Objective—To compare the disposition of lidocaine
administered IV in awake and anesthetized 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)
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.
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.
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.
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.
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
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)
Objective—To evaluate the use of xylazine and ketamine
for total IV anesthesia in 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
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)
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
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
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)
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
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)
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.