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National Women’s Health Clinical Guideline / Recommended Best Practice
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NIFEDIPINE TOCOLYSIS
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Background
Drug Protocol
Monitoring
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Nifedipine Tocolysis Flowchart
References
Purpose
The purpose of this document is to outline background information and protocol supporting the use
of Nifedipine for women with pre term labour
Scope
Medical and midwifery staff in Women’s Assessment Unit, Labour & Birthing Suite/ Ward 96/98.
Developed by:
Authorised by:
Nifedipine Tocolysis
Clinical Director Maternal Fetal Med
Clinical Director O&G
Classification:
Date Issued:
NMP200/SSM/041
Updated October 2009
Page:
1 of 7
Background
Why Nifedipine?
Spontaneous preterm birth (<37 weeks) occurs in 5% of pregnancies in New Zealand (New
Zealand mothers and babies HFA report), accounting for two thirds of normally formed perinatal
deaths and is the leading cause of admission to neonatal intensive care units (Lockwood et al.
1999).
Preterm labour is multifactorial and can result from a range of pathologies, eg infection, bleeding,
multiple pregnancy. However in many cases there is no clinically obvious cause.
If there is no reason to expedite the delivery and the gestation is <34 weeks, then current
management is to administer a tocolytic drug to delay delivery while corticosteroids are given for
lung maturation. Corticosteroids significantly reduce neonatal morbidity and mortality but take 48
hours to achieve the maximum effect (Liggins et al. 1972). Acute tocolytic treatment should be
discontinued 48 hours after the first dose of steriods as the primary objective of acute tocolysis is
not to prolong gestation, but prevent delivery until the corticosteroids can take effect.
A number of tocolytics have been used for maintenance tocolysis (betamimetics, magnesium
sulphate, prostaglandin synthetase inhibitors and oxytocin antagonists) (Sanchez-Ramos et al.
1999). None of these have been shown to be useful and all have significant side effects.
Furthermore, these agents need to given intravenously (atosiban) or have the potential to cause
maternal (betamimetics, magnesium sulphate) or fetal (indomethacin) side effects.
Nifedipine is a calcium-channel blocker, which is administered orally with very few side effects.
Evidence
Nifedipine has been shown to be more effective for acute tocolysis when compared to the most
commonly used agents- betamimetics (Papatonis et al. 1997). It is the only tocolytic yet described
which has been reported to reduce neonatal morbidity (Papatonis et al. 2000). A recent metaanalysis (Tsatsaris et al. 2001) showed that nifedipine was more effective than betamimetics in
delaying delivery at least 48 hours [OR 1.52, 95% CI 1.03-2.24], and was more likely to prolong
pregnancy beyond 34 weeks [OR 1.87, 95% CI 1.11-3.15]. Treatment with nifedipine was
associated with reduced neonatal respiratory distress syndrome [OR 0.57, 95% CI 0.37-0.89] and
fewer admissions to neonatal intensive care [OR 0.65, 95% CI 0.43-0.97]. Nifedipine is the only
tocolytic to date which has shown a benefit for the neonate.
The authors of the meta-analysis concluded “nifedipine appears to be more effective than beta
agonists for tocolysis, improves neonatal outcome and should be considered for use as a first-line
tocolytic agent” (Tsatsaris et al. 2001).
Side effects associated with nifedipine were uncommon and mild, including transient facial flushing
and mild headache. Treatment was much less likely to be interrupted due to side effects with
nifedipine [OR 0.12, 95% CI 0.05-0.29] compared to a betamimetic (Tsatsaris et al. 2001). To
evaluate safety of nifedipine, Ferguson and colleagues conducted a randomised study of nifedipine
versus ritodrine (Ferguson et al. 1989). They found that the cardiovascular and metabolic effects of
nifedipine were minimal, unlike ritodrine (a betamimetic). Nifedipine is commonly used in
pregnancy for the treatment of pre-eclampsia (elevated blood pressure), but normotensive women
on nifedipine have a minimal drop in blood pressure.
Developed by:
Authorised by:
Nifedipine Tocolysis
Clinical Director Maternal Fetal Med
Clinical Director O&G
Classification:
Date Issued:
NMP200/SSM/041
Updated October 2009
Page:
2 of 7
Drug Protocol
Trade Name
Nyefax Retard
Mechanism of
Action
Calcium Channel Blocker
Indications
Acute Tocolysis
Threatened preterm labour at less than 34 weeks where the clinician
decides tocolysis is warranted to achieve steroid administration.
Indications
Acute Tocolysis
Threatened preterm labour at less than 34 weeks where the clinician
decides tocolysis is warranted to achieve steroid administration.
Contraindications /
Indications for
Tocolysis
Maternal
Absolute:
• Suspected intrauterine infection
• Suspected placental abruption
• Hypotension
• Shock
• Previous allergic response to Nifedipine
Relative:
Use of a ß-blocker (risk hypotension)
Use of magnesium sulfate (risk hypotension)
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Fetal:
• Congenital anomalies of the fetus incompatible with normal life
• Severe fetal growth restriction
• Gestational age >34 weeks
• Abnormal CTG
Possible Adverse
Effects
The most common side effects are: transient palpitations (0-6%),
headaches (5-6%), and facial flushing (5-18%) (Ferguson et al.
1990; Kupferminc et al. 1993).
Other less common side effects are: constipation, dizziness, nausea,
tachycardia, fatigue, peripheral edema, and increased liver
enzymes. Liver enzyme changes are not a concern with such limited
use, but care should be taken in those with known liver disease
Maximum Dose
160mg Nyefax Retard in 24 hours.
Continued on next page
Developed by:
Authorised by:
Nifedipine Tocolysis
Clinical Director Maternal Fetal Med
Clinical Director O&G
Classification:
Date Issued:
NMP200/SSM/041
Updated October 2009
Page:
3 of 7
Drug Protocol, Continued
Dose &
Administration
Initially 10mg orally (2x Nifedipine 5mg capsules) every 15 mins, up
to 4 doses of Nifedipine to stop contractions.
After this slow release nifedipine. It has been found that an 8 hourly
dosage of 40mg – 20mg – 40mg Nyefax Retard is suitable for most
women. On occasions a higher dose may be required up to the
maximum below.
Maximum nifedipine sustained release scheme: 60mg – 40mg 60mg Nyefax Retard.
Minimum nifedipine sustained release scheme: 20mg – 20mg 20mg Nyefax Retard.
The Nyefax Retard should be discontinued 24 hours after the last
steroid dose. There is no data supporting continued use.
Resource People
Developed by:
Authorised by:
Nifedipine Tocolysis
Dr Emma Parry, Associate Professor Lesley McCowan, Professor
Peter Stone for further information and advice.
Clinical Director Maternal Fetal Med
Clinical Director O&G
Classification:
Date Issued:
NMP200/SSM/041
Updated October 2009
Page:
4 of 7
Monitoring
Maternal
Pulse, blood pressure and temperature on admission. A speculum
examination should be performed and swabs taken for infection and
fetal fibronectin testing where indicated and available. If membranes
are intact and cervix has not been visualized sufficiently; a digital
examination should also be performed to check cervical dilatation.
During the first hour, pulse and blood pressure should be checked
every 30 minutes. After the first hour, pulse, blood pressure and
temperature should be checked every hour for 2 hours, then QID if
the uterine activity is diminishing. Once stable the woman can be
transferred to the A/N ward.
Fetal
Baseline CTG must be normal before commencement of therapy.
Also monitor with a CTG at the commencement of treatment. This
should be continuous for the first hour at least and until contractions
cease. CTG monitoring should then continue as clinically indicated.
If there is a change in the clinical situation e.g. increase in maternal
temperature or pulse rate or return/ increase in contractions, then
CTG monitoring should be recommenced.
Changing From
Salbutamol to
Nifedipine
If a woman has already commenced salbutamol tocolysis, then the
infusion should be stopped. Usual observations for salbutamol use
should be continued until the maternal pulse drops below 100. At
this stage the nifedipine protocol can commence with the 10mg
quick release tablets as above if the woman is still contracting or a
standard slow release protocol of 40-20-40mg if she is not.
Observations &
Documentation
Please see flow chart below.
Developed by:
Authorised by:
Nifedipine Tocolysis
Clinical Director Maternal Fetal Med
Clinical Director O&G
Classification:
Date Issued:
NMP200/SSM/041
Updated October 2009
Page:
5 of 7
Nifedipine Tocolysis Flowchart
Developed by:
Authorised by:
Nifedipine Tocolysis
Clinical Director Maternal Fetal Med
Clinical Director O&G
Classification:
Date Issued:
NMP200/SSM/041
Updated October 2009
Page:
6 of 7
References
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Carr, D. B., A. L. Clark, K. Kernek and J. A. Spinnato (1999). “Maintenance oral nifedipine for
preterm labor: A randomized clinical trial.” American Journal of Obstetrics and Gyneology 181:
822-827.
Ferguson, J. E., M. D. Dyson, R. H. Holbrook, T. Schutz and D. K. Stevenson (1989).
“Cardiovascular and metabolic effects associated with nifedipine and ritodrine tocolysis.”
American Journal of Obstetrics and Gyneology 161: 788-795.
Ferguson, J. E., M. D. Dyson, T. Schutz and D. K. Stevenson (1990). “A comparison of
tocolysis with nifedipine or ritodrine: Analysis of efficacy and maternal, fetal, and neonatal
outcome.” American Journal of Obstetrics and Gyneology 163: 105-111.
Kupferminc, M., J. B. Lessing, Y. Yaron and M. R. Peyser (1993). “Nifedipine versus ritodrine
for suppression of preterm labour.” British Journal of Obstetrics and Gynaecology 100: 10901094.
Liggins, G. C. and R. N. Howie (1972). “A controlled trial of antepartum glucocorticoid treatment
for prevention of the respiratory distress syndrome in premature infants.” Pediatrics 50: 515525.
Lockwood, C. J. and E. Kuczynski (1999). “Markers of risk for preterm delivery.” Journal of
Perinatal Medicine 27(1): 5-20.
Papatonis, D. N. M., J. H. Kok, H. P. Van Geijn, O. P. Bleker, H. J. Ader and G. A. Dekker
(2000). “Neonatal effects of nifedipine and ritodrine for preterm labor.” Obstetrics & Gynecology
95(95): 477-481.
Papatonis, D. N. M., H. P. Van Geijn, H. J. Ader, F. M. Lange, O. P. Bleker and G. A. Dekker
(1997). “Nifedipine and Ritodrine in the Management of Preterm Labor: A Randomized
Multicenter Trial.” Obstetrics & Gynecology 90(2): 230-234.
Sanchez-Ramos, L., A. M. Kaunitz, F. L. Gaudier and L. Delke (1999). “Efficacy of
maintenance therapy after acute tocolysis: A meta-analysis.” American Journal of Obstetrics
and Gyneology 181: 484-490.
Tsatsaris, V., D. Papatsonis, F. Goffinet, G. Dekker and B. Carbonne (2001). “Tocolysis with
nifedipine or beta-adrenergic agonists: a meta-analysis.” Obstetrics and Gynecology 97: 840847
Developed by:
Authorised by:
Nifedipine Tocolysis
Clinical Director Maternal Fetal Med
Clinical Director O&G
Classification:
Date Issued:
NMP200/SSM/041
Updated October 2009
Page:
7 of 7