A variety of opioid analgesics has been used in the UK to reduce the pain of labour, and none has been found adequate for the majority of mothers. Pethidine is the most commonly used systemic analgesic in England and Wales, whereas in Scotland diamorphine is also common. Shorter-acting opioids such as fentanyl, alfentanil and remifentanil have also been used (see Chapter 25, Intravenous patient-controlled analgesia for labour). All opioid agents, given in equianalgesic doses, have similar advantages and disadvantages, and the widespread use of pethidine is largely due to historical reasons.
The major advantages of systemic opioid analgesia for labour are ease of administration, low cost, midwife autonomy of use and acceptability by many mothers. The major disadvantages are failure to provide adequate analgesia for many women (a third of women using pethidine will request epidural analgesia), general opioid side effects for the mother and rapid placental transfer to the fetus.
Drugs and administration
Midwives in the UK are authorised to give a total of 200 mg pethidine to a labouring mother, provided that the dose is divided, without a doctor’s prescription. It is common practice to give 100 mg intramuscularly as the first dose. Blood levels of pethidine following intramuscular injection are unpredictable, and it is not possible to achieve therapeutic levels reliably with this standardised approach to administration. There is also little correlation between the weight of the mother, the amount of pethidine given and subsequent plasma concentration of pethidine. Pethidine has a long-acting metabolite, norpethidine, which accumulates in both the mother and fetus and has significant opioid activity. Its half-life is 21 hours in the mother and 63 hours in the fetus, compared with 3-7 hours and 13-23 hours respectively for pethidine. Norpethidine also has proconvulsant activity, and therefore on theoretical grounds pethidine is not an ideal analgesic for women with epilepsy or pre-eclampsia.
Intravenous administration of pethidine, either by medical staff or as patient-controlled analgesia (PCA; see Chapter 25), is more likely to achieve therapeutic plasma concentrations of the drug, but the intramuscular route remains the most commonly used.
Diamorphine is also used in some units, in doses of 5.0-7.5 mg intramuscularly. A recent UK-based randomised controlled trial found that diamorphine provided a modest improvement in analgesia over pethidine at the expense of a significantly longer labour.
Morphine has also been used but produces similar effects to pethidine and diamorphine; it is therefore rarely used in labour other than for miscarriage or terminations around 18-22 weeks.
Fentanyl has been used intravenously to provide labour analgesia, usually as PCA (see Chapter 25). The advantages are a rapid onset and short duration of action due to its high lipid solubility and volume of distribution. The general risks and benefits of opioid analgesics in labour apply, although severe neonatal depression is uncommon.
Remifentanil is a very short-acting opioid with characteristics that make it ideal for PCA in labour. It has been used to provide analgesia for women unable to have epidural analgesia, or in certain units as a less effective alternative to epidural analgesia for women not wishing to have an epidural but wanting something more effective than other methods of pain relief. It is only administered by PCA (see Chapter 25).
Side effects
These are common to all opioid drugs. Maternal side effects include:
• Altered respiratory pattern - hypoventilation occurs between contractions, but inadequate analgesia is accompanied by hyperventilation during contractions
• Reduced gastric motility
• Nausea and vomiting
• Sedation, dysphoria and euphoria
Mothers should be warned of the implications for other modes of analgesia if opioids are administered because of these side effects; for example, a period of 4 hours has traditionally been advocated after pethidine administration before an epidural solution containing fentanyl can be given, although this restriction is no longer widespread. Labouring women should also not go into a birthing pool if drowsy, or for at least 2 hours after opioids.
Drugs such as promethazine and promazine are still occasionally administered with pethidine in an attempt to reduce the incidence of nausea and vomiting, and these drugs considerably enhance the sedative effects of pethidine, sometimes to the extent that the mother has no clear recall of the events surrounding delivery.
All opioids cross the placenta freely because of their low molecular weight and high lipid solubility, and the fetus is particularly susceptible due to its reduced metabolism and elimination in comparison to the mother and its immature blood-brain barrier. Fetal effects include:
• Loss of heart-rate variability - the typical ‘flat’ cardiotocographic trace that results may make interpretation of any other changes difficult, but alone is not usually associated with worsening fetal acid-base balance.
• Neonatal respiratory depression, especially if given within 2-4 hours of delivery for pethidine or diamorphine (reversible with naloxone, although it is important to remember that naloxone is a short-acting drug and may need to be given either as an infusion or in repeated boluses). Studies have shown an increased need for neonatal resuscitation with maternal parenteral opioids in comparison with epidural analgesia.
• Depression of neonatal neurobehavioural scores for up to 3 days - the significance of this is not clear.
• Smaller likelihood of successful breastfeeding in babies whose mothers have received pethidine in labour, although there may be other psychosocial factors relevant to these findings.
Management options
The advantages of intramuscular opioid analgesia (simplicity of administration, low cost and acceptability to many midwives and mothers) have to be balanced against the disadvantages for both mother and baby, and the fact that the quality of analgesia is generally poor, although it may be useful in very early labour or prelabour. For mothers with significant medical disease and those at increased risk of operative delivery, regional analgesia is usually preferable. However, women unable to have regional analgesia (e.g. those with coagulation disorders) may benefit from PCA as an alternative.
Women receiving systemic opioid analgesia should be considered at risk of gastric stasis and advised accordingly regarding oral intake. Concurrent administration of H2- antagonists should also be considered. In some units, metoclopramide is given concurrently to women receiving opioids as a non-sedating antiemetic.
Key points
• Pethidine is the most commonly used opioid analgesic for labour in the UK.
• Other opioids have similar risks and benefits.
• Patient-controlled analgesia (PCA) may improve efficacy and reduce side effects.
• Systemic opioid analgesia is not advisable for women at increased risk of operative delivery.
• Neonatal respiratory depression and impaired neurobehavioural scores may follow maternal administration of opioids.
Further reading
Littleford J. Effects on the fetus and newborn of maternal analgesia and anesthesia: a review. Can J Anaesth 2004; 51: 586-609.
Phillips SN, Fernando R, Girard T.
Parenteral opioid analgesia: does it still have a role? Best Pract Res Clin Anaesthesiol 2017; 31: 3-14.
Smith LA, Burns E, Cuthbert A. Parenteral opioids for maternal pain management in labour. Cochrane Database SystRev 2018; (6): CD007396.