Objective—To determine pharmacokinetics and
selected cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys.
Animals—6 adult male rhesus monkeys.
Procedure—Fentanyl (8 mg/kg of body weight, IV)
was administered to 6 monkeys anesthetized with
isoflurane. End-tidal isoflurane concentration and
esophageal temperature were kept constant, and
ventilation was mechanically assisted. Heart rate,
rhythm, aortic blood pressure, and blood pH, gas, and
fentanyl concentrations were determined before and
for 8 hours after administration of fentanyl.
Pharmacokinetics of fentanyl were derived by use of
noncompartmental methods based on statistical
Results—Heart rate and mean arterial pressure
decreased transiently following fentanyl administration.
Maximal decreases were observed 5 to 15 minutes
after administration. Arterial pH, PaCO2, and PaO2
ranged from 7.46 ± 0.04 to 7.51 ± 0.05 units, 29.2 ± 3
to 34.6 ± 4.4 mm Hg, and 412.6 ± 105.3 to 482.9 ±
71.2 mm Hg, respectively. The clearance, volume of
distribution area, volume of distribution steady state,
mean residence time, area under the curve, elimination
rate constant, and half-life were 32.5 ± 2.48
ml/kg/min, 9.04 ± 1.91 L/kg, 7.0 ± 1.2 L/kg, 218.5 ±
35.5 min, 0.247 ± 0.019 mg/ml/min, 0.004 ±
0.001/min, and 192.0 ± 33.5 min, respectively.
Conclusions and Clinical Relevance—Transient but
potentially clinically important decreases in heart rate
and mean arterial pressure were observed following
fentanyl administration. Distribution and clearance
data were similar to those reported for dogs and
humans. (Am J Vet Res 2000;61:931–934)
Objective—To determine the effect of a constant-rate
infusion of fentanyl on minimum alveolar concentration
(MAC) of isoflurane and to determine the interaction
between fentanyl and a benzodiazepine agonist
(diazepam) and antagonist (flumazenil) in isoflurane-anesthetized
Animals—8 mixed-breed adult dogs.
Procedure—Dogs were anesthetized with isoflurane
3 times during a 6-week period. After a 30-minute
equilibration period, each MAC determination was
performed in triplicate, using standard techniques.
Fentanyl was administered as a bolus (10 µg/kg of
body weight, IV) that was followed by a constant infusion
(0.3 µg/kg per min, IV) throughout the remainder
of the experiment. After determining isoflurane-fentanyl
MAC in triplicate, each dog received saline
(0.9% NaCl) solution, diazepam, or flumazenil. After
30 minutes, MAC was determined again.
Results—Fentanyl significantly decreased isoflurane
MAC (corrected to a barometric pressure of 760 mm
Hg) from 1.80 ± 0.21 to 0.85 ± 0.14%, a reduction of
53%. Isoflurane-fentanyl-diazepam MAC (0.48 ±
0.29%) was significantly less than isoflurane-fentanylsaline
MAC (0.79 ± 0.21%). Percentage reduction in
isoflurane MAC was significantly greater for fentanyldiazepam
(74%), compared with fentanyl-saline (54%)
or fentanyl-flumazenil (61%). Mean fentanyl concentrations
for the entire experiment were increased over
time and were higher in the diazepam group than the
saline or flumazenil groups.
Conclusion and Clinical Relevance—Fentanyl
markedly decreased isoflurane MAC in dogs.
Diazepam, but not flumazenil, further decreased
isoflurane-fentanyl MAC. Our results indicate that
diazepam enhances, whereas flumazenil does not
affect, opioid-induced CNS depression and, possibly,
analgesia in dogs. (Am J Vet Res 2001;62:555–560)
Objective—To quantitate effects of dose of sevoflurane
and mode of ventilation on cardiovascular and
respiratory function in horses and identify changes in
serum biochemical values associated with sevoflurane
Animals—6 healthy adult horses.
Procedure—Horses were anesthetized twice: first, to
determine the minimum alveolar concentration (MAC)
of sevoflurane and second, to characterize cardiopulmonary
and serum biochemical responses of horses
to 1.0, 1.5, and 1.75 MAC multiples of sevoflurane during
controlled and spontaneous ventilation.
Results—Mean (± SEM) MAC of sevoflurane was
2.84 ± 0.16%. Cardiovascular performance during
anesthesia decreased as sevoflurane dose
increased; the magnitude of cardiovascular depression
was more severe during mechanical ventilation,
compared with spontaneous ventilation.
Serum inorganic fluoride concentration increased to
a peak of 50.8 ± 7.1 µmol/L at the end of anesthesia.
Serum creatinine concentration and sorbitol
dehydrogenase activity reached their greatest values
(2.0 ± 0.8 mg/dL and 10.2 ± 1.8 U/L, respectively)
at 1 hour after anesthesia and then returned
to baseline by 1 day after anesthesia. Serum creatine
kinase, aspartate aminotransferase, and alkaline
phosphatase activities reached peak values by
the first (ie, creatine kinase) or second (ie, aspartate
aminotransferase and alkaline phosphatase) day
Conclusions and Clinical Relevance—Sevoflurane
causes dose-related cardiopulmonary depression,
and mode of ventilation further impacts the magnitude
of this depression. Except for serum inorganic
fluoride concentration, quantitative alterations in
serum biochemical indices of liver- and muscle-cell
disruption and kidney function were considered clinically
unremarkable and similar to results from comparable
studies of other inhalation anesthetics. (Am J Vet Res 2005;66:606–614)
Objective—To evaluate effects of injection with a nonsteroidal anti-inflammatory drug (NSAID) followed by oral administration of an NSAID on the gastrointestinal tract (GIT) of healthy dogs.
Animals—6 healthy Walker Hounds.
Procedures—In a randomized, crossover design, dogs were administered 4 treatments consisting of an SC injection of an NSAID or control solution (day 0), followed by oral administration of an NSAID or inert substance for 4 days (days 1 through 4). Treatment regimens included carprofen (4 mg/kg) followed by inert substance; saline (0.9% NaCl) solution followed by deracoxib (4 mg/kg); carprofen (4 mg/kg) followed by carprofen (4 mg/kg); and carprofen (4 mg/kg) followed by deracoxib (4 mg/kg). Hematologic, serum biochemical, and fecal evaluations were conducted weekly, and clinical scores were obtained daily. Endoscopy of the GIT was performed before and on days 1, 2, and 5 for each treatment. Lesions were scored by use of a 6-point scale.
Results—No significant differences existed for clinical data, clinicopathologic data, or lesion scores in the esophagus, cardia, or duodenum. For the gastric fundus, antrum, and lesser curvature, an effect of time was observed for all treatments, with lesions worsening from before to day 2 of treatments but improving by day 5.
Conclusions and Clinical Relevance—Sequential administration of NSAIDs in this experiment did not result in clinically important gastroduodenal ulcers. A larger study to investigate the effect of sequential administration of NSAIDs for longer durations and in dogs with signs of acute and chronic pain is essential to substantiate these findings.
Objective—To determine plasma concentrations and behavioral, antinociceptive, and physiologic effects of methadone administered via IV and oral transmucosal (OTM) routes in cats.
Animals—8 healthy adult cats.
Procedures—Methadone was administered via IV (0.3 mg/kg) and OTM (0.6 mg/kg) routes to each cat in a balanced crossover design. On the days of drug administration, jugular catheters were placed in all cats under anesthesia; a cephalic catheter was also placed in cats that received methadone IV. Baseline measurements were obtained ≥ 90 minutes after extubation, and methadone was administered via the predetermined route. Heart and respiratory rates were measured; sedation, behavior, and antinociception were evaluated, and blood samples were collected for methadone concentration analysis at predetermined intervals for 24 hours after methadone administration. Data were summarized and evaluated statistically.
Results—Plasma concentrations of methadone were detected rapidly after administration via either route. Peak concentration was detected 2 hours after OTM administration and 10 minutes after IV administration. Mean ± SD peak concentration was lower after OTM administration (81.2 ± 14.5 ng/mL) than after IV administration (112.9 ± 28.5 ng/mL). Sedation was greater and lasted longer after OTM administration. Antinociceptive effects were detected 10 minutes after administration in both groups; these persisted ≥ 2 hours after IV administration and ≥ 4 hours after OTM administration.
Conclusions and Clinical Relevance—Despite lower mean peak plasma concentrations, duration of antinociceptive effects of methadone was longer after OTM administration than after IV administration. Methadone administered via either route may be useful for perioperative pain management in cats.
Objective—To determine the anesthetic-sparing effect of maropitant, a neurokinin 1 receptor antagonist, during noxious visceral stimulation of the ovary and ovarian ligament in dogs.
Animals—Eight 1-year-old female dogs.
Procedures—Dogs were anesthetized with sevoflurane. Following instrumentation and stabilization, the right ovary and ovarian ligament were accessed by use of laparoscopy. The ovary was stimulated with a traction force of 6.61 N. The minimum alveolar concentration (MAC) was determined before and after 2 doses of maropitant.
Results—The sevoflurane MAC value was 2.12 ± 0.4% during stimulation without treatment (control). Administration of maropitant (1 mg/kg, IV, followed by 30 μg/kg/h, IV) decreased the sevoflurane MAC to 1.61 ± 0.4% (24% decrease). A higher maropitant dose (5 mg/kg, IV, followed by 150 μg/kg/h, IV) decreased the MAC to 1.48 ± 0.4% (30% decrease).
Conclusions and Clinical Relevance—Maropitant decreased the anesthetic requirements during visceral stimulation of the ovary and ovarian ligament in dogs. Results suggest the potential role for neurokinin 1 receptor antagonists to manage ovarian and visceral pain.
Objective—To verify the isoflurane anesthetic minimum alveolar concentration (MAC)-sparing effect of a previously administered target plasma fentanyl concentration of 16 ng/mL and characterize an anticipated further sparing in isoflurane MAC associated with higher target plasma fentanyl concentrations.
Procedures—Horses were assigned 2 of 3 target plasma fentanyl concentrations (16, 24, and 32 ng/mL), administered in ascending order. Following determination of baseline MAC, horses received a loading dose of fentanyl followed by a constant rate infusion; MAC determination was performed in triplicate at baseline and at each fentanyl concentration. Venous blood samples were collected throughout the study for determination of actual plasma fentanyl concentrations. Recovery from anesthesia was monitored, and behaviors were rated as excellent, good, fair, or poor.
Results—Mean ± SD fentanyl plasma concentrations were 13.9 ± 2.6 ng/mL, 20.1 ± 3.6 ng/mL, and 24.1 ± 2.4 ng/mL for target concentrations of 16, 24, and 32 ng/mL, respectively. The corresponding changes in the MAC of isoflurane were −3.28%, −6.23%, and +1.14%. None of the changes were significant. Recovery behavior was variable and included highly undesirable, potentially injurious excitatory behavior.
Conclusions and Clinical Relevance—Results of the study did not verify an isoflurane-sparing effect of fentanyl at a plasma target concentration of 16 ng/mL. Furthermore, a reduction in MAC was not detected at higher fentanyl concentrations. Overall, results did not support the routine use of fentanyl as an anesthetic adjuvant in adult horses.
Objective—To evaluate the sedative and analgesic effects of subanesthetic doses of ketamine in horses sedated with xylazine, with or without butorphanol.
Design—Prospective, randomized, controlled study.
Animals—10 adult horses.
Procedures—Each horse was sedated multiple times by administration of xylazine (treatment X), xylazine and butorphanol (treatment XB), xylazine with 1 of 2 dosages of ketamine (treatment XK1 or XK2), or xylazine and butorphanol with 1 of 2 dosages of ketamine (treatment XBK1 or XBK2). Head height and various behaviors, including responses to noise, insertion of a dental float, needle prick on the flank, algometer pressure on the scapula, and bilateral carpal arthrocenteses, were evaluated.
Results—No significant differences were detected among sedation treatments for head height, response to noise, or response to arthrocenteses. Insertion of a dental float was easiest with treatment XBK2 and most difficult with treatments XK1 and XK2. Response to a needle prick on the flank was lowest with treatment XB and highest with treatment XK2. Tolerance to algometer pressure over the scapula was highest with treatment XBK2 and lowest with treatment X.
Conclusions and Clinical Relevance—Administration of a subanesthetic dosage of ketamine with xylazine and butorphanol may facilitate certain procedures, such as insertion of a dental float, in horses and enhance tolerance to pressure stimulation, but it may worsen responses to acute pain, such as that caused by a needle prick. Further evaluation is needed to determine whether subanesthetic dosages of ketamine might be useful when performing certain clinical procedures in horses.