Elephant specific information, if available, is in blue.

Chemistry – Xylazine HCl is a alpha2-adrenergic agonist structurally related to clonidine. The pH of the commercially prepared injections is approximately 5.5. Dosages and bottle concentrations are expressed in terms of the base.

 

Storage/Stability/Compatibility – Do not store above 30°C (86°F). Xylazine is reportedly compatible in the same syringe with several compounds, including: acepromazine, buprenorphine, butorphanol, chloral hydrate, and meperidine.

 

Pharmacology – A potent alpha2-adrenergic agonist, xylazine is classified as a seda­tive/analgesic with muscle relaxant properties. Although xylazine possesses several of the same pharmacologic actions as morphine, it does not cause CNS excitation in cats, horses or cattle, but causes sedation and CNS depression. In horses, the visceral analgesia pro­duced has been demonstrated to be superior to that produced by meperidine, butorphanol or pentazocine.

 

Xylazine causes skeletal muscle relaxation through central mediated pathways. Emesis is often seen in cats, and is also seen occasionally in dogs receiving xylazine. While thought to be centrally mediated, neither dopaminergic blockers (e.g., phenothiazines) or alpha-blockers (yohimbine, tolazoline) block the emetic effect. Xylazine does not cause emesis in horses, cattle, sheep or goats. Xylazine depresses thermoregulatory mechanisms and either hypothermia or hyperthermia is a possibility depending on ambient air temperatures.

 

Effects on the cardiovascular system include an initial increase in total peripheral resistance with increased blood pressure followed by a longer period of lowered blood pressures (below baseline). A bradycardic effect can be seen with some animals developing a second degree heart block or other arrhythmias. An overall decrease in cardiac output of up to 30% may be seen. Xylazine has been demonstrated to enhance the arryhthmogenic effects of epinephrine in dogs with or without concurrent halothane.

 

Xylazine’s effects on respiratory function are usually clinically insignificant, but at high dosages, it can cause respiratory depression with decreased tidal volumes and respiratory rates and an overall decreased minute volume. Brachycephalic dogs and horses with upper airway disease may develop dyspnea.

 

Xylazine can induce increases in blood glucose secondary to decreased serum levels of insulin. In nondiabetic animals, there appears to be little clinical significance associated with this effect.

 

In horses, sedatory signs include a lowering of the head with relaxed facial muscles and drooping of the lower lip. The retractor muscle is relaxed in male horses, but unlike acepromazine, no reports of permanent penile paralysis has been reported. Although, the animal may appear to be thoroughly sedated, auditory stimuli may provoke arousal with kick­ing and avoidance responses.

 

With regard to the sensitivity of species to xylazine definite differences are seen. Ruminants are extremely sensitive to xylazine when compared with horses, dogs, or cats. Ruminants generally require approximately 1/10th the dosage that is required for horses to exhibit the same effect. In cattle (and occasionally cats and horses), polyuria is seen fol­lowing xylazine administration, probably as a result of decreased production of vaso­pressin (anti-diuretic hormone, ADH). Bradycardia and hypersalivation are also seen in cattle and are diminished by pretreating with atropine. Swine, require 20-30 times the ru­minant dose and therefore, xylazine is not routinely used in this species.

 

Uses/Indications – Xylazine is approved for use in dogs, cats, horses, deer, and elk. It is indicated in dogs, cats and horses to produce a state of sedation with a shorter period of analgesia, and as a preanesthetic before local or general anesthesia. Because of the emetic action of xylazine in cats, it is occasionally used to induce vomiting after ingesting toxins.

 

Pharmacokinetics – Absorption is rapid following IM injection, but bioavailabilities are incomplete and variable. Bioavailabilities of 40-48% in the horse, 17-73% in the sheep, and 52-90% in the dog have been reported after IM administration.

 

In horses, the onset of action following IV dosage occurs within 1-2 minutes with a maximum effect 3-10 minutes after injection. The duration of effect is dose dependent but may last for approximately 1.5 hours. The serum half-life after a single dose of xylazine is approximately 50 minutes in the horse and recovery times generally take from 2-3 hours.

 

In dogs and cats, the onset of action following an IM or SQ dose is approximately 10-15 minutes, and 3-5 minutes following an IV dose. The analgesic effects may persist for only 15-30 minutes, but the sedative actions may last for 1-2 hours depending on the dose given. The serum half-live of xylazine in dogs has been reported as averaging 30 minutes. Complete recovery after dosing may take from 2-4 hours in dogs and cats.

 

Xylazine is not detected in milk of lactating dairy cattle at 5 & 21 hours post-dose, but the FDA has not approved the use of this agent in dairy cattle and no meat or milk with­drawal times have been specified.

 

Contraindications/Precautions – Xylazine is contraindicated in animals receiving epinephrine or having active ventricular arrhythmias. It should be used with extreme cau­tion in animals with preexisting cardiac dysfunction, hypotension or shock, respiratory dysfunction, severe hepatic or renal insufficiency, preexisting seizure disorders, or if severely debilitated. Because it may induce premature parturition, it should generally not be used in the last trimester of pregnancy, particularly in cattle.

 

Be certain of product concentration when drawing up into syringe, especially if treating ruminants. Do not give to ruminants that are dehydrated, have urinary tract obstruction, or are debilitated. It is not approved for any species to be consumed for food purposes.

 

Horses have been known to kick after a stimulatory event (usually auditory); use caution. Avoid intra-arterial injection; may cause severe seizures and collapse. The manufacturers warn against using in conjunction with other tranquilizers.

 

Adverse Effects/Warnings – Emesis is generally seen within 3-5 minutes after xylazine administration in cats and occasionally in dogs. To prevent aspiration, do not induce fur­ther anesthesia until this time period has lapsed. Other adverse effects listed in the package insert (Gemini®, Butler) for dogs and cats include: muscle tremors, bradycardia with par­tial A-V block, reduced respiratory rate, movement in response to sharp auditory stimuli, and increased urination in cats.

 

Dogs may develop bloat from aerophagia which may require decompression. Because of gaseous distention of the stomach, xylazine’s use before radiography can make test inter­pretation difficult.

 

Adverse effects listed in the package insert (AnaSed®, Lloyd) for horses include: muscle tremors, bradycardia with partial A-V block, reduced respiratory rate, movement in response to sharp auditory stimuli, and sweating (rarely profuse). Additionally, large ani­mals may become ataxic following dosing and caution should be observed.

 

Adverse reactions reported in cattle include salivation, ruminal atony, bloating and regur­gitation, hypothermia, diarrhea, and bradycardia. The hypersalivation and bradycardia may be alleviated by pretreating with atropine. Xylazine may induce premature parturition in cattle.

 

Overdosage – In the event of an accidental overdosage, cardiac arrhythmias, hypotension, and profound CNS and respiratory depression may occur.  Seizures have also been re­ported after overdoses. There has been much interest in using alpha-blocking agents as an­tidotes or reversal agents to xylazine. Yohimbine or tolazoline have been suggested to be used alone and in combination to reverse the effects of xylazine or speed recovery times. A separate monograph for yohimbine is available which discusses suggested doses, etc.

 

To treat the respiratory depressant effects of xylazine toxicity, mechanical respiratory support with respiratory stimulants (e.g., doxapram) have been recommended for use.

 

Drug Interactions – The use of epinephrine with & without the concurrent use of halothane concomitantly with xylazine may induce the development of ventricular ar­rhythmias.  The combination use of acepromazine with xylazine is generally considered to be safe, but there is potential for additive hypotensive effects and this combination should be used cautiously in animals susceptible to hemodynamic complications. Other CNS depressant agents (barbiturates, narcotics, anesthetics, phenothiazines, etc.) may cause additive CNS depression if used with xylazine. Dosages of these agents may need to be reduced.  A case report of a horse developing colic-like symptoms after reserpine and xylazine has been reported. Until more is known about this potential interaction, use together of these two agents together should be avoided. The manufacturers warn against using xylazine in conjunction with other tranquilizers.

 

Doses –

Horses:

a)   1.1 mg/kg IV; 2.2 mg/kg IM. Allow animal to rest quietly until full effect is reached. (Package Insert; Rompun® – Miles)

b)   Sedative/analgesic for colic: 0.3 – 0.5 mg/kg IV; repeat as necessary (Muir 1987)

c)   Prior to guaifenesin/thiobarbiturate anesthesia: 0.55 mg/kg IV; Prior to ke­tamine induction: 1.1 mg/kg IV; In combination with opioid/tranquilizers (all IV doses):

1)   xylazine 0.66 mg/kg; meperidine 1.1 mg/kg

2)   xylazine 1.1 mg/kg; butorphanol 0.01 – 0.02 mg/kg

3)   xylazine 0.6 mg/kg; acepromazine 0.02 mg/kg

Note: the manufacturers state that xylazine should not be used in conjunction with tranquilizers (Thurmon and Benson 1987)

 

Elephants:

 

CAUTION!  Sedative and anesthetic drug dosages for African elephants often vary from those for Asian elephants.  Do not assume that the recommendations for one species can be applied to the other.  Significant variation may also occur between individual elephants.  Higher doses may be needed in wild or excited animals. Unless otherwise specified, doses refer to captive elephants.  The information provided here should be used as a guideline only.  Consultation with experienced colleagues is advised.

 

a,l) Xylazine 100-200 mg/metric ton for Asian elephants. Extreme aggressiveness, musth, painful conditions, and ambient disturbances may necessitate higher doses (Cheeran, et.al. 2002,1992).

 

b) 0.10-0.11 mg/kg xylazine IM for Asian elephants; can be combined with acepromazine or ketamine; the dose of individual drugs can be reduced up to 50% when combinations are used (Nayer et.al. 2002).

 

c) Xylazine at a dose of 100-300 mg in adult Asian elephants (approximately 4-10 mg/ 100 kg body weight) injected slowly intravenously resulted in good sedative, analgesic, and muscle relaxing effects in 21 Asian elephants undergoing blood collection, biopsies and ultrasound examinations.  The author advises that yohimbine or atipamezole be readily available in case of overdose or inadvertent human exposure (1mg/kg can be lethal in

man) (Rietschel et.al. 2001).

 

d) In Asian elephants: xylazine alone (0.1 mg/kg) or in combination with ketamine (1.25: 1 ratio) (Sarma et al. 2001).

 

e) Xylazine at dosages of 0.18-0.33 mg/kg (total doses 600-1000 mg) was used to sedate 3 African elephants to load into a trailer a distance of about 50 m away.  The procedure was accomplished but the sedation was rated as fair (Ramsey, 2000).

 

f) * Adverse effect: A 27 year-old male Asian elephant with mild bilateral corneal opacities was laid in  lateral recumbency, injected with 150 mg xylazine slowly via the caudal auricular vein and then allowed to stand. After 2.5 minutes he tilted his head upwards and backwards in a tentative gait.  At 4-5 minutes he trumpetted loudly and started to shake his head vigorously, followed by complete delirium.  After 10 minutes of violent excitement, he gradually became normal but his degree of sedation was minimal.  An additional 50 mg of xylazine was given IV and the elephant became profoundly sedated.   He was reversed with 60 mg yohimbine IV. The author suggests that the elephant’s visual impairment may have caused the reaction (Sarma, 1999).

 

g) Intravenous xylazine (33-72 µg/kg) was titrated to achieve standing sedation with responsiveness to voice commands in a 5000 kg male Asian elephant sedated on 3 occasions for treatment of a foot abscess. Partial reversal with atipamezole made the animal more responsive in cases of heavy sedation (Honeyman et.al. 1998).

 

h) Xylazine doses ranging from 100-550 mg with a mean of 0.209 mg/kg body weight were used to capture 8 wild Asian elephants (Bosi et.al. 1997).

 

i) Captive Asian elephants: For sedation: 0.04-0.08 mg/kg (180-360 mg total dose);

For immobilization 0.15-0.20 mg/kg alone or 0.12 mg/kg xylazine in combination with 0.33 mg/kg ketamine.

 

Captive African elephants: For sedation: 0.08-0.10 mg/kg (100-640 mg total dose);

For immobilization (opiates are preferred): 0.15-0.20 mg/kg xylazine;

For babies and juveniles: 0.14 mg/kg xylazine in combination with 1.14 mg/kg ketamine (Fowler, 1995).

 

j) Adult 700 mg; juvenile-adult 200-600mg; baby-juvenile 20-160 (species not specified); adult

Asian elephant for translocation 150-2850 mg (Kock et.al. 1993). (Author’s (Mikota) note:  The

animal category and drug dose column headings for xylazine are misaligned in this reference and may cause confusion. The doses listed here have been correctly matched to their respective age categories.  Regarding the Asian elephant dose, also note that in the original source (Lahiri-Choudhury, 1992), 2850 mg represents a combination of xylazine and ketamine. It does not represent a high end dose of xylazine alone. In this comparative study, 2850 mg was the maximum given to an individual elephant (over the time period that included capture and translocation, not as a single dose) and the maximum dose used during 24 hours. 

 

k) 100 mg/ton is an ideal dose for Asian elephants (Appayya, 1992).

 

l) see (a)

 

m) In a comparison of Asian elephant capture and translocation techniques, 400 mg xylazine was the maximum single dose used in Malaysia (tusker over 9’6”) and 150 mg was the maximum dose used in West Bengal (tusker 8’2”).  Maximum total on a single elephant were 2100 mg over 4 days (Malaysia) and 1525 mg (West Bengal).  Maximum during 24 hours was 1500 mg (Malaysia) and 925 mg (West Bengal). (Lahiri- Choudhury, 1992).

 

n) Xylazine, administered IM was used to induce surgical anesthesia in 8 Asian elephants. A dose of 150 mg in a

1500 kg baby tusker and a dose of 400 mg in a 3000 kg tusker resulted in standing immobilization. Recumbent

immobilization was achieved with doses of 400 mg (3500 kg tuskers) and 450 mg (4000 kg tusker), and with

combinations of 350 mg xylazine + 350 mg ketamine (3000 kg cow), 300 mg xylazine + 150 mg acepromazine

(2500 kg cow) and 350 mg xylazine + 150 mg acepromazine (3000 kg cow).  Induction occurred in 10-15 minutes

and duration of anesthesia varied from 30-60 minutes and provided sufficient analgesia for a variety of surgical

procedures (Nayar, et.al. 1992).

 

o) A mixture containing 100-150 mg xylazine and 50-100 mg ketamine injected intravascularly to the laterally

recumbent Asian elephant produced quick, safe and dependable analgesia, anesthesia, and muscular relaxation.

Surgical operations like tusk extraction, bullet extraction, umbilical and pleural herniorraphy, trunk injury, extensive

wound repair, etc. were performed in 53 elephants (Pathak, 1991).

 

p) A dose of 0.16 mg/kg was adequate to produce sedation, analgesia, and muscle relaxation to perform a ventral

herniorrhaphy in an Asian elephant (Pathak et.al. 1990).

 

q) An African elephant weighing 650 kg was premedicated with 0.27 mg/kg ketamine and 0.23 mg/kg xylazine IM

followed 20 minutes later by etorphine (Welsch et.al. 1989).

 

r) Xylazine (0.1 ± 0.04 mg/kg of body weight, mean ± SD) and ketamine (0.6 ± 0.13 mg/kg) administered IM induced

good chemical restraint in standing juvenile African elephants during a 45-minute transport period before

administration of general anesthesia (Heard et.al. 1988).

 

s) A group of 15 African elephants (Loxodonta africana) were immobilized with a combination of xylazine (0.2 mg/kg

of body weight, IM) and ketamine (1 to 1.5 mg/kg of body weight, IM) (Allen, 1986).

 

t) .08 mg/kg given IM (up to 0.15 mg/kg in an excited animal). Causes first degree heart block and is contraindicated

in cases of known heart disease. The administration of atropine (4 to 5 mg/ 100 kg) should be administered to

elephants that lie down following xylazine to prevent hypostatic congestion and cardiodepressant effects. Xylazine

can be give IV at 0.04 mg/kg, however, the induction may not be as smooth and the elephant may risk falling

(Schmidt, 1986).  Author’s (Mikota) note: No species differences listed. 

 

u) Twenty-two juvenile African elephants were given a combination of xylazine (mean +/- SD = 0.14 +/- 0.03 mg/kg

of body weight) and ketamine (1.14 +/- 0.21 mg/kg) as a single IM injection. See abstract below (Jacobson et.al.

1985).

 

v) An Asian elephant (approx 3500 kg) was given three doses of xylazine over the course of approximately 1 hour 20 minutes (4-5 times the usual dose).  Xylazine was antagonized with 4-aminopyridine and yohimbine. Three hours and 40 minutes after reversal, 1000 mg of xylazine given IM resulted in the death of the elephant. Although this elephant was scheduled for euthanasia, the author suggests that following reversal, additional doses of xylazine should not be given for 24 hours (Schmidt, 1983).

 

w) Doses of 100 to 300 mg of a 10% solution of xylazine satisfactorily sedated 6 Asian elephants ranging from 150

to 255 cm shoulder height.  At these dosages, all animals were sedated in the standing position (Bongso, 1980).

 

Elephant References:

a) Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K. 2002. Tranquilization and translocation of elephants. Journal of Indian Veterinary Association Kerala 7:(3):42-46

b) Nayar,K.N.M., Chandrasekharan,K., and Radhakrishnan,K. 2002. Management of surgical affections in captive elephants. Journal of Indian Veterinary Association Kerala 7:(3):55-59

c) Rietschel,W., Hildebrandt,T., Goritz,F., and Ratanakorn,P.  2001. Sedation of Thai Working Elephants with Xylazine and Atipamezole as a Reversal.  A Research Update on Elephants and Rhinos; Proceedings of the International Elephant and Rhino Research Symposium, Vienna, June 7-11, 2001. Pages: 121-123

d) Sarma,K.K. and Pathak,S.C. 2001. Cardio vascular response to xylazine and Hellabrunn mixture with Yohimbine as reversal agent in Asian elephants. Indian Veterinary Journal 78:(5):400-492  Abstract:  Xylazine (0.1 mg/kg body weight) produced highly significant bradycardia and hypotension in recumbent Asian elephants, with a peak depression observed at the 30th minute for heart rate and 30th minute in the mean arterial pressure (MAP). Ketamine (1.25 : 1 ratio with xylazine) mildly marginalised the bradycardia, but remarkably improved the MAP. Yohimbine, used to reverse the sedation produced by xylazine did not appear to influence these parameters to any appreciable levels.

e) Ramsay,E.  2000. Standing sedation and tranquilization in captive African elephants (Loxodonta africana). Proc. Am. Assoc. Zoo Vet. Pages: 111-114

f) Sarma,K.K. 1999. Bizarre behaviour of an elephant during xylazine anaesthesia. Indian Veterinary Journal 76:(11):1018-1019

g) Honeyman,V.L., Cooper,R.M., and Black,S.R.  1998. A protected contact approach to anesthesia and medical management of an Asian elephant (Elephas maximus).  Proceedings AAZV and AAWV Joint Conference. Pages: 338-341

h) Bosi,E.J., Kilbourn,A.M., Andau,M., and Tambing,E.  1997. Translocation of wild Asian elephants (Elephas maximus) in Sabah, Malaysia. Proceedings American Association of Zoo Veterinarians. Pages: 302  Abstract:The East Malaysian State of Sabah is believed to be home to about 1000 wild Asian elephants (Elephas maximus).  Some forest habitat has been lost through agricultural development.  In some cases, elephants are stranded in small pockets of forest which are unable to sustain them.  The Wildlife Department of Sabah has adopted a policy of capturing and translocating these animals to wildlife forest reserves.  The capture of these wild animals is made possible using chemicals such as Immobilon^® (etorphine HCl and acepromazine maleate) and Xylazine-100 (xylazine HCl).  The reversal agents are Revivon (Diprenorphine) and Reverzine (Yohimbine), respectively.  A recent capture and translocation exercise carried out involving eight wild elephants employed xylazine hydrochloride. The dose of xylazine used was calculated based on the diameter of the front footprint which provides information on body dimensions when actual weights are not available.  Xylazine doses used ranged from 100-550 mg with a mean of 0.209 mg/kg body weight.  Sedation was observed within 26 min after the darting.  The animals were then shackled and tethered.  The time for the capture operations ranged from 27-110 mins, with a mean of 72 min.  Xylazine is used again during the loading of the animals onto the lorries.  It is an effective sedative for wild elephants which can be adjusted or reversed.  The choice and used of this drug depends entire on the ability to track the animal after darting and the ability to maneuver the captive elephants into suitable locations for tethering prior to loading.  Heavy machinery is required to load the animals, unlike most other wild Asian elephant translocations were trained elephants are used to facilitate loading.

i) Fowler,M.E., 1995. Elephants. In: Restraint and handling of wild and domestic animals. Iowa State University Press, Ames, Iowa, USA pp. 265-269

j) Kock,R.A., Morkel,P., and Kock,M.D., 1993. Current immobilization procedures used in elephants. In: Fowler,M.E. (Editor), Zoo and Wild Animal Medicine Current Therapy 3. W.B. Saunders Company, Philadelphia, PA, USA pp. 436-441

k) Appayya,M.K. and Khadri,S.S.M.S., 1992. Chemical capture of wild elephants and their translocation carried out in Karnataka state. In: Silas,E.G., Nair,M.K., and Nirmalan,G. (Editors), The Asian Elephant: Ecology, Biology, Diseases, Conservation and Management (Proceedings of the National Symposium on the Asian Elephant held at the Kerala Agricultural University, Trichur, India, January 1989). Kerala Agricultural University, Trichur, India pp. 107-112

l) Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K., 1992. Tranquilization and translocation of elephants. In: Silas,E.G., Nair,M.K., and Nirmalan,G. (Editors), The Asian Elephant: Ecology, Biology, Diseases, Conservation and Management (Proceedings of the National Symposium on the Asian Elephant held at the Kerala Agricultural University, Trichur, India, January 1989). Kerala Agricultural University, Trichur, India pp. 176  Abstract: (Full text):  A total of 140 captive rogue tuskers were successfully tranquilized and translocated during the period for April 1979 to December 1988.  Most of the animals were those used in festivals or in lumbering operations.  The requests handled by the tranquilization team were of urgent nature and no kunkies were available to assist the operation.  Hence the animals were tranquilized retaining certain amount of ambulatory property and not allowing the animals to assume recumbency.  After ascertaining complete sedation which took nearly 45 minutes after darting the limbs were noosed were polypropylene ropes and pulled by volunteers numbering from 15 to 20 on each rope on the forelimb.  The animals were also given oral and percussion commands and coaxed to move.  Animals could be moved on an average of 100 meters to be tied in a safe tethering area.  The chemical used at first was nicotine and was subsequently replaced by xylazine alone or its combinations for better margin of safety.  The combination of xylazine with acepromazine and ketamine was discarded due to photosensitization of elephants and subsequent skin lesions on the back of the elephants. The dose of xylazine varied from 100 to 120 mg/ton body weight.  The data show that 85% of the cases were attended while the bulls were in premusth or post-musth period indicating lack of sufficient precaution taken by the mahouts.

m) Lahiri-Choudhury,D.K., 1992. Translocation of wild elephants. In: Silas,E.G., Nair,M.K., and Nirmalan,G. (Editors), The Asian Elephant: Ecology, Biology, Diseases, Conservation and Management (Proceedings of the National Symposium on the Asian Elephant held at the Kerala Agricultural University, Trichur, India, January 1989). Kerala Agricultural University, Trichur, India pp. 91-106

n) Nayar,K.N.M., Radhakrishnan,K., Chandrasekharan,K., Cheeran,J.V., Ravindran,S., and George,P.O., 1992. Anaesthesia for surgical manipulations in the elephant. In: Silas,E.G., Nair,M.K., and Nirmalan,G. (Editors), The Asian Elephant: Ecology, Biology, Diseases, Conservation and Management (Proceedings of the National Symposium on the Asian Elephant held at the Kerala Agricultural University, Trichur, India, January 1989). Kerala Agricultural University, Trichur, India pp. 156-158  Abstract: Anaesthesia using chloral hydrate, thiopentone sodium, xylazine and ketamine was induced in ten elephants. The effects, duration of induction and anaesthesia were recorded. Post anaesthesia complications were not encountered in any of the animals. Surgical manipulations could be carried out under anaesthesia induced with these drugs.

o) Pathak,S.C. 1991. Xylazine-ketamine anesthesia in Indian elephant (Elephas maximus indicus). – trial on 53 clinical cases. International Seminar on Veterinary Medicine in Wild and Captive Animals, Nov. 8-10, Bangalore, India. Pages: 21  Abstract: Veterinarians are often required to attend and undertake surgery on elephants.  Unless the animal is deeply sedated or anesthetized certain works become impractical.  Xylazine has proved to be a good sedative and analgesic in elephants.  This drug is not freely available in India and is costly.  The drug is usually used by intramuscular route but to reduce the dose it has been used intravenously.  Intravenous use may be risky for its bradycardia effect and fall in cardiac output.  Ketamine, on the other hand, has no depressant effect on the cardiovascular and respiratory system but produces muscular tremor and stiffness of the skeletal muscle.  Combination of Xylazine and Ketamine minimizes the undesirable aspects of both the drugs.  A mixture containing 100-150 mg xylazine and 50-100 mg ketamine injected intravascularly to the laterally recumbent elephant produced quick, safe and dependable analgesia, anesthesia, and muscular relaxation.  Surgical operations like tusk extraction, bullet extraction, umbilical and pleural herniorraphy, trunk injury, extensive wound repair, etc. were performed in 53 elephants.  Recovery followed without excitement and untoward effect based on the observations of this trial on clinical cases, combination of Xylazine and Ketamine is recommended in elephant.

p) Pathak,S.C., Saikia,J., Lahon,D.K., Deka,K.N., Barua,S.K., Dewan,J.N., and Vety,A.H. 1990. Attempted ventral herniorrhaphy in an Asian elephant (Elephas maximus) using xylazine sedation. Journal of Zoo and Wildlife Medicine 21:(2):234-235  Abstract: Ventral herniorrhaphy in a female Asian elephant (Elephas maximus) under xylazine hydrochloride sedation was attempted.  A dose of 0.16 mg/kg body weight was adequate to produce sedation, analgesia, and muscle relaxation for the procedure.  The postoperative management of the surgical wound was difficult and resulted in the failure of the surgery.

q) Welsch,B., Jacobson,E.R., Kollias,G.V., Kramer,L., Gardner,H., and Page,C.D. 1989. Tusk extraction in the African elephant (Loxodonta africana). Journal of Zoo and Wildlife Medicine 20:(4):446-453   Abstract:Unilateral dentoalveolar abscesses and/or tusk fractures were identified and tusk extractions performed in seven 3.5-21-yr-old African elephants (Loxodonta africana) of both sexes weighing 650-3,000 kg.  Following immobilization with etorphine hydrochloride or carfentanil citrate, six of seven elephants were intubated and maintained on a 1-1.5% halothane in oxygen mixture; one elephant was maintained in lateral recumbency by multiple i.v. injections of etorphine.  All elephants were positioned with the affected tusk up.  For one elephant, two surgical procedures were required to remove the tusk.  In six of seven elephants, the tusks were sectioned transversely and the tusk wall thinned by enlarging the pulp cavity with carbide burs.  In those tusks with remaining pulp, the pulp was removed with stainless steel rods and hooks.  Next, the tusk was sectioned longitudinally into three or four segments using a wood saw within the pulp chamber.  bone gouges, osteotomes, and a mallet were used to free the outer epithelial and alveolar attachments from the tusk.  Starting with the smallest segment, the sections were removed using long screwdriver-shaped stainless steel rods.  The alveolar chamber was then periodically flushed postsurgically with a dilute organic iodine solution.  For six of seven elephants, complete granulation of the alveolar chamber was evident by 4 mo postsurgery; the seventh elephant showed partial healing with granulation tissue at 2 mo following surgery.

r) Heard,D.J., Kollias,G.V., Webb,A.I., Jacobson,E.R., and Brock,K.A. 1988.  Use of halothane to maintain anesthesia induced with etorphine in juvenile African elephants.  Journal of the American Veterinary Medical Association 193:254-256  Excerpts: Sixteen 3- to 5-year-old African elephants were anesthetized one or more times for a total of 27 diagnostic and surgical procedures.  Xylazine (0.1 ± 0.04 mg/kg of body weight, mean ± SD) and ketamine (0.6 ± 0.13 mg/kg) administered IM induced good chemical restraint in standing juvenile elephants during a 45-minute transport period before administration of general anesthesia.  After IM or IV administration of etorphine (1.9 ± 0.56 micrograms/kg), the mean time to lateral recumbency was 20 ± 6.6 and 3 ± 0.0 minutes, respectively.  The mean heart rate, systolic blood pressure, and respiration rate during all procedures was 50 ± 12 beats/min, 106 ± 19 mm of Hg, and 10 ± 3 breaths/min, respectively. 

Cardiac arrhythmias were detected during 2 procedures.  In one elephant paroxysmal ventricular tachycardia was detected and the procedure terminated when the arrhythmia failed to stabilize after multiple doses of lidocaine (1 mg/kg, IV).  In another elephant, second degree atrioventricular block returned to normal sinus rhythm after IV administration of atropine (0.04 mg/kg).

In one elephant, low mean blood pressure (54 mm of Hg) responded to reduction in halothane (vaporizer setting 1 to 0.75%) and slow infusion of dobutamine HCl ((250 mg/1,000 ml) given to effect. The systolic blood pressure increased to 90 mm of Hg and remained high with a continuous infusion of dobutamine (5 µg/kg/min).

Immediately after induction in another elephant, profound respiratory depression (< 1 breath / minute) and palpably weak arterial pulse were identified.  Intravenous administration of diprenorphine at half the recommended reversal dose resulted in improvement of respiration and palpable arterial pulse, without the elephant developing signs of complete anesthetic reversal.  

Alterations in systolic blood pressure, ear flapping, and trunk muscle tone were useful for monitoring depth of anesthesia.  Results indicated that halothane in oxygen was effective for maintenance of surgical anesthesia in juvenile African elephants after induction with etorphine.  Note: A correction appeared in a later volume 193(6): p.721.

s) Allen,J.L. 1986. Use of tolazoline as an antagonist to xylazine-ketamine-induced immobilization in African elephants. American Journal of Veterinary Research 47:(4):781-783  Abstract:  A group of 15 African elephants (Loxodonta africana) were immobilized with a combination of xylazine (0.2 mg/kg of body weight, IM) and ketamine (1 to 1.5 mg/kg of body weight, IM). Ten of the African elephants were allowed to remain recumbent for 30 minutes and the remaining 5 elephants, for 45 minutes before they were given tolazoline (0.5 mg/kg of body weight, IV). For the group of 15, the mean induction time (the time required from injection of the xylazine-ketamine combination until onset of recumbency) was 14.2 ± 4.35 minutes (mean ± SD), and standing time (the time required from the tolazoline injection until the elephant stood without stimulation or assistance) was 2.8 ± 0.68 minutes. All of the elephants were physically stimulated (by pushing, slapping, shouting) before they were given tolazoline, and none could be aroused. After tolazoline was given and the elephant was aroused, relapses to recumbency did not occur. Recovery was characterized by mild somnolence in an otherwise alert and responsive animal. Failure (no arousal) rates were 0% (95% confidence interval, 0 to 0.3085) for elephants given tolazoline after 30 minutes of recumbency and 100% for elephants that were not given tolazoline. There was no significant (P less than 0.05) difference in standing time 30 or 45 minutes after tolazoline injection.

t) Schmidt,M.J., 1986. Proboscidea (Elephants). In: Fowler,M.E. (Editor), Zoo and wild animal medicine. W.B. Saunders, Philadelphia,PA, USA pp. 884-923

u) Jacobson,E.R., Allen,J., Martin,H., and Kollias,G.V. 1985. Effects of yohimbine on combined xylazine-ketamine-induced sedation and immobilization in juvenile African elephants. Journal of the American Veterinary Medical Association 187:(11):1195-1198  Abstract: Twenty-two juvenile African elephants were given a combination of xylazine (mean +/- SD = 0.14 +/- 0.03 mg/kg of body weight) and ketamine (1.14 +/- 0.21 mg/kg) as a single IM injection; one elephant was immobilized twice, 77 days apart. After injection, 14 elephants were immobilized, 4 were sedated deeply, 2 were sedated moderately, and 2 were sedated minimally. Immobilized elephants had a mean immobilization time of 11.6 +/- 6.9 minutes. At the conclusion of a variety of clinical procedures, 12 of the 14 elephants immobilized with a single dose combination of xylazine and ketamine were given yohimbine (0.13 +/- 0.03 mg/kg) IV, and the remaining 2 elephants were allowed to recover spontaneously; the elephants given yohimbine had a mean standing time of 2.4 +/- 1.1 minutes. Of the 8 sedated elephants, 5 were given an additional dose of combined xylazine (0.08 +/- 0.03 mg/kg), and ketamine (0.61 +/- 0.19 mg/kg) IM, and 1 elephant was given ketamine (0.47 mg/kg) IV. After injection, 4 of the 8 elephants were recumbent laterally within 17 minutes and 2 remained standing, under deep sedation. Seven of the 8 elephants were given yohimbine (0.13 +/- 0.03 mg/kg) IV; all were ambulatory in 2 minutes. Results indicated that yohimbine may be useful in controlling duration of xylazine-ketamine sedation and immobilization in juvenile African elephants.

v) Schmidt,M.J. 1983. Antagonism of xylazine sedation by yohimbine and 4-aminopyridine in an adult Asian elephant (Elephas maximus). Journal of Zoo Animal Medicine 14:94-97   Abstract: Heavy xylazine sedation was successfully antagonized by intravenous injection of yohimbine and 4-aminopyridine (4-AP) in an adult female Asian elephant (Elephas maximus) prior to euthanasia.  A total xylazine dose of 1,200 mg intramuscularly plus 600 mg intravenously (approximately 0.33 mg/kg body weight) was given resulting in heavy sedation.  After 50 minutes of deep recumbent sedation, 425 mg yohimbine and 1,000 mg of 4-AP were administered intravenously.  Xylazine sedation was antagonized and the elephant was up and walking around within 5 minutes of antagonist administration.  The elephant remained standing for other 3 hours; at which point euthanasia was performed.

w) Bongso,T.A. 1980. Sedation of the Asian elephant with xylazine. Journal of the American Veterinary Medical Association 177:(9):783  Abstract: (Full text): Doses of 100 to 300 mg of a 10% solution of xylazine satisfactorily sedated 6 elephants ranging from 150 to 255 cm shoulder height.  At these dosages, all animals were sedated in the standing position.  The time taken to produce the initial signs of sedation ranged from 10+4 to 20+4 minutes, and the effects lasted from 60+8 to 100+15 minutes.  The time taken from injection to complete recovery ranged from 360+31 to 540+21 minutes.  Recovery was uncomplicated.  Repeated administration of as much as 7 injections per animal at intervals of 3 to 4 days had no adverse effects.  Disturbances during induction delayed the onset of action of the drug –also see T.A. Bongso in Vet Rec, 105, (November 10, 1979): 442.

See also:

Sharma S.P. 1997.  Surgical treatment of gunshot wounds under xylazine and ketamine anaesthesia in an elephant: clinical case report. Indian Veterinary Journal 74:(11):973-974

Aik,S.S. 1992. Preliminary observations on the training of Burmese elephants using xylazine. New Zealand Veterinary Journal 40:(2):81-84  Abstract: A traditional elephant training method was chosen to be modified by the use of xylazine as a sedative and muscle relaxant. Three elephant calves with different degrees of tameness were trained using xylazine. The drug was helpful in the training process. Xylazine made restraint of the elephants much easier and safer. During training, repeated doses of xylazine were used to prevent beatings, the wounds worsening and to pacify the elephants. The tamest elephant calf was punished less and took less time to be trained than the others. It is concluded that it is important to play with elephant calves to win their acceptance of man.

Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K., 1992. Transportation of elephants by rail. In: Silas,E.G., Nair,M.K., and Nirmalan,G. (Editors), The Asian Elephant: Ecology, Biology, Diseases, Conservation and Management (Proceedings of the National Symposium on the Asian Elephant held at the Kerala Agricultural University, Trichur, India, January 1989). Kerala Agricultural University, Trichur, India pp. 120-12

Lance,W.R. 1991. New pharmaceutical tools for the 1990’s. Proceedings of the American Association of Zoo Veterinarians 354-359

Morton,D.J. and Kock,M.D. 1991. Stability of hyaluronidase in solution with etorphine and xylazine. J.Zoo and Wildlife Medicine 22:(3):345-347  Abstract: During capture of free-living wildlife, stress is potentially the greatest problem encountered. For this reason, reduction in induction time during immobilization is of paramount importance. Hyaluronidase reduces induction times, although no reports have assessed stability of the enzyme in drug mixtures used for chemical capture. This report presents information on the stability of hyaluronidase in combination with etorphine and xylazine, one of the most common drug mixtures used in chemical immobilization of wildlife. Hyaluronidase activity remains high for at least 48 hr, provided storage temperatures can be maintained at less than or equal to 30º C. Storage at greater than or equal to 40ºC is associated with rapid loss of enzyme activity in the mixture.

Jacobson,E.R.  1988. Chemical restraint and anesthesia of elephants. Proc.Ann.Elephant Workshop 9. Pages: 112-119

Heard,D.J., Jacobson,E.R., and Brock,K.A. 1986. Effects of oxygen supplementation on blood gas values in chemically restrained juvenile African elephants.  Journal of the American Veterinary Medical Association 189:(9):1071-1074  Abstract: Arterial oxygen and carbon dioxide tensions were determined in sedated immature African elephants and in elephants immobilized with etorphine hydrochloride or with an etorphine-ketamine combination.  For manipulative and surgical procedures, the Hudson demand value was used for oxygen supplementation during 6 procedures, and insufflation was used during 2 procedures.  The Hudson demand value was more effective than insufflation in sustaining adequate arterial oxygenation.

Kock,N., Kock,M., Arif,A., and Wahid,M.N.S.A.  1984. Immobilization techniques and complications associated with a bull Indian elephant (Elephas maximus indicus) during musth. Proc.Am.Assoc.Zoo Vet. Pages: 68-74   Summary: An Asian bull in musth (estimated weight 4500 kg) was immobilized six times. Three drugs were used either alone or in combination.  A mixture of etorphine and acetylpromazine (Immobilon^®)  was used effectively on three occasions at an average dose of 0.48 ml/1000kg. Xylazine (0.1 mg/kg)  used alone was ineffective on two occasions and was supplemented with Immobilon. When Immobilon was used after the xylazine, the dose was reduced to 0.2 ml / 1000 kg. (Kock et.al. 1984). (Author’s (Mikota) note: xylazine dose given as mg/kg and etorphine dose given as ml in original article).

 

Jacob,V., Cheeran,K., Chandrasekharan,K., and Radhakrishnan,K.  1983. Immobilization of elephant in musth using xylazine hydrochloride.  7th Annual Symposium of the Indian Society of Veterinary Surgeons. Pages: 62

Fowler,M.E. 1981. Problems with immobilizing and anesthetizing elephants. Proceedings of the American Association of Zoo Veterinarians 87-91

Bongso,T.A. 1980. Use of xylazine for the transport of elephants by air. Vet Rec 107:(21):492

Schmidt,M.J.  1975. The use of xylazine in captive Asian elephants. Proc.Am.Assoc.Zoo Vet. Pages: 1-11

Schmidt,M.J. 1975. A preliminary report on the use of rompun in captive Asian elephants. Journal of Zoo Animal Medicine 6:13-21

Monitoring Parameters – 1) Level of anesthesia/analgesia; 2) Respiratory function; car­diovascular status (rate, rhythm, BP if possible); 3) Hydration status if polyuria present

 

Client Information – Xylazine should only be used by individuals familiar with its use.

 

Dosage Forms/Preparations/FDA Approval Status/Withholding Times –

Veterinary-Approved Products:

Rompun®  (Bayer) Gemini®  (Butler); AnaSed®  (Lloyd);Sedazine® (Fort Dodge)  (Rx)  Approved for use (depending on strength) in dogs, cats, horses, deer, and elk.

 

While xyalzine is not approved for use in cattle in the USA, at labeled doses in Canada it reportedly has been assigned withdrawal times of 3 days for meat and 48 hours for milk. FARAD has reportedly suggested a withdrawal of 7 days for meat and 72 hours for milk for extra-label use in the USA.

 

Human-Approved Products: None