In order to consider how to work with pain in labour it is important to understand its function in labour and birth. By understanding the physiological role of intrapartum pain, it is possible to evaluate the risk/benefit ratio of the use of pain management more accurately.
The term ‘pain’ itself is controversial in some circles. as some believe that the delicate hormonal balance of naturally occurring endorphins and birth hormones can be negatively influenced by a variety of psychological factors, including the use of language. Some authors therefore prefer to use alternative terminology (Gaskin, 2002). While considering the physiological aspects of pain, this review will use the matching medically orientated terminology.
During the onset of spontaneous, non-augmented labour, there is a complex interplay between naturally occurring hormones, such as ß-endorphins, that are stimulated by pain receptors and which subsequently stimulate the production of oxytocin (Lowe, 2002), forming a feedback loop and promoting the progression of labour (Foureur, 2008).
However, pain is widely perceived as an unwanted aspect of labour, and a source of distress to women, their birth partners and their carers. Writings indicate that there are variations in the manner in which labour pain is perceived, interpreted and managed, depending on individuals' viewpoints (Leap, 2010; Madden et al, 2013). In a classic text on childbirth, Grantly Dick-Read (1954) discussed the fear-tension-pain relationship. In this, he proposed that women experience greater levels of distress (equated in this context with pain) in labour if they had an expectation that labour and childbirth would be painful. This is supported by more recent literature, which has stated that women report lower levels of pain if they have continual support in labour, as this lowers the level of distress (Hodgett et al, 2011). This is one of several studies and reviews that have indicated that psychological factors have a measurable and significant impact on pain levels in labour and cannot be considered independently of the physiological process (Leap et al, 2010; Green et al, 2003).
One of the historic justifications for the introduction of opiates in intrapartum care in the early 1900s was to shorten labour by relaxing women (Goodson and Martis, 2014)—although this is not supported by more recent findings. Other researchers have highlighted that high distress levels in birthing women contribute to and increase respiratory rate and circulating catecholamine levels. These are then linked to a range of possible adverse outcomes for the neonate, including fetal distress caused by prolonged labour and increased metabolic acidosis in the neonate, which is in turn linked to poor neonatal outcome (Reynolds, 2010). This suggests a need to manage labour pain in order to achieve optimal outcomes for mother and fetus/neonate but not necessarily by automatic recourse to pharmacological methods.
Guidance from the National Institute for Health and Care Excellence (NICE) on intrapartum care states that women should be offered a range of pain management options in labour (NICE, 2014). This includes access to water, inhaled analgesia, intramuscular opiates and regional analgesia. NICE guidelines also recommend that women in established labour receive continual one-to-one support, which is congruent with research that has linked reduced pharmacological pain relief with increased support in labour (Hodgett et al, 2011). The adoption of these policies into local guidance appears widespread, according to surveys of practice across the UK, which see some form of intrapartum opioids routinely available to birthing women in the majority of institutional settings (Tuckey et al, 2008).
Use of intramuscular opiates—a history
Pethidine, diamorphine and morphine are all opiates listed under the midwives' exemptions for intramuscular administration in labour for pain management (Nursing and Midwifery Council (NMC), 2011). Pethidine has historically been the most widely used opiate in labour (Reynolds, 2010) and, as such, has been subject to the largest body of research. Although it is given as an analgesic, the research suggests that its usefulness for the management of intrapartum pain is variable (Halls, 2008; Ullman et al, 2010), and that its primary action is as a sedative (Anderson, 2011). It is questionable as to whether this is desirable in labour, as it may impair a woman's ability to make informed choices, engage in her care and mobilise during labour—all of which are cornerstones to optimal midwifery care (Lawrence et al, 2009). Morphine and diamorphine have been relatively recent additions to the midwives' exemptions list (NMC, 2011). Early recorded uses of morphine in childbirth date from the 1900s, and it has been used previously under prescription. However, morphine is not frequently used in obstetric practice in the UK (Tveit et al, 2009).
Historically, there has been some suggestion that the use of pethidine can shorten labour and this was the justification for much of its use. An examination of the evidence for this (Thomson and Hillier 1994) suggested that the quality of the earlier studies was not robust, bringing their validity into question. The authors also stated that similar results had been found in animal studies. Shipton (2006) discussed the lack of clinical evidence of effectiveness of pethidine in labour before its introduction in New Zealand, including challenging the assumption that it shortens labour.
A study by Fairlie et al (1999) compared the use of intramuscular pethidine and diamorphine; results suggested that diamorphine has fewer adverse effects than pethidine. Fairlie et al acknowledged their trial was small (n=133), however, it appears to have informed a shift towards diamorphine usage, as there is little additional evidence available on this topic after this date, but a 2008 survey indicated that it was used in 34% of UK maternity units (Tuckey et al, 2008).
Wee et al (2014a) found an increased level of analgesia with diamorphine over pethidine, but also an increase in the length of labour. Diamorphine is also cited as having a more rapid onset (Fairlie et al, 1999). Montgomery et al (2014) highlighted that there was a lack of data regarding the use of rescue analgesia, or the use of a second dose of diamorphine, due to the increased length of labour and shorter half-life of diamorphine compared to pethidine. Further analysis suggested that, whatever other differences were found between the two opiates, neither were effective, as women in both groups continued to report significant pain levels and frequently requested additional analgesia (Wee et al, 2014b).
Wee et al (2014a) concluded that their results did not support the use of diamorphine for labour pain and called for further research into the long-term effects on the neonate.
How do opiates work?
All opiates act by binding to opioid receptors within the host. There are three classes of opiate receptors: vas deferens opiate receptors (DOP), morphine opiate receptors (MOP), and ketocyclazocine opiate receptors (KOP). The opioids in modern clinical practice are associated with the MOP receptors (Pathan and Williams, 2012). These receptors, in addition to mediating pain, are also associated with sedation, vomiting, respiratory depression, pruritus, euphoria, and urinary retention (Anderson, 2011).
Pethidine, morphine and diamorphine cross the placenta into fetal circulation. Additionally, diamorphine is metabolised to form morphine for use in the mother (Anderson, 2011). Diamorphine is more lipid soluble than morphine, so can cross the placenta more readily in this form. In doing so, it is hydrolysed to form morphine and cannot pass back as easily, so cannot re-enter maternal circulation as readily, diminishing the perceived analgesic effects and preventing its transportation to the maternal liver for extraction. Instead, there is reliance on the less mature fetal and neonatal liver. This results in increased circulating levels of morphine in the neonate, which is associated with an increased need for resuscitation (Rawal et al, 2007).
Pethidine is metabolised to form norpethidine (Goodson and Martis, 2014). Although the half-life of morphine is much shorter than that of norephedrine (Table 1), it is still significant, and both will impact on neonatal behaviours in the first hours of life.
| Opiate | Metabolite | Half life | |
|---|---|---|---|
| Opiate | Metabolite | ||
| Pethidine | Norpethidine | Maternal: 3–7 hours |
Adults: 21 hours |
| Morphine (from diamorphine) | Morphine-3-glucuronide |
Maternal: 43 minutes |
Adults: 2–4 hours |
Physiological individual difference in response to opiates
Anderson (2011) gives a comprehensive overview of the pharmacokinetics of the opiates that are commonly used in labour. Of particular interest is the discussion of the individual differences in the way women respond to opiates, which are linked to several variables including genetic variations in the MOP receptors (Trescot et al, 2008). There is evidence that certain polymorphisms can cause a variable response to the drug's action (Argoff, 2010) or cause an enzyme variation that results in the metabolism of the opiate taking place at an unexpected rate, resulting in higher than average levels of the metabolite to be present in the circulation (Zhou, 2009). Anderson states that this is a rapidly emerging field, and as such, this only represents a potentially small proportion of the genetic factors involved. This may explain the variations observed in women's responses to opiates, and it is logical to assume that the neonate will also have individual differences in their responses to opiates and their metabolites, yet there is nothing in the research to discuss this in relation to intrapartum analgesia.
Drug interactions
Anderson also highlights the interactions between some commonly used medications and the effects of opioids (Table 2). This includes erythromycin, an antibiotic that is commonly used in the UK for the treatment of pre-labour rupture of membranes (NICE, 2015) and which is stated to increase opioids' effects. National guidance on the use of opiates in the intrapartum period makes no reference to consideration of these individual differences other than the standard awareness of the need to individualise care and monitor women following any intervention (Anderson, 2011; NICE, 2014).
| Opioid | Drug | Effect |
|---|---|---|
| All | Alcohol | Increased central nervous system (CNS) depressant effect |
| All | Amphetamines | Increased analgesic effect of opioid |
| All | Phenothiazines | Increased hypotensive effect of opioid; some increase in respiratory-depressant effects, sedation, and/or analgesic effect |
| All | Antihistamines | Potentiates sedation and respiratory depression |
| All | CNS depressants (e.g. barbiturates) | Potentiates sedation and respiratory depression |
| All | Cimetidine (Tagamet) | Inhibits opioid metabolism; increased CNS toxicity |
| All | Erythromycin | Increased opioid effects |
| All | Selective serotonin reuptake inhibitors (SSRIs) | Increased serotonergic effect of SSRI; may cause serotonin syndrome |
| All | Antihypertensives | Increased orthostatic hypotension |
| Increased orthostatic hypotension | Monoamine oxidase inhibitors (MAOIs) | Increased respiratory depression, hyperpyrexia, CNS excitation, delirium, seizures; enhances serotonergic effect of meperidine |
| Fentanyl ketoconazole (Nizoral) | Ketoconazole (Nizoral) Itraconazole (Sporanox) | CYP34A inhibitor; increases fentanyl blood levels |
| Fentanyl | Selected HIV retrovirals | CYP34A inhibitor; increases fentanyl blood levels |
| Remifentanil, fentanyl | Beta blockers | Increased bradycardic and hypotensive effect |
| Remifentanil, fentanyl | Calcium channel blockers | Increased bradycardic and hypotensive effect |
| All | Herbs: valerian, St. John's wort, kava, gotu kola | May increase CNS depression |
Intramuscular opiate versus alterative pain management
Inhaled analgesia
Studies have indicated that the level of analgesia provided by opiates is less than inhaled analgesia (Alleemudder et al, 2015). Entonox is the most commonly used inhaled analgesic and is well documented as having a very short half-life, minimal maternal side effects, and no known adverse outcomes on the neonate (Reynolds, 2010).
Epidurals and spinal blocks
Neuro-axial analgesia has been found to have a more effective level of analgesia than opiates (Jones et al, 2012). There are known maternal side effects, including hypotension, intrapartum fever and an increase in instrumental delivery but no direct links with increased neonatal morbidity and mortality (Reynolds, 2011). Although an opiate is used within neuraxial analgesia, significantly lower levels are found in fetal circulation compared to intramuscular opiates (Wang et al, 2014). Epidural use has been linked to increased instrumental delivery (Anim-Somuah et al, 2011). There is a gap in the research picture regarding the long-term impact of instrumental delivery on maternal mental health.
Remifentanil in a patient-controlled device is used in some units, but there are concerns regarding respiratory depression, which requires increased surveillance of the mother, without providing any higher level of analgesia than more traditional intramuscular opiates (Howie et al, 2011; Van de Velde, 2008).
Hydrotherapy
The use of water and continuous support have been shown to improve maternal satisfaction with birth where opiates have not (Jones et al, 2012; Hodgett et al, 2011). It is unclear, however, if this is due to a reduction in the woman's experience of pain or an increase in her ability to cope with the pain, and further research is required.
Intravenous paracetamol
There have been some small-scale studies that have considered the use of intravenous paracetamol for pain management in labour (Abdollahi et al, 2014; Fletcher, 2010; Lallar et al, 2015) finding favourable results without the side effects associated with opiate-based analgesics.
Why are opiates still used so frequently?
One reason suggested in the literature for why opioids are still so frequently used, despite limited evidence for their effectiveness, is the ‘rescuer’ effect hypothesised by Leap and Anderson (2004). This research suggests caregivers' need to ‘do something’ to assist labouring women in distress. It has been highlighted elsewhere that intramuscular opiates are relatively cheap, easy to administer and accessible in hospital settings when compared to epidurals (Ullman et al, 2010). Leap's research examines perceptions of women's intrapartum pain from the perspective of the women, their birth partners, and midwives. She suggests two predominant models for reactions to pain from midwives, which can be broadly classified as the ‘working with pain’ paradigm (equated with a social model of birth) and the ‘pain relief’ paradigm (more closely aligned with the medical model of care). Leap's theory is supported by her other work that explores a decrease in the use of pharmacology pain management tools when women were able to establish long-term continuity of care (Leap, 2010; Leap et al, 2010). Leap's work uses small samples, as is common to qualitative work. It does not allow extrapolation to the general population but it includes in-depth exploration of discussions and engagements with women, both of which have been missing in previous studies.
A study by Madden et al (2013) concluded that women's least preferred form of pain management in labour was opiates. This study was a survey conducted in the postnatal period. Madden et al's analysis also concluded that antenatal preference for pain management may alter in labour but still provided a strong predictor of intrapartum preference. The midwives' survey in the same study reported disliking epidural pain management the most. Given the importance of women-centred care, this suggests a need for midwives to ensure their own preferences are not displayed when facilitating informed choice for women in their care, either antenatally or during the intrapartum period. This is reflected in the NICE intrapartum guidance, which states that health providers should be aware that their own views can influence choices for women in pain management (NICE, 2014).
‘NICE guidelines recommend that women in established labour receive continual one-to-one support, congruent with research that has linked reduced pharmacological pain relief with increased support in labour’
Tuckey et al (2008) also highlight that the use of opiates has persisted for so many years that they are often requested by women, who view them as a standard tool in the intrapartum period. A survey of practice in Norway (Tveit et al, 2009) suggested that continued systematic opioid use was due to tradition, rather than representing the most recent evidence-based practice.
Limitations
As intramuscular opiates for pain management are so common, it is surprising to note that a series of Cochrane Reviews in the area have failed to conclude that parental opioids are effective for pain management in labour (Bricker and Lavender, 2002; Jones et al, 2012; Ullman et al, 2010).
Bricker and Lavender's 2002 review of parental opiates for labour highlighted a gap in the research with regard to neonatal outcomes, specifically mother-baby interactions. There have been some studies that have considered breastfeeding as an outcome measure but there is extremely limited data considering any other postnatal effects of opiates on the neonate.
Much of the available research in the area is dated: some of the studies included in the most recent Cochrane Review date from the 1960s (Ullman et al, 2010). It is suggested that attitudes to care in labour have shifted over time, and that this would alter a holistic assessment of pain management in labour if some of the earlier studies were replicated today.
Conclusion
Intramuscular opioids remain a highly used component of modern intrapartum care. Research suggests that they are not necessarily an effective tool, and there are gaps regarding their longer terms effects. However, they have the advantage of being relative cheap, easy and timely to administer in comparison to other pain management options, as well as being a historically well-established part of intrapartum care for both women, their families and care givers. As such, it is unlikely that their use will be become less frequent in the near future—unless more viable alternatives, with a robust evidence base, can be identified.