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Meta-Analysis
. 2018 Jun 7;6(6):CD005456.
doi: 10.1002/14651858.CD005456.pub3.

Prophylactic use of ergot alkaloids in the third stage of labour

Tippawan Liabsuetrakul  1 , Thanapan Choobun, Krantarat Peeyananjarassri, Q Monir Islam
Affiliations
Meta-Analysis

Prophylactic use of ergot alkaloids in the third stage of labour

Tippawan Liabsuetrakul et al. Cochrane Database Syst Rev. .

Abstract

Background: Previous research has shown that the prophylactic use of uterotonic agents in the third stage of labour reduces postpartum blood loss and moderate to severe postpartum haemorrhage (PPH). PPH is defined as a blood loss of 500 mL or more within 24 hours after birth. This is one of a series of systematic reviews assessing the effects of prophylactic use of uterotonic drugs; in this review prophylactic ergot alkaloids as a whole, and different regimens of administration of ergot alkaloids, are compared with no uterotonic agents. This is an update of a Cochrane Review which was first published in 2007 and last updated in 2011.

Objectives: To determine the effectiveness and safety of prophylactic use of ergot alkaloids in the third stage of labour by any route (intravenous (IV), intramuscular (IM), or oral) compared with no uterotonic agents, for the prevention of PPH.

Search methods: For this update, we searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (19 September 2017); we also searched reference lists of retrieved studies.

Selection criteria: We included all randomised controlled trials or cluster-randomised trials comparing prophylactic ergot alkaloids by any route (IV, IM, or oral) with no uterotonic agents in the third stage of labour among women giving birth vaginally.

Data collection and analysis: Two review authors independently assessed trials for inclusion, extracted data and checked them for accuracy; they also assessed the risk of bias in included studies. Two review authors assessed the quality of the evidence using the GRADE approach.

Main results: There were eight included studies: three studies had a low risk of bias and five studies had high risk of bias. The studies compared ergot alkaloids with no uterotonic agents, with a total of 2031 women in the ergot alkaloids group and 1978 women in the placebo or no treatment group. Seven studies used the IV/IM route of administration and one study used the oral route.Ergot alkaloids (any route of administration) versus no uterotonic agentsUse of ergot alkaloids in the third stage of labour decreased mean blood loss (mean difference (MD) -80.52 mL, 95% confidence interval (CI) -96.39 to -64.65 mL; women = 2718; studies = 3; moderate-quality evidence); decreased PPH of at least 500 mL (average risk ratio (RR) 0.52, 95% CI 0.28 to 0.94; women = 3708; studies = 5; I2 = 83%; low-quality evidence); increased maternal haemoglobin concentration (g/dL) at 24 to 48 hours postpartum (MD 0.50 g/dL, 95% CI 0.38 to 0.62; women = 1429; studies = 1; moderate-quality evidence); and decreased the use of therapeutic uterotonics (average RR 0.37, 95% CI 0.15 to 0.90; women = 2698; studies = 3; I2 = 89%; low-quality evidence). There were no clear differences between groups in severe PPH of at least 1000 mL (average RR 0.32, 95% CI 0.04 to 2.59; women = 1718; studies = 2; I2 = 74%; very low-quality evidence). The risk of retained placenta or manual removal of the placenta, or both, were inconsistent with high heterogeneity. Ergot alkaloids increased the risk of elevated blood pressure (average RR 2.60, 95% CI 1.03 to 6.57: women = 2559; studies = 3; low-quality evidence) and pain after birth requiring analgesia (RR 2.53, 95% CI 1.34 to 4.78: women = 1429; studies = 1; moderate-quality evidence) but there were no differences between groups in vomiting, nausea, headache or eclamptic fit.Results for IV/IM ergot alkaloids versus no uterotonic agents were similar to those for the main comparison of ergot alkaloids administered by any route, since most of the studies (seven of eight) used the IV/IM route. Only one small study (289 women) compared oral ergometrine with placebo and it showed no benefit of ergometrine over placebo. No maternal adverse effects were reported.None of the studies reported on any of our prespecified neonatal outcomes AUTHORS' CONCLUSIONS: Prophylactic IM or IV injections of ergot alkaloids may be effective in reducing blood loss, reducing PPH (estimated blood loss of at least 500 mL), and increasing maternal haemoglobin. Ergot alkaloids may also decrease the use of therapeutic uterotonics, but adverse effects may include elevated blood pressure and pain after birth requiring analgesia. There were no differences between groups in terms of other adverse effects (vomiting, nausea, headache or eclamptic fit). There is a lack of evidence on the effects of ergot alkaloids on severe PPH, and retained or manual removal of placenta. There is also a lack of evidence on the oral route of administration of ergot alkaloids.

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Conflict of interest statement

Tippawan Liabsuetrakul: none known.

Thanapan Choobun: none known.

Krantarat Peeyananjarassri: none known.

Q Monir Islam: none known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 1 Mean blood loss (mL).
1.2
1.2. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 2 Estimated or measured blood loss of at least 500 mL.
1.3
1.3. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 3 Estimated or measured blood loss of at least 1000 mL.
1.4
1.4. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 4 Maternal haemoglobin concentration at 24 to 48 hours postpartum (g/dL).
1.5
1.5. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 5 Blood transfusion.
1.6
1.6. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 6 Use of therapeutic uterotonics.
1.7
1.7. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 7 Length of third stage of labour (minutes).
1.8
1.8. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 8 Retained placenta or manual removal of placenta, or both.
1.9
1.9. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 9 Vomiting.
1.10
1.10. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 10 Nausea.
1.11
1.11. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 11 Elevation of blood pressure.
1.12
1.12. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 12 Pain after birth requiring analgesia (not prespecified).
1.13
1.13. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 13 Headache (not prespecified).
1.14
1.14. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 14 Eclamptic fit (not prespecified).
1.15
1.15. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 15 Uterine subinvolution at routine follow up (not prespecified).
1.16
1.16. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 16 Postpartum febrile morbidity (not prespecified).
1.17
1.17. Analysis
Comparison 1 Ergot alkaloids (any route of administration) versus no uterotonic agents, Outcome 17 Postnatal haemoglobin < 10 g/dL (not prespecified).
2.1
2.1. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 1 Mean blood loss (mL).
2.2
2.2. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 2 Estimated or measured blood loss of at least 500 mL.
2.3
2.3. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 3 Estimated or measured blood loss of at least 1000 mL.
2.4
2.4. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 4 Maternal haemoglobin concentration at 24 to 48 hours postpartum (g/dL).
2.5
2.5. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 5 Blood transfusion.
2.6
2.6. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 6 Use of therapeutic uterotonics.
2.7
2.7. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 7 Length of third stage of labour (minutes).
2.8
2.8. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 8 Retained placenta or manual removal of placenta, or both.
2.9
2.9. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 9 Vomiting.
2.10
2.10. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 10 Nausea.
2.11
2.11. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 11 Elevation of blood pressure.
2.12
2.12. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 12 Pain after birth requiring analgesia (not prespecified).
2.13
2.13. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 13 Headache (not prespecified).
2.14
2.14. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 14 Eclamptic fit (not prespecified).
2.15
2.15. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 15 Uterine subinvolution at routine follow up (not prespecified).
2.16
2.16. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 16 Postpartum febrile morbidity (not prespecified).
2.17
2.17. Analysis
Comparison 2 Intravenous/intramuscular ergot alkaloids versus no uterotonic agents, Outcome 17 Postnatal haemoglobin < 10 g/dL (not prespecified).
3.1
3.1. Analysis
Comparison 3 Oral ergot alkaloids versus no uterotonic agents, Outcome 1 Mean blood loss (mL).
3.2
3.2. Analysis
Comparison 3 Oral ergot alkaloids versus no uterotonic agents, Outcome 2 Estimated or measured blood loss of at least 500 mL.
3.3
3.3. Analysis
Comparison 3 Oral ergot alkaloids versus no uterotonic agents, Outcome 3 Estimated or measured blood loss of at least 1000 mL.
3.4
3.4. Analysis
Comparison 3 Oral ergot alkaloids versus no uterotonic agents, Outcome 4 Blood transfusion.
3.5
3.5. Analysis
Comparison 3 Oral ergot alkaloids versus no uterotonic agents, Outcome 5 Use of therapeutic uterotonics.
3.6
3.6. Analysis
Comparison 3 Oral ergot alkaloids versus no uterotonic agents, Outcome 6 Retained placenta or manual removal of placenta, or both.
4.1
4.1. Analysis
Comparison 4 Sensitivity analysis based on trial quality comparing ergot alkaloids (any routes) and no uterotonic agents, Outcome 1 Mean blood loss (mL).
4.2
4.2. Analysis
Comparison 4 Sensitivity analysis based on trial quality comparing ergot alkaloids (any routes) and no uterotonic agents, Outcome 2 Estimated or measured blood loss of at least 500 mL.
4.3
4.3. Analysis
Comparison 4 Sensitivity analysis based on trial quality comparing ergot alkaloids (any routes) and no uterotonic agents, Outcome 3 Length of third stage of labour (minutes).
4.4
4.4. Analysis
Comparison 4 Sensitivity analysis based on trial quality comparing ergot alkaloids (any routes) and no uterotonic agents, Outcome 4 Retained placenta or manual removal of placenta, or both.
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