Parenteral opioids, such as fentanyl, diamorphine and pethidine, are recommended options for healthy pregnant women requesting pain relief during labour, depending on a woman’s preferences. Show (Recommended)
Publication history First published: February 2018 Updated: No update planned Assessed as up-to-date: February 2018
Remarks
Background Globally, approximately 140 million births occur every year (1). The majority of these are vaginal births among pregnant women with no identified risk factors for complications, either for themselves or their babies, at the onset of labour (2, 3). However, in situations where complications arise during labour, the risk of serious morbidity and death increases for both the woman and baby. Over a third of maternal deaths and a substantial proportion of pregnancy-related life-threatening conditions are attributed to complications that arise during labour, childbirth or the immediate postpartum period, often as result of haemorrhage, obstructed labour or sepsis (4, 5). Similarly, approximately half of all stillbirths and a quarter of neonatal deaths result from complications during labour and childbirth (6). The burden of maternal and perinatal deaths is disproportionately higher in low- and middle-income countries (LMICs) compared to high-income countries (HICs). Therefore, improving the quality of care around the time of birth, especially in LMICs, has been identified as the most impactful strategy for reducing stillbirths, maternal and newborn deaths, compared with antenatal or postpartum care strategies (7). Over the last two decades, women have been encouraged to give birth in health care facilities to ensure access to skilled health care professionals and timely referral should the need for additional care arise. However, accessing labour and childbirth care in health care facilities may not guarantee good quality care. Disrespectful and undignified care is prevalent in many facility settings globally, particularly for underprivileged populations, and this not only violates their human rights but is also a significant barrier to accessing intrapartum care services (8). In addition, the prevailing model of intrapartum care in many parts of the world, which enables the health care provider to control the birthing process, may expose apparently healthy pregnant women to unnecessary medical interventions that interfere with the physiological process of childbirth. As highlighted in the World Health Organization (WHO) framework for improving quality of care for pregnant women during childbirth, experience of care is as important as clinical care provision in achieving the desired person-centred outcomes (9). This up-to-date, comprehensive and consolidated guideline on intrapartum care for healthy pregnant women and their babies brings together new and existing WHO recommendations that, when delivered as a package of care, will ensure good quality and evidence-based care in all country settings. In addition to establishing essential clinical and non-clinical practices that support a positive childbirth experience, the guideline highlights unnecessary, non-evidence-based and potentially harmful intrapartum care practices that weaken women’s innate childbirth capabilities, waste resources and reduce equity. To ensure that each recommendation is correctly understood and applied in practice, the context of all context-specific recommendations is clearly stated within each recommendation, and the contributing experts provided additional remarks where needed. In accordance with WHO guideline development standards, these recommendations will be reviewed and updated following the identification of new evidence, with major reviews and updates at least every five years.
Methods These recommendations were developed using standard operating procedures in accordance with the process described in the WHO handbook for guideline development (10). Briefly, these procedures include: (i) identification of priority questions and outcomes; (ii) evidence retrieval and synthesis; (iii) assessment of the evidence; (iv) formulation of the recommendations; and (v) planning for implementation, dissemination, impact evaluation and updating of the guideline. The quality of the scientific evidence underpinning the recommendations was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) (11) and Confidence in the Evidence from Reviews of Qualitative research (CERQual) (12) approaches, for quantitative and qualitative evidence, respectively. Up-to-date systematic reviews were used to prepare evidence profiles for priority questions. The GRADE evidence-to-decision (EtD) framework (13), an evidence-to-decision tool that includes intervention effects, values, resources, equity, acceptability and feasibility criteria, was used to guide the formulation of recommendations by the Guideline Development Group (GDG) – an international group of experts assembled for the purpose of developing this guideline – at two technical consultations in May and September 2017. In addition, relevant recommendations from existing WHO guidelines approved by the Guidelines Review Committee (GRC) were systematically identified and integrated into this guideline for the purpose of providing a comprehensive document for end-users.
Further information on procedures for developing this recommendation are available here.
Recommendation question For this recommendation, we aimed to answer the following question:
Evidence summary This evidence is derived from an updated Cochrane systematic review, with 61 trials involving over 8000 women contributing data (14). The trials were conducted in hospital settings in 21 countries: Argentina, Austria, Canada, China, Denmark, Egypt, Germany, Hong Kong Special Administrative Region, India, Iran, the Netherlands, Nigeria, Norway, Pakistan, Singapore, South Africa, Sweden, Thailand, Turkey, the United Kingdom and the USA. The trials were published between 1958 and 2017. Duration of labour was not reported in the review.
Comparison 1: Parenteral opioids compared with placebo or no opioids Opioids that have been compared with placebo or no analgesia in RCTs include pethidine, pentazocine, tramadol and fentanyl.
Pethidine (intramuscular [IM]) compared with placebo Four trials involving 406 women compared IM pethidine with a saline placebo. The trials were conducted in hospital settings in Hong Kong Special Administrative Region, Iran (2 trials) and South Africa. Sample sizes in the individual trials ranged from 50 to 150. The trials were published between 1970 and 2014. Two trials used IM pethidine doses of 50 mg and two used doses of 100 mg. Use of subsequent doses was not well described. All used IM saline as placebo. Maternal outcomes Pain relief: Low-certainty evidence suggests that IM pethidine may reduce pain scores 30 minutes after administration (reduction of 40 mm on a 100-mm scale) (1 trial, 50 women, RR 25.00, 95% CI 1.56–400.54). Likewise, low-certainty evidence suggests that women receiving pethidine compared with placebo may be more likely to rate pain relief as “good” or “fair” 1 hour after administration (1 study, 116 women, RR 1.75 low-certainty evidence suggests that IM pethidine may reduce the use of other analgesia (1 trial, 50 women, RR 0.71, 95% CI 0.54–0.94), the evidence on its effect on epidural use is of very low certainty. It is unclear whether satisfaction with pain relief is improved with IM pethidine, as the certainty of the evidence is very low. Mode of birth: Low-certainty evidence suggests that IM pethidine may make little or no difference to caesarean section rates (2 trials, 380 women, RR 0.79, 95% CI 0.50–1.26). Evidence on any effect on instrumental vaginal birth is of very low certainty. Side-effects: Low-certainty evidence suggests that IM pethidine may increase maternal drowsiness during labour (2 trials, 166 women, RR 4.67, 95% CI 2.43–8.95). Moderate-certainty evidence suggests IM pethidine increases nausea and vomiting compared to placebo (3 trials, 406 women, RR 1.90, 95% CI 1.06–3.40). Birth experience, mother–baby interaction, breastfeeding: These were not reported in any of the included trials. Fetal and neonatal outcomes Perinatal hypoxia-ischaemia (Apgar scores < 7): The evidence is of very low certainty. Long-term adverse infant outcomes: These were not reported in any of the included trials.
Pethidine (intravenous [IV]) compared with placebo One trial with 240 women conducted in Egypt compared IV pethidine with placebo. Maternal outcomes Pain relief: Low-certainty evidence suggests that IV pethidine may reduce pain scores (1 trial, 240 women, MD -4.1, 95% CI -3.64 to -4.56). Mode of birth: Evidence of any effect on instrumental vaginal birth and caesarean section is of very low certainty. Side-effects: Low-certainty evidence suggests that nausea and vomiting may be increased for women receiving IV pethidine (1 trial, 240 women, RR 2.43, 95% CI 1.05–5.64). No other side-effects were reported. Birth experience, mother–baby interaction, breastfeeding: These were not reported in the included trial. Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: This was not reported in the included trial. Long-term neonatal outcomes: These were not reported in the included trial.
Pentazocine (IM) compared with placebo One three-arm trial conducted in Pakistan involving 150 women compared pentazocine (IM, 30 mg) with a saline placebo. The trial was published in 2016. Maternal outcomes Pain relief: Low-certainty evidence suggests that IM pentazocine may make little or no difference to pain scores compared with placebo (1 trial, 89 women, MD -3.6, 95% CI -9.91 to 2.71). Mode of birth: Low-certainty evidence suggests IM pentazocine may make little or no difference to caesarean or instrumental vaginal birth (1 trial, 89 women, RR 0.89, 95% CI 0.24–3.25 and RR 0.60, 95% CI 0.10–3.39, respectively). Side-effects: None of the women in this trial reported vomiting. Other side-effects were not reported. Birth experience, mother–baby interaction, breastfeeding: These were not reported in this trial. Fetal and neonatal outcomes No fetal or neonatal outcomes were reported in this trial.
Tramadol (IM) compared with no analgesia One trial involving 60 women compared women receiving tramadol (IM, 100 mg) with a group receiving no analgesia. The trial was conducted in a hospital setting in China, and published in 1994. The evidence of the effects of tramadol on labour pain relief and other outcomes is very uncertain.
Fentanyl (IV) compared with no analgesia One trial involving 70 women compared fentanyl (IV, 2 doses of 25 mcg, an hour apart) with a control group receiving no analgesia. The trial was conducted in a hospital setting in Iran, and published in 2016. The evidence of the effects of fentanyl on labour pain relief and other outcomes is very uncertain.
Summary of the main findings for comparison 1 The evidence suggests that pethidine may provide labour pain relief but may also be associated with more side-effects (nausea, vomiting and drowsiness) compared with placebo. Pentazocine may make little difference to pain scores. Evidence on the effects of tramadol and fentanyl on pain relief in labour and other outcomes is of very low certainty. Additional considerations The Cochrane systematic review (14) also included other comparisons– between different opioids, and between opioids and other analgesia (inhaled analgesia, transcutaneous electrical nerve stimulation [TENS] and complementary methods) – which were not presented in this framework; evidence on these options was predominantly from single studies and assessed in the review to be of low or very low certainty. Evidence from another Cochrane systematic review (15) of epidural analgesia included a comparison of epidural analgesia with opioids (35 trials, 10 835 women). Findings suggest that epidural may be more effective in reducing pain during labour compared to parenteral opioids. With epidural analgesia, pain scores in women during labour may be reduced compared with parenteral opioid analgesia, women may be more likely to rate pain relief as excellent or very good, and the need for any additional analgesia may be reduced (all low-certainty evidence). However, epidural analgesia probably increases labour duration (moderate-certainty evidence) and may increase the need for interventions during labour (e.g. labour augmentation, instrumental vaginal birth) (low-certainty evidence). There is probably little or no difference between the two pain relief options in relation to low Apgar scores (low-certainty evidence). Repeated use of opioid analgesics is associated with the development of psychological and physical dependence. In view of worldwide drug addiction problems and associated adverse events, there have been recent concerns expressed about prescribing opioids for the relief of acute and chronic pain (16). These concerns are probably less applicable to use of opioids for pain relief in labour (17, 18); however, the long-term effects of opioid analgesia on women and their offspring are not known. Values In a review of qualitative studies looking at what matters to women during intrapartum care (19), findings suggest that most women, especially those giving birth for the first time, are apprehensive about childbirth (high confidence in the evidence), and in certain contexts and/or situations may welcome interventions that provide relief from pain (low confidence in the evidence). When interventions are being considered, women would like to be informed about the nature of the interventions and, where possible, given a choice (high confidence in the evidence). A qualitative systematic review exploring women’s experiences of opioid use during labour could only identify very low-confidence evidence (20). The findings suggest that some women value opioids to help them cope with intense and unmanageable labour pains. Mixed responses were identified in terms of whether the pain relief was effective or ineffective and whether it had a positive or negative impact on their labour and childbirth experience. The data available for this qualitative review were very limited: only three studies, including two in HICs and one in an upper-middle-income country. One study contained minimal data to inform the review, and one involved qualitative interviews with women involved in an RCT evaluating different opioid regimens. All participants were women who had requested pain relief. It was not possible to identify, within the included studies, whether women had had augmentation, induction of labour or other forms of intervention that may have influenced their valuation of the outcomes associated with this form of pain relief. Resources No evidence on the relative cost or cost-effectiveness of the different opioid analgesics was found. However, a USA review of the cost-effectiveness of epidural analgesia compared with opioid analgesia found opioid analgesia to be more cost-effective than epidural analgesia, due to the higher costs of health care professionals associated with administering epidural, as well as higher costs associated with managing complications (21). Opioid administration in a Dutch study published in 2016 was associated with an estimated unit cost of €15 (about US$ 18) per procedure (including staff costs) (22). While in some high-resource settings parenteral opioid medicines are considered relatively inexpensive, these medicines may not be accessible in all settings, and in some LMICs they may not be affordable (18, 23). A dose of pethidine or fentanyl can cost less than US$ 1; tramadol can cost about US$ 1.30; diamorphine and meptazinol can cost around US$ 3 per dose; and remifentanil can cost around US$ 6.50 per dose. Naloxone (to reverse respiratory depression) costs about US$ 6 per dose. Equity No direct evidence was found on the impact of pain relief with parenteral opioids on equity. Indirect evidence from a review of facilitators and barrier to facility-based birth (8) indicates that “neglect and delays in receiving care” probably acts as a barrier to facility-based birth (moderate confidence in the evidence). Such neglect and delays might be applicable to labour pain management. The review also highlights that many women in LMICs fear “unfamiliar and undesirable” birth practices, which are barriers to facility-based birth (high confidence in the evidence). It is possible that some women might perceive injections to be unfamiliar and undesirable practices. Additional considerations: WHO’s 2015 State of inequality report concluded that there are still large gaps in skilled birth attendance coverage (24). Providing effective and timely labour pain relief to disadvantaged women might help to reduce inequalities in intrapartum care directly. Based on the limited evidence above, it might also impact equity indirectly, by encouraging more disadvantaged women to access facility-based care. However, in LMIC settings, some women may perceive medical pain relief options as unfamiliar and undesirable, which could act as a barrier to facility-based birth, particularly for women who believe that labour and childbirth are natural processes that do not need intervention, and those who would prefer a traditional approach to pain management. If women requesting pain relief are offered a choice of pharmacological and non-pharmacological (including traditional and cultural preferences) options, it might help to address inequalities in intrapartum care. Women requesting pain relief should be informed of the effects (desirable and undesirable) of the respective pharmacological options and be empowered to participate in the decision-making processes relating to labour and childbirth, including pain management. It has been argued that changing the attitudes of health care professionals and women surrounding labour pain (and reducing the medicalization of labour discomfort) could empower women to rediscover their innate birthing capabilities (25), which might positively impact equity by reducing the medicalization of childbirth among more advantaged women. Acceptability In a qualitative systematic review exploring women’s experiences of opioid use for pain relief during labour, there were mixed views (20). Some women requested opioids due to intense and unmanageable labour pains (very low confidence in the evidence). Opioids were reported to be an effective (very low confidence in the evidence) or ineffective form of pain relief (very low confidence in the evidence). Women continued to experience pain due to the pain relief method being ineffective, being provided too late or wearing off too early (very low confidence in the evidence). Some women experienced negative physiological (e.g. sickness, distorted cognitive processes, inability to achieve a physiological birth) and psychological (e.g. disappointment) impacts (very low confidence in the evidence). However, other review findings highlight that opioids increased women’s enjoyment, shortened and reduced the intensity of the contractions, and aided them to achieve a physiological birth (very low confidence in the evidence). Following opioid use, some women were disappointed due to an over-reliance on staff to administer the medication for them, and a lack of caregiver support (very low confidence in the evidence). Women were also not always fully aware of the route of administration or the risks of opioid use (very low confidence in the evidence). In another review that included health care provider experiences (21), no qualitative accounts of health care professionals’ views of opioid use in women during labour and childbirth were identified. Additional considerations: Overall, the review on women’s experiences of pain relief options (20) highlights the lack of high-quality qualitative evidence. While confidence in the evidence is very low, the majority of negative comments were expressed towards IM pethidine use, whereas opinions on intranasal and subcutaneous fentanyl were generally far more positive. It was not possible to identify, within the included studies, whether women valued the outcomes associated with opioids differently if they had had augmentation, induction of labour or other forms of intervention. It has been suggested in other studies that the care context and the type of care provision and care provider have a strong effect on the need for labour pain relief, and on the kinds of choices women make in relation to this need (21, 27). Feasibility In a qualitative systematic review exploring women’s experiences of opioid use during labour (21), the lack of effectiveness of opioids to relieve pain was sometimes attributed to late administration (very low confidence in the evidence), which suggests the need for more timely and sensitive use of this pain relief method. Additional considerations: In low-resource settings, where opioids are not so widely available and used, there are likely to be financial implications as well as additional training requirements for their administration and for the management of potential maternal and neonatal side-effects.
Comparison 2: Parenteral opioids (various types) compared with pethidine Meptazinol (IM) compared with pethidine (IM) Eight trials involving 2222 women compared IM meptazinol with IM pethidine. Trials were conducted in hospital settings in Denmark (2 trials), South Africa (2 trials) and the United Kingdom (6 trials). Sample sizes in individual trials ranged from 46 to 1100. The trials were published between 1981 and 1988. Maternal outcomes Pain relief: Compared with pethidine, it is not clear whether IM meptazinol makes any difference to pain scores, or to the use of additional analgesia or epidural, as the certainty of the evidence is very low. Low-certainty evidence suggests there may be little or no difference between groups for rating pain relief as “poor” (more than 60% in both groups) (1 trial, 801 women, RR 1.01, 95% CI 0.91–1.12). Mode of birth: Low-certainty evidence suggests there may be little or no difference in assisted vaginal birth (3 trials, 1266 women, RR 1.00, 95% CI 0.81–1.22), while it is not clear whether there is a difference between meptazinol and pethidine for caesarean birth, as the certainty of the evidence is very low. Side-effects: Moderate-certainty evidence suggests vomiting is increased with meptazinol (3 trials, 1589 women, RR 1.25, 95% CI 1.06–1.47), while low-certainty evidence suggests there is little or no difference between groups for maternal drowsiness (3 trials, 1590 women, RR 0.55, 95% CI 0.28–1.07). Breastfeeding: It is not clear whether meptazinol affects breastfeeding, as the certainty of the evidence is very low. Other maternal outcomes were not reported in the included trials. Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: It is not clear whether meptazinol makes any difference to FHR changes or Apgar scores more than 7 at 5 minutes, as the certainty of the evidence is very low. Side-effects: Low-certainty evidence suggests that meptazinol may make little or no difference to naloxone administration (1 trial, 975 babies, RR 0.89, 95% CI 0.77–1.02) or neonatal resuscitation (2 trials, 1333 babies, RR 1.0, 95% CI 0.95–1.05) in babies born at 36 weeks of gestation or later. Long-term adverse infant outcomes: These were not reported in the included trials.
Tramadol (IM) compared with pethidine (IM) Six trials involving 483 women compared IM tramadol versus IM pethidine. Trials were conducted in hospital settings in Austria, Germany, Iran, Thailand, Turkey and the United Kingdom. Sample sizes in individual trials ranged from 45 to 160. The trials were published between 1980 and 2009. Maternal outcomes Pain relief: Low-certainty evidence suggests that compared with pethidine, tramadol may increase the number of women reporting poor pain relief (38.8% vs 25.4%) (4 trials, 243 women, RR 1.56, 95% CI 1.10–2.21). Compared with pethidine, it is not clear whether IM tramadol makes any difference to women’s need for additional analgesia, as the certainty of the evidence is very low. Mode of birth: The evidence on the effect of tramadol compared with pethidine on caesarean birth or assisted vaginal birth is of very low certainty. Side-effects: Low-certainty evidence suggests that maternal sleepiness may be reduced with tramadol (5 trials, 409 women, RR 0.57, 95% CI 0.33–0.97), but it is unclear if the opioids are any different in terms of vomiting, as the certainty of the evidence is very low. Other maternal outcomes were not reported in the trials. Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: When compared with pethidine, it is not clear whether tramadol makes any difference to low Apgar scores at 5 minutes, as no events were reported in either group. Side-effects: It is unclear whether tramadol makes any difference to neonatal respiratory distress, as the certainty of the evidence is very low. There were no neonatal resuscitation events in trials where tramadol was compared with pethidine. Long-term adverse infant outcomes: These were not reported in the trials.
Tramadol (IM) with triflupromazine compared with pethidine (IM) with triflupromazine A single trial with 40 women conducted in Germany which was published in 1992 compared IM tramadol with IM pethidine; both groups also received triflupromazine (an antipsychotic sometimes used as an anti-emetic). Maternal outcomes Side-effects: It is not clear whether there is any difference between groups for vomiting or sleepiness, as the certainty of the evidence is very low. Other maternal outcomes were not reported in the trial Fetal and neonatal outcomes Fetal/neonatal outcomes were not reported in the trial.
Morphine or diamorphine (IM) compared with pethidine (IM) Maternal outcomes Pain relief: One trial involving 484 women in the United Kingdom which was published in 2014 compared IM diamorphine with pethidine. High-quality evidence suggests diamorphine probably slightly lowers maternal pain scores at 30 and 60 minutes compared with pethidine (MD -0.8, 95% CI -1.24 to -0.36 and MD -0.8, 95% CI -1.26 to 0.34, respectively, measured on a 10-point scale) and slightly increases the number of women satisfied with pain relief (RR 1.13, 95% CI 1.02–1.26). From another trial published in 1986 involving 135 women in Thailand, it is unclear whether IM morphine makes any difference to pain relief when compared with pethidine. Moderate-certainty evidence suggests there is little or no difference in the need for additional analgesia between morphine or diamorphine compared with pethidine (2 trials, 574 women, RR 1.00, 95% CI 0.92–1.10). Side-effects: Evidence on vomiting and sleepiness from the trial in Thailand with 135 women comparing IM morphine with pethidine is of very low certainty. Another trial in the United Kingdom with 161 women (133 analysed), published in 1999, examined diamorphine versus pethidine, with both groups receiving the anti-emetic prochlorperazine. Low-certainty evidence suggests that IM diamorphine plus prochlorperazine may reduce vomiting compared with pethidine plus prochlorperazine (RR 0.39, 95% CI 0.17–0.86). Mode of birth: Moderate-certainty evidence suggests there is little or no difference between the groups for caesarean birth (RR 0.94, 95% CI 0.66–1.35) or assisted vaginal birth (RR 1.28, 95% CI 0.91–1.80). Other maternal outcomes were not reported in these trials. Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: Moderate-certainty evidence suggests there is little or no difference between diamorphine or morphine compared with pethidine in neonatal resuscitation (2 trials, 574 babies, RR 0.96, 95% CI 0.66–1.41). Long-term adverse neonatal outcomes: These were not reported.
Dihydrocodeine (IM) compared with pethidine (IM) One trial conducted in South Africa with 196 women, which was published in 1970, is included in this comparison. Maternal outcomes Pain relief: The certainty of this evidence is very low. Side-effects: The certainty of evidence on vomiting and sleepiness is very low. Other maternal outcomes were not reported in the trial. Fetal and neonatal outcomes Fetal/neonatal outcomes were not reported in the trial.
Pentazocine (IM) compared with pethidine (IM) Six trials compared pentazocine with pethidine (IM); all the trials except one are more than 40 years old – the most recent was published in 1980. The certainty of the evidence for all but one of the outcomes reported is very low. Maternal outcomes Side-effects: Low-certainty evidence suggests nausea may be lower with pentazocine (3 trials, 391 women, RR 0.46, 95% CI 0.24–0.90). Other maternal outcomes were not reported in the trials. Fetal and neonatal outcomes Fetal/neonatal outcomes were not reported in the trials.
Nalbuphine (IM) compared with pethidine (IM) Three trials with 430 women conducted in Argentina, Germany and the United Kingdom, and published between 1986 and 1999, are included in this comparison. The certainty of the evidence is very low for most of the outcomes reported. Maternal outcomes Pain relief: Low-certainty evidence from a single trial with 72 women suggests maternal satisfaction with pain relief may be reduced with nalbuphine (RR 0.73, 95% CI 0.55–0.96). Low-certainty evidence suggests that nalbuphine makes little or no difference to the use of epidural as additional analgesia (1 trial, 307 women, RR 1.65, 95% CI 0.55–4.94) Side-effects: Moderate-certainty evidence suggests nausea and vomiting is less frequent with nalbuphine (1 trial, 72 women, RR 0.41, 95% CI 0.18–0.94). Mode of birth: Low-certainty evidence suggests there may be little or no difference between groups for caesarean birth (1 trial, 310 women, RR 0.45, 95% CI 0.12–1.69). Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: One study with 72 babies compared infant behavioural scores at 2–4 hours after birth and low-certainty evidence suggests slightly lower (worse) scores in infants whose mothers received nalbuphine (MD -3.7, 95% CI -1.26 to -6.14). Long-term adverse neonatal outcomes: These were not reported in the trials.
Phenazocine (IM) compared with pethidine (IM) A single trial with 212 women conducted in the United Kingdom and published in 1970 compared IM phenazocine versus pethidine. Maternal outcomes Pain relief: The certainty of the evidence is very low for use of epidural analgesia as additional intervention. Side-effects: Low-certainty evidence suggests vomiting may be less frequent with phenazocine (RR 0.39, 95% CI 0.20–0.78). Other maternal outcomes were not reported in the trial. Fetal and neonatal outcomes Fetal/neonatal outcomes were not reported in the trial.
Butorphanol (IM) compared with pethidine (IM) A single trial with 80 women conducted in Germany and published in 1978 is included in this comparison. It is not clear whether the medications have any differential effect on outcomes, as the certainty of the evidence is very low for all outcomes reported.
Fentanyl (IV) compared with pethidine (IV) A single trial with 105 women conducted in the USA and published in 1989 is included in this comparison. The certainty of the evidence for most outcomes reported is very low. Maternal outcomes Pain relief: Low-certainty evidence suggests women receiving fentanyl may need slightly more doses of the medication (MD 0.4 higher, 95% CI 0.14–0.66 higher), but may report slightly reduced maternal pain scores 1 hour after administration compared with pethidine (MD 0.20 lower, 95% CI 0.34–0.06 lower). Side-effects: Low-certainty evidence suggests maternal sedation may be slightly less with fentanyl (RR 0.05, 95% CI 0.00–0.82). Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: Low-certainty evidence suggests that infant neuro-behavioural scores at 1–2 hours after birth may be higher if mothers received fentanyl rather than pethidine (MD 1.30, 95% CI 0.15–2.45 higher). Long-term adverse neonatal outcomes: These were not reported in the trial.
Nalbuphine (IV) compared with pethidine (IV) A single trial with 28 women conducted in the USA and published in 1995 examined this comparison. Maternal outcomes Mode of birth: The certainty of the evidence is very low for caesarean birth. No other relevant maternal outcomes were reported in this trial. Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: There were no babies with low Apgar scores at 5 minutes. Long-term adverse neonatal outcomes: These were not reported in the trial.
Phenazocine (IV) compared with pethidine (IV) A single trial with 194 women conducted in the USA and published in 1964 examined this comparison. The certainty of the evidence is very low for all outcomes reported or there are no events. Most outcomes were not reported. Perinatal death: none were reported (low-certainty evidence).
Butorphanol (IV) compared with pethidine (IV) Three studies with 330 women, all conducted in the USA and published between 1979 and 2005, compared IV butorphanol with IV pethidine. Maternal outcomes Pain relief: Low-certainty evidence suggests that pain scores may be slightly lower and pain relief slightly higher for women in the butorphanol group (1 trial, 80 women, MD -0.6, 95% CI -1.02 to -0.18 and MD 0.67, 95% CI 0.25 to 1.09, respectively). The certainty of the evidence is very low for use of epidural analgesia or the need for further analgesia. Mode of birth: The certainty of the evidence is very low for assisted vaginal birth and caesarean section. Side-effects: Low-certainty evidence suggests vomiting may be reduced with butorphanol (1 trial, 200 women, RR 0.04, 95% CI 0.00–0.67). No other relevant maternal outcomes were reported in these trials. Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: The evidence regarding low infant Apgar scores at 5 minutes is of very low certainty. Long-term adverse neonatal outcomes: These were not reported in the trials.
Morphine (IV) compared with pethidine (IV) Two studies with 163 women conducted in Sweden (1996) and the USA (1961) provided data for this comparison. Maternal outcomes Pain relief: Low-certainty evidence suggests that women may be slightly less satisfied with pain relief with morphine (1 trial, 141 women, RR 0.87, 95% CI 0.78–0.98), and may be more likely to require additional doses of analgesia (1 trial, 143 women, RR 3.41, 95% CI 1.90–6.12). Mode of birth: In a study with 20 women, no women required caesarean section. No other guideline outcomes were reported in these trials.
Alphaprodine (IV) compared with pethidine (IV) A single USA trial published in 1958 with data for 395 women compared IV alphaprodine with IV pethidine. Maternal outcomes Side-effects: Moderate-certainty evidence suggests vomiting is less frequent with alphaprodine (RR 0.38, 95% CI 0.22–0.66). No other relevant maternal outcomes were reported in these trials. Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: The evidence on neonatal resuscitation is of very low certainty. Long-term adverse neonatal outcomes: These were not reported in the trial.
Patient-controlled analgesia (PCA) pentazocine compared with PCA pethidine A single trial with 29 women conducted in South Africa examined this comparison. The certainty of the evidence is very low for all reported outcomes.
PCA remifentanil compared with PCA pethidine Three trials with 237 women conducted in the United Kingdom (2 trials) and the Netherlands (1 trial) published between 2001 and 2010 are included in this comparison. Maternal outcomes Pain relief: Low-certainty evidence suggests there may be little or no difference between groups for maternal pain scores in labour (2 trials, 122 women, MD -8.59, 95% CI -27.61 to 10.44). Moderate-certainty evidence suggests use of epidural analgesia is lower with remifentanil (2 trials, 122 women, RR 0.42, 95% CI 0.20–0.89). Mode of birth: Low-certainty evidence suggests that there may be little or no difference for assisted vaginal or caesarean births (2 trials, 97 women, RR 0.96, 95% CI 0.46–2.00 and RR 1.81, 95% CI 0.60–5.46, respectively). Birth experience: Moderate-certainty evidence suggests that satisfaction with childbirth experience was slightly higher with remifentanil (1 trial, 68 women, MD 1.1, 95% CI 0.46–1.74). Side-effects: Moderate-certainty evidence from a single trial with 105 women suggests that sleepiness is slightly increased with remifentanil (MD 0.4, 95% CI 0.14–0.66). Low-certainty evidence suggests there may be little or no difference between groups for nausea and vomiting (2 studies, 119 women, RR 0.95, 95% CI 0.61–1.49). Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: Low-certainty evidence suggests there may be little or no difference in Apgar scores at 5 minutes (1 trial, 17 infants, RR 0.13, 95% CI 0.01–2.16). The certainty of the evidence is very low for naloxone administration. Low-certainty evidence suggests there may be little or no difference in neuro-behavioural scores in infants after 2 hours (1 trial, 56 infants, MD 0.6, 95% CI -0.66 to 1.86). Long-term adverse neonatal outcomes: These were not reported in the trials.
PCA nalbuphine compared with PCA pethidine This comparison is examined in a single study with 60 women conducted in the United Kingdom published in 1987. Maternal outcomes Pain relief: Low-certainty evidence suggests that maternal pain scores in labour may be slightly reduced by PCA nalbuphine compared with PCA pethidine (MD -0.51, 95% CI -1.02 to 0). The relative effects of the interventions are unclear, as the certainty of the evidence is very low for all outcomes reported. No other relevant maternal outcomes were reported in this trial. Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: These outcomes were not reported in the trial. Long-term adverse neonatal outcomes: These outcomes were not reported in the trial.
PCA fentanyl compared with PCA pethidine A single trial with data for 120 women is included in this comparison. The study was conducted in the Netherlands and published in 2010. Maternal outcomes Pain relief: Low-certainty evidence suggests there may be little or no difference between the interventions for maternal pain scores (MD -0.65, 95% CI -1.56 to 0.26). Moderate-quality evidence suggests that use of epidural analgesia is lower in women receiving PCA fentanyl (RR 0.44, 95% CI 0.21–0.92). Mode of birth: Low-certainty evidence suggests there may be little or no difference between the interventions for assisted vaginal birth (RR 0.57, 95% CI 0.22–1.49) or caesarean birth (RR 0.25, 95% CI 0.03–2.34). Side-effects: Low-certainty evidence suggests there may be little or no difference in maternal sleepiness scores (MD -0.16, 95% CI -0.25 to 0.13) or vomiting (RR 0.87, 95% CI 0.55–1.37). Fetal and neonatal outcomes Perinatal hypoxia-ischaemia: Low-certainty evidence suggests little or no difference in infant neurobehavioral scores at 2 hours after birth (MD 0.5, 95% CI -1.95 to 0.95). Additional considerations The data available for the qualitative review on women’s experiences of opioid use during labour were very limited – they were obtained from just three studies (2 in high-income countries and 1 in an upper-middle-income country) (21). One of these studies contained minimal data to inform the review, and one involved qualitative interviews with women involved in an RCT of different opioid regimens. All participants were women who had requested pain relief. It was not possible to identify, within the included studies, whether women had had augmentation, induction of labour or other forms of intervention that may have influenced their valuation of the outcomes associated with this form of pain relief. Resources No evidence on the relative cost or cost-effectiveness of the different opioid analgesics was found. However, a USA review of the cost-effectiveness of epidural analgesia compared with opioid analgesia found opioid analgesia to be more cost-effective than epidural analgesia, due to the higher costs of health care professionals associated with administering epidural, as well as higher costs associated with managing complications (22). Opioid administration in a Dutch study published in 2016 was associated with an estimated unit cost of €15 (about US$ 18) per procedure (including staff costs) (23). Additional considerations While in some high-resource settings parenteral opioid medications are considered relatively inexpensive, these medications may not be accessible in all settings and in some LMICs they may not be affordable (136, 137). A dose of pethidine or fentanyl can cost less than US$ 1; tramadol can cost about US$ 1.30; diamorphine and meptazinol can cost around US$ 3 per dose; and remifentanil can cost around US$ 6.50 per dose. Naloxone (to reverse respiratory depression) costs about US$ 6 per dose.1 Equity No direct evidence was found on the impact of pain relief with any parenteral opioids on equity. Indirect evidence from a review of facilitators and barrier to facility-based birth (8) indicates that “neglect and delays in receiving care” probably acts as a barrier to facility-based birth (moderate confidence in the evidence). Such neglect and delays might be applicable to labour pain management. The review also highlights that many women in LMICs fear “unfamiliar and undesirable” birth practices, which are barriers to facility-based birth (high confidence in the evidence). It is possible that some women might perceive injections to be unfamiliar and undesirable practices. Additional considerations If women requesting pain relief are informed about and offered a choice of pharmacological and nonpharmacological (including traditional and cultural preferences) options, it might help to address inequalities in intrapartum care, by giving women more control of their childbirth experience. Women requesting pain relief should be informed of the effects (desirable and undesirable) of the respective available pharmacological options and be empowered to participate in the decision-making processes relating to labour and childbirth, including pain management. Use of expensive opioid alternatives might have a negative impact on equity if these are preferentially used in high-resource settings and more advantaged populations. It has been argued that changing the attitudes of health care professionals and women surrounding labour pain (and reducing the medicalization of labour discomfort) could empower women to rediscover their innate birthing capabilities (29), which might positively impact equity by reducing the medicalization of childbirth among more advantaged women. Acceptability In a qualitative systematic review exploring women’s experiences of opioid use for pain relief during labour, there were mixed views (21). Some women requested opioids due to intense and unmanageable labour pains (very low confidence in the evidence). Opioids were reported to be an effective (very low confidence in the evidence) or ineffective form of pain relief (very low confidence in the evidence). Women continued to experience pain due to the pain relief method being ineffective, being provided too late or wearing off too early (very low confidence in the evidence). Some women experienced negative physiological (e.g. sickness, distorted cognitive processes, inability to achieve a physiological birth) and psychological (e.g. disappointment) impacts (very low confidence in the evidence). However, other review findings highlight that opioids increased women’s enjoyment, shortened and reduced the intensity of the contractions, and aided them to achieve a physiological birth (very low confidence in the evidence). Following opioid use, some women were disappointed due to an over-reliance on staff to administer the medication for them, and a lack of caregiver support (very low confidence in the evidence). Women were also not always fully aware of the route of administration or the risks of opioid use (very low confidence in the evidence). In another review that included health care provider experiences (30), no qualitative accounts of health care professionals’ views of opioid use were identified. Additional considerations Overall, the review on women’s experiences of pain relief options (21) highlights the lack of high-quality qualitative evidence. While confidence in the evidence is very low, the majority of negative comments were expressed towards IM pethidine use, whereas opinions on intranasal and subcutaneous fentanyl were generally far more positive. It has been suggested in other studies that the care context and the type of care provision and care provider have a strong effect on the need for labour pain relief, and on the kinds of choices women make in relation to this need (27, 28). Feasibility In a qualitative systematic review exploring women’s experiences of opioid use during labour (21), the lack of effectiveness of opioids to relieve pain was sometimes attributed to late administration (very low confidence in the evidence), which suggests the need for more timely and sensitive use of this pain relief method. Additional considerations In lower-resource settings, where opioids are not so widely available and used, there are likely to be financial implications as well as additional training requirements for their administration and for the management of potential maternal and neonatal side-effects. It is likely that the type of opioid used in different settings and countries would be influenced by the cost of the medication.
Further information and considerations related to this recommendation can be found in the WHO guidelines, available at: http://apps.who.int/iris/bitstream/10665/250796/8/9789241549912-websupplement-eng.pdf?ua=1 http://apps.who.int/iris/bitstream/handle/10665/260178/9789241550215-eng.pdf;jsessionid=7E800B590A164DC7FC879E73B480D6FC?sequence=1
Implementation considerations The successful introduction of evidence-based policies related to intrapartum care into national programmes and health care services depends on well-planned and participatory consensus-driven processes of adaptation and implementation. These processes may include the development or revision of national guidelines or protocols based on this recommendation. The recommendation should be adapted into locally-appropriate documents and tools that are able to meet the specific needs of each country and health service. Modifications to the recommendation, where necessary, should be justified in an explicit and transparent manner. An enabling environment should be created for the use of this recommendation, including changes in the behaviour of health care practitioners to enable the use of evidence-based practices. Local professional societies may play important roles in this process and an all-inclusive and participatory process should be encouraged.
Health policy considerations
Organizational or health-system-level considerations
Community-level sensitization activities should be undertaken to disseminate information about:
Research implications The GDG identified these priority questions related to this recommendation:
Related links WHO recommendations on intrapartum care for a positive childbirth experience (2018) - full document and evidence tables Managing Complications in Pregnancy and Childbirth: A guide for midwives and doctors Pregnancy, Childbirth, Postpartum and Newborn Care: A guide for essential practice WHO Programmes: Sexual and Reproductive health Maternal Health
References
Citation: WHO Reproductive Health Library WHO recommendation on opioid analgesia for pain relief during labour. (February 2018). The WHO Reproductive Health Library; Geneva: World Health Organization. You may also want to readWHO recommendation on interventions targeted at women for the reduction of unnecessary caesarean sections Health education for women is an essential component of antenatal care Read ArticlePlanned elective repeat caesarean section versus planned vaginal birth for women with a previous caesarean birth Citation: Dodd JM, Crowther CA, Huertas E, Guise JM, Horey D. Planned elective repeat caesarean section versus planned vaginal birth for women with a previous caesarean birth Cochrane Database of Systematic Review 2013, Issue 12. Art. No.: CD004224. DOI: 10.1002/14651858.CD004224.pub3. Read ArticleWHO recommendation on respectful maternity care during labour and childbirth Respectful maternity care – which refers to care organized for and provided to all women in a manner that maintains their dignity, privacy and confidentiality, ensures freedom from harm and mistreatment, and enables informed choice and continuous support during labour and childbirth – is... What opioid is used in epidural?Morphine. The first reported opioid used in the epidural space, and perhaps the most widely studied after epidural administration, is morphine. Moreover, morphine was the first opioid approved by the Food and Drug Administration for intraspinal administration.
Which opioid used for epidural analgesia has the shortest duration of action?In general, lipophilic opioids produce short-term analgesia (1-4 hours), which is very useful for immediate postoperative pain. However, morphine produces intense analgesia for up to 24 hours with doses as low as 100 μg.
What drug is used in epidural block?Typically, an epidural injection includes a corticosteroid, such as methylprednisolone, betamethasone, or triamcinolone, plus a small amount of a local anesthetic, such as lidocaine or bupivacaine.
What is the use of epidural analgesia?Anesthesiologists use epidural analgesia for people who are in labor and are delivering a baby. They inject the epidural into your lower back to provide pain relief for the lower part of your body due to contractions and childbirth. Anesthesia is the loss of physical sensation with or without loss of consciousness.
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