Women and Birth 32 (2019) 356–363 Contents lists available at ScienceDirect Women and Birth journal homepage: www.elsevier.com/locate/wombi High-dose versus low-dose of oxytocin for labour augmentation: a randomised controlled trial a,b, c d a,e Lotta Selin *, Ulla-Britt Wennerholm , Maria Jonsson , Anna Dencker , c f b g a,h Gunnar Wallin , Eva Wiberg-Itzel , Elisabeth Almström , Max Petzold , Marie Berg a University of Gothenburg, Institute of Health and Care Sciences, Sahlgrenska Academy, Gothenburg, Sweden b NU-Hospital Group, Department of Obstetrics and Gynecology, Trollhättan, Sweden c University of Gothenburg, Department of Obstetrics and Gynecology, Institute for Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden d Uppsala University, Department of Women’s and Children’s Health, Uppsala, Sweden e University of Gothenburg, Centre for Person-centred Care, Sahlgrenska Academy, Gothenburg, Sweden f Karolinska Institute, Soder Hospital, Department of Clinical Science and Education, Section of Obstetrics and Gynaecology, Stockholm, Sweden g University of Gothenburg, Health Metrics Unit, The Sahlgrenska Academy, Gothenmurg, Sweden h Sahlgrenska University Hospital, Obstetric Unit, Gothenburg, Sweden A R T I C L E I N F O A B S T R A C T Article history: Problem: Delayed labour progress is common in nulliparous women, often leading to caesarean section Received 6 July 2018 despite augmentation of labour with synthetic oxytocin. Received in revised form 8 September 2018 Background: High- or low-dose oxytocin can be used for augmentation of delayed labour, but evidence for Accepted 10 September 2018 promoting high-dose is weak. Aim To ascertain the effect on caesarean section rate of high-dose versus low-dose oxytocin for Keywords: augmentation of delayed labour in nulliparous women. Augmentation of labour Methods Multicentre parallel double-blind randomised controlled trial (ClinicalTrials.gov: NCT01587625) in Delayed labour six labour wards in Sweden. Healthy nulliparous women at term with singleton cephalic fetal presentation, Oxytocin fi Caesarean spontaneous labour onset, con rmed delay in labour and ruptured membranes (n = 1351) were randomised to Nulliparous labour augmentation with either high-dose (6.6 mU/minute) or low-dose (3.3 mU/minute) oxytocin infusion. Findings: 1295 women were included in intention-to-treat analysis (high-dose n = 647; low-dose n = 648). Caesarean section rates didnot differ betweengroups (12.4% and 12.3%, 95% ConfidenceInterval À3.7 to 3.8). Womenwith high-dose oxytocin had: shorter labours (À23.4 min); more uterine tachysystole (43.2% versus 33.5%); similar rates of instrumental vaginal births, with more due to fetal distress (43.8% versus 22.7%) and fewer due to failure to progress (39.6% versus 58.8%). There were no differences in neonatal outcomes. Discussion: Our study could not confirm results of two systematic reviews indicating, with weak evidence, that use of high-dose oxytocin was associated with lower frequency of caesarean section. Conclusion: We found no advantages for routine use of high-dose oxytocin in the management of delay in labour. Low-dose oxytocin regimen is recommended to avoid unnecessary events of tachysystole and fetal distress. © 2018 The Authors. Published by Elsevier Ltd on behalf of Australian College of Midwives. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). oxytocin is usually used for augmentation of labour, but Statement of significance does have side-effects. What is already known Problem Evidence for promoting high-dose synthetic oxytocin for Delayed labour progress is common in nulliparous women, augmentation of labour, above low-dose, is weak. and often leads to emergency caesarean section. Synthetic What this paper adds * Corresponding author at: Institute of Health and Care Sciences, Sahlgrenska High-dose oxytocin as compared to low-dose was not Academy at the University of Gothenburg, 405 30 Gothenburg, Sweden. associated with a lower frequency of caesarean section E-mail address: [email protected] (L. Selin). https://doi.org/10.1016/j.wombi.2018.09.002 1871-5192/© 2018 The Authors. Published by Elsevier Ltd on behalf of Australian College of Midwives. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). L. Selin et al. / Women and Birth 32 (2019) 356–363 357 and led to more uterine tachysystole (43.2% versus 33.5%), 2.2. Participants and similar rates of instrumental vaginal births, with more due to fetal distress (43.8% versus 22.7%) and fewer due to 21 Eligible for inclusion were healthy, nulliparous women with failure to progress (39.6% versus 58.8%). Low-dose oxytocin normal singleton pregnancies at term (37 + 0 to 41 + 6 gestational is preferable for use to avoid unnecessary events of weeks), cephalic presentation, spontaneous onset of labour, active tachysystole and fetal distress. phase of labour (regular painful contractions and effaced cervix and dilation 3–4 cm), confirmed delayed labour progress, and ruptured membranes. Exclusion criteria were: age < 18 years, non-Swedish speaking, previous uterine surgery, clinically significant vaginal 1. Introduction bleeding during labour, delayed labour progress with fetal head station below the ischial spines in second stage, suspected dispropor- Delayed labour progress is common in nulliparous women, and tion between fetal head and maternal pelvis, abnormal vertex is among the leading indications for emergency caesarean section <À 1–4 presentation, suspected fetal growth restriction ( 2 standard (CS). Synthetic oxytocin is one of the most frequently used 22 5 deviations [SD]), abnormal fetal heart rate (FHR) (suspicious or medications in obstetric care and the common routine for pathological cardotocograph), heavy meconium stained amniotic augmentation of labour. However, the effectiveness of oxytocin fl fi > 3,6,7 uid, uterine tachysystole (de ned as 5 contractions during 10 min for treating abnormal progress has been questioned. Despite for >20 min), maternal fever, and known hypersensitivity to oxytocin that, over time an increased use of oxytocin during labour has been 8,9 therapy. If any eligible women were already receiving oxytocin they noted. An unstructured manner of using the drug prevails, and were not included in the study, and women could be admitted to the its use can lead to hyperactive uterine contractions, which have fi 10–12 study when delayed progress was identi ed at any stage of dilation been associated with negative effects on the fetus. Therefore, – 13 (greater than 3 4 cm), or even in the second stage. oxytocin has been designated as a high-alert medication. Checklists and standardised protocols for the use of oxytocin have 2.3. Randomisation and procedure been recommended with the aim of reducing adverse neonatal outcomes.14,15 The study was conducted according to the study protocol with A meta-analysis of 8 trials comparing high and low dose two exceptions: women were asked to participate when delayed oxytocin for induction of labour found no difference in CS rates, labour was confirmed instead of being asked to participate at although more “uterine hyperstimulation” was noted in the high 16 admission and, there was a change to a computer-generated dose group. Knowledge and consensus are lacking, however, randomisation system instead of using sealed envelopes. regarding the proper dosage when oxytocin is used for accelerating fi 17 Delayed labour was de ned in accordance with the Swedish slow progress of labour. Women’s experience of childbirth and 23 National recommendations, by using a three-hour partogram action pain in relation to oxytocin dosage is also insufficiently studied. fi 17,18 line for delay during the rst stage of labour or an arrest of the descent Systematic reviews on the dosage of oxytocin have found that a of the fetal head for one to two hours during the second stage of labour. high-dose (4–10 mU/min) compared to low-dose (1–4 mU/min) If a delayed labour was diagnosed together with intact membranes, oxytocin regimen for treating delayed labour progress may reduce 18 17 amniotomy was performed. One hour later, an assessment was the risk of CS by 15%, or by as much as 46%, without any performed and, if there was no further progress, augmentation with negative maternal or neonatal outcomes. However, the evidence oxytocin infusion was indicated. The woman received written and oral for prioritising high-dose oxytocin is weak, and the Cochrane information about the study from the midwife. review on this topic (based on only four trials) recommended 17 Consenting women were randomly allocated to receive a further research. The need for further investigations has been regimen of either a high-dose or a low-dose of oxytocin (33.2 or highlighted, especially on neonatal outcomes and on women’s m 18,17 16.6 g oxytocin in 1000 ml isotonic saline solution), respectively). childbirth experiences in relation to oxytocin dosage. More These doses were chosen based on the definitions for low and high randomised controlled trials (RCTs) are justified to determine the 17 dose included in the latest Cochrane review on this topic. effect of oxytocin augmentation on the likelihood of CS and other Randomisation was generated by an external information technol- outcomes including women’s satisfaction with care, which has ogy-consultant using a computer-generated randomisation se- been emphasised by the British Maternal and Foetal Medicine quence, with allocation 1:1 ratio. There was no stratification by Society.19 maternity unit. Randomisation and preparation of the oxytocin The overall aim of the study was to ascertain the effect on infusion according to the allocated dosage were handled by caesarean section rate of high-dose versus low-dose oxytocin for external staff, not working at the labour ward. Allocation was augmentation of delayed labour in nulliparous women. The blinded for responsible staff, the woman in labour and for the hypothesis, based on weak evidence form a previous Cochrane 17 research team.