Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): double blind randomised controlled trial
BMJ 2021; 373 doi: https://doi.org/10.1136/bmj.n716 (Published 14 April 2021) Cite this as: BMJ 2021;373:n716
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Dear Editor,
We recently had the good fortune to read your article entitled ‘Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX) : double blind randomized controlled trial’ by Sidsel Boie.[1] This is an enthralling and stimulating article on a much needed topic because there is still no consensus on whether oxytocin should be continued or discontinued after the active phase of labour has been reached. It is a fascinating topic and we would like to thank the authors and everyone involved in this and we would also like to share our insight that according to us will help in augmenting and enhancing the paper further.
We know that once labour contractions are established the endogenous production of prostaglandin from the endometrium may be enough to maintain appropriate uterine activity without further stimulation of oxytocin.[2] It’s true that stopping IV oxytocin once active phase of labour has reached could result in a more natural childbirth, particularly when risk of uterine overstimulation and need for immediate caesarean section is reduced and with dose reduction adverse effects can also be minimized.[3] Continuous oxytocin infusion not only increases the chance of caesarean section but also increases the rate of postpartum hemorrhage and also neonatal asphyxia, hyperbilirubenemia; several authors have also observed that prolonged oxytocin use can lead to progressive myocyte desensitization and thus decreased uterine contractile capacity.[4][5] But stopping oxytocin infusion during labour has little or no impact on use of analgesia and epidural compared to the group receiving continuous oxytocin.[3]
The assumption that discontinuing oxytocin may prolong labour is not supported by the Daniel Spigel study. The result of the study conducted by Lutfun Naher Begum and team on this topic also supports the hypothesis that continuing oxytocin infusion after active phase of labour is established may complicate labour and effect maternal and neonatal outcome.[4]
I think further research and study is needed to establish optimum protocol for the effective use of oxytocin. Since this study has increased risk of bias. Thus future studies and trials conducted with increased sample size are needed.
REFERENCES:
1) Sidsel Boie, Julie Glavind, Niels Uldbjerg, Philip J Steer, Pinar Bor. Continued versus discontinued stimulation in the active phase of labour(CONDISOX)
2) M. Mitra, M. Sengupta, R. Ghosal, C. Saha, D.Bandhya, D. Ghosh . Continuation versus discontinuation of oxytocin in active phase of labour- A randomized trial
3) Boie S, Glavind J, Velu AV, Mol BWJ, Uldbjerg N, de Graaf I, Thornton JG, Bor P, Bakker JJH. Discontinuation of intravenous oxytocin in the active phase of induced labour(review)
4) Lutfun Naher Begum, Munawar Sultana, Shamsun Nahar ,Rokeya Begum, Shaibal Barua. A 3randomized clinical trial on the need of continuing oxytocin infusion in active phase of induced labour
5) Antonio Hernández-Martínez, Angel Arias-Ariasb, Antonio Morandeira-Rivasc, Ana I. Pascual-Pedreñoa, Elias J. Ortiz-Molinaa, Julian Rodriguez-Almagrod. Oxytocin discontinuation after the active phase of induced labour:A systematic review
Competing interests: No competing interests
Dear Editor
Dear Alicia Sanchez
The trial was double blind, with independent generation of the randomisation sequence, preparation of drug and placebo, and blinded collection of all outcome data. The chief investigator, SB, assisted the trial statistician to prepare data. Although those data were by group labelled A and B, i.e. without revealing which group was experimental, it would have been fairly easy for a clinician to infer the intervention group. However, the chief investigator SB was not at the time recruiting participants, and was not empowered to alter the sample size.
Kind regards
Sidsel Boie
Competing interests: No competing interests
Dear Editor,
I would like to ask if you really did a double blind trial. I´ve seen you reference it as a double blind controlled trial, however in the paragraph were you talk about the "Randomisation and masking" you literally say: "Accordingly, women, care givers, and trial managers were all blinded to the allocation."
If I read this, I understand it is a triple blind trial because neither women, caregivers nor trial managers knew the allocations. So, I may be pleased if you could clarify this information.
Thank you very much.
Competing interests: No competing interests
Dear Editor
Dear Souhail Alouini
Thank you for your interest in the trial and for your comments on both the objective and the conclusion.
It is important to note that the trial population consisted only of women with induced labour. Different approaches for cervical ripening and induction of labour are used worldwide, but uterine stimulation by continuous oxytocin infusion is widely employed as a major component. The current approach for oxytocin stimulation recommends that the stimulation continues until delivery, unless adverse events (e.g. hyperstimulation) occur. Other approaches for oxytocin stimulation have been suggested: pulsatile administration, an automatic feed-back controlled oxytocin infusion system, high dose (>2.5 mU/min) or low dose (<2.5mU/min), and discontinuation of the stimulation when the active phase of induced labour is reached, but none of these have to date achieved widespread clinical acceptance.
The underlying logic for discontinuation is that once uterine contractions are established and labour is progressing, the endogenous production of prostaglandin from the endometrium, initiated by contractions and sustained by cervical dilatation and stretching of the lower segment, may be sufficient to maintain labour progress without further stimulation. Discontinuation of oxytocin shortens the total duration of oxytocin infusion, releasing production of endogenous oxytocin and reducing the risk of oxytocin receptor desensitisation. It has been suggested that this enables endogenous oxytocin to retain its potency, and maintain effective uterine contractions, thereby maintaining labour progress.
Our hypothesis was that these effects could increase the chance of full cervical dilatation and vaginal birth by reducing the risk of exogenous oxytocin induced adverse effects, both hyperstimulation by excessive infusion of exogenous oxytocin, and postpartum haemorrhage due to desensitised oxytocin receptors. Although previous small randomised controlled trials had supported this hypothesis, we considered that only a much larger high-quality randomised trial comparing current practice with discontinued oxytocin stimulation in the active phase of induced labour would test this hypothesis adequately.
On behalf of the authors,
Sidsel Boie
Competing interests: No competing interests
Dear Editor
What is the sense behind such a randomized controlled trial (RCT), to have a continuous perfusion of oxytocin during labour or to have a discontinuous perfusion of oxytocin? (1)
Why do we prescribe oxytocin during labour? All obstetricians ask to perfuse oxytocin because there is no uterine contractions mainly due to peridural analgesia. When there are natural and efficient contractions during labour, we do not perfuse pregnant women with oxytocin. There is no systematic perfusion of oxytocin, we adapt the administration of oxytocin to uterine contractions during labour. What is the significance of the findings that discontinuous perfusion increases the rate of caesarean deliveries? Therefore, we should prescribe continuous perfusion of oxytocin even if the pregnant women have natural and efficient contractions?
The other conclusion is that discontinuous perfusion of oxytocin decreases the stimulation of the uterus, what a fantastic discovery! All obstetricians and midwives know the mechanism of action of oxytocin that it induces uterine contractions (or uterine stimulation) and that it is responsible for more fetal acidosis when compared to labour without oxytocin.
I do not understand the objective of such an RCT and the absence of conclusions of this paper.
References
1. Boie S, Glavind J, Uldbjerg N, Steer PJ, Bor P; CONDISOX trial group. Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): double blind randomised controlled trial. BMJ. 2021 Apr 14;373:n716. doi: 10.1136/bmj.n716.
Competing interests: No competing interests
Re: Continued versus discontinued oxytocin stimulation in the active phase of labour (CONDISOX): double blind randomised controlled trial
Dear Navya Jayakrishnan
Thank you for your interest and your comments on the trial.
In spite of your arguments primarily based on non-blinded, small RCTs, we find that our conclusion based on the results from this RCT and the metaanalysis of the Cochrane Review (1) expresses the state of the art: “In a setting where monitoring of the fetal condition and the uterine contractions can be guaranteed, routine discontinuation of oxytocin stimulation may lead to a small increase in caesarean section rate but a significantly reduced risk of uterine hyperstimulation and abnormal fetal heart rate patterns.”
However, we agree with you concerning the need for further studies. They may not ask the question “to continue oxytocin or not?” Instead, they may ask “who will benefit from oxytocin discontinuation and who will benefit from oxytocin continuation?”
Thus, we are aware of the relatively high number of women in our trial not receiving trial medication throughout labor. One hypothesis could be that the women who discontinued the assigned treatment had characteristics that increased their risk for slow progress of labour. We do plan to look further into this.
On behalf of the authors,
Sidsel Boie
1) Boie S, Glavind J, Velu AV, Mol BWJ, Uldbjerg N, de Graaf I, Thornton JG, Bor P, Bakker JJH. Discontinuation of intravenous oxytocin in the active phase of induced labour, The Cochrane Database of Systematic Reviews, 8, doi:10.1002/14651858.CD012274.pub2
Competing interests: No competing interests