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Using remifentanil in labour via patient-controlled analgesia

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Lynn Grigg, BA (Hons), RGN; Ruth Day, MA, BA (Hons), RGN.

Lynn-Lecturer/Practitioner in Pain Management; Ruth-Nurse Consultant in Pain Management, Luton and Dunstable Hospital NHS Trust and University of Luton, Bedfordshire

The use of intravenous (IV) remifentanil through patient-controlled analgesia (PCA) for women in labour within a delivery ward is being advocated by some pain teams. This paper will discuss the evidence to support its use and a comparison will be made regarding its efficacy and safety with some of the more commonly used analgesics in the labour ward.
The use of intravenous (IV) remifentanil through patient-controlled analgesia (PCA) for women in labour within a delivery ward is being advocated by some pain teams. This paper will discuss the evidence to support its use and a comparison will be made regarding its efficacy and safety with some of the more commonly used analgesics in the labour ward.

Attitudes to pain relief in labour
The pain of labour has evoked many responses over the centuries. With the rise of Christianity in the Western world the Bible taught women that child-bearing meant pain: 'I shall give you intense pain in childbearing, you will give birth to your children in pain' (Genesis 3:16). Before Christianity it seems that the pains of labour were seen as the action of evil spirits (Bonica, 1990). This acceptance that pain was inevitable and a normal part of labour, was questioned by Dick-Read in 1933. His text was seminal in re-thinking the role of midwives in labour and in the 'natural childbirth' movement.

Whatever a society's understanding about the reason for labour pain, a variety of ways of trying to control it have been used. Soranus, writing in the first century for Roman midwives, suggests both physical and psychological approaches: 'For normal childbirth have the following ready ... hot compresses to relieve the labour pain ... two couches, the one made up with soft coverings for rest after giving birth, the other hard for lying down on between labour pains... Three women should stay ready who are able gently to calm the fears of the woman who is giving birth...' (Lefkowitz and Fant, 1982).

Some pharmacological agents were also used such as concoctions made from plants (poppy, mandragora and henbane) and alcohol (Bonica, 1990). Anaesthetic agents, such as ether and chloroform, were available in the mid-1800s (Queen Victoria being the most famous user) but little changed for most women until a 100 years later. Bonica (1990) suggests that the reasons for change in the West in the past 50 years include:

- A growing number of anaesthetists with an interest in obstetrics

- An increasing number of hospital births

- A growing interest by women in receiving effective pain relief

- A recognition by obstetricians of the benefits to mother and child

- A decline in the influence of religion in such matters.

Incidence of labour pain
McCaffery's statement that 'the 'gold standard' for assessing the existence and intensity of pain is the patient's self-report' holds true for labour pain as much as that of any other type (McCaffery and Pasero, 1999). It is affected by previous experience and expectations, as well as the size of the baby and primiparity (Mander, 1998). Research by Melzack (1984) confirmed that first-time mothers reported higher pain scores than multiparae (Table 1).

Comparison using the McGill Pain Questionnaire (Melzack, 1975) showed that pain scores for labour pain in both primiparae and multiparae were greater than the scores given by patients with chronic back pain, post-herpatic neuralgia and phantom limb pain (Melzack and Katz, 1999).

This objective data confirms the subjective opinion that many women hold - that labour pain is one of the most painful experiences a woman may have. It is little surprise that over the centuries (and sometimes against the will of doctors and priests) people have searched for ways of alleviating labour pain. The objective of good pain relief in labour must be to provide the best relief possible to the mother with the least risk to mother and child.

Pain-relief options
Pain relief can be viewed in three main groups, some of which overlap with each other. These groupings are physical, psychological and pharmacological.

Physical This would include the hot compresses mentioned above, transcutaneous electrical nerve stimulation (TENS) (McQuary and Moore, 1998) and massage. A warm bath would be included in this group as would acupuncture. There is limited evidence to support the efficacy of these treatments but many women find them useful (Mander, 1998) These modalities activate the sensory modulation of pain - see Mander (1998) for an explanation of the gate-control theory of pain - and are thought to 'close the gate' to pain impulses.

Psychological Soranus's three women provided psychological support for the woman in labour by trying to alleviate her fears. As well as having a partner for support, women in labour may make use of a number of approaches such as relaxation, guided imagery and hypnotherapy. There is less evidence available for the efficacy of these treatments but Melzack and Wall (1996) suggest that they work by activating the descending mechanisms to 'close the gate'. They also say that 'different psychological procedures may each have different predominant effects, so that several procedures together work better'.

Pharmacological Entonox (an inhaled agent) is frequently used in the control of pain in labour. Time has moved on since drops of opium were given but opiates are still often a mainstay of pain relief in labour. However opioids are not without side-effects, both for the mother and child (Mander, 1998; Moore, 1997). There is some research comparing opioids (Torrance et al, 2003) but no particular opioid appears better than another. Opioids are often given intramuscularly (IM) or in combination with local anaesthetics in a spinal or epidural injection. They can also be used intravenously via PCA equipment; the use of the short-acting opioid remifentanil is explored below.

What is remifentanil?
Remifentanil is an opioid with mu-specific activity, antagonised by naloxone, and is most commonly used in anaesthesia. It is usually given during the induction of a general anaesthetic, supplementing other analgesic regimens intra-operatively. It has a very rapid onset and short duration of action due to its unique metabolism, giving it a half-life of only three minutes (Volikas and Male, 2001). The pharmacokinetic properties of this opioid have, therefore, led to investigations for use in the field of obstetrics.

According to Volikas and Male, despite the expected rapid transfer, fetal exposure appears to be low because of rapid metabolism and/or redistribution. When administered as a continuous IV infusion, remifentanil rapidly crosses the placenta and is quickly metabolised and redistributed in the fetus. However, when intermittent boluses were given, Olufolabi et al (2000) reported that there were no reports of associated increases in newborn respiratory depression or lower Apgar scores.

The study by Olufolabi et al (2000) looked at the feasibility of giving bolus doses of remifentanil to patients in labour for whom epidural analgesia was contraindicated (see Box 1). This method soon evolved to using PCA for delivery of the drug as giving the drug by a third party proved to be ineffective because of the communication lag and subsequent onset delay (Dhileepan, 2001). When offered through a PCA system, patients can learn to anticipate contractions and make an early effective demand (Dhileepan, 2001).

PCAs are not new in the labour ward arena and PCA is the standard method of delivery for Entonox. In the past, pethidine (Evans et al, 1976), butorphanol tartrate (Vogelsang and Hayes, 1991), tramadol (Lewis and Han, 1997), nalbuphine (Frank et al, 1987) and fentanyl (Kleiman et al, 1991; Rosaeg et al, 1992) have all been used in labour via a PCA. However, personal observation and anecdotal evidence suggests that, in most labour wards, the choice for a vaginal delivery is between an epidural or IM pethidine supplemented with Entonox. If the patient is not suitable for an epidural then the choices are limited, a view supported by Owen et al (2002).

There have been mixed reports regarding the use of PCA remifentanil in labour and, according to Thurlow and Waterhouse (2000), there have been no controlled studies regarding its use. Nevertheless, results from some small studies are encouraging, including those of Thurlow and Waterhouse (2000), Volikas and Male (2001) and Owen et al (2002). As remifentanil is such a short-acting drug with a rapid onset - time to peak effect is 60 to 90 seconds according to Saunders and Glass, (2002) - it appears to be an acceptable alternative when an epidural is contraindicated.

PCA is simple and uncomplicated to use and boluses can easily be increased as contractions become more painful. The alternative may be painful IM injections of pethidine. Treating pain with pain is actively discouraged by most pain teams and intermittent IM injections do not allow for matching analgesic delivery to the pain. Furthermore, pethidine is less used as a drug of choice because of its side-effects (Mann and Redwood, 2000). However, as Owen et al (2002) point out, remifentanil is not approved for obstetric use and further studies need to be carried out to ascertain its safety and appropriateness in the management of labour. This does not mean that we have to deprive the very small minority of patients deemed unsuitable for an epidural of this drug because prescribing clinicians can use drugs outside the licensed indication if they consider this appropriate. (Many drugs used at present epidurally are not licensed for that route.)

Case study: experience with remifentanil
In our trust, a large district general hospital with a well-established obstetric unit, we have used remifentanil intravenously by PCA for three patients for whom epidural analgesia was contraindicated. One of these patients was a 32-year-old primigravida, born with spina bifida occulta (a bony defect in the bony arch of the spine), making her unsuitable for epidural insertion. She presented to the labour ward at 38 weeks' gestation with spontaneous rupture of membranes and in active labour. Entonox was given for the first two hours before the decision was made, by the on-call anaesthetist, to offer her a remifentanil PCA.

Midwives were understandably apprehensive for several reasons. They had never heard of remifentanil and therefore were unaware of the side-effects or the monitoring required. The anaesthetist explained that the potential side-effects were respiratory depression, sedation, nausea and vomiting, facial pruritus, fetal bradycardia and chest-wall rigidity. Some of these are reported side-effects of any opioid, although respiratory depression and sedation are rare (Mann, 2003). This was explained to the patient and she was assured that the PCA would be stopped immediately if any adverse effects were observed.

Continuous monitoring of both mother and fetus was continued every 15 minutes until discontinuation of the PCA and delivery of the baby. Entonox was given as supplementary analgesia and the anaesthetist was available at all times throughout the labour. The bolus dose was increased and titrated to pain as the labour progressed. The woman was assessed continually throughout labour to ensure she had adequate pain relief and was questioned soon after the birth about the efficacy of the analgesia she had received.

Although the PCA had not taken away all the pain of labour, she said that it had helped considerably. She said that the main advantage was the degree of control she had had to manage the contractions. The woman commented that she had felt slightly drowsy between contractions but this had quickly worn off. She experienced no nausea and no pruritus. A healthy baby girl was born by normal vaginal delivery and no neonatal resuscitation was needed. The day after delivery the woman was asked to rate the quality of analgesia as excellent, very good, good, poor or very poor. She responded that it was 'very good'.

It may be that remifentanil will become a new way forward in providing labouring women with another option, to provide optimal pain relief for mother and safety for the child.

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