Objective—To quantitate dose- and time-related
magnitudes of interactive effects of morphine (MOR)
and isoflurane (ISO) in horses and to characterize
pharmacokinetics of MOR in plasma and the ventilatory
response to MOR during administration of ISO.
Animals—6 adult horses.
Procedure—Horses were anesthetized 3 times to
determine the minimum alveolar concentration (MAC)
of ISO in O2 and then to characterize the change in
anesthetic requirement as defined by the alteration in
ISO MAC following IV administration of saline (0.9%
NaCl) solution and 2 doses of MOR (low dose, 0.25
mg/kg; high dose, 2.0 mg/kg). Arterial blood samples
were obtained before and after MOR and analyzed.
Results—Mean ± SD baseline ISO MAC was 1.43 ±
0.06%. The ISO MAC did not change with time after
administration of saline solution. Effects of MOR on
ISO MAC varied. Maximal change in MAC ranged
from –20.2 to +28.3% and –18.9 to +56.2% after low
and high doses of MOR, respectively. Typical half-life
of MOR in plasma was 40 to 60 minutes and related
to dose. Mean PaCO2 increased from 70 mm Hg
before MOR to 88 to 102 mm Hg for 30 to 240 minutes
after the high dose of MOR. Recovery from
anesthesia after administration of the high dose of
MOR was considered undesirable and dangerous.
Conclusions and Clinical Relevance—Our results
do not support routine clinical use of MOR administered
IV at dosages of 0.25 or 2.0 mg/kg as an adjuvant
to anesthesia in horses administered ISO. (Am J Vet Res 2003;64:166–175)
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)