Prophylactic use of oxytocin in the third stage of labour

92 Pages·2017·1.13 MB·English

Prophylactic oxytocin for the third stage of labour (Review)
Cotter AM, Ness A, Tolosa JE
ThisisareprintofaCochranereview,preparedandmaintainedbyTheCochraneCollaborationandpublishedinTheCochraneLibrary
2001,Issue4
http://www.thecochranelibrary.com
Prophylacticoxytocinforthethirdstageoflabour(Review)
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
DATAANDANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Analysis1.1.Comparison1Oxytocinversusnouterotonics(alltrials),Outcome1PPH(clinicallyestimatedbloodloss>
or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Analysis1.2.Comparison1Oxytocinversusnouterotonics(alltrials),Outcome2SeverePPH(clinicallyestimatedblood
loss>or=1000ml). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Analysis1.3.Comparison1Oxytocinversusnouterotonics(alltrials),Outcome3Meanbloodloss(ml). . . . . 31
Analysis1.4.Comparison1Oxytocinversusnouterotonics(alltrials),Outcome4Maternalhaemoglobinconcentration
(Hb)<9gm/deciltre24to48hourspostpartum. . . . . . . . . . . . . . . . . . . . . . 31
Analysis1.5.Comparison1Oxytocinversusnouterotonics(alltrials),Outcome5Bloodtransfusion. . . . . . 32
Analysis1.7.Comparison1Oxytocinversusnouterotonics(alltrials),Outcome7Therapeuticuterontonics. . . . 33
Analysis1.10. Comparison 1Oxytocinversusno uterotonics(alltrials), Outcome10Mean lengthofthirdstage
(minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Analysis1.11.Comparison1Oxytocinversusnouterotonics(alltrials),Outcome11Manualremovaloftheplacenta. 34
Analysis1.15.Comparison1Oxytocinversusnouterotonics(alltrials),Outcome15Nauseabetweendeliveryofthebaby
anddischargefromthelabourward. . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Analysis2.1.Comparison2Oxytocinversusnouterotonics(randomisedtrialsonly),Outcome1PPH(clinicallyestimated
bloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Analysis2.2.Comparison2Oxytocinversusnouterotonics(randomisedtrialsonly),Outcome2SeverePPH(clinically
estimatedbloodloss>or=1000ml). . . . . . . . . . . . . . . . . . . . . . . . . . 37
Analysis2.3.Comparison2Oxytocinversusnouterotonics(randomisedtrialsonly),Outcome3Meanbloodloss(ml). 38
Analysis2.4.Comparison2Oxytocinversusnouterotonics(randomisedtrialsonly),Outcome4Maternalhaemoglobin
concentration(Hb)<9gm/deciltre24to48hourspostpartum. . . . . . . . . . . . . . . . . 38
Analysis2.5.Comparison2Oxytocinversusnouterotonics(randomisedtrialsonly),Outcome5Bloodtransfusion. 39
Analysis 2.7. Comparison 2 Oxytocin versus no uterotonics (randomised trials only), Outcome 7 Therapeutic
uterontonics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Analysis2.10.Comparison2Oxytocinversusnouterotonics(randomisedtrialsonly),Outcome10Meanlengthofthird
stage(minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Analysis2.11.Comparison2Oxytocinversusnouterotonics(randomisedtrialsonly),Outcome11Manualremovalofthe
placenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Analysis2.15.Comparison2Oxytocinversusnouterotonics(randomisedtrialsonly),Outcome15Nauseabetween
deliveryofthebabyanddischargefromthelabourward. . . . . . . . . . . . . . . . . . . . 42
Analysis3.1.Comparison 3Oxytocinversusnouterotonics(activemanagementonly),Outcome1PPH(clinically
estimatedbloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Analysis3.2.Comparison3Oxytocinversusnouterotonics(activemanagementonly),Outcome2SeverePPH(clinically
estimatedbloodloss>or=1000ml). . . . . . . . . . . . . . . . . . . . . . . . . . 43
Analysis3.11.Comparison3Oxytocinversusnouterotonics(activemanagementonly),Outcome11Manualremovalof
theplacenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Analysis4.1.Comparison4Oxytocinversusnouterotonics(expectantmanagementonly),Outcome1PPH(clinically
estimatedbloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Prophylacticoxytocinforthethirdstageoflabour(Review) i
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Analysis4.2.Comparison4Oxytocinversusnouterotonics(expectantmanagementonly),Outcome2SeverePPH
(clinicallyestimatedbloodloss>or=1000ml). . . . . . . . . . . . . . . . . . . . . . . 44
Analysis4.3.Comparison4Oxytocinversusnouterotonics(expectantmanagementonly),Outcome3Meanbloodloss
(ml). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Analysis4.4. Comparison 4Oxytocin versusnouterotonics (expectantmanagement only),Outcome 4Maternal
haemoglobinconcentration(Hb)<9gm/deciltre24to48hourspostpartum. . . . . . . . . . . . . 45
Analysis4.5.Comparison4Oxytocinversusnouterotonics(expectantmanagementonly),Outcome5Bloodtransfusion. 46
Analysis4.7.Comparison4Oxytocinversusnouterotonics(expectantmanagementonly),Outcome7Therapeutic
uterontonics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
Analysis4.11.Comparison4Oxytocinversusnouterotonics(expectantmanagementonly),Outcome11Manualremoval
oftheplacenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Analysis5.1.Comparison5Oxytocinversusnouterotonics(givenbeforeplacentaldelivery),Outcome1PPH(clinically
estimatedbloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Analysis5.2.Comparison5Oxytocinversusnouterotonics(givenbeforeplacentaldelivery),Outcome2SeverePPH
(clinicallyestimatedbloodloss>or=1000ml). . . . . . . . . . . . . . . . . . . . . . . 48
Analysis5.3.Comparison5Oxytocinversusnouterotonics(givenbeforeplacentaldelivery),Outcome3Meanbloodloss
(ml). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Analysis5.4.Comparison5Oxytocinversusnouterotonics(givenbeforeplacentaldelivery),Outcome4Maternal
haemoglobinconcentration(Hb)<9gm/deciltre24to48hourspostpartum. . . . . . . . . . . . . 49
Analysis 5.5. Comparison 5 Oxytocin versusno uterotonics (givenbefore placentaldelivery), Outcome 5Blood
transfusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
Analysis5.7.Comparison5Oxytocinversusnouterotonics(givenbeforeplacentaldelivery),Outcome7Therapeutic
uterontonics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Analysis5.10.Comparison5Oxytocinversusnouterotonics(givenbeforeplacentaldelivery),Outcome10Meanlengthof
thirdstage(minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Analysis5.11.Comparison5Oxytocinversusnouterotonics(givenbeforeplacentaldelivery),Outcome11Manual
removaloftheplacenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Analysis5.15.Comparison5Oxytocinversusnouterotonics(givenbeforeplacentaldelivery),Outcome15Nauseabetween
deliveryofthebabyanddischargefromthelabourward. . . . . . . . . . . . . . . . . . . . 53
Analysis6.1.Comparison6Oxytocinversusnouterotonics(givenafterplacentaldelivery),Outcome1PPH(clinically
estimatedbloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Analysis6.3.Comparison6Oxytocinversusnouterotonics(givenafterplacentaldelivery),Outcome3Meanbloodloss
(ml). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Analysis6.7.Comparison6Oxytocinversusnouterotonics(givenafterplacentaldelivery),Outcome7Therapeutic
uterontonics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Analysis7.1.Comparison7Oxytocinversusergotalkaloids(alltrials),Outcome1PPH(clinicallyestimatedbloodloss>
or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Analysis7.2.Comparison7Oxytocinversusergotalkaloids(alltrials),Outcome2SeverePPH(clinicallyestimatedblood
loss>or=1000ml). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Analysis7.3.Comparison7Oxytocinversusergotalkaloids(alltrials),Outcome3Meanbloodloss(ml). . . . . 56
Analysis7.5.Comparison7Oxytocinversusergotalkaloids(alltrials),Outcome5Bloodtransfusion. . . . . . 57
Analysis7.7.Comparison7Oxytocinversusergotalkaloids(alltrials),Outcome7Therapeuticuterontonics. . . . 58
Analysis7.8.Comparison7Oxytocinversusergotalkaloids(alltrials),Outcome8Thirdstage>20minutes. . . . 58
Analysis7.9.Comparison7Oxytocinversusergotalkaloids(alltrials),Outcome9Thirdstage>40minutes. . . . 59
Analysis7.10. Comparison 7Oxytocinversusergotalkaloids (alltrials),Outcome10 Meanlengthof thirdstage
(minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Analysis7.11.Comparison7Oxytocinversusergotalkaloids(alltrials),Outcome11Manualremovaloftheplacenta. 60
Analysis7.13.Comparison7Oxytocinversusergotalkaloids(alltrials),Outcome13Diastolicbloodpressure>100mm
Hgbetweendeliveryofthebabyanddischargefromthelabourward. . . . . . . . . . . . . . . 60
Analysis8.1.Comparison8Oxytocinversusergotalkaloids(randomisedtrialsonly),Outcome1PPH(clinicallyestimated
bloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Analysis8.2.Comparison8Oxytocinversusergotalkaloids(randomisedtrialsonly),Outcome2SeverePPH(clinically
estimatedbloodloss>or=1000ml). . . . . . . . . . . . . . . . . . . . . . . . . . 61
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Analysis8.3.Comparison8Oxytocinversusergotalkaloids(randomisedtrialsonly),Outcome3Meanbloodloss(ml). 62
Analysis8.5.Comparison8Oxytocinversusergotalkaloids(randomisedtrialsonly),Outcome5Bloodtransfusion. 63
Analysis 8.7. Comparison 8 Oxytocin versus ergot alkaloids (randomised trials only), Outcome 7 Therapeutic
uterontonics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Analysis8.8.Comparison8Oxytocinversusergotalkaloids(randomisedtrialsonly),Outcome8Thirdstage>20
minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
Analysis8.9.Comparison8Oxytocinversusergotalkaloids(randomisedtrialsonly),Outcome9Thirdstage>40
minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
Analysis8.11.Comparison8Oxytocinversusergotalkaloids(randomisedtrialsonly),Outcome11Manualremovalofthe
placenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Analysis10.1.Comparison10Oxytocinversusergotalkaloids(expectantmanagementonly),Outcome1PPH(clinically
estimatedbloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Analysis10.2.Comparison10Oxytocinversusergotalkaloids(expectantmanagementonly),Outcome2SeverePPH
(clinicallyestimatedbloodloss>or=1000ml). . . . . . . . . . . . . . . . . . . . . . . 66
Analysis10.3.Comparison10Oxytocinversusergotalkaloids(expectantmanagementonly),Outcome3Meanbloodloss
(ml). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
Analysis10.5. Comparison 10 Oxytocin versusergot alkaloids (expectantmanagement only), Outcome 5Blood
transfusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Analysis10.7.Comparison10Oxytocinversusergotalkaloids(expectantmanagementonly),Outcome7Therapeutic
uterontonics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Analysis10.11.Comparison10Oxytocinversusergotalkaloids(expectantmanagementonly),Outcome11Manual
removaloftheplacenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
Analysis11.1.Comparison11Oxytocinversusergotalkaloids(givenbeforeplacentaldelivery),Outcome1PPH(clinically
estimatedbloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . 68
Analysis11.2.Comparison11Oxytocinversusergotalkaloids(givenbeforeplacentaldelivery),Outcome2SeverePPH
(clinicallyestimatedbloodloss>or=1000ml). . . . . . . . . . . . . . . . . . . . . . . 69
Analysis11.3.Comparison11Oxytocinversusergotalkaloids(givenbeforeplacentaldelivery),Outcome3Meanblood
loss(ml). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Analysis11.5. Comparison 11Oxytocinversusergotalkaloids(givenbeforeplacentaldelivery),Outcome5Blood
transfusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Analysis11.7.Comparison11Oxytocinversusergotalkaloids(givenbeforeplacentaldelivery),Outcome7Therapeutic
uterontonics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Analysis11.8.Comparison11Oxytocinversusergotalkaloids(givenbeforeplacentaldelivery),Outcome8Thirdstage>
20minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Analysis11.9.Comparison11Oxytocinversusergotalkaloids(givenbeforeplacentaldelivery),Outcome9Thirdstage>
40minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Analysis11.10.Comparison11Oxytocinversusergotalkaloids(givenbeforeplacentaldelivery),Outcome10Meanlength
ofthirdstage(minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Analysis11.11.Comparison11Oxytocinversusergotalkaloids(givenbeforeplacentaldelivery),Outcome11Manual
removaloftheplacenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Analysis11.13.Comparison11Oxytocinversusergotalkaloids(givenbeforeplacentaldelivery),Outcome13Diastolic
bloodpressure>100mmHgbetweendeliveryofthebabyanddischargefromthelabourward. . . . . . 73
Analysis12.1.Comparison12Oxytocinversusergotalkaloids(givenafterplacentaldelivery),Outcome1PPH(clinically
estimatedbloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Analysis12.7.Comparison12Oxytocinversusergotalkaloids(givenafterplacentaldelivery),Outcome7Therapeutic
uterontonics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Analysis13.1.Comparison13Oxytocin+ergometrineversusergotalkaloidsalone(alltrials),Outcome1PPH(clinically
estimatedbloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Analysis13.2.Comparison13Oxytocin+ergometrineversusergotalkaloidsalone(alltrials),Outcome2SeverePPH
(clinicallyestimatedbloodloss>or=1000ml). . . . . . . . . . . . . . . . . . . . . . . 75
Analysis13.5. Comparison 13 Oxytocin+ergometrine versusergotalkaloidsalone (alltrials),Outcome5Blood
transfusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Prophylacticoxytocinforthethirdstageoflabour(Review) iii
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Analysis13.8.Comparison13Oxytocin+ergometrineversusergotalkaloidsalone(alltrials),Outcome8Thirdstage>20
minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Analysis13.11.Comparison13Oxytocin+ergometrineversusergotalkaloidsalone(alltrials),Outcome11Manual
removaloftheplacenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Analysis14.1.Comparison14Oxytocin+ergometrineversusergotalkaloidsalone(randomisedtrials),Outcome1PPH
(clinicallyestimatedbloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . 78
Analysis14.8.Comparison14Oxytocin+ergometrineversusergotalkaloidsalone(randomisedtrials),Outcome8Third
stage>20minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Analysis15.1.Comparison15Oxytocin+ergometrineversusergotalkaloidsalone(activemanagement),Outcome1PPH
(clinicallyestimatedbloodloss>or=500ml). . . . . . . . . . . . . . . . . . . . . . . 79
Analysis15.8.Comparison15Oxytocin+ergometrineversusergotalkaloidsalone(activemanagement),Outcome8Third
stage>20minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Analysis15.11.Comparison15Oxytocin+ergometrineversusergotalkaloidsalone(activemanagement),Outcome11
Manualremovaloftheplacenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Analysis17.1.Comparison17Oxytocin+ergometrineversusergotalkaloidsalone(givenbeforeplacentaldelivery,
Outcome1PPH(clinicallyestimatedbloodloss>or=500ml). . . . . . . . . . . . . . . . . 81
Analysis17.2.Comparison17Oxytocin+ergometrineversusergotalkaloidsalone(givenbeforeplacentaldelivery,
Outcome2SeverePPH(clinicallyestimatedbloodloss>or=1000ml). . . . . . . . . . . . . . 81
Analysis17.5.Comparison17Oxytocin+ergometrineversusergotalkaloidsalone(givenbeforeplacentaldelivery,
Outcome5Bloodtransfusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Analysis17.8.Comparison17Oxytocin+ergometrineversusergotalkaloidsalone(givenbeforeplacentaldelivery,
Outcome8Thirdstage>20minutes. . . . . . . . . . . . . . . . . . . . . . . . . . 83
Analysis17.11.Comparison17Oxytocin+ergometrineversusergotalkaloidsalone(givenbeforeplacentaldelivery,
Outcome11Manualremovaloftheplacenta. . . . . . . . . . . . . . . . . . . . . . . . 83
FEEDBACK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
WHAT’SNEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
INDEXTERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Prophylacticoxytocinforthethirdstageoflabour(Review) iv
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[InterventionReview]
Prophylactic oxytocin for the third stage of labour
AmandaMCotter1,AmenNess2,JorgeETolosa3
1DepartmentofObstetricsandGynecology,UniversityofMiami,Miami,Florida,USA.2DepartmentofObstetricsandGynecology,
ThomasJeffersonUniversity,Philadelphia,USA.3DepartmentofObstetricsandGynecology,OregonHealthandSciencesUniversity,
Portland,Oregon,USA
Contactaddress:AmandaMCotter,DepartmentofObstetricsandGynecology,UniversityofMiami,POBox016960(D-53),Miami,
Florida,33101,[email protected].
Editorialgroup:CochranePregnancyandChildbirthGroup.
Publicationstatusanddate:Edited(nochangetoconclusions),publishedinIssue2,2010.
Reviewcontentassessedasup-to-date: 30November2004.
Citation: CotterAM,NessA,TolosaJE.Prophylacticoxytocinforthethirdstageoflabour.CochraneDatabaseofSystematicReviews
2001,Issue4.Art.No.:CD001808.DOI:10.1002/14651858.CD001808.
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
Complicationsofthethirdstageoflabourareasignificantcauseofmaternalmortalityworldwide.
Objectives
Toexaminetheeffectofoxytocingivenprophylacticallyinthethirdstageoflabouronmaternalandneonataloutcomes.
Searchmethods
WesearchedtheCochranePregnancyandChildbirthGroup’sTrialsRegister(December2004).Weupdatedthissearchon1October
2009andaddedtheresultstotheawaitingclassificationsection.
Selectioncriteria
Randomisedorquasi-randomisedcontrolledtrialsincludingpregnantwomenanticipatingavaginaldeliverywhereoxytocinwasgiven
prophylacticallyforthethirdstageoflabour.
Datacollectionandanalysis
The review authors independently assessed trial quality and extracted data. Analysis was by intention to treat. Subgroup analyses
werebasedonextentofselectionbias,oxytocininthecontextofactiveorexpectantmanagementofthethirdstage,andtimingof
administration.Resultsarepresentedasrelativerisks,andweightedmeandifference,bothwith95%confidenceintervalsusingafixed-
effectmodel.
Mainresults
Fourteentrialsareincluded.
Inseventrialsinvolvingover3000women,prophylacticoxytocinshowedbenefits(reducedbloodloss(relativerisk(RR)forbloodloss
greaterthan500ml0.50;95%confidenceinterval(CI)0.43to0.59)andneedfortherapeuticoxytocics(RR0.50;95%CI0.39to
0.64)comparedtonouterotonics.
Prophylacticoxytocinforthethirdstageoflabour(Review) 1
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Insixtrialsinvolvingover2800women,therewaslittleevidenceofdifferentialeffectsforoxytocinversusergotalkaloids,exceptthat
oxytocinwasassociatedwithfewermanualremovalsoftheplacenta(RR0.57;95%CI0.41to0.79),andwiththesuggestionofless
raisedbloodpressure(RR0.53;95%CI0.19to1.52)thanwithergotalkaloids.
In five trials involving over 2800 women, there was little evidence of asynergistic effectof adding oxytocin to ergometrine versus
ergometrinealone.
Authors’conclusions
Oxytocinappearstobe beneficialforthepreventionofpostpartumhaemorrhage.However,thereisinsufficient information about
otheroutcomesandside-effectshenceitisdifficulttobeconfidentaboutthetrade-offsforthesebenefits.Thereseemslittleevidence
infavourofergotalkaloidsalonecomparedtoeitheroxytocinalone,ortoergometrine-oxytocin,butthedataaresparse.Moretrials
areneededindomiciliarydeliveriesindevelopingcountries,whichshouldermostoftheburdenofthirdstagecomplications.
[Note:Thetencitationsintheawaitingclassificationsectionofthereviewmayaltertheconclusionsofthereviewonceassessed.]
PLAIN LANGUAGE SUMMARY
Prophylacticoxytocinforthethirdstageoflabour
Oxytocinusedroutinelyafterbirthcanreducebloodloss,butmoreresearchisneededonpossibleadverseeffects.
Thethirdstageoflabouristhatperiodfrombirthofthebabyuntildeliveryoftheplacenta.Thedegreeofbloodlossdependsonhow
quicklytheplacentaseparatesfromtheuterinewallandtheuterinemusclecontracts.Severebloodloss-postpartumhaemorrhage,is
amajorproblem,particularlywherethereispoornutritionandlackofaccesstotreatment.Thereviewoftrialsfoundroutineuseof
oxytocin,adrugwhichhelpstheuteruscontract,mayreducetheamountofbloodloss,butthereisnotenoughevidenceaboutadverse
effects.Moreresearchisneeded.
Moderate loss of blood is physiological and unlikely to lead to
BACKGROUND
laterproblemsexceptforwomenwhoarealreadyanaemic.The
majorcomplicationassociatedwiththisstageispostpartumhaem-
The most reliable estimates of global mortality for mothers in
orrhage(PPH).Thisisnotnecessarilytorrentialbleeding,andis
childbirtharereportedasbetween500,000and600,000annually
usuallydefinedasbleedingfromthegenitaltractof500mlormore
(UNICEF1996;WHO1990).Manyofthesedeathsresultfrom
in the first 24 hours following delivery of the baby. Alternative
complicationsofthethirdstageoflabour.
cut-offpointsof600ml(Beischer1986)and1000ml(Burchell
Thethirdstageoflabouristhatperiodfromdeliveryofthebaby 1980)havealsobeensuggested,andithaslongbeenrecognised
untildeliveryoftheplacenta.Afterdeliveryofthebabyandces- thatsuchclinicalestimationislikelytounderestimatetheactual
sationofumbilicalcordpulsationtheplacentaseparatesfromthe volumeofbloodlostby34%to50%(Newton1961).Thismay
uterinewallthroughthespongyliningofthewomb(deciduaspon- inpartexplainthevariation in estimatedincidence ofPPH be-
giosa)andisdeliveredthroughthebirthcanal.Theplacentasep- tween5%and18%(Hall1985;Gilbert1987;Prendiville1988a),
aratesasaresultofcapillaryhaemorrhageandtheshearingeffect evenwithinasinglecountryliketheUK,wherePPHremainsan
ofuterinemusclecontraction.Thedegreeofbloodlossassociated important cause of maternal mortality (DoH 2004; Hall 1985;
with placental separation and delivery depends on how quickly Gilbert1987).Effectsonmaternalmorbidityarelesswelldocu-
theplacentaseparatesfromtheuterinewallandhoweffectively mented,butarelikelytoincludesuchinter-relatedoutcomesas
uterinemusclecontractsaroundtheplacentalbed(wherethepla- anaemia,fatigueanddepression.
centaisattachedtothewalloftheuterus),andthebloodvessels,
duringandafterseparation,andexpelstheplacentathroughthe Nearlyallmaternaldeaths(99%)occurinthedevelopingworld
birthcanal. (Kwast 1991), where other factors, such as infection (especially
Prophylacticoxytocinforthethirdstageoflabour(Review) 2
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
HIVinfection),poornutritionalstatusandlackofeasyaccessto OBJECTIVES
treatment,maycontributetodeathinthepresenceofseverepost-
Theobjectiveofthisreviewistoexaminetheeffectofoxytocin
partumhaemorrhage.Manymorewomensurviveandsufferseri-
givenprophylacticallyinthethirdstageoflabour,definedasthat
ousillnessasaresult,notonlyfromtheeffectsofacuteanaemia
periodfrombirthofthebaby until deliveryoftheplacenta,on
butalsofromtheinterventionswhichaseverehaemorrhagemay
outcomessuchasmaternalbloodlossandthelengthofthethird
necessitate (such as general anaesthesia, manual removal of the
stageoflabour,othereffectsonthemother,andtheoutcomefor
placenta,bloodtransfusion,hysterectomy).Otheraspectsofthe
thenewbornbaby.Theobjectivesofthisreviewwillconsiderthe
management of labour such as induction and augmentation of
followingcomparisons:
labour,orthedurationofthesecondstageinthecontextofepidu-
ralanaesthesiamayalsohaverelevanceforthethirdstage.Reduc-
1. oxytocinversusnouterotonics;
ingthelikelihoodofpostpartumhaemorrhagebyavoidingtheuse
ofbirthchairsinthesecondstage (Crowley1991)couldplaya 2. oxytocinversusergotalkaloids;
partinreducingmaternalmorbidityandmortality.
3. oxytocinplusergometrineversusergotalkaloids.
Thisreviewconcentratesoncomponentsofsuchmanagementin
thethirdstageoflabour.Onecomponentmaybeuterotonicdrugs METHODS
whichincreasethetoneoftheuterinemuscles.Theseuterotonics
wereinitiallyintroducedforthetreatmentofPPH.Moir (Moir
1932)showedthatergometrinewastheactiveprincipleonwhich
Criteriaforconsideringstudiesforthisreview
theknownuterotoniceffectofergothaddepended.Reviewingits
useinobstetricpracticebytheearly1950s,hisopinionwasthat
“Fewdrugscanhavebecomesofirmlyestablishedinsoshortatime
Typesofstudies
andfewdrugscanbesocompletelyindispensableasergometrineis
Allacceptablyrandomised orquasi-randomised controlledtrials
now”(Moir1955).Ergometrine(ergonovineintheUnitedStates)
wereconsideredforinclusion,withexclusionsonqualitygrounds
becamepopularforroutinemanagementintheearly1950s.Oxy-
iftherewaspotentialforsignificantselectionbiasaftertrialentry.
tocinisanaturallyoccurringuterotonic,whichDuVigneaudetal
synthesisedandreportedin1953(DuVigneaud1953).Embrey
etal(Embrey1963)reportedadvantagesofcombiningthiswith
Typesofparticipants
ergometrine(asSyntometrine-oxytocinfiveinternational units
Alltrialsincludingpregnantwomenanticipatingavaginaldeliv-
plusergometrine 0.5 mg). In order topreventblood loss, these
erywereconsidered,regardlessofotheraspectsofthirdstageman-
uterotonicsand,morerecently,prostaglandinsarealsobeingused
agement.
forprophylacticthirdstagemanagement.
Whilefewwoulddisputethecontributionofuterotonicdrugsin Typesofinterventions
thetreatmentofPPH,theirroleinroutineprophylaxisislessclear. Oxytocingivenprophylacticallyfor thethirdstage oflabour, at
Thisreviewconsiderstheprophylacticroleofoneoftheseutero- whateverdose.Thecurrentreviewconcentratesonoxytocingiven
tonics,oxytocin,inthethirdstageoflabour.Otherrelevantpub- byinjection, usually intoamaternalveinor amuscle.Therole
lishedreviewsarebyPrendiville2000,whichcompareactivewith ofprophylacticprostaglandinsorergotalkaloids,anduterotonics
expectantthirdstagemanagement(whereactivemanagementin- giventhroughtheumbilicalvein,orforthetreatmentofbloodloss
volvesthepackageofinterconnectedinterventionsofprophylactic orretainedplacenta,willbethesubjectofotherreviewsandare
uterotonics,earlycuttingandclampingoftheumbilicalcord,and notincludedhere.Similarly,endogenousoxytocin(nipplestimu-
controlledcordtraction);Gülmezoglu2004andMcDonald2004, lation)isnotincludedinthisreview.
whichbothconsidertheroleofdifferentprophylacticuterotonics
(prostaglandins,andergometrine-oxytocincomparedtooxytocin,
respectively)inthirdstagemanagement;andCarroli2001look- Typesofoutcomemeasures
ingattheroleofumbilicalveininjectionforthetreatmentofre- • Postpartumhaemorrhage(PPH)(reportedestimatesof
tainedplacenta.Subsequentthirdstagemanagementreviewswill bloodlossgreaterthanorequalto500ml)
considertheroleofprophylacticuterotonicsmoregenerally,and • SeverePPH(clinicallyestimatedbloodlossgreaterthanor
ofprophylacticergotalkaloidsparticularly.Astheseinterventions equalto1000ml)
areveryinter-related,someaspectsoftheroleofoxytocinmaybe • Meanbloodloss(ml)
foundintheseotherreviews(e.g.Prendiville2000;Gülmezoglu • Maternalhaemoglobinconcentration(Hb)lessthan9gm/
2004;McDonald2004). decilitre24to48hourspostpartum
Prophylacticoxytocinforthethirdstageoflabour(Review) 3
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
• Bloodtransfusion rialinformation about the CochranePregnancyandChildbirth
• Irontabletsduringthepuerperium Group.
• Therapeuticuterotonics Trialsidentifiedthroughthesearchingactivitiesdescribedabove
• Thirdstagegreaterthan20minutes areeachassignedtoareviewtopic(ortopics).TheTrialsSearch
• Thirdstagegreaterthan40minutes Co-ordinatorsearchestheregisterforeachreviewusingthetopic
• Meanlengthofthirdstage(minutes) listratherthankeywords.
• Manualremovaloftheplacenta
• Subsequentsurgicalevacuationofretainedproductsof
conception Datacollectionandanalysis
• Diastolicbloodpressuregreaterthan100mmHgbetween
Forthefirstpublication,tworeviewauthorscheckedthetitlesand
deliveryofbabyanddischargefromthelabourward
• Vomitingbetweendeliveryofbabyanddischargefromthe abstractsidentifiedfromthesearch.Twoofthereviewauthorsob-
tainedthefulltextofallstudiesofpossiblerelevanceforindepen-
labourward
• Nauseabetweendeliveryofbabyanddischargefromthe dentassessment. The methodological quality of the studies was
assessedwithparticularconcentrationonallocationconcealment,
labourward
• Headachebetweendeliveryofbabyanddischargefromthe rankedusingtheCochraneapproachofadequate,uncertainorin-
adequate.Tworeviewauthorsperformedthedataextraction.Trial
labourward
• Maternalpainduringthirdstageoflabour authorswerecontactedfor clarification whererelevant.Analysis
• Maternaldissatisfactionwiththirdstagemanagement wasbyintentiontotreat.
• SecondaryPPH(after24hoursandbeforesixweeks) Forthisupdatethefollowingmethodswereused.
• Bleedingneedingreadmissionorantibiotics
• Maternalfatigueatsixweeks
Selectionofstudies
• Apgarscorelessthansevenatfiveminutes
• Admissiontospecialcarebabyunit Weassessed forinclusion allpotential studiesweidentified asa
• Jaundice(asdefinedbytheauthors) resultofthesearchstrategy.Weresolvedanydisagreementthrough
• Notbreastfeedingatdischargefromhospital discussion.
• Notbreastfeedingatsixweeks
Assessmentofmethodologicalqualityofincluded
studies
Searchmethodsforidentificationofstudies Weassessedthevalidityofeachstudyusingthecriteriaoutlined
intheCochraneReviewers’Handbook(Alderson2004).
Electronicsearches (1)Selectionbias(randomisationandallocation
WesearchedtheCochranePregnancyandChildbirthGroupTrials concealment)
RegisterbycontactingtheTrialsSearchCo-ordinator(December Weplannedtoassignaqualityscoreforeachtrial,usingthefol-
2004).Weupdatedthissearchon1October2009andaddedthe lowingcriteria:
resultstoStudiesawaitingclassification. (A) adequate concealment of allocation, such as telephone ran-
TheCochranePregnancyandChildbirthGroup’sTrialsRegister domisation,consecutivelynumberedsealedopaqueenvelopes;
ismaintainedbytheTrialsSearchCo-ordinatorandcontainstrials (B)unclearwhetheradequateconcealmentofallocation;suchas
identifiedfrom: listortableused,sealedenvelopes,orstudydoesnotreportany
1. quarterlysearchesoftheCochraneCentralRegisterof concealmentapproach;
ControlledTrials(CENTRAL); (C) inadequate concealment of allocation, such as open list of
2. weeklysearchesofMEDLINE; randomnumbertables,useofcaserecordnumbers,datesofbirth
3. handsearchesof30journalsandtheproceedingsofmajor ordaysoftheweek.
conferences;
4. weeklycurrentawarenessalertsforafurther44journals
plusmonthlyBioMedCentralemailalerts. (2)Performancebias(blindingofparticipants,researchers
DetailsofthesearchstrategiesforCENTRALandMEDLINE, andoutcomeassessment)
thelistofhandsearchedjournalsandconferenceproceedings,and Weplannedtoassessblindingusingthefollowingcriteria:
thelistofjournalsreviewedviathecurrentawarenessservicecan (A)blindingofparticipants(yes/no/unclear);
be found in the ‘Specialized Register’ section within the edito- (B)blindingofcaregiver(yes/no/unclear);
Prophylacticoxytocinforthethirdstageoflabour(Review) 4
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
(C)blindingofoutcomeassessment(yes/no/unclear). Subgroup analyses were planned based on extent of control for
selectionbias,onwhethertheoxytocinisadministeredwithinthe
contextofactiveor expectantmanagementofthethirdstage of
(3)Attritionbias(lossofparticipants,e.g.withdrawals,
labour, and on the timing of administration. Further subgroup
dropouts,protocoldeviations)
analyses may consider the effects of different doses or different
Weplannedtoassesscompletenesstofollowupusingthefollowing routesofadministrationifappropriatedatabecomeavailable.
criteria: Resultsarepresentedasrelativerisksfordichotomousdata,and
(A)lessthan5%lossofparticipants; weighted mean difference for continuous data, both with 95%
(B)5%to10%lossofparticipants; confidence intervalsusingafixed-effectmodel.Ifsufficienthet-
(C)morethan10%andlessthan20%lossofparticipants; erogeneityexisted,sensitivityanalyseswouldhavebeperformed.
(D)morethan20%lossofparticipants.
Dataextractionandmanagement
We plannedfor all threereview authors to extractthedata and
RESULTS
to resolve discrepancies through discussion. We planned to use
theReviewManagersoftware(RevMan2003)todouble-enterthe
data.
Descriptionofstudies
Measuresoftreatmenteffect
See:Characteristicsofincludedstudies;Characteristicsofexcluded
WeplannedtocarryoutstatisticalanalysisusingtheReviewMan-
studies.
agersoftware(RevMan2003)andwouldhaveusedafixed-effect
Forty-sixtrialswereidentifiedasbeingpotentiallyeligibleforthis
meta-analysisforcombiningdataiftrialsweresufficientlysimilar.
review.Twenty-nineofthesetrialswereexcludedbecause:oxytocin
Fordichotomousdata:weplannedtopresentresultsassummary
was being compared to ergometrine-oxytocin (Docherty 1982;
relativeriskwith95%confidenceintervals.
Dumoulin 1981; Soriano 1995; Symes 1984; Yuen 1995); no
Forcontinuousdata:weplannedtousetheweightedmeandiffer-
clinicaloutcomedatawereavailable(Hacker1979;Muller1996;
enceifoutcomesweremeasuredinthesamewaybetweentrials.
VaughanWilliams1974);verystronglikelihoodofselectionbias
Weplannedtousethestandardisedmeandifferencetocombine
(Friedman1957;Nieminen1963;Stearn1963;Thornton1988);
trialsthatmeasuredthesameoutcome,butuseddifferentmeth-
comparison ofoxytocin given bydifferentroutesor atdifferent
ods. Iftherewasevidence ofskewness thiswouldhavebeenre-
times(Francis(1)1965b;Huh2000;Khan1997;Thornton1988;
ported.
Hoffman2004;Jackson2001;Porter1991;Schaefer2004)(see
Weplannedtoanalysedataonanintention-to-treatbasis.There-
Characteristicsofexcludedstudies).Theremaining14trialscon-
fore,allparticipantswithavailabledatawouldhavebeenincluded
ducted in hospital and/or developed country settings were in-
intheanalysisinthegrouptowhichtheywereallocated,regardless
cludedinthisreview(seeCharacteristicsofincludedstudies).(Ten
ofwhetherornottheyreceivedtheallocatedintervention. Ifin
reportsfromanupdatedsearchinOctober2009havebeenadded
theoriginalreportsparticipantswerenotanalysedinthegroupto
toStudiesawaitingclassification.)
whichtheywererandomised,andtherewassufficientinformation
inthetrialreport,wewould haveattemptedtorestore themto
thecorrectgroup.
Riskofbiasinincludedstudies
Assessmentofheterogeneity
Testsofheterogeneitybetweentrialswouldhavebeenappliedif
appropriate using the I² statistic. If we identified high levels of
ComparisonA:oxytocinversusnouterotonics
heterogeneityamongthetrials,(exceeding50%),wewouldhave
exploreditbyprespecifiedsubgroupanalysisandhaveperformed Eighttrialsarepotentiallyincludedinthiscomparison(DeGroot
sensitivity analysis. A random-effects meta-analysis would have 1996;Howard1964;Ilancheran1990;McGinty1956;Newton
beenusedasanoverallsummaryifconsideredappropriate. 1961; Nordstrom 1997; Pierre 1992; Poeschmann 1991), but
Threecomparisonswouldhavebeenconsidered: McGinty1956providesnousabledataforthispartofthereview.
(a)oxytocinversusnouterotonics; Fouroftheremainingsevenhadadequateallocationconcealment
(b)oxytocinversusergotalkaloids; (DeGroot1996;Howard1964;Nordstrom1997;Poeschmann
(c)oxytocinplusergometrineversusergotalkaloids. 1991).
Prophylacticoxytocinforthethirdstageoflabour(Review) 5
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.