OBJECTIVE To evaluate hemodynamic, respiratory, and sedative effects of buccally administered detomidine gel and reversal with atipamezole in dogs.
ANIMALS 8 adult purpose-bred dogs.
PROCEDURES Arterial and venous catheters were placed. Baseline heart rate, respiratory rate, cardiac output (determined via lithium dilution with pulse contour analysis), oxygen delivery, systemic vascular resistance, arterial blood gas values, and sedation score were obtained. Detomidine gel (2.0 mg/m2) was administered on the buccal mucosa. Cardiopulmonary data and sedation scores were obtained at predetermined times over 180 minutes. Atipamezole (0.1 mg/kg) was administered IM at 150 minutes. Reversal of sedation was timed and scored. Data were analyzed with an ANOVA.
RESULTS Compared with baseline values, heart rate was lower at 45 to 150 minutes, cardiac output and oxygen delivery were lower at 30 to 150 minutes, and systemic vascular resistance was increased at 30 to 150 minutes. There were no significant changes in Paco2, Pao2, or lactate concentration at any time point, compared with baseline values, except for lactate concentration at 180 minutes. All dogs became sedated; maximum sedation was detected 75 minutes after administration of detomidine. Mean ± SD time to recovery after atipamezole administration was 7.55 ± 1.89 minutes; sedation was completely reversed in all dogs. No adverse events were detected.
CONCLUSIONS AND CLINICAL RELEVANCE Buccally administered detomidine gel was associated with reliable and reversible sedation in dogs, with hemodynamic effects similar to those induced by other α2-adrenoceptor agonists. Buccally administered detomidine gel could be an alternative to injectable sedatives in healthy dogs.
Objective—To determine the pharmacokinetics of
fluconazole in horses.
Animals—6 clinically normal adult horses.
Procedure—Fluconazole (10 mg/kg of body weight)
was administered intravenously or orally with 2
weeks between treatments. Plasma fluconazole concentrations
were determined prior to and 10, 20, 30,
40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48,
60, and 72 hours after administration. A long-term oral
dosing regimen was designed in which all horses
received a loading dose of fluconazole (14 mg/kg) followed
by 5 mg/kg every 24 hours for 10 days.
Fluconazole concentrations were determined in aqueous
humor, plasma, CSF, synovial fluid, and urine after
administration of the final dose.
Results—Mean (± SD) apparent volume of distribution
of fluconazole at steady state was 1.21 ± 0.01
L/kg. Systemic availability and time to maximum plasma
concentration following oral administration were
101.24 ± 27.50% and 1.97 ± 1.68 hours, respectively.
Maximum plasma concentrations and terminal halflives
after IV and oral administration were similar.
Plasma, CSF, synovial fluid, aqueous humor, and urine
concentrations of fluconazole after long-term oral
administration of fluconazole were 30.50 ± 23.88,
14.99 ± 1.86, 14.19 ± 5.07, 11.39 ± 2.83, and 56.99 ±
32.87 µg/ml, respectively.
Conclusion and Clinical Relevance—Bioavailability
of fluconazole was high after oral administration to
horses. Long-term oral administration maintained plasma
and body fluid concentrations of fluconazole above
the mean inhibitory concentration (8.0 mg/ml) reported
for fungal pathogens in horses. Fluconazole may be
an appropriate agent for treatment of fungal infections
in horses. (Am J Vet Res 2001;62:1606–1611).
Objective—To determine whether treatment of horses with firocoxib affects recovery of ischemic-injured jejunum, while providing effective analgesia.
Procedures—Horses (n = 6 horses/group) received saline (0.9% NaCl) solution (1 mL/50 kg, IV), flunixin meglumine (1.1 mg/kg, IV, q 12 h), or firocoxib (0.09 mg/kg, IV, q 24 h) before 2 hours of jejunal ischemia. Horses were monitored via pain scores and received butorphanol for analgesia. After 18 hours, ischemic-injured and control mucosa were placed in Ussing chambers for measurement of transepithelial resistance and permeability to lipopolysaccharide. Histomorphometry was used to determine denuded villus surface area. Western blots for cyclooxygenase (COX)-1 and COX-2 were performed. Plasma thromboxane B2 and prostaglandin E2 metabolite (PGEM) concentrations were determined.
Results—Pain scores did not significantly increase after surgery in horses receiving flunixin meglumine or firocoxib. Transepithelial resistance of ischemic-injured jejunum from horses treated with flunixin meglumine was significantly lower than in saline- or firocoxib-treated horses. Lipopolysaccharide permeability across ischemic-injured mucosa was significantly increased in horses treated with flunixin meglumine. Treatment did not affect epithelial restitution. Cyclooxygenase-1 was constitutively expressed and COX-2 was upregulated after 2 hours of ischemia. Thromboxane B2 concentration decreased with flunixin meglumine treatment but increased with firocoxib or saline treatment. Flunixin meglumine and firocoxib prevented an increase in PGEM concentration after surgery.
Conclusions and Clinical Relevance—Flunixin meglumine retarded mucosal recovery in ischemic-injured jejunum, whereas firocoxib did not. Flunixin meglumine and firocoxib were effective visceral analgesics. Firocoxib may be advantageous in horses recovering from ischemic intestinal injury.
Objective—To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum.
Procedures—Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed.
Results—Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flu-nixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cy-clooxygenase-independent effects.
Conclusions and Clinical Relevance—Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.
Objective—To determine appropriate intraocular lens (IOL) implant strength to approximate emmetropia in horses.
Sample Population—16 enucleated globes and 4 adult horses.
Procedures—Lens diameter of 10 enucleated globes was measured. Results were used to determine the appropriate-sized IOL implant for insertion in 6 enucleated globes and 4 eyes of adult horses. Streak retinoscopy and ocular ultrasonography were performed before and after insertion of 30-diopter (D) IOL implants (enucleated globes) and insertion of 25-D IOL implants (adult horses).
Results—In enucleated globes, mean ± SD lens diameter was 20.14 ± 0.75 mm. Preoperative and postoperative refractive state of enucleated globes with 30-D IOL implants was −0.46 ± 1.03 D and −2.47 ± 1.03 D, respectively; preoperative and postoperative difference in refraction was 2.96 ± 0.84 D. Preoperative anterior chamber (AC) depth, crystalline lens thickness (CLT), and axial globe length (AxL) were 712 ± 0.82 mm, 11.32 ± 0.81 mm, and 40.52 ± 1.26 mm, respectively; postoperative AC depth was 10.76 ± 1.16 mm. Mean ratio of preoperative to postoperative AC depth was 0.68. In eyes receiving 25-D IOL implants, preoperative and postoperative mean refractive error was 0.08 ± 0.68 D and −3.94 ± 1.88 D, respectively. Preoperative AC depth, CLT, and AxL were 6.36 ± 0.22 mm, 10.92 ± 1.92 mm, and 38.64 ± 2.59 mm, respectively. Postoperative AC depth was 8.99 ± 1.68 mm. Mean ratio of preoperative to postoperative AC depth was 0.73.
Conclusions and Clinical Relevance—Insertion of 30-D (enucleated globes) and 25-D IOL implants (adult horses) resulted in overcorrection of refractive error.
Objective—To investigate effects of lidocaine hydrochloride administered IV on mucosal inflammation in ischemia-injured jejunum of horses treated with flunixin meglumine.
Procedures—Horses received saline (0.9% NaCl) solution (SS; 1 mL/50 kg, IV [1 dose]), flunixin meglumine (1 mg/kg, IV, q 12 h), lidocaine (bolus [1.3 mg/kg] and constant rate infusion [0.05 mg/kg/min], IV, during and after recovery from surgery), or both flunixin and lidocaine (n = 6/group). During surgery, blood flow was occluded for 2 hours in 2 sections of jejunum in each horse. Uninjured and ischemia-injured jejunal specimens were collected after the ischemic period and after euthanasia 18 hours later for histologic assessment and determination of cyclooxygenase (COX) expression (via western blot procedures). Plasma samples collected prior to (baseline) and 8 hours after the ischemic period were analyzed for prostanoid concentrations.
Results—Immediately after the ischemic period, COX-2 expression in horses treated with lidocaine alone was significantly less than expression in horses treated with SS or flunixin alone. Eighteen hours after the ischemic period, mucosal neutrophil counts in horses treated with flunixin alone were significantly higher than counts in other treatment groups. Compared with baseline plasma concentrations, postischemia prostaglandin E2 metabolite and thromboxane B2 concentrations increased in horses treated with SS and in horses treated with SS or lidocaine alone, respectively.
Conclusions and Clinical Relevance—In horses with ischemia-injured jejunum, lidocaine administered IV reduced plasma prostaglandin E2 metabolite concentration and mucosal COX-2 expression. Coadministration of lidocaine with flunixin ameliorated the flunixin-induced increase in mucosal neutrophil counts.