Scholarly article on Benzaldehyde, phenyl(2-phenylethyl)hydrazone 65249-05-0 from Collection of Czechoslovak Chemical Communications p. 322,325

Sufentanil and medetomidine anaesthesia in the

rat and its reversal with atipamezole and

butorphanol

P. Hedenqvist1, J. v. Roughan2 & P. A. Flecknell2

lKarolinska Institutet, Stockholm, Sweden and 2Comparative Biology Centre, Medical School,

Framlington Place, Newcastle upon Tyne, NE2 4HH, UK

Summary

Injectable anaesthetics are widely used to anaesthetize rats, but recovery times are often

prolonged. Reversible anaesthetic regimens have the advantage that animals may be

recovered quickly, thus reducing the incidence of postoperative complications such as

hypothermia, and also providing a means of treating inadvertent anaesthetic overdose. This

study assessed and compared the characteristics of anaesthesia induced with combinations of

sufentanil and medetomidine administered as a single subcutaneous or intraperitoneal dose,

and reversal with butorphanol and atipamezole. Combinations of sufentanil/medetomidine

at 40 /lg/150 /lg and 50 /lg/150 /lg/kg administered subcutaneously, and 80 /lg/300/lg/kg by

intraperitoneal injection were found to produce surgical anaesthesia for 101± 49, 124± 45 and

76 ± 23 min (means ± SD) respectively. All three combinations produced marked respiratory

depression 30min after injection

«

50% of resting respiratory rate). Oxygen saturation,

measured by pulse oximetry, was < 50% in all groups 30min following drug administration.

Subcutaneous administration is recommended since it resulted in a more reliable and more

rapid induction of anaesthesia than intraperitoneal administration. The administration of

butorphanol and atipamezole (O.2/0.5mg/kg s.c.) resulted in a rapid « 7min) reversal of

anaesthesia and an associated respiratory depression. The induction of anaesthesia with

sufentanil/medetomidine and its reversal with a combination of atipamezole and

butorphanol is an effective technique for anaesthetizing rats. However, due to the marked

respiratory depression and the resulting hypoxia, we recommend that this regimen should

only be used in animals which are free from respiratory disease and that oxygen should be

provided during anaesthesia.

Keywords Rat; anaesthesia; sufentanil; medetornidine; atipamezole; butorphanol

In most instances injectable anaesthetics are 1996). These problems can be reduced if the

administered by the intraperitoneal, sub-

cutaneous or intramuscular routes. This,

anaesthetic regimen can be completely or

partially reversed using specific antagonist

however, does not allow an adjustment of the drugs. A number of different combinations

anaesthetic dose to meet the requirements of have been described, for example partial

the individual animal, and the relatively high reversal of fentanyl/fluanisone (Flecknell

dose rates required, in comparison to those

associated with intravenous administration,

et al. 1989),ketamine/xylazine (Lipman et

al. 1987),and ketamine/medetomidine

result in prolonged recovery times (Flecknell (Morris 1991).The effects of combinations of

fentanyl, a /l-agonist opioid, and medetomi-

Correspondence

to; Professor P. A. Flecknell

dine, an a-adrenoceptor agonist, have been

Accepted 23 November 1999

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245

Sufentanil/medetomidine anaesthesia in the rat

described in the rat (Hu et al. 1992). This

combination, however, has the disadvantages

of requiring a relatively large volume of

injectate (lml/lOOg i.p.) and it was reported

that subjects developed severe respiratory

depression. Sufentanil, another Il-agonist

opioid, has been reported to be 16 times more

potent in rats than fentanyl, and reported to

provide safe and effective anaesthesia (Nie-

megeers et al. 1976). When used alone,

potent Il-opioids produce marked skeletal

muscle rigidity, and are not generally con-

sidered acceptable within anaesthetic regi-

mens. When combined with sedatives or

tranquillizers, balanced anaesthesia can be

produced. This study investigates the effects

of sufentanil in combination with medeto-

midine and its reversal with butorphanol and

atipamezole in rats.

The intraperitoneal administration of

opioids results in a high first-pass liver

metabolism and subcutaneous administra-

tion has been shown to be more effective

(Cerletti et al. 1980). Subcutaneous admin-

istration of low volumes of anaesthetic is

also a simpler and subjectively less stressful

means of induction than intraperitoneal

injection. We therefore examined the effects

was used as bedding. Body weights were

recorded for 2 days prior to anaesthesia.

Anaesthesia

Basic methodology

Medetomidine (Domitor, Pfizer Animal

Health, UKl was mixed with water for injec-

tion, to allow accurate dosing, and combined

with sufentanillSufenta

Forte, Janssen, Bel-

gium) resulting in a volume for injection of

1.5 or 2.0 ml/kg. Drugs were administered by

intraperitoneal or subcutaneous injection

into the skin overlying the scapulae on up to

four occasions. A minimum of one week

elapsed between successive anaesthetics.

Following drug administration, the time

required for animals to lose the ability to

perform a righting reflex when placed in

dorsal recumbency was recorded. During

anaesthesia, the parameters which were used

to assess depth of anaesthesia were the

strength of the tail-pinch and pedal with-

drawal reflexes. These were assessed by

pinching the tip of the tail and the hind-foot

metacarpal region between the index finger

and thumb. Responses were scored on a scale

of 0-3, with complete reflex absence scoring

0, and a strong withdrawal response scoring 3.

Complete loss of both the tail-pinch and

of sufentanil/medetomidine

administered

both by the intraperitoneal and subcutaneous

routes.

pedal withdrawal reflexes characterized

a

plane of anaesthesia sufficient for performing

surgical procedures (surgical anaesthesia).

The duration of surgical anaesthesia was

measured as the latency of return of either

the tail-pinch or pedal withdrawal reflexes (a

score>O) from the time of loss of the righting

reflex. Body temperature was maintained at

36-38°C during anaesthesia using a homeo-

thermic heating blanket (Harvard Apparatus,

Edenbridge, Kent, UK). Reflex responses were

recorded every 15 min during anaesthesia, as

were blood O2 saturation, heart rate and

Materials and methods

Twenty-three adult Wistar outbred rats (12

females, 11 males), aged between 6 and 8

weeks, were obtained from the barrier

maintained breeding unit of the Comparative

Biology Centre of the University of New-

castle upon Tyne. Animals from this colony

showed no serological evidence of infection

with rat respiratory pathogens. They were

housed in a temperature regulated room

(20 ± 3°C) with 15 air changes per hour and a respiratory rate. Oxygen saturation was

13h:11 h light-dark cycle (lights on 06:00h;

off 19:00h). The animals were group-housed

(5-6) in solid floored caging (RC1, North Kent

Plastics Ltd, Erith, UK; 56cm x 38 em, height

18cm) and received a commercial pelleted

diet (R&M No.3, Special Diets Services Ltd,

Essex, UK) and water ad libitum. Sawdust

('Gold Chip', BS and S Ltd, Edinburgh, UK)

measured by pulse oximetry (D-YS clip-on

probe; Nellcor, Hayward, California, USA)

with the sensor placed on one of the hind-

feet. After completion of the main study, six

animals were terminally anaesthetized and

blood gas tensions were measured in carotid

arterial blood samples using a blood gas ana-

lyser (Stat Profile 5, Nova Biomedical,

Laboratory Animals (2000) 34

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Hedenqvist, Roughan & Flecknell

246

Table

2

The dose combinations of sufentanil and

Waltham, Massachusetts, USA). A further six

animals from the main study were used to

assess the efficacy of the reversal of anaes-

thesia (see below).

medetomidine which were administered either sub-

cutaneously or intraperitoneally

study

to rats in the main

Sufentanil/

Dose ranging study

Injectable vol. No. of

medetomidine

(Ilg/kg)

Route of

(mIjkg)

rats

administration

In a preliminary study, seven male and seven

female rats were given combinations of

sufentaniljmedetomidine administered sub-

cutaneously or intraperitoneally. Doses were

between 10-50 !lgjkg for sufentanil and 150-

300 !lgjkg for medetomidine (Table 1). These

data were used to determine an appropriate

range of doses for the main study, and these

animals were later used in the main study.

Subcutaneous

Intraperitoneal

1.5

2.0

6

10

6

40/1 SO

50/1 SO

50/300

60/300

80/300

6

cutaneous injection. Reversal was assessed

according to the latency of return of the

ability to perform the righting reflex, and by

monitoring the respiratory rate.

Main study

Five dose combinations were selected for

more detailed assessment (Table 2). To

reduce the effects of variations in responses

between animals, and the number of animals

used, each rat received three anaesthetics,

with an interval of at least one week between

successive treatments. The treatment order

was randomized for each group of rats, and

equal numbers of females and males were

used for each dose combination.

Evaluation of blood oxygen saturation

The six rats used in the main study were

given a single subcutaneous dose of sufenta-

niljmedetomidine (40j150 !lgjkg). Following

the onset of surgical anaesthesia, the right

carotid artery was cannulated with a 22G Lv.

catheter (VygonBiovalve, Ecouen, France)

under local lignocaine analgesia. Between

one and five blood samples were obtained

from each animal for blood gas analysis.

Pulse oximetry data were collected at the

time of each sample. The animals were killed

with an overdose of pentobarbital on return

of the pedal withdrawal reflex.

Reversal of anaesthesia

Following completion of the main study, six

of the rats received 40j150 !lgjkg sufenta-

niljmedetomidine subcutaneously. Thirty

minutes following induction of anaesthesia,

atipamezole (0.5mgjkg) and butorphanol

(0.2mgjkg) were given as a single sub-

Data analysis

In addition to calculations of the latency

until loss of both the righting reflex and tail-

pinch and pedal withdrawal reflexes, mean

respiratory rate, blood O2 saturation and tail-

pinch and pedal withdrawal scores were col-

lected at 30 and 60 min post-injection for

each dose combination. The mean duration

of surgical anaesthesia was also calculated.

From previous experience we have found

restoration of the righting reflex to be extre-

mely variable, and that a better assessment of

the duration of the anaesthesia may be

obtained by also recording the latency to first

(spontaneous) movement (usually limb

Table

1

The dose combinations

and routes of

injection of sufentanil and medetomidine

the dose ranging study

used in

Sufentanilj

medetomidine

(Ilg/kg)

Route of

No. of

rats

administration

10/200

20/200

30/200

30/300

40/300

50/300

15/150

20/150

40/300

50/200

Intraperitoneal

Subcutaneous

2

1

movements and partial righting). In the fol-

lowing description of the results obtained

from this study, where the number of ani-

Laboratory Animals (2000) 34

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247

Sufentanil/medetomidine

anaesthesia in the rat

mals for which the data were obtained differs (± SO)for the loss of the righting reflex were

from that originally entered into the study

(as shown in Table 1), this was due to cases

in which the righting reflexes were not

abolished. Using each type of assessment, the

effects of anaesthesia following intraper-

itoneal or subcutaneous administration were

compared between drug dosages using

ANOVA, computed with SPSSsoftware

(SPSS,Chicago, USA).

not significantly different between sub-

cutaneous doses (3.7± 1.2 d . 3.2±2 min,

respectivelyl·

Of 22 rats injected intraperitoneally, five

did not lose the ability to perform a righting

reflex following placement in dorsal recum-

bency (two which received 50/150 Ilgjkg, one

which received 60/300 J.lg(kgand two which

received 80/300 Ilgjkg). Animals which

received the 50/300 Ilg(kg combination lost

their righting reflex between 4 and 24 min

following injection (11.5± 7.8; mean±SOj.

Following the administration of 60/300

Ilg/kg, the time to the loss of righting reflex

varied between 1 and 17min (7.2 ± 6) and

between 4 and 15min 18.2± 5.3) in animals

given 80/300 Ilg/kg.

Results

Dose ranging study

The two rats which received 50/200 Ilg/kg

subcutaneously and 50/300 Ilg/kg intraperi-

toneally lost the ability to perform the

righting reflex and lost their pedal with-

drawal responses within 15min. The animal

which received a subcutaneous dose of

50/200 Ilg/kg became cyanotic and was

reversed with atipamezole/butorphanol

(0.5/0.2mg/kg s.c.). The animal which

received the 40/300 Ilg/kg dose sub-

Time to loss of tail-pinch and pedal

~thdravva1 reflexes

All the 16 rats given subcutaneous sufenta-

nil/medetomidine lost their pedal with-

drawal and tail-pinch reflexes. For the

40/150 Ilg/kg combination, the mean times

(± SO)for loss of each respective reflex were

11.7± 10.6min and 4.3± 2.6 min. For the

animals given the 50/150 Ilg/kg combina-

tion, the comparable times were 14.6± 6.7

and 7.7± 5.3min. The loss of the pedal

withdrawal and tail-pinch reflexes were not

significantly different between the sub-

cutaneous doses used (P> 0.1 j.

cutaneously was found dead the following

day. All other dose combinations failed to

result in loss of the pedal withdrawal reflex.

Main study

Time to loss of the righting reflex

Oata for the latency of loss of the righting

reflex, tail-pinch and pedal withdrawal

reflexes are shown in Table 3. All animals

given sufentanil/medetomidine sub-

cutaneously at combinations of 40/150 Ilg/kg

or 50/150 Ilg/kg showed an abolition of the

righting reflex within 7min. Mean times

Of the 22 rats administered drugs intra-

peritoneally, 12 lost their pedal withdrawal

reflex, while 17 lost their tail-pinch reflex.

Times to loss of reflexes varied between 3

Table

3

The latency until loss of the righting reflex and tail-pinch and pedal withdrawal reflexes in groups of

rats administered combinations of sufentanil and medetomidine either subcutaneously or intra peritoneally.

Data are means ± SO

Sufentanil/

medetomidine

~g/kg (route)

Latency to loss of pedal

withdrawal reflex (min)

Latency to loss of

Valid n

tail-pinch reflex (min)

righting reflex (min)

Valid n

40/150 (s.c.)

50/150 (s.c.)

50/300 (i.p.)

60/300 (i.p.)

80/300 (i.p.)

11.7±10.6

14.6±6.7

9.5±3.9

6

10

4

4.3±2.6

7.7±5.3

11±8

3.7±1.2

3.2±2

6

10

8

5

4

11.5±7.8

7.2±6

15.3±10.9

13.5± 12

4

7.2±6

4

6.7±3.7

8.2±5.3

s.c.= subcutaneous, i.p. = intraperitoneal

Laboratory Animals (2000) 34

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Hedenqvist, Roughan & Flecknell

248

the three intraperitoneal doses used, animals

which received the 80/300 Ilg/kg combina-

tion showed a significantly greater reduction

and 24 min for the tail-pinch, and 4 and

30 min for the pedal withdrawal reflex.

Increasing the dose of sufentanil adminis-

tered did not result in a significant change in in O2 saturation values at both the 30 and

the time required for the loss of either the

pedal withdrawal or tail-pinch reflexes.

60 min time points than animals which

received the 50/300 Ilg/kg combination. For

the higher dose combination, mean satura-

tion values (± SD) for the 30 and 60min

samples were, respectively, 40±26% and

49± 13%, compared to 77± 12% and 81± 9%

in animals which received the 50/300 Ilg/kg

dose combination (P = 0.015; P < 0.001 for

each respective time).

Respiratory rate and O2 saturation

Data for mean respiratory rate and blood O2

saturation levels at 30 and 60 min following

drug administration are shown in Table 4.

The mean (± SD) resting respiratory rate of

the rats used in this study was 79± 3 breaths

per minute (Hu et al. 1992).With the excep-

tion of animals given 50/300 Ilg/kg intra-

peritoneally, all developed respiratory

Duration of surgical anaesthesia

All the animals which received subcutaneous

sufentanil;medetomidine were surgically

anaesthetized. The duration of surgical anaes-

thesia (mean± SD)for the 40/150 Ilg/kgand

50/150 J.lg/kgcombinations administered

subcutaneously were 101± 49 min and

124± 45 min respectively (Table51.These

times were not significantly differentbetween

dosages (P> 0.1).Equivalent times for the

animals which received intraperitoneal

sufentanil/medetomidine showed that the

highest dose given 180/300 Ilg/kg)gave a

significantly greater duration of surgical

anaesthesia (76± 23 min) than either the

50/300 ~g/kg dose (13± 15min; P < 0.0011

or the 60/300 Ilg/kg dose (21± 20min;

P=0.002).

depression

«

50% of resting rate) within

30 min of drug administration. This persisted

for up to one hour in animals which received

either 40/150 Ilg/kg or 50/150 Ilg/kg sub-

cutaneously, and in the animals which

received the 80/300 Ilg/kg dose combination

intraperitoneally. No significant differences

were found in respiratory rates at either the

30 or 60 min time samples in comparisons

between each subcutaneous dose, or between

the three intraperitoneal doses used. Four

animals in each of the groups were adminis-

tered 50/150 Ilg/kg and 40/150 Ilg/kg sufen-

tanil/medetomidine subcutaneously, and

four animals which received 60/300 Ilgjkg

intraperitoneally were visibly cyanotic. One

male which received 40/150 Ilg/kg sub-

cutaneously showed several periods of

Latency of first movement and total sleep

time

apnoea lasting 15 to 30 s, but recovered

without the need for reversal with atipame-

zole/butorphanol. In comparisons between

The times for latency of first movement and

total sleep time are also shown in Table 5.

Comparisons between the doses given by

Table 4 Measurements of respiratory rate and blood oxygen saturation at 30

and 60 min time intervals following drug administration for each anaesthetic

combination used. O2 saturation values were obtained by pulse oximetry.

Data are means ± SD

Sufentanil/

Resp. rate

medetomidine

l1g/kg (route)

Resp. rate

O2 sat

at 30 min

at 60 min

at 30 min

at 60 min

Valid n

40/150 (s.c.)

50/150 (s.c.)

50/300 (i.p.)

60/300 (i.p.)

80/300 (i.p.)

29± 11

33± 12

41 ±15

35±9

32± 12

39± 15

44± 15

42± 12

27±6

49±16

47±16

77±12

67 ±13

40±26

52± 15

59± 11

S1±9

6

10

S

75± 10

49± 13

5

26±10

4

O2 sat= oxygen saturation, Resp.= respiratory, S.c. = subcutaneous, i.p. = intraperitoneal

Laboratory Animals (2000) 34

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249

Sufentanil/medetomidine anaesthesia in the rat

either the subcutaneous or intraperitoneal

routes showed no significant differences in

the latency of first movement or total sleep

time.

Discussion

This study found differences in the char-

acteristics of anaesthesia in animals which

receive a range of doses of sufentanilj

medetomidine either subcutaneously or

Reversal of anaesthesia with atipamezole

and butorphanol

intraperitoneally.

Subcutaneous administra-

tion was more effective than intraperitoneal

injection in that all animals given drugs by

the former route reached a surgical plane of

anaesthesia. There are two plausible expla-

nations for this difference in anaesthetic

efficacy. Drugs administered intraperi-

All six animals had regained the ability to

perform at least one instance of a righting

reflex within 7 min of drug administration.

Recovery of the righting reflex was abrupt,

and animals characteristically adopted a

'straub-tail' response during this period. The

mean respiratory rate 15 min before reversal

was 32±4bpm, which rose to 127± 15bpm

within 10 min of drug administration. Within

15 min of reversal all animals appeared fully

recovered, resuming normal exploratory

activities.

toneally are subject to a high degree of first-

pass hepatic metabolism

since they are

absorbed into the portal system. A second

factor is the possibility of drug loss into the

gastrointestinal tract or extraperitoneally.

The latter possibility is emphasized by an

examination of the number of animals for

which latency to first movement and total

sleep time data were obtained (Table 5). In

several cases, intraperitoneallyadministered

drug dosages were shown to produce surgical

anaesthesia in some animals but failed to

result in loss of the righting reflex in others.

In contrast, subcutaneous administration

avoids liver metabolism of the drugs imme-

diately following absorption, allowing the

use of a lower dose to achieve an equivalent

depth and duration of anaesthesia.

Evaluation of reliability of pulse oximeter

readings

Table 6 shows data for six rats in which

arterial oxygen and carbon dioxide partial

pressures (p02 and pC02) were obtained at

the same time as blood oxygen saturation (02

sat) measured using pulse oximetry. Inspec-

tion of these data indicates that low O2 sat

was generally associated with low arterial

p02 and elevated pC02.

Subcutaneous injections are also much

more easily accomplished by inexperienced

workers and, based on our subjective assess-

ments of the animals' reactions to injections,

this method is seemingly less stressful or

painful. Onset of anaesthesia after sub-

Post-anaesthetic recovery

Animals recovered uneventfully from anaes-

thesia. No clinically detectable adverse

reactions to either subcutaneous or intraper-

itoneal injection were noted.

cutaneous administration

was also more

Table

total

5

The duration of surgical anaesthesia. latency to first movement

and

sleep time in rats for each combination

sufentaniljmedetomidine

administered subcutaneously or intraperitoneal/y.

Data are means ± SO

Sufentanil/

medetomidine

I1g/kg (route)

Duration of surgical

anaesthesia (min)

Latency of first

Total sleep

time (min)

movement (min)

Valid

n

40/1 50 (s.c.)

50/150 (s.c.)

50/300 (i.p.)

60/300 (i.p.)

80/300 (i.p.)

101 ±49

124±45

13± 15

21±20

141 ±26

140±31

112±42

119±28

155± 12

183±42

145±31

130±43

122±29

169±18

6

10

8

5

76±23

4

s.c.= subcutaneous,i.p. = intraperitoneal

Laboratory Animals (2000) 34

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Hedenqvist, Roughan & Flecknell

250

rapid than after intraperitoneal administra-

tion, indicating that this route is to be pre-

ferred.

associated with severe hypoxia. The direct

measurements of arterial blood gases also

enabled measurements of pe02 in these

Although pedal withdrawal responses were animals. It can be seen that reduced arterial

quickly abolished after drug treatment, it was p02 was always associated with hypercapnia.

apparent that muscle relaxation resulting

from the action of medetomidine was not

maximized for approximately 10 to IS min.

This delay in peak action is consistent with

reports of the pharmacodynamics of mede-

tomidine in the rat [Salonen 19891. It is

therefore advisable to incorporate a delay

prior to commencing operative procedures

when using this anaesthetic regimen. As in

other studies [Hu et al. 1992) we have

Although pulse oximetry makes no measure

of arterial carbon dioxide tensions, when

hypercapnia is due to respiratory depression

it almost invariably accompanies hypoxia.

Table 6 indicates that this trend was present

in rats in which direct assessments of arterial

blood gases were made. It therefore seems

reasonable to assume that the majority of

rats in the main study which showed

evidence of hypoxia based on pulse

demonstrated that administration of Il-ago-

oximetry readings were both hypoxic and

nist opioids such as sufentanil may be asso- hypercapnic.

ciated with an increased risk of respiratory

depression. As this is further potentiated by

co-administration with medetomidine, this

anaesthetic regimen can only be recom-

mended for use in healthy, respiratory

disease-free animals. Subsequent clinical

All animals which received drugs sub-

cutaneously recovered uneventfully, and

reversal of anaesthesia using atipamezole and

butorphanol proved effective, so we consider

this anaesthetic regimen to be a safe and

effective means of anaesthetizing healthy,

experience with this regimen has shown that respiratory disease-free rats. Furthermore, as

the hypoxia which occurs can be avoided by

provision of oxygen, but pronounced hyper-

capnia will still be produced.

Pulse oximetry provides a simple and

Table

6

Values of simultaneously

recorded blood

relatively inexpensive means of monitoring

respiratory function. However, at low

oxygenation saturation.

and oxygen and CO2 partial

pressures in each of six rats administered with

a

saturations

«

80%) the technique becomes

single subcutaneous dose of sufentanil and medeto-

midine (40 •.•g./150 •.•g./kg)

less reliable (Sevinghaus &. Naifeh 19871. In

practice, this is not usually a significant

problem since detection of oxygen saturation

levels below 80% requires corrective action.

A second factor that can affect pulse oxim-

etry readings is peripheral vasoconstriction,

which is known to be produced by medeto-

midine (SavoIa 1989). In the present study,

pulse oximetry was used to assess the degree

of respiratory depression. It was thought

advisable to compare pulse oximetry readings

with measurements of arterial blood oxygen

tension to determine how effective pulse

oximetry was in detecting respiratory

O2 saturation (% )

Rat

p02 (KPa)

1

2

3

5

6

7

55

48

58

62

72

81

90

40

50

6.3

5.1

7.7

8.0

7.8

7.7

5.8

7.4

6.4

7.2

3.5

5.7

6.6

7.4

7.9

4.5

5.4

6.1

4.9

7.9

7.1

6.8

10.3

10.6

10.5

6.3

7.8

55

7.6

7.0

50

11.9

9.4

23

45

20

86

82

69

46

30

5.2

depression in rats using this particular

6.6

anaesthetic regimen. Oxygen saturations

below 80% were usually associated with

arterial p02 of < 10kPa, and those below

40% with p02 values of < 6 kPa. It seems

likely, therefore, that the low O2 saturations

detected in animals in the main study were

5.0

11.5

10

8.7

6.4

7.0

Laboratory Animals (2000) 34

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251

Sufentanil/medetomidine anaesthesia in the rat

References

butorphanol is a mixed agonist/antagonist,

having agonist activity at both sigma and

kappa receptors in addition to marked

antagonistic properties at mu receptors, a

further significant advantage of this anaes-

thetic technique is the provision of some

degree of analgesia following operative

procedures lFlecknell et al. 1989). If major

surgery has been undertaken, additional

analgesia can be provided by using NSAIDs

such as carprofen or additional doses of

butorphanol or other opioids (Flecknell &

Waterman-Pearson 2000).

We consider the rapid and complete rever-

sal of anaesthesia to be a significant advan-

tage of the presently investigated anaesthetic

technique. During recovery from anaes-

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Laboratory Animals (2000) 34

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