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Tolazoline-Induced Apnea in Mule Deer (Odocoileus hemionus)Author(s): Jack Alan Mortenson, D.V.M., M.S. and Jason Andrew Robison, M.S.Source: Journal of Zoo and Wildlife Medicine, 42(1):105-107. 2011.Published By: American Association of Zoo VeterinariansDOI: http://dx.doi.org/10.1638/2010-0058.1URL: http://www.bioone.org/doi/full/10.1638/2010-0058.1

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TOLAZOLINE-INDUCED APNEA IN MULE DEER (ODOCOILEUS

HEMIONUS)

Jack Alan Mortenson, D.V.M., M.S., and Jason Andrew Robison, M.S.

Abstract: Eighteen mule deer (Odocoileus hemionus) and six Columbia black-tailed deer (Odocoileus hemionus

columbianus) were held in pens and repeatedly anesthetized from April 2004 through June 2005 as part of an

external parasite study. Deer were anesthetized using a combination of TelazolH and xylazine hydrochloride (HCL)

administered intramuscularly. Tolazoline HCL was slowly administered at 4 mg/kg intravenously to reverse the

effects of xylazine with good results. For 17 of the 19 mule deer anesthesias in the fall of 2004, a mean dose of

7.3 mg/kg of intravenous tolazoline (range 6.1–8.4 mg/kg) was given by mistake. This paper describes clinical signs

of apnea, muscle tensing, and fasciculations immediately following intravenous administration of tolazoline HCL

in mule deer (O. hemionus) at 1.5–3 times the recommended dose. Mean dose for black-tailed deer during this time

was 8.1 mg/kg (range 5.5–12.4 mg/kg) with no clinical signs as seen in the mule deer. Based on these findings,

intravenous tolazoline use in mule deer is recommended at #4 mg/kg.

Key words: Apnea, mule deer, Odocoileus hemionus, tolazoline, toxicosis.

INTRODUCTION

Tolazoline hydrochloride (HCL) is an a-

adrenergic blocking agent within the group of

imidazoline derivatives with mixed pharmacolog-

ic properties. The a2-adrenergic antagonist effects

of tolazoline are greatest, but there are also

additional receptor effects that can create adverse

side effects, including tachycardia, hypotension,

and gastrointestinal hypermotility.14 Tolazoline

has been used for more than two decades as an

effective reversal agent for xylazine, an a2-

adrenergic agonist tranquilizer commonly used

in conjunction with anesthetic agents for cer-

vids.3,4,8,10 Tolazoline was established as the

preferred reversal agent for xylazine use in

white-tailed deer (Odocoileus virginianus) over

yohimbine and atipamezole because of faster and

more complete reversals.12 Intravenous tolazoline

doses reported for deer vary from 2 to 5 mg/

kg.3,9,12 This paper describes clinical signs of

apnea, muscle tensing, and fasciculations imme-

diately following intravenous administration of

tolazoline HCL in mule deer (Odocoileus hemi-

onus) at 1.5 to 3 times the recommended dose.

CASE REPORT

Eighteen mule deer (seven males, 11 females)

were held in a long-term study examining

transmission potential of an exotic chewing louse

of deer1,6 from Columbia black-tailed deer

(Odocoileus hemionus columbianus), hereafter

referred to as black-tailed deer. Mule deer and

black-tailed deer (three males, three females)

fawns were captured and held for 15 mo with

appropriate husbandry at E. E. Wilson Wildlife

Management Area, Corvallis, Oregon, in control

(n 5 6) and treatment (n 5 18) groups. From

April 2004 through June 2005, each deer was

anesthetized approximately every 6 wk to collect

external parasite observations, blood samples,

morphometric data, and body weight (measured

to 60.5 lb [0.2 kg]). TelazolH (Fort Dodge

Laboratories, Inc., Fort Dodge, Iowa 50501,

USA), a 1:1 mixture of tiletamine HCL and

zolazepam HCL, in combination with xylazine

HCL (TranquiVedTM, Vedco, Inc., St. Joseph,

Missouri 64507, USA) at 4.0 mg/kg and 2.0 mg/kg,

respectively, was used to anesthetize all deer.12

Vital signs were monitored throughout the

procedures using pulse oximeter O2 percentages,

heart rates, and respiratory rates. Tolazoline

HCL 100 mg/ml (TolazineH, Lloyd Laboratories,

Shenandoah, Iowa 51601, USA) was prescribed at

a protocol dose of 4.0 mg/kg12 and slowly

administered intravenously after handling and

biologic sampling were completed. A reference

table was used based on the above doses that

divided animal weight categories by 11.4-kg (25-

lb) intervals for anesthesia and tolazoline doses.

Deer were handled and sampled by teams of

student research technicians with various levels of

From the U.S. Department of Agriculture, Veteri-

nary Services, 530 Center Street NE, Suite 335, Salem,

Oregon 97301, USA (Mortenson); and the Department

of Fisheries and Wildlife, Oregon State University, 104

Nash Hall, Corvallis, Oregon 97301, USA (Mortenson,

Robison). Present address (Robison): Coquille Indian

Tribe, P.O. Box 783, North Bend, Oregon 97459, USA.

Correspondence should be directed to Dr. Mortenson

(jack.a.mortenson@usda.gov). The author(s) prepared

this manuscript as part of their duties with the U.S.

Government and are unable to assign rights to the

American Association of Zoo Veterinarians.

Journal of Zoo and Wildlife Medicine 42(1): 105–107, 2011

105

experience, and supervised by one of the authors

(JAR). During the first 4 mo of the study,

tolazoline doses varied according to a dosing

interval table divided by weight categories.

However, because of human error, tolazoline

doses used to reverse anesthesias conducted in

August and September 2004 were substantially

greater than established guidelines. Immediately

following this period, the anesthetic protocol was

reviewed and the accidental tolazoline dose

increase determined. Statistical analysis was done

using standard t-tests, and P 5 0.05 indicated

statistically significant difference on mean tolaz-

oline doses between study periods.

Deer were anesthetized 207 times with a mean

induction time from anesthetic injection to lateral

recumbency of 9.5 (range 2–46) min. Depth of

anesthesia varied with each deer, but all were at a

deep enough plane of anesthesia to be handled

and sampled. Mean handling times for black-

tailed deer and mule deer were similar at 19.4

(range 4–45) and 22.2 (range 5–49) min, respec-

tively. Respiration rates were high because of a

light plane of anesthesia achieved in most deer.

Mean rates for black-tailed and mule deer were

56 (range 32–108) and 63 (range 36–108) bpm,

respectively. Average time from injection of

tolazoline intravenously to standing was 33.8

(range 9–52) min. No abnormal behavior or side

effects were noted upon injection of tolazoline

intravenously during the months of April

through July 2004. Tolazoline doses given in

those months ranged from 2.2 to 5 mg/kg, with a

mean of 4.6 mg/kg. The mule deer mean

tolazoline dose administered during August and

September 2004 was higher than that adminis-

tered during the previous months (P 5 0.054).

Seventeen of the 19 mule deer were given a mean

dose of 7.3 mg/kg intravenous tolazoline (range

6.1–8.4 mg/kg), and immediately developed acute

apnea and skeletal muscle fasciculations. The

other two mule deer were given tolazoline doses

of 4.0 and 4.1 mg/kg and did not exhibit clinical

signs. Of the six black-tailed deer given tolazoline

at the dose range of 5.5–12.4 mg/kg, none

developed abnormal clinical signs during admin-

istration of and recovery from anesthesia. Af-

fected mule deer exhibited apnea, with immediate

tensing and shaking of the shoulders, neck, and

abdomen. In all deer, breathing was regular and

at nearly one breath per second when tolazoline

was injected intravenously. Breathing was imme-

diately interrupted with no movement of the

chest or abdomen. Deer were stimulated with

brisk rubs on the head and shoulders and, in the

case of lateral recumbency, moved to a sternal

position. Normal breathing and chest expansion

resumed in 8–10 sec and no respiratory stimulant

was administered to counteract the apnea. Deer

showing apnea and abnormal muscle activity

upon intravenous tolazoline administration had

mean recovery periods of equal length to those of

black-tailed deer and mule deer not showing

clinical signs. After re-establishing the protocol

tolazoline dose at 4 mg/kg, no further complica-

tions were noted during reversals for the remain-

der of the study. The rate of intravenous

tolazoline injection remained constant through-

out the anesthesias.

DISCUSSION

Apnea has not been described as a potential

side effect of tolazoline administration. More

commonly reported clinical signs of toxicosis

include tachycardia, gastrointestinal hypermotil-

ity in the form of vomiting, diarrhea, abdominal

discomfort, and death.11,14 The mechanisms of

these effects, as described, relate to the blocking

of peripheral a2-adrenoreceptors, activation of

cholinergic and histamine receptors, and hista-

mine release, but are poorly understood.14

Little information is available on species

differences of preferred tolazoline doses. One

elk (Cervus elaphus) calf given 10 mg/kg of

tolazoline intravenously displayed muscle tensing

and fasciculations immediately and recovered

uneventfully (M. G. Bjorklund, 2007, pers.

comm.). Similar signs of muscle tensing were

observed in cattle calves that were not sedated,

but given 2.0 mg/kg of tolazoline intravenously.15

The recommended tolazoline dose for cattle is

approximately 0.25–0.50 that of horses.13,16 Also,

cattle given tolazoline as an intravenous bolus

quickly can exhibit signs of coughing, gasping,

and tachycardia (J. Denhart, 2007, pers. comm.).

The apnea, muscle fasciculations, and tensing

observed in mule deer of this study was

immediate upon intravenous injection of tolazo-

line and quickly resolved, without any deaths.

Apnea is described as the temporary cessation of

breathing2 and length of time is generally

undefined in veterinary anesthesia textbooks.

Recognition of apnea will depend on species

handled and individual animal physiologic needs.

Clearly, each animal affected in this study

showed a pronounced cessation of what was a

regular breathing rate. It is unknown if tachy-

cardia was present, because heart rate monitoring

with the pulse oximeter was stopped just prior to

the tolazoline being injected. The use of dosing

106 JOURNAL OF ZOO AND WILDLIFE MEDICINE

tables based on weight categories leads to the

mistaken use of a standard dose across weights of

deer handled. Adverse effects were seen only in

mule deer given tolazoline at doses above 6 mg/kg

and were not seen in black-tailed deer given doses

up to three times the recommended dose. It is

unknown why these two subspecies of deer

reacted differently to tolazoline in this study.

There are many examples of specific breeds or

species showing a sensitivity to diverse drug

classes including avermectins, antineoplastic

agents, synthetic opioids, and antibiotics.5,7 How-

ever, minimal data are available on adverse drug

affects in wildlife species. Based on these findings,

i.v. tolazoline use in mule deer is recommended at

#4 mg/kg.

Acknowledgments: The authors thank the

Oregon State University Department of Fisheries

and Wildlife students who provided assistance

with deer husbandry and data collection. In

addition, the authors wish to thank Ray Fiori,

Oregon Department of Fish and Wildlife, E. E.

Wilson Wildlife Area, for facility management.

Funding for this project was provided, in part,

from the Oregon Department of Fish and

Wildlife, the Black-tailed Deer Foundation, the

Oregon Hunters Association, the Benton Bow-

men, and the Oregon Wildlife Heritage Founda-

tion. This study was conducted with approval by

the Oregon State University Institutional Animal

Care and Use Committee.

LITERATURE CITED

1. Bildfell, R. J., J. W. Mertins, J. A. Mortenson,

and D. F. Cottam. 2004. Hair-loss syndrome in black-

tailed deer of the Pacific Northwest. J. Wildl. Dis. 40:

670–681.

2. Blood, D. C., V. P. Studdert, and C. C. Gay.

2007. Saunders Comprehensive Veterinary Dictionary.

3rd ed. Elsevier, London, England.

3. DelGiudice, G. D., P. R. Krausman, E. S.

Bellantoni, R. C. Etchberger, and U. S. Seal. 1989.

Reversal by tolazoline hydrochloride of xylazine hydro-

chloride–ketamine hydrochloride immobilizations in free-

ranging desert mule deer. J. Wildl. Dis. 25: 347–352.

4. Dew, T. L. 1988. Use of tolazoline hydrochloride

to reverse multiple anesthetic episodes induced with

xylazine hydrochloride and ketamine hydrochloride in

white-tailed deer and goats. J. Zoo Anim. Med. 19: 8–13.

5. Fleischer, S., M. Sharkey, K. Mealey, E. A.

Ostrander, and M. Martinez. 2008. Pharmacogenetic

and metabolic differences between dog breeds: their

impact on canine medicine and the use of the dog as a

preclinical animal model. AAPS J. 10: 110–119.

6. Foreyt, W. J., P. B. Hall, and L. C. Hall. 2004.

Evaluation of ivermectin for the treatment of hair-loss

syndrome in black-tailed deer. J. Wildl. Dis. 40: 434–443.

7. Hopper, K., J. Aldrich, and S. C. Haskins. 2002.

Ivermectin toxicity in 17 collies. J. Vet. Intern. Med. 16:

89–94.

8. Klein, L.V., and A. M. Klide. 1989. Central a2-

adrenergic and benzodiazepine agonists and their

antagonists. J. Zoo Wildl. Med. 20: 138–153.

9. Kreeger T. J, J. M. Arnemo, and J. P. Rath. 2002.

Handbook of Wildlife Chemical Immobilization. Wildlife

Pharmaceuticals, Fort Collins, Colorado. Pp. 187–188.

10. Kreeger T. J, G. D. Del Giudice, U.S. Seal, and

P. D. Karns.1986. Immobilization of white-tailed deer

with xylazine hydrochloride and ketamine hydrochlo-

ride and antagonism by tolazoline hydrochloride. J.

Wildl. Dis. 22: 407–412.

11. Lloyd Laboratories, Inc. 2007. Tolazoline [pack-

age insert]. Lloyd Laboratories, Inc., Shenandoah,

Iowa.

12. Miller, B. F., L. I. Muller, T. Doherty, D. A.

Osborn, K. V. Miller, and R. J. Warren. 2004.

Effectiveness of antagonists for tiletamine–zolazepam/

xylazine immobilization in female white-tailed deer. J.

Wildl. Dis. 40: 533–537.

13. Powell, J. D., J. W. Denhart, and W. E. Lloyd.

1998. Effectiveness of tolazoline in reversing xylazine-

induced sedation in calves. J. Am. Vet. Med. Assoc.

212: 90–92.

14. Read, M. R., T. Duke, and A. R. Toews. 2000.

Suspected tolazoline toxicosis in a llama. J. Am. Vet.

Med. Assoc. 216: 227–229.

15. Ruckebush, Y., and P. L. Toutain. 1984. Specific

antagonism of xylazine effects in reticulorumen motor

function in cattle. Vet. Med. Rev. 1: 3–12.

16. Takase, K., Y. Hikasa, and S. Ogasawara. 1986.

Tolazoline as an antagonist of xylazine to cattle. Jap. J.

Vet. Sci. 48: 859–862.

Received for publication 29 March 2010

MORTENSON AND ROBISON—TOLAZOLINE INDUCED APNEA 107