Objective—To determine whether butorphanol induces thermal antinociception in green iguanas (Iguana iguana) and assess the human observer effect on quantitative evaluation of butorphanol-induced analgesia.
Animals—6 juvenile green iguanas.
Procedures—Skin temperature was recorded, and then a direct increasing heat stimulus was applied to the lateral aspect of the tail base of each iguana. Temperature of the stimulus at which the iguana responded (thermal threshold) was measured before and for 8 hours after IM injection of either butorphanol tartrate (1.0 mg/kg) or an equal volume of saline (0.9% NaCl) solution. Six experiments (butorphanol [n = 3] and saline solution ) were conducted with the observer in the iguanas' field of vision, and 11 experiments (butorphanol [n = 5] and saline solution ) were conducted with the observer hidden from their view. The interval between treatments or tests was ≥ 1 month.
Results—Temperature difference between thermal threshold and skin temperature when iguanas were administered saline solution did not differ from temperature difference when iguanas were administered butorphanol regardless of whether the observer was or was not visible. Temperature difference between thermal threshold and skin temperature was significantly lower when iguanas were tested without the observer in visual range, compared with the findings obtained when iguanas were tested with an observer in view, at multiple times after either treatment.
Conclusions and Clinical Relevance—Intramuscular administration of 1.0 mg of butorphanol/kg did not induce thermal antinociception in juvenile green iguanas. The visible presence of an observer appeared to influence the results of noxious stimulus testing in this reptile species.
Objective—To determine the effects of IV administration of lidocaine on thermal antinociception in conscious cats. Animals—6 cats.
Procedure—2 experiments were performed in each cat (interval of at least 2 months). In experiment 1, lidocaine pharmacokinetics were determined for each conscious cat following IV administration of a bolus of lidocaine (2 mg/kg). In experiment 2, data from experiment 1 were used to calculate appropriate doses of lidocaine that would achieve predetermined plasma lidocaine concentrations in the cats; lidocaine (or an equivalent volume of saline [0.9% NaCl] solution as the control treatment) was administered IV to target pseudo–steady-state plasma concentrations of 0, 0.5, 1, 2, 5, and 8 μg/mL. Skin temperature and thermal threshold were determined at the start of the experiment (baseline) and at each concentration. Samples of venous blood were obtained at each target concentration for plasma lidocaine concentration determination.
Results—In experiment 2, actual plasma lidocaine concentrations were 0.00 ± 0.00 μg/mL, 0.25 ± 0.18 μg/mL, 0.57 ± 0.20 μg/mL, 1.39 ± 0.13 μg/mL, 2.33 ± 0.45 μg/mL, and 4.32 ± 0.66 μg/mL for target plasma concentrations of 0, 0.5, 1, 2, 5, and 8 μg/mL, respectively. Compared with baseline values, no significant change in skin temperature or thermal threshold was detected at any lidocaine plasma concentration (or saline solution equivalent). Skin temperature or thermal threshold values did not differ between lidocaine or control treatments.
Conclusions and Clinical Relevance—Results indicated that these moderate plasma concentrations of lidocaine did not affect thermal antinociception in cats.
Objective—To characterize the antinociceptive
actions of several doses of butorphanol by use of a
thermal threshold testing device specifically designed
Animals—6 domestic shorthair cats.
Procedure—The study was a masked, randomized,
crossover design. Thermal thresholds were measured
by use of a thermal threshold-testing device specifically
developed for cats. A small probe containing a
heater element and temperature sensor was held
with consistent contact against a shaved area of the
cat's skin with an elasticized band. Skin temperature
was recorded before each test, prior to activation of
the heater. On detection of a response (eg, the cat
flinched, turned, or jumped), the stimulus was terminated
and the threshold temperature recorded. Three
baseline measurements were recorded before IV
injection of 0.1, 0.2, 0.4, or 0.8 mg of butorphanol/kg.
Each cat received all doses in a randomized order at
least 1 week apart. The investigator was unaware of
the treatment received. Thermal thresholds were
measured every 15 minutes for 6 hours.
Results—Mean ± SD pretreatment threshold temperature
for all cats was 40.8 ± 2.2°C. There were no
dose-related differences among treatments. There
was a significant increase in threshold values for all
treatments from 15 to 90 minutes after injection.
Mydriasis was detected in all cats after treatment
with butorphanol and dysphoric behavior was frequently
Conclusions and Clinical Relevance—Results
obtained by use of a thermal stimulus indicated that
the duration of antinociceptive action of butorphanol
was 90 minutes and there was no dose-response relationship
in cats. (Am J Vet Res 2004;65:1085–1089)
Objective—To characterize the antinociceptive action of IM-administered butorphanol, buprenorphine, or a combination of both by use of a thermal threshold method in cats.
Animals—2 male and 4 female domestic cats.
Procedures—In a controlled, masked, randomized, crossover study design, thermal thresholds were measured by use of a thermal threshold–testing device developed for cats. Each cat received 4 treatments 1 week apart, consisting of 2 simultaneous IM injections in a random order (butorphanol-saline [0.9% NaCl] solution, buprenorphine-saline solution, butorphanol-buprenorphine, and saline solution-saline solution). The tester was unaware of the treatment given. Thermal thresholds were measured prior to injection, at intervals up to 12 hours, and at 22 hours after injection.
Results—There was no significant change in threshold over time after saline solution administration. All 3 opioid treatment groups had significant increases in thermal threshold, compared with pretreatment values (butorphanol, from 50 minutes to 8 hours; buprenorphine, from 35 minutes to 5 hours; and butorphanol-buprenorphine, from 50 minutes to 8 hours). Thermal thresholds did not differ significantly among opioid treatments at any time points, and thermal thesholds of only 2 opioid treatments (butorphanol at 50 minutes and butorphanol-buprenorphine at 8 hours) were significantly different from that of saline solution.
Conclusions and Clinical Relevance—All 3 opioid treatments provided similar antinociception, although there was considerable intercat variability in the response to the different opioid treatments. This emphasizes the importance of assessing each patient individually and applying the treatment that works best for that patient.
Objective—To evaluate effects of butorphanol, acepromazine, and N-butylscopolammonium bromide (NBB) on visceral and somatic nociception and duodenal motility in conscious, healthy horses.
Animals—6 adult horses.
Procedures—Visceral nociception was evaluated by use of colorectal distention (CRD) and duodenal distention (DD) threshold. Somatic nociception was evaluated via thermal threshold (TT). Nose-to-ground height, heart rate, and respiratory rate were also measured. Each horse received each treatment in randomized order; investigators were not aware of treatments. Butorphanol was administered IV as a bolus (18 μg/kg) followed by constant rate infusion at 13 μg/kg/h for 2 hours, whereas acepromazine (0.04 mg/kg), NBB (0.3 mg/kg), and saline (0.9% NaCl) solution (2 mL) were administered IV as a bolus followed by constant rate infusion with saline solution (10 mL/h) for 2 hours. Variables were measured before and for 3 hours after treatment. Data were analyzed by use of a 3-factor ANOVA followed by a Bonferroni t test for multiple comparisons.
Results—Nose-to-ground height decreased after acepromazine. Respiratory rate decreased after acepromazine and increased after butorphanol. Heart rate increased briefly after NBB. Some horses had an increase in TT after butorphanol and acepromazine, but there was not a significant treatment effect over time. Drug effect on DD or motility was not evident. The CRD threshold increased significantly at 5, 65, 155, and 185 minutes after acepromazine and from 5 to 65 minutes after NBB.
Conclusions and Clinical Relevance—Each drug caused predictable changes in sedation and vital signs, but consistent anti-nociceptive effects were not evident.
Objective—To compare the time to desaturation in healthy dogs that breathed oxygen or room air for 3 minutes before induction of anesthesia.
Animals—20 healthy dogs.
Procedures—Dogs were sedated with morphine and acepromazine maleate. Dogs received a 3-minute treatment of room air or oxygen (100 mL/kg/min) via face mask. Arterial blood samples were collected before and after treatment to determine PaCO2, PaO2, pH, and SaO2; propofol (6 mg/kg, IV) was injected during a 7-second period, and the dogs were intubated. A lingual pulse oximeter probe was placed. Dogs remained disconnected from the breathing circuit until SpO2 equaled 90% (desaturation point) and then connected and ventilated until the SpO2 was ≥ 97%. Arterial blood samples were collected and SpO2 was recorded every 30 seconds for 4 minutes and then every minute until the desaturation point. Times to first breath and the desaturation point were recorded. Data were collected at 0, 5, 30, 60, 90, 120, and 150 seconds.
Results—Mean ± SEM time to desaturation differed significantly between dogs treated with room air (69.6 ± 10.6 seconds) and oxygen (297.8 ± 42.0 seconds). Lowest mean PaO2 and SaO2 when dogs were breathing room air were 62 ± 6.3 mm Hg and 82.3 ± 4%, respectively, at 30 seconds.
Conclusions and Clinical Relevance—Preoxygenation for 3 minutes increased the time to desaturation in healthy dogs sedated with acepromazine and morphine in which anesthesia was induced with propofol.
Objective—To assess the influence of preanesthetic
administration of acetylpromazine or morphine and
fluids on urine production, arginine vasopressin (AVP;
previously known as antidiuretic hormone) concentrations,
mean arterial blood pressure (MAP), plasma
osmolality (Osm), PCV, and concentration of total
solids (TS) during anesthesia and surgery in dogs.
Animals—19 adult dogs.
Procedure—Concentration of AVP, indirect MAP,
Osm, PCV, and concentration of TS were measured at
5 time points (before administration of acetylpromazine
or morphine, after administration of those
drugs, after induction of anesthesia, 1 hour after the
start of surgery, and 2 hours after the start of
surgery). Urine output and end-tidal halothane concentrations
were measured 1 and 2 hours after the
start of surgery. All dogs were administered lactated
Ringer's solution (20 ml/kg of body weight/h, IV) during
Results—Compared with values for acetylpromazine,
preoperative administration of morphine resulted in
significantly lower urine output during the surgical
period. Groups did not differ significantly for AVP concentration,
Osm, MAP, and end-tidal halothane concentration;
however, PCV and concentration of TS
decreased over time in both groups and were lower in
dogs given acetylpromazine.
Conclusions and Clinical Relevance—Preanesthetic
administration of morphine resulted in significantly
lower urine output, compared with values after
administration of acetylpromazine, which cannot be
explained by differences in AVP concentration or MAP.
When urine output is used as a guide for determining
rate for IV administration of fluids in the perioperative
period, the type of preanesthetic agent used must be
considered.(Am J Vet Res 2001;62:1922–1927)
Objective—To determine and compare the effects of caffeine and doxapram on cardiorespiratory variables in foals during isoflurane-induced respiratory acidosis.
Animals—6 clinically normal foals (1 to 3 days old).
Procedures—At intervals of ≥ 24 hours, foals received each of 3 IV treatments while in a steady state of hypercapnia induced by isoflurane anesthesia (mean ± SD, 1.4 ± 0.3% endtidal isoflurane concentration). After assessment of baseline cardiorespiratory variables, a low dose of the treatment was administered and variables were reassessed; a high dose was then administered, and variables were again assessed. Sequential low- and high-dose treatments included doxapram (loading dose of 0.5 mg/kg, followed by a 20-minute infusion at 0.03 mg/kg/min and then 0.08 mg/kg/min), caffeine (5 mg/kg and 10 mg/kg), and saline (0.9% NaCl) solution (equivalent volumes).
Results—Administration of doxapram at both infusion rates resulted in a significant increase in respiratory rate, minute ventilation, arterial blood pH, PaO2, and arterial blood pressure. These variables were also significantly higher during doxapram administration than during caffeine or saline solution administration. There was a significant dose-dependent decrease in PaCO2 and arterial bicarbonate concentration during doxapram treatment. In contrast, PaCO2 increased from baseline values after administration of saline solution or caffeine. The PaCO2 value was significantly lower during doxapram treatment than it was during caffeine or saline solution treatment.
Conclusions and Clinical Relevance—Results indicated that doxapram restored ventilation in a dose-dependent manner in neonatal foals with isoflurane-induced hypercapnia. The effects of caffeine on respiratory function were indistinguishable from those of saline solution.
Objective—To compare cardiac output (CO) measured by lithium arterial pressure waveform analysis (PULSECO) and CO measured by transpulmonary pulse contour analysis (PICCO) in anesthetized foals, with CO measured by use of lithium dilution (LIDCO) considered the criterion-referenced standard.
Sample Population—6 neonatal (1- to 4-day-old) foals that weighed 38 to 45 kg.
Procedures—Foals were anesthetized and instrumented to measure direct blood pressure, heart rate, arterial blood gases, and CO. The CO was measured by use of PULSECO, PICCO, and LIDCO techniques. Measurements were converted to specific CO (sCO) values for statistical analysis. Measurements were obtained during low, intermediate, and high CO states.
Results—sCO ranged from 75.5 to 310 mL/kg/min. Mean ± SD PICCO bias varied significantly among CO states and was −51.9 ± 23.1 mL/kg/min, 20.0 ± 19.5 mL/kg/min, and 87.2 ± 19.5 mL/kg/min at low, intermediate, and high CO states, respectively. Mean PULSECO bias (11.0 ± 37.5 mL/kg/min) was significantly lower than that of PICCO and did not vary among CO states. Concordance correlation coefficient between LIDCO and PULSECO was significantly greater than that between LIDCO and PICCO. The proportion of observations with a relative bias < ± 30% was significantly lower with the PULSECO method than with the PICCO method.
Conclusions and Clinical Relevance—Values for the PULSECO method were more reproducible and agreed better with values for the LIDCO method than did values for the PICCO method and were able to more accurately monitor changes in CO in anesthetized newborn foals.
PROCEDURES Baseline rectal temperature, heart rate, and respiratory rate were recorded prior to premedication with buprenorphine (0.02 mg/kg, IM) and acepromazine (0.05 mg/kg, IM). Anesthesia was induced with midazolam or diazepam (0.25 mg/kg, IV) plus ketamine (5 mg/kg, IV; n = 11) or propofol (4 mg/kg, IV; 12) and maintained with isoflurane in oxygen. Rectal temperature was measured at hospital intake, prior to premedication, immediately after anesthetic induction, and every 5 minutes after anesthetic induction. Esophageal temperature was measured every 5 minutes during anesthesia, beginning 30 minutes after anesthetic induction. After anesthesia, dogs were covered with a warm-air blanket and rectal temperature was measured every 10 minutes until normothermia (37°C) was achieved.
RESULTS Dogs in both treatment groups had lower rectal temperatures within 5 minutes after anesthetic induction and throughout anesthesia. Compared with dogs that received a benzodiazepine plus ketamine, dogs that received a benzodiazepine plus propofol had significantly lower rectal temperatures and the interval from discontinuation of anesthesia to achievement of normothermia was significantly longer.
CONCLUSIONS AND CLINICAL RELEVANCE Dogs in which anesthesia was induced with a benzodiazepine plus propofol or ketamine became hypothermic; the extent of hypothermia was more profound for the propofol combination. Dogs should be provided with adequate heat support after induction of anesthesia, particularly when a propofol-benzodiazepine combination is administered.