Effectiveness of uterotonics at caesarean birth

Caesarean births are one of the most common major surgeries performed on women worldwide. It is therefore noteworthy that postpartum haemorrhage (PPH) is a leading global cause of avoidable maternal mortality with uterine atony the single greatest risk factor. For these reasons the prophylactic administration of an uterotonic is a key step in clinical practice to ensure that adequate uterine tone is maintained to prevent significant bleeding. However, there may be significant variation in uterotonic usage practices which may impact on maternal outcomes. The overall aims of this research were to determine the uterotonic usage practices and the effectiveness of prophylactic low-dose oxytocin protocols at scheduled caesarean birth on PPH outcomes; and to compare the effectiveness of carbetocin with oxytocin on PPH at caesarean birth. In study 1 (Chapter 2) uterotonic usage practices and beliefs (at scheduled caesarean birth) were determined by surveying anaesthetists of Australia and New Zealand (n=900). There was significant variation in oxytocin usage practices among respondents and this variation may be underpinned by a perceived lack of strong evidence to guide practice. This emphasises the need for high quality trials in this clinically important area. In study 2 (Chapter 3) a systematic review was performed comparing the effectiveness of prophylactic low dose oxytocin protocols (less than 5 IU) with 5 IU (delivered as a bolus alone, or bolus plus continuous infusion, or continuous infusion alone) on volume of postpartum blood loss in women undergoing elective caesarean birth. Remarkably, despite an exhaustive search, there were no trials that had investigated the oxytocin regimes under investigation; specifically the effectiveness of prophylactically administering less than 5 IU doses in comparison to British guideline recommended 5 IU on postpartum blood loss. Overall, there was a paucity of evidence for the effectiveness of prophylactic low-dose oxytocin protocols (<5 IU) compared with 5 IU on postpartum blood loss in women undergoing elective caesarean birth. Study 3 (Chapter 4) sought to determine whether low dose oxytocin at 3IU was non-inferior to the British guideline recommended 5IU dosage with respect to 24 hour postpartum blood loss in women undergoing elective caesarean birth. This study found that administration of 3IU oxytocin was non-inferior to British guideline recommended 5IU with respect to blood loss in women undergoing elective caesarean birth. These findings suggest that lowering the oxytocin dose to 3IU may be considered effective for routine clinical use. Study 4 (Chapter 5) examined whether carbetocin is associated with a lower risk of postpartum haemorrhage (blood loss ‚Äöv¢‚Ä¢1000 ml) in comparison to oxytocin for the third stage of labour in a large cohort of women who underwent caesarean births at one of Australia's largest tertiary maternity centres, the Mater Mothers' Hospital, Queensland. The risk of postpartum haemorrhage associated with carbetocin was lower than that associated with oxytocin in women undergoing caesarean birth. There is a need for further high quality trials to confirm these results. In summary, this thesis revealed extensive variation in uterotonic usage practices underpinned by a paucity of evidence from randomised controlled trials, particularly for low dose oxytocin protocols at scheduled caesarean birth. However, some evidence for the routine usage of low-dose oxytocin protocol at scheduled caesarean birth were provided, albeit from an observational study design. Finally, carbetocin was found to be more effective in lowering the risk of major postpartum haemorrhage at caesarean birth. Altogether, these studies substantially advance the understanding of the effectiveness of uterotonics at caesarean birth and highlights that there is a lack of evidence from large, multicentre trials. In the absence of large trials, the signal from a large observational study indicates that carbetocin may be the first-line uterotonic of choice in women undergoing caesarean births.