The dose-sparing effect of clonidine added to ropivacaine for labor epidural analgesia.
ABSTRACT To determine the effects of clonidine with ropivacaine during epidural labor analgesia, we studied 66 nulliparous women in early active labor. Women were randomized to receive ropivacaine 0.1% 8 mL plus 75 microg of clonidine (Group 1), ropivacaine 0.2% 8 mL plus 0.5 mL of NaCl 0.9% (Group 2), or ropivacaine 0.2% 8 mL plus 75 microg of clonidine (Group 3) 5 min after a bupivacaine 7.5 mg with epinephrine 15 microg test dose. Upon request, additional analgesia with ropivacaine 0.1% 8 mL followed by ropivacaine 0.2% 8 mL/h was administered. With clonidine, duration of analgesia was increased (132 +/- 48 min [Group 1] and 154 +/- 42 min [Group 3] versus 91 +/- 44 min [Group 2]; P < 0.05), and total ropivacaine dose over the first 4 h was significantly reduced (40.5 +/- 15 mg [Group 1] and 47.0 +/- 16 mg [Group 3] versus 72.5 +/- 18 mg [Group 2]; P < 0.01). The incidence of more profound motor block was more frequent in Group 2 (P < 0.05). Although there was a trend for more women receiving clonidine to require ephedrine for treatment of hypotension, this did not seem to have an impact on fetal outcome or incidence of cesarean deliveries for nonreassuring fetal heart rate tracings. This study demonstrates the dose-sparing effect of clonidine when added to ropivacaine. IMPLICATIONS: The effect of adding 75 microg of clonidine to ropivacaine for epidural labor analgesia was studied. Clonidine increased analgesia duration and produced dose sparing compared with ropivacaine alone. Despite a tendency for hypotension in women receiving clonidine, there was no apparent effect on delivery mode or neonatal outcome.
Article: A comparison of epidural analgesia with 0.125% ropivacaine with fentanyl versus 0.125% bupivacaine with fentanyl during labor.[show abstract] [hide abstract]
ABSTRACT: We previously found that the extent of an epidural motor block produced by 0.125% ropivacaine was clinically indistinguishable from 0.125% bupivacaine in laboring patients. By adding fentanyl to the 0. 125% ropivacaine and bupivacaine solutions in an attempt to reduce hourly local anesthetic requirements, we hypothesized that differences in motor block produced by the two drugs may become apparent. Fifty laboring women were randomized to receive either 0. 125% ropivacaine with fentanyl 2 microg/mL or an equivalent concentration of bupivacaine/fentanyl using patient-controlled epidural analgesia (PCEA) with settings of: 6-mL/hr basal rate, 5-mL bolus, 10-min lockout, 30-mL/h dose limit. Analgesia, local anesthetic use, motor block, patient satisfaction, and side effects were assessed until the time of delivery. No differences in verbal pain scores, local anesthetic use, patient satisfaction, or side effects between groups were observed; however, patients administered ropivacaine/fentanyl developed significantly less motor block than patients administered bupivacaine/fentanyl. Ropivacaine 0.125% with fentanyl 2 microg/mL produces similar labor analgesia with significantly less motor block than an equivalent concentration of bupivacaine/fentanyl. Whether this statistical reduction in motor block improves clinical outcome or is applicable to anesthesia practices which do not use the PCEA technique remains to be determined. Implications: By using a patient-controlled epidural analgesia technique, ropivacaine 0.125% with fentanyl 2 microg/mL produces similar analgesia with significantly less motor block than a similar concentration of bupivacaine with fentanyl during labor. Whether this statistical reduction in motor block improves clinical outcome or is applicable to anesthesia practices which do not use the patient-controlled epidural analgesia technique remains to be determined.Anesthesia & Analgesia 04/2000; 90(3):632-7. · 3.29 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Dilute concentrations of bupivacaine combined with fentanyl have recently been used to initiate labor epidural analgesia in an attempt to balance adequate analgesia and minimal maternal motor blockade. Similar concentrations of ropivacaine have not been evaluated. This prospective, randomized, double-blinded study was designed to compare the efficacy of 20 mL of either 0.08% bupivacaine plus 2 microg/mL fentanyl or 0.08% ropivacaine plus 2 microg/mL fentanyl to initiate ambulatory labor epidural analgesia. Forty nulliparous women in early (</=5 cm) established labor received either 20 mL of 0.08% bupivacaine plus 2 microg/mL fentanyl (BF) or 0.08% ropivacaine plus 2 microg/mL fentanyl (RF) to initiate epidural analgesia. One woman (BF) required supplemental analgesia, and two (one BF and one RF) had visual analog scale scores > 0 but < 20 at 20 min. The time (mean +/- SD) to visual analog scale score = 0 was BF (n = 18): 12.0 +/- 4.5 min and RF (n = 19): 12.4 +/- 4.0 min (P > 0.05). Spontaneous micturition was observed in 65% (13 of 20) BF compared with 100% (20 of 20) RF (P < 0.01), and ambulation was demonstrated in 75% (15 of 20) BF compared with 100% (20 of 20) RF (P < 0.03). The incidence of forceps delivery was 35% (7 of 20) BF compared with 10% (2 of 20) RF (P < 0.04). The results of this study indicate that dilute ropivacaine combined with fentanyl effectively initiates epidural analgesia while concurrently preserving maternal ability to void and ambulate. Implications: As compared with a similar dilute concentration of bupivacaine, 20 mL of dilute (0.08%) ropivacaine combined with fentanyl (2 microg/mL) effectively initiates epidural analgesia in nulliparous women in early, established labor while preserving their ability to micturate and ambulate. Of importance, it appears that a true ambulatory epidural analgesic for women in labor is now possible.Anesthesia & Analgesia 06/2000; 90(6):1384-9. · 3.29 Impact Factor
Article: Extradural analgesia with clonidine and fentanyl compared with 0.25% bupivacaine in the first stage of labour.[show abstract] [hide abstract]
ABSTRACT: Conventional extradural analgesia during labour with 0.25-0.375% bupivacaine may induce motor weakness and subjective sensory deficit, reducing maternal satisfaction. Even in a regimen for ambulatory extradural analgesia (0.1% bupivacaine-fentanyl 2 micrograms ml-1), a potential for proprioreception impairment exists, which may impair safe ambulation. We have combined fentanyl with clonidine for extradural analgesia in labour, and compared its effects with 0.25% bupivacaine, in a randomized, double-blind study. We studied 28 women requesting extradural analgesia for labour; they were allocated randomly to either group 1, who received clonidine 120 micrograms with fentanyl 50 micrograms, or group 2, who received bupivacaine 25 mg. Detailed clinical neurological examination was undertaken 30 min later. Pain was assessed subjectively using a 10-cm visual analogue scale (VAS). There were no significant differences in VAS between the groups at any time. Median onset of analgesia was longer in group 1 (24.3 (interquartile range 20-35) compared with 17.5 (15-25) min) (P < 0.05) and 79% of group 1 vs 86% of group 2 patients reported a high degree of satisfaction with extradural analgesia. Patients in group 2 had a much higher incidence of motor weakness (P < 0.01), impaired perception of pinprick (P < 0.01) and impaired distal joint proprioception (P < 0.05) than group 1. We conclude that clonidine 120 micrograms-fentanyl 50 micrograms provided comparable extradural analgesic efficacy as 0.25% bupivacaine for the first stage of labour. Furthermore, unwanted neurological effects were significantly less.BJA British Journal of Anaesthesia 02/1996; 76(2):319-21. · 4.24 Impact Factor
DAVID J. BIRNBACH
The Dose-Sparing Effect of Clonidine Added to Ropivacaine
for Labor Epidural Analgesia
Ruth Landau, MD*, Eduardo Schiffer, MD*, Michel Morales, MD†, Georges Savoldelli, MD*,
and Christian Kern, MD*
*Division d’Anesthe ´siologie, De ´partement d’Anesthe ´siologie, Pharmacologie et Soins Intensifs de Chirurgie (APSIC), and
†Clinique d’Obste ´trique, De ´partement de Gyne ´cologie et Obste ´trique, Ho ˆpitaux Universitaires de Gene `ve (HUG),
Gene `ve, Suisse
To determine the effects of clonidine with ropiva-
caine during epidural labor analgesia, we studied 66
nulliparous women in early active labor. Women
were randomized to receive ropivacaine 0.1% 8 mL
plus 75 ?g of clonidine (Group 1), ropivacaine 0.2%
8 mL plus 0.5 mL of NaCl 0.9% (Group 2), or ropiva-
caine 0.2% 8 mL plus 75 ?g of clonidine (Group 3)
5 min after a bupivacaine 7.5 mg with epinephrine 15
?g test dose. Upon request, additional analgesia with
ropivacaine 0.1% 8 mL followed by ropivacaine 0.2%
8 mL/h was administered. With clonidine, duration
of analgesia was increased (132 ? 48 min [Group 1]
and 154 ? 42 min [Group 3] versus 91 ? 44 min
[Group 2]; P ? 0.05), and total ropivacaine dose over
the first 4 h was significantly reduced (40.5 ? 15 mg
[Group 1] and 47.0 ? 16 mg [Group 3] versus 72.5 ?
18 mg [Group 2]; P ? 0.01). The incidence of more
profound motor block was more frequent in Group 2
(P ? 0.05). Although there was a trend for more
women receiving clonidine to require ephedrine for
treatment of hypotension, this did not seem to have
an impact on fetal outcome or incidence of cesarean
deliveries for nonreassuring fetal heart rate tracings.
This study demonstrates the dose-sparing effect of
clonidine when added to ropivacaine.
(Anesth Analg 2002;95:728–34)
gesia delivered by the epidural route. Clonidine is a
?2-adrenergic agonist that produces analgesia via a
non-opioid mechanism, and the combination of epi-
dural clonidine with bupivacaine for labor analgesia
has been previously studied (3–11). However, the fact
that clonidine has not been approved by the Food and
Drug Administration for use in obstetric anesthesia
and its relatively high cost in certain countries have
limited its use (12). Despite the continuing concern
about its hemodynamic effects (maternal hypotension
and bradycardia) and potential consequences on
uteroplacental flow, in addition to maternal sedative
effects, clonidine has not been clearly associated with
opivacaine produces less motor block than bu-
pivacaine with similar analgesia (1,2), which
makes it an interesting drug for obstetrical anal-
altered Apgar scores or poor neonatal outcomes. In
fact, only few cases of abnormal fetal heart rate trac-
ings were reported with the use of epidural clonidine
for labor analgesia; these have been shown to occur
either when clonidine was given as a bolus of 150 ?g
(4) or with repeated boluses of 75 ?g (5).
We postulated that adding clonidine to ropivacaine
for epidural analgesia during labor should allow good
analgesia with minimal motor block. The purpose of
this prospective, randomized, double-blinded study
was to examine whether 75 ?g of clonidine increases
the analgesic properties (intensity and duration) of an
initial ropivacaine dose and produces dose sparing of
ropivacaine. We also collected data on any adverse
neonatal outcome occurring after the epidural admin-
istration of clonidine.
After approval from the Institutional Ethics Commit-
tee and obtaining informed written consent, we stud-
ied 66 healthy (ASA physical status I or II) nulliparous
women in active labor. Women requesting epidural
analgesia were considered for inclusion in the study if
they presented with a singleton pregnancy of more
Presented, in part, at the 31st Annual Meeting of the Society for
Obstetric Anesthesia and Perinatology (SOAP), Denver, CO, May
1999, and the Annual Meeting of the American Society of Anesthe-
siologists (ASA), Dallas, October 1999.
Accepted for publication May 14, 2002.
Address correspondence and reprint requests to Ruth Landau,
MD, Division d’Anesthe ´siologie, APSIC, Ho ˆpitaux Universitaires de
Gene `ve (HUG), Rue Micheli-du-Crest 12, 1211 Gene `ve 14, Switzer-
land. Address e-mail to email@example.com.
©2002 by the International Anesthesia Research Society
Anesth Analg 2002;95:728–340003-2999/02
than 37 wk gestation in early labor (cervix dilation ?5
cm) with a normal fetal heart rate tracing. Exclusion
criteria included pregnancy-induced hypertension,
multiple pregnancies, breech presentation, multipar-
ity, and gestational diabetes.
Women were randomly assigned in a double-
blinded fashion to one of three groups. Group 1 re-
ceived 8 mL of ropivacaine 0.1% with clonidine 75 ?g
(0.5 mL), Group 2 received 8 mL of ropivacaine 0.2%
with NaCl 0.9% (0.5 mL), and Group 3 received 8 mL
of ropivacaine 0.2% with clonidine 75 ?g (0.5 mL).
Randomization was performed by random computer
allocation with numbered envelopes. The study sy-
ringe was prepared at the time of randomization by a
nurse anesthetist who was not present on the labor
floor and not involved with the study case. Pharma-
cological preparations for epidural infusion of ropiva-
caine (Naropin®, Astra-Zeneca, Switzerland) with the
addition of clonidine (Catapressan®, Boehringer, Ger-
many) were tested for safety in terms of solubility and
chemical stability (HUG, Central Pharmacy, Geneva,
Switzerland). Since the time of this study design, com-
patibility of ropivacaine with clonidine has further
been demonstrated (13). Placement of the epidural
catheter, management of labor analgesia, and all data
recordings were performed by members of the anes-
thesia team blinded to group allocation throughout
the entire case.
Before epidural analgesia, IV fluid loading was ini-
tiated with 500 mL of Ringer’s lactate solution.
Women were placed in the left lateral decubitus posi-
tion, and local anesthesia of skin and subcutaneous
tissues was performed at lumbar level L2-3 or L3-4
with lidocaine 1% 1–2 mL. Thereafter, the epidural
space was localized with the loss of resistance to saline
technique using an 18-gauge Tuohy needle. A 20-
gauge multi-orifice epidural catheter was then in-
serted 5 cm into the epidural space in a cephalad
direction and aspirated for detection of cerebrospinal
fluid or blood. After the catheter was taped, subjects
were repositioned with left uterine displacement, and
3 mL of 0.25% bupivacaine with 15 ?g of epinephrine
as a test dose was administered, as was standard
practice at our institution at the time of this study. In
the absence of intravascular or intrathecal placement
of the catheter, the study drug was administered 5 min
after the test dose. Timing of the injection of study
drug was defined as T ? 0, and assessments were
scheduled accordingly. Pain was assessed with a
10-cm linear visual analog scale (VAS) immediately
before epidural placement and at 5, 10, 15, 20, 30, 60,
120, 180, and 240 min after injection of the study drug.
Onset of analgesia was taken as time to achieve VAS
?3. Duration of analgesia was considered as time
elapsed between T ? 0 and breakthrough pain, which
was defined as VAS ?3, and/or request for additional
analgesia and treated in a similar fashion in all three
groups. Management of breakthrough pain consisted
of a bolus of 8 mL of ropivacaine 0.1% followed by a
continuous infusion of ropivacaine 0.2% 8 mL/h and
additional doses of 6–8 mL of ropivacaine 0.1% when
required. A maximum of three top-ups over the first
4 h of the study was allowed before alteration of the
epidural analgesic regimen and removal of the case
from the study. On the first postpartum day, global
maternal satisfaction was assessed with a 10-cm VAS
by a blinded observer, 10 being maximal satisfaction.
Sensory levels were determined with changes to
cold (ether) at 5, 10, 15, 20, 30, 60, 120, 180, and 240 min
after study drug injection. Motor block using a mod-
ified Bromage scale (0 ? no block, 1 ? inability to raise
extended leg, 2 ? inability to flex knee, and 3 ?
inability to flex ankle and foot) were also recorded at
the same intervals. With a Bromage score ?2, the
infusion rate of ropivacaine was reduced until the
Bromage score was found to be ?1. Sedation was
recorded with a four-point score (0 ? no sedation, 1 ?
slight sedation or patient responding to verbal stimu-
lation, 2 ? moderate sedation or patient responding to
tactile stimulation, and 3 ? deep sedation or patient
not responding to tactile stimulation) as used by oth-
Maternal monitoring included arterial blood pres-
sure every 5 min during the first hour and then every
15 min and continuous heart rate measures and axil-
lary temperature once every hour. Cervical dilation at
entry of study, duration of first and second stage of
labor, and oxytocin use for the induction or augmen-
tation of labor were recorded. Hemodynamic vari-
ables, motor, and sensory assessments were discontin-
ued after 4 h, but recording of total and hourly drug
administration was continued until delivery.
Adverse effects, such as nausea, vomiting, itching,
maternal bradycardia, or hypotension were reported.
Hypotension was defined as systolic blood pressure
measurement ?100 mm Hg and/or ?25% baseline
decrease and was treated with 5–10 mg of ephedrine
with additional doses when required.
Fetal heart rate was recorded continuously on a
cardiotocograph (Hewlett-Packard 80300A, Hewlett
Packard, Palo Alto, CA). Fetal heart rate tracings were
monitored by obstetricians blinded to group allocation
and reviewed again postpartum for detection of fetal
heart rate abnormalities (MM). Analysis compared
tracings obtained at least 30 min before epidural place-
ment with those recorded during epidural analgesia.
Fetal heart rate abnormalities such as late decelera-
?100 bpm lasting for 5 min or more), and decreased
fetal heart rate variability according to criteria used at
our institution (at least two accelerations of 15 bpm
lasting 15 s for 40 min) were noted. Fetal events were
managed with standard measures such as oxygen, left
or right lateral uterine displacement, ephedrine when
as fetal heart rate
OBSTETRIC ANESTHESIALANDAU ET AL.
ADDITION OF CLONIDINE TO ROPIVACAINE FOR LABOR
required, cessation of oxytocin, and tocolytic treat-
ment when required. Fetal scalp pH value was deter-
mined when appropriate, and instrumental or cesar-
ean delivery was performed when indicated. Mode of
delivery, neonatal weight, and umbilical cord blood-
gas were recorded. Apgar scores and clinical evalua-
tion at 24 h after birth were performed in all neonates
by pediatricians blinded to group allocation.
Expecting that clonidine will prolong analgesia du-
ration by approximately 60 min (15), thus decreasing
by 20% the dose of ropivacaine administered over 4 h
(40 mL to 32 mL of ropivacaine 0.2%), power test
analysis resulted in a calculated sample of 22 subjects
per group to obtain statistical relevance of our hypoth-
esis (assuming a ? error of 0.05 and a power of 0.80).
Data are presented as mean ? sd. For all calculations,
INSTAT computer software package (GraphPad In-
stat, San Diego, CA) and Statistica for Windows 1993,
Release 4.5A (Statsoft Inc, Tulsa, OK) were used. The
statistical analysis was performed using analysis of
variance for comparison between groups and Fisher’s
exact test for categorical variables. A value of P ? 0.05
was considered significant.
Seventy-two women were enrolled in the study and
six cases were excluded (four unilateral blocks identi-
fied within the first hour of the study and two dis-
placed catheters requiring replacement of the catheter
within the first 4 h). Groups were comparable with
regard to demographic data and cervical dilation
upon entry, duration of first and second stages, oxy-
tocin use for the induction or augmentation of labor,
mode of delivery, and Apgar scores (Table 1).
Onset of analgesia was shorter in Group 3, with a
trend at 5 min (P ? 0.07) becoming significant at
10 min (Table 2). At 10 and 30 min, the number of
subjects reporting a pain score ?3 was significantly
more in Group 3 (Table 2). Duration of analgesia was
significantly prolonged with the addition of clonidine
(Table 2). The number of women requiring additional
boluses of ropivacaine was significantly greater in
Group 2 (Fig. 1). There was no difference in sensory
level among groups throughout the study. Despite a
trend for a higher satisfaction score in Group 3 on the
first postpartum day, there was no difference in ma-
ternal satisfaction among groups (8.7 ? 1.4 in Group 1,
8.5 ? 2.0 in Group 2, and 9.5 ? 0.8 in Group 3; P ?
During the first hour, there was no difference in the
incidence of motor block among groups, with no
woman developing a significant motor block (i.e., Bro-
mage score ?2) (Fig. 2). However, with time and
during the 4 h of the study, the incidence of motor
block was significantly more frequent in Group 2 ver-
sus Groups 1 and 3 (Fig. 2). The total ropivacaine dose
was also different among groups, with Group 2 re-
quiring significantly more ropivacaine (Table 2).
The mean dose of ephedrine among women requiring
ephedrine for hypotension was similar among groups
(16 ? 9 mg in Group 1, 14 ? 5 mg in Group 2, and 11 ?
6 mg in Group 3; P ? 0.30). There was a tendency for
Table 1. Patient Demographics and Obstetric Characteristics
Gestational age (wk)
Oxytocin for induction (n)
Oxytocin for augmentation (n)
Cervical dilation at entry (cm)
Labor duration (min)
Mode of delivery
Spontaneous vaginal (n)
Birth weight (g)
Apgar ? 7 at 5 min (n)
28 ? 4
72 ? 9
164 ? 6
27 ? 5
74 ? 13
163 ? 6
29 ? 4
72 ? 13
162 ? 7
38.9 ? 1.0
2.6 ? 0.4
227 ? 119
39.0 ? 1.2
2.4 ? 0.2
249 ? 103
39.6 ? 1.3
2.5 ? 0.4
270 ? 160
110 ? 41 105 ? 43119 ? 37
3335 ? 330
3550 ? 350
3340 ? 407
Unless indicated, data presented as mean ? sd. No significant differences exist among groups.
aRopivacaine 0.1% 8mL with clonidine 75 ?g.
bRopivacaine 0.2% 8mL with NaCl 0.9%.
cRopivacaine 0.2% 8mL with clonidine 75 ?g.
dDuration of first stage from epidural insertion
ADDITION OF CLONIDINE TO ROPIVACAINE FOR LABOR
LANDAU ET AL.ANESTH ANALG
more women in Group 1 (n ? 7 of 22) and Group 3 (n ?
9 of 22) versus women in Group 2 (n ? 4 of 22) to be
treated with ephedrine during the 4 h of the study;
however, this did not reach statistical significance (rela-
tive risk, 0.55; 95% confidence interval, 0.19–1.31; P ?
0.16). All women were treated with incremental doses of
5 mg of ephedrine, with no woman requiring more than
Table 2. Analgesia Characteristics, Ropivacaine Dose, and Side Effects
VAS before study drug
VAS at 5 min
Subjects with VAS ?3 at 5 min (n)
VAS at 10 min
Subjects with VAS ?3 at 10 min (n)
VAS at 30 min
Subjects with VAS ?3 at 30 min (n)
Analgesia duration (min)
Dose over 4 h (mg)d
Sedation score ? 0 (n)
Sedation score ? 1 (n)
Sedation score ? 2 (n)
Sedation score ? 3 (n)
9.1 ? 1.2
4.4 ? 2.7
3.3 ? 2.7
1.4 ? 2.2
132 ? 48
8.7 ? 1.3
5.4 ? 2.3
3.8 ? 2.5
2.0 ? 2.6
91 ? 44
8.6 ? 1.0
3.5 ? 3.0
1.9 ? 2.2*
0.4 ? 0.9*
154 ? 42†
40.5 ? 15 72.5 ? 18 47.0 ? 16†
Unless indicated, data presented as mean ? sd.
VAS ? visual analogue scale (for pain).
* Group 3 versus Groups 1 & 2 (P ? 0.05, analysis of variance)
† Group 2 versus Groups 1 & 3 (P ? 0.05, analysis of variance)
aRopivacaine 0.1% 8mL with clonidine 75?g.
bRopivacaine 0.2% 8mL with NaCl 0.9%.
cRopivacaine 0.2% 8mL with clonidine 75?g.
dData presented for 20 women in each group (two cases per group delivered before completion of the 4 h of the study).
eSedation score: 0 ? no sedation; 1 ? slight sedation; 2 ? moderate sedation; and 3 ? deep sedation.
Figure 1. Distribution of additional doses after the study drug
during the 4 h of the study. With the first additional dose (ropiva-
caine 0.1% 8 mL), a continuous infusion of ropivacaine 0.2% was
started at 8 mL/h. After the study drug, two women in Group 2,
versus seven in Group 1 and 11 in Group 3, never requested addi-
tional dosing until delivery (relative risk, 1.59; 95% confidence
interval, 1.19–2.13; P ? 0.01). Overall, women in Group 2 required
significantly more additional doses than women in Groups 1 and 3
(*P ? 0.05, analysis of variance). Group 1, ropivacaine 0.1% 8 mL
with clonidine 75 ?g; Group 2, ropivacaine 0.2% 8 mL with NaCl
0.9%; and Group 3, ropivacaine 0.2% 8 mL with clonidine 75 ?g.
Figure 2. Number of women with motor block (Bromage score 1)
at 60, 120, 180, and 240 min (shaded bars). Number of women
developing more intense motor block (Bromage score 2) are
represented with hatched vertical bars (one woman in Group 1,
six women in Group 2, and three women in Group 3). Because the
ropivacaine infusion rate was reduced in women developing an
intense motor block, Bromage score 2 was never noted twice (on
two different assessment times) in the same woman. Women in
Group 2 developed significantly more motor block than women
in Groups 1 and 3 (*P ? 0.05, analysis of variance). Group 1,
ropivacaine 0.1% 8 mL with clonidine 75 ?g; Group 2, ropiva-
caine 0.2% 8 mL with NaCl 0.9%; and Group 3, ropivacaine 0.2%
8 mL with clonidine 75 ?g.
OBSTETRIC ANESTHESIALANDAU ET AL.
ADDITION OF CLONIDINE TO ROPIVACAINE FOR LABOR
30 mg. Three women in each group required multiple
ephedrine doses; all women were treated within the first
hour of the study, with the exception of one woman in
Group 3 requiring 20 mg of ephedrine 120 min after the
study dose (case h, Table 3).
There was no difference in the incidence of nau-
sea, vomiting, or sedation (Table 2). There were no
cases of maternal bradycardia, itching, or hyper-
thermia (T ?37.8°C) recorded at any time during the
Fetal heart rate abnormalities were diagnosed in
10 different parturients and managed with standard
measures (Table 3). No tocolytic treatment was re-
quired. Fetal heart rate variability was normal in all
cases. Episodes of fetal bradycardia directly related
to maternal hypotension were observed in one
woman per group and required no other treatment
than ephedrine. These events occurred 60 (case b),
20 (case c), and 120 (case h) min after the study
drug, respectively (Table 3). In Group 1, one case of
fetal bradycardia was associated with a prolapsed
cord and required an immediate cesarean delivery
(case a). In Group 2, two cases of bradycardia
shortly after study drug administration (cases c and
d) and two cases of late decelerations (cases e and f)
were recorded. In Group 3, one case of late deceler-
ation occurring 80 min after study drug administra-
tion not related to an episode of maternal hypoten-
sion required an immediate cesarean delivery (case
i). No neonate was admitted to the neonatal inten-
sive care unit. Pediatricians reported a normal clin-
ical status within the first 24 h in all six neonates
born to mothers receiving clonidine in which abnor-
mal fetal heart rate tracings had been recorded.
This is the first study demonstrating the additive an-
algesic effect in the first stage of labor of an epidural
bolus of 75 ?g of clonidine administered with ropiva-
caine. We decided to study two doses of ropivacaine,
8 mg (0.1%) and 16 mg (0.2%), because ropivacaine
dose-response studies for initiation of epidural anal-
gesia were not available at the time of study design. In
addition, because ropivacaine was studied without
opioids, we decided not to administer the smaller dose
(8 mg) without clonidine because we expected this
dose to be insufficient to provide adequate analgesia.
This assumption was confirmed in a study showing
that the optimal concentration of ropivacaine as a sole
anesthetic for the initiation of epidural analgesia is
0.2% (13 mL) (16). We are aware that the administra-
tion of 7.5 mg of bupivacaine with 15 ?g of epineph-
rine as a test dose could interfere with the interpreta-
tion of our results; yet, at the time of the study design,
it was felt that ropivacaine was not a suitable drug to
detect an intravascular or intrathecal catheter and
should not be used as a test dose. Nonetheless, be-
cause all three groups received a similar bupivacaine-
epinephrine test dose, this should minimize any con-
Clonidine was administered as a bolus of 75 ?g
because smaller doses (30 ?g) have been shown not to
improve analgesia significantly (8), whereas larger
doses (150 ?g) have resulted in maternal bradycardia
(one case requiring atropine) (4), decreased fetal heart
rate variability and late decelerations (4), and maternal
sedation (120 ?g) (15). In an early dose-finding study,
75 ?g of clonidine was indeed the optimal epidural
Table 3. Characteristics of the 10 Cases in Which Fetal Heart Rate Abnormalities Were Noted
Late decelaration (min)c
Blood pressure (mmHg)d
Mode of delivery
Apgar score (1 min/5 min)
Umbilical arterial pH value
Umbilical venous pH value
S ? spontaneous vaginal; F ? forceps; C/S ? cesarean section delivery.
aStudy drug according to group: Group 1 ? Ropivacaine 0.1% 8 mL with clonidine 75 ?g; Group 2 ? Ropivacaine 0.2% 8 mL with NaCl 0.9%; Group 3 ?
Ropivacaine 0.2% 8 mL with clonidine 75 ?g.
bTime between study drug and bradycardia (fetal heart rate ?100 bpm lasting ?5 min).
cTime between study drug and late deceleration.
dSystolic blood pressure at time of fetal heart rate abnormality.
eTime between study drug and delivery.
fEmergency cesarean delivery because of cord prolapse.
ADDITION OF CLONIDINE TO ROPIVACAINE FOR LABOR
LANDAU ET AL.ANESTH ANALG
dose to add to bupivacaine for labor analgesia1and
provided approximately two hours of satisfactory an-
algesia when added to bupivacaine (5). Furthermore,
we decided to limit the clonidine administration to
one single bolus because fetal heart rate abnormalities
have been associated with repeated doses of 75 ?g of
Our findings are consistent with several studies ex-
amining the effect of clonidine added to ropivacaine in
peripheral blocks (17,18) as a spinal adjunct for ortho-
pedic surgery (19) or by the caudal route for pediatric
surgery (20), which all showed prolongation of
In our study, onset of analgesia was significantly
shorter among women receiving clonidine with the
larger dose of ropivacaine 0.2% (8 mL). A reduced
onset of action with clonidine has not been reported in
previous studies examining the combination of
clonidine with bupivacaine (4,6,15). It is possible that
our definition of analgesia onset differs from that of
other authors. We defined good analgesia as a VAS ?3
and recorded VAS precisely at five and 10 minutes to
determine the number of cases reporting VAS scores
?3 at these time intervals. Our data strongly suggest
that the addition of clonidine impacts favorably both
on the number of women with a VAS ?3 and on the
average VAS at 10 minutes. The exact mechanism by
which the addition of clonidine might shorten the
onset of analgesia produced by ropivacaine is not
clear; the possibility of a positive interaction between
the intrinsic vasoconstricting effect of ropivacaine (21)
and clonidine remains to be determined.
Duration of action was substantially increased in
both groups with clonidine. There was no significant
advantage of ropivacaine 0.2% 8 mL with clonidine
over ropivacaine 0.1% 8 mL with clonidine in terms of
duration of analgesia. The addition of clonidine to
0.2% ropivacaine prolonged by approximately one
hour the analgesia time produced by 0.2% ropivacaine
alone. The hourly dose for the four first hours was
significantly reduced by the addition of clonidine,
with no difference in dose of ropivacaine between the
two groups receiving clonidine. This is because of the
fact that in Group 1, the smaller initial ropivacaine
dose was compensated with subsequent ropivacaine
doses when required, and in Group 3, fewer addi-
tional doses were required after a larger initial study
bolus. Furthermore, the reduced dose of ropivacaine
required over the study period in both groups receiv-
ing clonidine produced less motor block over time.
We report no episodes of maternal bradycardia in
women receiving clonidine, probably as a result of the
relatively small dose of clonidine administered. Seda-
tion has been reported to occur as soon as 15 to
60 minutes after doses of 120 ?g of clonidine (15) and
60 to 120 minutes after 150 ?g of clonidine (14) or 75
?g of clonidine with 50 ?g of fentanyl (14). We did not
observe significant sedation in either group, probably
because of the small dose of clonidine and the absence
of concurrent opioid administration.
In our study, 44 women (Groups 1 and 3) received
75 ?g of epidural clonidine. Episodes of fetal brady-
cardia directly attributed to maternal hypotension oc-
curred between 20 and 120 minutes after the injection
of the study drug. This finding is consistent with other
reports of decreased mean arterial blood pressure oc-
curring 20 to 140 minutes after the clonidine adminis-
tration (4). Although there was a tendency for more
women who received clonidine to require ephedrine,
this did not seem to impact fetal outcomes, as moni-
tored by Apgar scores and umbilical cord blood-gas
values. Our data show that despite some changes in
maternal hemodynamic status, which may occur up to
two hours after 75 ?g of epidural clonidine, hypoten-
sion can be managed efficiently with ephedrine, with
no apparent adverse effect on obstetrical and fetal
outcome. However, because our study was not specif-
ically designed to detect differences in adverse neona-
tal effects, larger studies are required to further con-
firm that 75 ?g of epidural clonidine does not impact
on neonatal well being.
In conclusion, our results demonstrate a dose-
sparing effect of clonidine added to ropivacaine for
epidural labor analgesia during the first stage of labor,
resulting in a reduced motor block. However, because
of the potential for maternal hypotension, we recom-
mend that laboring women be closely monitored for
several hours after receiving epidural clonidine.
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LANDAU ET AL.ANESTH ANALG