Effects of preoperative administration of butorphanol or meloxicam on physiologic responses to surgery in ball pythons

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Pain is subjective and is defined as an unpleasant sen-sory or emotional experience associated with actual

or potential tissue damage.1 Animals greatly vary in their behavioral responses to pain. Immediate respons-es include vocalization and attempts to escape, whereas longer term responses also include loss of appetite or lack of grooming.1 Most of these responses are very dif-ficult to assess in ectothermic vertebrates, which often remain motionless and have a behavioral repertoire that is considerably more difficult to interpret than that of mammals. In mammals, pain also elicits consistent physiologic responses, including increased heart rate and blood pressure,2 altered breathing patterns,2 and increased plasma concentrations of epinephrine3 and cortisol.3,4 Administration of analgesics consistently reduces these behavioral and physiologic responses in mammals.2,5 It follows that such physiologic responses would provide a useful means of assessing the sensa-tion of pain in amphibians and reptiles.

Effects of preoperative administration of butorphanol or meloxicam on physiologic responses

to surgery in ball pythons

Mette G. Olesen, msc; Mads F. Bertelsen, dvm, dvsc; Steve F. Perry, phd; Tobias Wang, phd

Objective—To characterize physiologic responses of ball pythons (Python regius) following a minor surgical procedure and investigate the effects of 2 commonly used analgesics on this response.Animals—15 healthy ball pythons.Procedures—Snakes were randomly assigned to receive 1 of 3 treatments: meloxicam (0.3 mg/kg [0.14 mg/lb]; n = 5), butorphanol (5 mg/kg [2.3 mg/lb]; 5), or saline (0.9% NaCl) solution (5) before catheterization of the vertebral artery. Plasma concentrations of cat-echolamines and cortisol, blood pressure, heart rate, and blood gas values were measured at various times for 72.5 hours after catheterization. The 72.5-hour point was defined as baseline.Results—Heart rate of ball pythons increased significantly during the first hour following surgery. Mean plasma epinephrine concentration increased slightly at 2.5 hours after sur-gery, whereas mean plasma cortisol concentration increased beginning at 1.5 hours, reach-ing a maximum at 6.5 hours. Mean blood pressure increased within the first hour but returned to the baseline value at 2.5 hours after surgery. After 24.5 hours, blood pressure, heart rate, and plasma hormone concentrations remained stable at baseline values. There were no significant differences in values for physiologic variables between snakes that re-ceived saline solution and those that received meloxicam or butorphanol.Conclusions and Clinical Relevance—Measurement of physiologic variables provides a means of assessing postoperative pain in snakes. Meloxicam and butorphanol at the dosages used did not decrease the physiologic stress response and did not appear to provide analgesic effects in ball pythons. (J Am Vet Med Assoc 2008;233:1883–1888)

Pain and pain management in nonmammalian ver-tebrates remain poorly understood. Results of several studies indicate that reptiles,6–8 fish,9 and birds10 react to painful stimuli and that analgesia relieves pain, yet the basic physiologic response to painful stimuli has not been described to our knowledge. In a survey,11 98.4% of 367 members of the Association of Reptile and Amphibian Veterinarians stated that they believe reptiles can feel pain. Nonetheless, only 39% of those veterinarians reported using analgesics during surgical procedures in reptiles. According to results of the same survey, butorphanol (a mixed opioid receptor agonist-antagonist) and NSAIDs are the most commonly used analgesics for reptiles,11 even though their effects on reptiles are largely unknown.

The aim of the study reported here was to charac-terize the physiologic responses of ball pythons (Python regius) following a minor surgical procedure, to assess whether physiologic variables can be used as a measur-able indicator of pain, and to assess whether preoperative administration of butorphanol and the NSAID meloxi-cam affects postoperative physiologic responses.

Materials and Methods

Animals—Fifteen ball pythons of undetermined sex, with a mean ± SEM body weight of 0.5 ± 0.06 kg (1.1 ± 0.14 lb), were obtained from commercial sup-pliers and housed in temperature-controlled (30°C

From the Department of Biological Sciences, University of Aarhus, DK-8000 Århus C, Denmark (Olesen, Wang); Centre for Zoo and Wild Animal Health, Copenhagen Zoo, Roskildevej 38, DK-2000 Frederiksberg C, Denmark (Bertelsen); and Department of Biology, Faculty of Science, University of Ottawa, Ottawa, ON K1N 6N5, Canada (Perry).

Supported by the Danish Research Council (Forskningsrådet for Na-tur og Univers).

Address correspondence to Ms. Olesen.

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[86°F]) 25 X 30 X 20-cm terrariums within the animal care facility at Aarhus University. Snakes were fed mice once or twice a week and had free access to clean water. Food was withheld 5 days before experiments. Experi-mental protocols were approved by the Danish Experi-mental Animal Inspectorate.

Analgesia and anesthesia—Snakes were randomly allocated to 3 groups of 5 snakes each. A control group received an IM injection of 1 mL of isotonic saline (0.9% NaCl) solution, a second group was treated with meloxicam (0.3 mg/kg [0.14 mg/lb], IM), and the third group received butorphanol (5 mg/kg [2.3 mg/lb], IM) 3 hours before surgery. The IM injections were given in the right side of the dorsal portion of the tail. Snakes were maintained in a climatic chamber at 30°C for 24 hours prior to surgery and kept there for 72.5 hours after the procedure.

For induction of anesthesia, snakes were placed in an induction chamber containing 5% isoflurane for 20 minutes until tactile reflexes decreased so the glot-tis could be intubated with soft rubber tubing for ar-tificial ventilation.a The isoflurane concentration was then maintained at 4% in room airb until snakes lost the righting reflex and local rippling of the ventral scales when snakes were lightly touched along the midline was no longer evident. The isoflurane concentration was subsequently reduced to 2% during the remainder of the procedure.12 Snakes were positioned on a heating mat to maintain body temperature at 28° to 30°C (82.4° to 86°F) during surgery.

Surgical procedure—The painful stimulus chosen was surgical cannulation of the vertebral artery, which is a procedure commonly used in physiologic research to obtain blood samples from undisturbed snakes during experiments. Briefly, a 4-cm longitudinal incision was made cranial to the heart on the left side of the ventral scales. The vertebral artery was located and cannulated with a polyethylene catheterc containing heparinized saline solution (50 U/mL). Following occlusive fixation in the artery, the catheter was tunneled into and direct-ed out of the skin on the dorsum of the snake, and the incision was closed with interrupted everting sutures. Finally, the catheter was secured via 2 sutures on the dorsum of the snake. The surgical procedure lasted ap-proximately 30 minutes, after which administration of isoflurane was discontinued. Artificial ventilation was continued until the snakes resumed spontaneous ven-tilation. Snakes were maintained on the heat mat for 1 hour and then transferred to the climatic chamber. Measurements of physiologic variables were obtained during the subsequent 72.5 hours.

Hematologic analysis—Blood samples (0.2 to 0.3 mL each) were collected from catheters at 0.5, 1.0, 1.5, 2.0, 2.5, 4.5, 6.5, 20.5, 24.5, 48.5, and 72.5 hours after surgery concluded. Subsequently, plasma was separat-ed and stored immediately at –80°C (112°F) for later analysis. The remaining RBCs from each blood sam-ple were diluted in saline solution and injected back into the snakes through the catheter. At 1.5 and 72.5 hours, an additional blood sample (0.3 mL) was col-lected for measurements of arterial pH, Paco

2, Pao

2, and

Hct. Blood pH was measured at 30°C by means of a

capillary pH electrode connected to a pH meter.d Values of Pao

2 were measured at 30°C by use of an electrode.e

Plasma concentrations of co2 were measured as de-

scribed elsewhere.13 Plasma bicarbonate concentrations were calculated as Ctco

2 – (Pco

2 X α

CO2), where Ctco

2

is the total plasma concentration of CO2 and α

CO2 is

the plasma solubility coefficient for CO2, which has a

value of 0.0366 mmol/L.14 The Henderson-Hasselbalch equation was used to calculate Paco

2 as follows: Paco

2

= Ctco2/(α

CO2[1 + 10(pH – pK′)]), where pK′ represents the

value determined for Python molurus (pK′ = –0.0763 X pH + 6.7283).15 Hematocrit was determined in dupli-cate as the fractional red cell volume after centrifuga-tionf at 20,000 X g for 3 minutes.

Determination of plasma concentrations of cat-echolamines and cortisol—Plasma concentrations of epinephrine and norepinephrine were determined via high-pressure liquid chromatography. Plasma cor-tisol concentration was determined by use of a time-resolved fluoroimmunoassay,g an electronic counter,h and commercial softwarei in accordance with a protocol provided by the manufacturer of the immunoassay kit. All plasma samples were measured for each hormone in duplicate.

Determination of heart rate and blood pressure—After each blood sample was collected, the catheter was connected to a pressure transducerj for determination of blood pressure and heart rate, allowing a 30-minute interval before each measurement was obtained, except at 0.5 hours and 1.5 hours. The signal was amplified by means of a preamplifier that was built in-house, and data were collected via a computerized acquisition system.k The transducer was calibrated daily against a static water column.

Behavioral observations—Snakes were observed when undisturbed and when handled for catheter ma-nipulations. Specifically, snakes were monitored for degree of activity and their tendency to protect their wound, compared with their typical behavior (curled up under their drinking tray).

Statistical analysis—In the control group, plasma catecholamine and cortisol concentrations, blood pres-sure, heart rate, and blood gas values from 0.5 hours through 48.5 hours after surgery were compared with values obtained at 72.5 hours by means of 1-way re-peated-measures ANOVA. Values at 72.5 hours were selected to represent baseline values because it was presumed that the variables measured would have re-turned to regular values by this time. For Hct, the value at 1.5 hours was used as a baseline measurement.

Values for variables in the 3 treatment groups at all time points were compared by means of 2-way re-peated-measures ANOVA. A value of P ≤ 0.05 was used to indicate a significant difference. Summary data are presented as mean ± SEM.

Results

Hematologic analysis—In general, values of arte-rial blood gases were not affected by surgical cannula-tion of the vertebral artery, regardless of whether snakes were treated beforehand with saline solution, butor-

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phanol, or meloxicam (Table 1). There was, however, a significant reduction in Hct during the experiment. Values for 2 snakes at 72.5 hours are missing because of technical difficulties.

Plasma concentrations of catecholamines and cor-tisol—At 72.5 hours after surgical cannulation of the vertebral artery was performed, mean ± SEM plasma con-centration of epinephrine in control snakes was 1.9 ± 0.6 nM. Plasma epinephrine concentrations generally did not change during the 72.5-hour postoperative period, re-gardless of the preoperative treatment (Figure 1). Plasma norepinephrine concentrations remained low (< 0.1 ± 0 nM) during the entire experiment in all 3 groups (data not shown). Plasma cortisol concentrations did not change

significantly during the postoperative period in any of the groups, although concentrations in control snakes rose slightly from 69 ± 21 ng/mL to 107 ± 48 ng/mL at 1.5 hours after surgery.

Blood pressure and heart rate—Blood pressure remained remarkably stable during the postoperative period, and there were no differences between effects of the 3 experimental treatments. Mean blood pressure at 72.5 hours (baseline value) was 7.14 ± 0.3 kPa, and this value was not significantly different from values at 0.5 through 48.5 hours (Figure 2). Mean heart rate, which initially significantly increased, decreased signif-icantly during the first hour of the postoperative period in the control snakes. Similar but insignificant changes

Saline solution Meloxicam Butorphanol

Variable 1.5 h (5) 72.5 h (4) 1.5 h (5) 72.5 h (4) 1.5 h (5) 72.5 h (5)

pH 7.57 0.03 7.67 0.04 7.61 0.0 7.68 0.03 7.69 0.05 7.65 0.03Bicarbonate (mmol/L) 15.8 0.7 15.9 0.4 13.0 0.8 16.2 1.6* 16.7 1.0 19.2 2.2Paco2 (mm Hg) 16.0 2.4 13.0 1.5 12.4 1.3 13.1 1.9 13.0 0.9 16.4 1.3Pao2 (mm Hg) 60.3 10.0 68.9 11.7 45.9 10.1† 44.7 7.4 32.1 9.8 69.6 12.0Hct (%) 20 0.8 16 1.9* 20 0.8 15 1.2* 19 0.9 14 1.4*

Values in parentheses indicate number of snakes evaluated.*Value is significantly (P 0.05) different between time points. †Value for control snakes is significantly

(P 0.05) different from that of treated snakes at the given time point.

Table 1— Mean ± SEM hematologic values in ball pythons that received a preoperative dose of saline (0.9% NaCl) solution (1 mL, IM; control snakes), meloxicam (0.3 mg/kg [0.14 mg/lb], IM), or butorpha-nol (5 mg/kg [2.3 mg/lb], IM) before surgical cannulation of the vertebral artery, as measured 1.5 and 72.5 hours after surgery.

Figure 1—Mean ± SEM plasma concentrations of epinephrine (A) and cortisol (B) in 15 ball pythons at various time points after surgical cannulation of the vertebral artery. Before surgery, 5 snakes received saline solution (1 mL, IM; black circles), whereas 5 others received meloxicam (0.3 mg/kg [0.14 mg/lb], IM; white circles) and another 5 received butorphanol (5 mg/kg [2.3 mg/lb], IM; black inverted tri-angles). The shaded area indicates the time at which snakes were anesthetized for the surgery. The hatched area indicates the recovery period after the anesthetic. *Value is significantly (P ≤ 0.05) different from value in same group of snakes at 72.5 hours after surgery, at which time snakes were presumed to have fully recovered.

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in mean heart rate were evident in snakes treated with butorphanol or meloxicam. There were no significant differences in heart rate among the 3 groups. Baseline heart rate at 72.5 hours was 35 ± 3 beats/min.

Behavioral observations—In general, the behavior of the snakes was not measurably different before and af-ter surgery. Snakes were observed curled up under their water tray and stayed there during sample collection. However, when the incision was touched, snakes pro-tected the site by changing position or moving away. No behavioral differences among groups were detected.

Discussion

In the study reported here, the effects of surgery on postoperative physiologic variables in reptiles were investigated. The results indicated that, following a transient increase, heart rate, blood pressure, and concentrations of stress hormones returned to stable baseline values within 24.5 hours after surgical can-nulation of the vertebral artery in ball pythons. No-tably, we found that preoperative administration of 2 different analgesics, meloxicam and butorphanol, did not have an effect on these physiologic variables. In all groups, heart rates were increased for the first hour postoperatively but decreased to baseline values 2.5 hours after surgery. Plasma epinephrine concen-trations increased slightly but insignificantly at 2.5 hours, as did plasma cortisol concentrations by 1.5 hours, which slowly returned to initial values within the next 20.5 hours. Thus, cardiovascular changes did

not correspond to changes in plasma concentrations of epinephrine or cortisol.

Snakes were affected by anesthesia during the first hours after surgery and were not considered fully re-covered from anesthesia until 2.5 hours after surgery. The transient but insignificant increase in plasma epi-nephrine concentration that coincided with recovery of snakes from anesthesia may have reflected loss of the analgesic effect of isoflurane. The increase in plasma catecholamine concentrations, however, was modest in comparison with the 3- to 5-fold increase that was de-tected after handling of another species of snake, the black racer (Coluber constrictor).16 In anesthetized py-thons, injections of 3 nmol of bradykinin/kg (1.4 nmol of bradykinin/lb) caused a 10-fold rise in plasma con-centrations of norepinephrine but did not affect plasma concentrations of epinephrine,17 which suggests that these hormones were released from sympathetic neurons rather than adrenal glands. In our study, the increased plasma epinephrine concentrations at 2.5 hours (with unchanged plasma norepinephrine concentrations) indi-cated that epinephrine was being released from the ad-renal medulla. Nonetheless, it remains unclear whether the low concentrations of epinephrine measured at 0.5 hours in our study were attributable to the anesthetic or whether concentrations of catecholamines simply do not increase in response to surgery in ball pythons.

The increases in heart rate and blood pressure dur-ing the first hour occurred despite low concentrations of circulating epinephrine, and these increases were likely to have resulted from increased sympathetic tone

Figure2—Mean±SEMbloodpressure(A)andheartrate(B)in15ballpythonsatvarioustimepointsaftersurgicalcannulationofthevertebralartery.SeeFigure1forkey.

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of the heart. Isoflurane usually depresses heart rate and blood pressure in reptiles18,19 and would therefore have caused opposite effects. In mammals, blood pressure and heart rate typically increase during the postopera-tive period,2,20 and these responses are often interpreted as indicators of pain and used to determine the need for analgesia.2 Nevertheless, it has been proposed that the heart rate in mammals rarely increases as a result of pain when other obvious signs of distress are lacking.21 Because the snakes in our study were still recovering from anesthesia during the first hours after surgery, it was not possible to reconcile the tachycardia with be-havioral observations, and it remains unknown there-fore whether increased heart rate can be used as an in-dicator of pain in reptiles.

In general, the surgery had little effect on blood gas values. Pain and shock often induce hyperventila-tion, which would have resulted in decreased Paco

2 and

caused Pao2 and pH to increase. The stable values for

blood gas measurements indicated that the snakes were ventilated adequately during surgery and that their ventilation was not affected after surgery. The signifi-cant reduction in Hct as the experiment progressed was evident in all snakes regardless of whether preoperative analgesics were administered and was likely caused by frequent blood sampling and intraoperative blood loss.

Postoperative stress has received little attention in reptiles, and information about concentrations of stress hormones during the postoperative period is not avail-able. The low plasma epinephrine concentrations that we detected in snakes during anesthesia and immedi-ately after surgery differed from the situation in mam-mals, in which plasma catecholamine concentrations increase markedly within the first minutes, followed by gradual decrease toward baseline concentrations sev-eral hours after a painful procedure.22,23 In contrast, the increase in plasma cortisol concentration was detect-ed early (1.5 hours) after surgery in the snakes in our study. Plasma cortisol concentrations in mammals also increase 1 hour after surgery, and that increase is used as an indicator of pain in mammals.3,4 Plasma cortisol concentration in ball pythons has not been reported, but plasma concentration of corticosterone, the pre-dominant reptilian glucocorticoid, reportedly increas-es from 40 to 60 ng/mL during container restraint in ball pythons.24 The increase in plasma concentrations of glucocorticoids, corticosterone, and cortisol when snakes are exposed to stressful and painful procedures suggests that plasma concentrations of these hormones could be used in assessment of pain in ball pythons.

We were unable to detect discernable effects of pre-operative administration of meloxicam or butorphanol on physiologic variables in snakes after surgery. In rep-tiles, the absorption time and half-life of both drugs are unknown. However, because of the slower metabolic rate of reptiles versus mammals, both drugs are likely to be absorbed and metabolized slower than they are in mammals. This would imply that both drugs were in effect at the time of surgery.

Researchers in other studies8,19,l also failed to detect an analgesic effect of butorphanol in reptiles, whereas the analgesic potential of meloxicam, to our knowl-edge, has not been investigated. In mammals, preopera-

tive treatment with butorphanol results in a lowering of the plasma cortisol concentration (except at 1 hour after surgery), compared with the value obtained before surgery (baseline). On the other hand, treatment with meloxicam before surgery results in an increase in plas-ma cortisol concentration during the first 3 hours after surgery, and afterward, the concentration decreases to lower than baseline values.25

The results of our study indicated that surgery in ball pythons is associated with a transient increase in blood pressure, heart rate, and plasma cortisol concen-tration. Clearly, more research on pain and pain man-agement in reptiles is needed.

a. HI 665 ventilator (tidal volume of 50 mL/kg [22.7 mL/lb] at 10 breaths/min), Harvard Apparatus, Holliston, Mass.

b. Fluotec, Cyprane Ltd, Keighley, England.c. PE50, SIMS Portex Ltd, Hythe, England.d. PH radiometer (PHM73) connected to Blood Micro System

(BMS2), Radiometer, Copenhagen, Denmark.e. Oxygen radiometer connected to Blood Micro System (BMS2),

Radiometer, Copenhagen, Denmark.f. Haemofuge, Heraeus Sepatech GmbH, Osterode/Harz, Germany.g. Delfia Cortisol 1244-060, PerkinElmer Life and Analytical Sci-

ences, Turku, Finland.h. Victor3 1420 multilabel counter, PerkinElmer Life and Analyti-

cal Sciences, Hvidovre, Denmark.i. Workout, version 1.0, PerkinElmer Life and Analytical Sciences,

Hvidovre, Denmark.j. Model Px600, Baxter-Edward, Irvine, Calif.k. AcqKnowledge MP 100, BioPac Systems, Santa Barbara, Calif.l. Fleming JG, Robertson AS. Use of thermal threshold test re-

sponse to evaluate the antinociceptive effects of butorphanol in juvenile green iguanas (Iguana iguana) (abstr), in Proceedings. Annu Conf Am Assoc Zoo Vet 2006;279.

References1. Bateson P. Assessment of pain in animals. Anim Behav 1991;42:

827–839.2. Hummel P, Dijk MV. Pain assessment: current status and chal-

lenges. Semin Fetal Neonatal Med 2006;11:237–245.3. Naito Y, Tamai S, Shingu K. Responses of plasma adrenocortico-

tropic hormone, cortisol and cytokines during and after upper abdominal surgery. Anesthesiology 1992;77:426–431.

4. Devitt CM, Cox RE, Hailey JJ. Duration, complications, stress and pain of open ovariohysterectomy versus a simple method of laparoscopic-assisted ovariohysterectomy in dogs. J Am Vet Med Assoc 2005;227:921–927.

5. Roughan JV, Flecknell PA. Evaluation of a short duration behav-ior-based post-operative pain scoring system in rats. Eur J Pain 2003;7:397–406.

6. Kanui TI, Hole K, Miaron JO. Nociception in crocodiles: capsa-icin instillation, formalin and hot plate test. Zoolog Sci 1990;7: 537–540.

7. Kanui TI, Hole K. Morphine and pethidine antinociception in the crocodile. J Vet Pharmacol Ther 1992;15:101–103.

8. Sladky KK, Paul-Murphy J, Miletic V, et al. Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles. J Am Vet Med Assoc 2007;230:1356–1362.

9. Sneddon LU. The evidence for pain in fish: the use of morphine as an analgesic. Appl Anim Behav Sci 2003;83:153–162.

10. Paul-Murphy JR, Brunson DB, Miletic V. Analgesic effects of bu-torphanol and buprenorphine in conscious African grey parrots (Psittacus erithacus erithacus and Psittacus erithacus timneh). Am J Vet Res 1999;60:1218–1221.

11. Read MR. Evaluation of the use of anesthesia and analgesia in reptiles. J Am Vet Med Assoc 2004;224:547–552.

12. Avery RB. Reptile anesthesia. Semin Avian Exot Pet Med 1998;7:30–40.13. Cameron JN. Rapid method for determination of total carbon di-

oxide in small blood samples. J Appl Physiol 1971;31:632–634.

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14. Heisler N. Acid-base regulation in fishes. In: Hoar WS, Randall DJ, eds. Fish physiology. New York: Academic Press Inc, 1984;315–401.

15. Overgaard J, Wang T. Increased blood oxygen affinity during diges-tion in the snake Python molurus. J Exp Biol 2002;205:3327–3334.

16. Stinner JN, Ely DL. Blood pressure during routine activity, stress, and feeding in black racer snakes (Coluber constrictor). Am J Physiol 1993;264:79–84.

17. Wang T, Axelsson M, Jensen J, et al. Cardiovascular actions of py-thon bradykinin and substance P in the anesthetized python, Python regius. Am J Physiol Regul Integr Comp Physiol 2000;279:531–538.

18. Maas A, Brunson DB. Comparison of anesthetic potency and cardio-pulmonary effects of isoflurane and sevoflurane in colubrid snakes, in Proceedings. Annu Conf Am Assoc Zoo Vet 2002;306–308.

19. Mosley CA, Dyson D, Smith DA. The cardiovascular dose-re-sponse effects of isoflurane alone and combined with butor-phanol in the green iguana (Iguana iguana). Vet Anaesth Analg 2004;31:64–72.

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21. Hansen DB. Analgesia and sedation in the critically ill. J Vet Emerg Crit Care 2005;15:285–294.

22. Benson GJ, Wheaton LG, Thurmon JC, et al. Postoperative cate-cholamine response to onychectomy in isoflurane-anesthetized cats: effect of analgesics. Vet Surg 1991;20:222–225.

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Selected abstract for JAVMA readers from the American Journal of Veterinary Research

Pharmacokinetics of butorphanol in cats after intramuscular and buccal transmucosal administration

Sean M. Wells et al

Objective—To determine the pharmacokinetics of butorphanol in cats following IM and buccal transmucosal (BTM) administration, to determine the relative bioavailability of butorphanol follow-ing BTM administration, and to extrapolate a plasma concentration associated with antinociception on the basis of existing data from pharmacologic studies of butorphanol in cats.Animals—6 healthy adult cats.Procedures—Following IM or BTM butorphanol tartrate (0.4 mg/kg) administration to cats in a 2-way crossover trial, plasma samples were obtained from blood collected via a central venous catheter during a 9-hour period. Plasma butorphanol concentrations were determined by high-per-formance liquid chromatography.Results—Data from 1 cat contained outliers and were excluded from pharmacokinetic analysis. Terminal (mean ± SD) half-life of butorphanol for the remaining 5 cats was 6.3 ± 2.8 hours and 5.2 ± 1.7 hours for IM and BTM administration, respectively. Peak plasma butorphanol concentra-tions were 132.0 and 34.4 ng/mL for IM and BTM administration, respectively. Time to maximal plasma concentration was 0.35 and 1.1 hours for IM and BTM administration, respectively. Extent of butorphanol absorption was 37.16% following BTM application. On the basis of data from extant pharmacologic studies of butorphanol in cats, duration (mean ± SD) of antinociception was 155 ± 130 minutes. The estimated plasma concentration corresponding to this time point was 45 ng/mL.Conclusions and Clinical Relevance—In cats, IM butorphanol administration at 0.4 mg/kg could maintain a plasma concentration of > 45 ng/mL for 2.7 ± 2.2 hours, whereas BTM administration at the same dose would not be effective at maintaining plasma concentrations at > 45 ng/mL. (Am J Vet Res 2008;69:1548–1554)

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