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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)

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in American Journal of Veterinary Research

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.

Full access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association

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)

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in American Journal of Veterinary Research

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.

Full access
in American Journal of Veterinary Research

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.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine pharmacokinetics and pharmacodynamics of buprenorphine after IV and SC administration and of sustained-release (SR) buprenorphine after SC administration to adult alpacas.

ANIMALS 6 alpacas.

PROCEDURES Buprenorphine (0.02 mg/kg, IV and SC) and SR buprenorphine (0.12 mg/kg, SC) were administered to each alpaca, with a 14-day washout period between administrations. Twenty-one venous blood samples were collected over 96 hours and used to determine plasma concentrations of buprenorphine. Pharmacokinetic parameters were calculated by use of noncompartmental analysis. Pharmacodynamic parameters were assessed via sedation, heart and respiratory rates, and thermal and mechanical antinociception indices.

RESULTS Mean ± SD maximum concentration after IV and SC administration of buprenorphine were 11.60 ± 4.50 ng/mL and 1.95 ± 0.80 ng/mL, respectively. Mean clearance was 3.00 ± 0.33 L/h/kg, and steady-state volume of distribution after IV administration was 3.8 ± l.0 L/kg. Terminal elimination half-life was 1.0 ± 0.2 hours and 2.7 ± 2.8 hours after IV and SC administration, respectively. Mean residence time was 1.3 ± 0.3 hours and 3.6 ± 3.7 hours after IV and SC administration, respectively. Bioavailability was 64 ± 28%. Plasma concentrations after SC administration of SR buprenorphine were below the LLOQ in samples from 4 alpacas. There were no significant changes in pharmacodynamic parameters after buprenorphine administration. Alpacas exhibited mild behavioral changes after all treatments.

CONCLUSIONS AND CLINICAL RELEVANCE Buprenorphine administration to healthy alpacas resulted in moderate bioavailability, rapid clearance, and a short half-life. Plasma concentrations were detectable in only 2 alpacas after SC administration of SR buprenorphine.

Full access
in American Journal of Veterinary Research

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.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine pharmacokinetic and pharmacodynamic properties of midazolam after IV and IM administration in alpacas.

Animals—6 healthy alpacas.

Procedures—Midazolam (0.5 mg/kg) was administered IV or IM in a randomized crossover design. Twelve hours prior to administration, catheters were placed in 1 (IM trial) or both (IV trial) jugular veins for drug administration and blood sample collection for determination of serum midazolam concentrations. Blood samples were obtained at intervals up to 24 hours after IM and IV administration. Midazolam concentrations were determined by use of tandem liquid chromatography–mass spectrometry.

Results—Maximum concentrations after IV administration (median, 1,394 ng/mL [range, 1,150 to 1,503 ng/mL]) and IM administration (411 ng/mL [217 to 675 ng/mL]) were measured at 3 minutes and at 5 to 30 minutes, respectively. Distribution half-life was 18.7 minutes (13 to 47 minutes) after IV administration and 41 minutes (30 to 80 minutes) after IM administration. Elimination half-life was 98 minutes (67 to 373 minutes) and 234 minutes (103 to 320 minutes) after IV and IM administration, respectively. Total clearance after IV administration was 11.3 mL/min/kg (6.7 to 13.9 mL/min/kg), and steady-state volume of distribution was 525 mL/kg (446 to 798 mL/kg). Bioavailability of midazolam after IM administration was 92%. Peak onset of sedation occurred at 0.4 minutes (IV) and 15 minutes (IM). Sedation was significantly greater after IV administration.

Conclusions and Clinical Relevance—Midazolam was well absorbed after IM administration, had a short duration of action, and induced moderate levels of sedation in alpacas.

Full access
in American Journal of Veterinary Research