Objective—To determine whether the variability of cardiorespiratory measurements is smaller when administering desflurane at a multiple of the individual's minimum alveolar concentration (MAC) or at a predetermined, identical concentration in all subjects.
Procedures—Desflurane was administered at 1.5 times the individual's MAC (iMAC) and 1.5 times the group's MAC (gMAC). The order of concentrations was randomly selected. Heart rate, respiratory rate, arterial blood pressure, central venous pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, arterial and mixed-venous blood gas tensions and pH, and cardiac output were measured. The desflurane concentration required to achieve a mean arterial pressure (MAP) of 60 mm Hg was then determined. Finally, the desflurane concentration required to achieve an end-tidal PCO2 of 55 mm Hg was measured.
Results—Variances when administering 1.5 iMAC or 1.5 gMAC were not significantly different for any variable studied. Differences between the MAC multiples needed to reach an MAP of 60 mm Hg and the mean of the sample were significantly larger when gMAC was used, compared with iMAC, indicating that a multiple of iMAC better predicted the concentration resulting in a MAP of 60 mm Hg.
Conclusions and Clinical Relevance—Results suggest that, in a small group of dogs, variability in cardiorespiratory measurements among dogs is unlikely to differ whether an inhalant anesthetic is administered at a multiple of the iMAC in each dog or at an identical gMAC in all dogs.
Objective—To characterize the relationship between plasma dexmedetomidine concentration and the temperature difference between the thermal threshold and skin temperature (ΔT) and between plasma dexmedetomidine concentration and sedation score in healthy cats.
Animals—5 healthy adult spayed female cats.
Procedures—Cats received IV administrations of saline (0.9% NaCl) solution, dexmedetomidine (5, 20, or 50 μg/kg), or acepromazine (0.1 mg/kg). Blood samples were collected and thermal threshold and sedation score were determined before and at various times up to 8 hours after drug administration. In addition, cats received an IV infusion of dexmedetomidine that targeted a concentration achieving 99% of the maximum effect on ΔT.
Results—No change in ΔT over time was found for the saline solution and acepromazine treatments; ΔT increased for 45 minutes when cats received dexmedetomidine at 5 and 20 μg/kg and for 180 minutes when cats received dexmedetomidine at 50 μg/kg. No change in sedation score over time was found for saline solution. Sedation score increased for 120 minutes after cats received acepromazine and for 60, 120, and 180 minutes after cats received dexmedetomidine at 5, 20, and 50 μg/kg, respectively. The plasma dexmedetomidine concentration–effect relationships for the effect on ΔT and sedation score were almost identical. The plasma dexmedetomidine concentration after infusion was lower than targeted, and ΔT was not significantly affected.
Conclusions and Clinical Relevance—Dexmedetomidine administration to cats resulted in thermal analgesia and also profound sedation. These data may be useful for predicting the course of thermal analgesia and sedation after dexmedetomidine administration to cats.
Objective—To characterize the pharmacokinetics of dexmedetomidine after IV administration of a bolus to conscious healthy cats.
Animals—5 healthy adult spayed female cats.
Procedures—Dexmedetomidine was administered IV as a bolus at 3 doses (5, 20, or 50 μg/kg) on separate days in a random order. Blood samples were collected immediately before and at various times for 8 hours after drug administration. Plasma dexmedetomidine concentrations were determined with liquid chromatography–mass spectrometry. Compartment models were fitted to the concentration-time data by means of nonlinear regression.
Results—A 2-compartment model best fit the concentration-time data after administration of 5 μg/kg, whereas a 3-compartment model best fit the data after administration of 20 and 50 μg/kg. The median volume of distribution at steady-state and terminal half-life were 371 mL/kg (range, 266 to 435 mL/kg) and 31.8 minutes (range, 30.3 to 39.7 minutes), respectively, after administration of 5 μg/kg; 545 mL/kg (range, 445 to 998 mL/kg) and 56.3 minutes (range, 39.3 to 68.9 minutes), respectively, after administration of 20 μg/kg; and 750 mL/kg (range, 514 to 938 mL/kg) and 75.3 minutes (range, 52.2 to 223.3 minutes), respectively, after administration of 50 μg/kg.
Conclusions and Clinical Relevance—The pharmacokinetics of dexmedetomidine was characterized by a small volume of distribution and moderate clearance and had minimal dose dependence within the range of doses evaluated. These data will help clinicians design dosing regimens once effective plasma concentrations are established.
Objective—To determine the hemodynamic effects
of lidocaine (administered IV to achieve 6 plasma concentrations)
in isoflurane-anesthetized cats.
Procedure—Cats were anesthetized with isoflurane in
oxygen (end-tidal isoflurane concentration set at 1.25
times the predetermined individual minimum alveolar
concentration). Lidocaine was administered IV to each
cat to achieve target pseudo–steady-state plasma concentrations
of 0, 3, 5, 7, 9, and 11 µg/mL, and isoflurane
concentration was reduced to an equipotent concentration.
At each plasma lidocaine concentration, cardiovascular
and blood gas variables; PCV; and plasma total protein,
lactate, lidocaine, and monoethylglycinexylidide
concentrations were measured in cats before and during
noxious stimulation. Derived variables were calculated.
Results—In isoflurane-anesthetized cats, heart rate,
cardiac index, stroke index, right ventricular stroke
work index, plasma total protein concentration,
mixed-venous PO2 and hemoglobin oxygen saturation,
arterial and mixed-venous bicarbonate concentrations,
and oxygen delivery were significantly lower
during lidocaine administration, compared with values
determined without lidocaine administration. Mean
arterial pressure, central venous pressure, pulmonary
artery pressure, systemic and pulmonary vascular
resistance indices, PCV, arterial and mixed-venous
hemoglobin concentrations, plasma lactate concentration,
arterial oxygen concentration, and oxygen
extraction ratio were significantly higher during
administration of lidocaine, compared with values
determined without lidocaine administration. Noxious
stimulation did not significantly affect most variables.
Conclusions and Clinical Relevance—In isofluraneanesthetized
cats, although IV administration of lidocaine
significantly decreased inhalant requirements, it
appeared to be associated with greater cardiovascular
depression than an equipotent dose of isoflurane
alone. Administration of lidocaine to reduce isoflurane
requirements is not recommended in cats. (Am J Vet Res 2005;66:661–668)
Objective—To determine the pharmacokinetics of
ketamine and norketamine in isoflurane-anesthetized
Procedure—The minimum alveolar concentration
(MAC) of isoflurane was determined in each dog.
Isoflurane concentration was then set at 0.75 times
the individual's MAC, and ketamine (3 mg/kg) was
administered IV. Blood samples were collected at various
times following ketamine administration. Blood
was immediately centrifuged, and the plasma separated
and frozen until analyzed. Ketamine and norketamine
concentrations were measured in the plasma
samples by use of liquid chromatography–mass spectrometry.
Ketamine concentration-time data were fitted
to compartment models. Norketamine concentration-time
data were examined by use of noncompartmental
Results—The MAC of isoflurane was 1.43 ± 0.18%
(mean ± SD). A 2-compartment model best described
the disposition of ketamine. The apparent volume of
distribution of the central compartment, the apparent
volume of distribution at steady state, and the clearance
were 371.3 ± 162 mL/kg, 4,060.3 ±
2,405.7 mL/kg, and 58.2 ± 17.3 mL/min/kg, respectively.
Norketamine rapidly appeared in plasma following
ketamine administration and had a terminal
half-life of 63.6 ± 23.9 minutes. A large variability in
plasma concentrations, and therefore pharmacokinetic
parameters, was observed among dogs for ketamine
Conclusions and Clinical Relevance—In isoflurane-anesthetized
dogs, a high variability in the disposition
of ketamine appears to exist among individuals. The
disposition of ketamine may be difficult to predict in
clinical patients. (Am J Vet Res 2005;66:2034–2038)
Objective—To determine hemodynamic effects of 3
concentrations of sevoflurane in cats.
Procedure—Cats were anesthetized with sevoflurane
in oxygen. After instruments were inserted, endtidal
sevoflurane concentration was set at 1.25, 1.5, or
1.75 times the individual minimum alveolar concentration
(MAC), which was determined in another
study. Twenty-five minutes were allowed after each
change of concentration. Heart rate; systemic and
pulmonary arterial pressures; central venous pressure;
pulmonary artery occlusion pressure; cardiac
output; body temperature; arterial and mixed-venous
pH, PCO2, PO2, oxygen saturation, and hemoglobin
concentrations; PCV; and total protein and lactate
concentrations were measured for each sevoflurane
concentration before and during noxious stimulation.
Arterial and mixed-venous bicarbonate concentrations,
cardiac index, stroke index, rate-pressure product,
systemic and pulmonary vascular resistance
indices, left and right ventricular stroke work indices,
PaO2, mixed-venous partial pressure of oxygen (Pv–O2),
oxygen delivery, oxygen consumption, oxygen-extraction
ratio, alveolar-to-arterial oxygen difference, and
venous admixture were calculated. Spontaneous and
mechanical ventilations were studied during separate
Results—Mode of ventilation did not significantly
influence any of the variables examined. Therefore,
data from both ventilation modes were pooled for
analysis. Mean arterial pressure, cardiac index, stroke
index, rate-pressure product, left ventricular stroke
work index, arterial and mixed-venous pH, PaO2, and
oxygen delivery decreased, whereas PaCO2, Pva–O2, and
mixed-venous partial pressure of CO2 increased significantly
with increasing doses of sevoflurane.
Noxious stimulation caused a significant increase in
most cardiovascular variables.
Conclusions and Clinical Relevance—Sevoflurane
induces dose-dependent cardiovascular depression in
cats that is mainly attributable to myocardial depression.
( Am J Vet Res 2004;65:20–25)
Objective—To compare cardiovascular effects of
equipotent infusion doses of propofol alone and in
combination with ketamine administered with and
without noxious stimulation in cats.
Procedure—Cats were anesthetized with propofol
(loading dose, 6.6 mg/kg; constant rate infusion [CRI],
0.22 mg/kg/min) and instrumented for blood collection
and measurement of blood pressures and cardiac
output. Cats were maintained at this CRI for a further
60 minutes, and blood samples and measurements
were taken. A noxious stimulus was applied for 5 minutes,
and blood samples and measurements were
obtained. Propofol concentration was decreased to
0.14 mg/kg/min, and ketamine (loading dose, 2
mg/kg; CRI, 23 µg/kg/min) was administered. After a
further 60 minutes, blood samples and measurements
were taken. A second 5-minute noxious stimulus
was applied, and blood samples and measurements
Results—Mean arterial pressure, central venous
pressure, pulmonary arterial occlusion pressure,
stroke index, cardiac index, systemic vascular resistance
index, pulmonary vascular resistance index,
oxygen delivery index, oxygen consumption index,
oxygen utilization ratio, partial pressure of oxygen in
mixed venous blood, pH of arterial blood, PaCO2, arterial
bicarbonate concentration, and base deficit values
collected during propofol were not changed by the
addition of ketamine and reduction of propofol.
Compared with propofol, ketamine and reduction of
propofol significantly increased mean pulmonary arterial
pressure and venous admixture and significantly
Conclusions and Clinical Relevance—Administration
of propofol by CRI for maintenance of anesthesia
induced stable hemodynamics and could prove
to be clinically useful in cats. (Am J Vet Res 2003;64:913–917)
Objective—To determine the thermal antinociceptive effect of oral administration of tramadol hydrochloride at doses between 0.5 and 4 mg/kg in cats.
Animals—6 healthy adult domestic shorthair cats.
Procedures—Baseline (before drug administration; time 0) thermal threshold was determined by applying a thermal probe to the thorax of each cat. Tramadol (0.5, 1, 2, 3, or 4 mg/kg) or a placebo was then administered orally in accordance with a Latin square design. Thermal threshold was determined by an observer who was unaware of treatment at various times until thermal threshold returned to baseline values or 6 hours had elapsed. Plasma tramadol and O-desmethyl-tramadol concentrations were measured prior to drug administration and at 1-hour intervals thereafter. Effect-concentration data were fitted to effect maximum models.
Results—Highest plasma tramadol and O-desmethyl-tramadol concentrations increased with increasing tramadol dose. Significant effects of dose and time on thermal threshold were detected. Thermal threshold was significantly higher than the baseline value at 80 and 120 minutes for the 0.5 mg/kg dose, at 80 and from 120 to 360 minutes for the 2 mg/kg dose, from 40 to 360 minutes for the 3 mg/kg dose, and from 60 to 360 minutes for the 4 mg/kg dose.
Conclusions and Clinical Relevance—Tramadol induced thermal antinociception in cats. Doses of 2 to 4 mg/kg appeared necessary for induction of significant and sustained analgesic effects. Simulations predicted that 4 mg/kg every 6 hours would maintain analgesia close to the maximum effect of tramadol.
Objective—To determine the minimum infusion rate
(MIR50) for propofol alone and in combination with
ketamine required to attenuate reflexes commonly
used in the assessment of anesthetic depth in cats.
Procedure—Propofol infusion started at 0.05 to 0.1
mg/kg/min for propofol alone or 0.025 mg/kg/min for
propofol and ketamine (low-dose [LD] constant rate
infusion [CRI] of 23 µg/kg/min or high-dose [HD] CRI
of 46 µg/kg/min), and after 15 minutes, responses of
different reflexes were tested. Following a response,
the propofol dose was increased by 0.05 mg/kg/min
for propofol alone or 0.025 mg/kg/min for propofol
and ketamine, and after 15 minutes, reflexes were
Results—The MIR50 for propofol alone required to
attenuate blinking in response to touching the medial
canthus or eyelashes; swallowing in response to
placement of a finger or laryngoscope in the pharynx;
and to toe pinch, tetanus, and tail-clamp stimuli were
determined. Addition of LD ketamine to propofol significantly
decreased MIR50, compared with propofol
alone, for medial canthus, eyelash, finger, toe pinch,
and tetanus stimuli but did not change those for laryngoscope
or tail-clamp stimuli. Addition of HD ketamine
to propofol significantly decreased MIR50, compared
with propofol alone, for medial canthus, eyelash,
toe pinch, tetanus, and tail-clamp stimuli but did
not change finger or laryngoscope responses.
Conclusions and Clinical Relevance—Propofol
alone or combined with ketamine may be used for
total IV anesthesia in healthy cats at the infusion rates
determined in this study for attenuation of specific
reflex activity. ( Am J Vet Res 2003;64:907–912)
Objective—To determine effects of epidural administration of morphine and buprenorphine on the minimum alveolar concentration of isoflurane in cats.
Animals—6 healthy adult domestic shorthair cats.
Procedures—Cats were anesthetized with isoflurane in oxygen. Morphine (100 μg/kg diluted with saline [0.9% NaCl] solution to a volume of 0.3 mL/kg), buprenorphine (12.5 μg/kg diluted with saline solution to a volume of 0.3 mL/kg), or saline solution (0.3 mL/kg) was administered into the epidural space according to a Latin square design. The minimum alveolar concentration (MAC) of isoflurane was measured in triplicate by use of the tail clamp technique. At least 1 week was allowed between successive experiments.
Results—The MAC of isoflurane was 2.00 ± 0.18%, 2.13 ± 0.11%, and 2.03 ± 0.09% in the morphine, buprenorphine, and saline solution groups, respectively. No significant difference in MAC was detected among treatment groups.
Conclusions and Clinical Relevance—A significant effect of epidural administration of morphine or buprenorphine on the MAC of isoflurane in cats could not be detected. Further studies are needed to establish whether epidural opioid administration has other benefits when administered as a component of general anesthesia in cats.