Objective—To quantitate the dose and time-related
effects of morphine sulfate on the anesthetic sparing
effect of xylazine hydrochloride in halothane-anesthetized
horses and determine the associated plasma
xylazine and morphine concentration-time profiles.
Animals—6 healthy adult horses.
Procedure—Horses were anesthetized 3 times to
determine the minimum alveolar concentration (MAC)
of halothane in O2 and characterize the anesthetic
sparing effect (ie, decrease in MAC of halothane) by
xylazine (0.5 mg/kg, IV) administration followed
immediately by IV administration of saline
(0.9% NaCl) solution, low-dose morphine (0.1 mg/kg),
or high-dose morphine (0.2 mg/kg). Selected parameters
of cardiopulmonary function were also determined
over time to verify consistency of conditions.
Results—Mean (± SEM) MAC of halothane was
1.05 ± 0.02% and was decreased by 20.1 ± 6.6% at
49 ± 2 minutes following xylazine administration. The
amount of MAC reduction in response to xylazine was
time dependent. Addition of morphine to xylazine
administration did not contribute further to the
xylazine-induced decrease in MAC (reductions of
21.9 ± 1.2 and 20.7 ± 1.5% at 43 ± 4 and 40 ± 4 minutes
following xylazine-morphine treatments for low-and
high-dose morphine, respectively). Overall, cardiovascular
and respiratory values varied little among
treatments. Kinetic parameters describing plasma
concentration-time curves for xylazine were not
altered by the concurrent administration of morphine.
Conclusions and Clinical Relevance—Administration
of xylazine decreases the anesthetic requirement
for halothane in horses. Concurrent morphine
administration to anesthetized horses does not alter
the anesthetic sparing effect of xylazine or its plasma
concentration-time profile. (Am J Vet Res 2004;
Objective—To compare detomidine hydrochloride
and romifidine as premedicants in horses undergoing
Animals—100 client-owned horses.
Procedure—After administration of acepromazine
(0.03 mg/kg, IV), 50 horses received detomidine
hydrochloride (0.02 mg/kg of body weight, IV) and 50
received romifidine (0.1 mg/kg, IV) before induction
and maintenance of anesthesia with ketamine
hydrochloride (2 mg/kg) and halothane, respectively.
Arterial blood pressure and blood gases, ECG, and
heart and respiratory rates were recorded. Induction
and recovery were timed and graded.
Results—Mean (± SD) duration of anesthesia for all
horses was 104 ± 28 minutes. Significant differences
in induction and recovery times or grades were not
detected between groups. Mean arterial blood pressure
(MABP) decreased in both groups 30 minutes
after induction, compared with values at 10 minutes.
From 40 to 70 minutes after induction, MABP was
significantly higher in detomidine-treated horses,
compared with romifidine-treated horses, although
more romifidine-treated horses received dobutamine
infusions. In all horses, mean respiratory rate ranged
from 9 to 11 breaths/min, PaO2 from 200 to 300 mm
Hg, PaCO2 from 59 to 67 mm Hg, arterial pH from 7.33
to 7.29, and heart rate from 30 to 33 beats/min, with
no significant differences between groups.
Conclusions and Clinical Relevance—Detomidine
and romifidine were both satisfactory premedicants.
Romifidine led to more severe hypotension than detomidine,
despite administration of dobutamine to more
romifidine-treated horses. Both detomidine and romifidine
are acceptable α2-adrenoceptor agonists for
use as premedicants before general anesthesia in
horses; however, detomidine may be preferable
when maintenance of blood pressure is particularly
important. (Am J Vet Res 2001;62:359–363)
OBJECTIVE To assess the possible impact of medetomidine on concentrations of alfaxalone in plasma, when coadministered as a constant rate infusion (CRI) to dogs, and to determine the possible impact of medetomidine on the cardiopulmonary effects of alfaxalone during CRI.
ANIMALS 8 healthy adult Beagles.
PROCEDURES 3 treatments were administered in a randomized crossover design as follows: 1 = saline (0.9% NaCl) solution injection, followed in 10 minutes by induction of anesthesia with alfaxalone (loading dose, 2.4 mg/kg; CRI, 3.6 mg/kg/h, for 60 minutes); 2 = medetomidine premedication (loading dose, 4.0 μg/kg; CRI, 4.0 μg/kg/h), followed by alfaxalone (as in treatment 1); and, 3 = medetomidine (as in treatment 2) and MK-467 (loading dose, 150 μg/kg; CRI, 120 μg/kg/h), followed by alfaxalone (as in treatment 1). The peripherally acting α2-adrenoceptor antagonist MK-467 was used to distinguish between the peripheral and central effects of medetomidine. Drugs were administered IV via cephalic catheters, and there was a minimum of 14 days between treatments. Cardiopulmonary parameters were measured for 70 minutes, and jugular venous blood samples were collected until 130 minutes after premedication. Drug concentrations in plasma were analyzed with liquid chromatography–tandem mass spectrometry.
RESULTS The characteristic cardiovascular effects of medetomidine, such as bradycardia, hypertension, and reduction in cardiac index, were obtunded by MK-467. The concentrations of alfaxalone in plasma were significantly increased in the presence of medetomidine, indicative of impaired drug distribution and clearance. This was counteracted by MK-467.
CONCLUSIONS AND CLINICAL RELEVANCE The alteration in alfaxalone clearance when coadministered with medetomidine may be attributed to the systemic vasoconstrictive and bradycardic effects of the α2-adrenoceptor agonist. This could be clinically important because the use of α2-adrenoceptor agonists may increase the risk of adverse effects if standard doses of alfaxalone are used.
PROCEDURES In a randomized crossover study, each dog received 5 premedication protocols (medetomidine [10 μg/kg, IV] alone [MED] and in combination with MK-467 at doses of 50 [MMK50], 100 [MMK100], and 150 [MMK150] μg/kg and 15 minutes after glycopyrrolate [10 μg/kg, SC; MGP]), with at least 14 days between treatments. Twenty minutes after medetomidine administration, anesthesia was induced with ketamine (0.5 mg/kg, IV) and midazolam (0.1 mg/kg, IV) increments given to effect and maintained with isoflurane (1.2%) for 50 minutes. Cardiovascular variables were recorded, and blood samples for determination of plasma dexmedetomidine, levomedetomidine, and MK-467 concentrations were collected at predetermined times. Variables were compared among the 5 treatments.
RESULTS The mean arterial pressure and systemic vascular resistance index increased following the MED treatment, and those increases were augmented and obtunded following the MGP and MMK150 treatments, respectively. Mean cardiac index for the MMK100 and MMK150 treatments was significantly greater than that for the MGP treatment. The area under the time-concentration curve to the last sampling point for dexmedetomidine for the MMK150 treatment was significantly lower than that for the MED treatment.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated concurrent administration of MK-467 with medetomidine alleviated medetomidine-induced hemodynamic changes in a dose-dependent manner prior to isoflurane anesthesia. Following MK-467 administration to healthy dogs, mean arterial pressure was sustained at acceptable levels during isoflurane anesthesia.