REVERSIBLE ANESTHESIA OF SOUTHEAST ASIAN PRIMATES WITH

MEDETOMIDINE, ZOLAZEPAM, AND TILETAMINE

Author(s): Åsa FahlmanD.V.M., Vet.Med.Lic., Edwin J. BosiD.V.M., M.Phil., Görel NymanD.V.M.,
Ph.D., Dipl. E.C.V.A.
Source: Journal of Zoo and Wildlife Medicine, 37(4):558-561. 2006.
Published By: American Association of Zoo Veterinarians
DOI: 10.1638/05-044.1
URL: http://www.bioone.org/doi/full/10.1638/05-044.1

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 Journal of Zoo and Wildlife Medicine 37(4): 558–561, 2006
Copyright 2006 by American Association of Zoo Veterinarians

REVERSIBLE ANESTHESIA OF SOUTHEAST ASIAN PRIMATES

WITH MEDETOMIDINE, ZOLAZEPAM, AND TILETAMINE

Åsa Fahlman, D.V.M., Vet.Med.Lic., Edwin J. Bosi, D.V.M., M.Phil., and Görel Nyman, D.V.M.,
Ph.D., Dipl. E.C.V.A.

Abstract: Medetomidine (0.02–0.06 mg/kg) in combination with zolazepam-tiletamine (0.8–2.3 mg/kg) were eval-
uated for reversible anesthesia in four species of Southeast Asian primates: Bornean orangutan (Pongo pygmaeus
pygmaeus), Bornean gibbon (Hylobates muelleri), long-tailed macaque (Macaca fascicularis), and pig-tailed macaque
(Macaca nemestrina). Twenty-three anesthetic procedures of captive-held and free-ranging primates were studied in
Sabah, Malaysia. The induction was smooth and rapid. Respiratory and heart rates were stable throughout anesthesia,
whereas body temperature and systolic arterial blood pressure decreased significantly. Atipamezole at five times the
medetomidine dose effectively reversed anesthesia, with first signs of recovery within 3–27 min.
Key words: Immobilization, medetomidine, atipamezole, orangutan, gibbon, macaque.

BRIEF COMMUNICATION fascicularis), and pig-tailed macaque (Macaca ne-

Bornean orangutans (Pongo pygmaeus pyg-
maeus) that are stranded in forest fragments within
the state of Sabah, Malaysia, are captured for trans-
location to protected habitat.1 At the Sepilok Orang-
utan Rehabilitation Center, orphaned and injured
primates are raised and treated before release into
the wild. Health examination and treatment of cap-
tive-held primates, as well as translocations in the
field, require safe and effective immobilization pro-
cedures. Reversible immobilization is desirable, be-
cause smooth and rapid reversal minimizes the risk
of injury during the recovery period. When zola-
zepam-tiletamine (ZT) is used for immobilization
of free-ranging orangutans, the induction time is
shorter and the drug volume smaller than when us-
ing xylazine-ketamine.4 In a variety of species,
when medetomidine (M) is combined with ZT, the
dose of ZT can be reduced by at least 50%, and
reversal with the alpha2-antagonist atipamezole re-
sults in a rapid and smooth recovery.5 We evaluated
the anesthetic and cardiorespiratory effects of MZT
and anesthetic reversal with atipamezole in South-
east Asian primates.
Four species of Southeast Asian primates were
studied: Bornean orangutan, Bornean gibbon (Hy-
lobates muelleri), long-tailed macaque (Macaca
From the Department of Clinical Sciences, Swedish
University of Agricultural Sciences, P.O. Box 7018, SE-
750 07 Uppsala, Sweden (Fahlman, Nyman); and the Se-
pilok Orangutan Rehabilitation Center, Wildlife Depart-
ment Sabah, W.D.T. 200, 90009 Sandakan, Sabah, Malay-
sia (Bosi). Present addresses (Fahlman): Department of
Wildlife, Fish, and Environment, National Veterinary In-
stitute of Sweden, SE-751 89 Uppsala, Sweden; (Bosi):
P.O. Box 39, 89507 Penampang, Sabah, Malaysia. Cor-
respondence should be directed to Dr. Fahlman.
mestrina) (Table 1). Eighteen animals (American
Society of Anesthesiologists physical status cate-
gory I or II) were anesthetized for 23 procedures
including physical examination, intradermal tuber-
culin testing, skin tattooing, blood sampling, wound
treatment, and translocation. All were adults except
for three orangutans (two adolescents and one in-
fant). Captive-held animals were fasted for 12–18
hr before drug administration. Medetomidine
(Domitor威, 1 mg/ml, Orion Pharma, 02200 Espoo,
Finland) in combination with zolazepam and tile-
tamine (Zoletil威100, 100 mg/ml, VIRBAC S.A.,
06516 Carros, France) were injected i.m. by hand-
held syringe to captive-held animals that were
physically restrained, whereas free-ranging orang-
utans were darted with MZT while in trees (Telin-
ject Vario 4V Rifle, Telinject USA Inc., Saugus,
California 91350, USA). Initially, four captive-held
primates were hand-injected with medetomidine,
followed by ZT 13–49 min later, but for the re-
mainder of the procedures, medetomidine and ZT
were mixed in the same syringe prior to adminis-
tration. All animals were weighed during anesthesia
and the actual drug doses were calculated (Table
1). When anesthesia needed prolongation, supple-
mental injections of ZT were given i.m. at half the
initial dose. For reversal, atipamezole (Antisedan威,
5 mg/ml, Orion Pharma) was injected i.m. at five
times the medetomidine dose.
Times from administration of MZT to first sign
of sedation, recumbency (induction time), and in-
jection of atipamezole were recorded. Times from
injection of atipamezole to first signs of recovery
and, if obvious, to full recovery were recorded also.
Respiratory rate was monitored by observation of
thorax, and heart rate was determined by cardiac
auscultation. Mucous membrane color, capillary re-

558
 FAHLMAN ET AL.—REVERSIBLE PRIMATE ANESTHESIA 559

Table 1. Animal data and doses of medetomidine (MED), zolazepam-tiletamine (ZT), and atipamezole (ATI) in a
study of reversible anesthesia of Southeast Asian primates in Malaysia.

Mean doses (range)

Body
Sex weight Number of MED ZT ATI
Species n (M/F)a (kg) proceduresb (␮g/kg) (mg/kg) (mg/kg)

Bornean orangutan 12 (4/8) 3.9–45.5 Captive, 13 20 1.1 0.1

(18–23) (0.9–1.3)
20.0–26.0 Free-ranging, 3 23 1.3 0.1
(19–25) (1.2–1.3)
Bornean gibbon 2 (–/2) 2.9–3.0 Captive, 2 20c 0.9 0.1
(0.8–0.9)
Long-tailed macaque 2 (2/–) 2.6–3.4 Captive, 3 42 1.5 0.2
(23–52) (0.9–1.9) (0.1–0.3)
Pig-tailed macaque 2 (2/–) 2.2–3.7 Captive, 2 60 2.0 0.3
(55–64) (1.7–2.3)
a
n ⫽ number of animals; M ⫽ male; F ⫽ female.
b
A total of 23 anesthetic procedures involving 18 individual primates was evaluated. Twenty procedures involved temporarily captive-
held primates at the Sepilok Orangutan Rehabilitation Center, and three procedures were immobilizations in the field for translocation
of free-ranging orangutans within the state of Sabah, Malaysia.
c
Actual body weight was known before anesthesia of both gibbons, which were given 20 ␮g/kg medetomidine (no range).

fill time, and presence of palpebral reflex were
monitored. Body temperature was measured using
a rectal thermometer and a tympanic membrane
thermometer (Braun ThermoScan Instant Ther-
mometer IRT 1020, Thermoscan Inc., San Diego,
California 92121, USA). Hemoglobin oxygen sat-
uration (SpO2) was monitored by pulse oximetry
(Engström Eos Pulse Oximeter, Gambro Engström
AB, Bromma, Sweden). Systolic arterial blood
pressure was measured oscillometrically in adult
orangutans only, with a 140-mm cuff placed over
the left brachial artery (Omron Digital Blood Pres-
sure Monitor Model HEM-400 C, Omron Corp.,
Tokyo 105, Japan). Ambient temperature ranged
from 30–33⬚C.
In all four species of primates, MZT rapidly in-
duced immobilization with good muscle relaxation.
The induction period was smooth and the most
common signs of sedation were drowsiness and
lowering of the head. First sign of sedation was
seen within 1–3 min and recumbency was seen
within 1–7 min of injection. All individuals, except
one free-ranging orangutan, became completely im-
mobilized after the initial MZT injection and could
be handled safely within 2 min after recumbency.
In contrast, the four animals that first received med-
etomidine alone became only lightly sedated and
were aroused easily by noise or manipulation; sub-
sequent injection of ZT rapidly produced complete
immobilization.
The combination of MZT resulted in a small
drug volume of less than 1.5 ml, which is favorable
for remote dart injection. When darting two of the
three free-ranging orangutans, the induction was
excellent: during descent from the trees, the ani-
mals remained able to grip branches and to lower
themselves, which made the fall gradual with less
risk for injury. In comparison, orangutans darted
with ZT alone at 3 mg/kg quickly become com-
pletely immobilized and fall unconscious from the
tree (E. J. Bosi and E. Tambing, pers. comm.). The
third free-ranging orangutan in our study, an adult
female carrying an infant, required an additional
dose of ZT (1.2 mg/kg i.m.) to induce complete
immobilization. Once recumbent, it had developed
an elevated rectal temperature (40.0⬚C) and tachy-
pnea followed by apnea, which probably was due
to capture stress and hyperthermia or an adverse
drug effect. Spontaneous ventilation returned after
resuscitation and the orangutan recovered without
further problems.
In captive-held orangutans, respiratory and heart
rates were stable throughout anesthesia (Table 2),
whereas body temperature and systolic arterial
blood pressure decreased significantly (P ⬍ 0.05,
repeated measures analysis of variance, Procedure
Mixed, SAS威 System 9.1, SAS Institute Inc., Cary,
North Carolina 27513, USA). Systolic arterial
blood pressure decreased below 80 mmHg in four
orangutans. A decrease in blood pressure associated
with medetomidine use has been reported in other
primate species.3 The pulse oximeter failed to de-
termine oxygen saturation in several animals and
occasional measurements were below 90%. Low
SpO2 values may indicate hypoxemia due to im-
paired pulmonary gas exchange or hypoventilation.
560 JOURNAL OF ZOO AND WILDLIFE MEDICINE

Table 2. Physiological parameters for Bornean orangutans anesthetized with medetomidine-zolazepam-tiletamine

at the Sepilok Orangutan Rehabilitation Center, Malaysia.a

Parameter 0–10 min 11–20 min 21–30 min 31–40 min

RR (breaths/min) 41 ⫾ 11 47 ⫾ 23 48 ⫾ 25 38 ⫾ 10
(24–60) (26–112) (22–120) (24–54)
n ⫽ 10 n ⫽ 12 n ⫽ 11 n⫽8
HR (beats/min) 84 ⫾ 15 90 ⫾ 13 88 ⫾ 13 85 ⫾ 13
(64–114) (68–112) (64–104) (66–106)
n ⫽ 11 n ⫽ 12 n ⫽ 10 n⫽8
Rectal temp. (⬚C) 37.2 ⫾ 0.7 37.2 ⫾ 0.8 36.8 ⫾ 1.1bc 36.1 ⫾ 0.6bc
(35.7–38.4) (35.4–38.3) (34.7–38.6) (35.0–36.9)
n⫽9 n ⫽ 11 n⫽9 n⫽6
Tympanic temp. (⬚C) 37.1 ⫾ 0.8 37.0 ⫾ 0.8 36.7 ⫾ 1.0bc 36.4 ⫾ 1.3bc
(35.4–38.0) (35.5–38.4) (34.8–38.3) (34.7–38.6)
n⫽8 n⫽9 n⫽9 n⫽6
SAP (mmHg) 125 ⫾ 12 106 ⫾ 22b 94 ⫾ 14b 92 ⫾ 11bc
(111–148) (74–134) (71–118) (80–111)
n⫽5 n⫽6 n⫽7 n⫽5
SpO2 (%) 88 ⫾ 0 92 ⫾ 1.3 92 ⫾ 1.0 92 ⫾ 2.0
(88–88) (90–93) (82–93) (89–94)
n⫽2 n⫽4 n⫽4 n⫽4
a
RR ⫽ respiratory rate; HR ⫽ heart rate; SpO2 ⫽ pulse oximetry derived hemoglobin oxygen saturation; SAP ⫽ systolic arterial
blood pressure measured noninvasively. Values expressed as mean ⫾ SD (range).
b
Significant difference from the 0–10 min value.
c
Significant difference from the 11–20 min value.

Although low SpO2 values also may be an artifact
due to peripheral vasoconstriction induced by a
high dose of alpha2-agonists, our medetomidine
doses were low. Mucous membranes were pink and
capillary refill times were ⬍2 sec in all animals,
and the palpebral reflex was absent in all but four.
Rectal temperature decreased below 36⬚C in three
orangutans. Paired measurements of rectal and tym-
panic temperature were in good agreement (intra-
class correlation coefficient model 2 ⫽ 0.88). Tem-
perature measurement with the tympanic thermom-
eter was rapid and simple in adult and adolescent
orangutans, but in younger orangutans and the
smaller primate species the ear canal was too nar-
row. For accurate measurement the thermometer
needs to be in close contact with the tympanic
membrane, and thus, the ear canal conformation
can limit its use in different animals.2 Physiological
parameters in Bornean gibbons and long-tailed and
pig-tailed macaques ranged as follow: respiratory
rate 20–56 breaths per minute, heart rate 68–160
beats per minute, SpO2 88–99%, and rectal tem-
perature 37.0–40.1⬚C. Initially elevated rectal tem-
peratures probably developed because the smaller
species were physically restrained for drug admin-
istration. No animals experienced side effects such
as excessive salivation or vomiting.
During anesthesia, three captive-held orangutans
displayed voluntary movements 19–40 min after
initial administration of MZT and required two sup-
plemental doses of ZT. All three free-ranging
orangutans needed supplemental drug administra-
tion within 9–29 min of darting, because the im-
mobilization was incomplete in one animal and of
insufficient duration in the other two. The initial
MZT dose presumably could be higher to prevent
the need for additional drug administration, but fur-
ther study is needed.
Atipamezole was administered 23–54 min after
injection of MZT or the last additional dose of ZT.
The first signs of recovery were movements of the
head or the extremities 3–27 min after reversal. Re-
coveries were smooth and calm for orangutans, gib-
bons, and long-tailed macaques, whereas excite-
ment and muscle tremors were observed in the two
pig-tailed macaques. These adverse reactions could
be due to a tiletamine residual effect or an exces-
sive dose ratio of atipamezole relative to medetom-
idine. The two gibbons were fully recovered 11 and
20 min after reversal, respectively. Four orangutans
were fully recovered and nine recovered to being
only lightly sedated within 8–42 min after reversal.
Advantages of MZT at the doses used in this
study included rapid and smooth induction, good
 FAHLMAN ET AL.—REVERSIBLE PRIMATE ANESTHESIA
muscle relaxation, and stable respiratory and heart
rates. Body temperature should be monitored
throughout anesthesia to detect hyper- or hypother-
mia. Intravenous fluid could prevent development
of hypotension, and oxygen supplementation could
be beneficial if hypoxemia is present. The small
amount of ZT needed with medetomidine enabled
smooth anesthetic reversal with atipamezole in
three of the four species. The MZT combination
was promising for darting free-ranging orangutans,
because the drug volume was small, the gradual
descent from the trees reduced risk of injury during
the induction, and the anesthesia was reversible.
However, further investigation is needed to evaluate
physiologic effects and determine optimal MZT
doses for free-ranging orangutans.
Acknowledgments: We thank the personnel at the
Sepilok Orangutan Rehabilitation Center for their
excellent assistance during the immobilizations. We
also thank the International Office at the Swedish
University of Agricultural Sciences, Orion Pharma
561
Animal Health, and the Fredrika Bremer Associa-
tion for supporting this study.
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Received for publication 2 May 2005