Procedure—Dogs were anesthetized with glycopyrrolate,
morphine, propofol, and isoflurane. Thirteen
dogs were treated with ketamine IV, as follows: 0.5
mg/kg (0.23 mg/lb) as a bolus before surgery, 10
µg/kg/min (4.5 µg/lb/min) during surgery, and 2
µg/kg/min (0.9 µg/lb/min) for 18 hours after surgery.
Fourteen dogs received the same volume of saline
(0.9% NaCl) solution. All dogs received an infusion of
fentanyl (1 to 5 µg/kg/h [0.45 to 2.27 µg/lb/h]) for the
first 18 hours after surgery. Dogs were evaluated for
signs of pain before surgery, at the time of extubation,
and 1, 2, 3, 4, 12, and 18 hours after extubation.
Owners evaluated their dogs' appetite, activity, and
wound soreness on postoperative days 2, 3, and 4.
Results—Dogs that received ketamine infusions had
significantly lower pain scores 12 and 18 hours after
surgery and were significantly more active on postoperative
day 3 than dogs that received saline solution
Conclusions and Clinical Relevance—Results suggest
that perioperative administration of low doses of
ketamine to dogs may augment analgesia and comfort
in the postoperative surgical period. (J Am Vet
Med Assoc 2002;221:72–75)
OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug.
ANIMALS 11 Thoroughbred horses enrolled in a fitness training program.
PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed.
RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration.
CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.
Objective—To evaluate μ-opioid receptors in synovial
membranes of horses and determine whether these
receptors are up-regulated in nerve endings during
Sample Population—Synovial tissue obtained from
39 client-owned horses during arthroscopy and 14
research horses during necropsy; brain and synovial
tissues were obtained during necropsy from 1 horse,
and control tissues were obtained from a mouse.
Procedure—Horses were classified into 7 groups on
the basis of histologically determined degree of
inflammation. Binding of primary rabbit antibody
developed against μ-opioid receptors in equine synovial
tissue was studied, using western blot analysis.
Synovial membranes were tested for μ-opioid receptors
by immunohistochemical staining, using a
diaminobenzidine-cobalt chloride chromogen.
Homogenates of synovial membranes were evaluated
by use of radioligand binding.
Results—Examination of western blots of equine
thalamus revealed that rabbit antibody developed
against μ-opioid receptors yielded a band (molecular
weight, 55 kd) that corresponded with that of other
opioid receptors. Use of immunohistochemical staining
of synovial tissue revealed considerable staining
in the proliferative lining layer and in regions surrounding
vascular structures. Specific radioligand
binding of tissue homogenates was found in all
groups. We did not detect significant differences in
binding between horses with inflammation and horses
Conclusions and Clinical Relevance—Results of
immunohistochemical analysis and radioligand binding
of tissue homogenates suggest that there are opioid
receptors in synovial membranes of horses. Our
results support the practice of intra-articular administration
of opioids to relieve pain after arthroscopic
surgery in horses. (Am J Vet Res 2001;62:1408–1412).
Objective—To evaluate the use of xylazine and ketamine
for total IV anesthesia in horses.
Procedure—Anesthetic induction was performed on
4 occasions in each horse with xylazine (0.75 mg/kg,
IV), guaifenesin (75 mg/kg, IV), and ketamine
(2 mg/kg, IV). Intravenous infusions of xylazine and
ketamine were then started by use of 1 of 6 treatments
as follows for which 35, 90, 120, and 150 represent
infusion dosages (µg/kg/min) and X and K represent
xylazine and ketamine, respectively: X35+K90
with 100% inspired oxygen (O2), X35+K120-O2,
X35+K150-O2, X70+K90-O2, K150-O2, and X35+K120
with a 21% fraction of inspired oxygen (ie, air).
Cardiopulmonary measurements were performed.
Response to a noxious electrical stimulus was
observed at 20, 40, and 60 minutes after induction.
Times to achieve sternal recumbency and standing
were recorded. Quality of sedation, induction, and
recovery to sternal recumbency and standing were
Results—Heart rate and cardiac index were higher
and total peripheral resistance lower in K150-O2 and
X35+K120-air groups. The mean arterial pressure was
highest in the X35+K120-air group and lowest in the
K150-O2 group (125 ± 6 vs 85 ± 8 at 20 minutes,
respectively). Mean PaO2 was lowest in the
X35+K120-air group. Times to sternal recumbency
and standing were shortest for horses receiving
K150-O2 (23 ± 6 minutes and 33 ± 8 minutes, respectively)
and longest for those receiving X70+K90-O2
(58 ± 28 minutes and 69 ± 27 minutes, respectively).
Conclusions and Clinical Relevance—Infusions of
xylazine and ketamine may be used with oxygen supplementation
to maintain 60 minutes of anesthesia in
healthy adult horses. (Am J Vet Res 2005;66:1002–1007)
Objective—To assess the pharmacokinetics and pharmacodynamics of morphine in llamas.
Animals—6 healthy adult llamas.
Procedures—Llamas received morphine sulfate in a randomized crossover design. In phase 1, they received IV or IM administration of morphine at 0.05 or 0.5 mg/kg, respectively; in phase 2, they received IV administration of morphine at 0.05, 0.25, or 0.5 mg/kg. Plasma morphine and morphine-6-glucuronide concentrations were determined by validated methods. Body temperature, heart rate, respiratory rate, sedation, and analgesia were assessed and compared with plasma concentrations by regression analysis.
Results—Total body clearance was similar between IV administration of morphine sulfate at 0.25 and 0.5 mg/kg (mean ± SD, 25.3 ± 6.9 mL/min/kg and 27.3 ± 5.9 mL/min/kg, respectively), and linearity was demonstrated between these doses. Bioavailability of morphine following IM administration at 0.5 mg/kg was 120 ± 30%. Body temperature and sedation increased as the dose of morphine administered increased. Heart rate was unaffected by varying doses. Respiratory rate decreased as dose increased. Analgesia was difficult to assess as a result of high individual variability. Intravenous administration of morphine at 0.25 mg/kg provided the most consistent increase in tolerance to electric stimulation. Pharmacodynamic modeling revealed a sigmoidal relationship between plasma concentration and sedation score.
Conclusions and Clinical Relevance—Morphine was characterized by a large apparent volume of distribution and high systemic clearance in llamas. A prolonged half-life was observed with IM injection. Intravenous administration of morphine sulfate at 0.25 mg/kg every 4 hours is suggested for further study.
Objective—To compare characteristics of horses recovering from 4 hours of desflurane anesthesia with and without immediate postanesthetic IV administration of propofol and xylazine.
Animals—8 healthy horses (mean ± SEM age, 6.6 ± 1.0 years; mean body weight, 551 ± 50 kg).
Procedures—Horses were anesthetized twice. Both times, anesthesia was induced with a combination of xylazine hydrochloride, diazepam, and ketamine hydrochloride and then maintained for 4 hours with desflurane in oxygen. Choice of postanesthetic treatment was randomly assigned via a crossover design such that each horse received an IV injection of propofol and xylazine or saline (0.9% NaCl) solution after the anesthetic episode. Recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and after anesthesia for determination of serum creatine kinase activity and plasma propofol concentration.
Results—Anesthetic induction and maintenance were unremarkable in all horses. Compared with administration of saline solution, postanesthetic administration of propofol and xylazine resulted in an increased interval to emergence from anesthesia but improved quality of recovery-related transition to standing. Compared with administration of saline solution, administration of propofol also delayed the rate of decrease of end-tidal concentrations of desflurane and carbon dioxide and added to conditions promoting hypoxemia and hypoventilation.
Conclusions and Clinical Relevance—Propofol and xylazine administered IV to horses after 4 hours of desflurane anesthesia improved the quality of transition from lateral recumbency to standing but added potential for harmful respiratory depression during the postanesthetic period.
To determine the pharmacokinetics of a single bolus of intravenous (IV) propofol after intramuscular administration of etorphine, butorphanol, medetomidine, and azaperone in 5 southern white rhinoceros to facilitate reproductive evaluations. A specific consideration was whether propofol would facilitate timely orotracheal intubation.
5 adult, female, zoo-maintained southern white rhinoceros.
Rhinoceros were administered etorphine (0.002 mg/kg), butorphanol (0.02 to 0.026 mg/kg), medetomidine (0.023 to 0.025 mg/kg), and azaperone (0.014 to 0.017 mg/kg) intramuscularly (IM) prior to an IV dose of propofol (0.5 mg/kg). Physiologic parameters (heart rate, blood pressure, respiratory rate, and capnography), timed parameters (eg, time to initial effects and intubation), and quality of induction and intubation were recorded following drug administration. Venous blood was collected for analysis of plasma propofol concentrations using liquid chromatography-tandem mass spectrometry at various time points after propofol administration.
All animals were approachable following IM drug administration, and orotracheal intubation was achieved at 9.8 ± 2.0 minutes (mean ±SD) following propofol administration. The mean clearance for propofol was 14.2 ± 7.7 ml/min/kg, the mean terminal half-life was 82.4 ± 74.4 minutes, and the maximum concentration occurred at 2.8 ± 2.9 minutes. Two of 5 rhinoceros experienced apnea after propofol administration. Initial hypertension, which improved without intervention, was observed.
This study provides pharmacokinetic data and insight into the effects of propofol in rhinoceros anesthetized using etorphine, butorphanol, medetomidine, and azaperone. While apnea was observed in 2 rhinoceros, propofol administration allowed for rapid control of the airway and facilitated oxygen administration and ventilatory support.
OBJECTIVE To evaluate agreement among diplomates of the American College of Veterinary Anesthesia and Analgesia for scores determined by use of a simple descriptive scale (SDS) or a composite grading scale (CGS) for quality of recovery of horses from anesthesia and to investigate use of 3-axis accelerometry (3AA) for objective evaluation of recovery.
ANIMALS 12 healthy adult horses.
PROCEDURES Horses were fitted with a 3AA device and then were anesthetized. Eight diplomates evaluated recovery by use of an SDS, and 7 other diplomates evaluated recovery by use of a CGS. Agreement was tested with κ and AC1 statistics for the SDS and an ANOVA for the CGS. A library of mathematical models was used to map 3AA data against CGS scores.
RESULTS Agreement among diplomates using the SDS was slight (κ = 0.19; AC1 = 0.22). The CGS scores differed significantly among diplomates. Best fit of 3AA data against CGS scores yielded the following equation: RS = 9.998 × SG0.633 × ∑UG0.174, where RS is a horse's recovery score determined with 3AA, SG is acceleration of the successful attempt to stand, and ∑UG is the sum of accelerations of unsuccessful attempts to stand.
CONCLUSIONS AND CLINICAL RELEVANCE Subjective scoring of recovery of horses from anesthesia resulted in poor agreement among diplomates. Subjective scoring may lead to differences in conclusions about recovery quality; thus, there is a need for an objective scoring method. The 3AA system removed subjective bias in evaluations of recovery of horses and warrants further study.