oxcitoxin

Research www.AJOG.org

OBSTETRICS

Oxytocin discontinuation during active laborin women who undergo labor inductionLiany C. Diven, MD; Meredith L. Rochon, MD; Julia Gogle, MSN, RNC; Sherrine Eid, MPH;John C. Smulian, MD, MPH; Joanne N. Quiñones, MD, MSCE

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OBJECTIVE: The purpose of this study was to determine whether thereis an increase in the cesarean delivery rate in women who undergo in-duction when oxytocin is discontinued in the active phase of labor.

STUDY DESIGN: We conducted a prospective randomized controlledtrial of women who underwent induction of labor at term; they were as-signed randomly to either routine oxytocin use (routine) or oxytocin dis-continuation (DC) once in active labor. Analysis was by intention to treat.

RESULTS: Two hundred fifty-two patients were eligible for study analy-sis: 127 patients were assigned randomly to the routine group and 125
patients were assigned randomly to the DC group. Cesarean delivery
2012;207:471.e1-8.

tcmdrti

discontinuation of oSee related editorial, page 439

rate was similar between the groups (routine, 25.2% [n � 32] vs the DCgroup, 19.2% [n � 24]; P � .25). There was a higher chorioamnionitisate and slightly longer active phase in those women who were as-igned to the DC group. In adjusted analysis, the rate of chorioamnioni-is was not different by randomization group but was explained by theuration of membrane rupture and intrauterine pressure catheterlacement.

CONCLUSION: Discontinuation of oxytocin in active labor after labor in-duction does not increase the cesarean delivery rate significantly.

Key words: cesarean delivery, labor induction, oxytocin

Cite this article as: Diven LC, Rochon ML, Gogle J, et al. Oxytocin discontinuation during active labor in women who undergo labor induction. Am J Obstet Gynecol

Oxytocin is the most common agentused to induce and augment labor.1

Known benefits of oxytocin include theinitiation and/or improvement of contrac-tions to achieve labor, whereas risks in-clude uterine overactivity, water intoxica-tion, and, albeit rare, uterine rupture.2-4

Despite its widespread use, optimal proto-cols for oxytocin use as an induction agenthave not been identified.5

From the Division of Maternal-Fetal Medicine (DrsRochon, Smulian, and Quiñones), theDepartment of Obstetrics and Gynecology (DrDiven and Ms Gogle), and the Department ofCommunity Health and Health Studies (Ms Eid),Lehigh Valley Health Network, Allentown, PA.

Received June 3, 2012; revised Aug. 8, 2012;accepted Aug. 27, 2012.

The authors report no conflict of interest.

Presented at the 32nd annual meeting of theSociety for Maternal-Fetal Medicine, Dallas, TX,Feb. 6-11, 2012.

Reprints not available from the authors.

0002-9378/free© 2012 Mosby, Inc. All rights reserved.http://dx.doi.org/10.1016/j.ajog.2012.08.035

For Editors’ Commentary, seeContents

The relationship of oxytocin and itsreceptor is crucial in obtaining adequateuterine activity.6 The myometrium con-ains receptors that are specific to oxyto-in, which, when occupied, stimulateyometrial contraction and prostaglan-

in formation in the decidua.7 Oxytocineceptors increase with advancing gesta-ion, and uterine sensitivity to oxytocinncreases rapidly in spontaneous labor.8

A lower number of receptors have alsobeen noted in women who have beengiven larger doses or a longer infusion ofoxytocin compared with those who havebeen given shorter treatments or lowerdoses,9,10 which suggests receptor down-regulation in this environment. As such,prolonged oxytocin use and receptor de-sensitization may lead to poor uterinecontractility, atony,11 and potential la-bor dysfunction.

Various oxytocin regimens for the in-duction of labor have been described,12

although limited data are available re-garding which is superior. Particularlyunclear is whether oxytocin should becontinued once active labor is achieved.13

Although traditional thinking is that
xytocin, once la-
DECEMBER 2012 Americ

bor is achieved, may prolong labor lengthand/or increase the cesarean delivery rate,given what is known about prolonged oxy-tocin use, there actually may be benefit todiscontinuing oxytocin once active labor isachieved. Studies in populations with alower cesarean rate suggest that, once ac-tive labor is achieved, oxytocin may be dis-continued without altering labor progres-sion or the cesarean delivery rate.14,15 It isunclear whether oxytocin discontinuationwould lead to a higher rate of cesarean de-livery in a population such as ours. Thus,the objective of this study was to determinein our population whether there is anincrease in the cesarean delivery rate inwomen who undergo labor inductionwhen oxytocin is discontinued in the activephase of labor. We hypothesized that oxy-tocin discontinuation, once active labor isachieved, would not increase the risk of la-bor abnormalities or cesarean delivery.

MATERIALS AND METHODSThis was a prospective randomized con-trolled trial of women who underwentinduction of labor from February 2009to August 2011 at Lehigh Valley HealthNetwork. The primary outcome was therate of cesarean delivery among women
for whom oxytocin was either discontin-
an Journal of Obstetrics & Gynecology 471.e1

http://dx.doi.org/10.1016/j.ajog.2012.08.035

FMcowdy

Research Obstetrics www.AJOG.org

ued or continued once in active labor.Institutional review board approval wasobtained, and written informed consentwas obtained from participants. The trialwas registered at ClinicalTrials.gov, IDNCT00957593.

Our inclusion criterion was a single-ton gestation of �37 weeks that wasscheduled for labor induction, regardlessof indication for induction, Bishopscore, or parity. Patients were recruitedat the time of admission to Labor andDelivery. Exclusion criteria were multi-ple gestations, previous cesarean deliv-ery, active labor, and documented fetalanomalies. Method of induction was atthe provider’s discretion. Cervical ripen-ing before the initiation of oxytocin wasallowed in the study protocol. In our in-

FIGUREFlow diagram

Patients approached

n = 493

Declined n = 190

Accn =

Not eligible

n =13 Rand

n =

ROUTINE Intention to treat analysis

n = 127

All women received oxytocin

13 cesareans before active labor114 achieved active labor

DC, oxytocin discontinuation group; ROUTINE, routine oxytocin us

Diven. Discontinuation of oxytocin in active labor. Am J Obs

stitution, women whose induction re-

471.e2 American Journal of Obstetrics & Gynecolo

quires cervical ripening undergo ripeningwith either misoprostol or intracervicalFoley bulb placement with or without oxy-tocin. Women with a favorable Bishopscore are induced with oxytocin alone.

At enrollment, patients were assignedrandomly to either routine treatmentor discontinuation (DC). The routinegroup followed a standard institutionaloxytocin protocol in which oxytocin istitrated to target 3-5 contractions in a 10-minute period. Usual practice is to con-tinue oxytocin until delivery, unlessthere is an indication to stop the infu-sion. The DC group followed an oxyto-cin protocol by which oxytocin was dis-continued once the patient was deemedto be in active labor by the obstetrician.Active labor was defined by the clinician’s

ted 3

ized 2

DC Intention to treat analysis

n = 125

Not enrolled

n = 38

31 oxytocin not discontinued 58 had oxytocin restarted 25 remained discontinued

9 cesareans before active labor2 never received oxytocin

up.

ynecol 2012.

assessment of regular uterine contrac-

gy DECEMBER 2012

tions with a cervical examination thatconfirmed dilation of �4 cm.16,17

The study’s primary outcome was thedifference in the rate of cesarean deliverybetween the groups. Secondary out-comes included the length of latent andactive phases of labor and maternal andneonatal outcomes including chorioam-nionitis. Chorioamnionitis was diag-nosed by clinical criteria: maternaltemperature of �100.4°F and maternaltachycardia, fetal tachycardia, or both. Thedecision to perform a cesarean deliverywas according to standard obstetric indica-tions and ultimately was decided by thetreating physician, regardless of treatmentassignment. The treating physician wasable at any time to restart the oxytocin in-fusion in patients who assigned to the DCgroup if they believed it was indicatedclinically.

Using a power of 80% and an alphalevel of .05, we estimated that 304women (152 in each group) would beneeded to show an increase in the cesar-ean delivery rate from a baseline rate of25% to 40% for women who had oxyto-cin discontinuation. Four-block ran-domization was used that was stratifiedfor parity. For statistical analysis, weused Stata software (version 9.0 SE;StataCorp, College Station, TX). Com-parisons were made with the Student ttest or the Mann Whitney U test for con-tinuous variables and �2 analysis or

isher exact test for categoric variables.ultinomial logistic regression models,

ontrolled for confounding, were devel-ped; adjusted relative risk ratios (RRR)ith 95% confidence interval (CI) wereerived from the models. Statistical anal-sis was by intention to treat.

RESULTSThree hundred three patients agreed toenroll in the study (Figure); 38 womendid not complete the enrollment pro-cess, and 13 pregnancies were screen fail-ures, allowing 252 patients for enroll-ment and participation in the study.Enrollment was stopped after 30 monthsprimarily because of enrollment chal-lenges.Onehundredtwenty-sevenwomen(50.4%) were randomly assigned to the

ep 30

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routine group, and 125 women (49.6%)

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www.AJOG.org Obstetrics Research

were randomly assigned to the DC grouponce active labor was achieved. Demo-graphic and antepartum characteristicswere similar between the routine groupand DC groups (Table 1). There was nodifference in indication for induction ormethod of induction between groups(Table 2). Most women were induced ini-tially with oxytocin (77.2% in the routinegroup vs 72.0% in the DC group; P � .26).

he use of Foley bulb ripening was alsoimilar between the groups (P � .10;able 2).The primary outcome, cesarean deliv-

ry, was similar between groups (25.2%n the routine group vs 19.2% in the DCroup (RR, 0.76; 95% CI, 0.48 –1.21; P �25; Table 3). The difference in the rate ofesarean delivery for an arrest disorderarrest of the active phase or arrest of de-cent) was not significant by randomiza-ion (59.4% in the routine group vs0.8% in the DC group; RR, 1.19; 95%I, 0.81–1.75; P � .38; Table 3). Al-

though intrapartum complications, as awhole, were similar by randomization,the rate of chorioamnionitis was higheramong those who were assigned ran-domly to the DC group (5.5% in the rou-tine group vs 12.8% in the DC group;P � .05; Table 4). Postpartum complica-ions were similar among randomizedroups (Table 4).The median active phase of labor was

onger among women who were as-igned randomly to the DC group by 1our (3.0 hours in the routine group vs.9 hours in the DC group; P � .01; Table). Duration of ruptured membranesas also higher in women assigned ran-omly to the DC group (median, 6.1ours in the routine group vs 8.0 hours

n the DC group; P � .01; Table 3). La-ent phase and second stage of labor du-ation were similar (Table 3), as wereeonatal outcomes (Table 5).Thirty-one participants (24.8%) in theC group had the oxytocin infusion

ontinued once active labor was achieved,espite randomization to the DC groupFigure). Data regarding rationale for thisccurrence were not always available. Dis-ussion with participating nurses and pro-iders identified reasons for this likely to berovider preference to continue the infu-
ion, provider being unaware that the pa- (
ient was enrolled in the DC group, or ahort active phase. Oxytocin was restartedn an additional 58 patients from the DCroup (46.4%), which was allowed by thetudy protocol. Restarting oxytocin was

ostly due to a lack of cervical change

TABLE 1Demographic characteristics of thepopulation by randomization group

Characteristic

Maternal age, ya

...................................................................................................................

Nulliparity, n (%)...................................................................................................................

Marital status, n (%)..........................................................................................................

Married..........................................................................................................

Divorced/widow..........................................................................................................

Never married...................................................................................................................

Race/ethnicity, n (%)..........................................................................................................

White..........................................................................................................

African American..........................................................................................................

Latina..........................................................................................................

Other...................................................................................................................

Insurance, n (%)..........................................................................................................

Government..........................................................................................................

Private..........................................................................................................

Self-pay...................................................................................................................

Private service vs resident service, n (%)...................................................................................................................

Tobacco use, n (%)...................................................................................................................

Alcohol use, n (%)...................................................................................................................

Drug use, n (%)...................................................................................................................

Body mass index (kg/m2)a...................................................................................................................

Obesity: body mass index �30, n (%)...................................................................................................................

Pregestational diabetes mellitus, n (%)...................................................................................................................

Gestational diabetes mellitus, n (%)...................................................................................................................

Essential hypertension, n (%)...................................................................................................................

Gestational hypertension or preeclampsia, n (...................................................................................................................

Any comorbidity, n (%)...................................................................................................................

History of preterm birth, n (%)...................................................................................................................

Gestational age at first prenatal visit, wka

...................................................................................................................

Group B streptococcus, n (%)...................................................................................................................

Data were analyzed with the Student t test, the �2 test, and tha Data are expressed as mean � SD.

Diven. Discontinuation of oxytocin in active labor. Am J O

44.8%) or a decrease in contraction fre- g


uency (39.7%). Among the 58 patientshose infusion was restarted, 51 womenelivered vaginally (87.9%). Of the re-aining 36 patients from the DC group, 9omen never achieved active labor; 2omen achieved active labor after under-

tient

Group

Routine(n � 127)

Oxytocindiscontinuation(n � 125)

27.1 � 5.6 27.7 � 5.7..................................................................................................................

63 (49.6) 64 (51.2)..................................................................................................................

..................................................................................................................

56 (44.1) 66 (52.8)..................................................................................................................

1 (0.8) 1 (0.8)..................................................................................................................

70 (55.1) 58 (46.4)..................................................................................................................

..................................................................................................................

86 (67.7) 82 (65.6)..................................................................................................................

8 (6.3) 7 (5.6)..................................................................................................................

27 (21.3) 30 (24.0)..................................................................................................................

6 (4.7) 6 (4.8)..................................................................................................................

..................................................................................................................

52 (41.0) 45 (36.0)..................................................................................................................

60 (47.2) 61 (48.8)..................................................................................................................

15 (11.8) 19 (15.2)..................................................................................................................

70 (55.1) 67 (53.6)..................................................................................................................

17 (13.4) 18 (14.4)..................................................................................................................

0 1 (0.8)..................................................................................................................

0 2 (1.6)..................................................................................................................

31.7 � 7.3 31.0 � 7.4..................................................................................................................

75 (59.1) 64 (51.2)..................................................................................................................

1 (0.8) 1 (0.8)..................................................................................................................

14 (11.0) 17 (13.6)..................................................................................................................

5 (3.9) 6 (4.8)..................................................................................................................

46 (36.2) 41 (32.8)..................................................................................................................

89 (70.6) 82 (65.6)..................................................................................................................

3 (2.4) 8 (6.4)..................................................................................................................

12.5 � 6.7 12.2 � 6.1..................................................................................................................

34 (27.4) 24 (19.4)..................................................................................................................

her exact test, as appropriate.

t Gynecol 2012.

pa

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.........

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.........

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.........

.........

.........

.........

.........

.........

.........

.........

%).........

.........

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oing cervical ripening alone, and 25


maenIts(lgpt1

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women never had the oxytocin infusionrestarted, of whom 84% (n�21) deliveredvaginally.

Because of the number of patients inthe DC group who had oxytocin infusioncontinued, analyses were performed byactual treatment received (Table 6). Ce-sarean delivery rates were similar by ac-tual treatment received (22.8% in thosetreated as routine vs 21.3% in thosetreated as DC; P � .78); the medianactive phase of labor was prolonged inthe discontinuation group when ana-lyzed by actual treatment received (3.0

TABLE 2Admission characteristics of the papopulation by randomization group

Characteristic

Gestational age at admission, wka

...................................................................................................................

Indication for induction of labor, n (%)..........................................................................................................

Prolonged pregnancy..........................................................................................................

Premature rupture of membranes..........................................................................................................

Nonreassuring antenatal testing..........................................................................................................

Oligohydramnios..........................................................................................................

Gestational hypertension or preeclampsia..........................................................................................................

Intrauterine growth restriction..........................................................................................................

Diabetes mellitus, any..........................................................................................................

Elective..........................................................................................................

Otherb

...................................................................................................................

First method of induction, n (%)..........................................................................................................

Misoprostol..........................................................................................................

Oxytocin..........................................................................................................

Foley bulb and oxytocin...................................................................................................................

Cervical ripening, n (%)...................................................................................................................

Bishop scorec

...................................................................................................................

Bishop score �4, n (%)...................................................................................................................

Membrane status, n (%)..........................................................................................................

Amniotomy..........................................................................................................

Spontaneous rupture of membranes..........................................................................................................

Premature rupture of membranes...................................................................................................................

Data were analyzed with the Student t test, the �2 test, and tha Data are expressed as mean � SD; b Other indications in

essential hypertension, renal disease, history of abruptio plabolism; c Data are expressed as median (range).


hours when oxytocin was continued vs a


4.2 hours in the group where oxytocinwas discontinued; P � .004).

Because chorioamnionitis was diag-nosed more commonly in the DC group,secondary analyses were performed. Themedian latent phase, active phase, sec-ond stage of labor, and duration of rup-tured membranes were longer in womenwho were diagnosed with chorioamnio-nitis (Table 7). Intrauterine pressurecatheter (IUPC) use was also higher inwomen with chorioamnionitis (69.6% vs29.7% in those without chorioamnioni-tis; P � .001). Chorioamnionitis was di-

nt

Group

P valueRoutine(n � 127)


39.8 � 1.3 40.0 � 1.0 .18..................................................................................................................

.52..................................................................................................................

32 (25.2) 36 (28.8)..................................................................................................................

6 (4.7) 9 (7.2)..................................................................................................................

14 (11.0) 5 (4.0)..................................................................................................................

14 (11.0) 12 (9.6)..................................................................................................................

21 (16.5) 19 (15.2)..................................................................................................................

1 (0.8) 1 (0.8)..................................................................................................................

10 (7.9) 13 (10.4)..................................................................................................................

19 (15.0) 15 (12.0)..................................................................................................................

10 (7.9) 15 (12.0)..................................................................................................................

.26..................................................................................................................

22 (17.3) 21 (16.8)..................................................................................................................

98 (77.2) 90 (72.0)..................................................................................................................

7 (5.5) 14 (11.2)..................................................................................................................

29 (22.8) 35 (28.0) .35..................................................................................................................

5 (0–10) 5 (0–10) .84..................................................................................................................

81 (63.8) 80 (64.0) .97..................................................................................................................

.84..................................................................................................................

103 (81.1) 101 (80.8)..................................................................................................................

15 (11.8%) 13 (10.4%)..................................................................................................................

9 (7.1%) 11 (8.8%)..................................................................................................................

her exact test, as appropriate.

d conditions such as intrahepatic cholestasis of pregnancy,e, history of fetal death, history of deep venous thromboem-

t Gynecol 2012.

gnosed in 4 women before IUPC place-

gy DECEMBER 2012

ent, in 11 women after IUPC placement,nd in 1 woman retrospectively after deliv-ry because of persistently elevated mater-al temperature (with 15.7 hours betweenUPC placement and delivery). Medianime from IUPC placement to the diagno-is of chorioamnionitis was 5.4 hoursrange, 0.8 –15.7 hours). The medianength of the active phase of labor was lon-er in women who underwent IUPClacement (3.9 hours; range, 0.9–15.5) vshose who did not (3.2 hours; range, 0.1–5.0; P � .02).Univariate analyses were performed to

valuate risk factors for chorioamnioni-is besides randomization (Table 8).oth the number of cervical examina-

ions and active labor length were asso-iated with chorioamnionitis. Logisticegression models were constructed tovaluate the relationship between ran-omization and chorioamnionitis, con-rolling for confounders that were iden-ified in univariate analysis (P � .20;able 8). With the use of stepwise regres-

ion, the active phase of labor, not theumber of cervical examinations, wasssociated significantly with chorioam-ionitis (RRR, 1.26; 95% CI, 1.08 –1.47;� .004]). In the final model, discontin-ation no longer was associated signifi-antly with chorioamnionitis (RRR, 0.90;5% CI, 0.23–3.44; P � .87); however,

IUPC placement and duration of rupturedmembranes remained significantly associ-ated with chorioamnionitis (RRR, 4.39;95% CI, 1.17–16.4; P � .03 and RRR, 1.19;5% CI, 1.08–1.31; P � .001, respectively)ndependent of randomization. There was

trend towards significance between ac-ive labor length and chorioamnionitisRRR, 1.16; 95% CI, 0.99–1.36; P � .08).esults were the same when they were an-lyzed by actual treatment received (dataot shown).

COMMENTOur data suggest that, once labor is activein women being induced, oxytocin maybe discontinued if regular contractionscontinue to generate cervical change,without increasing the cesarean deliveryrate. Restarting oxytocin for arrest of di-lation and/or decrease in contractions

tie

.........

.........

.........

.........

.........

.........

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.........

.........

.........

.........

.........

.........

.........

.........

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cludecenta

does not appear to be associated with an

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increased risk of cesarean delivery forarrest disorders. However, oxytocindiscontinuation can lead to labor pro-longation and a higher rate of chorioam-nionitis; the latter is related to IUPC useand duration of membrane rupture. Ourdata suggest that, if oxytocin is discon-tinued, such practice should take placeonly after careful assessment of the laborcurve and contraction frequency, withIUPC placement only when strictly indi-cated because of the potential forinfection.

An Israeli study randomly assigned104 women to either oxytocin infusionuntil 5 cm dilation with maintenancethereafter or oxytocin discontinuationonce the cervix was 5 cm dilated.14

Length of the active phase was similar be-tween groups, as was the mode of deliv-ery, with a low cesarean rate among bothgroups (11.5% in continuation and 5.8%in discontinuation). A Turkish studyalso evaluated oxytocin discontinuationin active labor and found a longer activephase and second stage in those women

hose oxytocin was discontinued, al-hough the difference was not statisticallyignificant.15 Cesarean delivery rates were

also similar between groups. A Frenchequivalence study found a longer activephase of labor but a lower cesarean deliveryrate when oxytocin was discontinued.13

Although the above populations and theUS populations differ by rate of cesareandelivery, the aforementioned results areconsistentwithourfindings, even inapop-ulation with a higher baseline cesarean de-livery rate.

Univariate analysis suggested that therate of chorioamnionitis was higher inwomen who had a longer active phase oflabor; in adjusted analysis, the durationof membrane rupture and IUPC place-ment, not oxytocin discontinuation,were associated independently with anincreased risk of chorioamnionitis. Thisis consistent with previously publisheddata on risk factors for chorioamnioni-tis, in which the duration of rupturedmembranes and the placement of intra-uterine monitoring were identified as in-dependent risk factors for intraamnioticinfection.18 Other variables that were as-ociated with infection included the
umber of vaginal examinations and the q
uration of total labor,18 the latter a po-ential risk factor in our study. Althoughhe presence of intraamniotic infection

ay lead to abnormalities in the laborurve, which then may lead to increasedUPC use, in our study only 25% of pa-ients were diagnosed with chorioam-ionitis before IUPC placement, whichuggests that IUPC placement was therimary risk factor for chorioamnionitis.he utility of the routine use of IUPCs toonitor contractions has been ques-

ioned previously,19 and a recent studyound that the routine placement of in-ernal monitoring during induced orugmented labor does not decreasehe rates of operative deliveries ordverse neonatal outcomes.20 Althoughur study was not designed specifically toddress this, our data suggest that IUPClacement should be performed only af-er careful evaluation of the labor curvend when absolutely necessary (inabilityo externally monitor contraction fre-

TABLE 3Primary outcome and length of lab

Characteristic

G

R(n

Cesarean delivery, n (%) 32...................................................................................................................

Indications for cesarean delivery, n (%)..........................................................................................................

Nonreassuring fetal heart tracing 8..........................................................................................................

Arrest of the active phase 12..........................................................................................................

Arrest of descent 7..........................................................................................................

Failed induction of labor 2..........................................................................................................

Malpresentation 2..........................................................................................................

Other 1...................................................................................................................

Latent phase of labor, hra,b n7

...................................................................................................................

Active phase of labor, hra,b n3

...................................................................................................................

Second stage of labor, hra,b n0

...................................................................................................................

Ruptured membranes, hra n6

...................................................................................................................

Data were analyzed with the Mann Whitney U test, the �2 testa Data are expressed as median (range); b The lengths of the fi

who completed each phase or stage.


uency and/or strength or titrate oxyto-


in) because of the potential for infec-ion. Our data suggest that patients with

longer active phase had more IUPCslaced, which then may have increasedhe risk of chorioamnionitis. In ourtudy, labor length was longer, and ce-arean delivery was more common inomen who were diagnosed with cho-

ioamnionitis, which confirms previousbservations that have associated cho-ioamnionitis with labor prolongation.21

Strengths of our study include its pro-spective randomized nature, its rela-tively large sample size, and the ability ofobstetricians to alter labor managementas they believed clinical circumstanceswarranted, such as restarting oxytocinwhen indicated. Allowing such decisionsby the obstetrician as part of the studyprotocol makes our study results gener-alizable to “real life obstetrics” where cli-nicians make decisions that are based onthe overall clinical picture. We also be-lieved it would be unethical to omit this

by randomization group

P valuene127)


5.2) 24 (19.2) .25..................................................................................................................

.74..................................................................................................................

5.0) 7 (29.2)..................................................................................................................

7.5) 11 (45.8)..................................................................................................................

1.9) 6 (25.0)..................................................................................................................

.3) 0

..................................................................................................................

.3) 0

..................................................................................................................

.1) 0

..................................................................................................................

14(1.3–54.6)

n � 11710.4 (0.3–23.7)

.05

..................................................................................................................

02(0.1–15.3)

n � 1073.9 (0.1–15.5)

.01

..................................................................................................................

5(0–6.7)

n � 1010.5 (0–6.5)

.97

..................................................................................................................

27(0.1–32.7)

n � 1258.0 (0–37.4)

.01

..................................................................................................................

the Fisher exact test, as appropriate.

nd second stages of labor were calculated for those patients

t Gynecol 2012.

or

roup

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Diven. Discontinuation of oxytocin in active labor. Am J Obstet Gynecol 2012.

Diven. Discontinuation of oxytocin in active labor. Am J Obstet Gynecol 2012.


471.e6 American Journal of Obstetrics & Gynecology DECEMBER 2012

In 31 patients who were assigned ran-domly to discontinuation, the oxytocininfusion was continued, despite the pa-tient’s enrollment into discontinuation.An inability to account why this oc-curred in all cases is a limitation that mayhave introduced bias, if such patientswere perceived to be at a higher risk ofabnormal labor progression. We ac-knowledge this limitation because only94 patients remained in the DC groupwhen we evaluated the actual treatmentreceived. Although when evaluated bothby intent to treat and by the actual treat-ment received, the cesarean deliveryrates were not different between the 2groups, we do acknowledge that oursample size was limited by the continua-tion of oxytocin in 31 patients who wereassigned originally to the DC group.

Clinicians were asked to documentwhen labor was deemed to be active inwomen who were assigned randomly todiscontinuation based on the clinical ex-amination, contraction regularity, andpatient’s perception of pain and labortransition. We would not expect the na-ture of the study to cause clinicians toeither overdiagnose or underdiagnoselabor as being active, but the relativelysubjective nature of the diagnosis inwomen whose labor is induced is a po-tential limitation of our study. The rangeof cervical dilation in centimeters oncein active labor was higher for thosewomen in the DC group, likely beca-use clinicians ensured that labor was in-deed active by the examination, contrac-tion regularity, and symptoms before de-ciding to stop the oxytocin infusion. Wethus do not believe that labor that wasinduced with a Foley bulb would havebeen diagnosed as active labor with thecervical examination alone. However,we do acknowledge that our study defi-nition can be somewhat subjective whenthe patient is dilated (but not effaced)because of a Foley bulb. Another poten-tial limitation is our original definitionof active labor, because the active phaseof labor in women who undergo induc-tion of labor may actually be reached at 6cm.22 Premature diagnosis of active la-bor by our definition therefore poten-tially resulted in inadequate induction

TABLE 4Labor and delivery characteristics among the patientpopulation by randomization group

Characteristic

Group

P valueRoutine(n � 127)


Oxytocin dose in active labor, mU/mina 9.8 � 5.4 10.8 � 6.2 .23..............................................................................................................................................................................................................................................

Maximum oxytocin dose, mU/mina 13.0 � 6.8 13.1 � 6.6 .87..............................................................................................................................................................................................................................................

Cervical dilation once diagnosed in active labor, cmb 5 (3–7) 5 (3–9.5) � .001..............................................................................................................................................................................................................................................

Use of intrauterine pressure catheter, n (%) 42 (33.1) 42 (33.6) .93..............................................................................................................................................................................................................................................

Cervical examinations, nb 7 (1–17) 7 (2–13) .03..............................................................................................................................................................................................................................................

Epidural anesthesia, n (%) 122 (96.1) 118 (94.4) .54..............................................................................................................................................................................................................................................

Intrapartum complications, n (%) .24.....................................................................................................................................................................................................................................

Preeclampsia 5 (3.9) 3 (2.4).....................................................................................................................................................................................................................................

Chorioamnionitis 7 (5.5) 16 (12.8).....................................................................................................................................................................................................................................

Abruptio placentae 1 (0.8) 1 (0.8).....................................................................................................................................................................................................................................

Other 12 (9.5) 8 (6.4)..............................................................................................................................................................................................................................................

Postpartum complications, n (%).....................................................................................................................................................................................................................................

Postpartum hemorrhage 8 (6.3) 8 (6.4).....................................................................................................................................................................................................................................

Preeclampsia diagnosed after delivery 1 (0.8) 0.....................................................................................................................................................................................................................................

Endometritis 0 1 (0.8).....................................................................................................................................................................................................................................

Acute blood loss anemia 10 (7.9) 17 (13.6).....................................................................................................................................................................................................................................

Other 2 (1.6) 3 (2.4) .48..............................................................................................................................................................................................................................................

Data were analyzed with the Student t test, the Mann Whitney U test, the �2 test, and the Fisher exact test, as appropriate.a Data are expressed as mean � SD; b Data are expressed as median (range).

TABLE 5Neonatal outcomes by randomization group

Characteristic

Group

P valueRoutine (n�127)


Male sex, n (%) 70 (55.1) 66 (52.8) .71..............................................................................................................................................................................................................................................

Apgar score.....................................................................................................................................................................................................................................

At 1 mina 8 (1–9) 8 (1–9) .27.....................................................................................................................................................................................................................................

At 5 mina 9 (6–10) 9 (8–10) .27..............................................................................................................................................................................................................................................

Neonatal weight, ga 3475 (2345–4495) 3475 (2715–4650) .55..............................................................................................................................................................................................................................................

Arterial cord pHa 7.26 (6.94–7.64) 7.27 (7.08–7.68) .21..............................................................................................................................................................................................................................................

Neonatal resuscitation, n (%) 9 (7.1) 7 (5.6) .63..............................................................................................................................................................................................................................................

Admission to neonatal intensivecare unit, n (%)

10 (7.95) 9 (7.25) .84

..............................................................................................................................................................................................................................................

Neonatal antibiotic use, n (%) 9 (7.1) 16 (12.8) .13..............................................................................................................................................................................................................................................

Length of stay, da 3 (2–7) 3 (2–8) .79..............................................................................................................................................................................................................................................

Data were analyzed with the Mann Whitney U test, the �2 test, and the Fisher exact test, as appropriate.a Data expressed in median (range).

for patients in the DC group, which

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would presumably increase the cesar-ean delivery rate in this group. Becausethere was no difference in the cesareandelivery rate between the groups, we donot believe that our original definitionsignificantly impacted our results. Theblinding of clinicians to the studygroups would have been difficult toachieve given the nature of the studywith management of the oxytocin in-fusion (discontinuation, continuation,or restarting) requiring knowledge ofthe intervention by both nurses andclinicians.

Our sample size calculation was basedon finding a 40% cesarean delivery ratein women whose oxytocin was discon-tinued in active labor. We chose 40% asa significantly increased rate based onthe investigators’ consensus because thisrate would represent a considerable in-crease from the baseline population rate.Enrollment was stopped after 30 monthsprimarily because of growing cliniciananxiety about potentially prolonging thelength of labor inductions in a very busylabor unit with difficult-to-navigate-throughput issues. Using the cesarean de-livery rates that were produced by thisanalysis, we estimate that �1500 deliverieswould be needed to show that the observedrates are significantly different. We ac-knowledge that our study was underpow-ered for our primary outcome because en-rollment was stopped after 30 months,although our results likely would not bedifferent if we had enrolled an additional52 patients. To have found an increase inthe cesarean delivery rate from 25% to ei-ther 35% or 30% would have required theenrollment of either 329 or 1251 patients,respectively, per group.

Oxytocin is one of the most commonmedications used in obstetrics; despiteits widespread use, optimal protocols forthe use of oxytocin as an induction agenthave not been identified.5 Identification

f optimal clinical protocols and their as-ociated risks is important in the treat-

ent of patients who undergo labornduction. Our study attempts to in-estigate 1 aspect of oxytocin usage:hether to continue or discontinue oxy-

ocin once active labor has been achievedn women undergoing induction. Our
tudy suggests that discontinuation in
he active phase of labor can be consid-red in women who undergo labor in-uction without increasing the risk of ce-arean delivery. However, the finding ofhigher rate of chorioamnionitis must

TABLE 6Labor and neonatal outcomes by a

Characteristic

Gr

Ro(n


Oxytocin dose once active, mU/mina 10...................................................................................................................

Maximum dose of oxytocin, mU/mina 13...................................................................................................................

Length of latent phase of labor, hrb,c n �8

...................................................................................................................

Length of active phase of labor, hrb,c n �3

...................................................................................................................

Length of second stage of labor, hrb,c n �0

...................................................................................................................

Chorioamnionitis, n (%) 9...................................................................................................................

Intrauterine pressure catheter, n (%) 52...................................................................................................................

Admission to neonatal intensive careunit, n (%)

10

...................................................................................................................

Neonatal antibiotic use, n (%) 11...................................................................................................................

Length of stay, db 3...................................................................................................................

Data were analyzed with the Student t test, the Mann Whitneya Data are expressed as mean � SD; b Data expressed as me

were calculated for those patients who completed each phas


TABLE 7Labor characteristics in women wi

CharacteristicsNo(n �

Length of latent phase, hra 8....................................................................................................................

Length of active phase, hra 3....................................................................................................................

Length second stage, hra 0....................................................................................................................

Length of ruptured membranes, hra 6....................................................................................................................

Intrauterine pressure catheter use, n (%) 68...................................................................................................................


Admission to neonatal intensive careunit, n (%)

11

...................................................................................................................

Neonatal antibiotic use, n (%) 3...................................................................................................................

Length of stay, da 3...................................................................................................................

Data were analyzed with the Mann Whitney U test and the �2

a Data are expressed as median (range).

Diven. Discontinuation of oxytocin in active labor. Am J Obste


e taken into consideration when the de-ision is made to discontinue oxytocin inhe active phase for women who are be-ng induced, with careful assessment ofhe labor progress before proceeding

al treatment received

P valuee

158)


.8) 20 (21.3) .78..................................................................................................................

5.8 10.5 � 5.9 .67..................................................................................................................

7.1 12.4 � 6.0 .27..................................................................................................................

440.3–54.6)

n � 879.2 (2.3–23.7)

.76

..................................................................................................................

300.1–15.3)

n � 794.2 (0.1–15.5)

.004

..................................................................................................................

220–6.7)

n � 740.4 (0–4.7)

.47

..................................................................................................................

7) 14 (14.9) .01..................................................................................................................

.9) 32 (34.0) .85..................................................................................................................

3) 9 (9.6) .35

..................................................................................................................

0) 14 (14.9) .04..................................................................................................................

7) 3 (2–8) .51..................................................................................................................

st, and the �2 test, as appropriate.

(range); c The lengths of the first and second stages of laborstage.

t Gynecol 2012.

and without chorioamnionitis

rioamnionitis29)

Chorioamnionitis(n � 23) P value

.3–54.6) 11.9 (2.5–23.7) .004..................................................................................................................

.1–15.2) 7.8 (2.2–15.5) � .001..................................................................................................................

–6.7) 1.2 (0.1–3.6) .02..................................................................................................................

–32.8) 17.7 (7.3–37.4) � .0001..................................................................................................................

.7) 16 (69.6) � .001..................................................................................................................

.5) 9 (39.1) .04..................................................................................................................

) 8 (34.8) � .001

..................................................................................................................

) 22 (95.7) � .001..................................................................................................................

7) 3 (3–8) .004..................................................................................................................

as appropriate.

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with IUPC placement. Given the impor-tance of this clinical issue, future studiesshould continue to focus on the identifi-cation of optimal clinical protocols foroxytocin use. f

REFERENCES1. Zeeman GG, Khan-Dawood FS, DawoodMY. Oxytocin and its receptor in pregnancy andparturition: current concepts and clinical impli-cations. Obstet Gynecol 1997;89:873-81.2. Simpson KR, James DC. Effects of oxytocin-induced uterine hyperstimulation during laboron fetal oxygen status and fetal heart rate pat-terns. Am J Obstet Gynecol 2008;199:34.e1-5.3. Whalley PJ, Pritchard JA. Oxytocin and waterintoxication. JAMA 1963;186:601-3.4. Walsh CA, Baxi LV. Rupture of the primi-gravid uterus: a review of the literature. Obstet

TABLE 8Unadjusted analyses of potential p

Potential predictor

Oxytocin discontinuation group...................................................................................................................

Length latent phase...................................................................................................................

Length active phase...................................................................................................................

Duration of membrane rupture...................................................................................................................

Cervical examinations...................................................................................................................

Nulliparity...................................................................................................................

Bishop score �4...................................................................................................................

Body mass index �30 kg/m2

...................................................................................................................

Intrauterine pressure catheter use...................................................................................................................

Any comorbidity...................................................................................................................

Private obstetrician vs resident...................................................................................................................

CI, confidence interval.


Gynecol Surv 2007;62:327-34.


5. Mozurkewich EL, Chilimigras JL, BermanDR, et al. Methods of induction of labour: a sys-tematic review. BMC Pregnancy Childbirth2011;11:84.6. Kimura T, Takemura M, Nomura S, et al. Ex-pression of oxytocin receptor in human preg-nancy myometrium. Endocrinology 1996;137:780-5.7. Blanks AM, Thornton S. The role of oxytocinin parturition. BJOG 2003;110(suppl 20):46-51.8. Caldeyro-Barcia R, Sereno JA. The responseof human uterus to oxytocin throughout preg-nancy. In: Caldeyro-Barcia R, Heller H, eds.Oxytocin. London: Pergamon Press; 1959:177-200.9. Phaneuf S, Asboth G, Carrasco, MP, et al.Desensitization of oxytocin receptors in humanmyometrium. Hum Reprod Update 1998;4:625-33.10. Phaneuf S, Rodriguez Linares B, Tamby Raja

ictors of chorioamnionitis

horioamnionitis

elative risk (95% CI) P value

.32 (0.99–5.45) .04..................................................................................................................

.07 (1.01–1.14) .03..................................................................................................................

.36 (1.19–1.55) � .001..................................................................................................................

.20 (1.13–1.28) � .001..................................................................................................................

.45 (1.22–1.73) � .001..................................................................................................................

.56 (2.00–21.5) .0002..................................................................................................................

.36 (0.16–0.81) .01..................................................................................................................

.75 (0.34–1.62) .46..................................................................................................................

.57 (1.96–10.7) .0001..................................................................................................................

.61 (0.28–1.32) .21..................................................................................................................

.45 (0.20–1.02) .05..................................................................................................................

t Gynecol 2012.

RL, MacKenzie IZ, Lopez Bernal A. Loss of myo-

gy DECEMBER 2012

metrial oxytocin receptors during oxytocin-induced and oxytocin-augmented labour. JReprod Fertil 2000;120:91-7.11. Combs CA, Murphy EL, Laros RK Jr. Fac-tors associated with postpartum hemorrhagewith vaginal birth. Obstet Gynecol 1991;77:69-76.12. American College of Obstetricians and Gy-necologists. ACOG practice bulletin, no. 107:induction of labor. Obstet Gynecol 2009;114:386-97.13. Girard B, Vardon D, Creveuil C, HerlicoviezM, Dreyfus M. Discontinuation of oxytocin in theactive phase of labor. Acta Obstet GynecolScand 2009;88:172-7.14. Daniel-Spiegel E, Weiner Z, Ben-Shlomo I,Shalev E. For how long should oxytocin be con-tinued during induction of labor? BJOG 2004;111:331-4.15. Ustunyurt E, Ugur M, Ustunyurt BO, Isk-ender TC, Ozkan O, Mollamahmutoglu L. Pro-spective randomized study of oxytocin discon-tinuation after the active stage of labor isestablished. J Obstet Gynaecol Res 2007;33:799-803.16. Friedman E. The graphic analysis of labor.Am J Obstet Gynecol 1954;68:1568-75.17. Peisner DB, Rosen MG. Transition from la-tent to active labor. Obstet Gynecol 1986;68:448-51.18. Soper DE, Mayhall CG, Dalton HP. Risk fac-tors for intraamniotic infection: a prospectiveepidemiologic study. Am J Obstet Gynecol1989;161:562-8.19. Lucidi RS, Chez RA, Creasy RK. The clinicaluse of intrauterine pressure catheters. J MaternFetal Med 2001;10:420-2.20. Bakker JJ, Verhoven CJ, Janssen PF, et al.Outcomes after internal versus external tocody-namometry for monitoring labor. N Engl J Med2010;362:306-13.21. Mark SP, Croughan-Minihane MS, Kilpat-rick SJ. Chorioamnionitis and uterine function.Obstet Gynecol 2000;95:909-12.22. Harper LM, Caughey AB, Odibo AO, RoehlKA, Zhao Q, Cahill AG. Normal progress ofinduced labor. Obstet Gynecol 2012;119:

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