Royal College of Obstetricians and Gynaecologists Setting standards to improve women’s health Risk Management and Medico-Legal Issues In Women’s Health Joint RCOG/ENTER Meeting Please turn off all mobile phones and pagers

Abstract Presentation Risk Management Conference April 2008 A DOUBLE BLIND RANDOMISED CONTROLLED TRIAL COMPARING THE EFFICACY OF INTRAMUSCULAR SYNTOMETRINE AND INTRAVENOUS SYNTOCINON, IN PREVENTING POST PARTUM HAEMORRHAGE Mohammed Rashid, Medical Student, Imperial College Dr Mumtaz, Consultant O&G, James Paget Hospital, Norfolk

Introduction Post partum haemorrhage (PPH) remains the leading cause of maternal death in the developing world, accounting for 25-33% of all maternal deaths 1 The most common cause of PPH is uterine atony 2 Prevention of PPH is of great importance in the pursuit of improved health care for women, even more so in developing countries where parity, and therefore the risk of uterine atony, is higher

Existing Knowledge Routine prophylactic administration of an oxytocic during the third stage of labour reduces the risk of PPH by 40% 3 In the UK and Ireland, intramuscular syntometrine is most commonly used, while in the rest of Europe, the USA and Canada, syntocinon is most commonly used 4 But which is better? This study is the first randomised controlled trial comparing intramuscular syntometrine and intravenous syntocinon in a population group that included high risk women.

Method Study done in a high risk population in the Gulf Patients who were seen in the obstetric clinic at 36 weeks of gestation were invited to participate in the trial Strict inclusion/exclusion criteria 686 patients were randomly allocated to receive either one vial of intramuscular syntometrine or 10 units of intravenous syntocinon Each patient received their allocated drug with the delivery of the anterior shoulder of the baby

Outcome measures The primary outcome measure was the amount of blood loss during delivery Secondary outcome measures included other indicators of blood loss and possible side effects

Quick look at demographics 340 women received intramuscular syntometrine and 346 women received intravenous syntocinon 37% of maternities were para four or above, 27% were para five or above, 16% were para six or above and the highest parity was thirteen.

Results Syntometrine n = 340 Syntocinon n = 346 Size of estimated difference* 95% CI Average Blood loss during delivery (ml) (135.86) (124.03)2.68(-16.82,22.17) p = Postpartum haemorrhages (> 500 ml) 8 (2.35)9 (2.60)0.90(0.35,2.32) p = Post partum haemorrhages (> 1000 ml) 6 (1.76)8 (2.31)0.76(0.27,2.18) p = * The size of the estimated difference is the difference in means for the continuous outcomes and the relative risk for the binary outcomes Primary outcome measure

Results Secondary outcome measures There was an increase in the incidence of having a diastolic blood pressure of between 90 and 100, thirty minutes after the delivery (p=0.004), with intramuscular syntometrine

Discussion In higher parity women, the myometrium is gradually replaced by more and more fibrous tissue. Syntocinon contracts the myometrium, but has little effect on fibrous tissue thus theoretically making it less effective in such women, however this was not supported by our study The superior effect of intravenous syntocinon compared its intramuscular counterpart may be related to the earlier onset of action expected when using an intravenous administration

Discussion continued The increased incidence of having diastolic hypertension was demonstrated (>90 mm Hg thirty minutes after delivery) in the syntometrine group, was supported by findings in other studies 5,6 and is thought to be due to the vasoconstriction effect of syntometrine

Strengths and Weaknesses +The researchers, the patients and the midwives were blinded +Midwives were carefully instructed on how to properly measure blood loss +Every measurement was repeated -Visual estimation of blood loss is known to be inaccurate

Conclusion Intramuscular syntometrine and intravenous syntocinon are equally effective in preventing postpartum haemorrhage, in a high risk population. There is an increased risk of diastolic hypertension after the delivery with intramuscular syntometrine.

References 1.Duffy S. Global perspective Obstetric haemorrhage in Gimbie, Ethiopia. TOG 2007;9: Lewis, G. The Confidential Enquiry into Maternal and Child Health (CEMACH) ‘Saving mother’s lives: Reviewing maternal deaths to make motherhood safer’ The seventh report on Confidential Enquiry into Maternal Deaths in the United Kingdom. 2007, London. CEMACH. 3.Prendiville WJ, Elbourne D, McDonald S. Active versus expectant management in the third stage of labour. Cochrane Database Syst Rev 2003:CD Winter C, Macfarlane A, Deneux-Tharaux C, Zhang WH, Alexander S, Brocklehurst P, Bouvier-Colle MH, Prendiville W, Cararach V, van Roosmalen J, Berbik I, Klein M, Ayres- de-Campos D, Erkkola R, Chiechi LM, Langhoff-Roos J, Stray-Pedersen B, Troeger C. Variations in policies for management of the third stage of labour and the immediate management of postpartum haemorrhage in Europe. BJOG 2007;114(7) : Choy CMY, Lau WC, Tam WH, Yuen PM. A Randomised controlled trial of intramuscular syntometrine and intravenous oxytocin in the management of the third stage of labour. BJOG 2002;109 (2): Khan G Q, John I S, Chan T, Wani S, Hughes A O, Stirrat G M. Abu Dhabi third stage trial: oxytocin versus Syntometrine in the active management of the third stage of labour. Eur J Obstet Gynecol Reprod Biol 1995; 58(2):

Questions & Answers Thank you for listening

Flowchart

Recruitment Statistics Total number of deliveries in the hospital 6950 Number of women delivered within the trial 686 Number of women delivered not in the trial 5095 Number not fulfilling the criteria 2021 Number who refused870 Language barrier2104

Characteristics of the study population Syntometrine n = 340 Syntocinon n = 346 Age in years29.43 (5.64)29.17 (6.41) Gestation at delivery (weeks)39.25 (1.14)39.43 (1.08) Nulliparity56 (16.47)59 (17.05) Average parity3.03 (2.40)3.03 (2.47) Parity of 4 or more91 (26.77)97 (28.52) Previous Caesarean Section (1 missing)28 (8.26)30 (8.67) Previous manual removal of placenta7 (2.06)7 (2.02) Spontaneous onset of labour280 (82.35)296 (85.55) Augmentation with Syntocinon198 (58.24)189 (54.62) Spontaneous vaginal delivery319 (93.82)322 (93.06) Episiotomy39 (11.47)47 (13.58) Genital tract trauma189 (55.59)192 (55.49) Instumental Delivery319 (93.82)322 (93.06) Birthweight (g) (445.33) (442.25) Values are shown as mean (standard deviation) or n (%)

Primary outcome measures Syntometrine n = 340 Syntocinon n = 346 Size of estimated difference* 95% CI Average Blood loss during delivery (ml) (135.86) (124.03)2.68(-16.82,22.17) p = Postpartum haemorrhages (> 500 ml) 8 (2.35)9 (2.60)0.90(0.35,2.32) p = Post partum haemorrhages (> 1000 ml) 6 (1.76)8 (2.31)0.76(0.27,2.18) p = * The size of the estimated difference is the difference in means for the continuous outcomes and the relative risk for the binary outcomes

Sub-group analysis of blood loss during delivery by parity Syntometrine n = 340 Syntocinon n = 346 Parityp = – (160.74) (112.72)p = (118.57) (126.78) p = > (109.99) (137.24) p =

Other indicators of blood loss Syntometrine n = 340 Syntocinon n = 346 Relative risk95% CI Duration of third stage 5.90 (4.75)6.14 (8.24)-0.24(-0.78,1.24) p = Prolonged third stage (greater than 30 minutes) 4 (1.18)3 (0.87)1.36(0.31,6.02) p = Repeated syntocinon 35 (10.29)34 (9.83)1.05(0.67,1.64) p = Post delivery haemoglobin (1.32)10.86 (1.38)-0.01(-0.21,0.20) p = Blood transfusion needed 6 (1.76)2 (0.58)3.05(0.62, 15.02) p = Secondary PPH

Blood pressure Syntometrine n = 340 Syntocinon n = 346 Relative risk95% CI Immediately after delivery SBP > (7.06)30 (8.67)0.81 (0.49,1.36) p = SBP > 1502 (0.59)4 (1.16)0.51 (0.09,2.76) p = DBP > 907 (2.06)10 (2.89)0.71 (0.27,1.85) p = DBP > minutes after delivery SBP > 1409 (2.65)12 (3.47)0.76 (0.33,1.79) p = SBP > 1504 (1.18)3 (0.87)1.36 (0.31,6.02) p =0.687 DBP > 9015 (4.41)3 (0.87)5.09 (1.49,17.42) p = DBP >

Other side effects Syntometrine n = 340 Syntocinon n = 346 Relative risk95% CI Headache2 (0.59)2 (0.58)1.02 (0.14, 7.18) p = Nausea12 (3.53)10 (2.89)1.22 (0.53,2.79) p = Vomiting4 (1.18)1 (0.29)4.07 (0.46,36.23(p = Chest pain2 (0.59)3 (0.87)0.68 (0.11,4.03) p = Shortness of breath 00-- Manual removal of placenta 01 (0.29)-p = 1.000

Royal College of Obstetricians and Gynaecologists Setting standards to improve women’s health Risk Management and Medico-Legal Issues In Women’s Health Joint RCOG/ENTER Meeting Please turn off all mobile phones and pagers