Obstetric Anesthesiology

Section Editor: Cynthia A. Wong

A Randomized Comparison of Low Doses of Hyperbaric

Bupivacaine in Combined Spinal-Epidural Anesthesia for
Cesarean Delivery
Serene Leo, MMED
Ban Leong Sng, MMED, FANZCA
Yvonne Lim, MMED
Alex T. H. Sia, MMED
BACKGROUND: The aim of our study was to investigate the block characteristics of
intrathecal hyperbaric bupivacaine 7, 8, or 9 mg administered during combined
spinal-epidural anesthesia for cesarean delivery and to elucidate the dose that
produces adequate sensory blockade for surgery while minimizing the inci-
dence of hypotension, high neuroblockade, and the need for intraoperative
epidural supplementation.
METHODS: Sixty women presenting for elective cesarean delivery were randomly
assigned to one of the 3 groups. Group 7 received intrathecal hyperbaric bupiva-
caine 7 mg, Group 8 received 8 mg, and Group 9 received 9 mg. Women in all 3
groups received intrathecal morphine 100 ␮g and IV hydroxyethyl starch 15
mL/kg at the time of initiation of combined spinal-epidural anesthesia. Surgery
began when a sensory level of T4 was achieved. Patients were monitored for block
characteristics and side effects by a blinded observer. Our primary outcome was
the maximum cephalad sensory block height.
RESULTS: There was a difference in the maximum extent of cephalad sensory block
among groups (Group 7: median T2 [interquartile range T2–T3]; Group 8: median
T2 [T1–T2]; Group 9: median T1 [C8 –T2]; P ⫽ 0.02). However, the time taken to
reach T4 was similar in all 3 groups. The incidence of hypotension requiring
vasopressors was different among groups (30% in Group 7, 55% in Group 8, and
70% in Group 9; P ⫽ 0.04). No patient had inadequate anesthesia. Neonatal
outcomes were similar in all 3 groups.
CONCLUSION: The lowest dose of hyperbaric bupivacaine (7 mg) provided equally
rapid onset and effective anesthesia for cesarean delivery while reducing the
incidence of hypotension compared with 8 and 9 mg. However, because of its
shorter duration of anesthesia, it may be feasible only when the block can be
reinforced using a functional epidural catheter.
(Anesth Analg 2009;109:1600 –5)

C ombined spinal-epidural (CSE) anesthesia is a

common technique for cesarean delivery anesthesia.1
The spinal component allows for rapid onset of dense
sensory and motor blockade. The indwelling epidural
catheter confers flexibility to supplement the neuraxial
block intraoperatively and to extend analgesia into the
postoperative period.
Earlier studies reported that the CSE technique was
associated with a higher level of sensory block and thus
a reduced need for local anesthetic as compared with a
From the Department of Women’s Anaesthesia, Kandang Ker-
bau Women’s and Children’s Hospital, Singapore.
Accepted for publication June 15, 2009.
Supported by KK Women’s and Children’s Hospital (Singapore)
for the value of SGD 4000 for the purchase of Voluven威 (hydroxy-
ethyl starch 130/0.4) for IV administration to study participants as
per protocol.
Address correspondence and reprint requests to Dr. Serene Leo,
Department of Women’s Anaesthesia, KK Women’s and Children’s
Hospital, 100 Bukit Timah Rd., Singapore 229899, Singapore. Ad-
dress e-mail to danxer159@yahoo.com.sg.
Copyright © 2009 International Anesthesia Research Society
DOI: 10.1213/ANE.0b013e3181b72d35
single-shot spinal anesthesia.2– 4 However, the most re-
cent trial, conducted by Horstman et al.,5 has suggested
that dose adjustment for the CSE compared with single-
shot spinal anesthesia may not be necessary.
In this study, we aimed to compare the neuroblock-
ade characteristics of 3 different intrathecal hyperbaric
bupivacaine doses (7, 8, and 9 mg) when administered
as part of a CSE technique in an attempt to elucidate
the dose that allows quick and adequate sensory
blockade for cesarean delivery while minimizing the
side effects of hypotension, nausea, and vomiting. We
hypothesized that there would be no difference in
block height among 7, 8, and 9 mg of intrathecal
hyperbaric bupivacaine used in CSE anesthesia for
cesarean delivery.
METHODS
With the approval of the hospital research ethics
committee and written informed patient consent, we
enrolled 60 ASA physical status I and II patients with
singleton full-term pregnancies who presented for
elective cesarean delivery into our study. We excluded

1600 Vol. 109, No. 5, November 2009

parturients who were in labor, those in whom tubal
ligation was planned in the same setting, those with
allergy to the study drugs, contraindications to central
neuraxial blockade, and obstetric complications, such
as preeclampsia, multiple gestation, or placenta pre-
via. Parturients who were at the extremes of height
and weight (body mass index ⬍20 or ⬎35 kg/m2,
height ⬍145 cm or ⬎180 cm) were also excluded.
Before the administration of neuraxial anesthesia,
an 18-gauge IV cannula was inserted and standard
monitors were applied to each patient. Baseline arte-
rial blood pressure (BP) and heart rate measurements
were recorded before the procedure and at 2.5-min
intervals throughout the period of study from a non-
invasive BP cuff on the right brachial artery with the
patients lying supine with a 15° left lateral tilt. All
procedures were performed by the principal investi-
gator and a coinvestigator who were proficient in CSE
anesthesia in the obstetric population and who each
had more than 5 yr of anesthetic experience.
Patients were randomized into 3 groups after en-
rollment. Group assignment was concealed in opaque
envelopes that had been sorted by computer-
generated random allocation. Group 7 received hyper-
baric bupivacaine 7 mg (1.4 mL of 0.5% bupivacaine
with 8% glucose) (Marcain, AstraZeneca, Sodertalje,
Sweden) and morphine 100 ␮g intrathecally. Group 8
received hyperbaric bupivacaine 8 mg (1.6 mL of 0.5%
bupivacaine with 8% glucose) with morphine 100 ␮g,
and Group 9 received hyperbaric bupivacaine 9 mg
(1.8 mL of 0.5% bupivacaine with 8% glucose) with
morphine 100 ␮g. Intrathecal drugs were drawn into a
3-mL syringe and administered over 10 –15 s. All
patients received a rapid infusion of warmed Volu-
ven威 (hydroxyethyl starch 130/0.4) 15 mL/kg (Frese-
nius Kabi, Bad Homburg, Germany), which was
commenced at the start of intrathecal drug adminis-
tration and completed within 10 –15 min (coload).6 –9
Patients were placed in the right lateral decubitus
position for the CSE procedure. An 18-gauge Tuohy
needle was inserted into the L3-4 interspace using loss
of resistance to 2 mL of air for identification of the
epidural space. The dura mater was punctured with a
27-gauge Whitacre spinal needle using a needle-
through-needle technique (Espocan, B. Braun, Melsun-
gen, Germany). After verifying free flow of cerebrospinal
fluid (CSF), the previously prepared spinal injectate was
administered with the spinal needle orifice facing cepha-
lad. An epidural catheter was inserted 4 cm into the
epidural space. Patients were immediately positioned
supine with a 15° left lateral tilt. If unintentional dural
puncture with the epidural needle occurred, the epidural
catheter was threaded into the subarachnoid space and
intrathecal drugs were administered via the catheter.
An anesthesiologist blinded to group allocation
was assigned to evaluate the patient’s hemodynamic
status and block profile at 2.5-min intervals for the
first 30 min and at 5-min intervals thereafter. The level
of dermatomal sensory block was tested bilaterally
Vol. 109, No. 5, November 2009
(defined by a complete loss of sensation to ice) after
the induction of spinal anesthesia, in an ascending
fashion starting from the T12 dermatome. Patient
assessment during this period included BP, heart rate,
respiratory rate and oxygen saturation, maximum
level of sensory block, time needed to reach maximal
sensory level, degree of lower limb motor blockade as
determined by the modified Bromage score (0 ⫽ no
impairment; 1 ⫽ unable to raise extended legs but able
to move knees and ankles; 2 ⫽ unable to raise ex-
tended legs or to flex knees but able to move feet; 3 ⫽
unable to flex ankles, knees, or hips), and time taken to
reach maximal Bromage score. In addition, the follow-
ing data were recorded: duration of surgery and total
dose of oxytocin administered postdelivery, neonatal
Apgar scores at 1 and 5 min, incidence of hypotension
(systolic BP ⬍90 mm Hg or decrease ⬎20% from
baseline BP), nausea, vomiting, and shivering (defined
as involuntary contraction or twitching of the
muscles). Treatment of hypotension consisted of ti-
trated IV boluses of phenylephrine 100 ␮g or ephed-
rine 5 mg (when maternal heart rate was ⬍60 bpm)
administered by an anesthesiologist blinded to group
allocation. Technical problems during CSE anesthesia,
such as venous puncture, paresthesia, inability to
obtain CSF backflow, and inadvertent dural puncture,
were also documented.
Surgery via a Pfannenstiel skin incision was al-
lowed to commence once a bilateral T4 sensory block
was demonstrated. If this were not achieved after 15
min, 5-mL aliquots of epidural solution comprising
alkalinized 1.5% lidocaine with epinephrine 5 ␮g/mL
was given for block supplementation, up to a maxi-
mum of 20 mL. Inadequate anesthesia was defined as
a sensory block that failed to reach T4 bilaterally 15
min after intrathecal block or that required epidural
supplementation before delivery of the baby. After
delivery, patients were given IV oxytocin 10 U in a
slow bolus over 10 min. Uterine tone was assessed by
the surgeon, and patients were started on an oxytocin
infusion (30 U oxytocin in 500 mL at 60 –100 mL/h) if
necessary. Uterine repair was performed using the
surgeon’s preferred technique. Patients were asked to
report any intraoperative pain or discomfort using a
visual analog scale (VAS) of 0 –100 mm. In the event
that the VAS was reported as 40 mm or more, or when
the sensory block level had receded to T6, boluses of
epidural solution would be administered in 5-mL
aliquots to supplement or extend the sensory block as
required. If patients reported pain or discomfort but
sensory block level was higher than T6 and VAS ⬍40
mm, adjuvant systemic analgesics (such as IV fentanyl
and inhaled nitrous oxide) or sedative drugs, such
as IV midazolam, were administered at the discre-
tion of the attending anesthesiologist blinded to
group allocation.
After surgery, all patients were cared for in the
recovery area. Hemodynamic and block profile moni-
toring was continued at 5-min intervals by qualified
© 2009 International Anesthesia Research Society 1601
postanesthetic care unit nurses. Patients were deemed Table 1. Patient Demographics
fit for discharge when sensory block level to cold had
7 mg 8 mg 9 mg
receded to T10 and the Bromage score had recovered
(N ⫽ 20) (N ⫽ 20) (N ⫽ 20) P
to 2. Perioperative data collection ended upon dis-
charge of the patients back to their wards. All patients Age (yr) 32 (3) 33 (6) 33 (5) 0.85
Height (cm) 159 (6) 158 (6) 160 (5) 0.44
were followed up the next day by a blinded observer Weight (kg) 71 (12) 72 (13) 72 (12) 0.93
for postprocedure complications, such as postdural BMI (kg/m2) 28 (5) 29 (5) 28 (4) 0.76
puncture headache, backache, urinary retention, and Time to complete 12 (5) 13 (3) 13 (5) 0.84
neurological deficits. colloid infusion
Our primary outcome was the maximum cephalad (min)
Duration of surgery 64 (31) 58 (19) 56 (17) 0.55
sensory block height. A sample size of 20 patients per (min)
group was calculated to detect a 2-segment difference Oxytocin dose (IU) 15 (11) 15 (11) 18 (13) 0.65
in maximum sensory block height, based on previous Baseline SBP 126 (16) 124 (14) 123 (11) 0.82
studies2,3 (Kruskal-Wallis test, assuming ␣ ⫽ 0.05, ␤ ⫽ (mm Hg)
0.20). Secondary outcomes included the incidence of Data are mean (SD).
hypotension, time taken for regression of sensory BMI ⫽ body mass index; SBP ⫽ systolic blood pressure.

block to T10, and recovery of modified Bromage

score to 2.
Patient demographic and parametric data (baseline
hemodynamic variables, duration of surgery, time to
maximal sensory block, and time for block regression)
were analyzed using the analysis of variance, with post
hoc Bonferroni correction applied if necessary. The
Kruskal-Wallis test was used to compare nonparamet-
ric data (maximal sensory block level) and post hoc
Mann-Whitney U-test for pairwise comparison with
Bonferroni adjustment if applicable. The ␹2 test was
used for categorical data, such as incidence of side
effects (shivering, nausea, vomiting, and high block).
A P value ⬍0.05 was considered significant. All sta-
tistical analyses were performed using Statistical
Package for Social Sciences Version 11.5™ software
(SPSS, Chicago, IL). Figure 1. Maximal cephalad sensory blockade. Box illustrates
interquartile range. Whiskers illustrate minimum and maxi-
mum values. Significant difference between Group 7 mg
versus Group 9 mg (P ⫽ 0.01). P value not significant for
RESULTS Group 7 mg versus Group 8 mg, and Group 8 mg versus
Sixty patients were recruited into our study over a Group 9 mg.
7-mo period between May 2007 and December 2007,
with 20 patients in each group. All 60 patients com- Table 2. Block Onset Characteristics
pleted the study. Baseline demographic profiles and
7 mg 8 mg 9 mg
patient characteristics were similar in all 3 groups
(N ⫽ 20) (N ⫽ 20) (N ⫽ 20) P
(Table 1).
The 3 groups differed in the maximum sensory Time to reach 4.7 (2.3) 4.2 (1.9) 3.9 (2.1) 0.52
T4 (min)
block height achieved (Fig. 1). Group 7 attained a Time to maximal 6.9 (1.7) 8.3 (1.9) 10.5 (2.4) ⬍0.01*
median block height of T2 (interquartile range T2–T3); sensory block
Group 8 attained a median block height of T2 (inter- (min)
quartile range T1–T2); and Group 9 attained a median Time to maximum 7.1 (2.9) 5.7 (2.1) 5.4 (1.7) 0.06
block height of T1 (interquartile range C8 –T2); P ⫽ motor block
(min)
0.02. Pairwise comparison showed a difference be-
Data are median (range) or mean (SD).
tween Groups 7 and 9 (P ⫽ 0.01). There was also a * Significant difference between Groups 7 mg and 9 mg, P ⬍ 0.01.
difference in the time taken to reach maximum sen-
sory block height among the 3 groups (Table 2). anesthetic before delivery of the baby and none re-
However, time taken to reach T4, defined as the quired conversion to general anesthesia. Five patients
adequate block height for surgery, was similar in all 3 in Group 9 developed blockade ⬎ T1, compared with
groups. No patient had inadequate anesthesia for one patient in Groups 7 and 8 (P ⫽ 0.08). None of the
surgery. All patients achieved a maximum Bromage patients reported any respiratory difficulties or exhib-
score of 3, and the time taken to reach Bromage score ited hypoxemia (defined as Spo2 ⬍92%).
of 3 was similar among groups (Table 2). None of the Eight patients in Group 7 required intraoperative
patients required additional boluses of epidural local block supplementation via the indwelling epidural

1602 Low-Dose Bupivacaine for Cesarean Delivery ANESTHESIA & ANALGESIA

Table 3. Block Recovery Characteristics
All patients including those who Patients without intra-operative
received epidural supplementation epidural supplementation

7 mg 8 mg 9 mg 7 mg 8 mg 9 mg
(N ⫽ 20) (N ⫽ 20) (N ⫽ 20) P (N ⫽ 12) (N ⫽ 16) (N ⫽ 17) P
Time to recede two segments 103 (40) 100 (20) 91 (20) 0.41 85 (19) 99 (19) 93 (19) 0.17
from maximum sensory
level (min)
Time to recede to T10 (min) 132 (39) 140 (24) 137 (24) 0.70 112 (22) 137 (24) 139 (25) 0.01*
Time for recovery to 111 (42) 106 (34) 132 (26) 0.06 92 (24) 95 (22) 130 (28) ⬍0.01†
Bromage score 2 (min)
Data are mean (SD).
* Significant difference between Group 7 mg versus Group 8 mg (P ⫽ 0.02) and between Group 7 mg versus Group 9 mg (P ⫽ 0.02).
† Significant difference between Group 7 mg versus Group 9 mg (P ⬍0.01) and between Group 8 mg versus Group 9 mg (P ⬍ 0.01).

Table 4. Hemodynamic Profiles and Side Effects

7 mg 8 mg 9 mg
(N ⫽ 20) (N ⫽ 20) (N ⫽ 20) P
No. of patients with 6 (30) 11 (55) 14 (70) 0.04*
hypotension
Lowest SBP recorded (mm Hg) 94 (12) 91 (14) 87 (10) 0.17
Lowest HR recorded (bpm) 76 (10) 81 (12) 73 (10) 0.07
Phenylephrine dosea (␮g) 0 (0–175) 100 (0–100) 100 (0–275) 0.12
Ephedrine dosea (mg) 0 (0) 0 (0) 0 (0) 0.35
Nausea 3 (15) 4 (20) 2 (10) 0.70
Vomiting 2 (10) 1 (5) 0 0.54
Shivering 2 (10) 0 1 (5) 0.35
Block ⬎ T1 1 (5) 1 (5) 5 (25) 0.08
No. of patients requiring epidural lidocaine bolus 8 (40) 4 (20) 3 (15) 0.16
Data are mean (SD), median (range), or n (%).
SBP ⫽ systolic blood pressure; HR ⫽ heart rate.
a
Data not normally distributed, thus expressed as median (interquartile range).
* Significant difference between Groups 7 mg and 9 mg (P ⫽ 0.03).

catheter, compared with 4 patients in Group 8 and 3
patients in Group 9 (P ⫽ 0.16). There was no difference
in the duration of motor blockade (recovery to Bro-
mage score 2) among groups. After excluding patients
who were given intraoperative epidural lidocaine,
recovery from sensory blockade to T10 dermatome
and recovery from lower limb motor blockade to a
Bromage score of 2 was longer in Group 9 compared
with Groups 7 and 8 (Table 3). The number of patients
requiring supplemental analgesics in all 3 groups was
similar. Two patients required Entonox during surgi-
cal closure (one from Group 7 and one from Group 8).
Eight patients required IV fentanyl postdelivery (4
from Group 7, 2 from Group 8, and 2 from Group 9).
There were significant differences in the incidence
of hypotension between Groups 7 and 9, although the
median total dosages of phenylephrine and ephedrine
administered for treatment of hypotension were simi-
lar among groups (Table 4). There were no differences
in the incidences of nausea, vomiting, and shivering.
No neonates had 1- or 5-min Apgar scores ⬍9.
Three patients (one from Group 7 and 2 from
Group 8) had inadvertent venous puncture. One pa-
tient in Group 9 had an inadvertent dural puncture.
Her spinal catheter was removed 24 h postdelivery,
and she did not develop a postdural puncture head-
ache during the first 2 postoperative days. All pa-
tients’ data were included in the analysis according to
intention-to-treat principles.
DISCUSSION
The feasibility of using low-dose CSE for cesarean
delivery has been explored in previous studies.10 –13
Most of these studies have included short-acting opi-
oids for block supplementation. However, the side
effects of such opioids, namely pruritus, may some-
times be uncomfortable or disconcerting in an awake
patient undergoing surgery under neuraxial anesthesia.
We designed our study to compare block characteris-
tics of varying low doses of hyperbaric bupivacaine
without short-acting opioids in order to elucidate an
optimal dose which provides rapid and effective an-
esthesia for cesarean delivery while minimizing side
effects. We found that the 3 groups differed in the
maximum sensory block height achieved. Although
this reached statistical significance, we thought that its
clinical significance was debatable, particularly be-
cause the cephalad extent of sensory blockade was T4
or higher in all patients, and the mean time to T4 was

Vol. 109, No. 5, November 2009 © 2009 International Anesthesia Research Society 1603
⬍5 min and similar in all 3 groups. We noticed that the
time taken to reach maximum block height was pro-
gressively longer with larger doses. This could be due
to a larger mass of drug taking a longer time to reach
equilibrium in the CSF.
We also found a significant reduction in the inci-
dence of hypotension when progressively smaller
doses were used. This concurs with a randomized
controlled trial conducted by Van de Velde et al.,14
which demonstrated that small-dose spinal anesthesia
(hyperbaric bupivacaine 6.5 mg) compared with
conventional-dose spinal anesthesia (hyperbaric bu-
pivacaine 9.5 mg) in combination with sufentanil
better preserves maternal hemodynamic stability with
equally effective anesthesia that is of shorter duration.
The literature has suggested that colloids may be
superior to crystalloids for fluid administration before
neuraxial anesthesia.6 –9 In addition, it is possible that
fluid coloading may be superior to preloading.15
However, despite our technique of coloading with
colloid, the overall incidence of hypotension was
rather high. One possible explanation is that our speed
of coloading was inadequate, because the mean time
to completion of IV 15 mL/kg hydroxyethyl starch
administered via pressurized infusion bags ranged
from 12 to 13 min. Also, we only studied the occur-
rence of hypotension and not its severity or duration.
The efficacy of intravascular volume expansion with
colloid may have been demonstrated in the relatively
small requirement for vasopressors in all 3 groups,
suggesting that the degree of postblock hypotension
was easily treated, perhaps by being of lesser severity
or shorter duration.
We acknowledge that there are certain limitations
in our study. For instance, we studied a homogeneous
population in a single obstetric unit and this may
influence the generalizability of our results to patients
from other centers. We did not conduct a detailed
analysis on the timeframe during surgery when our
patients developed hypotension. Hypotension imme-
diately after CSE anesthesia may be correlated with
the degree of ensuing sympathetic blockade, but hy-
potension postdelivery can be influenced by factors
such as rapidity of oxytocin infusion, surgical blood
loss, or extension of sympathetic blockade with epi-
dural local anesthetic administration. Our study was
underpowered to detect a difference in the need for
supplemental epidural anesthesia among groups. An-
other possible limitation lies in the difficulty of accu-
rately withdrawing 7, 8, and 9 mg of hyperbaric
bupivacaine into a 3-mL syringe. Lastly, we did not
record the time period from administration of
neuraxial blockade to first maternal request for
supplementary analgesia. It is possible that low-dose
CSE anesthesia, with its faster regression of sensory
blockade, may lead to larger consumption of nonste-
roidal antiinflammatory analgesics or additional opi-
oids in the first 24 h after surgery.
1604 Low-Dose Bupivacaine for Cesarean Delivery
We emphasize that the success of low-dose CSE
techniques depends on the placement of a catheter
into the epidural space that enables anesthesiologists
to extend the central neuraxial block intraoperatively
if surgical complications necessitate prolongation of
surgery. Unfortunately, accuracy of catheter place-
ment cannot be assessed before commencement of
surgery. In the event of catheter misplacement, the
faster regression of sensory block height associated
with low-dose CSE anesthesia may necessitate conver-
sion to general anesthesia if surgery is protracted. In
addition, performing CSE instead of a single-shot
spinal anesthesia exposes the patient to the risk of
postdural puncture headache from unintentional du-
ral puncture with a large-gauge Tuohy needle. There-
fore, the CSE technique should ideally be performed
by experienced anesthesiologists or under close super-
vision by trained anesthesiologists.
In conclusion, hyperbaric bupivacaine 7 mg with
100 ␮g morphine used in our study provided fast and
effective induction of surgical anesthesia for uncom-
plicated cesarean delivery while reducing the inci-
dence of maternal hypotension compared with 8 and 9
mg. However, the limited duration of surgical anes-
thesia necessitates the availability of a functioning
epidural catheter to supplement/extend neuroblock-
ade if necessary. The need for epidural supplementa-
tion may be reduced by using higher bupivacaine
doses of 8 and 9 mg, at the expense of increasing the
risk of maternal hypotension. Understanding the
block characteristics of different doses thus allows
better individualization of therapy, with adjustments
being made according to the estimated duration of
surgery or risk of maternal hypotension.
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© 2009 International Anesthesia Research Society 1605