WHO Recommendations for the Prevention of Postpartum Haemorrhage Results from a WHO Technical Consul

1
WHO Recommendations for the Prevention of
Postpartum HaemorrhageResults from a WHO
Technical Consultation October 18-20,
2006Deborah Armbruster, POPPHI/PATHMini-univers
ity/ POPPHIOctober 5, 2007

2
Summary of Recommendations

• Active management of the third stage of labor
  should be offered by skilled attendants to all
  women.
• In the context of AMTSL Skilled attendants
  should offer oxytocin in preference to
  ergometrine, methylergometrine, Syntometrine,
  misoprostol, Carboprost.
• In the absence of AMTSL, a uterotonic drug
  (oxytocin or misoprostol) should be offered by a
  health worker trained in its use for prevention
  of PPH.
• Because of the benefits to the baby, the cord
  should not be clamped earlier than is necessary
  for applying controlled cord traction in AMTSL.
• For the sake of clarity, it is estimated that
  this will normally take around 3 minutes

3
Background

• While there is general agreement on the
  beneficial effects of AMTSL, there are several
  unresolved issues
• Clear definitions of components
• AMTSL under conditions of limited resources
• Timing of uterotonic
• Drug to use
• Route of administration
• Can non-skilled providers use controlled cord
  traction?

4
Background

• Is early clamping of cord necessary?
• What does early mean?
• Suggestions to provide misoprostol where oxytocin
  not available to non-skilled providers and women
  themselves
• Concerns that misuse of misoprostol can lead to
  significant maternal morbidity and even death

5
Rationale for WHO Technical Consultation

• In light of these issues, WHO held a Technical
  Consultation on PPH in Geneva on 18-20 October
  2006 to
• Discuss various issues related to prevention of
  PPH
• Develop recommendations

6
Methods

• Questions drafted by WHO staff (MPS, RH,
  Medicines, Policies and Standards) on various
  intervention described for prevention of atonic
  PPH (AMTSL and its components)
• Each question was subdivided to address skilled
  or non-skilled provider
• These questions and proposed outcomes to consider
  were sent to international panel of experts (58
  experts in 6 WHO regions 37 responses received)

7
Methods

• Helped define critical outcomes vs. important
  but not critical
• Responses were reviewed by WHO core team
• External organization commissioned to review and
  grade the evidence to answer the questions, using
  the GRADE methodology

8
Methods

• Evidence-based recommendations in response to the
  questions asked were drafted
• Draft methodology, results, and recommendations
  were sent to sub-group of experts prior to their
  participation in the WHO Technical Consultation
  on PPH
• This draft and supporting evidence were reviewed
  at the Technical Consultation and changes made
  based on the recommendations of the expert panel.

9
Grades of Recommendation Assessment, Development
and Evaluation

• Assess the quality of evidence, prepare evidence
  profiles
• Choose questions and rate importance of outcomes
  for decision making (before considering the
  evidence)
• Assess the overall risk-benefit ratio,
  considering cost, access, and feasibility

10
Categories of quality

• High Further research is very unlikely to change
  our confidence in the estimate of effect.
• Moderate Further research is likely to have an
  important impact on our confidence in the
  estimate of effect and may change the estimate.
  
• Low Further research is very likely to have an
  important impact on our confidence in the
  estimate of effect and is likely to change the
  estimate.
• Very low Any estimate of effect is very
  uncertain.

11
Judgements about the balance between benefits and
harms

• Strong recommendation the panel is confident
  that the desirable effects of adherence to a
  recommendation outweigh the undesirable effects.
• Weak recommendation the panel concludes that the
  desirable effects of adherence to a
  recommendation probably outweigh the undesirable
  effects, but is not confident.

12
Critical beneficial outcomes

• What are the most important beneficial or
  priority outcomes of interventions to prevent
  PPH?
• Reduction in maternal mortality
• Less blood loss gt 1000 ml
• Less use of blood transfusion
• Less use of uterotonics (added by the expert
  panel)

13
Evidence and Recommendations
14
1. Should AMTSL be offered by skilled attendants
to all women

• Recommendation
• AMTSL should be offered by skilled attendants to
  all women
• Recommendation STRONG
• Quality of evidence MODERATE
• The panel does not recommend AMTSL by non-skilled
  attendants
• Remarks Although no evidence was found for or
  against the use of AMTSL by non-skilled
  providers, the group placed high value on the
  potential risks such as uterine inversion
  that may result from inappropriate cord traction.

1 systematic review 5 trials UK, Ireland,
UAE Different combinations of the components
15
2. Should oxytocin (10 IU parenterally) or
ergometrine/methylergometrine (0.25 mg
parenterally) be offered in AMTSL?

• Recommendation
• Oxytocin 10 IU IM should be offered to all women
  in preference to ergometrine
• If oxytocin is not available ergo/methylergo or
  syntometrine should be offered to women without
  hypertension and heart disease
• Recommendation STRONG
• Quality of evidence LOW
• Remarks The recommendation places a high value
  on avoiding the adverse effects of ergometrine,
  and assumes similar benefit for oxytocin and
  ergometrine.

2 systematic reviews gt 9,000 women Oxytocin vs.
ergometrine vs. syntometrine Oxytocin dose (2-10
IU), IM/IV Only one trial with direct comparison
(1049 women)
16
3. Should oral misoprostol (600 mcg) be offered
instead of oxytocin (10 IU IM) in AMTSL?

• Recommendation
• In the context of AMTSL skilled attendants should
  offer oxytocin in preference to oral misoprostol
  (600 mcg).
• Recommendation STRONG
• Quality of evidence HIGH
• Remarks This recommendation places a high value
  on the relative benefits of oxytocin in
  preventing blood loss compared to misoprostol, as
  well as the increased adverse effects of
  misoprostol compared to oxytocin

One systematic review 7 trials with direct
comparison Largest trial gt 18,000 women
17
4. Should sublingual misoprostol (600 mcg) be
offered instead of oxytocin (10 IU IM)?

• Recommendation
• In the context of AMTSL skilled attendants should
  not offer sublingual misoprostol for prevention
  of PPH in preference to oxytocin
• Recommendation STRONG
• Quality of evidence VERY LOW
• Remarks Further research is needed to define the
  role of sublingual misoprostol administration for
  prevention of PPH

One systematic review 2 trials lt 200 women 1
trial compared to syntometrine
18
5. Should rectal misoprostol (600 mcg) be
offered instead of oxytocin (10 IU IM)?

• Recommendation
• In the context of AMTSL skilled attendants should
  not offer rectal misoprostol for prevention of
  PPH in preference to oxytocin
• Recommendation STRONG
• Quality of evidence LOW
• Remarks This recommendation places a high value
  on the known benefits of oxytocin and notes the
  significant uncertainty about whether rectal
  misoprostol is equivalent. Misoprostol has more
  adverse effects and a higher purchase cost.

Two systematic reviews Two oxytocin trials (one
with 5 IU the other 10IU, 1221 women in
total) One misoprostol trial (1620 women,
auxiliary nurse-midwives)
19
6. Should carboprost 0.25 mg/sulprostone 0.5 mg)
be offered instead of oxytocin (10 IU IM)?

• Recommendation
• In the context of AMTSL skilled attendants should
  not offer carboprost/sulprostone in preference of
  oxytocin
• Recommendation STRONG
• Quality of evidence VERY LOW
• Remarks This recommendation is based on the
  paucity of evidence comparing the two treatments
  and the known effectiveness of oxytocin.

One systematic review Eight trials comparing
injectable prostaglandins with other injectable
uterotonics No study has compared
carboprost/sulprostone with 10 IU oxytocin IM
20
7. In the absence of AMTSL, should uterotonics
be used alone for prevention of PPH?

• Recommendation
• In the absence of AMTSL, a uterotonic drug
  (oxytocin or misoprostol) should be offered by a
  health worker trained in its use for prevention
  of PPH
• Recommendation STRONG
• Quality of evidence MODERATE
• Remarks For misoprostol, this recommendation
  places a high value on the potential benefits of
  avoiding PPH and ease of administration of an
  oral drug in settings where other care is not
  available, but notes there is only one study.
• The only trial relevant to this recommendation
  used 600 mcg of misoprostol. The efficacy of
  lower doses has not been evaluated. There is
  still uncertainty about the lowest effective dose
  and optimal route of administration.

Two systematic reviews Two oxytocin trials (one
with 5 IU the other 10IU, 1221 women in
total) One misoprostol trial (1620 women,
auxiliary nurse-midwives)
21
8. When should the cord be clamped to maximize
benefits for mother and baby?

• Recommendation
• Because of the benefits to the baby, the cord
  should not be clamped earlier than necessary for
  applying cord traction in AMTSL.
• Recommendation WEAK
• Quality of Evidence LOW
• For the sake of clarity, it is estimated that
  this will normally take around 3 minutes
• Early clamping may be required if the baby is
  asphyxiated and requires immediate resuscitation.

One systematic review three additional
trials varying definitions of early clamping (10
sec 1 min) and delayed (2 min stopping
pulsation) no priority outcomes reported, but
newborn anemia as an important outcome unclear
whether timing of cord clamping has an effect on
PPH
22
9. Should the placenta be delivered by
controlled traction in all women?

• Recommendation
• Given the current evidence for AMTSL includes
  cord traction, the panel does not recommend any
  change in the current practice. Further research
  is needed.
• Recommendation STRONG
• Quality of evidence VERY LOW

23
Key discussion points

• Who is a skilled attendant?
• Discussed extensively in context of components of
  AMTSL
• Combines WHO, FIGO, ICM definition of 2004 with
  earlier definition by WHO, UNFPA, UNICEF and
  World Bank
• Older definition is broader and considers
  variable conditions on many low and middle-income
  developing countries
• Can include auxiliary nurse-midwives, community
  midwives, village midwives and health visitors
  who have acquired appropriate skills, if
  specially trained

24
Key discussion points

• Implementation of recommendations
• Support from international professional
  organizations and partner agencies for changes in
  policy and regulation
• Work through regional and country offices (WHO
  and partners)
• Press release and co-publication
• Misoprostol in EDL for PPH indications
• Translation of recommendations
• Disseminaton and implementation of
  recommendations
• Develop a feedback mechanism
• Develop a virtual PPH network

25
Research Priorities

• Not in priority order
• What dose and route of administration of
  misoprostol are preferred for best risk-benefit
  ratio (in AMTSL and expectant management)
• Can oxytocin be administered safely by unskilled
  attendants?
• What is role of buccal and sublingual use of
  oxytocin?
• What is the effect of uterotonics on breastfeeding

26
Research Priorities

• With AMTSL, should misoprostol be used in
  addition to oxytocin
• What is the optimal time for cord clamping in the
  context of physiologic management and AMTSL?
• What is the optimum time for oxytocin
  administration in AMTSL to optimize the timing of
  cord clamping?
• What is the role of individual components of
  AMTSL?

27
Summary of Recommendations

• Active management of the third stage of labor
  should be offered by skilled attendants to all
  women.
• In the context of AMTSL Skilled attendants
  should offer oxytocin in preference to
  ergometrine, methylergometrine, Syntometrine,
  misoprostol, Carboprost.
• In the absence of AMTSL, a uterotonic drug
  (oxytocin or misoprostol) should be offered by a
  health worker trained in its use for prevention
  of PPH.
• Because of the benefits to the baby, the cord
  should not be clamped earlier than is necessary
  for applying controlled cord traction in AMTSL.
• For the sake of clarity, it is estimated that
  this will normally take around 3 minutes

28
Program Implications and Next Steps

• For you to define but could be
• Educate policy-makers about the need to adopt and
  operationalize these new guidelines
• Increase resources to fund AMTSL training or
  ensure that sufficient oxytocin is available for
  every women at birth.
• Get misoprostol registered in-country and create
  protocols for its use
• Document successes and communicate to the media
  and decision-makers