Oxytocin is the primary hormonal response to uterine atony in childbirth. Oxytocin has two main effects; contraction of the uterus and induction of lactation. Due to the effect it has on the uterus it is often used in the induction of labour (Hormone.org, 2017). Oxytocin binds to the oxytocin receptor (OTR) in the myometrium of a woman’s uterus in the hours and days leading to parturition. The OTR is a G-protein coupled receptor (GPCR) and triggers the Gq/11 pathway, which stimulates voltage-gated calcium channels increasing intracellular calcium levels. Calcium then binds to calmodulin, which activates myosin light chain kinase allowing myosin-actin cross-bridges to form. In addition to this phospholipase C is converted into IP3 and DAG. IP3 and DAG act on the sarcoplasmic reticulum and increase intracellular prostaglandins respectively (Arrowsmith and Wray, 2014) leading to contraction of the myometrium. Therefore, oxytocin is a very powerful agent that may have various therapeutic effects but may have effects on the cardiovascular system (CVS) of a woman in childbirth.
Under normal circumstances (without any birth complications or oxytocin use) several doctors in America found that there was no statistically significant difference in the cardiac output (CO) between caesarean section and parturition (Niswonger and Langmade, 1970). This tells us that the heart is working under the same load in both caesarean section and parturition. This may be due to the differing stresses associated with both scenarios, however this is difficult to quantify. A more recent study has shown that there is a “47% increase in the cardiac index and 39% decrease in systemic vascular resistance index at delivery” during caesarean section (Tihtonen et al., 2005), more data is needed surrounding parturition.
It has been suggested that oxytocin induces CVS changes in childbirth. A group of mares were divided into 3 groups and were treated with 20 I.U of oxytocin at varying points in parturition. It was found that heart rate (HR) and blood pressure (BP) had no significant change other than a slight rise in cortisol levels when administered 12 hours after childbirth (Nagel et al., 2017). This implies that oxytocin may be a myometrium specific agent as it has same CVS parameters as childbirth without oxytocin. The heart acts under the same strain with oxytocin as it does if there isn’t any oxytocin given at any point in parturition. The rise in cortisol when oxytocin is administered 12 hours after foaling may due to changes in the hypothalamic-pituitary-adrenal (HPA) axis (Iliadis et al., 2015).
One randomised trial used women who had planned or unplanned caesarean section, these women were then given a bolus of carbetocin or a short infusion of carbetocin and measured the uterine tone with manual palpation. Carbetocin is a synthetic oxytocin analogue that is used to increase uterine tone. This investigation was to determine the efficacy on the CVS. They found that oxytocin given in a short infusion “doesn’t compromise uterine tone” and had similar cardiovascular outcomes to that of bolus infusion (Dell-Kuster et al., 2017). This tells us that oxytocin is a very useful agent in caesarean section regardless of how it is administered. This is useful as it gives the obstetric team more treatment options, without compromising on uterine tone for CVS safety. The only downside to this study is that uterine tone was measured manually therefore there is a margin of error that can occur. Oxytocin is safer at earlier stages of labour than ergometrine however. Administering ergometrine before the 3rd stage of labour can induce hypertonus and foetal complications. Ergometrine cannot be used on anyone with any pre-existing CVS disorder, as it causes peripheral vasoconstriction (Electronic Medicines Compendium (eMC), 2017).
Carbetocin is often used to prevent postpartum haemorrhage. According to guidelines published by the Royal College of Obstetricians and Gynaecologists (RCOG) postpartum haemorrhage is defined as loss of at least 500ml of blood from the Genital Tract (Royal College of Obstetricians and Gynaecologists, 2017). A case was reported in Canada where a woman was given a 100mg bolus of carbetocin and presented with acute coronary syndrome (Jacquenod et al., 2015). Acute coronary syndrome is where blood flow to the heart via the coronary arteries is compromised in some way. The Canadian woman in question had never presented with any CVS risk factors or symptoms suggesting she had an underlying condition, however during the operation there were significant changes in her electrocardiogram (ECG) trace indicative of acute coronary syndrome. Upon reviewing similar cases at the hospital, they found an incidence of this occurring of around 1/245 caesarean sections. 1 in 4 UK mothers have a caesarean section and in 2015 777,167 children were live-born (Ons.gov.uk, 2017). This means that approximately 194,292 children were born by caesarean section so if you apply the 1/245 caesarean sections statistic it means approximately 793 women in the UK could’ve suffered from acute coronary syndrome after being given a standard carbetocin bolus. This is a significant number of women and therefore means that perhaps more testing and analysis should be done to determine the relative risk mothers have. In my opinion, perhaps the best way to cope with this is to have more in depth CVS screening for caesarean sections.
In another study oxytocin was given cows to see if any potential postpartum risks were worth the substantial uses during parturition. They gave the control group 5ml of saline and 20 I.U of oxytocin to the test group on days 2 and 5 postpartum. They then monitored the uterine blood flow on both these days using transrectal colour Doppler ultrasonography to measure the uterine blood flow volume and pulsatility index in the uterine arteries. They found that there was no restriction to blood flow to the uterus postpartum as they had expected there would be (Magata et al., 2013). This tells oxytocin has very few side-effects regarding postpartum in cows, more testing would be needed to see if this was the same in humans.
Conclusion, there is little to no effect of oxytocin on the cardiovascular integrity of mother’s in caesarean section or parturition. There are risks with use of oxytocin in caesarean section, but the real risk is the inability to detect acute coronary syndrome, perhaps more research needs to be done in this area to improve CVS screening in mothers ahead of caesarean section. However, oxytocin is a very powerful agent that provides the desired uterine atony that is needed during childbirth, without compromising CVS integrity regardless of the method of administration, which offers obstetric teams more treatment options in differing scenarios. Oxytocin is also a useful tool in preventing postpartum haemorrhage with animal models suggesting it is less likely to compromise uterine blood flow in the 5 days following parturition. 😊
References:
1. Arrowsmith, S. and Wray, S. (2014). Oxytocin: Its Mechanism of Action and Receptor Signalling in the Myometrium. Journal of Neuroendocrinology, 26(6), pp.356-369.
2. Ons.gov.uk. (2017). Births in England and Wales- Office for National Statistics. [online] Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/livebirths/bulletins/birthsummarytablesenglandandwales/2015#number-of-live-births-in-the-uk-rises [Accessed 19 May 2017].
3. Dell-Kuster, S., Hoesli, I., Lapaire, O., Seeberger, E., Steiner, L., Bucher, H. and Girard, T. (2017). Efficacy and safety of carbetocin given as an intravenous bolus compared with short infusion for Caesarean section – double-blind, double-dummy, randomized controlled non-inferiority trial. BJA: British Journal of Anaesthesia, 118(5), pp.772-780.
4. Electronic Medicines Compendium (eMC). (2017). Ergometrine Injection BP 0.5% W/V. [online] Available at: https://www.medicines.org.uk/emc/medicine/20884 [Accessed 22 May 2017].
5. Iliadis, S., Comasco, E., Sylvén, S., Hellgren, C., Sundström Poromaa, I. and Skalkidou, A. (2015). Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms. PLOS ONE, 10(8), p.e0135471.
6. Jacquenod, P., Cattenoz, M., Canu, G., Bois, E. and Lieutaud, T. (2015). Syndrome coronarien aigu après injection de carbétocine 100 µg au cours d’une césarienne en urgence. Canadian Journal of Anesthesia/Journal canadien d’anesthésie, 62(5), pp.513-517.
7. Magata, F., Hartmann, D., Ishii, M., Miura, R., Takahashi, H., Matsui, M., Kida, K., Miyamoto, A. and Bollwein, H. (2013). Effects of exogenous oxytocin on uterine blood flow in puerperal dairy cows: The impact of days after parturition and retained fetal membranes. The Veterinary Journal, 196(1), pp.76-80.
8. Nagel, C., Trenk, L., Wulf, M., Ille, N., Aurich, J. and Aurich, C. (2017). Oxytocin treatment does not change cardiovascular parameters, hematology and plasma electrolytes in parturient horse mares. Theriogenology, 91, pp.69-76.
9. Niswonger, J. and Langmade, C. (1970). Cardiovascular changes in vaginal deliveries and caesarean sections. American Journal of Obstetrics and Gynaecology, 107(3), pp.337-344.
10. Royal College of Obstetricians & Gynaecologists. (2017). Postpartum Haemorrhage, Prevention and Management (Green-top Guideline No. 52). [online] Available at: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg52/ [Accessed 19 May 2017].
11. Tihtonen, K., Kööbi, T., Yli-Hankala, A. and Uotila, J. (2005). Maternal hemodynamics during cesarean delivery assessed by whole-body impedance cardiography. Acta Obstetricia et Gynecologica Scandinavica, 84(4), pp.355-361.
12. Hormone.org. (2017). What Does Oxytocin Do & What is its Function | Hormone Health. [online] Available at: http://www.hormone.org/hormones-and-health/what-do-hormones-do/oxytocin [Accessed 16 May 2017].