MATERNITY UNIT
GUIDELINE:
INHIBITION OF PRETERM LABOUR
SCOPE:
All obstetricians and midwives working in maternity
AUTHOR:
Clinical Director Obstetrics
PURPOSE:
The aim of tocolysis is to inhibit uterine activity usually for a short term (48-72 hours),
in order to administer corticosteroids to enhance fetal lung maturity or to facilitate
transfer to Waikato Hospital or other Tertiary Hospital.
DEFINITIONS:
Preterm labour (PTL) is usually defined as occurring at less than 37 weeks gestation.
However, inhibition of labour is normally attempted only in EARLY preterm labour
occurring after 24 weeks and prior to 34 completed weeks gestation. For this
reason, the term PTL as used in this guideline, will be assumed to be labour between
24 and 34 weeks completed weeks.
GUIDELINE:
A diagnosis of PTL is made when regular uterine contractions, at least 3 in 30
minutes (i.e. 1:10), are present, accompanied by effacement and/or dilatation of the
cervix. Contractions alone without cervical changes are not definitive of labour. If
PTL is suspected the obstetrician on call should be notified.
Tocolytic therapy may abolish contractions temporarily, but it will not remove the
underlying stimulus which initiated the process or reverse the changes in the uterus.
The aims of inhibition of preterm labour are to:
1. Delay delivery by at least 48 hours so that steroids may be administered to
the mother and achieve their maximum effect on the fetus;
2. Provide time for safe transport of the mother to a tertiary facility;
3. Prolong pregnancy when there are underlying, self-limited conditions that can
cause labour such as pyelonephritis or abdominal surgery, and are unlikely to
cause recurrent PTL.
Tocolytic therapy in this guideline:
1. Salbutamol tocolysis (page 3)
2. Nifedipine tocolysis (page 7)
3. Magnesium sulfate tocolyis (page 11)
Contraindications and precautions:
Tocolysis is contraindicated when the maternal/fetal risks of prolonging pregnancy or
the risks associated with these drugs are greater than the risks associated with
preterm birth. Contraindications include:
 Intrauterine death
 Lethal fetal anomaly
 Non-reassuring fetal status
 Severe fetal growth restriction
 Maternal cardiac disease
 Maternal cardiac arrhythmia
 Placental abruption
 Thyrotoxicosis
 Uncontrolled diabetes
 Sensitivity to sympathomimetic drugs (does not apply to magnesium
sulfate or nifedipine use)
Relative contraindications of inhibition of preterm labour include:
 suspected amnionitis
 gestational age >34 weeks
 major fetal anomaly
 abnormal CTG
 suspected placental abruption
 severe pre-eclampsia
 intrauterine growth retardation
 intrauterine infection
Inhibition of PTL is less likely to be successful where cervical dilatation is greater
than 3cms. Tocolysis may still be beneficial however in order to administer maternal
steroids or safely transport the mother to a tertiary unit.
On admission - If PTL strongly suspected, go to management of preterm labour
guideline, otherwise assess situation and:
1. Inform Consultant Obstetrician immediately
2. Maternal examination for signs of infection - temp, pulse, respiration rate
3. Abdominal examination – palpate and assess for; uterine contractions, uterine
tone, uterine tenderness, fetal and uterine size. Palpate for lie, presentation,
position and engagement.
4. Ask woman for clean catch MSU specimen when possible and send to laboratory
5. Commence CTG and monitor continuously until consultant has made a decision
and management plan.
6. Any leakage of fluids or vaginal discharge – go to preterm premature rupture of
the membranes guideline
The Consultant will formulate a plan of care - This plan may include the following:
 Speculum examination – this will allow an inspection for ruptured membranes or
infection as well as cervical dilatation – take fetal fibronectin sample prior to any

digital examination and only lubricate the speculum with warm water - see fetal
fibronectin guideline and flow chart
AmniSure test for rupture of membranes

High vaginal swab (HVS), cervical cultures

Complete Blood Count and other blood tests as clinically indicated

Insert IV line and commence intravenous therapy

Inform Neonatal Unit staff/paediatrician of potential admission and update them
as to ongoing management plan

Corticosteroid injection if <34 weeks gestation unless delivery is imminent

Nifedipine, salbutamol, Terbutaline or Magnesium Sulphate regime as per
protocol as recommended by Consultant Obstetrician

Consideration of transfer out to a tertiary unit – see transfer out of maternity
patients guideline
The selection of an appropriate labour-inhibiting agent should be based upon efficacy
and safety. If the first tocolytic agent does not inhibit PTL successfully, the
obstetrician may consider discontinuing this and commencing a second agent.
However it is important to exclude intrauterine infection as this may be a
contraindication to continuing tocolytic therapy.
There is no high quality evidence of the efficacy of bedrest for the prevention or
treatment of PTL in singleton pregnancy.
1/ Salbutamol tocolysis
Salbutamol may be used in cases of threatened/confirmed pre term labour (PTL)
before 34 weeks with no obstetric pathology, until 24 hours after last dose of steroids
are given, and where the Nifedipine regime cannot be used.
An obstetrician must order and prescribe salbutamol.
Drug action and presentation
Salbutamol is a betametic agent and acts as uterine muscle relaxant, by stimulating
Beta-2 adrenergic receptors in smooth muscle. It comes in 0.5mg/ml and 1 mg/ml
ampoules
Dose
5mg Salbutamol in 100mls normal saline (gives a dilution of 50mcg/ml)
Administered via an electronic control device (e.g. IVAC, syringe driver), as a second
line, piggybacked into a mainline of Hartmans/Normal Saline.
Incompatibilities
Do not mix with any other drugs and only piggyback onto mainline Hartmans or
Normal Saline.
Contraindications, use with precaution and side effects
Contraindications:
 Where urgent delivery is appropriate, e.g. fetal distress or IUGR





Amnionitis
Significant antepartum haemorrhage
Significant pre-eclampsia or eclampsia
Thyrotoxicosis
Hypersensitivity to Beta-adrenergic drugs
Use with precaution:
 Any cardiac disease
 Diabetes (see side effects)
Side effects:
 General tachycardia (rise in heart rate by 20-50 bpm), palpitations, nausea and
vomiting, tremor, constipation and headaches are common.
 Pulmonary oedema, chest discomfort, cough, tachypnoea and shortness of
breath may indicate pulmonary oedema. Most cases are due to fluid overload and
can be prevented by using a concentrated solution of Salbutamol. It is more
common in women with twins and undiagnosed cardiac disease.
 Carbohydrate metabolism, blood glucose levels increase up to 40% and insulin
secretion increases. Hypokalaemia commonly occurs and may require treatment.
 Myocardial Ischaemia – due to increase cardiac output.(rare)
 Hypotension, secondary to vasodilatation (rare).
 Fetal tachycardia (rise by 20 bpm) for duration of Salbutamol.
 Maternal hyperglycaemia and hyperinsulinism can cause hypoglycaemia of the
infant after birth.
 Insulin dependent diabetics will rapidly become hyperglycaemic and may develop
ketoacidosis. It will be necessary to run an insulin infusion, monitored by hourly
blood glucose estimations. The combination of Salbutamol and steroids in a
diabetic may only be used with the approval of the on call obstetrician
Continuous infusion rate of salbutamol
If there are no side effects, add 5mg Salbutamol to 100mls of Normal Saline IV fluid
to give a dilution of 50mcg/ml
Administer infusion via the side arm, i.e. piggy backed into mainline using an
electronic control device, e.g. an IVAC
Commence at 2.5mcg/minute
Increase the rate every 10 minutes as outlined below, UNTIL contractions cease.
Rate (mls/hour) Dose (mcg/min)
3
2.5
6
5.0
12
10.0
18
15.0
24
20.0
30
25.0
36
30.0
42
35.0
48
40.0
Stop infusion if:
 Maternal pulse rate exceeds 140bpm
 Maternal systolic BP is less than 100mmHg
 Maternal respiration greater than 24/minute
 Coughing – see side effects



Chest pain – see side effects
Fetal heart rate greater than 180bpm
When contractions have ceased, or maximum dosage has been reached, this is
the maintenance dose. It may be necessary to reduce the dose slightly for
comfort.
Monitoring
During the establishment of an effective dosage, at 10 minute intervals and before
each increase in dose, record and document in the clinical notes the following:
Record at 10 minute intervals:
 Maternal pulse (must be less than 140 bpm)
 Maternal respiratory rate (must be no more than 24 rpm)
 Fetal heart rate (ensure it is less than 180 bpm)
 Frequency of contractions and dose of drug
Other records include:
 Baseline temperature, then 4 hourly
 Continuous CTG
 Commence fluid balance chart/records
 Test urine for glucose and protein 6 hourly
 Maternal blood tests:– electrolytes (U & E’s), glucose and CBC (for WBC)
At commencement, 6 hours after commencement and then 12 hourly while on
maintenance dose until completion.
Once on maintenance dose:
Observations are ½ hourly for 2 hours and then hourly.
After 6-8 hours of stable recordings reduce to:
 hourly maternal pulse
 hourly recording of contractions, record dosage of Salbutamol
 4 hourly BP, T&R
 Fetal heart – 8 hourly CTG for no less than 30 minutes
Note:
A progressive increase in fetal heart rate and/or maternal fever and/or abdominal
tenderness may indicate amnionitis.
Try to find an effective maintenance dose and continue at this level for 12 hours after
the last steroid has been given.
Antibiotics should be used when the membranes are ruptured or when the cervix is
3cm or more dilated with intact membranes as per PPROM and Group B Strep
guideline.
Steroids given as per obstetric orders
U&E results must be followed up promptly as oral or IV Potassium replacement
may be required.
Stopping the infusion
Keep Salbutamol at maintenance level for 12 hours following last steroid injection
then discontinue infusion. (1/2 life of Salbutamol is 4-6 hours).
2/ Nifedipine Tocolysis
Trade Name – Nyefax Retard 20 mgs tablets (slow release Nifedipine)
Adalat 5 mg capsules (short acting Nifedipine)
Mechanism of action – both forms of Nifedipine are calcium channel blockers and act
as uterine relaxants.
Indications:
Acute tocolysis in patients with pre-term labour after 24 weeks gestation and before
34 weeks gestation
Consent for procedure
Nifedipine 5 mg Capsules are covered under Section 29 and not registered for
use in New Zealand. Prior to commencing this procedure, information should
be given to the woman by the obstetrician or the midwife, about the drug and
why it is recommended and patient consent must be obtained and documented
in the clinical notes. A register of doses administered must be completed and is
found in the medical store room in DU.
Dose schedule (see flow chart on page 9)
Initial doses
Tocolysis with short acting Nifedipine is initiated with 10mgs orally. After 15 minutes,
if still uterine activity, then a second dose of short acting Nifedipine 10 mgs can be
given. If contractions still persist, further 10mg doses can be given every 15 minutes
for a maximum for 4 doses. Note that the maximum dose in the first hour is 40
mgs.
Maintenance dose
Depending on the effectiveness of the tocolytic given in the first hour, a maintenance
dose of 60 – 160 mgs per day of slow release Nifedipine is then given. The
obstetrician must chart the required dose regime (see page 8 for dosage
levels). This is until the steroid medication has been administrated and
completed.
The dose of slow release Nifedipine may be increased during the time of
administration.
The first slow release Nifedipine may be given at the same time as the last dose of
short acting Nifedipine.
It is preferable to give slow release Nifedipine 8 hourly to ensure a steady plasma
level.
Dosage levels:
It has been found that a dosage level of 20mgs – 40mgs – 20mgs of slow release
Nifedipine is suitable for most women. On occasions a higher dose may be
necessary in which case the maximum dose is 60mgs – 40mgs – 60mgs this is
given 8 hourly (160mgs in 24 hours).
Likewise the minimum dose of slow release Nifedipine is 20mgs - 20mgs – 20mgs
(8 hourly).
The obstetrician must prescribe which dose is required on an individual patient basis
on the medication chart or using a verbal telephone order (see safe management of
medicines policy)
The administration of Nifedipine (slow release) is usually discontinued 12
hours after the last steroid dose as there is currently insufficient evidence to
support the continued use after steroid administration is complete.
Maternal considerations:
Monitoring
 On administering Nifedipine during the first hour, pulse and blood pressure
should be checked every 30 minutes
 After the first hour, pulse and blood pressure should be checked every hour for
two hours.
 Three hours after commencement, pulse and blood pressure should be checked
four hourly once uterine activity has ceased.
 If there is any concern (fetal or maternal) then the observations should be
maintained at more frequent intervals as clinically indicated.
Please note:
Normotensive women on Nifedipine experience a minimal drop in blood
pressure, however, pre–eclamptic women can experience an acute drop in
blood pressure and this must be considered carefully before commencement.
Fetal considerations:
 Continuous CTG from commencement of Nifedipine therapy and then for at least
one hour until uterine activity ceases. Clinical assessment of uterine activity is
also important to assess and document.
 It is essential that the CTG be within normal limits before Nifedipine is
administered.
 If there is any change in the clinical situation at other intervals, e.g. increase in
maternal temperature or pulse rate or return/increase of uterine activity, then
CTG monitoring should be recommenced.
Contraindications
Maternal:
Absolute
 Suspected uterine infection
 Suspected placental abruption or significant APH
 Shock
 Hypotension
 Previous allergic response to Nifedipine
Relative
 Use of Magnesium Sulphate (risk hypotension)
 Use of Beta-blocker (risk hypotension)
Precautions
 Heart disease/arrhythmia’s
 Liver disease
Fetal:
 Severe IUGR
 Gestational age of >34 weeks
 Abnormal CTG/fetal distress
Side effects
 Transient palpitations (0 – 6%)
 Headaches (5 – 6%)
 Facial flushing (5 – 18%)
Less common side effects are: constipation, dizziness, nausea, tachycardia, fatigue,
peripheral oedema and increased liver enzymes. Liver enzyme changes are not a
concern with such limited use, but are of concern in those with known liver disease.
Changing from salbutamol to nifedipine
If a woman has already commenced on Salbutamol then the infusion should be
stopped. Usual observations for Salbutamol use should be continued until the
maternal pulse rate drops below 100. At this stage the Nifedipine protocol can
commence using short acting Nifedipine if the patient is contracting or slow release
Nifedipine at a dosage of 20 – 40 – 20mgs if uterine activity has ceased.
NIFEDIPINE TOCOLYSIS FLOWCHART-PLEASE SEE HARDCOPY IN
WARD
FOR THIS
3/ Magnesium Sulfate
The precise mechanism of magnesium’s effects on uterine contractions has not been
completely discovered, despite more than 40 years of study. Magnesium probably
competes with calcium at the level of the plasma membrane voltage-gated channels.
It hyperpolarizes the plasma membrane and inhibits myosin light-chain kinase activity
by competing with intracellular calcium at this site. Interference with the activity of
myosin light-chain kinase reduces myometrical contractility.
A randomised controlled trial comparing magnesium sulfate with nifedipine for acute
tocolysis found no significant differences in rate of delivery within 48 hours or in any
neonatal morbidity.
Contraindications:




Women with Myasthenia Gravis
Known myocardial compromise
Impaired renal function
Concurrent use with Nifedipine
Side effects
Maternal:
Rapid infusion causes:
 Flushing and warmth
 Diaphoresis (excessive sweating commonly associated with shock and other
medical emergency conditions)
Probably related to peripheral vasodilation and a drop in BP
Other side effects include:
 Nausea
 Vomiting
 Headache
 Visual disturbances
 Palpitations
 Loss of deep tendon reflexes (at doses of 9.6 to 12.0mg/dl)
 Respiratory paralysis (at doses of 12.0 to 18.0mg/dl)
 Cardiac arrest (at doses of 24.0 to 30.0mg/dl)
Fetal:
Conflicting data with regard to effect on perinatal mortality
 Slight decrease in fetal heart rate and variability (not clinically significant)
Doses:
4-6g bolus, followed by a maintenance dose of 1-2g/hr. The infusion rate should be
titrated based upon assessment of contraction frequency and maternal toxicity.
Calcium gluconate 1g IV over 5 to 10 minutes should be administered only to
counteract life-threatening symptoms of magnesium toxicity such as cardiorespiratory
compromise
When used with calcium-channel blockers there is a risk of suppression of heart rate,
contractility and left ventricular systolic pressure and neuromuscular blockade.
All preterm labour
In all cases of suspected preterm labour, please follow the flow chart in
appendix 1 in consultation with the obstetrician.
Premature labour <34weeks is a level 3 Section 88 referral, 34 – 36 weeks is a
level 2 referral.
Note that Terbutaline Sulfate is NOT AVAILABLE in New Zealand
ASSOCIATED DOCUMENTS
Maternity Unit guideline – Transfers out of maternity patients
Maternity Unit guideline - Fetal fibronectin
Maternity Unit guideline – Preterm labour and delivery
Maternity Unit guideline – Preterm rupture of the membranes
Maternity Unit guideline – Referral of neonates to the paediatric service
Maternity Unit guideline – Emergencies obstetric and neonatal
Organisational Policy - Safe management of medicines
Appendix 1 – Recommended management of woman with threatened preterm
labour
REFERENCES
Ministry of Health (2007) maternity Services: Notice Pursuant to Section 88 of the
New Zealand Public Health and Disability Act 2000.
Waikato guidelines for salbutamol and nifedipine tocolysis
Up to date on-line (2007) Inhibition of acute preterm laboutr. Downloaded on 7 may
2008 from:
http://www.utdol.com/online/content/topic.do?topicKey=pregcomp/11591&view=print
#
Date of Approval: May 2008
Next Review Date: May 2010
PLEASE SEE HARDCOPY IN WARD FOR APPENDIX 1