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The Clinical Effectiveness of
Epidural Bupivacaine,
Bupivacaine with Lidocaine,
and Bupivacaine with
Fentanyl for Labor Analgesia
J. Clin. Anesth. 1991;3:219-224
*Associate Professor of Anesthesiology
tClinica1 Fellow in Obstetrical Anesthesiology
$Assistant Professor of Anesthesiology
Address reprint requests to Dr. Sinatra at
the Department of Anesthesiology, T-3, Yale
University School of Medicine, Box 3333,
333 Cedar Street. New Haven, CT 06510,
USA.
Received for publication July 30, 1990; re-
vised manuscript accepted for publication
December 17, 1990.
Raymond S. Sinatra, MD, PhD,*
Robert Goldstein, MD,? Ferne B. Sevarino, MD+
Departments of Anesthesiology, Yale University School of Medicine and
Yale-New Haven Hospital, New Haven, CT.
Study Objective: To examine the efficacy of bupiuacaine alone and in combination
with lidocaine or fentanyl for epidural analgesia during labor.
Design: Randomized, single-blind study.
Setting: Labor and delivery unit at a university medical center.
Patients: Forty-five primiparas requesting epidural analgesia.
Interventions: Following epidural placement at L3-4 interspace, patients received
either bupivacaine 0.5% (Group I, n = 15), bupivacaine 0.25% with lidocaine
I % (Group 2, n = 15), or bupivacaine 0.5% with fentanyl50 pg in 10 ml of
saline (Group 3, n = 15). Patients in Groups 1 and 2 received 6 to 10 ml of
local anesthetic depending on patient height, while patients in Group 3 received 5
ml of local anesthetic plus 50 pg of fentanyl in IO ml of sa1in.e. All solutions
contained epinephrine 1:200,000.
Measurements and Main Results: Patients were assessed at regular intervals
,following administration of the epidural solution. Visual analog scale (VAS) scores
were used to measure onset of analgesia, time to complete pain relief, duration of
analgesia, and patient satisfaction with therapy. The frequency of shivering and
pruritus and the extent of sensorylmotor block also were evaluated. There were no
intragroup differences in time to complete pain relief or patient satisfaction. How-
ever, patients in Group 3 noted the most rapid onset and longest duration of pain
relief. Patients in Group 3 also experienced signzficantly less shivering and had
the lowest degree of motor block. Two patients in Group 3 experienced mild pruritus.
Conclusions: Epidurally administered fentanyl safely extended the duration of
labor analgesia while reducing bupivacaine dose requirements and magnitude of
motor block. In this setting, the combination of bupivacaine and lidocaine offered
no clinical advantage over bupivacaine alone.
0 1991 Butterworth-Heinemann Keywords: Anesthesia, obstetric; analgesia, epidural; local anesthetics,
bupivacaine, lidocaine; opioids, fentanyl.
.J. Clin. Anesth., vol. 3, May/June 1991 219
Introduction
The ideal epidurdl anesthetic for labor and delivery
should provide useful analgesia without significant
motor block or risk of maternal or fetal toxicity. In
this regard, 0.25% to 0.5% concentrations of bupi-
vacaine are commonly used, since they offer effective
and prolonged pain relief. 1,2 While bupivacaine’s pro-
longed duration of analgesia and lack of immediate
or long-term neonatal effects” offer advantages in this
setting, its slow onset and risk of maternal cardiotox-
icity, even in dilute concentrations,” represent unde-
sirable characteristics.
A number of pharmacologic adjuncts, including
bicarbonate,” opioids,6-n epinephriner and rapid-act-
ing local anesthetics, ‘“,‘1 have been added to solutions
of bupivacaine to speed analgesic onset, reduce dose
requirements, and lower risks of toxicity. Concomi-
tant administration of bupivacaine and opioid anal-
gesics appears to speed onset and improve the quality
of pain relief despite considerable reductions in local
anesthetic dose.7,1Z MaGee et al.” reported rapid onset
and reduced bupivacaine requirements when epi-
dural combinations of bupivacaine and lidocaine were
used for labor and delivery analgesia.
The following randomized, single-blind evaluation
studied the clinical effectiveness of epidural anes-
thesia observed with bupivacaine 0.5% against that
provided by combinations of bupivacaine 0.25%’ and
lidocaine 1% and bupivacaine 0.5% and fentanyl. The
evaluation measured time of onset and duration of
analgesia and determined the relative safety of each
solution administered as a single bolus dose in term
parturients in Stage I of active labor.
Materials and Methods
The study was approved by the Yale University School
of Medicine Human Investigation Committee, and
informed consent was obtained from all patients prior
to epidural placement. Forty-five term primiparas in
active labor (at 3 to 6 cm cervical dilation) requesting
epidural analgesia were randomly assigned to one of
three treatment groups. Patients selected were healthy
(ASA physical status II), had uncomplicated preg-
nancies with a singleton fetus in vertex position, had
not received parenteral analgesics or sedatives, were
at least 18 but no more than 40 years of age, weighed
no more than 110 kg, and were at least 152 cm but
no more than 183 cm in height. Patients with a history
of alcohol or drug abuse or a documented sensitivity
to opioids or local anesthetics were excluded from the
study.
Following prehydration with lactated Ringer’s so-
lution ( 15 ml/kg) and routine epidural placement at
the L3-4 interspace, patients received one of three
test solutions via a 19gauge single-port epidural cath-
eter (Kendall Curity, Mansfield, MA) inserted 2.5 cm
in randomized, single-blind fashion. Patients in Group
1 (bupivacaine, n = 15) received 5 ml of 0.5% bu-
pivacaine plus epinephrine 1:200,000 followed by ad-
ditional bolus doses based on height (per standard
routine, patients 152 cm tall received an additional 1
ml, those 160 cm tall received 3 ml, and those 170 cm
and taller received 5 ml). Patients in Group 2 (bupi-
vacaine with lidocaine, n = 15) received a 5 ml mix-
ture of 0.25% bupivacaine plus l.O%, lidocaine plus
epinephrine 1:200,000, followed by additional 1 to 5
ml doses as outlined for Group 1. Patients in Group
3 (bupivacaine with fentanyl, n = 15) were given 5
ml of 0.5% bupivacaine plus epinephrine I :200,000,
followed by 50 pg of fentanyl plus 9 ml of’O.<)O/r sterile
saline. All patients remaining uncomfortable 15 min-
utes after epidural administration were given supple-
mental 1 to 2 ml boluses of their respective stud)
solution as required. Epidural catheters \vere re-
checked in all patients remaining uncomf’ortable after
30 minutes. If a catheter was found to be misplaced,
the individual was dropped from evaluation and a
second epidural was inserted. ,411 medication was ad-
ministered in divided doses with patients supine and
in left uterine displacement. Patients were monitored
continuously with electrocardiogram (IX:(;) and au-
tomated spliygmoma~ionie~er cuff.
A blinded obstetric anesthesiologist collected data
prior to epidural placement (baseline), every 5 min-
utes for the first 30 minutes following drug admin-
istration, and then every 30 minutes until epidural
reinforcement was requested. At each data collection
interval, a 10 cm VAS (anchored with 0 representing
no pain and 10 representing the worst possible pain)
was used to assess analgesic onset, duration, and qual-
ity of pain relief. A similar VAS was used to assess
patient sat’ f t’ 1s ac ion with therapy, with 0 representing
least satisfaction and 10 reflecting most satisfaction.
Onset time represented the interval between drug
administration and the first VAS score lower than
baseline. Duration was defined as the interval from
onset of analgesia until the patient requested epidural
reinforcement.
‘l’he extent of dermatomal sensory block to pin-
prick and cold (alcohol swab) and the magnitude of
motor block were assessed at each data collection in-
terval, immediately following completion of VAS
scores. Motor blockade was tested by using a modi-
fication of Bromage’s scale, ‘:s in which 0 = the ability
to maintain a leg lift for prolonged periods; 1 = the
220 J. Clin. Anesth., vol. 3, May/June 1991
ability to lift legs briefly; 2 = the ability to bend knees;
3 = the ability to wiggle toes; and 4 = no movement
in lower extremities.
Maternal side effects, including nausea, pruritus,
and shivering, were scored as 0 = absent; 1 = mild;
2 = moderate; and 3 = severe. The blinded observer
also noted whether patients were started on intrave-
nous (IV) oxytocin following epidural placement, the
frequency of fetal bradycardia [heart rate (HR) less
than 110 beats per minute (bpm)], maternal hypoten-
sion [systolic blood pressure @BP) less than 100
mmHg], the need to administer ephedrine (as per
standard routine, a decrease in SBP below 100 mmHg
mandated administration of 5 mg of ephedrine), and
total ephedrine dose requirement.
Data were analyzed as follows: patient demograph-
ics and continuous variables, including VAS scores
and times, were analyzed by analysis of variance
(ANOVA) and compared with Tukey’s test of mul-
tiple comparison; differences in frequency of side ef-
fects were analyzed with chi-square tests. Data are
expressed as means 2 SD, median, or percentage. A
value of $I < 0.05 was considered to be significant.
Table 1. Patient IIemographics
Results
All patients included in the present evaluation com-
pleted the study protocol---&., there were no drop-
outs secondary to inadequate analgesia, maternal or
fetal morbidity, precipitous delivery, or emergency
cesarean section. There were no significant differ-
ences among the three treatment groups with respect
to patient demographics, cervical dilation at place-
ment of epidural analgesia, SBP, volume of lactated
Ringer’s solution infused prior to epidural placement,
or percentage of patients treated with oxytocin (Pi-
tocin) (Table 1).
Pain scores are presented in Tables 1 and 2. There
were no significant differknces among the three treat-
ment groups with respect to baseline VAS pain score
and lowest pain score achieved following administra-
tion of the study solutions. Patients in all the treatment
groups eventually attained very low pain scores (C 1);
however, individuals in Groups 1 and 2 required more
supplemental boluses and a greater amount of local
anesthetic than did those in Group 3 (Table3). Patients
in Group 1 experienced delayed analgesic onset when
Group 1 Group 2 Group 3
Age (yr)
(cm)
Wetght Height (kg)
Cervical dilation (cm)
Prehydration (ml)
Systolic blood pressure (mmHg)
Baseline pain VAS (cm)*
Percentage of patients receiving oxytocin
(4 to 6 kg/h)
iKotr: Data are means 2 SD.
*VAS = visual analog scale.
*Values are medians with range in parentheses.
27.7 5 6.7 28.7 k 5.0 27.7 k 7.0
160.2 2 5.8 164.8 ? 6.8 159.0 5 4.3
80.9 + 18.3 93.6 5 22.9 79.2 * 12.9
5.3 5 1.6 5.0 & 1.3 5.2 ? 1.2
1,423 * 252 1,515 + 288 1,390 5 277
123.7 t 12.2 125.3 2 11.7 121.7 + 9.9
9.0 (7.5 to 10.0) 8.4 (6.0 to 10.0) 8.7 (7.2 to 10.0)
38 27 35
Table 2. Pain and Satisfaction Visual Analog Scale (VAS) Scores
Group 1 Group 2 Group 3
Time to onset (min) 10.6 t 4.9t 8.2 2 3.9 5.1 +- 1.6
Time to lowest pain VAS score (min) 14.9 k 8.3 14.2 4 10.6 13.6 k 5.9
Lowest pain VAS score (cm)* 0.0 (0 to 0.3) 0.2 (0 to 0.6) 0.0 (0 to 0.3)
Time to highest satisfaction VAS score (min) 15.4 2 9.2 13.4 + 11.0 14.0 + 5.8
Highest satisfaction* VAS score (cm) 10.0 (9.8 to 10) 9.9 (9.2 to 10) 9.9 (9.6 to 10)
Duration of analgesia (min) 116.9 c 19.6 126.3 4 32.9 165.1 2 25.4$
Note: Data are means ? SD.
*Values are medians with range in parentheses.
tSignificant difference Group 1 us Group 3, p < 0.05.
$Significant difference Groups 1 and 2 US Group 3, p i 0.05.
J. Clin. Anesth., vol. 3, May/.June 1991 221
Table 3. Sensory Level and Adverse Effects
Group 1 Group 2 Group 3
Supplemental epidural bolus (ml) Total bupivacaine dose (mg) Total lidocaine dose (mg) Highest sensory block* Highest temperature block* Maximum motor blocki Number of patients experiencing hypotension
(SBP < 100 mmHg) Ephedrine dose/treated patient (mg) Shivering scale Number of patients reporting pruritus
I.8 -+ 1.3
44.6 * 10.1 -
9.4 !Z 1.2 9.2 + 1.3
1.53 5 0.0
6115
7.5 + 4.1 1.6 % 1.0
Oil5
I oi 15
9.0 i 3.9%
1.x 2 1.4
Oi l5
0.6 k I .‘L
26.” + 2.1
t-4.4 ?I- I.2
7.8 + 1.4 0.2 ” 0.4’i:
.il I .5
5.0 + 0.0
0.4 + 0.8 ‘L/l5
Note: Data are means t SD.
SBP = systolic blood pressure.
*Thoracic dermatomal level.
‘rModification of Bromage’s scale.
$Significant difference (;roups I and 2 US Group 3, /J -C 0.05.
PSignificant difference Group 2 11.‘ Group ?J, p < 0.05.
compared with individuals in Group 3. However, there
were no significant intergroup differences in time re-
quired to achieve lowest VAS score (Table 2).
There were no intergroup differences in satisfaction
or time necessary to achieve the highest satisfaction score
(TubG 2). Duration of analgesia was significantly longer
in Group 3 than in Groups 1 and 2.
Patients in Group 3 had a significantly lower degree
of motor block than those in Groups 1 and 2 (Tablr
3). There were no intergroup differences in sensory
block to pinprick or cold temperature (Table 3).
Following administration of epidural study solu-
tions, more episodes of maternal hypotension oc-
curred in Group 2 than in the other two groups (Tublp
3). Patients in Croup 2 required significantly more
IV ephedrine to maintain SBP above 100 mmHg, while
those in Group 3 required the least (Group 2 7)s Group
3). No episodes of fetal bradycardia or arrhythmia OI
need for emergency cesarean delivery occurred.
With regard to other adverse events, patients in Group
3 had a significantly lower frequency and severity of
shivering than individuals in Groups 1 and 2 (Table 3).
There were no episodes of increased maternal sedation
and no intergroup differences in sedation scores. Mild
abdominal pruritus, which did not require treatment,
was noted in two patients in Group 3.
Discussion
The goal of epidural analgesia for labor is to provide
rapid and reliable pain relief with minimal maternal
or fetal side effects. In this regard, the epidural so-
222 J. Clin. Anesth., vol. 3, May/June 1991
lutions used in the present investigation offered uni-
formly excellent analgesia and high patient satisfaction.
This single-bolus-dose study did not evaluate neonatal
outcome or mode of delivery, since analgesic tech-
niques following termination of the evaluation period
were varied and individualized to patient status. While
it is recognized that concentrations and total milli-
grams of local anesthetic administered are higher than
amounts reported to provide useful labor analge-
sia,‘,‘.‘-’ dosages represent standard of care at this in- c stitution in otherwise unmedicated primiparas.
Although there were no intergroup differences in time
until peak analgesia, defined as the lowest VAS pain
score, or in patient satisfaction with therapy, individ-
uals treated with bupivacaine and fentanyl experi-
enced rapid onset, the longest duration of pain relief,
the lowest degree of shivering, and the least motor
block. The mixture of bupivacaine and lidocaine of-
fered little clinical advantage in this setting.
A number of clinical studies have documented the
effectiveness and safety of epidurally administered
fentanyl.“,’ This highly lipid-soluble k-agonist rapidly
crosses dura, activates spinal opioid receptors in dor-
sal horn, and selectively suppresses c-fiber mediated
nociceptive input. I5 While not effective by itself,‘“,” it
appears to potentiate the activity of epidurally ad-
ministered local anesthetics and improves both the
quality and duration of labor analgesia. Onset of an-
algesia was particularly rapid in patients receiving fen-
tanyl. This finding may reflect rapid systemic uptake
and initial supraspinal effects in addition to spinal
cord-mediated activity .’ Supraspinal analgesia is of
short duration and provides negligible benefit after
20 minutes,” whereas more profound spinal modu-
lation of pain peaks at 10 to 15 minutes and is main-
tained for 2 or more hours.6,7J2 In this regard, patients
receiving bupivacaine with fentanyl experienced re-
ductions in pain at the first observation interval (5
minutes); however, analgesia was incomplete, and time
to lowest pain score was no more rapid than that ob-
served in the two nonopioid treatment groups.
The duration of pain relief in the bupivacaine with
fentanyl group was longer than that recently reported
by Lirzin et al. I8 Patients in that study, however, were
evaluated at a later stage of labor. It is also recognized
that duration of epidural fentanyl analgesia may be
increased when administered in larger volumes of so-
lution.‘” Increasing the volume of epidural injectate
is believed to provide greater dispersion in the epi-
dural space and to allow a larger number of fentanyl
molecules to reach opiate receptors concentrated in
the thoracic/lumbar spinal cord. The relatively large
volume of epidurally administered fentanyl solution
appeared to dilute the activity of bupivacaine and in-
fluenced its localization in that gross motor function
was virtually unaffected, while sensory blockade to
temperature tended to spread to higher dermatomal
levels. As in previous evaluations,‘,‘* this higher der-
matomal block was imperceptible to the patient, did
not influence sympathetic tone, and was not associ-
ated with a higher frequency of hypotension or need
for vasopressors. It is unclear whether dilution and
greater epidural dispersion would have influenced
the onset, duration, and effectiveness of analgesia
provided by bupivacaine and bupivacaine with lido-
Caine. It is conceivable that greater dispersion would
have reduced the magnitude of motor blockade.
Solutions of lidocaine are commonly used for ep-
idural analgesia in obstetrics because they provide
rapid onset of pain relief with minimal effects on uter-
ine tone”’ and neonatal outcome.21 In contrast to the
findings by MaGee et al, I1 the combination of bupi-
vacaine and lidocaine in the present study offered no
clinical advantage over bupivacaine alone in terms of
onset, duration of analgesia, or degree of motor block
and shivering. Duration of analgesia in this group was
significantly shorter than that noted with bupivacaine
and fentanyl. These findings reinforce the contention
that combinations of local anesthetics with different
pharmacodynamics offer no clinical advantage over
therapeutic doses of the individual agents used.*‘”
*Howell P, Davies W, Wrigley M, Tan P, Morgan B: Are two better
than one? An assessment of a mixture of bupivacaine and ligno-
Caine with adrenaline 1:200,000 for elective epidural caesarean
section. Proceedings of the Society qf Obstetric Anesthesia and Perinatology,
Madison, WI, May 1990;22:E-16.
Perhaps the only advantage to patients in this group
was a bupivacaine-sparing effect in which equivalent
quality of analgesia and overall patient satisfaction
were achieved with significant reductions in total bu-
pivacaine dosage. This finding mirrored a similar re-
duction observed in the bupivacaine with fentanyl
group. It remains unclear whether reductions in bu-
pivacaine dosage improve patient safety by lowering
risks of cardiotoxicity.lz
In the present study, patients receiving bupivacaine
and lidocaine tended to require a greater amount of
ephedrine to maintain SBP above 100 mmHg. How-
ever, transient episodes of hypotension and IV doses
of vasopressor did not influence fetal HR or varia-
bility. Few other maternal adverse events were noted
in any of the study groups. Patients receiving bupi-
vacaine with fentanyl had a lower frequency of shiv-
ering and a higher frequency of mild pruritus than
did individuals in the two other treatment groups.
Epidural opioids previously have been shown to re-
duce maternal shivering associated with lumbar epi-
dural analgesia.“R Whether this effect represents a
supraspinal mode of action or direct inhibition of spinal
reflexes remains unclear. Pruritus is a well-docu-
mented side effect associated with epidural opioids.
As in previous evaluations of epidural fentanyl,lZ,i’i
this effect was of mild severity and isolated to the
abdomen. The frequency of fentanyl-induced pruri-
tus may be directly related to the volume of solution
administered rather than the total dose.”
Finally, while patients treated with bupivacaine and
fentanyl noted prolonged analgesia, an absence of
shivering, and an intact ability to move and adjust
body position, such desirable characteristics did not
improve overall patient satisfaction. Thus, while pa-
tient satisfaction with therapy may reflect the com-
posite of useful analgesia with minimal adverse effects,
patients experiencing complete relief of labor pain
appear to overlook any associated inconveniences.
In conclusion, solutions of bupivacaine alone and
in combination with a second local anesthetic or opioid
provided useful epidural analgesia in laboring par-
turients. The combination of bupivacaine and fen-
tanyl offered the longest duration of analgesia and
the lowest frequency of shivering and motor block.
The combination of bupivacaine and lidocaine of-
fered little clinical advantage over bupivacaine alone.
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