OBSTETRIC ANESTHESIASECTION EDITOR

DAVID J. BIRNBACH

The Dose-Sparing Effect of Clonidine Added to Ropivacainefor Labor Epidural AnalgesiaRuth Landau, MD*, Eduardo Schiffer, MD*, Michel Morales, MD†, Georges Savoldelli, MD*,and Christian Kern, MD*

*Division d’Anesthesiologie, Departement d’Anesthesiologie, Pharmacologie et Soins Intensifs de Chirurgie (APSIC), and†Clinique d’Obstetrique, Departement de Gynecologie et Obstetrique, Hopitaux Universitaires de Geneve (HUG),Geneve, Suisse

To determine the effects of clonidine with ropiva-caine during epidural labor analgesia, we studied 66nulliparous women in early active labor. Womenwere randomized to receive ropivacaine 0.1% 8 mLplus 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 withropivacaine 0.1% 8 mL followed by ropivacaine 0.2%8 mL/h was administered. With clonidine, durationof 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 overthe 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 moreprofound motor block was more frequent in Group 2(P � 0.05). Although there was a trend for morewomen receiving clonidine to require ephedrine fortreatment of hypotension, this did not seem to havean impact on fetal outcome or incidence of cesareandeliveries for nonreassuring fetal heart rate tracings.This study demonstrates the dose-sparing effect ofclonidine when added to ropivacaine.

(Anesth Analg 2002;95:728 –34)

R opivacaine produces less motor block than bu-pivacaine with similar analgesia (1,2), whichmakes it an interesting drug for obstetrical anal-

gesia delivered by the epidural route. Clonidine is a�2-adrenergic agonist that produces analgesia via anon-opioid mechanism, and the combination of epi-dural clonidine with bupivacaine for labor analgesiahas been previously studied (3–11). However, the factthat clonidine has not been approved by the Food andDrug Administration for use in obstetric anesthesiaand its relatively high cost in certain countries havelimited its use (12). Despite the continuing concernabout its hemodynamic effects (maternal hypotensionand bradycardia) and potential consequences onuteroplacental flow, in addition to maternal sedativeeffects, clonidine has not been clearly associated with

altered Apgar scores or poor neonatal outcomes. Infact, only few cases of abnormal fetal heart rate trac-ings were reported with the use of epidural clonidinefor labor analgesia; these have been shown to occureither 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 ropivacainefor epidural analgesia during labor should allow goodanalgesia with minimal motor block. The purpose ofthis prospective, randomized, double-blinded studywas to examine whether 75 �g of clonidine increasesthe analgesic properties (intensity and duration) of aninitial ropivacaine dose and produces dose sparing ofropivacaine. We also collected data on any adverseneonatal outcome occurring after the epidural admin-istration of clonidine.

MethodsAfter approval from the Institutional Ethics Commit-tee and obtaining informed written consent, we stud-ied 66 healthy (ASA physical status I or II) nulliparouswomen in active labor. Women requesting epiduralanalgesia were considered for inclusion in the study ifthey presented with a singleton pregnancy of more

Presented, in part, at the 31st Annual Meeting of the Society forObstetric Anesthesia and Perinatology (SOAP), Denver, CO, May1999, 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’Anesthesiologie, APSIC, Hopitaux Universitaires deGeneve (HUG), Rue Micheli-du-Crest 12, 1211 Geneve 14, Switzer-land. Address e-mail to ruth.landau@hcuge.ch.

DOI: 10.1213/01.ANE.0000024265.35827.2D

©2002 by the International Anesthesia Research Society728 Anesth Analg 2002;95:728–34 0003-2999/02

than 37 wk gestation in early labor (cervix dilation �5cm) with a normal fetal heart rate tracing. Exclusioncriteria 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 mLof ropivacaine 0.2% with clonidine 75 �g (0.5 mL).Randomization was performed by random computerallocation with numbered envelopes. The study sy-ringe was prepared at the time of randomization by anurse anesthetist who was not present on the laborfloor and not involved with the study case. Pharma-cological preparations for epidural infusion of ropiva-caine (Naropin®, Astra-Zeneca, Switzerland) with theaddition of clonidine (Catapressan®, Boehringer, Ger-many) were tested for safety in terms of solubility andchemical stability (HUG, Central Pharmacy, Geneva,Switzerland). Since the time of this study design, com-patibility of ropivacaine with clonidine has furtherbeen demonstrated (13). Placement of the epiduralcatheter, management of labor analgesia, and all datarecordings were performed by members of the anes-thesia team blinded to group allocation throughoutthe 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 subcutaneoustissues was performed at lumbar level L2-3 or L3-4with lidocaine 1% 1–2 mL. Thereafter, the epiduralspace was localized with the loss of resistance to salinetechnique 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 cephaladdirection and aspirated for detection of cerebrospinalfluid or blood. After the catheter was taped, subjectswere repositioned with left uterine displacement, and3 mL of 0.25% bupivacaine with 15 �g of epinephrineas a test dose was administered, as was standardpractice at our institution at the time of this study. Inthe absence of intravascular or intrathecal placementof the catheter, the study drug was administered 5 minafter the test dose. Timing of the injection of studydrug was defined as T � 0, and assessments werescheduled accordingly. Pain was assessed with a10-cm linear visual analog scale (VAS) immediatelybefore 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 timeelapsed between T � 0 and breakthrough pain, whichwas defined as VAS �3, and/or request for additionalanalgesia and treated in a similar fashion in all three

groups. Management of breakthrough pain consistedof a bolus of 8 mL of ropivacaine 0.1% followed by acontinuous infusion of ropivacaine 0.2% 8 mL/h andadditional doses of 6–8 mL of ropivacaine 0.1% whenrequired. A maximum of three top-ups over the first4 h of the study was allowed before alteration of theepidural analgesic regimen and removal of the casefrom the study. On the first postpartum day, globalmaternal satisfaction was assessed with a 10-cm VASby a blinded observer, 10 being maximal satisfaction.

Sensory levels were determined with changes tocold (ether) at 5, 10, 15, 20, 30, 60, 120, 180, and 240 minafter study drug injection. Motor block using a mod-ified Bromage scale (0 � no block, 1 � inability to raiseextended leg, 2 � inability to flex knee, and 3 �inability to flex ankle and foot) were also recorded atthe same intervals. With a Bromage score �2, theinfusion rate of ropivacaine was reduced until theBromage score was found to be �1. Sedation wasrecorded with a four-point score (0 � no sedation, 1 �slight sedation or patient responding to verbal stimu-lation, 2 � moderate sedation or patient responding totactile stimulation, and 3 � deep sedation or patientnot responding to tactile stimulation) as used by oth-ers (4,14).

Maternal monitoring included arterial blood pres-sure every 5 min during the first hour and then every15 min and continuous heart rate measures and axil-lary temperature once every hour. Cervical dilation atentry of study, duration of first and second stage oflabor, 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 drugadministration was continued until delivery.

Adverse effects, such as nausea, vomiting, itching,maternal bradycardia, or hypotension were reported.Hypotension was defined as systolic blood pressuremeasurement �100 mm Hg and/or �25% baselinedecrease and was treated with 5–10 mg of ephedrinewith additional doses when required.

Fetal heart rate was recorded continuously on acardiotocograph (Hewlett-Packard 80300A, HewlettPackard, Palo Alto, CA). Fetal heart rate tracings weremonitored by obstetricians blinded to group allocationand reviewed again postpartum for detection of fetalheart rate abnormalities (MM). Analysis comparedtracings obtained at least 30 min before epidural place-ment with those recorded during epidural analgesia.Fetal heart rate abnormalities such as late decelera-tions, bradycardia (defined as fetal heart rate�100 bpm lasting for 5 min or more), and decreasedfetal heart rate variability according to criteria used atour institution (at least two accelerations of 15 bpmlasting 15 s for 40 min) were noted. Fetal events weremanaged with standard measures such as oxygen, leftor right lateral uterine displacement, ephedrine when

ANESTH ANALG OBSTETRIC ANESTHESIA LANDAU ET AL. 7292002;95:728–34 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 ofdelivery, neonatal weight, and umbilical cord blood-gas were recorded. Apgar scores and clinical evalua-tion at 24 h after birth were performed in all neonatesby pediatricians blinded to group allocation.

Expecting that clonidine will prolong analgesia du-ration by approximately 60 min (15), thus decreasingby 20% the dose of ropivacaine administered over 4 h(40 mL to 32 mL of ropivacaine 0.2%), power testanalysis resulted in a calculated sample of 22 subjectsper 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. Thestatistical analysis was performed using analysis ofvariance for comparison between groups and Fisher’sexact test for categorical variables. A value of P � 0.05was considered significant.

ResultsSeventy-two women were enrolled in the study andsix cases were excluded (four unilateral blocks identi-fied within the first hour of the study and two dis-placed catheters requiring replacement of the catheterwithin the first 4 h). Groups were comparable withregard 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 atrend at 5 min (P � 0.07) becoming significant at10 min (Table 2). At 10 and 30 min, the number ofsubjects reporting a pain score �3 was significantlymore in Group 3 (Table 2). Duration of analgesia wassignificantly prolonged with the addition of clonidine(Table 2). The number of women requiring additionalboluses of ropivacaine was significantly greater inGroup 2 (Fig. 1). There was no difference in sensorylevel among groups throughout the study. Despite atrend for a higher satisfaction score in Group 3 on thefirst 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 �0.07).

During the first hour, there was no difference in theincidence of motor block among groups, with nowoman developing a significant motor block (i.e., Bro-mage score �2) (Fig. 2). However, with time andduring the 4 h of the study, the incidence of motorblock was significantly more frequent in Group 2 ver-sus Groups 1 and 3 (Fig. 2). The total ropivacaine dosewas also different among groups, with Group 2 re-quiring significantly more ropivacaine (Table 2).

The mean dose of ephedrine among women requiringephedrine 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

Group 1a Group 2b Group 3c

Maternal characteristicsAge (yr) 28 � 4 27 � 5 29 � 4Weight (kg) 72 � 9 74 � 13 72 � 13Height (cm) 164 � 6 163 � 6 162 � 7

Obstetrical characteristicsGestational age (wk) 38.9 � 1.0 39.0 � 1.2 39.6 � 1.3Oxytocin for induction (n) 4 3 3Oxytocin for augmentation (n) 2 3 2Cervical dilation at entry (cm) 2.6 � 0.4 2.4 � 0.2 2.5 � 0.4Labor duration (min)

First staged227 � 119 249 � 103 270 � 160

Second stage 110 � 41 105 � 43 119 � 37Mode of delivery

Spontaneous vaginal (n) 10 11 12Instrumental (n) 7 8 6Cesarean (n) 5 3 4

Neonatal characteristicsBirth weight (g) 3335 � 330 3550 � 350 3340 � 407Apgar � 7 at 5 min (n) 0 0 0

Unless indicated, data presented as mean � sd. No significant differences exist among groups.a Ropivacaine 0.1% 8mL with clonidine 75 �g.b Ropivacaine 0.2% 8mL with NaCl 0.9%.c Ropivacaine 0.2% 8mL with clonidine 75 �g.d Duration of first stage from epidural insertion

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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 betreated 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 of5 mg of ephedrine, with no woman requiring more than

Table 2. Analgesia Characteristics, Ropivacaine Dose, and Side Effects

Group 1a Group 2b Group 3c

Analgesia characteristicsVAS before study drug 9.1 � 1.2 8.7 � 1.3 8.6 � 1.0VAS at 5 min 4.4 � 2.7 5.4 � 2.3 3.5 � 3.0Subjects with VAS �3 at 5 min (n) 6 3 9VAS at 10 min 3.3 � 2.7 3.8 � 2.5 1.9 � 2.2*Subjects with VAS �3 at 10 min (n) 11 6 16*VAS at 30 min 1.4 � 2.2 2.0 � 2.6 0.4 � 0.9*Subjects with VAS �3 at 30 min (n) 19 17 22Analgesia duration (min) 132 � 48 91 � 44 154 � 42†

Ropivacaine doseDose over 4 h (mg)d 40.5 � 15 72.5 � 18 47.0 � 16†

Side effectsNausea (n) 1 2 1Vomiting (n) 1 1 0Sedation score � 0 (n) 18 18 17Sedation score � 1 (n) 4 3 4Sedation score � 2 (n) 0 1 1Sedation score � 3 (n) 0 0 0

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)a Ropivacaine 0.1% 8mL with clonidine 75�g.b Ropivacaine 0.2% 8mL with NaCl 0.9%.c Ropivacaine 0.2% 8mL with clonidine 75�g.d Data presented for 20 women in each group (two cases per group delivered before completion of the 4 h of the study).e Sedation score: 0 � no sedation; 1 � slight sedation; 2 � moderate sedation; and 3 � deep sedation.

Figure 1. Distribution of additional doses after the study drugduring the 4 h of the study. With the first additional dose (ropiva-caine 0.1% 8 mL), a continuous infusion of ropivacaine 0.2% wasstarted 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% confidenceinterval, 1.19–2.13; P � 0.01). Overall, women in Group 2 requiredsignificantly more additional doses than women in Groups 1 and 3(*P � 0.05, analysis of variance). Group 1, ropivacaine 0.1% 8 mLwith clonidine 75 �g; Group 2, ropivacaine 0.2% 8 mL with NaCl0.9%; 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 womendeveloping more intense motor block (Bromage score 2) arerepresented with hatched vertical bars (one woman in Group 1,six women in Group 2, and three women in Group 3). Because theropivacaine infusion rate was reduced in women developing anintense motor block, Bromage score 2 was never noted twice (ontwo different assessment times) in the same woman. Women inGroup 2 developed significantly more motor block than womenin 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.

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30 mg. Three women in each group required multipleephedrine doses; all women were treated within the firsthour of the study, with the exception of one woman inGroup 3 requiring 20 mg of ephedrine 120 min after thestudy dose (case h, Table 3).

There was no difference in the incidence of nau-sea, vomiting, or sedation (Table 2). There were nocases of maternal bradycardia, itching, or hyper-thermia (T �37.8°C) recorded at any time during thestudy.

Fetal heart rate abnormalities were diagnosed in10 different parturients and managed with standardmeasures (Table 3). No tocolytic treatment was re-quired. Fetal heart rate variability was normal in allcases. Episodes of fetal bradycardia directly relatedto maternal hypotension were observed in onewoman per group and required no other treatmentthan ephedrine. These events occurred 60 (case b),20 (case c), and 120 (case h) min after the studydrug, respectively (Table 3). In Group 1, one case offetal bradycardia was associated with a prolapsedcord and required an immediate cesarean delivery(case a). In Group 2, two cases of bradycardiashortly after study drug administration (cases c andd) 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 (casei). 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 neonatesborn to mothers receiving clonidine in which abnor-mal fetal heart rate tracings had been recorded.

Discussion

This is the first study demonstrating the additive an-algesic effect in the first stage of labor of an epiduralbolus 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 ropivacainedose-response studies for initiation of epidural anal-gesia were not available at the time of study design. Inaddition, because ropivacaine was studied withoutopioids, we decided not to administer the smaller dose(8 mg) without clonidine because we expected thisdose to be insufficient to provide adequate analgesia.This assumption was confirmed in a study showingthat the optimal concentration of ropivacaine as a soleanesthetic for the initiation of epidural analgesia is0.2% (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 todetect an intravascular or intrathecal catheter andshould 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-founding effect.

Clonidine was administered as a bolus of 75 �gbecause smaller doses (30 �g) have been shown not toimprove analgesia significantly (8), whereas largerdoses (150 �g) have resulted in maternal bradycardia(one case requiring atropine) (4), decreased fetal heartrate variability and late decelerations (4), and maternalsedation (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

Case

a b c d e f g h i j

Groupa 1 1 2 2 2 2 3 3 3 3Bradycardia (min)b 15 60 20 15 – – – 120 – –Late decelaration (min)c 110 60 – – 160 270 375 – 80 240Blood pressure (mmHg)d 110 90 84 128 110 110 105 96 100 120Ephedrine use – � � – – – – � – –Mode of delivery C/Sf C/S S S F F F S C/S C/SDelivery (min)e 120 110 240 180 250 270 375 355 85 240Apgar score (1 min/5 min) 9/10 8/10 9/10 9/10 7/9 9/10 2/10 9/10 9/9 9/10Umbilical arterial pH value 7.14 7.10 7.20 7.16 6.95 7.32 7.17 7.22 7.17 7.25Umbilical venous pH value 7.28 7.15 7.30 7.25 7.15 7.39 7.32 7.29 7.25 7.30

S � spontaneous vaginal; F � forceps; C/S � cesarean section delivery.a Study 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.b Time between study drug and bradycardia (fetal heart rate �100 bpm lasting �5 min).c Time between study drug and late deceleration.d Systolic blood pressure at time of fetal heart rate abnormality.e Time between study drug and delivery.f Emergency cesarean delivery because of cord prolapse.

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dose to add to bupivacaine for labor analgesia1 andprovided approximately two hours of satisfactory an-algesia when added to bupivacaine (5). Furthermore,we decided to limit the clonidine administration toone single bolus because fetal heart rate abnormalitieshave been associated with repeated doses of 75 �g ofclonidine (5).

Our findings are consistent with several studies ex-amining the effect of clonidine added to ropivacaine inperipheral blocks (17,18) as a spinal adjunct for ortho-pedic surgery (19) or by the caudal route for pediatricsurgery (20), which all showed prolongation ofanalgesia.

In our study, onset of analgesia was significantlyshorter among women receiving clonidine with thelarger dose of ropivacaine 0.2% (8 mL). A reducedonset of action with clonidine has not been reported inprevious studies examining the combination ofclonidine with bupivacaine (4,6,15). It is possible thatour definition of analgesia onset differs from that ofother authors. We defined good analgesia as a VAS �3and recorded VAS precisely at five and 10 minutes todetermine the number of cases reporting VAS scores�3 at these time intervals. Our data strongly suggestthat the addition of clonidine impacts favorably bothon the number of women with a VAS �3 and on theaverage VAS at 10 minutes. The exact mechanism bywhich the addition of clonidine might shorten theonset of analgesia produced by ropivacaine is notclear; the possibility of a positive interaction betweenthe intrinsic vasoconstricting effect of ropivacaine (21)and clonidine remains to be determined.

Duration of action was substantially increased inboth groups with clonidine. There was no significantadvantage of ropivacaine 0.2% 8 mL with clonidineover ropivacaine 0.1% 8 mL with clonidine in terms ofduration of analgesia. The addition of clonidine to0.2% ropivacaine prolonged by approximately onehour the analgesia time produced by 0.2% ropivacainealone. The hourly dose for the four first hours wassignificantly reduced by the addition of clonidine,with no difference in dose of ropivacaine between thetwo groups receiving clonidine. This is because of thefact that in Group 1, the smaller initial ropivacainedose was compensated with subsequent ropivacainedoses when required, and in Group 3, fewer addi-tional doses were required after a larger initial studybolus. Furthermore, the reduced dose of ropivacainerequired over the study period in both groups receiv-ing clonidine produced less motor block over time.

We report no episodes of maternal bradycardia inwomen 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 to60 minutes after doses of 120 �g of clonidine (15) and60 to 120 minutes after 150 �g of clonidine (14) or 75�g of clonidine with 50 �g of fentanyl (14). We did notobserve significant sedation in either group, probablybecause of the small dose of clonidine and the absenceof concurrent opioid administration.

In our study, 44 women (Groups 1 and 3) received75 �g of epidural clonidine. Episodes of fetal brady-cardia directly attributed to maternal hypotension oc-curred between 20 and 120 minutes after the injectionof the study drug. This finding is consistent with otherreports of decreased mean arterial blood pressure oc-curring 20 to 140 minutes after the clonidine adminis-tration (4). Although there was a tendency for morewomen who received clonidine to require ephedrine,this did not seem to impact fetal outcomes, as moni-tored by Apgar scores and umbilical cord blood-gasvalues. Our data show that despite some changes inmaternal hemodynamic status, which may occur up totwo hours after 75 �g of epidural clonidine, hypoten-sion can be managed efficiently with ephedrine, withno apparent adverse effect on obstetrical and fetaloutcome. 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 impacton neonatal well being.

In conclusion, our results demonstrate a dose-sparing effect of clonidine added to ropivacaine forepidural labor analgesia during the first stage of labor,resulting in a reduced motor block. However, becauseof the potential for maternal hypotension, we recom-mend that laboring women be closely monitored forseveral hours after receiving epidural clonidine.

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