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101
Journal of Zoo and Wildlife Medicine 33(2): 101–107, 2002
Copyright 2002 by American Association of Zoo Veterinarians
CARDIORESPIRATORY EFFECTS OF MEDETOMIDINE–
BUTORPHANOL, MEDETOMIDINE–BUTORPHANOL–DIAZEPAM,
AND MEDETOMIDINE–BUTORPHANOL–KETAMINE IN CAPTIVE
RED WOLVES (CANIS RUFUS)
R. Scott Larsen, D.V.M., M.S., Michael R. Loomis, M.A., D.V.M., Dipl. A.C.Z.M., Brian T. Kelly,
M.S., Kurt K. Sladky, M.S., D.V.M., Michael K. Stoskopf, D.V.M., Ph.D., Dipl. A.C.Z.M., and
William A. Horne D.V.M., Ph.D., Dipl. A.C.V.A.
Abstract: Safe, effective, and reversible immobilization protocols are essential for the management of free-ranging
red wolves (Canis rufus). Combinations using an
a
2
-adrenoceptor agonist and ketamine have been shown to be effective
for immobilization but are not reversible and can produce severe hypertension and prolonged or rough recoveries. To
minimize hypertension and provide reversibility, 24 red wolves were immobilized using three medetomidine–butor-
phanol (MB) combinations without the use of ketamine in the initial injection. All wolves were administered mede-
tomidine (0.04 mg/kg i.m.) and butorphanol (0.4 mg/kg i.m.). Seven wolves received no other immobilization agents
(MB wolves), nine received diazepam (0.2 mg/kg i.v.) at the time they were instrumented (MBD wolves), and eight
received ketamine (1 mg/kg i.v.) 30 min after instrumentation (MBK30 wolves). Physiologic parameters were monitored
during immobilization. The heart rate was similar among the three groups for the first 30 min, and marked bradycardia
was noted in one wolf from each group. Hypertension was observed initially in all three groups but was resolved
within 10–30 min. The MBK30 wolves had significant elevations in heart rate and transient hypertension after intra-
venous ketamine administration. Most wolves had mild to moderate metabolic acidemia. Immobilizing drugs were
antagonized in all wolves with atipamezole (0.2 mg/kg i.m.) and naloxone (0.02 mg/kg i.m.). The medetomidine-
butorphanol-diazepam wolves were also given flumazenil (0.04 mg/kg i.v.). All wolves were standing within 12 min
and were fully recovered within 17 min. Medetomamine-butorphanol and MBD combinations provided effective and
reversible immobilization of red wolves without the sustained hypertension associated with the use of
a
2
-adrenoceptor
agonist–ketamine combinations. Delaying the administration of ketamine reduced its hypertensive effects.
Key words: Canis rufus, red wolf, medetomidine, butorphanol, immobilization, diazepam, ketamine, atipamezole,
naloxone, flumazenil.
INTRODUCTION
The red wolf (Canis rufus) is a critically endan-
gered species that was extirpated from the south-
eastern United States during the 20th century.
14
A
captive propagation and reintroduction program has
been undertaken to restore red wolves to a portion
of their former range.
14
Intensive management tech-
niques are necessary to monitor and maintain the
health of this free-ranging population. Consequent-
ly, many red wolves are immobilized on several
occasions during their lifetime, and some may be
From the Environmental Medicine Consortium, De-
partments of Clinical Sciences (Larsen, Loomis, Kelly,
Sladky, Stoskopf) and Anatomy, Physiological Sciences,
and Radiology (Horne), College of Veterinary Medicine,
North Carolina State University, 4700 Hillsborough
Street, Raleigh, North Carolina 27606, USA; the North
Carolina Zoological Park, Asheboro, North Carolina
27203, USA (Larsen, Loomis); and the United States Fish
and Wildlife Service, Alligator River National Wildlife
Refuge, Manteo, North Carolina 27954, USA (Kelly). Pre-
sent address (Kelly): P.O. Box 1306, Albuquerque, New
Mexico 87103, USA. Correspondence should be directed
to Dr. Horne.
immobilized many times in a year. A safe, effec-
tive, and rapidly reversible immobilization protocol
is essential for these procedures because many of
these animals are returned immediately to the wild.
For several years the United States Fish and
Wildlife Service (USFWS) has used a xylazine–ke-
tamine combination for immobilizing captive and
free-ranging red wolves. But rough and prolonged
recoveries have been a concern with the use of this
combination. Medetomidine is an
a
2
-adrenoceptor
agonist that is more potent and more highly
a
2
-re-
ceptor–selective than is xylazine.
19
It has been used
extensively for the immobilization of captive and
free-ranging carnivores
5
because it is rapidly and
completely antagonized by administration of ati-
pamezole, a specific
a
2
-adrenoceptor antagonist.
18
In 1998 an investigation was conducted with cap-
tive red wolves to evaluate the cardiorespiratory ef-
fects of xylazine–ketamine, medetomidine–keta-
mine, medetomidine–ketamine–acepromazine, and
medetomidine–ketamine–butorphanol.
17
Marked hyper-
tension was documented with each of the four drug
combinations. In humans, acute hypertensive events
of similar severity have caused cerebral infarction,
acute pulmonary edema, hypertensive encephalop-
102
JOURNAL OF ZOO AND WILDLIFE MEDICINE
athy, and acute congestive heart failure.
20
Pulsus al-
terans, a sign of imminent left ventricular failure,
has been observed in dogs with acute hypertension
after the combined administration of medetomidine
and atropine.
8
The additive hypertensive effects of medetomi-
dine and ketamine have been documented in do-
mestic dogs.
6
But medetomidine–butorphanol com-
binations have been shown to induce profound, re-
versible sedation in domestic dogs.
1
The purpose of
this investigation was to determine whether mede-
tomidine–butorphanol would provide safe, effec-
tive, and reversible immobilization of red wolves
while reducing acute hypertension. In this study the
sedative and cardiorespiratory effects of medetom-
idine–butorphanol were evaluated in the same pop-
ulation of captive red wolves as previously report-
ed.
17
Because of concerns that this combination
may not provide immobilization of adequate depth
or duration, medetomidine–butorphanol–diazepam
and medetomidine–butorphanol with delayed sup-
plementation of a low dosage of ketamine were also
investigated.
MATERIALS AND METHODS
Twenty-four adult, captive red wolves (12 male
and 12 female) were used in a between-subjects
experimental design, between November 1999 and
January 2000. The median age of wolves was 5 yr
(range
5
2–9 yr). Eight of the wolves were housed
at the North Carolina Zoological Park (NCZP), and
16 were housed at the USFWS, Alligator River Na-
tional Wildlife Refuge (ARNWR). The wolves
were housed outdoors in groups of one to four, with
access to den boxes. Average daily temperatures
from November to January for these regions are 3–
14
8
C (National Weather Service, http://
www.nws.mbay.net/normtemp.html). The wolves at
ARNWR were fed a commercial dry dog food diet
(Hill’s Pet Nutrition Inc., Topeka, Kansas 66601,
USA) and had access to water ad libitum. The
NCZP wolves were fed a commercial dry dog food
diet (Purina Mills, Inc., St. Louis, Missouri 63144,
USA) supplemented with Nebraska Canine Diet
(Nebraska Brand, North Platte, Nebraska 69103,
USA) and had access to water ad libitum.
Each wolf was randomly assigned to one of the
three experimental groups—medetomidine-butor-
phanol (MB), medetomidine-butorphanol-diazepam
(MBD), or medetomidine-butorphanol-ketamine
(MBK30). All wolves received an initial intramus-
cular injection of medetomidine hydrochloride
(Domitor, Pfizer Animal Health, Exton, Pennsyl-
vania 19341, USA; 0.04 mg/kg i.m.) and butorpha-
nol (Torbugesic, Fort Dodge Animal Health, Fort
Dodge, Iowa 50501, USA; 0.4 mg/kg). The MB
wolves (n
5
7) received no other immobilization
agents, the MBD wolves (n
5
9) received diazepam
(Valium, Hoffman-La Roche, Nutley, New Jersey
07110, USA; 0.2 mg/kg i.v.) at the time of instru-
mentation (T
5
0), and the MBK30 wolves (n
5
8) received ketamine hydrochloride (Ketaset, Fort
Dodge Animal Health, Fort Dodge, Iowa 50501,
USA; 1 mg/kg) 30 min after instrumentation (T
5
30).
The wolves were fasted for at least 24 hr before
immobilization but were allowed access to water.
The wolves were either hand-netted or confined to
a den box or canine transport kennel before drug
administration. Drug doses were based on estimates
of body weight. Actual body weights were mea-
sured at the end of each procedure, and absolute
dosages of immobilizing and reversal agents are re-
ported on the basis of these weights. Medetomidine
and butorphanol were combined in the same sy-
ringe and injected into the caudal hindlimb mus-
cles. The wolves were left undisturbed for 15 min
after injection (either the den box was closed or the
wolves’ eyes were covered with a towel).
Systolic, mean, and diastolic blood pressure were
determined oscillometrically 15 min after injection
with a cuff placed over the dorsal metatarsal artery
(Dinamap, Critikon, Tampa, Florida 33614, USA).
The cuff size (12–19 cm) was selected so that the
width was 40% of the circumference of the limb.
Wolves not fully immobilized at 15 min were left
undisturbed for an additional 5 min. The wolves
were then transported to a central processing area,
where recording instruments were applied. Initial
physiologic measurements (T
5
0) were recorded
within 3–5 min of the initial blood pressure mea-
surements. Measurements were then recorded every
10 min for 50 min. Body temperature was mea-
sured using a digital thermometer inserted into the
rectum. Heart rate and rhythm were monitored by
electrocardiography (Vet/ECG 2000, Heska-SDI,
Waukesha, Wisconsin 53186, USA). End-tidal CO
2
was measured using sidestream capnography (Vet/
Cap Plus 7100, Heska-SDI, Waukesha, Wisconsin
53186, USA), with the sampling port near the rima
glottis or within a naris. Respiratory rate was de-
termined by observing chest excursions and by cap-
nography. Indirect oxygen–hemoglobin saturation
(SpO
2
) was evaluated by pulse oximetry (Vet/Ox
4403, Heska-SDI, Waukesha, Wisconsin 53186,
USA), with the probe attached to the tongue or lip.
Blood gas determinations were done on samples
taken anaerobically from the femoral artery at T
5
0, 30, and 50 min. Arterial blood gas analysis
(PaO
2
, PaCO
2
, pH) was performed using a portable
103
LARSEN ET AL.—RED WOLF IMMOBILIZATION
clinical analyzer (iSTAT with G3
1
cartridge, Hes-
ka-SDI, Waukesha, Wisconsin 53186, USA). Blood
gas values were corrected for body temperature us-
ing the equations developed for humans.
2
An intra-
venous catheter was placed in the cephalic vein.
Procedures performed included annual health ex-
aminations, venous blood collection, vaccination,
dental prophylaxis, attachment of ear tags, and
placement or removal of radio collars. At the end
of the immobilizations (T
5
50 min), the catheters
were removed, the animals were transported to re-
covery areas, and antagonists were administered.
Wolves at ARNWR recovered in their pens, where-
as NCZP wolves recovered indoors in canine trans-
port kennels. To minimize postreversal trauma,
ARNWR wolves were gently restrained with a tow-
el over their eyes for 5 min after injection of an-
tagonists. All wolves received atipamezole hydro-
chloride (Antisedan, Pfizer Animal Health, Exton,
Pennsylvania 19341, USA; 0.2 mg/kg i.m.) and nal-
oxone (Naloxone HCl injection, Abbott Laborato-
ries, North Chicago, Illinois 60064, USA; 0.02 mg/
kg i.m.). Wolves in the MBD group also received
flumazenil (Romazicon, Hoffmann-La Roche Inc.,
Nutley, New Jersey 07110, USA; 0.04 mg/kg i.v.).
Times from administration of antagonists to stand-
ing and to complete recovery were recorded.
Physiologic measurements were not obtained for
all animals at all time points because of intentional
early reversals (two MB wolves and one MBD
wolf), one spontaneous reversal (MBD wolf), dif-
ficulties in obtaining arterial blood gas samples, and
difficulties with monitoring equipment. Statistical
analysis was performed using a Kruskall–Wallis
test (SAS, SAS Institute, Cary, North Carolina
27513, USA) to determine differences between
treatment group medians, at each time point, for all
physiologic data. Values of P
,
0.05 were consid-
ered statistically significant. Data are reported as
median values with ranges. The effects of the fluid
volumes administered were evaluated by determin-
ing correlation coefficients for each data set at each
time point (SAS, SAS Institute).
RESULTS
The first signs of drug effect were observed with-
in 5 min of medetomidine and butorphanol admin-
istration in all 24 wolves. The median (range) doses
administered were medetomidine 0.039 (0.033–
0.049) mg/kg and butorphanol 0.39 (0.33–0.49)
mg/kg. Of the 24 wolves, 21 could be moved from
their holding pens to the examination area within
15 min of drug administration. Two wolves re-
quired 20 min, and one wolf required 0.2 mg/kg
i.v. diazepam, for adequate sedation. This latter
wolf was included in the MBD group. Wolves in
the MBD group received a median diazepam dose
of 0.20 (0.19–0.24) mg/kg. Wolves in the MBK30
group received a median ketamine dose of 1.0
(0.92–1.05) mg/kg.
At the time of instrumentation (T
5
0) all wolves
were heavily sedated, were nonresponsive to exter-
nal stimuli, and had good muscle relaxation. By T
5
30, wolves in the MB and MBK30 groups were
noticeably less sedate and had less muscle relaxa-
tion than did wolves in the MBD group. During the
first 30 min, four of the seven MB wolves and six
of the eight MBK30 wolves exhibited at least one
of the following signs: muscle twitching, increased
jaw tone, slight head movement in response to loud
noises, ear manipulation, or dental scraping. These
signs were eliminated after ketamine administration
in all the MBK30 wolves. The MBD wolves were
essentially nonresponsive to stimuli until T
5
50,
except for one wolf that recovered spontaneously
at T
5
25.
Median body temperatures were elevated (39.6–
41.2
8
C; range
5
37.6–42.2
8
C) in all three groups
at T
5
0. Eight wolves (four MB wolves, two MBD
wolves, and two MBK30 wolves) had body tem-
peratures exceeding 40
8
C. These wolves were treat-
ed with ambient-temperature intravenous fluids,
isopropyl alcohol applied to the abdomen, footpads,
and ears, and abdominal cold packs. Temperatures
fell below 40
8
C within 30–40 min. Median tem-
peratures of all wolves declined steadily over time
and were not statistically different between groups
at any time. Median body temperatures for all
groups at T
5
50 were 37.7–38.6
8
C (range
5
36.4–
40.4
8
C). Two wolves immobilized on an unusual
day when ambient temperatures were
,
0
8
C devel-
oped body temperatures
,
36
8
C. These wolves were
reversed after 20 and 40 min, respectively.
The volume of fluids administered did not differ
significantly between the three groups (median
5
5.8 ml/kg). Small volumes (1–8 ml/kg) of lactated
Ringer’s solution were administered to 11 wolves
to maintain catheter patency. Hyperthermic animals
(T
.
40
8
C, N
5
9) received larger volumes (11–
26 ml/kg) of ambient-temperature fluids. There was
a significant correlation between volume of fluids
administered and body temperature at T
5
0, T
5
10, T
5
20, and T
5
30, but volume of fluids did
not show a statistically significant correlation to any
other physiologic parameter.
Heart rates were similar between all groups from
T
5
0toT
5
30 and until T
5
50 for the MB and
MBD groups. Median heart rates (Table 1) de-
creased over time in the MB and MBD groups. Two
MB wolves and one MBD wolf had heart rates be-
104
JOURNAL OF ZOO AND WILDLIFE MEDICINE
Table 1. Median (range) values for heart rate and respiratory rate in immobilized red wolves.
a
Time MB nMBD nMBK30 n
Heart rate (beats/minute)
0
10
20
30
40
50
76 (40–102)
60 (40–79)
63 (38–80)
57 (32–64)
50 (38–82)
56 (34–85)
7
6
6
5
5
5
66 (42–114)
56 (45–96)
57 (49–84)
60 (48–70)
59 (36–84)
59 (36–80)
7
8
7
6
6
6
77 (44–108)
76 (40–86)
64 (48–82)
72 (46–80)
80* (52–108)
88* (52–94)
8
8
8
7
8
7
Respiratory rate (breaths/minute)
0
10
20
30
40
50
25 (14–30)
26 (12–30)
21 (12–26)
12 (10–24)
19 (16–20)
22 (14–24)
5
5
5
5
3
3
16 (12–24)
17 (12–24)
14 (10–17)
16 (12–20)
16 (12–20)
16 (12–20)
7
8
6
6
6
6
20 (14–52)
16 (12–36)
18 (14–24)
17 (14–22)
18 (16–24)
16 (12–22)
8
7
8
8
8
7
a
MB, medetomidine–butorphanol; MBD, medetomidine–butorphanol–diazepam; MBK30, medetomidine–butorphanol–ketamine.
* Values for MBK30 are significantly different (P
,
0.05) from those of MB and MBD.
low 40 beats per minute at T
5
20, T
5
30, and T
5
40, respectively. Median heart rate increased in
the MBK30 group after ketamine administration
and differed significantly from both the MB group
and the MBD group at T
5
40 and T
5
50. Tran-
sient periods (5–10 min) of second-degree heart
block were seen in one MB wolf, two MBD
wolves, and one MBK30 wolf. Persistent second-
degree heart block was observed in two MBD
wolves.
Respiratory rates were similar between the three
groups at all time points. Median values ranged
from 12–26 breaths per minute (Table 1). One MB
wolf and one MBK wolf were panting at the be-
ginning of the procedure, and the MB wolf contin-
ued to pant until reversal agents were administered.
Systolic, mean, and diastolic arterial blood pres-
sure values were elevated when first measured but
decreased over time in all three groups (Table 2).
No statistically significant differences in blood-
pressure measurements were detected between
groups at any individual time point, but the lowest
(54 mm Hg) and the highest (170 mm Hg) mean
arterial pressures (MAPs) were observed in MBD
wolves. Two MBD wolves experienced transient
hypotension (MAP
,
60 mm Hg)
12
at T
5
10 and
T
5
30, respectively. Although 12 of the 24 wolves
were considered hypertensive (diastolic arterial
pressure
.
116 mm Hg)
15
when blood pressure was
first measured, only 2 of the 24 were hypertensive
at T
5
30. Blood pressure increased in MBK30
wolves after ketamine administration, with four of
the eight wolves experiencing hypertension, but the
median increase was not statistically significant.
No significant differences in PaO
2
, SpO
2
, PaCO
2
,
end-tidal CO
2
, arterial blood pH, or bicarbonate
were detected between groups at any time point.
Median PaO
2
values were
$
70 mm Hg throughout
the procedure. But at T
5
0, nine wolves (three
MB, two MBD, and four MBK30) had PaO
2
values
between 60 and 70 mm Hg, and one wolf (MB)
had a PaO
2
value of 51 mm Hg. PaO
2
values were
.
70 mm Hg for these 10 animals at subsequent
time points. Median SpO
2
was
$
93% (range
5
84–
99%) at all time points for all groups. Median
PaCO
2
values for all groups were 33–43 mm Hg
(range
5
25–50 mm Hg). Median end-tidal CO
2
values for all groups were 30–45 mm Hg (range
5
15–57 mm Hg). Median arterial blood pH values
were 7.26–7.34 (range
5
7.15–7.35). One wolf in
each of the MB and MBD groups had a pH value
below 7.20 at T
5
0, but pH increased above 7.20
for both these animals by T
5
30. Median bicar-
bonate values were 16–20 mM/L (range
5
13–24
mM/L).
For reversal, all wolves received a median dose
(range) of 0.19 (0.17–0.24) mg/kg atipamezole and
0.019 (0.017–0.024) mg/kg naloxone. MBD wolves
received a median dose of 0.041 (0.038–0.049) mg/
kg flumazenil. Of the 24 wolves, 21 recovered fully
within 10 min after administration of the reversal
agents. The three remaining wolves (one from each
group) were standing within 12 min and were fully
recovered at 17 min. Median time to standing and
median time to recovery did not differ among
groups. Median time to standing for all groups was
6 min, and median time to full recovery was 7 min.
MB and MBD wolves did not show postimmobil-
105
LARSEN ET AL.—RED WOLF IMMOBILIZATION
Table 2. Median (range) values for arterial blood pressure in immobilized red wolves.
a
Time MB nMBD nMBK30 n
Systolic arterial pressure (mmHg)
Initial
10
20
30
40
50
166 (124–182)
148 (114–172)
150 (88–162)
146 (61–162)
141 (117–150)
138 (123–152)
7
6
6
5
4
5
150 (98–194)
166 (82–201)
160 (88–183)
143 (80–172)
143 (96–162)
135 (116–178)
7
8
7
6
6
6
129 (90–188)
156 (114–176)
142 (127–168)
143 (128–166)
158 (140–162)
160 (138–165)
7
7
7
8
8
7
Mean arterial pressure (mmHg)
Initial
10
20
30
40
50
140 (94–156)
132 (78–142)
122 (76–130)
122 (61–128)
114 (83–128)
106 (96–126)
7
6
6
5
4
5
136 (74–170)
137 (54–149)
128 (76–140)
118 (58–151)
130 (70–142)
118 (106–146)
7
8
7
6
6
6
116 (66–158)
118 (94–148)
112 (92–146)
122 (112–131)
129 (105–148)
124 (106–142)
7
7
7
8
8
7
Diastolic arterial pressure (mmHg)
Initial
10
20
30
40
50
124 (74–140)
114 (60–120)
106 (58–114)
104 (39–114)
101 (64–112)
97 (86–116)
7
6
6
5
4
5
124 (56–161)
120 (48–132)
114 (60–122)
107 (42–138)
94 (64–122)
105 (78–132)
7
8
7
6
6
6
144 (52–144)
112 (76–132)
100 (82–130)
108 (98–115)
118 (92–130)
110 (78–128)
7
7
7
8
8
7
a
MB, medetomidine–butorphanol; MBD, medetomidine–butorphanol–diazepam; MBK30, medetomidine–butorphanol–ketamine.
ization drug effects, whereas MBK30 wolves ex-
hibited mild ataxia for 5–10 min after recovery.
Only one spontaneous recovery (one MBD wolf at
T
5
25) occurred before the end of the 50-min
procedure. One MBD wolf was found dead in its
den 5 days after being immobilized. At postmortem
examination this animal was found to have a gastric
dilatation and volvulus with signs of endotoxemia.
DISCUSSION
The results of this investigation demonstrate that
the combined effects of medetomidine and butor-
phanol provide a level of sedation and analgesia
that is adequate to perform many of the field tech-
niques required for red wolf population manage-
ment. Procedures such as physical examinations,
vaccination, blood collection, dental prophylaxis,
attachment of ear tags, and placement of radio col-
lars could readily be performed. The sedative ef-
fects of the MB combination lasted 30–50 min, and
the addition of either diazepam or ketamine pro-
longed the immobilization time and provided a
deeper plane of sedation.
Moderate to severe hyperthermia (T
.
40
8
C)
13
was evident in several of the wolves and was con-
sistent with other reports describing immobilization
of red and gray wolves.
4,17
High body temperatures
may have been caused by muscular exertion, phys-
ical restraint, stress, or drug interference with ther-
moregulatory mechanisms.
13
Hyperthermia re-
solved after treatment with intravenous fluids, iso-
propyl alcohol, and cold packs. Initial hyperthermia
is common in excited animals that must be pursued
for immobilization. It is important that mechanisms
for cooling animals be available when performing
immobilization procedures because hyperthermia
can cause marked hypotension, shock, severe car-
diac arrhythmias, and death.
13
Fluid administration was considerably variable
among the subjects, raising the possibility that
physiologic parameters might have been affected.
Administration of fluids can lower heart rate, in-
crease blood pressure, and improve tissue perfu-
sion.
16
Increased tissue perfusion may in turn alle-
viate metabolic acidosis, facilitating oxygen deliv-
ery and carbon dioxide transport. In this study the
volume of fluids administered did not have a sta-
tistically significant correlation with any physiolog-
ic parameter except for body temperature, so we do
not believe that fluids significantly affected the re-
sults.
Median heart rates of MB and MBD wolves were
lower than those previously reported for red wolves
immobilized with medetomidine–ketamine or xy-
lazine–ketamine,
17
although at most time points
they were within the range reported for healthy,
106
JOURNAL OF ZOO AND WILDLIFE MEDICINE
awake dogs (56–180 beats/min).
19
Heart rates were
highest in wolves receiving ketamine. Profound
bradycardia is commonly observed in domestic
dogs that receive
a
2
-adrenoreceptor agonists,
7
as a
result of a compensatory parasympathetic reflex to
peripheral vasoconstriction.
11
Such bradycardia oc-
curs independent of centrally mediated sedation and
analgesia and is best left untreated unless accom-
panied by hypotension. Although several wolves in
this study were bradycardic, they did not have con-
current hypotension. MAP remained above 60 mm
Hg in all but two MBD wolves that experienced
transient hypotension. Second-degree heart block
was detected in six of the wolves in this study, but
this condition is considered a common, benign,
parasympathetic reaction to
a
2
-adrenoreceptor ag-
onists.
7
Hypertension appears to be a common finding in
immobilized wild canids.
10,17
In the domestic dog,
hypertension has been defined as an indirect sys-
tolic arterial pressure greater than 202 mm Hg, an
indirect diastolic pressure greater than 116 mm Hg,
or both.
15
Normal resting blood pressure values are
not available for red wolves. But reports of median
blood pressure values in habituated gray wolves
(Canis lupus) suggest that they are similar to do-
mestic dogs,
10
so similar cutoff values for hyper-
tension would seem appropriate. Transient hyper-
tension was observed in immobilized wolves in this
study. Only 2 of the 24 wolves (8%) were consid-
ered hypertensive at T
5
30, in contrast to a pre-
vious study in which 23 out of 32 red wolves (72%)
immobilized with
a
2
-adrenoreceptor agonist–keta-
mine combinations had diastolic pressures that ex-
ceeded 116 mm Hg at T
5
30.
17
The transient hy-
pertension we observed was likely because of a
combination of elevated catecholamine levels and
transient drug effects. Without the sympathoadrenal
effects of ketamine, blood pressure decreased be-
low hypertensive levels over time. The MBK30
wolves experienced only a transient elevation in
blood pressure after ketamine administration, dem-
onstrating that, as in domestic dogs,
3
delaying the
administration of ketamine results in less severe hy-
pertension in wolves that have received
a
2
-adre-
noreceptor agonists.
Wolves in each of the three groups maintained
adequate ventilation and oxygenation. Respiratory
rates were within normal limits and were similar to
those previously reported for immobilized red
wolves, gray wolves, and domestic dogs.
4,9,17
Arte-
rial PaCO
2
and end-tidal CO
2
values were consis-
tent with each other and indicated adequate minute
ventilation. One wolf experienced transient hyp-
oxemia, suggesting that a source of 100% oxygen
should be available when using these drug combi-
nations. Median SpO
2
values for MB wolves were
higher than the mean values reported for the use of
medetomidine–butorphanol–ketamine (MBK) in
red wolves.
17
This indicates that, in addition to hav-
ing beneficial cardiovascular effects, MB also caus-
es less respiratory depression than does the MBK
combination.
Mild to moderate metabolic acidemia (low me-
dian bicarbonate values with median PaCO
2
within
normal limits) was observed in all but one wolf.
Metabolic acidosis occurs commonly with immo-
bilization of wildlife, particularly with excitement,
physical exertion, and associated anaerobic metab-
olism. These factors likely contributed to the mild
to moderate acidosis observed. The transient hyp-
oxemia documented in some wolves may also have
contributed to anaerobic metabolism and acidosis.
All three combinations were reliably reversible.
Such reversibility may be invaluable for working
with free-ranging red wolves because it will facil-
itate safe and rapid release of immobilized animals.
Wolves in the MBK30 group exhibited slight ataxia
for up to 5 min after reversal, probably due to the
residual effects of the low dosage of ketamine.
Wolves immobilized with this combination may
need to be held for an additional 10–15 min before
release.
In conclusion, all three protocols provided effec-
tive immobilization. But our results suggest that the
MB combination offers several advantages for rou-
tine field use (procedures lasting 20–30 min). These
two drugs, which can be mixed in the same syringe
and administered intramuscularly, are fast acting,
cause relatively mild adverse cardiorespiratory ef-
fects, and can be completely reversed at any time
during a procedure. For longer procedures, either
the MBD or the MBK30 combination can be used.
MBD induces more profound sedation, but the di-
azepam must be given intravenously. The water-
soluble benzodiazepine, midazolam, could be used
in place of diazepam, and mixed with medetomi-
dine and butorphanol in the same syringe, but both
benzodiazepines require the additional expense of
flumazenil reversal. The MBK30 combination is
useful for longer procedures but may cause some
unwanted cardiovascular effects. As ketamine is not
reversible, rough recoveries are expected if the oth-
er agents are antagonized within 30 min after ke-
tamine administration.
Further studies will be necessary to identify spe-
cific applications of the MB, MBD, and MBK30
regimens. By reducing the risk of severe hyperten-
sion and improving the quality of recovery, the use
of these combinations should have benefits for the
107
LARSEN ET AL.—RED WOLF IMMOBILIZATION
management of red wolves and other free-ranging
canids.
Acknowledgments: We thank A. Beyer, E. Chit-
tick, H. Decker, D. Hill, C. Lasher, T. Mengel, M.
Morse, A. Purdue, M. Randalls, M. Roetto, and B.
Wolfe for assistance during this investigation. We
are grateful to the staff at the North Carolina Zoo-
logical Park and the personnel with the U.S. Fish
and Wildlife Service Red Wolf Recovery Project.
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Received for publication 5 March 2001
