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 characterize the cardiovascular effects
of romifidine at doses ranging from 5 to 100 µg/kg of
body weight, IV.
Animals—25 clinically normal male Beagles.
Procedure—Romifidine was administered IV at a
dose of 5, 10, 25, 50, or 100 µg/kg (n = 5/group). Heart
rate, arterial pressure, central venous pressure, mean
pulmonary arterial pressure, pulmonary capillary
wedge pressure, body temperature, cardiac output,
and PCV were measured immediately prior to and at
selected times after romifidine administration.
Cardiac index, stroke index, rate-pressure product,
systemic and pulmonary vascular resistance indices,
and left and right ventricular stroke work indices were
calculated. Degree of sedation was assessed by an
observer who was blinded to the dose administered.
Results—Romifidine induced a decrease in heart
rate, pulmonary arterial pressure, rate-pressure product,
cardiac index, and right ventricular stroke work
index and an increase in central venous pressure, pulmonary
capillary wedge pressure, and systemic vascular
resistance index. In dogs given romifidine at a
dose of 25, 50, or 100 µg/kg, an initial increase followed
by a prolonged decrease in arterial pressure
was observed. Arterial pressure immediately
decreased in dogs given romifidine at a dose of 5 or
Conclusion and Clinical Relevance—Results suggest
that IV administration of romifidine induces
dose-dependent cardiovascular changes in dogs.
However, the 2 lowest doses (5 and 10 µg/kg) induced
less cardiovascular depression, and doses ≥ 25 µg/kg
induced similar cardiovascular changes, suggesting
that there may be a ceiling on the cardiovascular
effects of romifidine. (Am J Vet Res 2001;
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 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 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 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.
Procedures—Gabapentin was administered IV (4 mg/kg) or orally (10 mg/kg) in a crossover randomized design. Blood samples were obtained immediately before gabapentin administration and at various times up to 960 minutes after IV administration or up to 1,440 minutes after oral administration. Blood samples were immediately transferred to tubes that contained EDTA and were centrifuged at 4°C. Plasma was harvested and stored at −20°C until analysis. Plasma concentrations of gabapentin were determined by use of liquid chromatography-mass spectrometry. Gabapentin concentration-time data were fit to compartment models.
Results—A 3-compartment model with elimination from the central compartment best described the disposition of gabapentin administered IV to cats, but a 1-compartment model best described the disposition of gabapentin administered orally to cats. After IV administration, the mean ± SEM apparent volume of the central compartment, apparent volume of distribution at steady state, and clearance and the harmonic mean ± jackknife pseudo-SD for terminal half-life were 90.4 ± 11.3 mL/kg, 650 ± 14 mL/kg, 3 ± 0.2 mL/min/kg, and 170 ± 21 minutes, respectively. Mean ± SD systemic availability and harmonic mean ± jackknife pseudo-SD terminal half-life after oral administration were 88.7 ± 11.1% and 177 ± 25 minutes, respectively.
Conclusions and Clinical Relevance—The disposition of gabapentin in cats was characterized by a small volume of distribution and a low clearance.
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 thermal antinociceptive effect of various single doses of gabapentin administered orally in cats.
Animals—6 healthy adult domestic shorthair cats.
Procedures—Baseline skin temperature and baseline thermal threshold were determined via application of a thermal probe to the thorax of each cat prior to oral administration (in random order) of an empty capsule (placebo) or a capsule containing 5, 10, or 30 mg of gabapentin/kg (4 experiments/cat). After each treatment, thermal threshold was determined at intervals during an 8-hour period. Plasma gabapentin concentration was measured prior to and at 1-hour intervals after drug administration. Dose and time effects were analyzed by use of a repeated-measures ANOVA.
Results—Peak plasma gabapentin concentration increased with increasing gabapentin dose. After administration of the 5, 10, and 30 mg/kg doses, median interval until the greatest gabapentin concentration was detected was 60, 120, and 90 minutes, respectively (interval ranges were 60 to 120 minutes, 60 to 120 minutes, and 60 to 180 minutes, respectively). In the experiments involving administration of the placebo or increasing doses of gabapentin, mean ± SD baseline skin temperature and thermal threshold were 36.8 ± 1.21°C and 45.8 ± 4.4°C, 36.9 ± 1.1°C and 43.1 ± 2.4°C, 37.0 ± 0.7°C and 44.0 ± 1.5°C, and 36.1 ± 1.7°C and 43.3 ± 3.3°C, respectively. There was no significant effect of treatment on thermal threshold.
Conclusions and Clinical Relevance—At the doses evaluated, orally administered gabapentin did not affect the thermal threshold in healthy cats and therefore did not appear to provide thermal antinociception. (Am J Vet Res 2010;71:1027–1032)