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 2022-03-23 19:55:59

Carbetocin versus Oxytocin for the Prevention of Postpartum Haemorrhage
P Begum1, DR Saha2, Mahabuba3, L Sanjowal4, MK Hasan5

Abstract:
Postpartum haemorrhage is the leading cause of maternal mortality worldwide. Total 67-80% of cases are caused by uterine atony. Preventive measures include prophylactic drug use to aid uterine contraction after delivery, thus avoiding severe blood loss and reducing maternal morbidity and mortality. Carbetocin is a synthetic analogue of oxytocin with a long half-life which ensure more effective contraction and less adverse effects. It can be administered as a single dose injection either intravenously or intramuscularly rather than as an infusion over several hours as is the
case with oxytocin. Carbetocin is currently indicated for prevention of uterine atony after delivery by caesarean section in spinal or epidural anaesthesia. A reduced need for additional uterotonics was observed with carbetocin vs.oxytocin in high-risk women and carbetocin was at least as effective as syntometrine in low-risk women. Carbetocin is effective treatment for the prevention of postpartum haemorrhage not only following caesarean delivery but also after vaginal delivery in high-risk women and those who suffer from hypertensive disorders in pregnancy. Further research is required to assess whether prophylactic carbetocin is superior to conventional uterotonic agents following vaginal delivery in low-risk women.
Key words: Carbetocin, Postpartum Haemorrhage.
Introduction:
The risk of postpartum haemorrhage is much higher for women undergoing caesarean section1,2. particularly in developing countries where the majority of operations are carried out as an emergency procedure3. Postpartum haemorrhage occurs in up to 15% of vaginal deliveries4and represents the most important cause of maternal morbidity and mortality worldwide5,6. In most cases, uterine atony is responsible for the occurrence of excessive bleeding during or following childbirth7-9.Current strategies for preventing postpartum haemorrhage include the prophylactic use of uterotonic agents to enhance natural uterine contraction and retraction following caesarean section and in the third stage of labour for vaginal delivery9,10. Oxytocin is the most
widely used uterotonic agent, but only has a half-life of 4-10 min9-11. So must be administered as a continuous intravenous infusion to achieve sustained uterotonic activity. Another uterotonic drug frequently used in vaginal deliveries is syntometrine, which contains 5 IU/ml oxytocin and 0.5mg/ml ergometrine12,13.Syntometrine combines the rapid onset of action of oxytocin and the prolonged uterotonic effects of an ergot alkaloid. Intramuscular syntometrine use in active management of the third stage of labour is associated with a significant reduction in the risk of non-severe
postpartum haemorrhage (lt;1000ml of blood loss) compared with intramuscular oxytocin12,13. Although intramuscular syntometrine is equally effective as intravenous oxytocin14, gastrointestinal and cardiovascular side effects such as maternal nausea, vomiting and raised blood pressure 12-14 are more frequent due to stimulation of
smooth muscle contraction and vasoconstriction by ergometrine15,16. Oral and rectal administration of misoprostol, a synthetic analogue of prostaglandin E1, have demonstrated lower efficacy than injectable uterotonic agents in preventing excessive bleeding following vaginal delivery17,18 and are associated with a high incidence of
shivering, fever and a possible risk of severe hyperthermia19,20. These factors deem misoprostol unsuitable for routine prevention of excessive postpartum bleeding in developed countries, despite low cost and ease of use20,21. Although injectable
prostaglandins such as prostaglandin 15-methyl F2a or sulprostone can prevent excessive bleeding following vaginal delivery, safety concerns and cost limit their
suitability for routine use in active management of the third stage of labour. However, they remain useful therapeutic options for postpartum haemorrhage treatment when other interventions prove ineffective21.Recent interest has focused on the prophylactic use of the oxytocin receptor agonist carbetocin22-29. Here we review the most recent clinical data regarding the efficacy of carbetocin in the prevention of postpartum
haemorrhage following caesarean section and vaginal delivery, and provide an update on the safety and tolerability in comparison to conventional uterotonic agents.
Pharmacology:
Carbetocin is a long-acting synthetic analogue of oxytocin30,31 that can be administered as a single-dose injection, either intravenously or intramuscularly32. Intravenously administered carbetocin has a half-life of approximately 40 min, around 4-10 times longer than that reported for oxytocin. Following intramuscular
injection, carbetocin reaches peak plasma concentrations in less than 30 min and has 80% bioavailability32. The effect of various intravenous and intramuscular doses of carbetocin on the postpartum uterus has been evaluated by tocographic recordings of
uterine contractions 24-48h after vaginal delivery at term in 40 women33. A single intravenous bolus of 8-30 µg carbetocin or a single intramuscular injection of 10-70 µg carbetocin produced a tetanic uterine contraction within 2 min of drug administration. Uterine activity persisted for an average of 120 min following
intramuscular injection and an average of 60 min following intravenous injection33. Thus, these data show that carbetocin onset of action is rapid irrespe

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