1. Uterotonic drugs used for active management of the third stage of labor (AMTSL) Name of presenter Prevention of Postpartum Hemorrhage Initiative (POPPHI) Project
Adapted from JHPIEGO. Active Management of the Third Stage of Labor: Advances in Maternal and Neonatal Health. Available at: Accessed March 12, 2008.

2. By end of the session, participants will be able to:
Session Objectives
By end of the session, participants will be able to:
Identify Uterotonic Drugs used for AMTSL
Advantages and disadvantages
Stability in Tropical Climates
Describe aspects related to
Selection
Storage
Use and dosage

3. Uterotonic drugs used for AMTSL
Oxytocin- posterior pituitary extract
Ergometrine- preparation of ergot
Syntometrine- combination of oxytocin and ergometrine
Misoprostol- prostaglandin E1 analogue
Misoprostol holds promise for use as an uterotonic. It is effective, practical and inexpensive. In contrast to the other three uterotonics, misoprostol is stable (heat, light) and does not have to be given by injection. It can be given orally or rectally.

4. Oxytocin Advantages Acts within 2.5 minutes when given IM
Generally does not cause side effects
Does not have any contraindications for postpartum use
Is more stable than ergometrine when exposed to heat and light
Disadvantages
More expensive than ergometrine
IM or IV preparations only
Not heat stable
Dosage for AMTSL
10 IU IM or 5 IU IV slow push

5. Ergometrine Advantages Low price Effect lasts 2–4 hours Disadvantages
Takes 6–7 minutes to become effective when given IM; oral form insufficiently effective
Causes tonic uterine contraction
Increased risk of hypertension, vomiting, headache
Contraindicated in women with hypertension or heart disease
Not stable when exposed to heat, light, or freezing
Dosage for AMTSL
0.2 mg IM

6. Oxytocin vs Ergometrine
Results of trials do not show a difference in outcomes related to blood loss and transfusion between lower doses of oxytocin and the recommended dose of ergometrine
A lower rate of manual removal of placenta was seen in women treated with oxytocin
Ergometrine is associated with more adverse effects, especially with regard to causing high blood pressure

7. Recommendation: Oxytocin vs Ergometrine
In the context of active management of the third stage of labor, if all injectable uterotonic drugs are available:
Skilled attendants should offer oxytocin to all women for prevention of PPH in preference to ergometrine/methylergometrine to women without hypertension or heart disease for prevention of PPH.

8. Uterotonic Drugs: Syntometrine
Advantages
Combined effect of rapid action of oxytocin and sustained action of ergometrine
Disadvantages
More expensive than oxytocin or ergometrine alone
Same disadvantages as ergometrine:
Causes tonic uterine contraction
Increased risk of hypertension, vomiting, headache
Contraindicated in women with hypertension or heart disease
Not stable when exposed to heat, light, or freezing
Dosage for AMTSL
1 mL IM (ergometrine 0.5 mg + oxytocin 5 IU)

9. Oxytocin vs. Syntometrine: Results
Syntometrine was associated with a small reduction in risk of PPH < 1000 mL (OR 0.74, 95% CI )
Adverse effects of vomiting and hypertension were associated with the use of syntometrine
There were no differences in other maternal or neonatal outcomes
Conclusion
Need to weigh benefit of reduction in risk of PPH with risk of other adverse effects associated with syntometrine
McDonald, Prendiville and Elbourne 2000.

10. Recommendation: Oxytocin vs Syntometrine
In the context of active management of the third stage of labor, if all injectable uterotonic drugs are available:
Skilled attendants should offer oxytocin to all women for prevention of PPH in preference to the fixed drug combination of oxytocin and ergometrine to women without hypertension or heart disease for prevention of PPH.

11. Uterotonic Drugs: Misoprostol
Advantages
Effect lasts 75 minutes
Can be stored at room temperature but should be protected from humidity
Does not require injection skill or infection prevention measures required for giving an injection
Can be distributed at the community level
Disadvantages
Acts within 6 minutes.
Common side effects: shivering and elevated temperature
Dosage for AMTSL
600 mcg po

12. Oxytocin vs. Misoprostol: Conclusion
Oral misoprostol is not as effective as oxytocin when used for prevention of PPH
HOWEVER
Oral misoprostol:
is easy to administer
has no known contraindications for use in the postpartum
can be stored easily at room temperature (it is thermostable and light stable)
does not require specific conditions for transfer
has a shelf life of several years

13. Oxytocin vs. Misoprostol: Recommendations
In the context of active management of the third stage of labor:
Skilled attendants should offer oxytocin for prevention of PPH in preference to oral misoprostol (600 mcg).
In situations where oxytocin is not available or birth attendants’ skills are limited:
administer misoprostol 600 mcg by mouth soon after the birth of the baby to reduce the occurrence of hemorrhage
In the absence of active management of the third stage of labor, a uterotonic drug (oxytocin or misoprostol) should be offered by a health worker trained in its use for prevention of PPH.

14. Nipple Stimulation
Nipple stimulation has not been shown to reduce risk of PPH
Randomized controlled trial of suckling immediately after birth with over 4,000 subjects in Malawi showed no significant difference in frequency of PPH, mean blood loss or retained placenta
Advantages of early breastfeeding and nipple stimulation:
Stimulates natural production of oxytocin
May maintain tone of contracted uterus
Benefits baby
Conclusions:
When uterotonics are not available, use nipple stimulation and perform fundal massage after delivery of the placenta
When uterotonics are not available, CCT should NOT be performed even with nipple stimulation
Need uterotonics; efforts should be made to make it available at all levels of care.
Getting the uterus to contract probably requires some “surge” of oxytocin, such as that delivered by an injection of oxytocin. When uterotonics are not available, CCT and fundal massage should be performed.
Natural oxytocin produced by suckling of baby at breast may be useful for helping to maintain the tone of an already contracted uterus.
Bullough, Msuku and Karonde 1989.

15. Stability of Injectable Uterotonics in Tropical Climates: Objective and Design
To determine pattern of stability in long term dark storage, short term exposure to high temperature and light
To develop guidelines
Methods: Tested field samples of ergometrine and methylergometrine and also simulated field storage conditions at different temperature/light exposure
WHO 1993.

16. Stability of Injectable Uterotonics in Tropical Climates: Results
Field:
Ergometrine: only 31% of samples had compliant level of active ingredient
Oxytocin: one expired, 5 samples had 104–142% of stated amount of active ingredient
WHO 1993.

17. Stability of Injectable Uterotonics in Tropical Climates: Results (continued)
Simulation condition
Ergometrine/
methylergometrine
Oxytocin
Refrigeration for 12 months
Lost 4-5% active ingredient
No loss
30oC, dark
Lost 25%
Lost 14%
21–25oC, light
Lost 21–27% in one month
>90% in 12 months
Lost 5%
40oC dark
Lost > 50%
Lost 80%
WHO 1993.

18. Stability of Injectable uterotonics in Tropical Climates: Conclusions
Stability of oxytocin is better than ergometrine/ methylergometrine, especially regarding light
Carefully read the manufacturer’s recommendations for storage of injectable uterotonics – where possible, store uterotonics in refrigerator (2–8ºC) and away from light
Remove injectable uterotonics from box only for immediate use
Short periods unrefrigerated are fine (1 month at 30°C)
uterotonics are not heat stable, but oxytocin is better than ergometrine/methyl-ergometrine.
WHO 1993.

19. Storage of uterotonic drugs - In the Pharmacy
Make sure that there are adequate stocks of uterotonic drugs, syringes, and injection safety materials
Check manufacturer’s label for storage recommendations
Follow the rule of first expired – first out (or first in – first out) to reduce wastage of uterotonic drugs
If possible, keep injectable uterotonics refrigerated at 2–8°C
Store misoprostol at room temperature and away from excess heat and moisture
Protect ergometrine and syntometrine from freezing and light.
Make sure that there is a system in place to monitor the temperature of the refrigerator / cold box

20. Storage of uterotonic drugs In Delivery Rooms
Check manufacturer’s label for storage recommendations
Periodically remove ample amount of injectable uterotonics needed for expected client load from refrigerator
Avoid storage of injectable uterotonics in open kidney dishes, trays, or coat pockets
Store oxytocin outside the refrigerator at a maximum of 30°C (warm, ambient climate) for up to three months
Store misoprostol at room temperature away from excess heat and moisture
Store ergometrine and syntometrine vials outside the refrigerator in closed boxes and protected from the light for up to one month at 30°C

21. Recommendations Concerning Selection of Uterotonic for AMTSL
Oxytocin is the uterotonic of choice for AMTSL
If oxytocin is not available, use syntometrine or ergometrine
If injectable uterotonic drugs are not available, use misoprostol 600 mcg by mouth
Remember: Do not use ergometrine or syntometrine in women with hypertension or heart disease

22. Recommendations concerning management of the third stage of labor in the absence of an SBA
In situations where birth attendants’ skills are limited:
administer misoprostol 600 mcg by mouth soon after the birth of the baby to reduce the occurrence of hemorrhage
use nipple stimulation
do not perform CCT
perform uterine massage after delivery of the placenta

23. Summary Oxytocin is the uterotonic of choice for AMTSL
If oxytocin is not available, give ergometrine or syntometrine for AMTSL
If injectable uterotonics are not available, give oral misoprostol for AMTSL
If birth is not attended by an SBA, give oral misoprostol soon after birth of the baby to reduce PPH
Ensure the adequate storage and supply of uterotonic drugs

24. References
Bamigboye A et al Randomized comparison of rectal misoprostol with syntometrine for management of third stage of labor. Acta Obstet Gynecol Scand 77: 178–181.
Bullough CH, RS Msuku and I Karonde Early suckling and postpartum haemorrhage: Controlled trial in deliveries by traditional birth attendants. Lancet 2(8662): 522–525.
Carpenter JP. Misoprostol for Prevention of Postpartum Hemorrhage: An Evidence-Based Review by the US Pharmacopeia, Rockville, Maryland: United States Pharmacopeia, 2001.
International Confederation of Midwives (ICM), International Federation of Gynaecology and Obstetrics (FIGO). Prevention and Treatment of Post-partum Haemorrhage: New Advances for Low Resource Settings Joint Statement. The Hague: ICM; London: FIGO; Available at: Accessed April 2, 2007.

25. References (continued)
Irons DW, P Sriskandabalan and CHW Bullough A simple alternative to parenteral uterotonics for the third stage of labor. Int J Obstet Gynecol 46:15–18.
McDonald S, W Prendiville and D Elbourne Prophylactic syntometrine versus oxytocin for delivery of the placenta (Cochrane Review), in The Cochrane Library. Issue 4. Update Software: Oxford.
McDonald et al Randomized controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labor. BMJ 307(6913):1167–1171.
World Health Organization (WHO) Stability of injectable uterotonics in tropical climates: Results of field surveys and simulation studies on ergometrine, methylergometrine, and oxytocin. WHO: Geneva.