Objective—To investigate the effects of ketamine hydrochloride on the analgesic effects of tramadol hydrochloride in horses with signs of pain associated with naturally occurring chronic laminitis.
Animals—15 client-owned adult horses with chronic laminitis.
Procedures—Each horse received tramadol alone or tramadol and ketamine in a randomized, crossover study (≥ 2 months between treatments). Tramadol (5 mg/kg) was administered orally every 12 hours for 1 week. When appropriate, ketamine (0.6 mg/kg/h) was administered IV for 6 hours on each of the first 3 days of tramadol administration. Noninvasive systemic blood pressure values, heart and respiratory rates, intestinal sounds, forelimb load and off-loading frequency (determined via force plate system), and plasma tumor necrosis factor-α and thromboxane B2 concentrations were assessed before (baseline) during (7 days) and after (3 days) each treatment.
Results—Compared with baseline data, arterial blood pressure decreased significantly both during and after tramadol-ketamine treatment but not with tramadol alone. Forelimb off-loading frequency significantly decreased during the first 3 days of treatment with tramadol only, returning to baseline frequency thereafter. The addition of ketamine to tramadol treatment reduced off-loading frequency both during and after treatment. Forelimb load did not change with tramadol alone but increased with tramadol-ketamine treatment. Plasma concentrations of tumor necrosis factor-α and thromboxane B2 were significantly reduced with tramadol-ketamine treatment but not with tramadol alone.
Conclusions and Clinical Relevance—In horses with chronic laminitis, tramadol administration induced limited analgesia, but this effect was significantly enhanced by administration of subanesthetic doses of ketamine.
Objective—To describe the pharmacokinetics of
phenylbutazone and oxyphenbutazone after IV administration
in miniature donkeys.
Animals—6 clinically normal miniature donkeys.
Procedure—Blood samples were collected before
and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360,
and 480 minutes after IV administration of phenylbutazone
(4.4 mg/kg of body weight). Serum was analyzed
in triplicate by use of high-performance liquid
chromatography for determination of phenylbutazone
and oxyphenbutazone concentrations. The serum
concentration-time curve for each donkey was analyzed
separately to estimate model-independent pharmacokinetic
Results—Serum concentrations decreased rapidly
after IV administration of phenylbutazone, and they
reached undetectable concentrations within 4 hours.
Values for mean residence time ranged from 0.5 to
3.0 hours (median, 1.1 hour), whereas total body
clearance ranged from 4.2 to 7.5 ml/kg/ min (mean,
5.8 ml/kg/ min). Oxyphenbutazone appeared rapidly in
the serum; time to peak concentration ranged from
13 to 41 minutes (mean, 26.4 minutes), and peak concentration
in serum ranged from 2.8 to 4.0 mg/ml
(mean, 3.5 μg/ml).
Conclusion and Clinical Relevance—Clearance of
phenylbutazone in miniature donkeys after injection of
a single dose (4.4 mg/kg, IV) is rapid. Compared with
horses, miniature donkeys may require more frequent
administration of phenylbutazone to achieve therapeutic
efficacy. (Am J Vet Res 2001;62:673–675)
Objective—To compare serum disposition of sulfamethoxazole
and trimethoprim after IV administration
to donkeys, mules, and horses.
Animals—5 donkeys, 5 mules, and 3 horses.
Procedure—Blood samples were collected before
(time 0) and 5, 15, 30, and 45 minutes and 1, 1.25, 1.5,
1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 24 hours
after IV administration of sulfamethoxazole
(12.5 mg/kg) and trimethoprim (2.5 mg/kg). Serum
was analyzed in triplicate with high-performance liquid
chromatography for determination of sulfamethoxazole
and trimethoprim concentrations.
Serum concentration-time curve for each animal was
analyzed separately to estimate noncompartmental
Results—Clearance of trimethoprim and sulfamethoxazole
in donkeys was significantly faster
than in mules or horses. In donkeys, mean residence
time (MRT) of sulfamethoxazole (2.5 hours) was less
than half the MRT in mules (6.2 hours); MRT of
trimethoprim in donkeys (0.8 hours) was half that in
horses (1.5 hours). Volume of distribution at steady
state (Vdss) for sulfamethoxazole did not differ, but
Vdss of trimethoprim was significantly greater in horses
than mules or donkeys. Area under the curve for
sulfamethoxazole and trimethoprim was higher in
mules than in horses or donkeys.
Conclusions and Clinical Relevance—Dosing intervals
for IV administration of trimethoprim-sulfamethoxazole
in horses may not be appropriate for
use in donkeys or mules. Donkeys eliminate the
drugs rapidly, compared with horses. Ratios of
trimethoprim and sulfamethoxazole optimum for
antibacterial activity are maintained for only a short
duration in horses, donkeys, and mules. (Am J Vet Res
Objective—To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species.
Animals—5 clinically normal horses and 5 clinically normal donkeys.
Procedures—Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinetic variables.
Results—In horses and donkeys, mean ± SD area under the curve was 18.8 ± 7.31 μg/mL/h and 4.6 ± 2.55 μg/mL/h, respectively; mean residence time (MRT) was 9.6 ± 9.24 hours and 0.6 ± 0.36 hours, respectively. Total body clearance (CLT) was 34.7 ± 9.21 mL/kg/h in horses and 187.9 ± 147.26 mL/kg/h in donkeys. Volume of distribution at steady state (VDSS) was 270 ± 160.5 mL/kg in horses and 93.2 ± 33.74 mL/kg in donkeys. All values, except VDSS, were significantly different between donkeys and horses.
Conclusions and Clinical Relevance—The small VDSS of meloxicam in horses and donkeys (attributed to high protein binding) was similar to values determined for other nonsteroidal anti-inflammatory drugs. Compared with other species, horses had a much shorter MRT and greater CLT for meloxicam, indicating a rapid elimination of the drug from plasma; the even shorter MRT and greater CLT of meloxicam in donkeys, compared with horses, may make the use of the drug in this species impractical.
Objective—To compare plasma disposition of the
R(–) and S(+) enantiomers of carprofen after IV administration
of a bolus dose to donkeys and horses.
Animals—5 clinically normal donkeys and 3 clinically
Procedure—Blood samples were collected from all
animals at time 0 (before) and at 10, 15, 20, 30, and
45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24,
28, 32, and 48 hours after IV administration of a
bolus of carprofen (0.7 mg/kg). Plasma was analyzed
in triplicate via high-performance liquid chromatography
to determine the concentrations of the
carprofen enantiomers. A plasma concentration-time
curve for each donkey and horse was analyzed
separately to estimate noncompartmental pharmacokinetic
Results—In donkeys and horses, the area under the
plasma concentration versus time curve (AUC) was
greater for the R(–) carprofen enantiomer than it was
for the S(+) carprofen enantiomer. For the R(–) carprofen
enantiomer, the AUC and mean residence time
(MRT) were significantly less and total body clearance
(ClT) was significantly greater in horses, compared
with donkeys. For the S(+) carprofen enantiomer,
AUC and MRT were significantly less and ClT and
apparent volume of distribution at steady state were
significantly greater in horses, compared with donkeys.
Conclusions and Clinical Relevance—Results have
suggested that the dosing intervals for carprofen that
are used in horses may not be appropriate for use in
donkeys. (Am J Vet Res 2004;65:1479–1482)
Objective—To determine the pharmacokinetics and clinical effects of a subanesthetic, continuous rate infusion of ketamine administered to healthy awake horses.
Animals—8 adult horses.
Procedures—Ketamine hydrochloride was administered to 2 horses, in a pilot study, at rates ranging from 0.4 to 1.6 mg/kg/h for 6 hours to determine an appropriate dose that did not cause adverse effects. Ketamine was then administered to 6 horses for a total of 12 hours (3 horses at 0.4 mg/kg/h for 6 hours followed by 0.8 mg/kg/h for 6 hours and 3 horses at 0.8 mg/kg/h for 6 hours followed by 0.4 mg/kg/h for 6 hours). Concentration of ketamine in plasma, heart rate, respiratory rate, blood pressure, physical activity, and analgesia were measured prior to, during, and following infusion. Analgesic testing was performed with a modified hoof tester applied at a measured force to the withers and radius.
Results—No signs of excitement and no significant changes in the measured physiologic variables during infusion rates of 0.4 and 0.8 mg of ketamine/kg/h were found. At 6 hours following infusions, heart rate and mean arterial pressure were decreased, compared with preinfusion measurements. An analgesic effect could not be demonstrated during or after infusion. Pharmacokinetic variables for 0.4 and 0.8 mg/kg/h infusions were not significantly different.
Conclusions and Clinical Relevance—Ketamine can be administered to awake horses at 0.4 or 0.8 mg/kg/h without adverse behavioral effects. The observed pharmacokinetic values are different than those reported for single-dose IV bolus administration of this drug.
OBJECTIVE To identify risk factors for anesthetic-related death in pet dogs and cats.
DESIGN Matched case-control study.
ANIMALS 237 dogs and 181 cats.
PROCEDURES Electronic medical records from 822 hospitals were examined to identify dogs and cats that underwent general anesthesia (including sedation) or sedation alone and had death attributable to the anesthetic episode ≤ 7 days later (case animals; 115 dogs and 89 cats) or survived > 7 days afterward (control animals [matched by species and hospital]; 122 dogs and 92 cats). Information on patient characteristics and data related to the anesthesia session were extracted. Conditional multivariable logistic regression was performed to identify factors associated with anesthetic-related death for each species.
RESULTS The anesthetic-related death rate was higher for cats (11/10,000 anesthetic episodes [0.11%]) than for dogs (5/10,000 anesthetic episodes [0.05%]). Increasing age was associated with increased odds of death for both species, as was undergoing nonelective (vs elective) procedures. Odds of death for dogs were significantly greater when preanesthetic physical examination results were not recorded (vs recorded) or when preanesthetic Hct was outside (vs within) the reference range. Odds of death for cats were greater when intra-anesthesia records for oxygen saturation as measured by pulse oximetry were absent. Underweight dogs had almost 15 times the odds of death as nonunderweight dogs; for cats, odds of death increased with increasing body weight (but not with overweight body condition).
CONCLUSIONS AND CLINICAL RELEVANCE Several factors were associated with anesthetic-related death in cats and dogs. This information may be useful for development of strategies to reduce anesthetic-related risks when possible and for education of pet owners about anesthetic risks.