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- Author or Editor: Phillip Lerche x
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Abstract
Objective—To determine maximum extrarenal plasma clearance of technetium-99m-mercaptoacetyltriglycine (99mTc–MAG3) and maximum extrarenal hepatic uptake of 99mTc–MAG3 in cats.
Animals—6 clinically normal adult cats.
Procedure—Simultaneously, baseline plasma clearance and camera-based uptake of 99mTc–MAG3 were determined in anesthetized cats. Double exponential curves were fitted to plasma clearance data. Injected dose was divided by area under the curve and body weight to determine 99mTc–MAG3 clearance. Regions of interest were drawn around kidneys and liver, and percentage dose uptake was determined 1 to 3 minutes after injection. After bilateral nephrectomy, simultaneous extrarenal plasma clearance and camera- based hepatic uptake of 99mTc–MAG3 were evaluated in each cat.
Results—Mean ± SD baseline plasma clearance and extrarenal clearance were 5.29 ± 0.77 and 0.84 ± 0.47 mL/min/kg, respectively. Mean extrarenal clearance (as a percentage of baseline plasma clearance) was 16.06 ± 7.64%. For right, left, and both kidneys, mean percentage dose uptake was 9.42 ± 2.58, 9.37 ± 0.86, and 18.79 ± 2.47%, respectively. Mean hepatic percentage dose uptake before and after nephrectomy was 12.95 ± 0.93 and 21.47 ± 2.00%, respectively. Mean percentage change of hepatic uptake after nephrectomy was 166.89 ± 23.19%.
Conclusions and Clinical Relevance—In cats, extrarenal clearance of 99mTc–MAG3 is higher than that of other species; therefore, 99mTc–MAG3 is not useful for estimation of renal function in felids. Evaluation of renal function in cats may be more accurate via camera- based versus plasma clearance-based methods because camera-based studies can discriminate specific organs. (Am J Vet Res 2003;64:1076–1080)
Abstract
Objective—To determine the effect of dexmedetomidine, morphine-lidocaine-ketamine (MLK), and dexmedetomidine-morphine-lidocaine-ketamine (DMLK) constant rate infusions on the minimum alveolar concentration (MAC) of isoflurane and bispectral index (BIS) in dogs.
Animals—6 healthy adult dogs.
Procedures—Each dog was anesthetized 4 times with a 7-day washout period between anesthetic episodes. During the first anesthetic episode, the MAC of isoflurane (baseline) was established. During the 3 subsequent anesthetic episodes, the MAC of isoflurane was determined following constant rate infusion of dexmedetomidine (0.5 μg/kg/h), MLK (morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine, 0.6 mg/kg/h), or DMLK (dexmedetomidine, 0.5 μg/kg/h; morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine 0.6 mg/kg/h). Among treatments, MAC of isoflurane was compared by means of a Friedman test with Conover posttest comparisons, and heart rate, direct arterial pressures, cardiac output, body temperature, inspired and expired gas concentrations, arterial blood gas values, and BIS were compared with repeated-measures ANOVA and a Dunn test for multiple comparisons.
Results—Infusion of dexmedetomidine, MLK, and DMLK decreased the MAC of isoflurane from baseline by 30%, 55%, and 90%, respectively. Mean heart rates during dexmedetomidine and DMLK treatments was lower than that during MLK treatment. Compared with baseline values, mean heart rate decreased for all treatments, arterial pressure increased for the DMLK treatment, cardiac output decreased for the dexmedetomidine treatment, and BIS increased for the MLK and DMLK treatments. Time to extubation and sternal recumbency did not differ among treatments.
Conclusions and Clinical Relevance—Infusion of dexmedetomidine, MLK, or DMLK reduced the MAC of isoflurane in dogs. (Am J Vet Res 2013;74:963–970)
Abstract
Objective—To determine the effect of IV administration of crystalloid (lactated Ringer's solution [LRS]) or colloid (hetastarch) fluid on isoflurane-induced hypotension in dogs.
Animals—6 healthy Beagles.
Procedures—On 3 occasions, each dog was anesthetized with propofol and isoflurane and instrumented with a thermodilution catheter (pulmonary artery). Following baseline assessments of hemodynamic variables, end-tidal isoflurane concentration was increased to achieve systolic arterial blood pressure (SABP) of 80 mm Hg. At that time (0 minutes), 1 of 3 IV treatments (no fluid, LRS [80 mL/kg/h], or hetastarch [80 mL/kg/h]) was initiated. Fluid administration continued until SABP was within 10% of baseline or to a maximum volume of 80 mL/kg (LRS) or 40 mL/kg (hetastarch). Hemodynamic variables were measured at intervals (0 through 120 minutes and additionally at 150 and 180 minutes in LRS- or hetastarch-treated dogs). Several clinicopathologic variables including total protein concentration, PCV, colloid osmotic pressure, and viscosity of blood were assessed at baseline and intervals thereafter (0 through 120 minutes).
Results—Administration of 80 mL of LRS/kg did not increase SABP in any dog, whereas administration of ≤ 40 mL of hetastarch/kg increased SABP in 4 of 6 dogs. Fluid administration increased cardiac index and decreased systemic vascular resistance. Compared with hetastarch treatment, administration of LRS decreased blood viscosity. Treatment with LRS decreased PCV and total protein concentration, whereas treatment with hetastarch increased colloid osmotic pressure.
Conclusions and Clinical Relevance—Results indicated that IV administration of hetastarch rather than LRS is recommended for the treatment of isoflurane-induced hypotension in dogs.
Abstract
Objective—To evaluate the effects of the α2-adrenoceptor agonist medetomidine on respiratory rate (RR), tidal volume (VT), minute volume (VM), and central respiratory neuromuscular drive as determined by inspiratory occlusion pressure (IOP) during increasing fractional inspired concentrations of carbon dioxide (FiCO2) in conscious dogs.
Animals—6 healthy dogs (3 males and 3 females).
Procedure—Dogs were administered 0, 5, or 10 µg of medetomidine/kg IV. We measured RR, VT, VM, and IOP for the first 0.1 second of airway occlusion (IOP0.1) during FiCO2 values of 0%, 2.5%, 5.0%, and 7.5% at 15 minutes before and 5, 30, and 60 minutes after administration of medetomidine.
Results—Increases in FiCO2 significantly increased RR, VT, and VM. The IV administration of 5 and 10 µg of medetomidine/kg significantly decreased RR and VM at 5, 30, and 60 minutes for FiCO2 values of 2.5% and 5.0% and at 30 and 60 minutes for an FiCO2 value of 7.5%. The IOP0.1 was decreased after 30 minutes only for an FiCO2 value of 7.5% in dogs administered 5 and 10 µg of medetomidine/kg. The IOP0.1 was decreased at 60 minutes after administration of 10 µg of medetomidine/kg for an FiCO2 value of 7.5%.
Conclusions and Clinical Relevance—The IV administration of medetomidine decreases RR, VM, and central respiratory drive in conscious dogs. Medetomidine should be used cautiously and with careful monitoring in dogs with CNS depression or respiratory compromise. (Am J Vet Res 2004;65: 720–724)
Abstract
Objective—To evaluate the effect of medetomidine on minimum alveolar concentration (MAC), respiratory rate, tidal volume, minute volume (VM), and maximum inspiratory occlusion pressure (IOCPmax) in halothane- and isoflurane-anesthetized dogs.
Animals—6 healthy adult dogs (3 males and 3 females).
Procedure—The MAC of both inhalants was determined before and 5, 30, and 60 minutes after administration of medetomidine (5 μg/kg, IV). Dogs were subsequently anesthetized by administration of halothane or isoflurane and administered saline (0.9% NaCl) solution IV or medetomidine (5 μg/kg, IV). Respiratory variables and IOCPmax were measured at specific MAC values 15 minutes before and 5, 30, and 60 minutes after IV administration of medetomidine while dogs breathed 0% and 10% fractional inspired carbon dioxide (FICO2). Slopes of the lines for VM/FICO2 and IOCPmax/FICO2 were then calculated.
Results—Administration of medetomidine decreased MAC of both inhalants. Slope of VM/FICO2 increased in dogs anesthetized with halothane after administration of medetomidine, compared with corresponding values in dogs anesthetized with isoflurane. Administration of medetomidine with a simultaneous decrease in inhalant concentration significantly increased the slope for VM/FICO2, compared with values after administration of saline solution in dogs anesthetized with halothane but not isoflurane. Values for IOCPmax did not differ significantly between groups.
Conclusions and Clinical Relevance—Equipotent doses of halothane and isoflurane have differing effects on respiration that are most likely attributable to differences in drug effects on central respiratory centers. Relatively low doses of medetomidine decrease the MAC of halothane and isoflurane in dogs.
Abstract
OBJECTIVE
To determine the effect of oral administration of gabapentin (20 mg/kg) on the minimum alveolar concentration (MAC) of isoflurane in dogs.
ANIMALS
6 healthy adult dogs (3 males and 3 females with a mean ± SD body weight of 24.8 ± 1.3 kg).
PROCEDURES
Each dog was anesthetized twice. Dogs were initially assigned to 1 of 2 treatments (gabapentin [20 mg/kg, PO] followed 2 hours later by anesthesia maintained with isoflurane or anesthesia maintained with isoflurane alone). A minimum of 7 days later, dogs received the other treatment. The MAC of isoflurane was determined by use of an iterative bracketing technique with stimulating electrodes placed in the maxillary buccal mucosa. Hemodynamic variables and vital parameters were recorded at the lowest end-tidal isoflurane concentration at which dogs did not respond to the stimulus. Effect of treatment on outcome variables was analyzed by use of a paired t test.
RESULTS
Mean ± SD MAC of isoflurane was significantly lower when dogs received gabapentin and isoflurane (0.71 ± 0.12%) than when dogs received isoflurane alone (0.91 ± 0.26%). Mean reduction in MAC of isoflurane was 20 ± 14%. Hemodynamic variables did not differ significantly between treatments. Mean time to extubation was significantly less when dogs received gabapentin and isoflurane (6 ± 4 minutes) than when dogs received isoflurane alone (23 ± 15 minutes).
CONCLUSIONS AND CLINICAL RELEVANCE
Oral administration of gabapentin 2 hours before anesthesia maintained with isoflurane had a MAC-sparing effect with no effect on hemodynamic variables or vital parameters of dogs.
Abstract
Objective—To determine the effects of IV administration of perzinfotel and a perzinfotel-fentanyl combination on the minimum alveolar concentration (MAC) of isoflurane in dogs.
Animals—6 healthy sexually intact Beagles (3 males and 3 females).
Procedures—All dogs were instrumented with a telemetry device for continuous monitoring of heart rate, arterial blood pressure, and core body temperature (at a femoral artery). Dogs were anesthetized with propofol (6 mg/kg, IV) and isoflurane. Isoflurane MAC values were determined in 3 experiments in each dog, separated by at least 7 days, before (baseline) and after the following treatments: no treatment (anesthetic only), perzinfotel (20 mg/kg, IV), fentanyl (5 μg/kg bolus, IV, followed by a continuous IV infusion at 0.15 μg/kg/min), and a fentanyl-perzinfotel combination (20 mg of perzinfotel/kg, IV, plus the fentanyl infusion). Bispectral index and oxygen saturation as measured by pulse oximetry were also monitored throughout anesthesia.
Results—Without treatment, the mean ± SD isoflurane MAC for all 6 dogs was 1.41 ± 0.10%. Baseline MAC was 1.42 ± 0.08%. Intravenous administration of perzinfotel, fentanyl, and the perzinfotel-fentanyl combination significantly decreased the MAC by 39%, 35%, and 66%, respectively. Perzinfotel and perzinfotel-fentanyl administration yielded significant increases in the bispectral index. Mean, systolic, and diastolic arterial blood pressures significantly increased from baseline values when perzinfotel was administered. Systolic arterial blood pressure significantly increased from the baseline value when perzinfotel-fentanyl was administered. No adverse effects were detected.
Conclusions and Clinical Relevance—IV administration of perzinfotel, fentanyl, or a perzinfotel-fentanyl combination reduced isoflurane MAC in dogs and increased arterial blood pressure.
Abstract
Objective—To evaluate the use of midazolam, ketamine, and xylazine for total IV anesthesia (TIVA) in horses.
Animals—6 healthy Thoroughbred mares.
Procedures—Horses were sedated with xylazine (1.0 mg/kg, IV). Anesthesia was induced with midazolam (0.1 mg/kg, IV) followed by ketamine (2.2 mg/kg, IV) and was maintained with an IV infusion of midazolam (0.002 mg/kg/min), ketamine (0.03 mg/kg/min), and xylazine (0.016 mg/kg/min). Horses underwent surgical manipulation and injection of the palmar digital nerves; duration of the infusion was 60 minutes. Additional ketamine (0.2 to 0.4 mg/kg, IV) was administered if a horse moved its head or limbs during procedures. Cardiopulmonary and arterial blood variables were measured prior to anesthesia; at 10, 20, 30, 45, and 60 minutes during infusion; and 10 minutes after horses stood during recovery. Recovery quality was assessed by use of a numeric (1 to 10) scale with 1 as an optimal score.
Results—Anesthesia was produced for 70 minutes after induction; supplemental ketamine administration was required in 4 horses. Heart rate, respiratory rate, arterial blood pressures, and cardiac output remained similar to preanesthetic values throughout TIVA. Arterial partial pressure of oxygen and oxygen saturation of arterial hemoglobin were significantly decreased from preanesthetic values throughout anesthesia; oxygen delivery was significantly decreased at 10- to 30-minute time points. Each horse stood on its first attempt, and median recovery score was 2.
Conclusions and Clinical Relevance—Midazolam, ketamine, and xylazine in combination produced TIVA in horses. Further studies to investigate various dosages for midazolam and ketamine or the substitution of other α2-adrenoceptor for xylazine are warranted.
Abstract
OBJECTIVE
To determine pharmacokinetic and pharmacodynamic properties of the injectable formulation of dexmedetomidine administered via the oral transmucosal (OTM) route to healthy dogs.
ANIMALS
6 healthy dogs.
PROCEDURES
Injectable dexmedetomidine was administered IV (5 μg/kg) or via the OTM route (20 μg/kg) in a blinded, single-observer, randomized crossover study. Dogs received dexmedetomidine and a sham treatment at each administration. Serial blood samples were collected from a catheter in a saphenous vein. Heart rate, respiratory rate, and subjective sedation score were assessed for 24 hours after administration. Plasma samples were analyzed for dexmedetomidine concentrations by use of ultraperformance liquid chromatography–tandem mass spectrometry.
RESULTS
For the OTM route, the mean ± SD maximum plasma concentration was 3.8 ± 1.3 ng/mL, which was detected 73 ± 33 minutes after administration. The mean maximum concentration for the IV dose, when extrapolated to the time of administration, was 18.6 ± 3.3 ng/mL. The mean terminal-phase half-life was 152 ± 146 minutes and 36 ± 6 minutes for OTM and IV administration, respectively. After IV administration, total clearance was 8.0 ± 1.6 mL/min/kg and volume of distribution at steady state was 371 ± 72 mL/kg. Bioavailability for OTM administration of dexmedetomidine was 11.2 ± 4.5%. Peak sedation scores did not differ significantly between routes of administration. Decreases in heart rate, respiratory rate, and peak sedation score were evident sooner after IV administration.
CONCLUSIONS AND CLINICAL RELEVANCE
OTM administration of the injectable formulation of dexmedetomidine resulted in a similar degree of sedation and prolonged duration of action, compared with results for IV administration, despite relatively low bioavailability.
Abstract
OBJECTIVE To evaluate pharmacokinetic and pharmacodynamic characteristics of 3 doses of tapentadol hydrochloride orally administered in dogs.
ANIMALS 6 healthy adult mixed-breed dogs.
PROCEDURES In a prospective, randomized crossover study, dogs were assigned to receive each of 3 doses of tapentadol (10, 20, and 30 mg/kg, PO); there was a 1-week washout period between subsequent administrations. Plasma concentrations and physiologic variables were measured for 24 hours. Samples were analyzed by use of high-performance liquid chromatography–tandem mass spectrometry.
RESULTS Tapentadol was rapidly absorbed after oral administration. Mean maximum plasma concentrations after 10, 20, and 30 mg/kg were 10.2, 19.7, and 31 ng/mL, respectively. Geometric mean plasma half-life of the terminal phase after tapentadol administration at 10, 20, and 30 mg/kg was 3.5 hours (range, 2.7 to 4.5 hours), 3.7 hours (range, 3.1 to 4.0 hours), and 3.7 hours (range, 2.8 to 6.5 hours), respectively. Tapentadol and its 3 quantified metabolites (tapentadol sulfate, tapentadol-O-glucuronide, and desmethyltapentadol) were detected in all dogs and constituted 0.16%, 2.8%, 97%, and 0.04% of the total area under the concentration-time curve (AUC), respectively. Plasma AUCs for tapentadol, tapentadol sulfate, and tapentadol-O-glucuronide increased in a dose-dependent manner. Desmethyltapentadol AUC did not increase in a linear manner at the 30-mg/kg dose. Sedation scores and heart and respiratory rates were not significantly affected by dose or time after administration.
CONCLUSIONS AND CLINICAL RELEVANCE Oral administration of tapentadol was tolerated well, and the drug was rapidly absorbed. Adverse events were not apparent in any dogs at any doses in this study.