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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.

Full access
in American Journal of Veterinary Research

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)

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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 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 compare cardiovascular effects of equipotent infusion doses of propofol alone and in combination with ketamine administered with and without noxious stimulation in cats.

Animals—6 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 were obtained.

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 decreased PaO2.

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)

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 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

Summary

Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered to 24 isoflurane-anesthetized domestic chickens. Birds were randomly assigned to 4 groups, and atracurium was administered at dosage of 0.15, 0.25, 0.35 or 0.45 mg/kg of body weight. The time of onset of twitch depression, the amount of maximal twitch depression, and the duration of muscular relaxation were recorded. After return to control twitch height, atracurium was further administered to achieve > 75% twitch depression. When twitch depression reached 75% during noninduced recovery, 0 5 mg of edrophonium/kg was administered to reverse the muscle relaxation. Throughout the experimental period, cardiovascular, arterial blood gas, and acid-base variables were monitored.

The effective dosage of atracurium to result in 95% twitch depression in 50% of birds, (ed 95/50) was calculated, using probit analysis, to be 0.25 mg/kg, whereas the ed 95/95, the dosage of atracurium to result in 95% twitch depression in 95% of birds, was calculated by probit analysis to be 0.46 mg/kg. The total duration of action at dosage of 0.25 mg/kg was 34.5 ± 5.8 minutes; at the highest dosage (0 45 mg/kg), total duration increased 0 47.8 ± 10.3 minutes. The return to control twitch height was greatly hastened by administration of edrophonium. Small, but statistically significant changes in heart rate and systolic blood pressure, were associated with administration of atracurium and edrophonium. These changes would not be clinically relevant.

In this study, atracurium was found to be safe and reliable for induction of muscle relaxation in isoflurane-anesthetized chickens.

Free access
in American Journal of Veterinary Research

SUMMARY

The cardiovascular and respiratory effects of 3 rapidly acting barbiturates, thiopental sodium, thiamylal sodium, and methohexital sodium, were studied in dogs from completion of injection until 12.5 minutes after injection. The doses administered were 19.4 mg of thiopental/kg of body weight, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg, which were chosen as equipotent doses necessary to inhibit the laryngoscopic reflex in 50% of the population. To determine the cardiovascular and respiratory effects for each drug, the values at each measurement time following injection were compared with baseline values (T0). At the 15- and 30-second measurement times following thiopental administration, stroke volume (sv) decreased; heart rate (hr), left atrial pressure, and mean pulmonary arterial pressure increased; and cardiac index (ci), myocardial contractility, and systemic and pulmonary vascular resistances were not different from baseline values. Mean arterial pressure (map) was not different from the baseline value at 15 seconds, but was increased from 30 seconds to 2 minutes. All values except hr had returned to baseline values by 7.5 minutes. At all measurement times, arterial oxygen tension and arterial pH were decreased, and arterial carbon dioxide tension increased from baseline values.

Although the cardiovascular and respiratory changes following administration of thiamylal and methohexital were similar to those described for thiopental, some differences were found. Following thiamylal administration, systemic vascular resistance increased at 1 minute, pulmonary vascular resistance increased at 1 and 2 minutes, and myocardial contractility increased at 1 and 2 minutes. Following methohexital administration, map decreased at 15 seconds, and sv decreased at all measurement times. Cardiac index increased at 30 seconds, 1 minute, and 2 minutes; myocardial contractility increased at 1, 2, and 2.5 minutes; and blood-gas and pH had returned to baseline by 12.5 minutes. To determine differences between drugs, the cardiovascular and respiratory values for each drug were compared at each measurement time. Changes in hr and sv induced by the 3 drugs were similar at all measurement times. Mean arterial pressure at 15 and 30 seconds was lower following methohexital administration than after thiopental or thiamylal administration. Cardiac index was higher at 1 minute following methohexital administration, compared with that after thiamylal administration, whereas systemic vascular resistance was higher at 1 minute following thiamylal administration, compared with that after methohexital administration. The increase in left atrial pressure was greater following thiamylal administration than after thiopental administration at 30 seconds to 5 minutes or after methohexital administration at 1 to 5 minutes. Mean pulmonary arterial pressure was significantly higher at 2 to 4 minutes following thiamylal administration than after methohexital administration. Pulmonary vascular resistance was higher at 1 minute following thiamylal administration, compared with that after thiopental and methohexital administration. At 1 and 2 minutes, myocardial contractility was significantly higher following methohexital administration, compared with that after thiobarbiturate administration. Arterial oxygen tension was lower at 12.5 minutes following administration of the thiobarbiturates, compared with that after methohexital administration. When compared with methohexital administration, arterial carbon dioxide tension was higher at 7.5 and 12.5 minutes following thiamylal administration. The decrease in pH following thiamylal administration was greater at all measurement times, compared with that after thiopental and methohexital administration.

Free access
in American Journal of Veterinary Research

SUMMARY

Thiopental, thiamylal, and methohexital were administered to 30 dogs to determine equipotent doses necessary to inhibit laryngeal reflexes. The doses studied were 7.1, 10.0, 14.1, 20.0, and 28.3 mg of thiopental/kg of body weight; 5.7, 8.0, 11.3, 16.0, and 22.6 mg of thiamylal/kg; and 3.5, 5.0, 7.1, 10.0, and 14.1 mg of methohexital/kg. At 1, 2.5, 5, and 10 minutes after injection, the presence or absence of the laryngoscopic reflex, pedal reflex, and jaw tone were recorded. The times for return of each reflex, as well as the ability to walk 10 steps without assistance, were also recorded. Using the method of least squares, a probit analysis was performed on the quantal responses at 1 minute. The effective dose in 50% of the population for the laryngoscopic reflex was chosen as the end point for intubation, and the computed doses necessary to achieve this end point were 19.4 mg of thiopental/kg, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg. When potencies of the drugs were compared with that of thiopental (1), thiamylal was found to be equipotent (1.06) and methohexital twice as potent (2.0). At the accepted clinical dose, recovery times for thiopental (71.1 ± 7.2 minutes) and thiamylal (75.3 ± 7.7 minutes) were similar, and twice that for methohexital (33.9 ± 4.6 minutes).

Free access
in American Journal of Veterinary Research