Drug Evaluation

Drugs 36: 286-313 (1988)

00 12-666 7/88/0009-0286/S 14.00/0
© ADiS Press Limited
All rights reserved.

Sufentanil
A Review of its Pharmacological Properties and
Therapeutic Use

Jon P. Monk, Rosemary Beresford and Alan Ward

ADIS Drug Information Services, Auckland, New Zealand

Various sections of the manuscript reviewed by: J.G. Bovill, Academisch Ziekenhuis
Leiden, Leiden, The Netherlands; R.C. Cork, Department of Anesthesiology, The Uni-
versity of Arizona, Tucson, Arizona, USA; J. W. Flacke, Department of Anesthesiology,
UCLA, Los Angeles, California, USA; A..J. Gandolfi, Department of Anesthesiology, The
University of Arizona, Tucson, Arizona, USA; S. Lacoumenta, Department of Anaes-
thetics and Medicine, Royal Postgraduate Medical School, London, England; G. Rolly,
Department of Anaesthesia, State University of Ghent, Ghent, Belgium; C.E. RosoHl,
Department of Anesthesia, University of Massachusetts General Hospital, Boston, Mas-
sachusetts, USA; P.S. Sebel, Section of Anesthesiology, Emory University Hospital, At-
lanta, Georgia, USA; T.B. Stanley, Department of Anesthesiology, University of Utah,
Salt Lake City, Utah, USA.

Contents Summary .....................................................................................................................................287

I. Pharmacodynamic Studies .................................................................................................... 289
1.1 Effect on the Opiate Receptor ........................................................................................289
1.2 Analgesic Effect ................................................................................................................ 289
1.3 Effects on the EEG .......................................................................................................... 290
1.4 Effects on Stress-Related Hormones .............................................................................. 291
1.5 Cardiovascular Effects .....................................................................................................292
1.6 Effects on Respiration ..................................................................................................... 293
I. 7 Effects on Immune Function and Cell Growth ............................................................ 293
1.8 Effect on Peripheral Nerve Function ............................................................................. 294
2. Pharmacokinetic Studies ....................................................................................................... 294
2.1 Absorption and Plasma Concentrations ........................................................................ 294
2.2 Distribution ......................................................................................................................295
2.3 Metabolism ........................................................................................................................296
2.4 Elimination ....................................................................................................................... 296
2.5 Influences of Disease and Age on Sufentanil PharmacokInetics ................................. 297
3. Therapeutic Trials .................................................................................................................. 297
3.1 Anaesthesia Studies in Major Surgery ...........................................................................297
3.1.1 Non-Comparative Trials ........................................................................................297
3.1.2 Comparisons with Fentanyl ................................................................................... 299
3.1.3 Comparisons with Other Opioids ......................................................................... 299
3.1.4 Comparisons with Ketamine and Etomidate ....................................................... 301
3.1.5 Comparisons with Inhalational Anaesthetics ....................................................... 301
3.1.6 Sufentanil Infusion ...................................................................... ........................... 301
3.1.7 Use in Paediatric and Elderly Patients ................................................................. 302
3.2 Outpatient Anaesthesia Studies ...... .................... .................................... ........................ 302
Sufentanil: A Review 287

3.3 Epidural Administration .................................................................................................303

4. Adverse Effects ....................................................................................................................... 305
4.1 Intravenous Administration ........................................................................................... 305
4.2 Epidural Administration ................................................................................................. 306
5. Dosage and Administration ..................................................................................................307
6. Place of Sufentanil in Therapy .............................................................................................308

Summary
Synopsis Sufentanil, an opioid analgesic, is an analogue offentanyl, and has been used for the
induction and maintenance of anaesthesia, and for postsurgical analgesia. It has shorter
distribution and elimination half-lives, and is a more potent analgesic than fentanyl. In
clinical practice, however, intravenously administered sufentanil produces essentially
equivalent anaesthesia to fentanyl and is a better anaesthetic than morphine or pethidine
(meperidine) for major surgery. It would appear to maintain haemodynamic stability dur-
ing surgery better than other opioids or inhalational anaesthetics. Postoperative respiratory
depression has been reported in a few patients.
For outpatient surgery, intravenous sufentanil produces equivalent anaesthesia to is-
oflurane or fentanyl. Recovery tends to be more rapid after sufentanil and the requirement
for postoperative analgesia is less. Initial clinical trials with sufentanil administered epi-
durally to relieve pain during labour have produced encouraging results, but further studies
are required to establish the drug's role in this indication. Epidural sufentanil produces a
more rapid onset and better initial quality of analgesia than morphine, buprenorphine or
hydromorphine when administered postoperatively, but the duration of analgesia is shorter.
Thus, sufentanil's primary place in therapy at this time would appear to be as high
dose anaesthesia for major surgery such as cardiac surgery, and as low dose supplement
to balanced anaesthesia in general surgery. In addition, low doses administered epidurally
seem to have a potential role for analgesia during labour or after surgery although further
studies are required to clarify this situation.

Pharmacodynamic Studies Sufentanil, an analogue of fentanyl, is an opioid analgesic which is highly selective
for the It-receptor site. It is a very potent analgesic; in animals it is 625 to 4,000 times
more potent than morphine and 5 to 15 times more potent than fentanyl. It is also more
potent than morphine in man but produces a shorter duration of analgesia. Sufentanil
has a better cardiovascular safety margin in dogs undergoing deep surgical analgesia rel-
ative to morphine or fentanyl.
Like other opioids, sufentanil increases the amplitude and reduces the frequency of
the EEG. Unlike many other opioids, sufentanil produces very little haemodynamic in-
stability. It may produce a reduction in heart rate and blood pressure shortly after in-
duction, but the cardiovascular instability usually associated with surgery is largely avoided.
Some studies indicate that sufentanil maintains better haemodynamic stability than fen-
tanyl. Plasma catecholamine concentrations and concentrations of other 'stress hor-
mones' tend to remain stable following sufentanil administration, but still increase during
surgery. Sufentanil reduces mean minute volume and respiratory rate, and may produce
respiratory depression during or after surgery. This may be managed by the concomitant
use of muscle relaxants or reversed by the subsequent administration of naloxone.

Pharmacokinetics Studies Following intravenous administration, sufentanil disappears from the plasma in a
triexponential fashion. Sufentanil is highly lipophilic and is rapidly distributed into brain
and other tissues with an initial distribution phase (half-life 1.4 minutes) and a slower
distribution phase (half-life 18 minutes). It is highly protein-bound (92.5%) and has a
large apparent volume of distribution, in the range 1.74 to 5.17 L/kg and is extensively
taken up by tissues.
Sufentanil: A Review 288

The metabolic pathways of sufentanil in man have not yet been determined. but in
animals N-dealkylation and O-demethylation are involved. At least I metabolite retains
some of the activity of the parent molecule. although it appears at such low concentra-
tions as to be of questionable clinical significance. Sufentanil metabolites are eliminated
in urine and faeces. The reported elimination half-life has ranged from about 2 hours in
non-cardiac surgery patients to about 10 hours in patients undergoing cardiac surgery.
There is some evidence that the pharmacokinetics of sufentanil may be altered in patients
with reduced renal or hepatic function. although limited data are available in such sub-
jects. and the pharmacokinetics of sufentanil would seem to be more variable in neonates
compared with children or adults.
Following epidural administration to women following caesarean section the plasma
concentration of sufentanil reached a peak after about 10 minutes which was about 25%
of the peak reached after intravenous administration. The concentration then declined
graduall y over a period of I to 2 hours.

Therapeutic Trials Early clinical trials involving medium or high doses of sufentanil (up to 50 /Jg/ kg)
focussed on its use as a supplement to balanced anaesthesia in patients undergoing gen-
eral surgery or as the sole anaesthetic in cardiac or neurological surgery. Many of these
were controlled studies comparing sufentanil with other opioid analgesics or with an
inhalational anaesthetic agent. Sufentanil proved superior to morphine or pethidine in
its anaesthetic activity. and its haemodynamic and postoperative eflects. However. little
difference was demonstrated between sufentanil and fentan yl anaesthesia. although su-
fentanil maintained better haemodynamic stability and has been associ ated with a faster
recovery.
Low doses of sufentanil « I /Jg/ kg) have been employed in outpatient surgery as
premedication or for anaesthetic induction. allowing reduction of the amount of inhal-
ational anaesthetic and postoperative analgesic required. Initial recovery from anaes-
thesia was quicker after sufentanil than after isoflurane or fentan yl.
Epidural administration of sufentanil (10 to 100/Jg) has proven effective for pain relief
during labour or after surgery. When administered with bupivacaine during labour. su-
fentanil reduced the time to onset of analgesia and improved the qualit y of epidural
block compared with bupivacaine alone. Following abdominal. thoracic. orthopaedic.
urologic or general surgery. or after caesarean section. sufentanil induced rapid analgesia.
but the duration of analgesia was shorter than that after morphine. hydromorphine or
buprenorphine.

Side Effects The most frequently reported disturbing side effects following medium or high dose
intravenous sufentanil administration are hypotension. chest wall rigidity , tachycardia
and bradycardia. which occurred at incidences of 6%. 2.9%. 1.3% and 3.4%. rcspectively.
in I large multicentre trial. Nausea and/ or vomiting. pruritus and sedation also occur.
and are the most frequently reported events after epidural administration of sufentanil.
Other events reported in clinical trials included hypertension . dizziness. urinary retention
and headache. There have been some reports of myoclonus (which would not appear to
involve cortical seizure activity) and severe respiratory depression.

Dosage and Admin~stration For use in anaesthesia sufentanil may be given in low, moderate or high doses. Low
doses ("" 2 /Jg/ kg) are used in minor surgery. moderate doses (2 to 8 /Jg/ kg) in more
complex surgery and high doses (8 to 50 /Jg/kg) in cardiac and neuro-surgery. The dose
should be determined for each patient according to age. weight. general condition. other
medication and surgical procedure to be undertaken. For postsurgical epidural analgesia
optimal doses would appear to be 30 to 50/Jg administered at the first onset of pain and
repeated as necessary.
Sufentanil: A Review
1. Pharmacodynamic Studies
Sufentanil (fig. 1) is an opioid analgesic, the
thienyl analogue of the 4-anilinopiperidine, fen-
tanyl. Like fentanyl, it is a centrally acting anal-
gesic which is used in the induction and mainten-
ance of anaesthesia during cardiac surgery and as
a supplement to balanced anaesthesia in general
surgery. As yet, unlike other opioids, it is not used
in non-anaesthetic clinical practice.
1.1 Effect on the Opiate Receptor
The multiplicity of the opiate receptor was first
recognised by Martin et al. (1976), and the endog-
enous opioid system is now considered to involve
many receptor subtypes. The functional signifi-
cance of the 2 major subtypes /L and 0 has not yet
been elucidated fully, but it appears that the wsub-
type may mediate analgesia, and the o-subtype ca-
tatonia and other behavioural phenomena (Kos-
telitz et al. 1980).
In vitro ligand studies have shown that sufen-
tanil is highly selective for /L-receptors (James &
Goldstein 1984; Leysen & Gommeren 1982), being
more selective than fentanyl, methadone, pethi-
dine (meperidine) and morphine (Hermans et al.
1983). The binding affinity of sufentanil for the w
receptor site was 100 times greater than its affinity
for the o-binding .site (Leysen et al. 1983). In vivo
studies comparing receptor occupancy and phar-
macological effects in rats have also shown that su-
fentanil is highly selective for the /L-receptor site
(Colpaert et al. 1986; Rosenbaum et al. 1984).
1.2 Analgesic Effect
In animal studies, sufentanil has proven to be
a potent analgesic. Experiments using the tail with-
drawal and hot plate tests carried out in mice and
rats demonstrated its potency following intraven-
ous or subcutaneous injection to be 2,000 to 4,000
times that of morphine and 10 to 15 times that of
fentanyl (Niemegeers et al. 1976; Upton et al. 1982;
Van Bever et al. 1976; van den Hoogen & Colpaert
1983). Sufentanil was similarly effective when ad-
289
Fig. 1. Structural formulae of sufentanil and fentanyl.
ministered by other routes. When given by intra-
ventricular injection, sufentanil was more potent
than fentanyl (7 times) and morphine (410 times)
with regard to discriminative stimulus (cueing) ac-
tivity and analgesic activity in rats (Colpaert et al.
1978). Intrathecal administration of 4-anilinopi-
peridine analogues produced analgesia in rats (hot
plate and tail flick tests) and cats (skin twitch). Su-
fentanil was more potent than morphine, alfentanil
and fentanyl but less potent than lofentanil
(Noueihed et al. 1984; Yaksh et al. I 986b). The
analgesia produced in decerebrate cats by sufen-
tanil 2.5/Lg was similar to that produced by fen-
tanyl 25/Lg (Aoki et al. 1986). Although high doses
of int~athecal morphine produced hyperaesthesia
in cats and rats, no hyperaesthesia was produced
by comparable doses of sufentanil or alfentanil
(Yaksh et al. I 986a).
In dogs, the analgesic potency of sufentanil was
625 times that of morphine and 5 times that of
fentanyl, the minimal effective doses being 0.00025,
0.0012 and 0.15 mg/kg intravenously, respectively.
The safety margin for deep surgical analgesia in
dogs (ratio between the intravenous dose produc-
ing severe cardiovascular side effects and that pro-
ducing deep surgical analgesia), relative to mor-
phine, was 5 for fentanyl and 24 for sufentanil (De
Castro et al. 1979).
Sufentanil: A Review
The analgesic effect of sufentanil may be attrib-
utable in part to stimulation of serotonin (5-hy-
droxytryptamine) release, resulting in an anti-no-
ciceptive effect. High doses of sufentanil in rats,
which produced marked reductions in the mini-
mum alveolar anaesthetic concentration of halo-
thane, also produced some depletion in the sero-
tonin content of CNS tissue, which may have
resulted from increased serotonin release. Low
doses of sufentanil were without effect (Althaus et
al. 1985). Depletion of central serotonin, but not
catecholamines, with parachlorophenylalanine sig-
nificantly diminished the percentage minimum al-
veolar _anaesthetic concentration reduction in-
duced by high doses of sufentanil, again suggesting
that serotonin has a role in the anaesthetic effects
of this drug (Althaus et al. 1986). In more recent
studies sufentanil was found to have an enflurane-
sparing effect in dogs, and a halothane-sparing ef-
fect in rats, as measured by the effects of the vol-
atile anaesthetics on the minimal alveolar anaes-
thetic concentrations. The maximum effect of
sufentanil was a 70% reduction (Hall ef al. 1987)
and a 62% reduction (Hecker et al. 1983) in min-
imum alveolar anaesthetic concentration, respec-
tively.
The analgesic and other morphine-like effects of
sufentanil were rapidly antagonised by nalorphine
(Niemegeers et al. 1976) and were reduced in a
dose-related manner by naloxone in rats (Rosen-
baum et al. 1984; Yaksh et al. 1986b). Moreover,
naloxone rapidly reversed the effects of sufentanil
in man (De Castro 1976).
The analgesic potency of sufentanil (50~g) has
been assessed in 10 healthy subjects following ex-
tradural administration (Klepper et al. 1987). Seg-
mental analgesia to ice and pin-prick developed
within 15 minutes and extended to between Til
and T9. There was marked relief of pain associated
with the cold pressor response test: 70 to 90%
depression of pain for 1.25 hours in the foot, and
50% depression for about 1.5 hours in the hand.
Increased tolerance to periosteal pressure was most
pronounced for the tibia (increased by 40 to 50%)
and least pronounced for the forehead (10 to 20%
increase for 3 hours). Adrenaline (I: 200,000) [epi-
290
nephrine] intensified segmental analgesia and pro-
longed the duration of effect. Sufentanil produced
dose-related pain relief when given epidurally to
patients recovering from orthopaedic surgery, with
a dose of 50~g providing effective pain relief for a
mean duration of 372 minutes (Donadoni et al.
1985), and produced pain relief similar to that of
morphine in patients suffering from facial pain
(Cathelin et al. 1981). In the latter study, sufentanil
0.5 ~g/kg was equipotent with morphine 200 ~g/
kg but produced a shorter duration of analgesia (230
vs 290 minutes).
When given by the lumbar and subarachnoid
routes, at equipotent dosages to groups of 15
patients with intractable cancer pain, sufentanil was
700 times more potent than morphine and 7 times
more potent ·than fentanyl (Devaux et al. 1982).
The onset of analgesia occurred more rapidly with
sufentanil and fentanyl (6 to 8 minutes) than with
morphine (33 minutes), but the duration of max-
imal analgesia was also less (6 vs 20 minutes).
1.3 Effects on the EEG
Although it is not yet clear how the EEG relates
to the adequacy of opioid anaesthesia (Rosow
1984), most anaesthetics produce a slowing ofEEG
activity and a shift to the left of frequency and am-
plitude (Smith et al. 1984). Studies in dogs (Wau-
quier et al. 1981) and rabbits (Kubicki et al. 1977)
have shown that equianalgesic doses of sufentanil
and fentanyl produce similar changes in the EEG.
Both increase the amplitude and decrease the fre-
quency ofthe EEG. Similar effects are produced in
healthy subjects (Kugler et al. 1977) and in patients
undergoing cardiac surgery (Bovill et al. 1981 b,
1982; Kubicki et al. 1977; Sebel et al. 1981 b; Smith
et al. 1984; Wauquier et al. 1984; Zurick et al. 1983).
The changes described by Bovill et al. (1981b)
in -cardiac patients given sufentanil 15 ~g/kg intra:.
venously over 2 minutes are typical. Within a few
seconds of drug administration the fast {3 activity
(13.5 to 25Hz) which is characteristic ofthe awake
premedicated state disappeared, with slow a activ-
ity (7.5 to 13.5Hz) becoming prominent. Within 30
to 40 seconds of induction a activity disappeared
Sufentanil: A Review
and was replaced by diffuse 8 activity (3.5 to 7.5Hz)
and some {) waves (0.5 to 3.5Hz). Within 150 sec-
onds the EEG was monomorphic consisting almost
entirely of slow {) waves. No EEG changes occurred
during intubation or surgical incision. The reap-
pearance of some a activity towards the end of sur-
gery may have coincided with a lightening of an-
aesthesia since it disappeared when a small
incremental dose of sufentanil was given. A similar
pattern was seen after intravenous fentanyl 30 to
70 J,Lg/kg and alfentanil 50 to 180 J,Lg/kg although
more 8 activity was observed during anaesthesia
with the latter drug.
Some small sharp waves were observed by Bov-
ill et al. (1981 b, 1982) and Sebel et al. ( 1981 b) dur-
ing anaesthesia with sufentanil and fentanyl but the
neurophysiological significance of this observation
is uncertain (Bovill et al. 1982). No such sharp wave
activity was observed by Smith et al. (1984). Power
spectral analysis revealed a considerable increase
in total power following sufentanil administration
which was mainly due to an increase in the {) band
(Wauquier et al. 1984). Absolute {) power changed
with time but relative {j power remained constant
(Sebel et al. 1981b).
1.4 Effects on Stress-Related Hormones
Surgical procedures are usually associated with
a stress response and the release of hormones into
the bloodstream. Increased concentrations of cir-
culating catecholamines, cortisol, antidiuretic hor-
mone, human growth hormone, glucose, lactate and
pyruvate occur during general anaesthesia with in-
halational agents, and increase still further during
operation. Cardiac and abdominal surgery produce
particulary severe stress responses. These are un-
desirable since the result is haemodynamic instab-
ility which can have a deleterious effect on the
condition of the patient (Bovill et al. 1984b). An-
aesthesia with opioid analgesics tends to produce
smaller increases in stress hormones than does an-
aesthesia induced by inhalational or other intra-
venous anaesthetics (Bovill et al. 1984b; de Bruijn
& de Lange 1984; Rosow et al. 1984).
With sufentanil, plasma catecholamine concen-
291
trations changed little when low doses are used (de
Lange et al. 1982b; Hacke et al. 1985; Howie et al.
1985; Murkin et al. 1984). In patients undergoing
abdominal surgery or coronary bypass procedures
despite the much larger doses being used, cate-
cholamine concentrations increased (Fahmy 1983;
Philbin et al. 1984; Rolly et al. 1979; Samuelson
et al. 1986), although these increases are less than
those seen with alfentanil (Lipszyc et al. 1988) or
isoflurane (Roizen et al. 1987). In healthy athletes
subjected to strenuous exercise in normal, hyper-
capnic and hypoxic conditions, sufentani1 caused
a suppression of the catecholamine response to ex-
ercise, in addition to respiratory depression (Nitti
et al. 1986).
Plasma renin and aldosterone concentrations
increased slightly during sufentanil anaesthesia, but
less than they did with fentanyl (Philbin et al. 1984).
Antidiuretic hormone increased slightly or not at
all with sufentanil and alfentanil (Boulton et al.
1986; Bovill et al. 1983a; de Lange et al. 1982a;
Sebel et al. 1982) but did rise with fentanyl (de
Lange et al. 1982a).
Growth hormone concentrations did not in-
crease during cardiac surgery with sufentanil in
some studies (Bovill et al. 1983a; de Lange et al.
1982a), but was markedly increased during the cor-
onary bypass time in another study involving 2 dif-
ferent doses of sufentanil (10 and 20 J,Lg/kg) [La-
coumenta et al. 1987]; differences in patient
management between these studies may account
for this discrepancy. Larsen et al. (1980) observed
no change in glucose, lactate, pyruvate or free fatty
acid plasma concentrations during sufentanil an-
aesthesia, although during and after coronary by-
pass there have been reports of increases in plasma
glucose (Bovill et al. 1983a; Lacoumenta et al. 1987)
and free fatty acids (Bovill et al. 1983a). Cortisol
concentrations decreased after induction with . su-
fentanil and did not return to control levels until
after surgery was completed (de Lange et al. 1982b,
1983; Carreras et al. 1978) or were relatively un-
changed initially but increased on completion of
surgery (Bovill et al. 1983a; Lacoumenta et al.
1987). In neonates undergoing cardiac surgery, su-
fentanil inhibited the marked haemodynamic and
Sufentanil: A Review
hormonal stress responses induced by surgery (An-
and et al. 1987).
Sufentanil, therefore, appears to reduce the re-
lease of stress-related substances into the blood-
stream but does not prevent their release com-
pletely, especially during surgery and in the recovery
period (when sufentanil concentrations are de-
creasing).
1.5 Cardiovascular Effects
Cardiovascular problems can arise in patients
receiving anaesthetic drugs, and account for the
largest percentage of adverse reactions reported for
these drugs (Dundee & McCaughey 1987). These
effects include reductions of cardiac output, peri-
pheral resistance and blood pressure, and have
proved particularly troublesome with high dose
morphine anaesthesia. Sufentanil. anaesthesia,
however, like that of fentanyl (Stanley 1983), pro-
duces much less haemodynamic instability.
Studies in dogs have shown that anaesthesia with
high doses of sufentanil produced only minimal
haemodynamic changes (De Castro et al. 1979;
Eriksen et al. 1981; Philbin et al. 1984; Reddy et
al. 1980), even when the animals were subjected to
asphyxic stress (Parmentier et al. 1976) or pre-
treated with propranolol (Berthelsen et al. 1980,
1981 b). However, although sufentanil alone pro-
duced no haemodynamic dysfunction, concomi-
tant administration of nitrous oxide produced rapid
deterioration of myocardial function in the areas
of compromised blood flow in animals with cor-
onary artery stenosis (Philbin et al. 1984).
Clinical experience with sufentanil suggests that
the drug maintains cardiovascular stability, includ-
ing systemic and myocardial metabolic paramet-
ers, even during the stress of cardiac surgery (De
Castro 1976; Erpels et al. 1987; Kalenda & Sche-
ijgrond 1976a; O'Young et al. 1987; Sebel & Bovill
1982). Moreover, ventricular function was well
preserved and myocardial perfusion was main-
tained during coronary artery bypass graft surgery
after induction of anaesthesia with sufentanil (Lap-
pas et al. 1985). The incidence of prebypass myo-
cardial ischaemia was 26% in 1 study involving 27
292
patients, but there was a high incidence of pre-ex-
isting haemodynamic instability (hypertension,
hypotension or bradycardia) in these patients [Li-
tak et al. 1987].
The hypertensive response following sterno-
tomy (which may involve a cardiogenic reflex) can
be controlled in most patients with additional su-
fentanil (Sebel & Bovill 1982) or be largely pre-
vented by the use of a high (30 ~g/kg) induction
dose (Griesemer et al. 1982).
The haemodynamic effects of sufentanil have
been compared with those of other anaesthetics,
notably fentanyl (Boulton et al. 1984, 1986; Con-
seiller & Rouby 1978; de Lange 1983; Dubois-Primo
et al. 1976, 1979; Fahmy 1983; Gravlee et al. 1988;
Hempelmann et al. 1978; Howie et al. 1985; Klein-
man et a1. 1985; Komatsu et a1. 1985; Lake &
DiFazio 1987; Larsen et a1. 1980; Miller et al. 1986;
Murkin et a1. 1984; Rolly et a1. 1979; Rosow et a1.
1983; van de Walle et a1. 1976; Weltwood et a1.
1984), halothane/nitrous oxide (Khoury et a1. 1982)
and enflurane/nitrous oxide (Samuelson et a1.
1986). Four-way comparisons with morphine, fen-
tanyl and pethidine have also been carried out
(Flacke et a1. 1985; Ghoneim et al. 1984; Hem-
pelmann et al. 1976). Sufentanil doses have ranged
from 0.3 to 30 ~g/kg. Overall, sufentanil appeared
to be at least as effective in maintaining haemo-
dynamic stability during both cardiac surgery where
high doses were used and after the lower doses used
in general surgery. Heart rate and arterial blood
pressure tended to decrease immediately after in-
duction of anaesthesia with both drugs and to in-
crease after incision and sternotomy.
Patients undergoing general and orthopaedic
surgery experienced significantly greater haemo-
dynamic instability (increase in heart rate, mean
arterial blood pressure and rate-pressure product)
with morphine or pethidine than with sufentanil
or fentanyl (Flacke et al. 1985; Ghoneim et al.
1984). Neither sufentanil nor fentanyl caused sig-
nificant histamine release (Flacke et al. 1985; Ro-
sow et a1. 1984) which may account for their tend-
ency to produce less vasodilation and hypotension
than other narcotic agents.
Muscle relaxants used in conjunction with su-
Sufentanil: A Review
fentanil may affect the haemodynamic response.
Estafanous and Zurick (1985), and Gravlee et al.
(1988), both working with adult patients under-
going coronary artery surgery, found that after su-
fentanil and large doses of pancuronium in com-
bination, patients experienced an increase in heart
rate and cardiac output during operating proce-
dures. However, with sufentanil and metocurine or
vecuronium they did not. The cardiovascular re-
sponses to pancuronium could be prevented by pre-
operative treatment with propranolol. Similarly,
Stanley et al. (1982) showed that patients with cor-
onary artery disease who routinely used ~-blocking
drugs for their angina and hypertension required
less opioid anaesthetic and vasodilator supplemen-
tation during surgery than those not taking ~­
blockers. Other studies have reported haemodyn-
amic stability following induction of anaesthesia
with sufentanil in combination with pancuronium
or vecuronium in patients undergoing coronary ar-
tery surgery (Shulman et al. 1985; Waldmann et al.
1986). Both sufentanil and fentanyl may induce a
hypotensive response in 20 to 30% of patients pre-
viously treated with a benzodiazepine (Flacke et al.
1985; George et al. 1986). These effects have been
shown to be due to indirect effects on the auto-
nomic nervous system, not to direct cardiovascular
depression.
1.6 Effects on Respiration
Like other opioid analgesics, sufentanil pro-
duces a dose-dependent respiratory depression
which may occasionally be rapid and severe. In-
deed, there have been a number of individual case
reports of significant respiratory depression follow-
ing anaesthesia with sufentanil (Chang & Fish 1985;
Goldberg et al.1985; Wiggum et al. 1985).
Clinical studies have shown that sufentanil, 1
to 5~g, administered intravenously, reduces mean
minute volume and respiratory rate (Welchew &
Herbert 1986). Little or no respiratory depression
was observed in patients given sufentanil15 to 50~g
as an epidural analgesic following orthopaedic sur-
gery (Donadoni et al. 1985), although a decreased
ventilatory response to CO 2 was noted in children
293
receiving epidural sufentanil following urological
surgery (Benlabed et al. 1987). In healthy volun-
teers, extradural sufentanil 50~g depressed respi-
ration for about 3 hours (the duration of analgesia)
[Klepper et al. 1987).
Sufentanil also produces respiratory depression
when administered intravenously to induce anaes-
thesia. However, when compared with fentanyl
(usually in a I : 10 dose ratio) sufentanil produced
similar (de Lange et al. 1982b; Pace et al. 1983;
Rolly et al. 1979) or less respiratory depression
(Bailey et al. 1986; Clark et al. 1984; Kalenda &
Scheijgrond 1976b; Sanford et al. 1986; van de
Walle et al. 1976). The respiratory depression was
increased by non-narcotic CNS depressants and
abolished by naloxone (de Castro 1976). The dur-
ation of analgesia after sufentanil was equal to (Ka-
lenda & Scheijgrond 1976b) or greater than (Clark
et al. 1984; de Castro 1976) the duration of res-
piratory depression.
Sufentanil produced no significant changes in
blood gases in the low doses (15 to 50~g) given
epidurally for postoperative analgesia (Donadoni
et al. 1985). However, when given in large doses
intravenously (total dose 19 ~g/kg) in patients
undergoing cardiac surgery sufentanil significantly
altered arterial blood gas tensions and cessation of
spontaneous breathing. These blood gas values only
returned to 'acceptable' levels after a long period
(533 minutes) and only after artificial ventilation
was started. Nevertheless this was at much the same
time as they did after morphine 4.5 mg/kg or fen-
tanyl 95 ~g/kg (Sanford et al. 1986).
1. 7 Effects on Immune Function and
Cell Growth
Infection is still a problem following surgery, and
is made worse by the tendency of some volatile
and intravenous anaesthetics to cause immuno-
suppression (Moudgil et al. 1984). Preliminary
studies indicate that some analogues of fentanyl
may be less likely to affect the immune system.
Neither sufentanil nor alfentanil reduced the
chemotactic migration of neutrophils or mono-
cytes in vitro in blood obtained from healthy sub-
Sufentanil: A Review
jects. Fentanyl, however, reduced neutrophil mi-
gration by about 50% at the highest concentration
(0.1 mmol/L). None ofthe drugs affected mitogen-
or alloantigen-induced Iymphoproliferation in hu-
man blood (Moudgil et al. 1984) or mouse bone
marrow at concentrations far exceeding those found
in plasma during anaesthetic practice (Benestad et
al. 1982).
1.8 Effect on Peripheral Nerve Function
,I n patients undergoing cardiac surgery, induc-
tion of anaesthesia with sufentanil 5 ~gJkg followed
by continuous infusion 5 ~gJkgJh, had no clinically
significant effect on the latencies or amplitudes of
posterior tibial nerve somatosensory-evoked po-
tentials (Kalkman et al. 1987). Similar results were
seen by Bird et al. (1986) after doses of I ~gJkg
followed by bolus and infusion doses of median
nerve evoked potentials in intracranial surgery
patients. However, in patients undergoing lumbar
or thoracic spinal surgery, sufentanil 5 ~gJkg over
30 seconds with pancuronium produced minor
changes in somatosensory-evoked potentials within
the first few minutes after induction, but no further
change thereafter (Koht et al. 1986). High doses of
sufentanil in cardiac surgery patients increased the
latency period and decreased amplitude of median
nerve evoked potentials, although the responses
were not dose-related (Sebel et al. 1988).
In isolated rabbit vagus nerves sufentanil 100
mgJL inhibited the action potential amplitude of
A fibres, and to a lesser extent C fibres, in de-
sheathed nerves. Thus, very high concentrations of
sufentanil may exert weak local anaesthetic-type
activity on peripheral nerves (Gissen et al. 1987).
2. Pharmacokinetic Studies
The pharmacokinetics of sufentanil have been
studied in rats, dogs and man. Techniques used to
measure plasma drug concentrations have in-
cluded gas chromatography (Gillespie et al. 1981;
Woestenborghs et al. 1981) capillary gas chroma-
tography (Weldon et al. 1985) and radioimmu-
noassay (Michiels et al. 1983). The capillary gas
294
chromatographic technique of Weldon et al. (1985)
is claimed to be more sensitive than conventional
gas chromatography and may be able to detect and
discriminate between the 2 major metabolites of
sufentanil. However, radioimmunoassay is the most
sensitive technique and is as specific as capillary
gas chromatography (Heykants et al. 1986). The
pharmacokinetic characteristics of sufentanil are
presented in table I.
2.1 Absorption and Plasma Concentrations
Plasma concentrations of sufentanil decreased
rapidly after administration of a 5 ~gJkg bolus
intravenous injection to 10 surgical patients; 98%
of the dose was removed from the plasma within
30 minutes of administration (Bovill et al. I 984a).
In these patients (fig. 2), and those in 3 other'stud-
ies, the pharmacokinetics of sufentanil could be ex-
plained by a 3-compartment model (Cork et al.
1988b; Greeley et al. 1987; Michiels et al. 1983).
However, a number of authors have reported that
a biexponential equation provides the best fit for
this drug's kinetic profile (Davis et al. 1987; Fy-
man et al. 1987; Schwartz et al. 1987), although
these studies have tended to monitor plasma con-
centrations of sufentanil for shorter periods (::s:: 6
hours).
Mean plasma concentrations of sufentanil
achieved in obese and non-obese patients receiving
mean total doses of 0.96 and I. 50 ~gJkg, respec-
tively (administered by constant infusion for 45
minutes), were 1.29 and 1.41 ~gJL, respectively
(Vinik et al. 1986).
Cohen et al. (1988) compared the pharmacoki-
netic profile of sufentanil after intravenous and
epidural administration in women following cae-
sarean . section. After 30~g doses the mean peak
serum concentration of sufentanil was about 0.1
and 0.4 ~gJL 10 minutes after epidural and intra-
venous administration, respectively. Mean concen-
trations 60 minutes after administration were about
0.05 ~gJL in each treatment group. After a 50~g
epidural dose the mean peak serum concentration
was over 0.25 ~gJL, and remained above 0.1 ~gJL
for over 120 minutes. Nordberg et al. (1988) also
Sufentanil: A Review 295

Table I. Pharmacokinetic properties of sufentanil administered intravenously in adult patients undergoing various surgical procedures

Reference Type of surgery No. of Dosage Vc Vd t'h~ CL

patients lPg/kg) (L/kg) (L/kg) (min) (ml/min • kg)

Bovill et al. (1981a) Elective 5 5 0.104 2.48 149

Bovill et al. (1984a) Elective 10 5 0.164 1.74 164 12.66
Cork et al. (1988b) Various 12 1.5 0.107 6.13 283 15.5
Gregoretti & Vinik (1986) Skin grafts 7 3 0.71 2.59 175 11.15
Matteo et al. (1986) Various 5 2 0.52 4.17 141 21.0
Schwartz et al. (1987) Neurosurgery 5b 4 0.44 5.17 253 14.5
5c 4 0.39 3.00 119 17.4

a Reported at 793 ml/min.

b Hyperventilated patients.
c Non-hyperventilated patients.
Abbreviations: Vc = volume of central compartment; Vd = volume of distribution; t'h~ = elimination half-life; CL = plasma clearance.

administered sufentanil epidurally (75~g). Peak
plasma concentrations were achieved at 9 minutes.
Sufentantil is also absorbed transdermally, with
over 20% of an administered 3H-Iabelled dose being
recovered in the urine of healthy volunteers over
a period of 96 hours (Sebel et al. 1987). If an ap-
propriate transdermal formulation is developed it
may prove of value for long term or postoperative
pain relief. In 10 patients undergoing cardiopul-
monary bypass surgery, using a computer-assisted
continuous infusion system it was possible to
maintain plasma concentrations of sufentanil in the
range 2.5 to 5 ~gjL; however tissue accumulation
may occur (Aezzani et al. 1987).
2.2 Distribution

50.0

Sufentanil is highly protein-bound (about 92.5%

:J' in healthy male volunteers), mainly to ai-acid
~ 10.0 glycoprotein and in this respect differs quite mark-
c
o edly from fentanyl which is about 54% protein
~ bound (Meuldermans et al. 1982). Sufentanil pro-
"E
u
CD
tein binding in the plasma of mothers given epi-
c
o dural anaesthesia during childbirth, and in their
u
1.0
'E"
Ul
neonates was about 91 % and 80%, respectively
'"
a. (Meuldermans et al. 1986); possibly because very
'c young children have lower plasma concentrations
'"
"E of a-acid glycoprotein. The extent of binding de-
CD
"S
rJl pends on blood pH, increasing with increasing al-
2 3 4 5 678
Time (hours)
kalosis, but is independent of drug concentration
(Meuldermans et al. 1982). However, an increased
volume of distribution of sufentanil in hyperven-
Fig. 2. Mean (± SEM) plasma concentrations after bolus intra-
venous injection of sufentanil 5 ,ug/kg. The triexponential equa-
tilated patients with reduced blood pH (Schwartz
tion describes the line of best fit through the points (solid line) et al. 1987), may be explained by an increased ap-
[after Bovill et al. (1984a)]. parent partition coefficient in acid conditions.
Sufentanil: A Review
Sufentanil is distributed in 2 phases; the distri-
bution half-life of the rapid phase is 1.4 minutes
and that of the slow phase is 18 minutes (Bovill et
al. 1984a). The overall distribution half-life in
patients undergoing cardiac surgery is less than that
of fentanyl, being 15 vs 30 minutes (Howie et al.
I 984a). The volume of the initial or central com-
partment has been reported at 0.104 to 0.71 L/kg,
while the volume of distribution is in the range
1.74 to 5.17 L/kg (see table I).
Sufentanil is very lipophilic; its n-oc-
tanol : water partition coefficient is 1754 (com-
pared with 816 for fentanyl). Thus, sufentenil is
likely to penetrate cell membranes easily and rap-
idly (Meuldermans et al. 1982) and to remain in
the deep peripheral (third) compartment for some
time. The transfer rate constant into the peripheral
compartment is greater than the transfer rate out
of it (Bovill et al. 1984a).
Epidural administration of sufentanil 75~g was
extensively distributed to cerebrospinal fluid . Peak
concentrations were reached at 44 minutes and were
14-fold higher than in plasma (Nordberg et al.
1988).
2.3 Metabolism
Sufentanil is rapidly metabolised in rats and dogs
by N-dealkylation at the piperidine nitrogen and at
the amide nitrogen, by O-demethylation and aro-
matic hydroxylation (Meuldermans et al. 1987). At
least 1 metabolite, the O-demethylated product, re-
tains some of the pharmacological activity of su-
fentanil, but it was undetectable in plasma in I
patient after a 3 ~g/kg dose (Heykants et al. 1986).
The metabolic pathways occurring in man have not
been elucidated (Rosow 1984). The 2 primary me-
tabolites of sufentanil have been separated and
quantified in man by Weldon et al. (1985) using a
gas-chromatography technique, but the validity of
this technique has been questioned (Heykants et al.
1986). These same metabolites (norsufentanil and
desmethylsufentanil) were isolated by Timmer-
mans et al. (1988) in urine, but not in plasma.
296
2.4 Elimination
In rats and dogs sufentanil is eliminated in urine
and faeces, 86 to 88% and 70 to 83%, respectively,
being eliminated in 24 hours and over 95% in 4
days. Very little unchanged sufentanil is excreted.
Radiolabel was excreted somewhat differently be-
tween species, with 38% and 62% appearing in urine
and faeces of rats, and 60% appearing in urine and
faeces of rats, and 60% and 40% in urine and faeces
of dogs, respectively. Bile cannulation in rats
showed that this was the route of elimination of
68% of a dose in 24 hours, 22% of which under-
went enterohepatic circulation (Meuldermans et al.
1987).
The plasma clearance of sufentanil in surgical
patients has been reported to be in the range 11 to
21 ml/min· kg (table I).
The elimination half-life of intravenous sufen-
tanil reported in clinical studies is greater than that
of alfentanil but less than that of fentanyl (Bovill
et al. 1984a; Howie et al. I 984b), and ranges from
about 119 to 175 minutes in non-cardiac surgical
patients (table I). The half-life was longer in card-
iac surgery patients (595 minutes; Howie et al.
1984b), hyperventilated surgical patients (253 min-
utes; Schwartz et al. 1987) and after epidural
administration (276 minutes; Nordberg et al. 1988).
The variability in half-life values probably reflects
the physiological changes produced in patients by
anaesthesia and various surgical procedures. In hu-
mans, the elimination of sufentanil is primarily de-
pendent on liver blood flow (Bovill et al. 1984a;
Gregoretti & Vinik 1986). In 10 obese patients
undergoing gastroplastic surgery, who received
constant intravenous infusion of sufentanil for in-
duction, steady-state hepatic clearance of sufen-
tanil was 1100 ml/min/m2 (indicating 80% extrac-
tion.
Following intraportal injection of 3H-sufentanil
250~g in 3 patients, about 60% of the total dose of
radioactivity was accounted for by urinary excre-
tion within 6 hours; about 10% of the dose was
excreted in bile within 1 hour, and about 25% was
accounted for by splanchnic extraction (Schedewie
et al. 1987).
Sufentanil: A Review
2.5 Influence of Disease and Age on
Sufentanil Pharmacokinetics
The pharmacokinetic profile of sufentanil in
patients with chronic renal failure has only been
studied in a few patients. In patients undergoing
renal transplant the kinetics of sufentanil were sim-
ilar to those in otherwise healthy surgical patients
(Davis et al. 1988; Fyman et al. 1987), although
occasional case reports of abnormally high or pro-
longed plasma concentrations have been reported
(Wiggum et al. 1985). In obese patients, about 60%
of an administered dose was eliminated in the urine
after portal vein administration, indicating renal
function would influence sufentanil disposition
(Schedewie et al. 1987). In other studies in obese
individuals sufentanil has been shown to have an
increased elimination half-life and volume of dis-
tribution. Compared to normal patients (Schwartz
et al. 1988). Hepatic excretion and clearance of su-
fentanil has also been shown to be efficient (Sche-
dewie et al. 1987, 1988) and therefore hepatic dis-
ease may significantly affect the pharmacokinetic
profile of the drug, although this remains to be
studied directly.
There is evidence to suggest that the pharmaco-
kinetic disposition of sufentanil is dependent on
age, and is especially variable in neonates (table II;
Davis et al. 1987; Greeley & de Bruijn 1988; Gree-
ley et al. 1987). This may result from differences
in body composition or, more likely, is due to in-
complete to development of hepatic metabolism
systems in very young infants. However, the 3
studies which have reported the pharmacokinetics
of sufentanil in neonates have presented some con-
tradictory results, 1 indicating a reduction in vol-
ume of distribution and elimination half-life and
an increase in plasma clearance (Davis et al. 1987)
and the others indicating the opposite (Greeley &
de Bruijn 1988; Greeley et al. 1987). Further stud-
ies are required to clarify this situation. Meistel-
man et al. (1987) reported a highly significant de-
crease in the free fraction of sufentanil with
increasing age (from neonates to adults), and this
was inversely correlated with the highly significant
decrease in ai-acid glycoprotein plasma concentra-
297
tion with age. The pharmacokinetics of sufentanil
in children and adolescents were found to be sim-
ilar to those in adults (Greeley et al. 1987).
In elderly patients undergoing surgical proce-
dures, results are also variable between studies
(table II), although overall there does not seem
to be a clear case for assuming any differences in
the kinetic disposition of sufentanil in these
patients.
3. Therapeutic Trials
Most therapeutic trials with sufentanil in gen-
eral and cardiac surgery have focussed on its use
as either a primary anaesthetic agent or as an anal-
gesic adjunct to general anaesthesia. Some studies
were uncontrolled, some were dose comparison
studies, but most compared sufentanil with other
anaesthetic agents, notably fentanyl, morphine (and
other opioids) and inhalational agents such as ha-
lothane, enflurane or isoflurane. Studies conducted
in patients undergoing cardiac surgery have gen-
erally used much higher sufentanil doses than those
used in general surgery. In addition, some trials
have been performed to investigate the efficacy and
safety of sufentanil for outpatient anaesthesia. Most
recently, a clinical trial programme has be.en un-
dertaken to investigate the use of sufentanil ad-
ministered by epidural injection for analgesia dur-
ing labour, after surgery and for cancer pain.
3.1 Anaesthesia Studies in Major Surgery
3.1.1 Non-Comparative Trials
Sufentanil, 15 ~gjkg given over 2 minutes, pro-
duced satisfactory anaesthesia in 40 patients
undergoing routine cardiac surgery (Sebel et al.
1981a). Patients were premedicated with lonize-
pam, given pancuronium as a muscle relaxant and
ventilated with an air/oxygen mixture. All re-
mained haemodynamically stable during induction
and intubation but some experienced mild hyper-
tension during sternotomy. No other responses in-
dicative of a lightening of anaesthesia were re-
Sufentani1: A Review 298

Table II. Clinical pharmacokinetics of sufentanil in young and elderly patients

Reference Type of No. of Age Dosage Vd tv,# CL

surgery patients (pg/kg) (L/kg) (min) (ml/min • kg)

Young patients
Davis et al. Cardiac 7 ~ 10 months· 15 1.6e 53 27.5
(1987) 7 ~ 10 months b 15 3.7 120C 21.5
6 10-36 months 15 3.0 55 18.1
Greeley et al. Cardiac 9 0-1 month 10-15 4.15d 737 8 6.78
(1987) 7 1-24 months 10~15 3.09 214 18.1'
7 2-12 years 10-15 2.73 140 16.9'
5 12-18 years 10-15 2.75 209 13.1
Greeley & Cardiac 3g 2-7 days 10 2.73 635 4.23
de Bruijn 20-28 days 10 3.37 217 17.0
(1988)
Elderly patients
Helmers et a!. General 11 17-43 years 3 2.91 99 i 25.5
(1987) 10 69-87 years 3 3.78 146 24.7
Matteo et a!. Various 5 22-57 years 2 4.17 141 21.0
(1986) 5 71-80 years 2 2.55 156 12.7h
Spielvogel Orthopaedic 9 19-45 years 3 2.58 209 11.2
et a!. (1987) 9 71-82 years 3 3.16 267 11.1

a Non-surface-cooled infants.
b Surface-cooled infants.
c Different from the values in the other 2 groups in this study (p < 0.05).
d Different from thB values in patients aged 2 to 12 years and 12 to 18 years (p < 0.05).
e Different from the values in the other 3 groups in this study (p < 0.05).
f Different from the value in patients aged 12 to 18 years (p < 0.05).
g Some patients each undergoing 2 major cardiac operations. No statistical analysis in original study
h Different from the value in the younger group (p < 0.025).
i Different from the other group in this study (p < 0.05).
Abbreviations: Vd = volume of distribution; t'h# = elimination half-life; CL = plasma clearance.

ported; the EEG did not change with anaesthesia
or surgical procedures and no awareness of surgery
was later reported.
A comparison of 2 doses of sufentanil, 15 and
30 ~gjkg, by Griesemer et al. (1982) in a small
number of patients (12) indicated that the higher
dose produced more rapid induction of anaesthesia
(2.1 minutes compared with 2.7 minutes) and re-
duced intraoperational hYPertension (occurring in
1/6 compared with 4/6 patients) without prolong-
ing postoperative respiratory depression. Patients
were premedicated with propranolol (in addition
to diazepam, scopolamine and pancuronium) since
all were previously taking ,B-blocker medication.
High-dose sufentanil anaesthesia, it was concluded,
was preferable to low-dose anaesthesia.
Stanley et al. (1981) demonstrated that patients
given ,B-blockers required lower doses of sufentanil
to induce and maintain anaesthesia than patients
not given ,B-blockers; 11.4 ~gfkg compared with 14.8
~gjkg, respectively (p < 0.01). Similar results were
recorded by Estafanous and Zurick (1985) who also
recorded that the use of metocurine with sufentanil
for anaesthesia resulted in greater haemodynamic
stability, even without the use ofa ,B-blocking agent.
In uncontrolled, multicentre studies performed
in Canada, sufentanil was employed for anaes-
thetic induction in 177 patients undergoing cor-
Sufcntanil: A Review
onary artery bypass graft surgery (Railey et al. 1987)
and 616 patients undergoing other major surgery,
mainly gastrointestinal. genitourinary or general
orthopaedic (Murkin 1987). After premedication,
sufentanil was administered either in conjunction
with pancuronium (cardiac surgery) or with d-tub-
ocurarine, thiopentenone and suxamethonium
(general surgery). Additional doses of sufentanil
were administered as necessary, and the mean total
doses administered in the cardiac and general sur-
gery studies were 24.2 and 2.1 J.Lg/kg, respectively.
Anaesthesia was assessed as 'good' or 'satisfactory'
in over 90% of patients; additional inhalational
agents were required in 61 % of cardiac patients and
43% of general surgical patients. Only I patient ex-
perienced intraoperative awareness (Murkin 1987).
3.1.2 Comparisons with Fentanyl
The anaesthetic effects of sufentanil have been
extensively compared with those of fentanyl in
cardiac, neurological and general surgery (table 1II).
In addition, several other studies have compared
the effects of sufentanil and fentanyl on haemo-
dynamic stability, stress-related hormones, EEG
recordings and respiratory depression (see section
I).
In the anaesthetic studies, sufentanil was gen-
erally given in a dose of I to 50 J.Lg/kg intraven-
ously, which was about 5 to 10 times less than the
dose offentanyl employed. Comparison of data ob-
tained in these studies is complicated by the fact
that no 2 studies used the same combination of
other drugs (such as hypnotics, muscle relaxants,
anticholinergics or inhalational anaesthetics). In
addition, whilst patients undergoing cardiac sur-
gery have generally received much higher doses
than general surgery patients, within these 2 groups
of surgical patient there has been a wide range of
sufentanil doses employed (table III). However, su-
fentanil would appear to be at least as effective as
fentanyl in its ability to produce and maintain hyp-
nosis. The onset of anaesthesia occurred at least as
rapidly with sufentanil (1.2 to 6.5 minutes) as fen-
tanyl (1.8 to 5.3 minutes), and the time to recovery
was usually equivalent with each drug (table III).
During surgery sufentanil produced rather better
299
haemodynamic stability than fentanyl. Kalenda and
Schijgrond (l976b) reported a shorter period of
postoperative assisted ventilation in patients who
received sufentanil as opposed to fentanyl for gen-
eral surgery, while Clark et al. (1987) reported
suppression of the response to CO~ rebreathing
postoperatively after fentanyl but not sufentanil. In
contrast, some authors have recorded more fre-
quent respiratory depression after sufentanil (Shu-
pak & Harp 1985; van de Walle et al. 1976), and
others have shown no difference in the effect of
either drug as mean blood gases (Gauzit et al. 1987;
McKay et al. 1984; Rolly et al. 1979).
Chest wall rigidity may occur with either sufen-
tanil or fentanyl (as with any other potent opioid)
but can usually be prevented or reversed by muscle
relaxants (de Lange et al. 1982b; Gravlee et al.
1988).
3. /.3 Comparisons with Other Opioids
In several controlled studies, the anaesthetic ef-
fects of sufentanil have been compared with those
of other opioids. In cardiac surgery patients, su-
fentanil 15 or 19 J.Lg/kg, respectively, was compared
with alfentanil 125 J.Lg/kg (Bovill et al. 1984), and
morphine 4.4 mg/kg (Sanford et al. 1986). In other
surgical patients, sufentanil has been compared with
morphine 0.6 mg/kg and pethidine 5 J.Lg/kg (Flacke
et al. 1985), morphine 0.6 mg/kg (Ghoneim et al.
1984), and morphine 0.4 mg/kg (Kay & Rolly 1977)
in doses of 1.5 J.Lg/kg, 1.5 to 7.5 J.Lg/kg, and 4 J.Lg/
kg, respectively. In most of these studies, fentanyl
was also used in comparison with the other opioids.
Sufentanil was found to be equipotent in an-
aesthetic effect to fentanyl (Bovill et al 1984; Gho-
neim et al. 1984; Kay & Rolly 1977) as in results
presented in the previous section. However, sufen-
tanil was clearly superior to morphine and pethi-
dine. Sufentanil was the only agent which con-
trolled blood pressure and heart rate satisfactorily
(Flacke et al. 1985). Moreover, time to induction,
return of consciousness and extubation occurred
more rapidly with sufentanil than with morphine
or fentanyl (table IV). Morphine and pethidine were
the least satisfactory opioids with respect to depth
of anaesthesia, haemodynamic stability, respira-
tory depression and recovery time.
Sufentanil: A Review 300

Table III. Studies comparing theclinical efficacy 01 sulentanil (S) and lentanyl (F) lor anaesthesia in major surgery

Relerence Drug Dosage No. of Study Onset of Recovery Haemodynamic Other drugs usedd
IPg/kg) patients design effect time stability"
(min)" (h)b

Cardiac Surgery
de Lange et al. (1982b) S 13 18 1.3 1.8 S>F atr, lor, nit, pan,
F 122 19 4.68 2.1 phe, sux, N20
Dubois-Primo et al. S 0.2 27 r, db S<F dro, flu
(1979) F 2 27
Howie et al. (1985) S 20 26 6.5 S< F lor, pan
F 100 22 5.3
Murkin et al. (1984) S 30 6 r, db 1.2 S=F lor, met, mor, pan,
F 100 6 1.9 sux, il-blocker
Thomson et al. (1987) S 15 17 r, db 1.8 8.1 S=F met, mor, sco
F 100 16 1.8 7.4

Neurosurgery
Bristow et al. (1987) S 0.1' 10 r, db S=F S=F S=F dia, Iru, iso, thi,
F l' 10 vee, N20
McKay et al. (1984) S 6 15 S=F S>F dia, lig, nit, pan,
F 19 15 thi, N20/02
Shupak & Harp (1985) S 20 10 4.8 S=F S=F atr, dia, fru, pan, thi
F 100 10 4.3

Generel Surgery
Clark et al. (1987) S 2 15 0.5 S=F pan, sux, thi, N201
F 15 15 0.5 O2
Fahmy (1983) S 6 11 S>F S> F dia, pan, SUX, thi,
F 32 20 N20-curare
Gauzit et al. (1987) S 0.8 9 r, db S=F S=F atr, lor, sux, thi,
F 6.5 11 N20/02, hal
Kalenda & Scheijgrond S 50 22 S=F atr, dro, eto, niz,
(1976b) F 500 29 pan, sux, N20/02
Rolly et al. (1979) S 2 9 r, db S=F atr, deh/len, meh,
F 20 7 pan, N20
van de Walle et al. S 50 18 r, db S=F S> F eto, pan, sux, N201
(1976) F 500 18 O2

a Mean or median time to loss of consciousness, or comparative effects 01 sufentanil and fentanyl as claimed by the authors:
drugs equivalent (S = F); sufentanil has a more rapid onset 01 effect (S > F).
b Mean or median time to consciousness or orientation, or comparative effects of sulentanil and fentanyl as claimed by the authors:
drugs equivalent (S = F); sufentanil has a quicker recovery rate (S > F).
c Stability 01 cardiovascular parameters during induction 01 anaesthesia and surgery. Authors claim equivalent stability with su-
lentanil and fentanyl (S = F), greater (or tendency towards greater) stability with sulentanil (S > F) or tendency towards lesser
stability with sulentanil (S < F).
d Other drugs used during anaesthetic or surgical procedures: atr = atropine; deh/len = dehydrobenzperidoi/lentanyl;
dia = diazepam; dro = droperidol; eto = etonidate; Ilu = Ilunitrazepam; Iru = Irusemide; hal = halothane; iso = isoflurane;
lig = lignocaine; lor = lorazepam; meh = methohexitone; met = metocurine; mor = morphine; nit = nitroprusside; .liz = nitrazepam;
pan = pancuronium; phe = phentolamine; sco = scopolamine; sux = suxamethonium; thi = thiopentone; vee = vecuronium.
e Signilicantly later than with sulentanil (p < 0.01).
I Dosage in JlQ/kg/h.
Other abbreviations: db = double blind; r = randomised .
Sufentanil: A Review 301

Table IV. Comparison of the effects of sufentanil (18.9 #9/k9). 3.1.5 Comparisons with 1nhalational
fentanyl (95.4 #9/k9) and morphine (4.4 mg/kg) on the time course Anaesthetics
of anaesthesia (Sanford et al. 1986)
The anaesthetic effect of sufentanil 15 to 25 /Lg/
Stage of Time required (min) kg, used as the sole anaesthetic agent, has also been
anaesthesia compared with that of halothane/nitrous oxide
sufentanil fentanyl morphine
(n = 9) (n = 9) (n = 10)
(Estafanous & Zurick 1985; Khoury et al. 1982)
and enflurane/nitrous oxide (Samuelson et al. 1986)
Induction 3" 6 5
inhalational anaesthesia in patients undergoing
cardiac surgery. Patients treated with sufentanil
Return of 17" 62 110
were less haemodynamically unstable but still re-
consciousness
quired some treatment with vasodilators. Times to
Return of acceptable 174" 538 588 responsiveness and extubation were longer for su-
cardiovascular status
fentanil patients than for those treated either with
Extubation 533" 1006 1121 halothane (3.5 and 16.5 hours, respectively, for su-
fentanil; 2.7 and 11 hours, respectively, for halo-
a All sufentanil values significantly lower (p < 0.05) than
fentanyl and morphine values. thane) or enflurane (7.5 and 18 hours, respectively,
for sufentanil; 6.4 and 16 hours, respectively, for
enflurane).
In another study 17 patients were given sufen-
3.1.4 Comparisons with Ketamine and tanil 15 to 20 /Lg/kg and oxygen and 12 patients
Etomidate given 0.5 to 4% halothane and nitrous oxide/oxy-
In a controlled study involving 12 patients with gen. In the sufentanil group 2 patients experienced
cardiomyopathies, anaesthesia for cardiac trans- mild truncal rigidity during induction, 7 patients
plantation was induced with sufentanil 2 to 4.5 /Lg/ required propranolol and 15 required nitroprusside
kg or ketamine 1.5 mg/kg intravenously (Gutzke to control haemodynamic changes, and 8 experi-
et al. 1987). Anaesthesia induction was adequate enced respiratory depression which required 24
with both drugs, but they had differing haemodyn- hours of respiratory support. These effects were all
amic effects: with sufentanil there was no change less apparent in the halothane-treated patients
in wall tension or heart rate, cardiac index, stroke (Khoury et al. 1982). Sufentanil 10 /Lg/kg (and
work index or mean arterial blood pressure whereas maintenance doses where necessary) has also been
with ketamine the latter indices were maintained, compared with isoflurane regarding perioperative
but wall tension increased. It was concluded that outcome in 100 patients undergoing abdominal or
each drug would have benefits in certain subgroups thoracoabdominal aortic reconstruction. Sufen-
of patients with cardiomyopathies. tanil was associated with considerably fewer im-
portant or severe complications (16 events in 9
In a study of 20 patients undergoing coronary
patients vs 48 events in 20 patients), including renal
artery bypass grafting, induction of anaesthesia was
insufficiency (4 vs 16) and congestive heart failure
conducted using succinylcholine with either sufen- (4 vs 13) [Benefiel et al. 1986].
tanil 5 /Lg/kg or etomidate 0.4 mg/kg. Mean
haemodynamic values did not differ significantly 3.1.6 Sufentanil1nfusion
between groups or from baseline, however drug in- Cork et al. (1988a) compared two different an-
tervention was required in only 1 of 11 patients on aesthetic regimens involving sufentanil in 18
sufentanil compared with 8 of 9 patients on etom- patients scheduled for non-cardiac surgery. 12
idate. In addition, 3 etomidate-treated patients ex- patients received a bolus intravenous injection of
hibited ST-segment depression (Butterworth et al. sufentanil (1.5 /Lg/kg over 30 seconds), with slow
1988). infusion of thiopentone to achieve adequate an-
Sufentanil: A Review
Table V. Sufentanil in paediatric cardiovascular surgery
Reference No. of Age Sufentanil Onset of
patients (years) dosage
(pg/kg)
Hickey & Hansen 20 <1 5-10
(1984)
Moore et al. (1985) 20 4-12 5-20
Abbreviations: HR = heart rate; BP = systolic, diastolic and mean arterial blood pressure; SBP
Tco, = transcutaneous O2 monitor.
aesthesia, and insoflurane 0.5 to 1% with nitrous
oxide/oxygen to maintain anaesthesia. The infu-
sion group (n = 6) followed the same procedure,
but received an initial bolus of sufentanil of only
0.5 ~g/kg followed by an infusion of 0.5 ~g/min
adjusted to maintain anaesthesia; they did not re-
ceive isoflurane, and only received 100 or 150mg
of thiopentone. The sufentanil infusion main-
tained better haemodynamic stability throughout
the whole surgical procedure than the bolus dose
plus isoflurane. Recovery time was not signifi-
cantly different between groups. The authors sug-
gested that either of these two regimens involving
sufentanil avoid the risk of late respiratory depres-
sion, as noted in an earlier study involving repeat
bolus doses of sufentanil (Cork 1987).
3.1.7 Use in Paediatric and Elderly Patients
There are many differences between children
with congenital heart disease and adults with cor-
onary artery disease so it may not be correct to
extrapolate results from anaesthesia in adults to the
situation in paediatric patients. However, only 3
studies have been carried out with sufentanil in
children undergoing cardiac surgery (Anand &
Hickey 1987; Hickey & Hansen 1984; Moore et al.
1985), 2 of which are summarised in table V.
Sufentanil 5, i 0 and 20 ~g/kg and fentanyl 50
and 75 mg/L increased transcutaneous oxygen ten-
sion even in cyanotic patients and so may have
stabilised the pulmonary circulation during the
stress of surgery. In other respects sufentanil tended
to produce rather less haemodynamic instability
than fentanyl. Supplementary nitrous oxide was
302
Recovery Haemodynamic Respiratory
effect time effects effects
(min) (min)
2-4 294 j HR & BP on induction t Tco,
t SBP on incision/sternotomy
1-2 '" 230 t SBP with surgical stress
= systolic blood pressure;
given by Hickey and Hansen (1984) when systolic
blood pressure rose more than, 25% above normal.
No nitrous oxide was used by Moore et al. (1985)
whose patients experienced rather more haemo-
dynamic instability. Some myoclonic jerking oc-
curred during induction, and 'startle' arousal and
prolonged respiratory depression accompanied re-
covery. One patient (given 5 ~g/kg) was not com-
pletely amnesic (Moore et al. 1985). Using even
higher doses (35 to 40 ~g/kg as a continuous post-
operative infusion 2 ~g/kg/h) in neonates under-
going cardiac surgery sufentanil was associated with
a reduced metabolic stress response than neonates
who received conventional anaesthesia with halo-
thane, morphine and ketamine (Anand & Hickey
1987).
Elderly patients may have greater sensitivity to
opioids (Scott & Stanski 1987). In elderly patients
requiring hip arthroplasty sufentanil O. 78 ~g/kg and
fentanyl 6.45 ~g/kg produced equivalent anaes-
thesia, with a slightly longer duration of anaes-
thesia and a significantly greater delay before the
need for postoperative analgesia in the sufentanil
group (Gauzit et al. 1987).
3.2 Outpatient Anaesthesia Studies
White et al. (1985) performed a dose-response
study with sufentanil (5, 10,20 and 40~g intraven-
ously) as premedication in 80 women undergoing
minor outpatient gynaecological procedures. An-
aesthesia induction was with methohexitone, and
maintenance with nitrous oxide/oxygen and
methohexitone. They observed a dose-related de-
Sufentanil: A Review
crease in the maintenance requirement of metho-
hexitone with increasing doses of sufentanil. How-
ever, there was a dose-related increase in apnoea
and elevated end-tidal carbon dioxide, a prolonged
time to discharge, and a 45% incidence of chest
wall rigidity in the 40",g group. Thus, doses of 10
or 20",g sufentanil were considered optimal for pre-
medication for brief outpatient surgery.
Other comparative studies in outpatient surgery
have been employing sufentanil for anaesthesia in-
duction. Sufentanil 0.5 to I ",g/kg (plus incre-
mental doses as required) produced equivalent an-
aesthesia to isoflurane I to 3%, both in combination
with thiopentone or methohexitone and nitrous
oxide/oxygen, in patients undergoing elective la-
paroscopy (Wasudev et al. 1987) or arthroscopy of
the knee (Zuurmond & van Leeuwen 1987). Initial
recovery was more rapid with sufentanil, particu-
larly for the comparison with isoflurane (mean
times to eye opening were 2 and 10 minutes in the
sufentanil and isoflurane groups, respectively; p <
0.001). The requirement for postoperative analge-
sia was less after sufentanil than isoflurane in each
study but there was a higher incidence of nausea
and/or vomiting after sufentanil (9/20 vs 3/20
patients in the arthroscopy of the knee study. In
both studies it was concluded that sufentanil was
a suitable alternative to isoflurane for outpatient
surgery.
Phitayakorn et al. (1987) compared sufentanil
with fentanyl (mean total doses of 13 and 93J.tg,
respectively) for anaesthesia induction, in combin-
ation with thiopentone and nitrous oxide/oxygen,
in a controlled study in 50 patients undergoing out-
patient dilatation and curettage of the uterus. The
duration of anaesthesia was 24 minutes in each
treatment group, but the time spent in the recovery
room was significantly shorter for the sufentanil
group (47 vs 56 minutes). Chest wall rigidity oc-
curred in 2 patierits in the sufentanil group. Post-
operative analgesia was required in more patients
in the fentanyl group (6/25 vs 1/25) and the inci-
dence of nausea was significantly higher in this
group (13/25 vs 5/25). Thus, sufentanil was con-
sidered a more appropriate choice than fentanyl for
anaesthesia induction in this outpatient indication.
303
3.3 Epidural Administration
Sufentanil has been administered epidurally for
pain relief during labour, after abdominal, thor-
acic, orthopaedic, urological or general surgery, and
after caesarean section. It has usually been admin-
istered as a bolus injection of 10 to l00",g, via a
catheter placed at a lumbar site, at the first onset
of pain and repeated as necessary thereafter. A few
studies have employed thoracic epidural adminis-
tration, sufentanil infusion and/or introduction of
opioid analgesia prior to the completion of surgery.
For relief of pain during labour, sufentanil has
been administered with bupivicaine (Little et al.
1987; Phillips 1987; Phillips et al. 1988; Van Steen-
berge et al. 1987). A dose of 5 to 15",g reduced the
time to onset of analgesia, compared with bupi-
vicaine alone, from 9.8 to 4.6 minutes (Little et al.
1987) and from 10.3 to 8.5 minutes (Van Steen-
berge et al. 1987); the quality of epidural block was
also improved in these studies. Phillips (1987)
found no reduction in time to the onset of anal-
gesia with sufentanil compared with control but did
report a significant increase in the duration of an-
algesia with doses of 20 and 30",g (table VI). Using
lower doses of sufentanil (2",g), Phillips et al. (1988)
also found that it was possible to reduce the dose
of bupivicaine and the degree of nerve/muscle
complications without affecting time to onset,
quality or duration of analgesia, neonatal Apgar
scores or nausea/vomiting.
Dose-response studies with sufentanil identified
the optimum dose for rapid and satisfactory an-
algesia to be 50J.tg (Donadoni et al. 1985; Lema et
al. 1988; Madej & Strunin 1987) after caesarean
section or orthopaedic surgery (see table VI). With
a 50",g dose the mean onset of analgesia ranges from
about 7 to 8 minutes and the mean duration of
analgesia from about 140 to 410 minutes (see tables
VI and VII). The intensity and onset of analgesia
after epidural administration of sufentanil 30",g was
equivalent to that after intravenous administration
ofthe same dose following caesarean section (Cohen
et al. 1988), although the duration of analgesia was
about twice as long with epidural administration
(200 vs 108 minutes). Administration of adrenaline
Sufentanil: A Review 304

(O.2mg) with sufentanil increased the duration of
analgesia and reduced the requirement for addi-
tional morphine in a study in women undergoing
caesarean section (Lema et al. 1988). However, in
other studies adrenaline (I : 200,000) did not alter
the analgesic properties of sufentanil after caesa-
rean section (Cohen et al. 1988) or general or or-
thopaedic surgery (Parker et al. 1985).
After abdominal surgery, bolus epidural admin-
istration of sufehtanil at doses of 30, SO or 7SfJ,g in
10 patients each resulted in an onset of analgesia
of about S minutes and a duration of analgesia of
about 4 hours, independent of dose (Verborgh et
al. 1986). There was, however, greater sedation and
some respiratory depression after the 7SfJ,g dose.
With sufentanil infusion following abdominal sur-
gery, lumbar placement of the catheter produced
equivalent analgesia to thoracic placement with an
infusion rate of 10 to 12 fJ,g/h (Duckett et al.
1987).
In comparative studies, epidural sufentanil 10
to SOfJ,g produced equivalent postoperative anal-
gesia to fentanyl 100fJ,g (Madej & Strunin 1987),
and sufentanil 30 to 60fJ,g produced a more rapid
but shorter duration of analgesia than morphine
Smg (Rosen et al. 1985) in patients undergoing cae-
sarean section. Comparison of sufentanil 10 to SOfJ,g
with fentanyl 100fJ,g in patients undergoing general
or othopaedic surgery also revealed similar anal-
gesic efficacy with both drugs (Parker et al. 1985).
A more rapid onset and better initial quality of an-
algesia than morphine or nicomorphine (both Smg),
but shorter duration of action than morphine was
seen in thoracic surgery patients (Rosseel et al. 1987,
1988) or abdominal surgery patients (van der Au-
wera et al. 1987), than hydromorphone l.Smg in

Table VI. Dose-response studies with sufentanil administered epidurally for pain relief

Reference Indication Dosage No. of Study Onset of Duration of

(pg) patients design analgesia analgesia
(min) (min)

Phillips (1987) Labour Saline 10 db 16 90

10 10 13.6 114
20 10 15.5 137**
30 10 9.7 144**

Van Steenberge et al. Labour Control 34 r, db 10.3 85.5

(1987) 7.5 36 8.7* 131 .4**
15 37 8.3* 129.8**

Madej & Strunin (1987) Caesarean 10 10 r, db 83

section 20 10 107
30 10 119
50 10 137

Lema et al. (1988) Caesarean Saline 4 r, db 38

section 25 4 4->8 '" 170*
50 4 2-8 '" 320*
75 4 2-8 '" 275*
100 4 2-8

Donadoni et al. (1985) Orthopaedic 15 5 0 7.6 108

surgery 30 5 3.6 265
50 5 6.7 372
75 5 1.7 307

Statistically significant difference from saline control: * = p < 0.05; ** = P < 0.01 .
Abbreviations: db = double-blind; 0 = open; r = randomised.
Sufentanil: A Review 305

Table VII. Comparative studies 01 epidural sulentanil with other opioids used lor postoperative analgesia

Relerence Indication Treatment" No. 01 Study Onset 01 Duration 01

(pg) patients design analgesia analgesia
(min) (min)

Madej & Strunin Caesarean S 20 10 r, db 107

(1987) section S 50 10 137
F 100 10 131

Rosseel et al. Thoracic S 50b 12 7.3 414C

(1987) surgery M 5mg 10 33.5' 612"c

Parker et al. General or Placebo 3 r, db

(1985) orthopaedic S 10 6 22 132
surgery F 100 6 20 112
H 1.5mg 6 30 > 900

Donadoni & Rolly Orthopaedic S5()d 29 r, db 7.7 319

(1987) surgery B 0.3mg 1M 30 11.9 374'

van der Auwera et al. Abdominal S 50 15 r, db 10 > 240

(1987) surgery M 5mg 15 30 > 720

a All drugs administered by epidural injection with lumbar placement 01 the catheter tip, unless otherwise stated.
b Thoracic epidural sulentanil versus lumbar epidural morphine.
c Mean time between injections.
d Thoracic or high lumbar epidural sulentanil versus intramuscular buprenorphine.
Statistically significant difference between treatments: ' = p < 0.05; " = p < 0.01 .
Abbreviations: S = sulentani!; F = lentanyl; M = morphine; H = hydromorphone; B = buprenorphine; 1M intramuscular;
r = randomised; db = double blind.

general or orthopaedic surgery patients (Parker et 4. Adverse Effects

al. 1985) or than buprenorphine 0.3mg (intramus-
cularly) in orthopaedic surgery patients (Donadoni
& Rolly 1987) [see table VII].
In I study sufentanil 0.75 J,Lg/kg was admini-
stered epidurally to 15 children after urological sur-
gery. Effective analgesia was induced rapidly (mean
onset 3 minutes), and lasted for a mean of 198
minutes (Benlabed et al. 1987).
Sufentanil has also been administered epidur-
ally (as a continuous infusion) for the relief of can-
cer pain in 26 outpatients (Boersma et al. 1988).
Patients were in th~ terminal phase of their disease,
and received sufentanil via a subcutaneously im-
planted 'Port-a-Cath' system for a mean period of
infusion per patient of 79 (range 12 to 293) days.
All patients were discharged from hospital pain free,
and no complications were reported in the home
situation. The treatment was considered safe and
effective.
In clinical trials, sufentanil has invariably been
administered with a variety of other medications
necessary to induce or maintain anaesthesia, or re-
quired during the surgical procedure. This com-
plicates the evaluation of the tolerability of sufen-
tanil itself. Investigators have generally categorised
side effects as 'disturbing' or 'non-disturbing'. The
latter are those which are not unexpected, which
present no problem in patient management and
which may be due, at least in part, to I or more
of the other drugs used during the operating pro-
cedure.
4.1 Intravenous Administration
In 2 large, uncontrolled Canadian studies, in a
total of nearly 800 patients, the most frequently
reported disturbing side effects following intraven-
Sufcntanil: A Review 306

in 3. The overall incidence of side effects after su-

A. 10 JJ9/kg fentanil was significantly less than that after peth-
idine (p < 0.05).
-0

~
e::.- Four cases of tonic-clonic movement of the arms
<ll

:1
<.>
c and/or legs have been reported in patients receiv-
<ll
"0
·0 ing intravenous sufentanil ~ 50J.(g (Bowdle 1987;
.E Brian & Seifen 1987; Molbegott et al. 1987). In each
case the activity has occurred within 2 minutes of
sufentanil administration and has ceased spontan-
B. 1-3 JJ9/kg
eously (in 1 case) or after administration of thio-
6 ,..---
pentone (2 cases) or metocurine and pancuronium
(I case). An EEG was recorded in only 1 patient
l
<ll
4
.---
ro- (Bowdle 1987). An increase in 0 activity character-
<.>
c 2 istic of sufentanil was recorded prior to the myo-
<ll

I clonus but there was no cortical seizure activity.

"0
·0
.E 0 indicating that the myoclonus should not be re-
c c
'"
"6 0
u;
0
u;
c "iii '"
E
garded as a convulsion or seizure.
co As with other opioids. respiratory depression is
'"<.>>-
C ~
'"
<.> <ll <ll
>-
s::. (5
a.
t:
<ll en<ll .~ <ll
t/)
"0 dose-related with sufentanil. and isolated cases of
<.> a. "0 :J

cD'"
0>
'"
~
>-
:r:
s::.
:r:>- u ;: z'" significant respiratory depression have been re-
ported after administration of sufentanil for an-
aesthesia (Chang & Fish 1985; Goldberg et al. 1985;
Fig. 3. Incidence of drug-related disturbing side effects in (a)
177 patients receiving sufentanil 10 ,ug/kg intravenously for in- Robinson . 1988; Wiggum et al. 1985). Sufentanil
duction of anaesthesia before cardiac surgery (Railey et al. 1987): seems to produce an 'early' form of respiratory
(b) 616 patients receiving sufentanil 1 to 3 ,ug/kg intravenously depression, rather than a 'late' renarcotisation type
for induction of anaesthesia before elective major surgery (Mur- of depression.
kin 1987).

4.2 Epidural Administration

ous sufentanil administration for induction of an-
aesthesia were hypotension , chest wall rigidity,
tachycardia and bradycardia (Murkin 1987; Railey
et al. 1987; figure 3). Hypertension and nausea also
occurred in over I % of cardiac patients (Railey et
al. 1987).
Flacke et al. (1985) compared the tolerability
profiles of sufentanil 1.28 J.(g/kg, fentanyl 6.97 J.(g/
kg, morphine 0.59 mg/kg and pethidine 4.34 mg/
kg in a total of 60 patients undergoing general or
orthopaedic surgery. Among the disturbing events
reported, only hypotension and tachycardia oc-
curred in more than I patient (2 or 3) after either
sufentanil or morphine. Fentanyl produced chest
wall rigidity in 3 patients, hypertension in 6 and
nausea or vomiting in 3, while pethidine produced
hypotension in 5, hypertension in 4, tachycardia in
3, histamine release in 4 and nausea or vomiting
The most frequently reported adverse reactions
to sufentanil following epidural administration are
nausea, pruritus and sedation; vomiting, dizziness,
shivering and occasional urinary retention have also
been reported (see table VIII). Respiratory depres-
sion was not reported in most studies, but did oc-
cur in I patient receiving sufentanil 50J.(g (Madej
& Strunin 1987). Blackburn (1987) also reported 2
cases of respiratory arrest after several doses of epi-
dural sufentanil 50J.(g during abdominal surgery.
and Donadoni and Capiau (1987) reported I case
of cardiac arrest, probably secondary to respiratory
depression. in a patient who received sufentanil
100J.(g intrathecally for urethrectomy and cystos-
copy. The latter patient received the high dose of
sufentanil in error, and should have received only
10J.(g.
Sufentanil: A Review 307

Table VIII. Side effects reported following epidural administration of sufentanil for analgesia

Reference Indication Treatment No. of Percentage of patients with specific side effects
(.ug) patients
nausea vomiting pruritus urinary sedation other
retention"

Cohen et al. Caesarean S 50 20 25 10 40

(1988) section S 10 IV 20 25 5 5

Donadoni & Rolly Orthopaedic S 50 29 0 3 7 7 31 0

(1987) surgery B 0.3mg 1M 30 7 20 0 7 27 10

Donadoni et al. Orthopaedic S 15-75 20 5 0 15 10 80

(1985) surgery

Lema et al. Caesarean Control 7 71 14 28

(1988) section S 25-100 16 69 63 81
S 25-100 + 17 53 94 82
adrenaline

Madej & Strunin Caesarean S 10 10 60 .0 10 60 0

(1987) section S 20 10 30 10 50 80 0
S 30 10 60 30 20 80 0
S 50 10 30 40 90 90 lOb
F 100 10 20 10 40 50 30b

Van Steenberge Labour Control 34 23 17 3 15 24 c

et al. (1987) S 7.5 36 19 14 22 6 14C
S 15 37 14 8 43 5 27 c

a Not applicable to studies in patients undergoing caesarean section as all would be catheterised.
b Respiratory depression.
c Mainly dizziness.
Abbreviations: S = sufentanil; B = buprenorphine; F = fentanyl; IV = intravenous; 1M = intramuscular.

5. Dosage and Administration
For anaesthesia, the intravenous dose of sufen-
tanil should be determined for each patient inde-
pendently, with particular regard to weight, age, use
of other drugs, pathological condition and the type
of surgical procedure required.
Three types of dosage regimens have been rec-
ommended for general or major surgery; low, mod-
erate and high. Patients requiring general surgery
in which endotracheal intubation and mechanical
ventilation are required may be given a low dose
of sufentanil I to 2 J.Lg/kg, with nitrous oxide/oxy-
gen. Patients requiring more complicated general
surgery may be given a moderate dose of sufentanil
2 to 8 J.Lg/kg, with nitrous oxide/oxygen. Patients
requiring major surgery, such as cardiac or neu-
rological surgery, may be given a high dose of su-
fentanil, 8 to 50 J.Lg/kg, with 100% oxygen. How-
ever, the individual variation in anaesthetic,
analgesic and haemodynamic response to sufen-
tanil can be dramatic and doses should be titrated
according to response wherever possible. This may
be more achievable where the drug is administered
as a constant infusion than when given as a bolus
or rapid infusion dose.
Few problems occur with moderate doses of su-
fentanil; the patient usually remains haemodyn-
amically stable and recovers quickly. The use of
high doses, however, is often associated with pro-
longed respiratory depression. A muscle relaxant
should be given with the anaesthetic and postop-
erative mechanical ventilation maintained as long
as required.
Sufentanil: A Review
Lower doses should be used in elderly patients,
and in children under the age of 12 years the max-
imum dosage should generally not exceed 25 J.Lg/
kg, even during cardiovascular surgery. Sufentanil
should be used with caution in patients with renal
or hepatic disease. Only low doses of sufentanil «
I J.Lg/kg) are required for premedication or anaes-
thesia induction in outpatient surgery.
For postsurgical analgesia sufentanil has been
administered at doses of 10 to 100J.Lg epidurally,
usually at the first onset of pain, and repeated as
necessary; a dose of 30 to 50J.Lg would seem to be
optimal. For relief of pain during labour sufentanil
is usually administered with bupivicaine, and a
lower dose of 10 to 30J.Lg would seem effective.
6. Place of Sufentanil in Therapy
Animal studies with sufentanil have shown it to
be a potent opioid analgesic with a high safety ra-
tio. In theory, therefore, it should have a high de-
gree of specificity in clinical practice, and should
produce fewer side effects than other opioids such
as morphine or, more specifically, fentanyl.
Studies carried out to date appear to confirm
that sufentanil produces better anaesthesia for ma-
jor surgery than morphine or pethidine. However,
results obtained in comparisons with fentanyl are
less clearcut. Several studies found little difference
between sufentanil and fentanyl with regard to
quality of anaesthesia, EEG, metabolic and cardio-
vascular changes, chest wall rigidity and postop-
erative respiratory depression. However, in other
studies, sufentanilhas been reported to maintain
better haemodynamic stability during surgery than
fentanyl. It also maintains haemodynamic stability
better than inhalational anaesthetics. On the avail-
able clinical evidence sufentanil would seem to be
of particular valu.e as an anaesthetic for major sur-
gical procedures such as cardiac surgery, and as a
supplement to balanced anaesthesia in general sur-
gery.
Low dose sufentanil administered intraven-
ously is also a suitable alternative to isoflurane for
outpatient anaesthesia, and may provide quicker
initial recovery and better postoperative pain relief
308
than fentanyl. However, further controlled studies
involving larger patient populations are required to
establish the place for sufentanil in this indication.
Similarly, available evidence suggests a potential
role for epidural sufentanil in the relief of pain dur-
ing labour and for postsurgical analgesia, although
no comparative studies in the former indication
have yet been published. In the latter indication,
pain relief was more rapid but the duration of an-
algesia shorter with epidural sufentanil than after
epidural morphine or hydromorphone, or intra-
muscular buprenorphine.
Thus, intravenously administered sufentanil is
a potent anaesthetic agent, producing rapid anaes-
thesia with haemodynamic stability and allowing
rapid postoperative recovery. Its role as an anal-
gesic supplement administered epidurally after sur-
gery or during labour is promising but requires fur-
ther investigation.
References
Althaus JS, Miller ED, DiFazio CA, Moscicki JC, Engle JS. Fur-
ther evidence for central 5-HT participation in sufentanil-re-
duced MAC. Anesthesia and Analgesia 65 (Suppl. 2): S5, 1986
Althaus JS, Miller ED, Moscicki JC, Hecker BR, DiFazio CA.
Analgetic contribution of sufentanil during halothane anes-
thesia: a mechanism involving serotonin. Anesthesia and An-
algesia 64: 857-863, 1985
Anand KJS, Carr DB, Hickey PRo Randomised trial of high-dose
sufentanil anaesthesia in neonates undergoing cardiac surgery:
hormonal and hemodynamic stress responses. Anesthesiology
67: A501, 1987
Anand KJS, Hickey PR. Randomised trial of high-dose sufentanil
anaesthesia in neonates undergoing cardiac surgery: effects on
the metabolic stress response. Anesthesiology 67 (Suppl. 3A):
A502, 1987
Aoki M, Senami M, Kitahata LM, Collins JG. Spinal sufentanil
effects on pain-transmission neurons in cats. Anesthesiology
64: 225-229, 1986
Avram MJ, Henthorn TK, Krejcie TC. Assay for serum sufen-
tanil level is not sensitive. Anesthesiology 65: 110-111 , 1986
Bailey PL, Streisand JB, Pace NL, Bayless J, Stanley TH. Sufen-
tanil produces shorter lasting respiratory depression and longer
lasting analgesia than equipotent doses of fentanyl in human
volunteers. Anesthesiology 65 (Suppl. 3A): A493, 1986
Benefiel OJ, Roizen MF, Lampe CH, Sonn YJ, Fong KS. Mor-
bidity after aortic surgery with sufentanil vs isoflurane anes-
thesia. Anesthesiology 65 (Suppl. 3A): A516, 1986
Benestad HB, Bjertnaes U, Hersleth lB. Formation of granulo-
cytes and macrophages in mouse bone marrow cultures ex-
posed to various anaesthetics. Acta Anaesthesiologica Scan-
dinavica 26: 357-362, 1982
Benlabed M, Ecoffey C, Levron JC, Aaisler B, Gross JB. Anal-
gesia and ventilatory response to CO 2 following epidural su-
fentanil in children. Anesthesiology 67: 948-951, 1987
Berthelsen P, Eriksen J, Ahn NC, Rasmussen JP. Peripheral cir-
Sufentanil: A Review
culation during sufentanyl and morphine anaesthesia. Acta
Anaesthesiologica Scandinavica 24: 241-244. 1980
Berthelsen P, Eriksen J, Ahn NC, Rasmussen JP. Skeletal muscle
circulation during sufentanil and morphine anaesthesia in pro-
pranolol treated dogs. Acta Anaesthesiologica Scandinavica 25:
6-8, 1981a
Berthelsen P, Strom J, Eriksen J, Rasmussen JP. High-dose anal-
gesic anesthesia with morphine or sufentanil in propranolol-
treated dogs. Acta Anaesthesiologica Scandinavica 25: 447-452,
1981b
Bird J, Donegan J, Rupp S, White P, Sessler D. Effects ofsufen-
tanil bolus and two steady state infusions on median nerve
evoked potentials. Anesthesiology 65: A341 , 1986
Blackburn C. Respiratory arrest after epidural sufentanil. Anaes-
thesia 42: 665-666, 1987
Boersma FP, Noorduin H, Van den Bussche G. Continuous epi-
dural sufentanil infusion for relief of cancer pain on outpatient
basis. Proceedings of the 2nd International Symposium on Re-
gional Anesthesia, Williamsburg, Virginia, USA, 1988
Boulton AJ , Wilson N, Turnbull K, Yip R. A comparison of
haemodynamic and plasma vasopressin responses with high
dose fentanyl and sufentanil anaesthesia during aorto-coronary
bypass surgery. Canadian Anaesthetists' Society Journal 31
(Suppl.): S75-S76, 1984
Boulton AJ, Wilson N, Turnbull K, Yip R. Haemodynamic and
plasma vasopressin responses during high-dose fentanyl or su-
fentanil anaesthesia. Canadian Anaesthetists' Society Journal
33: 475-483, 1986
Bovill JG, Sebel Ps, Blackburn CL, Oei-Lim V, Heykants JJ. The
pharmacokinetics of sufentanil in surgical patients. Anesthe-
siology 61: 502-506, 1984a
Bovill JG, Sebel PS, Blackburn CL, Heykants J. Kinetics of al-
fentanil and sufentanil: a comparison. Anesthesiology 55: A 174,
1981a
Bovill JG, Sebel PS, Fiolet JWT, Touber JL, Kok K, et al. The
influence of sufentanil on endocrine and metabolic responses
to cardiac surgery. Anesthesia and Analgesia 62: 391-397, 1983a
Bovill JG, Sebel PS, Stanley TH. Opioid analgesics in anesthesia:
with special reference to their use in cardiovascular anaes-
thesia. Anesthesiology 61: 731-755, 1984b
Bovill JG, Sebel PS, Wauquier A, Rog P. Electroencephalographic
responses during high-dose opioid anaesthesia. In Spierdijk et
al. (Eds) Developments in drugs used in anaesthesia, pp. 110-
120, Leiden University Press, The Hague, 1981b
Bovill JG, Sebel PS, Wauquier A, Rog P. Electroencephalographic
effects of sufentanil anaesthesia in man. British Journal of An-
aesthesia 54: 45-52, 1982
Bovill JG, Warren PJ, Schuller JL, van Wezel HB, Hoeneveld
MH . Comparison of fentanyl, sufentanil and alfentanil anes-
thesia in patients undergoing valvular heart surgery. Anes-
thesia and Analgesia 63: 1081-1086, 1984
Bowdle TA. Myoclonus following sufentanil without EEG seizure
activity. Anesthesiology 67: 593-595, 1987
Brian JE, Seifen AB. Tonic-clonic activity after sufentanil. Anes-
thesia and Analgesia 66: 481-483, 1987
Bristow A, Shalev D, Rice B, Lipton JM, Giesecke AH. Low-dose
synthetic narcotic infusions for cerebral relaxation during
craniotomies. Anesthesia and Analgesia 66: 413-416, 1987
Butterworth JF, Bean VE, Boyster RL. Rapid sequence induction
of anesthesia for coronary artery bypass surgery: etomidate
versus sufentanil. Anesthesia and Analgesia 67: 525, 1988
Carreras JLA, Henriquez JM, Moreno FC, Perez LP, Esparza LG,
et al. Anestesia-analgesia secuencial: asociacion sulfentanyl -
buprenorfina. Revista Espanola de Anestesiologia y Reani-
macion 25: 149-157, 1978
Cathelin M, Vignes R, Malki A, Viars P. Le citrate de sulfentanil
administre par voie intra-musculaire activite analgesique chez
I'homme conscient. Anesthesie, Analgesie, Reanimation 38: 21-
25, 1981
309
Chang J, Fish KJ. Acute respiratory arrest and rigidity after anes-
thesia with sufentanil: a case report. Anesthesiology 63: 710-
711, 1985
Clark N, Liu WS, Meuleman T, Zwaniken P, Pace NL, et al.
Sufentanil versus fentanyl as a supplement to N 20 anesthesia
during general surgery. Anesthesia and Analgesia 63: 198, 1984
Clark NJ, Meuleman T, Liu WS, Zwanikken P, Pace NL, et al.
Comparison ofsufentanil- N 20 and fentanyl- N 20 in patients
without cardiac disease undergoing general surgery. Anesthe-
siology 66: 130-135, 1987
Cohen SE, Tan S, White PF. Sufentanil analgesia following ce-
sarean section: epidural versus intravenous administration.
Anesthesiology 68: 129-134, 1988
Colpaert FC, Leysen JE, Michiels M, van den Hoogen RHWM.
Epidural and intravenous sufentanil in the rat: analgesia, op-
iate receptor binding, and drug concentrations in plasma and
brain. Anesthesiology 65: 41-49, 1986
Colpaert FC, Niemegeers CJE, Janssen PAJ. Narcotic cueing
properties of intraventricularly administered sufentanil, fen-
tanyl, morphine and met-enkephalin. European Journal of
Pharmacology 47: 115-119, 1978
Conseiller C, Rouby JJ. Haemodynamic influence in deep coma
in man of equi-analgesic doses of morphine, fentanyl and su-
fentanil. In Wood (Ed.) Stress-free anaest~ia, pp. 36-37, Ac-
ademic Press, London, 1978
Cork RC. Sufentanil 0 isoflurane con atracurto 0 vecuronio: com-
paracion de resultatos en anestesia para cirugia general. Re-
vista Mexicana de Anestesiologia 10: 120-128, 1987
Cork RC, Gallo JA, Weiss LB. Sufentanil infusion: pharmaco-
dynamics compared to bolus. Anesthesia and Analgesia 67: 540,
1988a
Cork RC, Gallo JA, Weiss LB, Plezia P, Kramer T, et al. Sufen-
tanil infusion: pharmacokinetics compared to bolus. Anes-
thesia and Analgesia 67: 539, 1988b
Davis PJ, Cook DR, Stiller RL, Davin-Robinson KA. Pharma-
codynamics and pharmacokinetics of high-dose sufentanil in
infants and children undergoing cardiac surgery. Anesthesia
and Analgesia 66: 203-208, 1987
Davis PJ, Stiller RL, Cook DR, Brandom BW, Davin-Robinson
KA. Pharmcokinetics of sufentanil in adolescent patients with
chronic renal failure. Anesthesia and Analgesia 67: 268-271 ,
1988
de Bruijn NP, de Lange S. High dose opioids for coronary artery
surgery. In Stanley TH & Petty WC (Eds) Anesthesia and the
cardiovascular system, pp. 67-71, K1uwer Academic, 1984
De Castro J. Use of sulfentanil in analgesic anaesthesia. VIth World
Congress of Anaesthesiology, Mexico City, April 1976. Anes-
thesie et Reanimation Pratique 6, 96-114, 1976
De Castro J, Van de Water A, Wouters L, Xhonneux R, Reneman
R, et al. Comparative study of cardiovascular, neurological and
metabolic side-effects of eight narcotics in dogs. Acta Anaes-
thesiologica Belgica 30: 5-99, 1979
de Lange S. Clinical experiences with analogues offentanyl. Mount
Sinai Journal of Medicine 50: 312-315, 1983
de Lange S, Boscoe MJ, Stanley TH, de Bruijn N, Philbin DM ,
et al. Antidiuretic and growth hormone responses during cor-
onary artery surgery with sufentanil-oxygen and alfentanil-oxy-
gen anesthesia in man. Anesthesia and Analgesia 61: 434438,
1982a
de Lange S, Boscoe MJ, Stanley TH, Pace N. Comparison ofsu-
fentanil-0 2 and fentanyl-02 for coronary artery surgery. Anes-
thesiology 56: 112-118, 1982b
de Lange S, Stanley TH , Boscoe MJ, de Bruijn N, Berman L, et
al. Catecholamine and cortisol responses to sufentanil-02 and
alfentanil-0 2 anaesthesia during coronary artery surgery. Ca-
nadian Anaesthetists' Society Journal 30: 248-254, 1983
Devaux C, Tessier C, Zickler P, Deshayes P, Oksenhendler G, et
al. Subarachnoid opiates: a comparative study of morphine,
phenoperidine, fentanyl, sui fentanyl and buprenorphine. VIth
Sufentanil: A Review
European Congress of Anaesthesiology, London, September 8-
15, 1982
Donadoni R, Capiau P, Cardiac arrest after spinal sufentanil: case
report. Acta Anaesthesiologica Belgica 38: 175-177, 1987
Donadoni R, Rolly G. Epidural sufentanil versus intramuscular
buprenorphine for postoperative analgesia - a double-blind
comparative trial. Anaesthesia 42: 1171-1175, 1987
Donadoni R, Rolly G, Noorduin H, Vanden Bussche, G. Epi-
dural sufentanil for postoperative pain relief. Anaesthesia 40:
634-638, 1985
Dubois-Primo J, Dewachter B, Massaut J. Analgesic anaesthesia
with fentanyl (F) and sufentanil (SF) in coronary surgery. Acta
Anaesthesiologica Belgica 2: 113-126, 1979
Dubois-Primo J, Geens-Bastenier J, Genicot C. The use of fen-
tanyl and sulfentanil for analgesic anesthesia during cardiac
surgery with extracorporeal circulation. Vlth World Congress
of Anaesthesiology, Mexico City, April 1976. Anesthesie et
Reanimation Pratique 6: 175-179, 1976
Duckett JE, McDonnell T, Zebrowski M, Witte M. Lumbar ver-
sus thoracic continuous epidural sufentanil for postoperative
analgesia after upper abdominal surgery. Anesthesia and An-
algesia 66: S45, 1987
Dundee JW, McCaughey W. Drugs in anaesthetic practice. In
Speight TM (Ed.) Drug treatment, principles and practice of
clinical pharmacology and therapeutics, 3rd ed., pp. 303-359,
Adis Press, Auckland, 1987
Eriksen J, Berthelsen P, Ahn NC, Rasmussen JP. Early response
in central hemodynamics to high doses of sufentanil or mor-
phine in dogs. Acta Anaesthesiologica Scandinavica 25: 33-38,
1981
Erpels FA, Vermeyen KM, Beeckman CP, Hanegreefs GH. Con-
tinuous infusion of sufentanil in elderly patients undergoing
coronary bypass surgery. Presented at the European Associa-
tion of Cardiothoracic Anaesthesiologists, G6ttingen, May 19-
21, 1987
Estafanous FG, Zurick AM. Hemodynamic effects of sufentanilj
metocurine versus sufentaniljpancuronium in patients under-
going coronary artery surgery. Cleveland Clinic Quarterly 52:
391-397, 1985
Fahmy NH. Sufentanil as an analgesic supplement in general sur-
gical anesthesia. The Cleveland Clinic Foundation, In Opioids
in anesthesia, pp. 8-10, May 26-27, 1983
Flacke JW, Bloor BC, Kripke BJ, Flacke WE, Warneck CM, et
al. Comparison of morphine, meperidine, fentanyl and sufen-
tanil in balanced anesthesia. Anesthesia and Analgesia 64: 897-
910, 1985
Flezzani P, Alvis MJ , Jacobs JR, Schilling MM, Bai S, Reves JG.
Sufentanil disposition during cardiopulmonary bypass. Cana-
dian Journal of Anaesthesiology 34: 566-569, 1987
Fyman P, Avitable M, Moser F, Reynolds J, Casthely P, et al.
Sufentanil pharmacokinetics in patients undergoing renal
transplantation. Anesthesia and Analgesia 66 (Suppl.): 62, 1987
Gauzit R, Marty J, Couderc E, Bouyet I, Flaischler B, et al. Com-
parison of sufentanil and fentanyl with N20 halothane anes-
thesia for total hip arthroplasty in elderly patients. Anesthe-
siology 67: A120, 1987
George J, Samuelson PN, Lell WA, Kirklin JK, Bradley EL, et
al. Hemodynamic effects of diazepam-sufentanil compared to
diazepam-fentanyl.. Presented at the 8th Annual Meeting of the
Society of Cardiovascular Anesthesiologists, Montreal, April
27-30, 1986
Ghoneim MM, Dhanaraj J, Choi WW. Comparison offour opioid
analgesics as supplements to nitrous oxide anesthesia. Anes-
thesia and Analgesia 63: 405-412, 1984
Gillespie TJ, Jay Gandolfi A, Maiorino RM, Vaughan RW. Gas
chromatographic determination of fentanyl and its analogues
in human plasma. Journal of Analytical Toxicology 5: 133-
137, 1981
Gissen AJ, Gugino LD, Datta S, Miller J, Covino BG. Effects of
310
fentanyl and sufentanil on peripheral mammalian nerves.
Anesthesia and Analgesia 66: 1272-1276, 1987
Goldberg M, Ishak S, Garcia C, McKenna J. Postoperative rig-
idity following sufentanil administration. Anesthesiology 63:
199-201 , 1985
Gravlee GP, Ramsey FM, Roy RC, Angert KC, Rogers AT, et
al. Rapid administration of narcotic and neuromuscular blocker:
a hemodynamic comparison of fentan yl, sufentanil, pancuron-
ium and vecuronium. Anesthesia and Analgesia 67: 39-47, 1988
Greeley WJ, de Bruija NP. Changes in sufentanil pharmacokin-
etics within the neonatal period. Anesthesia and Analgesia 67:
89-90, 1988
Greeley WJ, de Bruijn NP, Davis DP. Sufentanil pharmacokin-
etics in pediatric cardiovascular patients. Anesthesia and An-
algesia 66: 1067-1072, 1987
Gregoretti S, Vinik HR. Sufentanil pharmacokinetics in burn
patients undergoing skin-grafting. Anesthesia and Analgesia 65
(Suppl. 2): 64, 1986
Griesemer RW, Moldenhauer CC, Hug Cc. Sufentanil anesthesia
for aortocoronary bypass surgery: 30 mcg/kg vs 15 mcg/kg.
Anesthesiology 57: A48, 1982
Gutzke GE, Shah K, Glisson SN, Griesemer R, Rao TlK. Su-
fentanil or ketamine: induction in cardiomyopathy patients.
Anesthesiology 67: A64, 1987
Hall RI, Murphy MR, Hug Cc. The enflurane sparing effect of
sufentanil in dogs. Anesthesiology 67: 518-525, 1987
Hecker BR, Lake CL, DiFazio CA, Moscicki JC, Engle JS. The
decrease of the minimum alveolar anesthetic concentration
produced by sufentanil in rats. Anaesthesia and Analgesia 62:
987-990, 1983
Helmers JHJH, Van Peer A, Noordnin H, Woestenbarghs R, Van
den Bussche G, et al. Sufentail kinetics in the elderly. Beitrage
zur Anaesthesiologie und Intensivmedizin 20: 376-377, 1987
Hempelmann G, Piepenbrock S, Rinke R, Weber K. A compar-
ative hemodynamic investigation in patients with myocardial
disease, using sulfentanil (R 30 730), fentanyl , pethidine, mor-
phine and f1unitrazepam. Anesthesie et Reanimation Pratique
6: 135-138, 1976
Hempelmann G, Seitz W, Piepenbrock S, Schleussner E. Com-
parative investigation on the cardiac and vascular effects of
sufentanil, a new analgesic, and fentanyl. Praktische Anaes-
thesie Wiederbelebung und Intensivtherapie 13: 429-437, 1978
Hermans B, Gommeren W, De Potter WP, Leysen JE. Interaction
of peptides and morphine-like narcotic analgesics with specif-
ically labelled mu- and delta-opiate receptor binding sites. Ar-
chives Internationales de Pharmacodynamie et de Therapie 263:
317-319,1983
Heykants J, Woestenborghs R, Timmerman P. Reliability of su-
fentanil plasma level assays in patients. Anesthesiology 65: 112-
113, 1986
Hickey PR, Hansen DD. Fentanyl- and sufentanil-oxygen-pan-
curonium anesthesia for cardiac surgery in infants. Anesthesia
and Analgesia 63: 117-124, 1984
Howie MB, McSweeney TD, Lingam RP, Maschke SP. A com-
parison of fentanyl-02 and sufentanil-0 2 for cardiac anes-
thesia. Anesthesia and Analgesia 64: 877-887, 1985
Howie MB, Smith DF, Dasta JF, Harrington K, Reitz J. Phar-
macokinetic comparison of sufentanil and fentanyl during
anesthesia for cardiac surgery. Anesthesiology 61: A377, 1984a
Howie MB, Smith DF, Harrington K, Dasta JF, Reilley TE, et
al. Serum concentrations of sufentanil and fentanyl in the post-
operative course in cardiac surgery patients. Anesthesiology 61 :
A13I , 1984b
James IF, Goldstein A. Site-directed alkylation of multiple opioid
receptors. I. Binding selectivity. Molecular Pharmacology 25:
337-342, 1984
Kalenda Z, Scheijgrond HW. R30730 (sulfentanil) in neuroanes-
thesia. Anesthesie et Reanimation Pratique 6: 182-189, 1976a
Kalenda Z, Scheijgrond HW. Anaesthesia with sulfentanil-anal-
Sufentanil: A Review
gesia in carotid and vertebral arteriography: a comparison with
fentanyl. Anaesthesist 25: 380-383, 1976b
Kalkman CJ, van Rheineck Leyssius AT, Hesselink EM, Bovill
JG. Effects of high dose sufentanil or alfentanil anesthesia on
posterior tibial nerve somatosensory evoked potentials. Anes-
thesiology 67: A386, 1987
Kay B, Rolly G . Duration of action of analgesic supplements to
anesthesia: a double-blind comparison of morphine, fentanyl
and sulfentanil. Acta Anaesthesiologica Belgica 28: 25-32, 1977
Khoury GF, Estafanous FG, Zurick AM, Lytle B. Sufentanil/pan-
curonium versus sufentanil/metocurine anesthesia for coron-
ary artery surgery. Anesthesiology 57: A47, 1982
Kleinman J, Marlar K, Silva DA, Miller R, Kaplan JA. Sufentanil
attenuation of the stress response during rapid sequence in-
duction. Anesthesiology 63: A379, 1985
Klepper ID, Sherrill DL, Boetger CL, Bromage PRoAnalgesic and
respiratory effects of extradural sufentanil in volunteers and
the influence of adrenaline as an adjuvant. British Journal of
Anaesthesia 59: 1147-1156, 1987
Koht A, Kimovec MA, Sloan TB, Carlvin AO. The effects of
sufentanil on median nerve somatosensory evoked potentials.
Anesthesia and Analgesia 65 (Suppl. 2): S81, 1986
Komatsu T, Shibutani K, Okamoto K, Kubal K, Bhalodia R. Is
sufentanil superior to fentanyl as an induction agent? Anes-
thesiology 63: A378, 1985
Kostelitz HW, Lord JAH, Peterson SJ, Waterfield AA. Effects of
changes in the structure of enkephillins and of narcotic anal-
gesic drugs on their interactions with Il or a-receptors. British
Journal of Pharmacology 68: 332-342, 1980
Kubicki ST, Freund G, Henschel FW, Schoppenhorst M. Fen-
tanyl und Sulfentanil im elektroenzephalographischen Ver-
g1eich. Anaesthesist 26: 333-342, 1977
Kugler J, Grote B, Laub M, Doenicke A, Dick E. Die hypnotische
Wirkung von Fentanyl und Sufentanil. Anaesthesist 26: 343-
348, 1977
Lacoumenta S, Yeo TH, Paterson JL, Burrin JM, Hall GM. Hor-
monal and metabolic responses to cardiac surgery with sufen-
tanil-oxygen anaesthesia. Acta Anaesthesiologica Scandinavica
31 : 258-263, 1987
Lake CL, DiFazio CA. Sufentanil versus fentanyl: hemodynamic
effects in valvular heart disease. Anesthesia and Analgesia 66:
S99, 1987
Lappas 00, Palacios I, Athanasiadis C, Mastrocostopoulos G,
Hilgenberg A, et al. Sufentanil dosage and myocardial blood
flow and metabolism in patients with coronary artery disease.
Anesthesiology 63: AS8, 1985
Larsen R, Sonntag H, Schenk HD, Radke J, Hilfiker O. Die Wir-
kungen von Sufentanil und Fentanyl auf Haemodynamik, Co-
ronardurchblutung und myocardialen Metabolismus des
Menschen. Anaesthesist 29: 277-279, 1980
Lema MJ, Sevarino FB, Datta S, Ostheimer G, Naulty JS. Epi-
dural administration of sufentanil for postcaesarean delivery
analgesia. Anesthesiology, in press, 1988
Leysen JE, Gommeren W. In vitro binding properties of 3H-su-
fentanil, a superior ligand for the Il-opiate receptor. Archives
Internationales de Pharmacodynamie et de Therapie 260: 287-
289, 1982
Leysen JE, Gommeren W, Niemegeers CJE. (lH) sufentanil, a
superior ligand for 1l-6piate receptors: binding properties and
regional distribution in rat brain and spinal cord. European
Journal of Pharmacology 87: 209-225, 1983
Lipszyc M, Engelman E, Gilbart E, Van der Linden P, de Rood
M. Postoperative catecholamine secretion. Influence of post-
operative sedation technique. Proceedings of the 9th World
Congress of Anaesthesiologists, Washington, USA, 1988
Litak CW, Railey FE, Wynands JE, Ansley DM, Sami MH.
Hemodynamic variables and the incidence of prebypass is-
chemia during sufentanil/02/pancuronium anesthesia in
311
patients undergoing coronary artery surgery. Journal of Car-
diothoracic Anesthesia I: 10-18, 1987
Little MS, McNitt JD, Choi HJ, Tremper KK. A pilot study of
low dose epidural sufentanil and bupivacaine for labor anes-
thesia. Anesthesiology 67: A444, 1987
Madej TH , Strunin L. Comparison of epidural fentanyl with su-
fentanil; analgesia and side effects after a single bolus dose
during elective Caesarean section. Anaesthesia 42: 1156-1161,
1987
Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE.
The effects of morphine and morphine-like drugs in the non-
dependent and morphine-dependent chronic spinal dog. Jour-
nal of Pharmacology and Experimental Therapeutics 197: 517-
732, 1976
Matteo RS, Ornstein E, Young WL, Schwartz AE, Port M, et al.
Pharmacokinetics of sufentanil in the elderly. Anesthesia and
Analgesia 65 (Suppl. 2): 94, 1986
McKay RD, Varner PD, Hendricks PL, Adams ML, Harsh GR.
The evaluation of sufentanil-N 20-0 2 versus fentanyl-N 20-02
anesthesia for craniotomy. Anesthesia and Analgesia 63: 250,
1984
Meistelman C, Benhamou D, Mahe V, Levron JC, Mazoit X, et
al. Effects of age on plasma protein binding of sufentanil.
Anesthesiology 67: A518, 1987
Meuldermans W, Hendrich J, Lauwers W, Hurkmans R, Sur-
ysen E, et al. Excretion and biotransformation of alfentanil and
sufentanil in rats and dogs. Drug Metabolism and Disposition
15: 905-913, 1987
Meuldermans WEG, Hurkmans RMA, Heykants JJP. Plasma
protein binding and distribution of fentanyl, sufentanil, alfen-
tanil and lofentanil in blood. Archives Internationales de Phar-
macodynamie et de Therapie 257: 4-19, 1982
Meuldermans W, Woestenborghs R, Noorduin H, Camu F, van
Steenberge A, et al. Protein binding ofthe analgesics alfentanil
and 'sufentanil in maternal and neonatal plasma. European
Journal of Clinical Pharmacology 30: 217-219, 1986
Michiels M, Hendriks R, Heykants JJ. Radioimmunoassay ofthe
new opiate analgesics alfentanil and sufentanil. Journal of
Pharmacy and Pharmacology 35: 86-93, 1983
Miller DR, Laidley D, Teasdale SJ, Young P, Ivanov J, et al.
Adverse myocardial function and metabolism on anesthetic
induction : a comparison offentanyl, sufentanil and alfentanil.
Anesthesiology 65 (Suppl.): A506, 1986
Molbegott LP, F1ashburg MH, Karasic HL, Karlin BL. Probable
seizures after sufentanil. Anesthesia and Analgesia 66: 91-93,
1987
Moore RA, Yang SS, McNicholas KM, Gallagher JD, Clark DL.
Hemodynamic and anesthetic effects of sufentanil as the sole
anesthetic for pediatric cardiovascular surgery. Anesthesiology
62: 725-731 , 1985
Moudgil GC, Singal DP, Gordon J, Forrest JB. Fentanyl, sufen-
tanil and alfentanil do not inhibit cell-mediated immune re-
sponses in vitro. Anesthesiology 61: A355, 1984
Murkin JM, Moldenhauer CC, Griesemer RW, Hug Cc. Fentanyl
vs sufentanil: comparison of hemodynamic and catecholamine
responses during coronary artery (CABG) surgery. Anesthe-
siology 61 : A375, 1984
Murkin JM. Multicentre clinical trial: sufentanil for major sur-
gery. Canadian Journal of Anaesthesia 34: S84, 1987
Niemegeers CJE, Schellekens KHL, Van Bever WFM, Janssen
PAJ. Sufentanil, a very potent and extremely safe intravenous
morphine-like compound in mice, rats and dogs. Arzneimittel-
Forschung 26: 1551-1556, 1976
Nitti GJ , Ward DS, Antron LM. The effect of sufentanil on the
catecholamine response to metabolic rate, hypercapnia and hy-
poxia. Anesthesiology 85: A563, 1986
Nordberg G , Hedner T. Sufentanil pharmacokinetics in plasma
Sufentanil: A Review
and CSF following epidural administration. Clinical Pharma-
cology and Therapeutics 43: 138, 1988
O'Young J, Mastrocastopoulos G, Hilgenberg A, Palacios I, Kyr-
itsis A, et al. Myocardial circulatory and metabolic effects of
isoflurane and sufentanil during coronary artery surgery. Anes-
thesiology 66: 653-658, 1987
Noueihed R, Durant P, Yaksh TL. Studies on the effects of in-
trathecal sufentanil, fentanyl and alfentanil in rats and cats.
Anesthesiology 61: A218, 1984
Pace NL, Van De Martin J, Liu WS, Andriano KP, Westenskow
DR, et al. Comparisons of postoperative ventilatory control
following anesthesia with fentanyl, alfentanil and sufentanil.
In Opioids in anesthesia, p. 27, The Cleveland Clinic Foun-
dation, May 26-27, 1983
Parker EO, Brookshire GL, Bartel SJ, Menard RG, Culverhouse
ED, et al. Effects of epinephrine on epidural fentanyl, sufen-
t,anil and hydromorphone for postoperative analgesia. Anes-
thesiology 63: A235, 1985
Parmentier P, Snoeckx L, Van de Water A, Wouters L. Massive
doses of sulfentanil after severe asphyxia in dogs: cardiovas-
cular and hemodynamic tolerance: effects on asphyxia toler-
ance. Anesthesie et Reanimation Pratique 6: 81-85, 1976
Philbin OM, Foex P, Drummond G, Ryder WA, Jones LA. Re-
gional ventricular function with sufentanil anesthesia: The ef-
fect of nitrous oxide. Anesthesia and Analgesia 63: 260, 1984
Phillips GH. Combined epidural sufentanil and bupivacaine for
labor analgesia. Regional Anesthesia 12: 165-168, 1987a
Phillips GH. Epidural sufentanil/bupivacaine combinations for
analgesia during labor: effect of varying sufentanil doses. Anes-
thesiology 67: 835-838, 1987b
Phitayakorn P, Melnick BM, Vicinie AF. Comparison of contin-
uous sufentanil and fentanyl infusions for outpatient anaes-
thesia. Canadian Journal of Anaesthesia 34: 242-245, 1987
Railey FE, Teasdale S, Wynands JE. Sufentanil for coronary ar-
tery bypass graft surgery: the Canadian experience. Canadian
Journal of Anaesthesia 34: SIlO-III, 1987
Reddy P, Liu W-S, Port 0, <;iillmor S, Stanley TH. Comparison
of haemodynamic effects M anaesthetic doses of alphaprodine
and sufentanil in the dog. Canadian Anaesthetists Society
Journal 27: 345-350, 1980
Robinson D. Respiratory arrest after recovery from anaesthesia
supplemented with sufentanil. Canadian Journal of Anaes-
thesia 35: 101-106, 1988
Roizen MF, Lampe GH, Benefiel OJ, Sohn YJ, Lichtor JL, et al.
Is increased operative stress associated with worse outcome.
Anesthesiology 67 (Suppl. 3A): AI, 1987
Rolly G, Kay B, Cockx F. A double blind comparison of high
doses fentanyl and sufentanil in men: influence on cardiovas-
cular, respiratory and metabolic parameters. Acta Anaesthe-
siologica Belgica 30: 247-254, 1979
Rosen MA, Dailey PA, Hughes SC, Leicht CH, Shnider SM, et
al. Epidural siJfentanil for postoperative analgesia after cae-
sarian section. Anesthesiology 68: 448-454, 1988
Rosenbaum JS, Holford NHG, Sadee W. Opiate receptor bind-
ing-effect relationship: sufentanil and etorphine produce an-
algesia at the It-site with low fractional receptor occupancy.
Brain Research 291: 317-324, 1984
Rosow CEo Sufentanil citrate: a new opioid analgesic for use in
anesthesia. Pharmacotherapy 4: 11-19, 1984
Rosow CE, Philbin OM, Keegan CR, Moss J. Hemodynamics
and histamine release during induction with sufentanil or fen-
tanyl. Anesthesiology 60: 489-491, 1984
Rosow CE, Philbin OM, Moss J, Keegan CR, Schneider RC. Su-
fentanil vs fentanyl: I. Suppression of hemodynamic re-
sponses. Anesthesiology 59: A323, 1983
Rosseel PMJ, van den Broek WGM, Boer EC, Prakash O. A com-
parison between epidural sufentanil and morphine for anal-
gesia after thoracic surgery. Presented at the Vlth Annual
312
Meeting of the European Society of Regionai Anaesthesia, Paris,
May 7-9, 1987
Rosseel PMJ, Smit HB, Bach Kolling J, Theunissen CMP, Van
der Starre PJA. Epidural sufentanil, nicomorphine or mor-
phine for postoperative pain after lung surgery. Proceedings of
the 2nd International Symposium on Regional Anesthesia,
Williamsburg, Virginia, USA, 1988
Samuelson PN, Reves JG, Kirklin JK, Bradley E, Wilson KD, et
al. Comparison of sufentanil and enflurane-nitrous oxide anes-
thesia for myocardial revascularization. Anesthesia and An-
algesia 65: 217-226, 1986
Sanford TJ, Smith NT, Dec-Silver H, Harrison WK. A compar-
ison of morphine, fentanyl and sufentanil anaesthesia for card-
iac surgery. Anesthesia and Analgesia 65: 259-266, 1986
Schedewie HK, Lee LA, Cowan GS, Gold RE, Bottorff MB, et
al. Hepatic clearance of sufentanil in humans. Anesthesiology
67: A291 , 1987
Schedawie M, Lee L, Gold R, Straughn A. Sufentanil and fentanyl
hepatic extraction rate and clearance in obese patients under-
going gastroplasty. Clinical Pharmacology and Therapeutics 43:
132, 1988
Schwartz AE, Matteo RS, Ornstein E, Thornhill M. Pharmaco-
kinetics of sufentanil in hyperventilated patients. Anesthesia
and Analgesia 66 (Suppl): 151, 1987
Schwartz AE, Matteo RS, Ornstein E, Young WL, Robinson ST.
Pharmacokinetics of sufentanil in the obese. Anaesthesiology
65 (Suppl. 3A): A562, 1988
Scott JC, Stanski DR. Decreased fentanyl and alfentanil dose re-
quirements with age: a simultaneous pharmacokinetic and
pharmacodynamic evaluation. Journal of Pharmacology and
Experimental Therapeutics 240: 159-166, 1987
Sebel PS, de Bruijn N, Jacobs J, Neville WK. Median nerve so-
matosensory evoked potentials during anaesthesia with sufen-
tanil or fentanyl. Proceedings of the 10th Annual Meeting of
the Society of Cardiovascular Anesthesiologists, p. 124, 1988
Sebel PS, Barrett CW, Kirk CJC, Heykants J. Transdermal ab-
sorption of fentanyl and sufentanil in man. European Journal
of Clinical Pharmacology 32: 529-531, 1987
Sebel PS, Bovill JG. Cardiovascular effects of sufentanil anaes-
thesia. Anesthesia and Analgesia 61 : 115-119, 1982
Sebel PS, Bovill JG, Fiolet J, Touber JL, Philbin OM. Hormonal
effects of sufentanil anesthesia. 56th Congress International
Anaesthesia Research Society, San Francisco, March 14-18, 1982
Sebel PS, Bovill JG, Wauquier A. Total narcotic anesthesia with
sufentanil. Anesthesia and Analgesia 60: 276, 1981a
Sebel PS, Bovill JG, Wauquier A, Rog P. Electroencephalographic
effects of sufentanil anesthesia in man. Anesthesiology 55: A254,
1981b
Shulman B, Manos J, Feinberg B, Mora C. LaMantia K, et al.
Hemodynamic effects of pancuronium vs vecuronium during
sufentanil induction for CABG. Anesthesiology 63 (Suppl.): A99,
1985
Shupak RC, Harp JR. Comparison between high-dcse sufentanil-
oxygen and high-dose fentanyl-oxygen for neuroanaesthesia.
British Journal of Anaesthesia 57: 375-381 , 1985
Smith NT, Dec-Silver H, Sanford TJ, Westover CJ, Quinn ML,
et al. EEGs during high dose fentanyl-, sufentanil-, or mor-
phine-oxygen anesthesia. Anesthesia and Analgesia 63: 386-393,
1984
Spielvogel C, Caron I, Levron JC, Leinhart A. Pharmacokinetic!
of sufentanil in the elderly. Anaesthesiology 67 (Suppl. 3A):
A389, 1987
Stanley TH. The new opioids. In Stanley TH & Petty WC (Eds)
New anesthetic agents, devices and monitoring techniques,
Annual Utah Postgraduate Course in Anesthesiology, pp. 120-
126, 1983
Stanley TH, de Lange S, Boscoe MJ. The influence of chronic
preoperative /3-adrenergic blocker therapy on intraoperative
Sufentanil: A Review
cardiovascular dynamics and narcotic requirements in patients
with coronary artery disease. Anesthesiology 55: A48, 1981
Stanley TH, de Lange S, Boscoe MJ, de Bruijn N. The influence
of chronic preoperative propranolol therapy on cardiovascular
dynamics and narcotic requirements during operation in
patients with coronary artery disease. Canadian Anaesthetists'
Society Journal 29: 319-324, 1982
Thomson IR, Hudson RJ, Rosenbloom M, Meatherall RC. A ran-
domized double-blind comparison of fentanyl and sufentanil
anaesthesia for coronary artery surgery. Canadian Journal of
Anaesthesia 34: 227-232, 1987
Timmerman P, Woestenborghs R, Meuldermans W, Helmers
JHJH, Heykants J. The metabolism and excretion of sufen-
tani! after intravenous administration in man. Data on file,
Janssen Laboratories
Upton N, Sewell RDE, Spencer PSJ. Differentiation of potent
mu- and kappa-opiate agonists using heat and pressure anti-
nocicepti,ve profiles and combined potency analysis. European
Journal of Pharmacology 78: 421-429, 1982
Van Bever WFM , Niemegeers CJE, Schellekens KHL, Janssen
PAJ. N-( 4-substituted-I-(2-arylethyl)-4-piperidinyl)-N-phenyl-
propanamides, a novel series of extremely potent analgesics
with unusually high safety margin. Arzneimittel-Forschung 26:
1548-1551 , 1976
Vanden Bussche G, Noorduin H. Alfentanil and sufentanil: to-
wards a more specific use of narcotics in anaesthesia. Drug
Development Research 8: 341-346, 1986
van den Hoogen RHWM, Colpaert FL. Analgesic and respiratory
effects of opiates in rats. Acta Anaesthesiologica Belgica 34
(Suppl. I): 85, 1983
van de Walle J, Lauwers P, Adriaensen H. Double blind com-
parison of fentanyl and sulfentanil in anesthesia. Acta Anaes-
thesiologica Belgica 27: 129-138, 1976
van der Auwera D, Verborgh C, Camu F. Analgesic and cardio-
respiratory effects of epidural sufentani! and morphine in hu-
mans. Anesthesia and Analgesia 66: 999-1003, 1987
Van Steenberge A, Debroux HC, Noorduin H. Extradural bupi-
vacaine with sufentanil for vaginal delivery - a double-blind
trial. British Journal of Anaesthesia 59: 1518-1522, 1987
Verborgh C, van der Auwera D, van Droogenbroek E, Camu F.
Epidural sufentanil for postsurgical pain relief. European Jour-
nal of Anaesthesiology 3: 313-320, 1986
Vinik HR, Gelman S, Proctor J, Halpern NB. Computerized in-
fusion of sufentani!: a comparison of morbidly obese and non-
obese patients. Anesthesia and Analgesia 65 (Suppl. 2): 161,
1986
Waldmann CS, Wark KJ, Sebel PS, Feneck RO. Haemodynamic
effects of atracurium, vecuronium and pancuronium during
sufentanil anaesthesia for coronary artery bypass. Acta Anaes-
thesiologica Scandinavica 30: 351-356, 1986
313
Wasudev G, Kambam JR, Hazlehurst WM, Hill P, Adkins R, et
al. Comparative study of sufentanil and isoflurane in out-
patient surgery. Anesthesia and Analgesia 66 (Suppl.): S186,
1987
Wauquier A, Bovill JC, Sebel PS. Electroencephalographic effects
of fentanyl, sufentanil and alfentanil anaesthesia in man . Neu-
ropsychobiology II: 203-206, 1984
Wauquier A, van den Broeck WAE, Niemegeers CJE, Janssen
PAJ. Effects of morphine, fentanyl, sufentanil and the short
acting morphine-like analgesic alfentanil on the EEG in dogs.
Drug Development Research I: 167-179, 1981
Welchew EA, Herbert P. Effects of sufentanil on respiration and
heart rate during nitrous oxide and halothane anaesthesia.
British Journal of Anaesthesia 58: 120P, 1986
Weldon ST, Perry DF, Cork RC, Gandolfi J. Detection of pi co-
gram levels of sufentanil by capillary gas chromatography.
Anesthesiology 63: 684-687, 1985
Weltwood M, Teasdale S, Ivanov J, Young P, Madonik M, et al.
The effects of fentanyl and its analogues (sufentanil and alfen-
tani!) on ventricular function. Anesthesiology 61: A55, 1984
White PF, Sung M-L, Doze VA. Use of sufentanil in outpatient
anesthesia - determining an optimal preinduction dose. Anes-
thesiology 63 (Suppl.): A202, 1985
Wiggum DC, Cork RC, Weldon ST, Gandolfi AJ, Perry DS. Post-
operati ve respiratory depression and elevated sufentanil levels
in a patient with chronic renal failure. Anesthesiology 63: 708-
710, 1985
Woestenborghs R, Michielsen L, Heykants J. Rapid and sensitive
gas chromatographic method for the determination of alfen-
tani! and sufentanil in biological samples. Journal of Chro-
matography 224: 122-127, 1981
Yaksh TL, Harty GJ, Onofrio BM. High doses of spinal morphine
produce a non-opiate receptor mediated hyperesthesia: prac-
tical and theoretical implications. Anesthesiology 64: 590-597,
1986a
Yaksh TL, Noueihed RY, Durant PAC. Studies of the pharma-
cology and pathology of intrathecally administered 4-anilino-
piperidine analogues in the rat and cat. Anesthesiology 64: 54-
66, 1986b
Zurick AM, Khoury GF, Estafanous FG, Lytle B. Sufentanil re-
quirement of surgical anesthesia (as determined by EEG) and
its effect on the awakening time. Anesthesia and Analgesia 62:
292, 1983
Zuurmond WW A, van Leeuwen L. Recovery from sufentanil an-
aesthesia for outpatient arthroscopy: a comparison with iso-
flurane. Acta Anaesthesiologica Scandinavica 31 : 154-156, 1987
Authors' address: Jon Monk, ADIS Press Limited, 41 Centorian
Drive, Private Bag, Mairangi Bay, Auckland 10 (New Zealand).