tocolytic therapy has been adopted for prevention of preterm labor. is this true: which tocolytic should we use?

1. Tocolytic Therapy
for preterm labor
Atosiban vs Nifedipine: meta-
analysis

2. The perfect tocolytic
 is uniformly effective with complete
fetomaternal safety does not exist

3. Types
 beta-agonists,
 Ca(2+) channel blockers
 oxytocin receptor antagonists.
 differ in cost, utero-specificity, safety,
efficacy

4. Tocolytic agents
 ß-agonist
 ß2-receptor: uterus, blood vessels,
bronchioles
 Stimulate receptoren -> adenyl
cyclase -> ↑ cAMP -> ↓ calcium
 Most important: ritodrine

5. Side Effects : Maternal

6. Side Effects: Fetal

7. RCOG, 2002
 If tocolysis is indicated, B2-agonist
should not be used
 Choice should be either CCB or
Atosiban

8. CCB: Nifdipine (Adalat )
 Effective
 SE: Hypotension & tachycardia
especially multiple pregnancy

9. Tractocile® : uterospecific
 Introduced in
Europe in 2000
 Atosiban =
structure similar to
oxytocine -> inhibit
uterus contractions

10. Tractocile®

11. Tractocile vs Nifedipine
 Both drugs are effective but maternal
adverse events are more with
Nifedipine (Al-Omari et al, 2006)

12. In another RCT
 Atosiban was effective in 75% of the cases,
and nifedipin in 65% of the cases, for
delaying delivery for more than 7 days.
 The maternal side effects in the atosiban
group were 17.5%, and in the nifedipin
group they were 40%, which had a
statistically significant difference (p=0.027).
(Kanashian et al, 2005)

13. How to use

14.  Injection
 Not longer than 48 hour infusion
 Total dose: < 330 mg atosiban

15. Interesting
 Both B2 agonists and Atosiban are
registered in Europe for management
of preterm labor
 Nifedipine: no

16. Objective of Meta-analysis
 to determine the comparative clinical
value of atosiban versus nifedipine in
women in preterm labor by evaluating
both, their comparative effectiveness
and safety profiles

17. Methodology: Meta-analysis
 Randomised controlled trials
 according to the guidelines of the
Cochrane handbook for systematic
reviews of interventions (version
5.0.1)

18. Outcomes
 Prolongation of pregnancy
 prevention of preterm labor
 maternal and fetal side effects and
infant morbidity and mortality

23. safety in favor of atosiban:
 there were lower incidence of adverse
drug reactions, flushing, GIT upset,
hypotension, palpitation, and
tachycardia in women prescribed
atosiban, with the exception of
nausea, which was more frequent in
such women

24. So
 The balance of evidence indicates
that atosiban is as effective as
nifedipine and is significantly safer
than it

25. However
We have two major problems:
 Cost
 Real value

26. Cost
 Atosiban is extremely expensive
compared to Nifidipine
 This is a major limiting issue in the
use of Atosiban

27. Sustained Tocolysis? Nifidipine
could be better choice
 406 women with threatened preterm
birth randomised to an additional 12
days of nifedipine or placebo after
completion of a 48-hour initial course of
tocolysis.
 The probability of adverse perinatal
outcomes was similar between groups,
as were mean gestational age and birth
weight and likelihood of neonatal
intensive care unit admission .

28. Moreover
 Among participants still using
Nifedipine at the time of delivery,
mean blood loss was higher in those
women assigned to nifedipine (432
mL vs. 307 mL; P=0.045). Journal Watch
Women's Health January 17, 2013

29. Why tocolysis?
 To allow for a course of corticosteroids
 To allow for in utero transfer (women
go to tertiary center)

30. Questioning Tocolysis!!!!
 Patient oriented outcome: neonatal
mortality ????

31. What a surprise!!!
 No clear evidence was found for the
relative effectiveness of any tocolytic
versus placebo being beneficial for
neonatal mortality

32. Fig Compared to Placebo
Haas D M et al. BMJ 2012;345:bmj.e6226
©2012 by British Medical Journal Publishing Group

33. No evidence !!
 No evidence of beneficial effect does
not mean Evidence of no value
 No evidence could be due to small
number of patients (type II error), or
heteregeneity of studies, or different
entry point at time of study

34. What to do now??
 we have become accustomed to the
fact that tocolytics buy us time.
 The question is : Does it Worth?

35. To get an answer
 is a large scale multi-centred
randomised non-blinded trial,
analysed by intention to treat.

36. Till then
 Tocolysis will continue
 So use the most cost effective
modality : CCB

37. Thank You