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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: http://www.reproline.jhu.edu/english/2mnh/2ppts/3rdstage/3rdstagepg.htm.
Accessed March 12, 2008.
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
Uterotonic drugs used for AMTSL
• Oxytocin- posterior pituitary extract
• Ergometrine- preparation of ergot
• Syntometrine- combination of oxytocin and
ergometrine
• Misoprostol- prostaglandin E1 analogue
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
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
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
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.
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)
Oxytocin vs. Syntometrine: Results
• Syntometrine was associated with a small reduction in risk of
PPH < 1000 mL (OR 0.74, 95% CI 0.65-0.85)
• 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.
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.
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
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
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.
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
Bullough, Msuku and Karonde 1989.
Stability of Injectable Uterotonics in
Tropical Climates: Objective and Design
• Objective:
• 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.
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.
Stability of Injectable Uterotonics in
Tropical Climates: Results (continued)
Simulation
condition
Refrigeration
for 12 months
30oC, dark
21–25oC, light
40oC dark
WHO 1993.
Ergometrine/
methylergometrine
Lost 4-5% active
ingredient
Lost 25%
Lost 21–27% in one
month
>90% in 12 months
Lost > 50%
Oxytocin
No loss
Lost 14%
Lost 5%
Lost 80%
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)
WHO 1993.
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
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
Recommendations Concerning
Selection of Uterotonic for AMTSL
• Oxytocin is the uterotonic of choice for AMTSL
• If oxytocin is not available, use syntometrine or
ergometrine
Remember: Do not use ergometrine or
syntometrine in women with hypertension or
heart disease
• If injectable uterotonic drugs are not available, use
misoprostol 600 mcg by mouth
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
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
References
Bamigboye A et al. 1998. 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. 1989. 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 Postpartum Haemorrhage: New Advances for Low Resource Settings Joint
Statement. The Hague: ICM; London: FIGO; 2006. Available at:
www.figo.org/docs/PPH%20Joint%20Statement%202%20English.pdf.
Accessed April 2, 2007.
References (continued)
Irons DW, P Sriskandabalan and CHW Bullough. 1994. 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. 2000. Prophylactic syntometrine
versus oxytocin for delivery of the placenta (Cochrane Review), in The
Cochrane Library. Issue 4. Update Software: Oxford.
McDonald et al. 1993. 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). 1993. Stability of injectable uterotonics in
tropical climates: Results of field surveys and simulation studies on
ergometrine, methylergometrine, and oxytocin. WHO: Geneva.