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Abstract

Objective—To compare the disposition of lidocaine administered IV in awake and anesthetized horses.

Animals—16 horses.

Procedure—After instrumentation and collection of baseline data, lidocaine (loading infusion, 1.3 mg/kg administered during 15 minutes (87 µg/kg/min); constant rate infusion, 50 µg/kg/min) was administered IV to awake or anesthetized horses for a total of 105 minutes. Blood samples were collected at fixed times during the loading and maintenance infusion periods and after the infusion period for analysis of serum lidocaine concentrations by use of liquid chromatography with mass spectral detection. Selected cardiopulmonary parameters including heart rate (HR), mean arterial pressure (MAP), arterial pH, PaCO2, and PaO2 were also recorded at fixed time points during lidocaine administration. Serum lidocaine concentrations were evaluated by use of standard noncompartmental analysis.

Results—Serum lidocaine concentrations were higher in anesthetized than awake horses at all time points during lidocaine administration. Serum lidocaine concentrations reached peak values during the loading infusion in both groups (1,849 ± 385 ng/mL and 3,348 ± 602 ng/mL in awake and anesthetized horses, respectively). Most lidocaine pharmacokinetic variables also differed between groups. Differences in cardiopulmonary variables were predictable; for example, HR and MAP were lower and PaO2 was higher in anesthetized than awake horses but within reference ranges reported for horses under similar conditions.

Conclusions and Clinical Relevance—Anesthesia has an influence on the disposition of lidocaine in horses, and a change in dosing during anesthesia should be considered. (Am J Vet Res 2005;66:574–580)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether infusion of xylazine and ketamine or xylazine and propofol after sevoflurane administration in horses would improve the quality of recovery from anesthesia.

Animals—6 healthy adult horses.

Procedures—For each horse, anesthesia was induced by administration of xylazine, diazepam, and ketamine and maintained with sevoflurane for approximately 90 minutes (of which the last 60 minutes were under steady-state conditions) 3 times at 1-week intervals. For 1 anesthetic episode, each horse was allowed to recover from sevoflurane anesthesia; for the other 2 episodes, xylazine and ketamine or xylazine and propofol were infused for 30 or 15 minutes, respectively, after termination of sevoflurane administration. Selected cardiopulmonary variables were measured during anesthesia and recovery. Recovery events were monitored and subjectively scored.

Results—Cardiopulmonary variables differed minimally among treatments, although the xylazine-propofol infusion was associated with greater respiratory depression than was the xylazine-ketamine infusion. Interval from discontinuation of sevoflurane or infusion administration to standing did not differ significantly among treatments, but the number of attempts required to stand successfully was significantly lower after xylazine-propofol infusion, compared with the number of attempts after sevoflurane alone. Scores for recovery from anesthesia were significantly lower (ie, better recovery) after either infusion, compared with scores for sevoflurane administration alone.

Conclusions and Clinical Relevance—Xylazine-ketamine or xylazine-propofol infusion significantly improved quality of recovery from sevoflurane anesthesia in horses. Xylazine-ketamine or xylazine-propofol infusions may be of benefit during recovery from sevoflurane anesthesia in horses for which a smooth recovery is particularly critical. However, oxygenation and ventilation should be monitored carefully.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare cardiovascular effects of sevoflurane alone and sevoflurane plus an IV infusion of lidocaine in horses.

Animals—8 adult horses.

Procedures—Each horse was anesthetized twice via IV administration of xylazine, diazepam, and ketamine. During 1 anesthetic episode, anesthesia was maintained by administration of sevoflurane in oxygen at 1.0 and 1.5 times the minimum alveolar concentration (MAC). During the other episode, anesthesia was maintained at the same MAC multiples via a reduced concentration of sevoflurane plus an IV infusion of lidocaine. Heart rate, arterial blood pressures, blood gas analyses, and cardiac output were measured during mechanical (controlled) ventilation at both 1.0 and 1.5 MAC for each anesthetic protocol and during spontaneous ventilation at 1 of the 2 MAC multiples.

Results—Cardiorespiratory variables did not differ significantly between anesthetic protocols. Blood pressures were highest at 1.0 MAC during spontaneous ventilation and lowest at 1.5 MAC during controlled ventilation for either anesthetic protocol. Cardiac output was significantly higher during 1.0 MAC than during 1.5 MAC for sevoflurane plus lidocaine but was not affected by anesthetic protocol or mode of ventilation. Clinically important hypotension was detected at 1.5 MAC for both anesthetic protocols.

Conclusions and Clinical Relevance—Lidocaine infusion did not alter cardiorespiratory variables during anesthesia in horses, provided anesthetic depth was maintained constant. The IV administration of lidocaine to anesthetized nonstimulated horses should be used for reasons other than to improve cardiovascular performance. Severe hypotension can be expected in nonstimulated horses at 1.5 MAC sevoflurane, regardless of whether lidocaine is administered.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine effects of a continuous rate infusion of lidocaine on the minimum alveolar concentration (MAC) of sevoflurane in horses.

Animals—8 healthy adult horses.

Procedures—Horses were anesthetized via IV administration of xylazine, ketamine, and diazepam; anesthesia was maintained with sevoflurane in oxygen. Approximately 1 hour after induction, sevoflurane MAC determination was initiated via standard techniques. Following sevoflurane MAC determination, lidocaine was administered as a bolus (1.3 mg/kg, IV, over 15 minutes), followed by constant rate infusion at 50 μg/kg/min. Determination of MAC for the lidocaine-sevoflurane combination was started 30 minutes after lidocaine infusion was initiated. Arterial blood samples were collected after the lidocaine bolus, at 30-minute intervals, and at the end of the infusion for measurement of plasma lidocaine concentrations.

Results—IV administration of lidocaine decreased mean ± SD sevoflurane MAC from 2.42 ± 0.24% to 1.78 ± 0.38% (mean MAC reduction, 26.7 ± 12%). Plasma lidocaine concentrations were 2,589 ± 811 ng/mL at the end of the bolus; 2,065 ± 441 ng/mL, 2,243 ± 699 ng/mL, 2,168 ± 339 ng/mL, and 2,254 ± 215 ng/mL at 30, 60, 90, and 120 minutes of infusion, respectively; and 2,206 ± 329 ng/mL at the end of the infusion. Plasma concentrations did not differ significantly among time points.

Conclusions and Clinical Relevance—Lidocaine could be useful for providing a more balanced anesthetic technique in horses. A detailed cardiovascular study on the effects of IV infusion of lidocaine during anesthesia with sevoflurane is required before this combination can be recommended.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the disposition of lidocaine after IV infusion in anesthetized horses undergoing exploratory laparotomy because of gastrointestinal tract disease.

Animals—11 horses (mean ± SD, 10.3 ± 7.4 years; 526 ± 40 kg).

Procedure—Lidocaine hydrochloride (loading infusion, 1.3 mg/kg during a 15-minute period [87.5 μg/kg/min]; maintenance infusion, 50 μg/kg/min for 60 to 90 minutes) was administered IV to dorsally recumbent anesthetized horses. Blood samples were collected before and at fixed time points during and after lidocaine infusion for analysis of serum drug concentrations by use of liquid chromatography-mass spectrometry. Serum lidocaine concentrations were evaluated by use of standard noncompartmental analysis. Selected cardiopulmonary variables, including heart rate (HR), mean arterial pressure (MAP), arterial pH, PaCO2, and PaO2, were recorded. Recovery quality was assessed and recorded.

Results—Serum lidocaine concentrations paralleled administration, increasing rapidly with the initiation of the loading infusion and decreasing rapidly following discontinuation of the maintenance infusion. Mean ± SD volume of distribution at steady state, total body clearance, and terminal half-life were 0.70 ± 0.39 L/kg, 25 ± 3 mL/kg/min, and 65 ± 33 minutes, respectively. Cardiopulmonary variables were within reference ranges for horses anesthetized with inhalation anesthetics. Mean HR ranged from 36 ± 1 beats/min to 43 ± 9 beats/min, and mean MAP ranged from 74 ± 18 mm Hg to 89 ± 10 mm Hg. Recovery quality ranged from poor to excellent.

Conclusions and Clinical Relevance—Availability of pharmacokinetic data for horses with gastrointestinal tract disease will facilitate appropriate clinical dosing of lidocaine.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effect of a constant-rate infusion of fentanyl on minimum alveolar concentration (MAC) of isoflurane and to determine the interaction between fentanyl and a benzodiazepine agonist (diazepam) and antagonist (flumazenil) in isoflurane-anesthetized dogs.

Animals—8 mixed-breed adult dogs.

Procedure—Dogs were anesthetized with isoflurane 3 times during a 6-week period. After a 30-minute equilibration period, each MAC determination was performed in triplicate, using standard techniques. Fentanyl was administered as a bolus (10 µg/kg of body weight, IV) that was followed by a constant infusion (0.3 µg/kg per min, IV) throughout the remainder of the experiment. After determining isoflurane-fentanyl MAC in triplicate, each dog received saline (0.9% NaCl) solution, diazepam, or flumazenil. After 30 minutes, MAC was determined again.

Results—Fentanyl significantly decreased isoflurane MAC (corrected to a barometric pressure of 760 mm Hg) from 1.80 ± 0.21 to 0.85 ± 0.14%, a reduction of 53%. Isoflurane-fentanyl-diazepam MAC (0.48 ± 0.29%) was significantly less than isoflurane-fentanylsaline MAC (0.79 ± 0.21%). Percentage reduction in isoflurane MAC was significantly greater for fentanyldiazepam (74%), compared with fentanyl-saline (54%) or fentanyl-flumazenil (61%). Mean fentanyl concentrations for the entire experiment were increased over time and were higher in the diazepam group than the saline or flumazenil groups.

Conclusion and Clinical Relevance—Fentanyl markedly decreased isoflurane MAC in dogs. Diazepam, but not flumazenil, further decreased isoflurane-fentanyl MAC. Our results indicate that diazepam enhances, whereas flumazenil does not affect, opioid-induced CNS depression and, possibly, analgesia in dogs. (Am J Vet Res 2001;62:555–560)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the use of xylazine and ketamine for total IV anesthesia in horses.

Animals—8 horses.

Procedure—Anesthetic induction was performed on 4 occasions in each horse with xylazine (0.75 mg/kg, IV), guaifenesin (75 mg/kg, IV), and ketamine (2 mg/kg, IV). Intravenous infusions of xylazine and ketamine were then started by use of 1 of 6 treatments as follows for which 35, 90, 120, and 150 represent infusion dosages (µg/kg/min) and X and K represent xylazine and ketamine, respectively: X35+K90 with 100% inspired oxygen (O2), X35+K120-O2, X35+K150-O2, X70+K90-O2, K150-O2, and X35+K120 with a 21% fraction of inspired oxygen (ie, air). Cardiopulmonary measurements were performed. Response to a noxious electrical stimulus was observed at 20, 40, and 60 minutes after induction. Times to achieve sternal recumbency and standing were recorded. Quality of sedation, induction, and recovery to sternal recumbency and standing were subjectively evaluated.

Results—Heart rate and cardiac index were higher and total peripheral resistance lower in K150-O2 and X35+K120-air groups. The mean arterial pressure was highest in the X35+K120-air group and lowest in the K150-O2 group (125 ± 6 vs 85 ± 8 at 20 minutes, respectively). Mean PaO2 was lowest in the X35+K120-air group. Times to sternal recumbency and standing were shortest for horses receiving K150-O2 (23 ± 6 minutes and 33 ± 8 minutes, respectively) and longest for those receiving X70+K90-O2 (58 ± 28 minutes and 69 ± 27 minutes, respectively).

Conclusions and Clinical Relevance—Infusions of xylazine and ketamine may be used with oxygen supplementation to maintain 60 minutes of anesthesia in healthy adult horses. (Am J Vet Res 2005;66:1002–1007)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the effects on oxygen delivery (DO2) of 2.5 and 5 cm H2O of positive end-expiratory pressure (PEEP) applied to the dependent lung during one-lung ventilation (OLV) in anesthetized dogs with a closed thoracic cavity.

Animals—7 clinically normal adult Walker Hound dogs.

Procedure—Dogs were anesthetized, and catheters were inserted in a dorsal pedal artery and the pulmonary artery. Dogs were positioned in right lateral recumbency, and data were collected during OLV (baseline), after application of 2.5 cm H2O of PEEP for 15 minutes during OLV, and after application of 5 cm H2O of PEEP for 15 minutes during OLV. Hemodynamic and respiratory variables were analyzed and calculations performed to obtain DO2, and values were compared among the various time points by use of an ANOVA for repeated measures.

Results—PEEP induced a significant decrease in shunt fraction that resulted in a significant increase in arterial oxygen saturation. However, it failed to significantly affect arterial oxygen content (CaO2) or cardiac output. Thus, DO2 was not affected in healthy normoxemic dogs as a net result of the application of PEEP.

Conclusions and Clinical Relevance—The use of PEEP during OLV in anesthetized dogs with a closed thoracic cavity did not affect DO2. Use of PEEP during OLV in dogs with a closed thoracic cavity is recommended because it does not affect cardiac output and any gain in CaO2 will be beneficial for DO2 in critically ill patients. (Am J Vet Res 2005;66:978–983)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the effects of one-lung ventilation (OLV) on oxygen delivery (DO2) in anesthetized dogs with a closed thoracic cavity.

Animals—7 clinically normal adult Walker Hound dogs.

Procedure—Dogs were anesthetized. Catheters were inserted in a dorsal pedal artery and the pulmonary artery. Dogs were positioned in right lateral recumbency. Data were collected at baseline (PaCO2 of 35 to 45 mm Hg), during two-lung ventilation, and 15 minutes after creating OLV. Hemodynamic and respiratory variables were analyzed and calculations performed to obtain DO2 , and values were compared among the various time points by use of an ANOVA for repeated measures.

Results—OLV induced a significant augmentation of shunt fraction that resulted in a significant reduction in PaO2, arterial oxygen saturation, and arterial oxygen content. Cardiac index was not significantly changed. The net result was that DO2 was not significantly affected by OLV.

Conclusions and Clinical Relevance—Use of OLV in healthy dogs does not induce significant changes in DO2, which is the ultimate variable to use when evaluating tissue oxygenation. One-lung ventilation can be initiated safely in dogs before entering the thoracic cavity during surgery. Additional studies are necessary to evaluate OLV in clinically affected patients and variations in age, body position, and type of anesthetic protocol. (Am J Vet Res 2005;66:973–977)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess the pharmacokinetics and pharmacodynamics of morphine in llamas.

Animals—6 healthy adult llamas.

Procedures—Llamas received morphine sulfate in a randomized crossover design. In phase 1, they received IV or IM administration of morphine at 0.05 or 0.5 mg/kg, respectively; in phase 2, they received IV administration of morphine at 0.05, 0.25, or 0.5 mg/kg. Plasma morphine and morphine-6-glucuronide concentrations were determined by validated methods. Body temperature, heart rate, respiratory rate, sedation, and analgesia were assessed and compared with plasma concentrations by regression analysis.

Results—Total body clearance was similar between IV administration of morphine sulfate at 0.25 and 0.5 mg/kg (mean ± SD, 25.3 ± 6.9 mL/min/kg and 27.3 ± 5.9 mL/min/kg, respectively), and linearity was demonstrated between these doses. Bioavailability of morphine following IM administration at 0.5 mg/kg was 120 ± 30%. Body temperature and sedation increased as the dose of morphine administered increased. Heart rate was unaffected by varying doses. Respiratory rate decreased as dose increased. Analgesia was difficult to assess as a result of high individual variability. Intravenous administration of morphine at 0.25 mg/kg provided the most consistent increase in tolerance to electric stimulation. Pharmacodynamic modeling revealed a sigmoidal relationship between plasma concentration and sedation score.

Conclusions and Clinical Relevance—Morphine was characterized by a large apparent volume of distribution and high systemic clearance in llamas. A prolonged half-life was observed with IM injection. Intravenous administration of morphine sulfate at 0.25 mg/kg every 4 hours is suggested for further study.

Full access
in American Journal of Veterinary Research