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  • Author or Editor: Bruno H. Pypendop x
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Abstract

Objective—To determine the pharmacokinetics of ketamine and norketamine in isoflurane-anesthetized dogs.

Animals—6 dogs.

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 analysis.

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 and norketamine.

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)

Full access
in American Journal of Veterinary Research

Abstract

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.

Animals—10 dogs.

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.

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in American Journal of Veterinary Research

Abstract

Objective—To determine the hemodynamic effects of lidocaine (administered IV to achieve 6 plasma concentrations) in isoflurane-anesthetized cats.

Animals—6 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)

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in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine hemodynamic effects of 3 concentrations of sevoflurane in cats.

Animals—6 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 experiments.

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)

Full access
in American Journal of Veterinary Research

Abstract

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 10 µg/kg.

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; 62:490–495)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of IV administration of lidocaine on thermal antinociception in conscious cats. Animals—6 cats.

Procedure—2 experiments were performed in each cat (interval of at least 2 months). In experiment 1, lidocaine pharmacokinetics were determined for each conscious cat following IV administration of a bolus of lidocaine (2 mg/kg). In experiment 2, data from experiment 1 were used to calculate appropriate doses of lidocaine that would achieve predetermined plasma lidocaine concentrations in the cats; lidocaine (or an equivalent volume of saline [0.9% NaCl] solution as the control treatment) was administered IV to target pseudo–steady-state plasma concentrations of 0, 0.5, 1, 2, 5, and 8 μg/mL. Skin temperature and thermal threshold were determined at the start of the experiment (baseline) and at each concentration. Samples of venous blood were obtained at each target concentration for plasma lidocaine concentration determination.

Results—In experiment 2, actual plasma lidocaine concentrations were 0.00 ± 0.00 μg/mL, 0.25 ± 0.18 μg/mL, 0.57 ± 0.20 μg/mL, 1.39 ± 0.13 μg/mL, 2.33 ± 0.45 μg/mL, and 4.32 ± 0.66 μg/mL for target plasma concentrations of 0, 0.5, 1, 2, 5, and 8 μg/mL, respectively. Compared with baseline values, no significant change in skin temperature or thermal threshold was detected at any lidocaine plasma concentration (or saline solution equivalent). Skin temperature or thermal threshold values did not differ between lidocaine or control treatments.

Conclusions and Clinical Relevance—Results indicated that these moderate plasma concentrations of lidocaine did not affect thermal antinociception in cats.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the use of a transesophageal echo-Doppler ultrasonography (TED) technique for measurement of aortic blood flow (ABF) in relation to cardiac output (CO) measured by use of a thermodilution technique in anesthetized cats.

Animals—6 adult cats (mean ± SD body weight, 5 ± 0.7 kg).

Procedures—Anesthesia was induced and maintained in cats by administration of isoflurane. A thermodilution catheter was placed in a pulmonary artery. The TED probe was positioned in the esophagus in the region where the aorta and esophagus are almost parallel. Five baseline values for ABF and CO were concurrently recorded. Cats were randomly assigned to a high or low CO state (increase or decrease in CO by at least 25% from baseline, respectively). Baseline conditions were restored, and the other CO state was induced, after which baseline conditions were again restored. For each CO state, ABF and CO were measured 5 times at 5-minute intervals. Correlation and agreement between the techniques were determined by use of the Pearson product-moment correlation and Bland-Altman method.

Results—CO ranged from 0.16 to 0.75 L/min and ABF from 0.05 to 0.48 L/min. Overall data analysis revealed a high correlation (r = 0.884) between techniques but poor agreement (limits of agreement, −0.277 to 0.028 L/min). During the low CO state, correlation between techniques was low (r = 0.413).

Conclusions and Clinical Relevance—TED did not accurately measure CO. However, it allowed evaluation of CO patterns and may be useful clinically in anesthetized cats.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics of gabapentin in cats after IV and oral administration.

Animals—6 healthy female adult domestic shorthair 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.

Full access
in American Journal of Veterinary Research