Parenteral opioids for maternal pain relief in labour
Opioids provide mild to moderate pain relief in labour, but are associated with side-effects. Although the review is inconclusive with regard to neonatal complications associated with the use of opioids, pethidine appears to be associated with a higher incidence of low Apgar scores.
RHL Commentary by Olayemi O
All women experience pain during labour. Its origin is physiological and it is caused by the contraction of uterine muscles and release of some pain signalling neurotransmitters (1). However, the perception of labour pain and the need for analgesia vary and several factors have been associated with both. These factors include educational status, parity, age of parturient, ethnicity and support during labour (2).
There are many methods of analgesia during labour, which are broadly classified into regional and non-regional techniques with the non-regional being further classified as pharmacological and non-pharmacological methods. Studies in New Zealand and the United Kingdom have found that more than 95% of hospitals surveyed routinely offered intramuscular pethidine (3, 4).
Parenteral opioids are part of standard care during labour in many obstetric units, although there is no firm evidence for their efficacy, safety (especially in the newborn) and the best route of administration. This Cochrane review (5) assessed the effectiveness, safety and acceptability to women of different types, doses and modes of administration of parenteral opioid analgesia during labour. A second objective was to assess the effects of opioids in labour on the baby in terms of safety, condition at birth and early feeding.
2. METHODS OF THE REVIEW
To identify relevant studies, the authors searched the literature extensively. Two of the authors used a data extraction and management form to assess independently the quality of included papers. Conflicts were resolved by discussion and occasionally by involving the third author. Assessment of risks of bias was also done appropriately by the authors and the quality of randomization process was assessed critically for each paper by assessing the steps of random generation and allocation concealment.
The authors sought to include studies that had included women in labour, except those at high risk and those in preterm labour. The primary outcome measures were maternal satisfaction with analgesia measured during labour as well as during the postnatal period. Secondary outcome measures for the mother were: maternal pain score or pain measured in labour; additional analgesia required (epidural); maternal sleepiness during labour; nausea and vomiting in labour; caesarean section; assisted vaginal birth; postpartum haemorrhage (as defined by the trial authors); breast-feeding at discharge; and breast-feeding in the postnatal period (four to six weeks). The secondary outcomes for the baby were: fetal heart rate changes in labour (persistent decelerations or tachycardia); naloxone administration; neonatal resuscitation; Apgar score less than seven at one minute; Apgar score less than seven at five minute; Apgar score less than seven at ten minute; admission to neonatal care unit; newborn neurobehavioral scores; and neurodevelopment outcomes during infancy. Assessment of cost was sought as a separate outcome measure.
3. RESULTS OF THE REVIEW
The review includes 54 trials involving over 7000 participants. However, for most of the analyses only one study contributed the data.
3.1 Maternal satisfaction and pain relief during labour
Intramuscular pethidine 100 mg versus placebo. Though maternal satisfaction was not significantly different in the two groups, pain relief was better with pethidine, 30 minutes after its administration [relative risk (RR) 1.75, 95% confidence interval (CI) 1.24–2.47]. In addition, in the pethidine group, a significantly proportion of women had a reduction in visual analogue scale (VAS) scores (RR 25.0, 95% CI 1.56–400.54). Use of additional analgesia was also significantly lower (RR 0.71, 0.54–0.94) in the pethidine arm.
3.2 Comparison of outcome between two or more drugs
Tramadol versus pethidine. Among women reporting poor relief, pain control was higher in those who had received pethidine (RR 1.56, 95% CI 1.10–2.21). In the comparison between intravenous Avacan® and intramuscular pentazocine, the latter was associated with reduced use of further analgesia (RR 2.02, 95% CI 1.16–3.53). The mean dose of analgesia required was higher with fentanyl compared to pethidine when both were given by the intramuscular route (mean difference in dose 0.40, 95% CI 0.14–0.66).
Intravenous butorphanol versus pethidine. Pain relief scores favoured butorphanol (mean difference 0.67, 95% CI 0.25–1.09). Also, pain score after 1 hour favoured butorphanol (mean difference 0.60, 95% CI 1.02–0.18). In trials comparing intramuscular morphine with intramuscular pethidine, satisfaction with analgesia (measured 3 days post partum) was found to be better with pethidine (RR 3.41, 95% CI 1.90–6.12). In the comparison between intravenous fentanyl and intramuscular butorphanol, use of additional doses of analgesia was more with fentanyl (RR 1.39 95% CI 1.05–1.85).
3.3 Side-effects: maternal sleepiness, nausea and vomiting in labour
Intramuscular pethidine 100 mg versus placebo. There was no significant difference in the occurrence of nausea and vomiting among the 83 participants in the trials included in the review. However, pethidine significantly increased maternal sleepiness (RR 4.67, 95% CI 2.43–8.95) compared with placebo. Meptazinol caused nausea and vomiting more frequently than pethidine (RR 1.25, 95% CI 1.06–1.47), but was not significantly different from pethidine as a cause of maternal sleepiness. There was less vomiting associated with pethidine and prochloperazine compared with diamorphine and procloperazine (RR 0.39 95% CI 0.17–0.86). Tramadol was associated with less maternal sleepiness compared with pethidine (RR 0.57 95% CI 0.33–0.97).
Compared with pethidine, nalbuphine was associated with less episodes of nausea alone (RR 0.62, 95% CI 0.42–0.91) or vomiting (RR 0.41, 95% CI 0.22–0.76). Phenazocine, when compared with pethidine, was associated with less episodes of vomiting (RR 0.39, 95% CI 0.20–0.78). Maternal sedation was less with intravenous fentanyl compared with pethidine by the same route of administration (RR 0.05, 95% CI 0.00–0.82). Intravenous butorphanol was associated with less vomiting compared with intravenous pethidine (RR 0.04, 95% CI 0.00–0.67). Intravenous nisentil was less likely to cause nausea and vomiting compared with pethidine (RR 0.38, 95% CI 0.22–0.66). None of the other trials showed significant differences.
3.4. Assisted vaginal delivery and caesarean section
There was no significant difference between intramuscular 100 mg pethidine and placebo in the incidence of assisted vaginal delivery or caesarean section. The studies comparing two or more drugs also did not show any significant differences in these outcome measures. In one trial involving 133 participants, pethidine and prochloprerazine were found to be associated with a higher incidence of Apgar score less than seven at 1 minute compared with diamorphine and prochloperazine (RR 0.41, 95% CI 0.18–0.91). Similarly, compared with dihydrocodeine, pethidine 100 mg was associated with an increased incidence of Apgar scores <7 at 1 minute (RR 0.57, 95% CI 0.39–0.84). There was no analysis of cost in the review, and postpartum haemorrhage was not an outcome in the studies included in the review.
4.1 Applicability of the results
At best, opioids provide mild to moderate analgesia in labour and are associated with side-effects. The findings related to neonatal side-effects were not conclusive because many of the studies did not have these as outcome measures. Since the studies included in this review involved participants from North America, South America, Middle-East, Asia and Africa, the findings of this review are applicable to all settings. Although pethidine was the main drug tested in the trials included in the review, other drug included in the comparisons may not be available in developing countries
4.2 Implementation of the intervention
The comparative advantages of the more sophisticated drugs such as butorphanol, metazinol and nalbuphine over the more easily available pethidine and pentazocine were not clearly shown in the trials in this review. Owing to their ease of availability and lower cost, pethidine and pentazocine may be preferred in developing countries instead of the newer, more expensive opioids. Although the review was inconclusive with regard to neonatal complications associated with opioids, pethidine appears to be associated with a higher in incidence of low Apgar scores. Hence, appropriate neonatal resuscitation support should always be in place in health-care units opting to provide this drug for labour analgesia. The lack of resuscitation support and storage facilities and controls in primary- and secondary-level health centres in developing countries may be a challenge to the provision of opioids for labour pain in those centres.
4.3 Implication for research
This review could not answer the question which opioid drugs are most effective for labour analgesia. Moreover, there were few studies on neonatal complications associated with opioid drugs. Further research is required to generate more data on these questions. Research into other non-parenteral modes of administration of opioids may make it easier to use these drugs in under-resourced settings. Studies focusing on comparison of costs associated with these drugs are also needed.
Acknowledgement: I acknowledge the assistance of Drs Oladapo and Fawole in the preparation of this commentary.
- Findley I, Chamberlain G. ABC of labour care: relief of pain. British Medical Journal 1999; 927-930.
- Olayemi O, Adeniji R A, Udoh E S, Akinyemi O.A, Aimakhu C.O, Shoretire K.A. Determinants of pain perception in labour among parturient at the University College Hospital, Ibadan. Journal of Obstetrics and Gynaecology 2005; 25; 128 – 130.
- Lee K, Ho K.M, Obstetrics regional analgesia services in New Zealand: a national survey. New Zealand Medical Journal 2004: 117: U177.
- Saravanakumar K, Garstang JS, Hasan K. Intravenous patient controlled analgesia for labour: a survey of UK Practice. International Journal of Obstetric Anaesthesia 2007; 16: 221–225.
- Ullman R, Smith LA, Burns E, Mori R, Dowswell T. Parenteral opioids for maternal pain relief in labour. Cochrane Database of Systematic Reviews 2010;Issue 9. Art. No.: CD007396; DOI: 10.1002/14651858.CD007396.pub2.
This document should be cited as: Olayemi O. Parenteral opioids for maternal pain relief in labour: RHL commentary (last revised: 1 June 2011). The WHO Reproductive Health Library; Geneva: World Health Organization.