Treatment for primary postpartum haemorrhage
Hatem A Mousa, Jennifer Blum, Ghada Abou El Senoun, Haleema Shakur, Zarko Alfirevic, Hatem A Mousa, Jennifer Blum, Ghada Abou El Senoun, Haleema Shakur, Zarko Alfirevic
Abstract
Background: Primary postpartum haemorrhage (PPH) is one of the top five causes of maternal mortality in both developed and developing countries.
Objectives: To assess the effectiveness and safety of any intervention used for the treatment of primary PPH.
Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013).
Selection criteria: Randomised controlled trials comparing any interventions for the treatment of primary PPH.
Data collection and analysis: We assessed studies for eligibility and quality and extracted data independently. We contacted authors of the included studies to request more information.
Main results: Ten randomised clinical trials (RCTs) with a total of 4052 participants fulfilled our inclusion criteria and were included in this review.Four RCTs (1881 participants) compared misoprostol with placebo given in addition to conventional uterotonics. Adjunctive use of misoprostol (in the dose of 600 to 1000 mcg) with simultaneous administration of additional uterotonics did not provide additional benefit for our primary outcomes including maternal mortality (risk ratio (RR) 6.16, 95% confidence interval (CI) 0.75 to 50.85), serious maternal morbidity (RR 0.34, 95% CI 0.01 to 8.31), admission to intensive care (RR 0.79, 95% CI 0.30 to 2.11) or hysterectomy (RR 0.93, 95% CI 0.16 to 5.41). Two RCTs (1787 participants) compared 800 mcg sublingual misoprostol versus oxytocin infusion as primary PPH treatment; one trial included women who had received prophylactic uterotonics, and the other did not. Primary outcomes did not differ between the two groups, although women given sublingual misoprostol were more likely to have additional blood loss of at least 1000 mL (RR 2.65, 95% CI 1.04 to 6.75). Misoprostol was associated with a significant increase in vomiting and shivering.Two trials attempted to test the effectiveness of estrogen and tranexamic acid, respectively, but were too small for any meaningful comparisons of pre-specified outcomes.One study compared lower segment compression but was too small to assess impact on primary outcomes.We did not identify any trials evaluating surgical techniques or radiological interventions for women with primary PPH unresponsive to uterotonics and/or haemostatics.
Authors' conclusions: Clinical trials included in the current review were not adequately powered to assess impact on the primary outcome measures. Compared with misoprostol, oxytocin infusion is more effective and causes fewer side effects when used as first-line therapy for the treatment of primary PPH. When used after prophylactic uterotonics, misoprostol and oxytocin infusion worked similarly. The review suggests that among women who received oxytocin for the treatment of primary PPH, adjunctive use of misoprostol confers no added benefit.The role of tranexamic acid and compression methods requires further evaluation. Furthermore, future studies should focus on the best way to treat women who fail to respond to uterotonic therapy.
Conflict of interest statement
Haleema Shakur and Zarko Alfirevic are investigators in the currently ongoing WOMAN trial. Jennifer Blum was a principal investigator in the Blum 2010, Winikoff 2010, Widmer 2010 and Zuberi 2008 trials. Hatem Mousa has received financial support from Novo Nordisk to investigate recombinant activated factor VII (rFVIIa) as a potential treatment for massive postpartum haemorrhage.
Figures
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 1 Maternal death.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 2 Serious maternal morbidity.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 3 Admission to intensive care unit.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 4 Hysterectomy.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 5 Average blood loss after enrolment in millilitres.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 6 Blood loss 500 mL or more after enrolment.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 7 Blood transfusion.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 8 Blood loss 1000 mL or more after enrolment.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 9 Additional uterotonics.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 10 Manual removal of the placenta after enrolment.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 11 Uterine tamponade after enrolment.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 12 Artery ligation (uterine and/or hypogastric arteries) after enrolment.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 13 Arterial embolisation after enrolment.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 14 Uterine compression stitch after enrolment.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 15 Evacuation of retained product of conception.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 16 Any surgical co‐interventions (uterine tamponade, artery ligations, arterial embolisation) excluding hysterectomy after enrolment.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 17 Nausea.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 18 Vomiting.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 19 Diarrhoea.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 20 Maternal pyrexia 38 degrees or more.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 21 Maternal pyrexia 40 degrees or more.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 22 Headache.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 23 Shivering.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 24 Feeling faint or fainting.
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 25 Allergy.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 1 Maternal mortality.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 2 Serious maternal morbidity.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 3 Admission to intensive care.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 4 Hysterectomy.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 5 Blood loss 500 mL or more after enrolment.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 6 Mean blood loss after enrolment.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 7 Blood loss 1000 mL or more after enrolment.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 8 Blood transfusion within 24 hours.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 9 Duration from randomisation till cessation of bleeding or satisfactory response.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 10 Additional uterotonics after enrolment.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 11 Examination under anaesthesia.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 12 Uterine tamponade after enrolment.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 13 Bimanual compression.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 14 Artery ligation (uterine and/or hypogastric arteries) after enrolment.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 15 Arterial embolisation after enrolment.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 16 Uterine tamponade after enrolment.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 17 Unsatisfactory response after enrolment after enrolment.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 18 Uterine compression stitch after enrolment.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 19 Any surgical co‐interventions (uterine tamponade, artery ligations, arterial embolisation) excluding hysterectomy after enrolment.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 20 Nausea.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 21 Vomiting.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 22 Diarrhoea.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 23 Headache.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 24 Shivering.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 25 Feeling faint or fainting.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 26 Maternal pyrexia 38 degrees or more.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 27 Maternal pyrexia 40 degrees or more.
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 28 Allergy.
Comparison 3 Rectal misoprostol versus combination of ergometrine and oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 1 Hysterectomy.
Comparison 3 Rectal misoprostol versus combination of ergometrine and oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 2 Persistent haemorrhage.
Comparison 3 Rectal misoprostol versus combination of ergometrine and oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 3 Additional uterotonics.
Comparison 3 Rectal misoprostol versus combination of ergometrine and oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 4 Surgical co‐interventions (excluding hysterectomy).
Comparison 4 Estrogen versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 1 Hysterectomy.
Comparison 4 Estrogen versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 2 Mean blood loss within two hours.
Comparison 4 Estrogen versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 3 Mean blood loss between two and 24 hours.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 1 Maternal mortality.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 2 Serious maternal morbidity (renal failure respiratory failure, cardiac arrest, multiple organ failure).
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 3 Admission to intensive care unit.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 4 Hysterectomy.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 5 Blood loss 500 mL or more after enrolment.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 6 Blood loss 1000 mL or more after enrolment.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 7 Total mean blood loss after enrolment.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 8 Blood transfusion within 24 hours.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 9 Additional uterotonics after enrolment.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 10 Unsatisfactory response after enrolment.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 11 Uterine compression stitch after enrolment.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 12 Interventions to control bleeding for secondary postpartum haemorrhage.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 13 Examination under anaesthesia.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 14 Uterine tamponade after enrolment.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 15 Artery ligation (uterine and/or hypogastric arteries) after enrolment.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 16 Arterial embolisation after enrolment.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 17 Headache.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 18 Nausea.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 19 Maternal pyrexia 38 degrees or more.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 20 Maternal pyrexia 40 degrees or more.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 21 Deep vein thrombosis.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 22 Seizures.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 23 Dizziness.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 24 Phosphenes.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 25 Secondary postpartum haemorrhage.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 26 Surgical evacuation for secondary postpartum haemorrhage.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 27 Intravenous iron therapy in the puerperium.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 28 Hospital re‐admission for secondary postpartum haemorrhage.
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 29 Postnatal depression at day 42 postpartum.
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 1 Maternal mortality.
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 2 Serious maternal morbidity.
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 3 Hysterectomy.
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 4 Blood loss 500 mL or more after enrolment.
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 5 Blood loss 1000 mL or more after enrolment.
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 6 Average blood loss after enrolment.
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 7 Blood transfusion.
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 8 Other surgical interventions to control bleeding (other than hysterectomy).
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 9 Unsatisfactory response after enrolment.
Source: PubMed