAP following administration of MIV at any of the 3 doses tested. Onset time to 100% neuromuscular blockade (TOF = 0) was 3.92 ± 1.7 min at 0.01 mg/kg, 2.42 ± 0.53 min at 0.02 mg/kg, and 1.63 ± 0.25 min at 0.05 mg/kg. Measurable neuromuscular blockade (TOF < 1) lasted 33.72 ± 12.73 minutes at 0.01 mg/kg, 65.38 ± 12.82 minutes at 0.02 mg/kg, and 151.0 ± 38.5 min at 0.05 mg/kg. MIV has a faster onset and longer duration in the dog than that reported for humans at dosages up to twice higher.
DECREASE IN BODY TEMPERATURE OF HORSES UNDER GENERAL ANESTHESIA.
M Tomasic,* University of Pennsylvania, Kennett Square, PA.
Anesthesia of mammals is generally associated with decrease in body temperature. This study investigated the effects of general anesthesia on body temperature in 5 mature horses (499-568 kg). A thermistor tipped catheter was passed into the pulmonary artery via the right jugular vein through a catheter introducer sheath allowing measurement of pulmonary arterial (CORE) temperatures. Prior to sedation with detomidine (5-7 mg IV), initial core temperatures were recorded. Following sedation, anesthesia was induced using rapid guaifenesin infusion (12.5-23 gm) and ketamine bolus (1.2-2 gm). Horses were positioned on a surgical table in left lateral recumbency, intubated, connected to a large animal rebreathing circuit, and allowed to breathe spontaneously. Anesthesia was maintained with halothane using a precision vaporizer adjusted to maintain end tidal halothane at 1.0%. After 150 minutes of anesthesia (END), the horses were disconnected from the breathing circuit and placed in left lateral recumbency in an adjoining recovery stall. CORE temperatures were recorded every 5 minutes during anesthesia and recovery until the animals stood, then every 15 minutes until CORE temperatures returned to initial values. Initial mean CORE temperature was 37.6% C. Temperatures dropped in a nearly linear fashion at a mean rate of 0.007%C/minute to a mean value of 36.6% C prior to moving horses to the recovery area. Placing horses in the recovery stall resulted in more rapid decrease in CORE temperature with the mean low of 35.5% C being reached in an average of 13 minutes after END. Mean time to sternal recumbency was 25 minutes after END at which time mean CORE temperature was 36.1% C. Mean time to standing was 34 minutes after END at which time mean CORE temperature was 36.6% C. CORE temperatures returned to initial values at a mean time of 74 minutes after END. These results show in horses that CORE temperature decreases steadily during 2.5 hours of general anesthesia and that movement of the animals to the recovery area is associated with further and more rapid decreases in CORE temperature.
THE EFFECT OF EPIDURAL MORPHINE ON THE MINIMUM ALVEOLAR CONCENTRATION OF ISOFLURANE IN CATS.
FJ Golder, PJ Pascoe,* CS Bailey, JE Ilkiw, LD Tripp. University of California- Davis, Davis, CA.
Epidural morphine has been evaluated in dogs but there is little information
on its use in cats. This study was undertaken to evaluate the effect of three
different doses of epidurally administered morphine sulfate on the MAC of
isoflurane in healthy cats. Five healthy 4 year old, spayed female,
conditioned domestic cats weighing 4.7 ± 0.8 kg were used in this study.
A chronically indwelling epidural catheter was implanted into each cat at least
2 weeks prior to the study. The placement of the catheter was confirmed before
and at the end of the study with contrast radiography. Three studies were
carried out with 2 weeks between studies. On each study day, cats were
anesthetized with isoflurane and instrumented. The cats were ventilated to
maintain PaCO2 at 35.8 ± 7.4 mm Hg. Body temperature was maintained at
38.2 ± 0.3% C. MAC of isoflurane was determined in triplicate and
morphine sulfate was administered epidurally via the epidural catheter at a
dose of 0.05 mg/kg, 0.10 mg/kg, or 0.20 mg/kg. Maximum MAC reduction was
determined over the following 2 hours. At the end of the study cats were
allowed to recover. Data are expressed as mean ± SD and were analyzed
with ANOVA for repeated measures with t-tests to confirm any differences with P
< 0.05 considered significant.
All doses of epidural morphine significantly decreased the MAC of isoflurane
in healthy cats (P < 0.01). The maximum reduction in MAC of isoflurane
after 0.05 mg/kg, 0.10 mg/kg, and 0.20 mg/kg morphine was 21.4 ± 9.7%,
30.8 ± 9.6%, and 30.2 ± 6.8% respectively. There were no
significant differences between doses. Epidural administration of morphine was
associated with a decrease in mean blood pressure (105 ± 26 to 64 ±
12 mm Hg) and heart rate (164 ± 26 to 123 ± 29 beats/minute). We
conclude that epidural morphine decreases MAC of isoflurane in healthy cats.
MODE OF VENTILATION INFLUENCES THE HORSE'S CARDIOVASCULAR RESPONSE TO THREE HOURS OF HYPOXEMIA.
EP Steffeyi,* K Jarvis, MJ Woliner, NH Willits. University of California - Davis, Davis, CA.
The focus of this study was to determine the influence of mode of ventilation on circulatory responses of six young adult, healthy, laterally recumbent, halothane (HALO) anesthetized horses to a 3 hour sustained level of hypoxemia. Horses were similarly anesthetized only with HALO on three separate occasions to facilitate study under conditions of spontaneous (SV) and controlled (CV) ventilation (Latin Square design). One hour after anesthetic induction inspired HALO (in O2) concentration was adjusted to maintain constant alveolar concentration of 1.06% (1.2 MAC). At 2 hours post-anesthetic induction, PaO2 was adjusted to either 120 or 50 mm Hg by varying inspired nitrogen concentration and conditions changed from SV to either SV and PaO2 of 120 (SV120) or 50 (SV50) mm Hg respectively, or CV and PaO2 of 50 mm Hg (CV50). Conditions of HALO dose, PaO2, mode of ventilation were then maintained constant for the next 3 hours. Circulatory measurements were made at 0.5 hours before altered PaO2 and at 0.5, 1, 2 and 3 hours during altered PaO2. Grouped results are described as mean ± SEM. Data were analyzed by log transformation and repeated-measured ANOVA with P oe 0.05 considered significant. During hypoxemia cardiac output was less (by 6.2 L/minute or 20%) during CV compared to SV because stroke volume was greater (by 692 ml or 21.2 %) during SV. Heart rate did not differ between SV and CV. As a result, O2 delivery was 20.3% less during CV vs SV. Mean arterial blood pressure was also significantly less during CV vs SV at all time points. Comparable pretreatment values did not differ for CV vs SV and change with time of hypoxemia did not occur regardless of the mode of ventilation. The PaCO2 averaged 44.5 ± 0.3, 60.4 ± 0.9, and 67.7 ± 0.9 mm Hg for CV50, SV50 and SV120 respectively. These results indicate that during hypoxemia and halothane anesthesia, circulatory function, and as a result O2 delivery, was better with SV and associated moderate hypercapnia than with CV and normocapnia.
EPIDURAL ENCAPSULATED MORPHINE IN DOGS: ANALGESIA AND KINETICS.
JC Dragani,+ ML Rathbun,+ TL Yaksh,+ FR Kohn,** RR Myers.+ +University of California - San Diego, La Jolla, CA; and **DepoTech Corp, San Diego, CA.
To extend the analgesic actions of epidural morphine, it may be possible to deliver higher doses in an encapsulated, persistent release form. To this end, we characterized the kinetics and analgesic effects of morphine sulfate (MS) injected epidurally in a multivesicular liposome (DepoFoam,® DF) formulation (DF-MS) in dogs. Adult male Beagles (12-15 kg) were prepared under halothane anesthesia with i) chronic lumbar epidural injection catheters (polyethylene, PE50) inserted percutaneously at the L7 interspace, passed rostrally to the T13/L1 spinal level and connected to subcutaneous injection ports and ii) with lumbar intrathecal sampling catheters passed to the L1 spinal level from the cisterna magna. The intrathecal catheter was externalized on the upper shoulder. Dogs were housed in individual runs. After a 3 day recovery, epidural injections were initiated in 10 dogs. Six dogs received epidural MS (5 mg) followed 48 hours later with epidural DF-MS (30 mg). Four dogs received injection of liposomes without morphine. Epidural MS showed higher lumbar cerebrospinal fluid concentration (Cmax) (34,942 ± 5578 vs 14,483 ± 3438 ng/ml) and shorter mean residency time (MRT) than DF-MS (0.8 ± 0.1 vs 12.8 ± 1.0 hours) (p < 0.05). Potent analgesia, as measured by latency of thermally- evoked skin twitch, was observed after both treatments. However, the analgesic index (area under the time effect curve) was significantly less for MS than for DF-MS (p < 0.05). DF-MS encapsulation thus yielded sustained release of MS after epidural delivery and extended duration of antinociception. Injection of liposomes without morphine had no analgesic or behavioral effects.
EVALUATION OF AUTOMATED METHODS OF MEASURING HEMOGLOBIN AND HEMATOCRIT IN HORSES.
LA Sorrell-Raschi and M Tomasic.* University of Pennsylvania, Philadelphia PA.
Blood gas analyzers require hemoglobin (Hb) values that are measured directly or derived from hematocrit (Hct) to determine various acid-base parameters and employ a variety of automated methods to obtain these values. Most of these automated methods are designed for use with human blood. This study was designed to determine how accurately three automated methods of Hb and Hct determination can measure these parameters in horses. Blood was obtained from 16 healthy horses. For each horse plasma was separated from the red blood cells (RBC's) and 6 Hct dilutions (0, 10, 20, 40, 60, and 70%) were created by adding aliquots of the plasma to the horse's RBC's. A small sample of each dilution was analyzed by two blood gas analyzers, the Corning 288® which measures Hb via a chemical method similar to the cyanmethemoglobin method, and the Nova Stat 1® which measures Hct via electrical impedance; and a co-oximeter, the Radiometer OSM3,® which measures Hb spectrophotometrically. Hct or Hb was then derived where appropriate so that there were Hct and Hb values for each dilution using each analyzer. The Wintrobe hematocrit method was used as the standard to compare the automated Hct values and the cyanmethemoglobin method was used as the standard for Hb measurement. Regression analyses and the Fisher's t test were used to determine if there was a significant difference between the Hb and Hct values obtained with the automated methods and the standards (P < 0.01). At the 0 and 10% Hct dilution the Nova Stat 1® consistently measured hematocrits of Æ 9% and Æ 13% respectively. At the 20% dilution the Nova Stat 1® consistently measured a higher Hct (± 2.9% units: range of 0.5-7 %) than the standard (P < 0.001). In the 40-70% Hct range there was no statistical difference between the Nova Stat 1® measurement and the standard (P = 0.08882). There was no difference between Hb and Hct values obtained from the Corning 288® and the Radiometer OSM3® automated methods and the standards. This study suggests that the electrical impedance method of Hct determination used by the Nova Stat 1® is not comparable to standard methods of measuring horse Hct in the low Hct range ( oe 20%). Hb values derived from this Hct measurement would be falsely elevated as would the acid-base parameters that the Nova Stat 1® derives from these Hb values.
PAIN-INDUCED DISTRESS IN THE CANINE OVARIOHYSTERECTOMY AND ITS ALLEVIATION WITH PERIOPERATIVE BUTORPHANOL.
SM Fox, DJ Mellor, CRO Lawoko, H Hodge, EC Firth. Massey University, Palmerston North, New Zealand.
Ovariohysterectomy, the most frequently performed surgical procedure in
companion animal veterinary practice, is regarded by many as being quite
benign. There are no satisfactory data available to determine how benign or
noxious this procedure might be, yet this query is of considerable clinical
importance. Most studies in this area have omitted satisfactory control or
baseline animals, i.e., the anesthetic or analgesic treatments were
rarely, if ever, applied to animals that were not also subjected to surgery.
Forty-four dogs were used in nine treatments: control; anesthesia (sodium
thiopentone, then halothane in oxygen); analgesia (0.4 mg/kg butorphanol IV);
analgesia + anesthesia; anesthesia + analgesia at intubation; anesthesia +
analgesia at extubation; anesthesia + surgery; analgesia + anesthesia +
surgery; and anesthesia + surgery + analgesia. Plasma cortisol responses were
observed pretreatment and at various times for five hours after extubation.
Data are reported as mean ± SEM and were compared using the Scheffe's
F-test for reporting with P < 0.05 considered significant. Integrated
cortisol response (ng/ml x min) was: control, 1,658 ± 420; anesthesia,
2,344 ± 637; analgesia, 6,554 ± 1,483; analgesia + anesthesia, 4886
± 1,575; anesthesia + analgesia at intubation, 6,655 ± 2,048;
anesthesia + analgesia at extubation, 9,996 ± 2,207; anesthesia +
surgery, 15,692 ± 3,169; analgesia + anesthesia + surgery, 15,659 ±
1,806; and anesthesia + surgery + analgesia, 10,159 ± 1,345. Psychogenic
stimuli in control bitches were responsible for a transient rise in cortisol
concentration not seen in anesthetized dogs. Butorphanol elicited a large
cortisol response, attributable to dysphoria, which again was prevented by
anesthetic administration. As judged by cortisol response there was no
apparent benefit of preoperative butorphanol administered IV 30 minutes prior
to or at the time of anesthetic induction. There was an earlier decline in
cortisol concentration when butorphanol was given at extubation, interpreted to
reflect an earlier decrease in postoperative pain-induced distress. Results
suggest analgesia is appropriate for the routine canine spay.
CALCIUM INDEPENDENT CONTRACTION OF EQUINE PULMONARY ARTERIAL SMOOTH MUSCLE.
M Tomasic* and KM Shuler. University of Pennsylvania, Kennett Square, PA.
Most smooth muscle types require extracellular calcium for sustained contraction, though recent studies have shown that protein kinase C mediated calcium independent contraction can occur in some smooth muscle. This study examined the effect of protein kinase C (PKC) stimulation and calcium independent tension development of small equine pulmonary arterial vascular rings. Isolated equine pulmonary arterial rings oe 1 mm O.D. were suspended in 10 ml organ baths in Earle's BSS at 37%C, and aerated with a normoxic gas mixture (18%O2/5%CO2/balance N2). Zero calcium conditions were imposed by replacing bath solution with a modified Earle's solution containing 0 mM Ca and 5 mM EGTA. Isometric developed tensions were recorded during response to addition of spasmogens to the bath solution. Data are reported as mean ± SD. In normal calcium bath PKC stimulation with phorbol 12,13-dibutyrate (PDBU) resulted in developed tensions 120 ± 48% (n = 7) of maximal KCl stimulation. Under zero-calcium condition and with depletion of intracellular calcium, PDBU stimulation still resulted in contraction though to a lesser degree (51 ± 8.2%, n = 6). U46619, a thromboxane A2 analogue, also resulted in tension development in the face of no external calcium and depleted intracellular stores. In this experiment, U46619 stimulation resulted in developed tensions approximately 18 ± 9.6 % of maximal histamine induced contraction. Contractions induced under conditions of zero external calcium and depleted cellular stores are slow in onset and difficult to wash out. Developed tension induced by both PDBU and U46619 were completely attenuated by inhibition of PKC activity with chelerythrine or staurosporine, both in normal and zero calcium conditions. These results show that protein kinase C mediated calcium independent contractions occur in equine pulmonary vascular smooth muscle and suggest a role for thromboxane A2 in modulation of pulmonary arterial tone in a calcium independent fashion.
CHARACTERIZATION OF THE RAT LUMBAR INTRATHECAL INFUSION MODEL.
SA Malkmus, RR Myers, TL Yaksh. University of California - San Diego, La Jolla, CA.
Large animal models have been developed for intrathecal (IT) drug delivery to permit evaluation of spinal pharmacology, drug kinetics and drug safety but there has been no systematic validation of a rat model of continuous intrathecal drug delivery. Moreover, while many studies on rodents are accomplished in a "clean" fashion, development of drug safety models would be best approached with implementation of an aseptic regimen. To accomplish this, male Holtzman rats (300-325 grams) were implanted following rigid aseptic technique with IT catheters sterilized by electron beam. In brief, rats were anesthetized with halothane (2.0%), placed in a stereotaxic head holder, then surgically prepped and draped. The cisternal membrane was exposed by a small skin incision and muscle retraction, and the catheter (polyethylene: OD = 0.014 mm) was inserted intrathecally 8.5 cm to the L1/L2 segment. The external end of the catheter was connected to a mini-osmotic pump (Alza 2002®) delivering sterile saline (0.9% USP) at 0.5 _L/hour for 14 days. After surgery and on post-operative day 1, the animals received subcutaneous injections (5 ml) of lactated Ringers. Behavioral assessment and body weight determination were carried out daily. On day 13, the animals were anesthetized and subjected to exsanguination and whole body fixation. Spinal columns were harvested and submitted for a detailed histopathological examination. All animals survived the surgery / study without functional deficit and thrived to sacrifice. Body weight showed a transient decrease on days 1 and 2, but recovered and continued growth occurred over the ensuing 10-11 days. In contrast to what has been seen with larger catheters, histopathology revealed no evidence of physical distortion of the spinal parenchyma, cell loss, or demyelination. The catheter was associated with very mild inflammatory response and fibrosis that occasionally affected adjacent nerve roots. The meninges displayed moderate thickening adjacent to the catheter tracts. Aseptic placement of small catheters into the lumbar intrathecal space may be reliably employed as a drug delivery system in rats with no behavioral consequences and minimal effect upon spinal morphology.
HYPEROXIA ATTENUATES THE HEMODYNAMIC RESPONSE TO NITRIC OXIDE INHIBITION IN ISOFLURANE-ANESTHETIZED, ENDOTOXEMIC PIGS.
PW Hellyer,* B Wright, AE Wagner,* JS Gaynor,* KR Mama.* Colorado State University, Fort Collins, CO.
Inhibition of nitric oxide synthase with L-NAME has been shown to worsen endotoxin-induced hypoxemia and to enhance increases in pulmonary and systemic vascular resistance index in anesthetized pigs. The effect of nitric oxide (NO) on acute cardiopulmonary response to endotoxin may in part be related to the relative balance of O2 and NO. In this study we tested the hypothesis that hyperoxia (100% O2) would attenuate the deleterious effects of L- NAME on endotoxin-induced cardiopulmonary alterations. Twenty-two pigs, weighing 15.4 ± 2.7 kg, were anesthetized with isoflurane in 100% O2, orotracheally intubated and ventilated to normocapnia. A thermodilution cardiac output catheter was advanced into the pulmonary artery. Additional catheters were inserted into the jugular and femoral veins and femoral artery. Following instrumentation, pigs were maintained at an end-tidal isoflurane concentration of 2%. Pigs were randomly assigned to treatment groups: saline + 30% O2 (control, n = 6); Escherichia coli endotoxin (5 µg/kg/hr from 1-2 hr followed by 2µg/kg/hr from 2-5 hr) + 30% O2 (n=4); L-NAME (0.5 mg/kg/hr from 0 to 5 hr) + endotoxin + 100% O2 (n=6); L-NAME + endotoxin + 30% O2 (n = 6). Data were analyzed with mixed model, least squares analysis of variance, for repeated measures. Analyses included the fixed effects of treatment, time, and treatment by time interaction. Subject nested within treatment was included as a random effect. Statistical significance was considered at P < 0.05. L-NAME and endotoxin significantly increased mean arterial pressure, mean pulmonary arterial pressure, systemic and pulmonary vascular resistance beginning at 90 minutes. Hyperoxia attenuated L-NAME and endotoxin-induced systemic and pulmonary vasoconstriction. These results suggest that the degree of oxygenation plays a critical role in the cardiopulmonary response to nitric oxide synthase inhibition in this model of porcine endotoxemia.
EFFECTS OF DIFFERENT COMBINATIONS OF HALOTHANE, BUTORPHANOL, AND OVARIOHYSTERECTOMY ON BEHAVIOR IN THE DOG.
SM Fox, DJ Mellor, CRO Lawoko, H Hodge, EC Firth. Massey University, Palmerston North, New Zealand.
Postoperative pain control is often inadequately addressed because
veterinary medicine lacks patient demand and requires careful observation and
interpretation of behavior to assess patient response to injury and to identify
behavior associated with pain. Forty-four dogs were used in nine treatments:
T1, control; T2, anesthesia (sodium thiopentone, then halothane in oxygen); T3,
analgesia (0.4 mg/kg butorphanol, IV); T4, analgesia + anesthesia; T5,
anesthesia + analgesia at intubation; T6, anesthesia + analgesia at extubation;
T7, anesthesia + surgery; T8, analgesia + anesthesia + surgery; and T9,
anesthesia + surgery + analgesia. Behavior was observed pretreatment and at
various times up to five hours after extubation. Of 166 behavioral parameters
(interactive and noninteractive), 76 occurred at insufficient frequencies as to
be valuable as indices of postoperative pain-induced distress. Noninteractive
canonical function mean values (canonical 1 and canonical 2, respectively) for
the nonsurgical groups were: T1, -1.45, -1.46; T7, 2.56, -0.33; T8, -0.70,
1.08; T9, -0.77, 1.11. Interactive canonical function mean values for the
nonsurgical groups were: T1, -0.20, -1.48; T2, -1.74, 0.36; T3, -0.71, 0.74;
T4, 0.21, 0.02; T5, 1.77, 0.39; T6, 0.21, 0.50. Noninteractive canonical
function mean values for the three surgical treatments were: (1) T1, -2.38,
-1.27; T2, -2.53, 1.24; T7, 4.5, 0.02, (2) T1, -2.17, -0.99; T4, -0.30, 1.77;
T8, 2.69, -0.68, (3) Tl, 0.44, -2.03; T6, -2.16, 0.73; T9, 1.89, 1.44.
Interactive canonical function mean values for the three surgical treatments
were: (1) T1, -4.19, -1.70; T2, -0.02, 3.51; T7, 3.86, -1.67, (2) T1, 15.83,
-1.97; T4, 1.71, 3.63; T8, -19.13, -1.47, (3) T1, 0.22, -3.60; T4, -8.74, 1.82;
T9, 9.37, 1.96. Among the discriminating, noninteractive variables
characteristic of the nonanalgesic surgical group were: drawing the rear limbs
up into a pike position, lip licking, cage circling, incision licking,
vomition, looking back (flank gazing) and marked restlessness. An extended
neck was a characteristic interactive behavior. Mean frequency of normal
greeting behaviors were suppressed by surgery. Vocalization was associated
with the dysphoria of analgesia rather than pain-induced distress. Use of
canonical discriminate analysis to differentiate treatment effect eliminates
the bias often associated with visual analogue and numerical rating scales.
The Z value (discriminate function) of the canonical analysis may substitute
for the intuitive insight used in judging whether an animal is experiencing
pain. Results suggest that the routine spay is a noxious and fatiguing
experience that changes normal behavior. Postoperative butorphanol provides
rest and influences return to more normal behavior.
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