Epidural Fentanyl Speeds the Onset of Sensory and Motor

Blocks During Epidural Ropivacaine Anesthesia

Chen-Hwan Cherng, MD, DMSc, Chih-Ping Yang, MD*, and Chih-Shung Wong, MD, PhD
Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; *Division
of Anesthesiology, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan
In this study we examined the onset times of sensory
and motor block during epidural ropivacaine anesthe-
sia with and without the addition of fentanyl to the epi-
dural solution. Forty-five young male patients under-
going knee arthroscopic surgery were randomly
allocatedinto 3 groups of 15 patients each: epidural fen-
tanyl (EF; epidural administration of 15 mL of 1%ropi-
vacaine plus 100 g fentanyl followedby IVinjection of
2 mLof normal saline); IVfentanyl (IF; epidural admin-
istration of 15 mL of 1% ropivacaine plus 2 mL of nor-
mal saline followed by IV injection of 100 g fentanyl);
and control (C; epidural administration of 15 mL of 1%
ropivacaine plus 2 mL of normal saline followed by IV
injection of 2 mL of normal saline). The sensory and
motor blocks were assessed by pinprick and modified
Bromage scale, respectively. The hemodynamic
changes, postepidural shivering, andside effects of epi-
dural fentanyl were also recorded. There was no differ-
ence in the distribution of age, weight, and height
among the 3 groups. The onset time of sensory block to
the T10 dermatome was significantly more rapid in the
EF group (13.0 3.0 min) than in the IF group (16.2
3.5 min, P 0.05) or Cgroup (17.7 3.6 min, P 0.05).
The onset times of motor block up to Bromage scale 1
and 2 were significantly more rapid in the EF group
(11.9 4.6 and24.4 5.9 min) than in the IF group(16.9
4.7 and30.8 5.6 min, P0.05) or Cgroup(18.3 4.9
and32.7 5.7 min, P0.05). There was nodifference in
the incidence of shivering among the three groups. Pru-
ritus was observedinthree patients of the EFgroupand
one patient of the IF group. No nausea, vomiting, respi-
ratory depression, urinary retention, or hypotension
was observedinany patient. We conclude that epidural
administrationof the mixture of 100 gfentanyl and1%
ropivacaine solution accelerated the onset of sensory
andmotor blocks during epidural ropivacaine anesthe-
sia without significant fentanyl-related side effects.
(Anesth Analg 2005;101:18347)
T
he delayed onset time of sensory block in epi-
dural anesthesia is sometimes a drawback for
clinical practice. Alkalinization of local anes-
thetic solution has been used to shorten the onset time
(1). Likewise, the addition of fentanyl to lidocaine (2),
bupivacaine (3), and mepivacaine (4) solutions pro-
duces a rapid onset of sensory block during epidural
anesthesia. Conversely, other investigators have re-
ported no change in the onset of analgesia with the
addition of fentanyl to epidural mepivacaine (5). Ropi-
vacaine, a long-acting amino-amide type local anes-
thetic, is widely used in epidural anesthesia. The aim
of this study was to examine the effect of epidural
fentanyl on the onset times of sensory and motor
blocks during epidural ropivacaine anesthesia.
Methods
This was a randomized, double-blind, prospective
study. After approval from the human research re-
view committee of our institute, each patient gave
informed consent. Forty-five young male patients,
ASA physical status I, undergoing knee arthroscopic
surgery were included. Exclusive criteria included
bleeding disorders, infection at puncture site, a history
of opioid dependence, allergy to study drugs, and
morbid obesity. Using sealed envelops, the patients
were randomly allocated into 3 groups: epidural fen-
tanyl (EF), IV fentanyl (IF), and a control (C) group,
with 15 patients in each group. The patients were
monitored with electrocardiogram, arterial blood
pressure, heart rate, and pulse oximetry during sur-
gery. With the patient in the left lateral decubitus
position, the epidural space was identified at L3-4
level with an 18-guage Tuohy needle (minipack, Por-
tex, UK) by the loss of resistance method. With the
bevel of the Tuohy needle in cephalic direction, an
epidural catheter was inserted 5 cm into the epidural
space. A test dose of 3 mL of 2% lidocaine (ASTRA,
Accepted for publication June 28, 2005.
Address correspondence and reprint requests to Chen-Hwan
Cherng, MD, DMSc, Department of Anesthesiology, Tri-Service
General Hospital, No. 325, Sec. 2, Cheng-Gung Road, Nei-Hu, 114,
Taipei, Taiwan. Address e-mail to cherng1018@yahoo.com.tw.
DOI: 10.1213/01.ANE.0000184131.06529.35
2005 by the International Anesthesia Research Society
1834 Anesth Analg 2005;101:18347 0003-2999/05
Sweden) containing 1:200,000 epinephrine (freshly
added) was administered to detect intrathecal or IV
injection. Three minutes later, the patients of group EF
received the epidural administration of 15 mL of 1%
ropivacaine plus 100 g (2 mL) fentanyl, followed by
an IV injection of 2 mL of normal saline. The patients
of group IF received the epidural administration of
15 mL of 1% ropivacaine plus 2 mL of normal saline,
followed by an IV injection of 100 g (2 mL) of fent-
anyl. The patients of group C received the epidural
administration of 15 mL of 1% ropivacaine plus 2 mL
of normal saline along with an IV injection of 2 mL of
normal saline. The speed of epidural ropivacaine ad-
ministration was consistent in all groups, with a rate
of 3 mL/10 s.
The sensory block was assessed by pinprick method
at 2.5-min intervals for 40 min. Pinprick sensation was
examined using a blunt 21-gauge needle in a cephalic-
to-caudal fashion along the left anterior axillary line.
The onset of sensory block was defined as the time
from epidural injection to the occurrence of sensory
block at the T10 dermatome. The upper level of sen-
sory block was recorded. The motor block was as-
sessed at 2.5-min intervals for 40 min by a modified
Bromage scale (03): 0, no motor impairment (able to
move joints of hip, knee, and ankle); 1, unable to raise
either extended leg (able to move joints of knee and
ankle); 2, unable to raise extended leg and flex knee
(able to move joint of ankle); 3, unable to move knee
and foot. The onset of motor block was defined as the
time from epidural injection to the occurrence of mo-
tor block at each scale. Both sensory and motor block
data were assessed by a blinded observer. Arterial
blood pressure and heart rate were measured every
2.5 min after epidural injection. Hypotension (systolic
blood pressure 100 mm Hg or a decrease of more
than 30% from baseline) was treated with 5 mg of IV
ephedrine as needed. Side effects such as nausea,
vomiting, pruritus, respiratory depression, or shiver-
ing were recorded during surgery, and difficulty in
micturition was also recorded for 24 h postopera-
tively. The pH of the 2 mixed ropivacaine solutions
used in this study was measured by using a pH meter.
Based on a previous study (6), an estimated stan-
dard deviation of 5 min for the onset of sensory block
during epidural ropivacaine anesthesia was used. A
decrease in the onset time of 30% was considered
clinically significant. On the basis of these estimates, a
sample size of 15 patients in each group would be
sufficient to get a two-tailed type I error of 0.05 and a
power of 80% (7). The results were expressed as mean
sd or median (range) for the level of sensory block.
The pH of the local anesthetic solutions was analyzed
by Students t-test. The difference of onset times of
sensory and motor block was analyzed using analysis
of variance and the Student-Newman-Keuls test for
post hoc comparison. The upper levels of sensory block
were compared using the Kruskal-Wallis test and the
Dunns multiple comparison procedure for post hoc
comparison. The incidences of side effects among
groups were analyzed by
2
test. A P value 0.05 was
considered significant.
Results
The three study groups were similar in age, weight,
and height (Table 1). The pH of the 2 mixed ropiva-
caine solutions was no different: 4.65 0.03 (n 3) in
the 15 mL of 1% ropivacaine plus 100 g (2 mL)
fentanyl, and 4.67 0.02 (n 3) in the 15 mL of 1%
ropivacaine plus 2 mL of normal saline. The anesthetic
characteristics of the 3 groups are shown in Table 2.
Onset time of sensory block up to T10 dermatome was
significantly more rapid in the EF group than in the IF
and C groups. The upper level of sensory block did
not differ among the 3 groups. Onset time of motor
block to the modified Bromage scores 1 and 2 was
significantly more rapid in the EF group compared
with the IF and C groups. Changes of arterial blood
pressure and heart rate were not different among the
3 groups. The incidence of shivering among the three
groups (5 of 15 in EF group, 7 of 15 in IF group, and 9
of 15 in C group) was not significant. Two patients
complained of dizziness in the IF group (not signifi-
cant). Mild pruritus was observed by three and one
patients in the EF and IF groups, respectively (not
significant). Nausea, vomiting, respiratory depression,
or urinary retention were not observed in any
patients.
Discussion
This study demonstrates that the addition of 100 g
fentanyl to 1% ropivacaine solution for epidural ropi-
vacaine anesthesia accelerates the onset of sensory and
motor blocks. Systemic fentanyl had no effect on this
response. The mechanisms by which fentanyl speeds
the onset of sensory and motor blocks are not clear.
From an animal study, the combination of ropivacaine
and fentanyl accelerated the onset of analgesia as com-
pared with ropivacaine alone for caudal epidural an-
esthesia in mares (8). Power et al. (9) demonstrated
Table 1. Demographic Data
EF
(n 15)
IF
(n 15)
C
(n 15)
Age (yr) 23.2 3.7 23.7 3.5 23.2 2.6
Weight (kg) 69.5 9.8 72.5 8.1 69.9 9.8
Height (cm) 171.7 5.5 173.5 4.9 175.7 6.6
Data are presented as mean sd. There were no differences between
groups.
EF epidural fentanyl; IF IV fentanyl; C control.
ANESTH ANALG REGIONAL ANESTHESIA CHERNG ET AL. 1835
2005;101:18347 EPIDURAL FENTANYL AND ROPIVACAINE
that fentanyl increased the degree of nerve conduction
block produced by bupivacaine in rabbit vagus nerve.
In a clinical study, systemic fentanyl enhanced the
spread of spinal analgesia produced by lidocaine (10).
These results suggested that fentanyl might enhance
the nerve block effect of local anesthetics.
A synergistic interaction between local anesthetics
and opioids with epidural administration has been
reported (11,12). It appears that local anesthetics and
opioids exert their action independently via different
mechanisms. Local anesthetics block propagation and
generation of neural action potentials by a selective
effect on sodium channels, whereas opioids act on the
opioid receptors creating an increase in a potassium
conductance. This action results in hyperpolarization
of the nerve cell membrane and a decrease in excit-
ability (13). Although sodium channel block is pro-
posed to be the primary mode of action, local anes-
thetics also have an effect on synaptic transmission
(14). Li et al. (14) showed that lidocaine inhibited both
substance P binding and substance P-evoked increase
in intracellular calcium. In contrast, in addition to the
considered primary mode of action, opioids were
found to directly suppress the action potential in
nerve fibers (15). Frazier et al. (16) showed that mor-
phine depressed both sodium and potassium currents
associated with the action potential in squid giant
axons. Therefore, the combination of local anesthetics
and opioids may effectively inhibit multiple areas of
neuronal excitability.
Regarding the possible mechanisms of the acceler-
ation of sensory and motor blocks produced by fent-
anyl in this study, we postulate that fentanyl might
enhance the nerve conduction block of spinal roots.
Cousins and Veering (17) stated that the initial onset
of epidural block is probably related to the conduction
block of spinal roots within the dural cuff because
large concentrations of local anesthetic solution build
up rapidly and the dura is very thin in this region.
Fields et al. (18) showed that primary afferent tissues
(dorsal roots) contain opioid binding sites; thus fent-
anyl might act directly on the spinal nerve or pene-
trate the dura and act at the spinal roots. In addition,
fentanyl has been reported to have a local anesthetic
action. Smith et al. (19) reported a case in which the
patient developed unilateral analgesia after injection
of fentanyl near the lumbosacral plexus, and a local
anesthetic effect of fentanyl was proposed. In an in
vitro electrophysiological study, Gissen et al. (20) dem-
onstrated that perineural fentanyl and sufentanil in-
hibited the action potential of A and C fibers, and
naloxone pretreatment did not prevent this inhibitory
effect. Similarly, Power et al. (9) showed that fentanyl
blocked the nerve conduction of A and C fibers, and
naloxone did not prevent this inhibitory effect. These
results suggested that fentanyl may have some effect
on nerve conduction that is not mediated via the opi-
oid receptors.
In conclusion, addition of 100 g fentanyl to 1%
ropivacaine solution shortened the onset times of sen-
sory and motor blocks during epidural anesthesia
without increased side effects.
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Onset time of sensory block to T10
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Onset time of motor block to
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Onset time of motor block to
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24.4 5.9* 30.8 5.6 32.7 5.7
Upper level of sensory block T5 (3-8) T6 (4-8) T6 (4-9)
Data are expressed as mean sd or median (range).
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* P 0.05 when compared with IF and C groups.
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