**Abstract**

There are no standardised recommendations for the use of oxytocin in obstetric indications. To prevent postpartum haemorrhage (PPH), the routine administration of oxytocin is standard practice. Failure of prophylactic therapy with oxytocin occurs commonly, necessitating the use of further oxytocin or other treatments to maintain haemodynamic stability. Oxytocin has its limitations as it requires cold storage and transport, and in low-resource settings, the cold chain is not commonly available. By modifying the oxytocin molecule, its half-life has been prolonged and its enzymatic degradation reduced. The modified molecule is named carbetocin. Heat-stable carbetocin is a promising alternative to oxytocin, which can overcome the persistent problems with oxytocin quality as it does not require a cold chain for storage and transport.

**Keywords:** postpartum haemorrhage, uterotonic, oxytocin, cold chain, heat-stable carbetocin

## **1. Introduction**

Oxytocin is used for induction of labor, augmentation of labor, and to reduce the risk of postpartum haemorrhage (PPH) [1]. Optimal management of oxytocin infusion requires effective interprofessional communication and collaboration. Oxytocin is a peptide generated from the hypothalamus in a pulsatile manner and secreted through the posterior pituitary, stimulating myometrial cells in the uterus and the myoepithelial cells around the mammary alveoli [2]. Oxytocin has a central role in labour. The oxytocin levels gradually increase during pregnancy, and the oxytocin receptors in the uterine muscles also gradually increase in number and become more sensitive to oxytocin in late pregnancy [3, 4]. During the labour initiation, there are fluctuations in the levels of oestrogen and progesterone alongwith changes in their receptors distribution. The effacement of the cervix happens during first stage of labour.

The uterus is supplied by the autonomic nervous system, which has a significant effect on the labour. Parasympathetic stimulation enhances contractility and circulation to the uterus and fetus, while sympathetic activation triggers ineffective contractions and inhibits uterine circulation [5]. Surroundings perceived as safe, familiar and friendly (e.g. a woman's own home) and a supportive environment (e.g. one to one nursing care) are likely to increase oxytocin release by parasympathetic stimulation

and facilitate the progression of labour, as well as lead to the beneficial central actions caused by oxytocin.

#### **1.1 Induction of labour with oxytocin**

Induction of labour (IOL) with oxytocin is the artificial initiation of uterine contractions which leads to progressive effacement and dilatation of the uterine cervix, and descent of the fetus. While IOL with oxytocin alone is indicated in women with ruptured membranes, it is not recommended in women with intact membranes [6]. The objective of this intervention is to give the minimum effective dose until optimal myometrial contractions are achieved. Oxytocin can be added to normal saline for infusion, but large volumes of oxytocin infusion must not be administered due to the risk of hyponatremia. Oxytocin infusion has a half-life of 30 minutes, and by 40 minutes achieves steady-state levels. Therefore, oxytocin dose is increased at intervals of about 40 minutes [7]. There is no evidence to show whether a low-dose or a shigh-dose oxytocin regimens are optimal, and this compounds the confusion in clinical practice [5].

Oxytocin has very variable effects in terms of uterine contractions and fetal hypoxia in different subjects, which results in unpredictability of response in clinical setting. During increments, a close monitoring of labour progress becomes essential, anticipating that adverse effects of oxytocin on uterine activity and the fetus are exclusively dose-related [5]. The attention must be on uterine contractions and the fetus rather than the dosage of oxytocin.

Synthetic oxytocin is frequently used for IOL [5]. But its use has not been standardised and reported to be used improperly. Desirable effects on the brain that are demonstrated with physiologic oxytocin are absent with exogenous oxytocin infusions. It is advised that a protocol and algorithms with oxytocin, needs to be followed [5]. It is recommended by various authors to have an interval of 40 minutes between increments while observing the uterine contractions and the fetus closely. The use of oxytocin needs continuous supervision [5].

#### **1.2 Oxytocics (also known as uterotonics)**

These are agents that stimulate the myometrium or promote uterine contractions and hence increase the tone of the uterus. Uterotonics are used to induce or augment labour to stimulate delivery of the placenta and to prevent or treat PPH. Common uterotonic agents are synthetic oxytocin, synthetic oxytocin analogue carbetocin, methylergometrine, carboprost and misoprostol.

### **1.3 Postpartum haemorrhage**

PPH is the leading cause of maternal morbidity and mortality globally, with atony of the uterus responsible for up to 80% of cases, thereby being the single most common cause [8, 9]. As is clear from **Figure 1**, retraction of uterine muscle fibres clamps the blood vessels and helps to stop bleeding postpartum. Therefore, uterine atony will result in clinical PPH. **Figure 2** shows why it is normal to expect bleeding postpartum, as placental site has a large surface area with cut blood vessels.

Conventionally, PPH is defined as blood loss of at least 500 ml after vaginal delivery and blood loss of >1000 ml after Caesarean section [10]. The American College of Obstetricians and Gynaecologists (ACOG) revitalise initiative defined PPH as cumulative blood loss of >1000 ml (irrespective of the route of delivery) or *Oxytocin and Its Congeners in Obstetrics Practice: An Update on Carbetocin DOI: http://dx.doi.org/10.5772/intechopen.112223*

#### **Figure 1.**

*Uterine contractions are essential to control bleeding after childbirth.*

**Figure 2.**

*Placental separation results in large wound that bleeds after childbirth.*

blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after the birth process.

It contributes greatly to significant maternal morbidity, long-term disability, and many other severe maternal conditions, which involve significant blood loss. These include anaemia, cardiac failure, and sepsis.

Carbetocin is a drug that precludes for additional uterotonic drugs in women at increased risk of PPH. Better trials are underway to evaluate carbetocin in preventing PPH in high-risk women [11].

#### **1.4 Therapies for PPH**

Oxytocin is the current standard drug for the prevention of PPH. Oxytocin availability in developing nations is limited by the requirement for temperature-regulated storage and administration by skilled nursing staff [12]. PPH prophylaxis with oxytocin fails commonly, necessitating the use of further oxytocin or other treatments to maintain stability [13]. The efficacy of uterotonics in causing uterine contractions

#### **Figure 3.**

*Classification of uterotonic drugs.*

to prevent haemorrhage can be impaired by improper storage. Where access to sustained cold-chain is unavailable, the efficacy of oxytocin cannot be ascertained as it is susceptible to heat [14, 15]. Being a short half-life drug, a continuous IV infusion is necessary for a sustained uterotonic effect. Boluses of oxytocin are associated with adverse effects like hypotension, nausea, vomiting, dysrhythmias, ST-T changes, pulmonary oedema and severe water intoxication with convulsions. Miscellaneous uterotonics include ergometrine/methylergometrine, and misoprostol. Ergometrine degrades on exposure to heat or light. Misoprostol degrades rapidly when exposed to moisture [16]. When degraded, the level of active ingredient is reduced, resulting in a loss of efficacy. The classication of uterotonic drugs is given in **Figure 3**.
