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Abstract

Labour is one of the most painful experiences women encounter. Modern practice encompasses a number of techniques to alleviate this, from complementary therapies to invasive procedures. Pain induces a physiological stress response which has a number of deleterious effects on the body. Pharmacological methods of pain relief are the most popular – namely nitrous oxide, opioids and epidural analgesia. The latter is by far the most effective and is regarded as the gold standard. Importantly, intrapartum opioid use may be associated with the risk of neonatal respiratory depression. Nonpharmacological techniques vary in their efficacy. Of these hydrotherapy, acupuncture, continuous labour support and intradermal water blocks show the most promise. None of the methods available constitute the ideal analgesic for labour and choice should be based on maternal preference, with regular re-evaluation to ensure adequate effect.

 

Keywords

epidural; labour analgesia; nitrous oxide; opioids; pain relief
 

Provision of analgesia for women in labour has come a long way since the seminal use of ether by James Young Simpson in 1846. Modern practice encompasses a wide variety of techniques, ranging from complementary therapies to invasive neuraxial blockade. In this article we will examine each of these in turn and look at some of the current controversies within this area of anaesthesia.

 

Pathophysiology of labour pain

In order to treat labour pain effectively a knowledge of the pathways involved is required. Pain during the first stage of labour results from uterine contraction, thus is visceral and mediated by spinal nerves T10-L1 which innervate the myometrium. An additional somatic component arises from perineal stretching, which begins late in the first stage and persists throughout the second stage. This is transmitted via the pudendal nerve (S2–S4). The third stage is usually not particularly painful in comparison.

 

Aside from the primordial desire to ease another person's suffering, there are several reasons why adequacy of analgesia in labour should be given due consideration. These are largely related to minimising the undesirable systemic effects of severe pain.

 

Pain induces a physiological stress response which results in increased circulating catecholamine levels. The resultant tachycardia, hypertension and rise in cardiac output all increase myocardial workload and hence oxygen demand. While this is not a problem for most women, it can precipitate heart failure and even ischaemia in those with poor cardiorespiratory reserve. This bares particular importance since cardiac disease remains the leading cause of maternal death in the UK.

 

Pain also decreases the rate of gastric emptying, increasing the risk of aspiration in the event of emergency general anaesthesia. Additionally, it has been suggested that postnatal depression may be less common among women who receive effective analgesia in labour and that the increased adrenaline levels may in fact prolong labour through beta-receptor mediated uterine relaxation.

 

Of course the need for maternal analgesia must always be balanced against any potential risks of harm to the foetus, and in the remainder of this article we shall explore this in more detail.

 

Nonpharmacological methods of analgesia

A huge variety of nonpharmacological approaches to labour pain have been tried over the years, with variable success. Recent clinical trials have yielded promising results for several modalities – namely continuous labour support, acupuncture, intradermal water blocks and hydrotherapy. The availability of these varies geographically, but warrants due consideration as they are largely cheap, with few side effects and may be offered in combination or as adjuncts to pharmacological methods. For many other methods there is insufficient evidence at present to promote their use. We will concentrate on the more popular and promising therapies below.

 

Arguably the simplest method is continuous labour support, which describes the non-medical care of a parturient throughout her labour and delivery. This may be provided by a variety of personnel, though studies show greatest benefit when trained lay women (doulas) are used rather than midwives or nursing staff. Such practice is currently more widespread in the USA than the UK. Several trials have demonstrated a significant reduction in reported pain and use of analgesia in women receiving such support.

 

Hydrotherapy is widely available and involves immersion in warm water during labour. It is associated with high maternal satisfaction and lower pain scores; women report an initial reduction in pain on entering the water followed by a slower increase in intensity thereafter when compared to control groups. However there is no evidence for shortening of labour duration or alteration in surgical delivery rates. This form of analgesia is cheap, relatively easy to administer with few side effects when guidelines are followed.

 

Intradermal water blocks are designed to ease lower back pain in labour, which has an incidence of up to 75%. The blocks involve intradermal injection of 0.05 millilitres sterile water over the posterior superior iliac spines and a point inferomedial to these. There are no known side effects. Although this technique has been shown to consistently reduce back pain, the effect is short-lived lasting between 45 and 120 minutes. Perhaps it is for this reason that it is not more popular. As the injections specifically relieve back pain, with no effect on abdominal pain, there is no reduction in overall analgesia use.

 

Maternal mobility has been the focus of a number of studies. Evidence suggests that the vast majority (70%) of women who deliver in the hospital setting do not mobilise following their admission to labour ward. The main reasons cited for this include attachment to monitoring equipment, discouragement from midwives or lack of confidence in motor ability after analgesia administration. This is a marked difference to the recent past when women were encouraged to walk “to bring the labour on”. In addition to hastening foetal descent, mobilisation is known to reduce the severity of pain, either due to a direct effect in altering pelvic outlet diameter or indirectly through distraction. When stationary the upright, sidelying and squatting positions are all reported to cause less pain than lying supine. For these reasons freedom of movement during labour should be encouraged.

 

Acupuncture is becoming increasingly available, with a number of midwives in the UK now trained to offer this. A traditional form of Chinese medicine, acupuncture involves insertion of fine needles at specific points along channels of energy or “meridians” in the body, followed by stimulation of the needle using electricity, rotation or heat. This is believed to exert an analgesic effect by increasing the release of endorphins. Several studies have demonstrated effective relief of labour pain, with subsequent reduction in pethidine use. Furthermore, there are no known risks to either the mother or foetus, making this a promising area for continued research.

 

Transcutaneous Electrical Nerve Stimulation (TENS) is a popular method for pain relief in early labour in the UK, with handsets readily available to rent from many pharmacies. The technique uses electrodes placed over dermatomes supplied by the nerves responsible for labour pain (T10-L1 and S2-4). A high frequency low voltage electrical impulse is then passed through these electrodes, which inhibits pain signal transmission in the nerve roots (Gate Theory of pain). Additionally, TENS directly stimulates opioid receptors in the spinal cord leading to a rise in circulating endorphins. Despite its robust scientific roots, there is little convincing evidence for efficacy of TENS, though it has been noted observationally to have a modest effect in the early stages of labour.

 

Alternative methods including heat and cold application, aromatherapy, massage, hypnosis and audioanalgesia have been the subject of small scale trials and are not in widespread use.

 

Pharmacological methods of analgesia

Inhalational agents

Perhaps the oldest means of providing pain relief in childbirth is inhalational analgesia, which has been employed for over 100 years. Indeed Queen Victoria famously received chloroform during the birth of two of her children. Historically a variety of agents have been used including trichloroethylene, cyclopropane and methoxyflurane as well as the more familiar nitrous oxide. Common to all is the application of subanaesthetic concentrations to provide analgesia whilst preserving conscious level and protective airway reflexes.

 

Nitrous oxide: in the UK the most widely used agent is nitrous oxide, estimated to be used by up to 75% of women in labour. It is usually delivered premixed in a 1:1 ratio with oxygen (Entonox). A demand valve attached to the mouthpiece acts as a safety mechanism – it only opens when negative pressure is applied during inspiration. Hence if the patient becomes drowsy with consequent reduction in respiratory effort, no more Entonox is delivered and the patient will rouse again once the gas is eliminated through expiration.

 

The mechanism of action of nitrous oxide is not fully understood, though it is believed to result from increasing the activity of inhibitory pain pathways in the brain. It undergoes minimal metabolism and is excreted mainly through expiration, therefore is not dependent on renal or hepatic function for elimination. Due to its low solubility in blood it has a very rapid onset and offset and in healthy individuals has little effect on the cardiorespiratory system.

 

There are many advantages of nitrous oxide. It can be used at any stage in labour, for any duration, either alone or with other agents. It is cheap, does not require increased levels of monitoring and has an encouraging safety profile, having been used for many years. The drug has no effect on uterine contractions and thus does not alter the progress of labour. In this way it differs from other inhalational agents which have been shown to markedly reduce contractility thereby slowing labour and increasing the risk of postpartum haemorrhage. Importantly nitrous oxide has no effect on the foetus, with several studies demonstrating no alteration in Apgar or neonatal neurobehaviour scores. It is also safe for breast-feeding.

 

Potential side effects include drowsiness, dizziness and more rarely paraesthesia. Unconsciousness per se is incredibly rare (less than 0.5%) and is safeguarded by the demand valve described above. There is a theoretical risk of oxygen desaturation which is more clinically relevant if given with pethidine. Nausea and vomiting occurs in up to one third of women. However the biggest clinical problem is low efficacy reported by many, particularly during the later stages of labour. This is believed in part to be due to improper timing of use with contractions, as it has been shown that with accurate use good analgesia is provided in over 50% of parturients. Since there is a time lag of 50 seconds to reach peak analgesic effect, for optimal analgesia inhalation should begin in anticipation, approximately 30 seconds before the onset of contraction. This requires meticulous attention to timing which is understandably difficult in such circumstances. The alternative technique of continuous delivery may be more effective but is associated with increased incidence of side effects.

 

Despite multiple studies there is still little objective evidence for the analgesic effect of nitrous oxide in labour. However its value in managing pain in the early stages is clear. Moreover a great many women who have used it in the past choose to use it again and consider it to be as effective as TENS and more effective than pethidine, though less than epidural analgesia.

 

Halogenated inhalational agents: isoflurane, sevoflurane and most recently desflurane have all been shown to be beneficial in treating labour pain. However significant maternal sedation precludes clinical use in a labour ward setting. There are a number of reports of use of low doses in conjunction with Entonox – so called “Sevonox” for example – which produces a far superior analgesia than Entonox alone but with minimal sedation. Difficulties encountered include the requirement for scavenging, which is not widely available, and the need for trained anaesthetists to administer the agent. For these reasons this form of analgesia is not commonly employed.

 

Parenteral opioids

The use of opiates in childbirth dates back to ancient Chinese civilisation, and today it remains one of the commonest forms of labour analgesia worldwide. In the UK use of parenteral opioids in labour is approximately 40%, which is mirrored in the USA. Meperidine (Pethidine) was the first synthetic opioid to be used for this purpose and continues to be the most common in clinical practice in the UK. However concerns regarding its side effects have lead to increased use of alternative drugs. As well as the more traditional diamorphine and morphine, agents include partial agonists meptazinol, butorphanol and pentazocine, weak opioids such as tramadol and, most recently, the shorter acting agents fentanyl and remifentanil.

 

Opioid analgesia in labour is most commonly delivered intramuscularly; in recent years the use of intravenous patient controlled analgesia (PCA) has become increasingly popular, though widespread use of this is limited by the need for midwife training, increased patient monitoring and a relative lack of familiarity with the drugs most suited to delivery by this method. Consequently the use of PCA in labour varies significantly between departments and is dependent on local policy.

 

Despite widespread acknowledgement that epidural analgesia is the gold-standard for labour analgesia, a number of women are not willing or able to have this technique and opt instead for parenteral opioids. Advantages include inexpense and wide availability, as well as ease of administration. However efficacy is questionable and they have been shown to be less effective than some nonpharmacological methods. One study demonstrated that 50 mg intramuscular meperidine provides comparable analgesia to 1 g paracetamol. There has been much research comparing the analgesic effect of the different intramuscular opioids in clinical use. Since meperidine has been in use the longest much of the work has involved comparison to this. Diamorphine has been shown to reduce pain scores to a greater extent than meperidine, though pain relief was only deemed adequate in 40% of the women in both groups. Studies have demonstrated little difference in the analgesic effects of intramuscular meptazinol, butorphanol or pentazocine when compared with intramuscular meperidine. Intramuscular tramadol has been shown to at best provide comparable analgesia to meperidine, with some studies reporting a lower analgesic benefit.

 

There are a number of clinical concerns regarding the use of intramuscular opioids in labour, both for the mother and her baby. All opioids can cause nausea, vomiting and sedation to a varying degree. In addition, their side effects may counteract physiological adaptations of pregnancy; for example the hyperventilation and respiratory alkalosis normally seen may be offset by respiratory depression, with resultant risk of hypoxia (in extreme circumstances). Similarly, opioids may further reduce already delayed gastric emptying and increase acid production, leading to greater risk of regurgitation and pulmonary aspiration.

 

It is the potential for harm to the foetus that gives greatest concern. All opioids are lipid soluble and therefore readily cross the placenta. The half-life of drugs is markedly prolonged in the foetus compared to the mother due to immature pathways of metabolism and excretion. This is most pronounced with meperidine, which is metabolised in the liver to the active compound normeperidine. This also crosses the placenta and is a potent respiratory depressant. The half-life of meperidine in the mother is approximately 3 hours while that of normeperidine is up to 21 hours; however these half lives are increased three-fold in the foetus and hence adverse effects may be seen up to 72 hours post delivery. Such adverse events include respiratory depression, reduced Apgar scores and altered neonatal behaviour as well as a delay in effective suckling and breast-feeding. This risk is highest if meperidine is administered 3–5 hours prior to delivery as this is when normeperidine concentration peaks. Diamorphine carries a similar side-effect profile but some studies suggest the incidence of adverse effects is lower than with meperidine, with neonatal respiratory depression occurring only after high doses. In contrast to meperidine, the shorter the time between maternal diamorphine administration and delivery the greater the risk of respiratory depression and need for resuscitation. There have been conflicting reports regarding neonatal side effects with meptazinol use, though the greater body of evidence suggests a lower incidence of respiratory depression and depressed neurobehavioural and Apgar scores. Tramadol appears to have little effect on neonatal outcome.

 

The newer shorter-acting opioids have a more favourable profile than their more traditional counterparts above. These include fentanyl and remifentanil, which are almost exclusively administered intravenously. Their pharmocokinetics renders them particularly suited to delivery by patient controlled analgesia (PCA) which is increasingly used in labour, particularly when regional analgesia is contraindicated or undesirable. Patient controlled analgesia intuitively has several advantages over bolus opioid administration including lower overall drug dose, less risk of maternal respiratory depression and greater patient satisfaction. It has also been proposed that the frequent administration of small drug doses in such regimens may result in a more steady state plasma concentration than if the same drug was delivered by intermittent bolus, which may in turn produce more satisfactory analgesia.

 

Fentanyl is an attractive drug for use in PCA as it has a rapid onset, short duration of action and no active metabolites. When given as an intravenous bolus it has been shown to produce less maternal sedation, nausea and neonatal respiratory depression than meperidine. When used as a PCA (typically 10–20 mcg bolus, 5 minute lockout) studies report a moderate analgesic effect. Due to the low incidence of adverse foetal effects fentanyl PCA can safely be continued right up to delivery.

 

Alfentanil is a synthetic derivative of fentanyl which has highly selective activity at mu-opioid receptors. It is only administered intravenously and is used for PCA in some labour units in the UK (typically 100–200 mcg bolus; 5 minute lockout). Compared to fentanyl it has a more rapid onset and offset of action and is associated with greater propensity for respiratory depression. One study comparing fentanyl and alfentanil PCA in labour reported equal analgesia to 6 cm cervical dilatation and thereafter a greater benefit with fentanyl. Interestingly there was no difference in maternal or neonatal adverse events between groups.

 

Remifentanil has an even faster onset than alfentanil, occurring within 30 seconds and reaching a peak effect at approximately 90 seconds. It undergoes a unique form of metabolism involving rapid hydrolysis by non-specific plasma and tissue esterases. Since this is independent of hepatic and renal function it has a constant context sensitive half-time of 3–5 minutes regardless of duration of infusion. In this way it is viewed by some to be more favourable than its main competitor fentanyl which can accumulate when given in high doses or with impaired renal function. There has been an explosion of work investigating the optimum dosing regimen of remifentanil PCA in labour in recent years, with some conflicting results and many questions still definitively unanswered. It is most commonly administered as a 0.2–0.5 mcg/kg bolus with 2 minute lockout. Remifentanil has been shown to provide greater analgesia than meperidine, fentanyl PCA and nitrous oxide though less effective analgesia compared to labour epidural. Although remifentanil appears to consistently produce good analgesia initially its benefit appears to reduce as labour progresses. This has led to the evaluation of titratable PCA regimens which can be increased accordingly over time; initial results suggest greater analgesic benefit of these though there are concerns regarding increased side effects at higher doses and consequently such regimens are not currently in common clinical use. Similarly the addition of background infusions has attracted interest but evidence to date is mixed.

 

All the above drugs have the potential to cause adverse effects. Remifentanil is associated with the highest rates of maternal sedation and itching. In addition, due to its potent respiratory depressant effect the frequency of maternal desaturation (<95%) requiring supplemental oxygen has been as high as 60% of cases in some studies; this risk is greater with increasing bolus dose and the use of background infusions. Nausea is experienced by up to 60% women receiving remifentanil. The incidence of respiratory depression with fentanyl has been reported to be equivalent to that seen with remifentanil. As a result of these potential effects the use of PCA in labour requires one-to-one midwifery care by appropriately trained staff. Recommendations include continuous monitoring of pulse oximetry and foetal heart rate, recording respiratory rate and sedation scores every 30 minutes and immediate availability of oxygen therapy which should be commenced if saturations fall consistently below 95%.

 

With respect to foetal adverse effects, remifentanil PCA appears to have minimal effect on neonatal outcome. There have been reports of transient changes in foetal heart rate immediately following administration but these are not reflected clinically – Apgar scores, neurobehavioural scores and cord gases are all comparable to controls. It is believed that this safety profile reflects the rapid metabolism of the drug. Evidence regarding the use of fentanyl is more limited and with some conflicting results.

 

Epidural analgesia

This is generally considered to be the gold standard of labour analgesia, and has consistently been shown to provide superior pain relief than all other methods. The technique describes injection of a combination of local anaesthetic and opioid analgesic into the lumbar epidural space, as shown in Figure 1. This then diffuses into the subarachnoid space where it acts on the spinal nerve roots to block action potential transmission, thus inhibiting nociception and the perception of pain. NICE recommends the use of bupivacaine 0.0625 – 0.1% with fentanyl 1–2 mcg per millilitre.

 

       
       
       

 

 

The inhibition of spinal nerve activity results in blockade of all modalities conveyed by the nerves – sensory, motor and sympathetic. This accounts for many of the potential side effects seen. Sensory blockade produces a dermatomal pattern of analgesia with respect to the specific nerves blocked. In labour this should extend to T10 to provide complete pain relief (see Section Pathophysiology of labour pain). However for caesarean section the sensory level must be significantly higher in order to eliminate pain from manipulation of the peritoneum (innervated by T4).

 

Technique

Prior to undertaking the procedure the patient must have intravenous access and have given appropriate consent. The procedure is performed under strict asepsis. The epidural space is first identified using a syringe and needle using the “loss of resistance” technique and a fine bore catheter is then threaded into the space which remains in situ for the remainder of labour. The first bolus of local anaesthetic/opioid mixture should be given by the anaesthetist to confirm correct catheter placement; thereafter there are several options for maintenance of analgesia. Traditionally midwives administer further boluses (typically 10–15 millilitres) at the patient's request in accordance with hospital guidelines. However patient controlled epidural analgesia (PCEA) is becoming increasingly common; this affords the parturient greater control over her pain relief, increases satisfaction scores and has been shown to reduce both the overall dose of analgesia required and the incidence of motor block. A newly developed regimen involves regular low volume intermittent boluses with additional patient-delivered boluses for breakthrough analgesia (Programmed Intermittent Bolus [PIB] regimen). Continuous epidural infusions are now largely obsolete in modern practice. Regardless of method each bolus typically takes 20–30 minutes to reach its maximal effect.

 

Women with an epidural require increased levels of monitoring. NICE guidelines recommend blood pressure measurement at 5 minute intervals for the 15 minutes following epidural insertion and each subsequent bolus of 10 millilitres or more. Similarly, foetal heart rate monitoring should be performed for 30 minutes at these times. Sensory level and motor function should be assessed every hour.

 

Recent years have seen the advent of combined spinal and epidural anaesthesia (CSE) as an alternative technique for analgesia in labour. The procedure, which is commonly used to provide anaesthesia for caesarean section, involves passing a spinal needle through the epidural needle to puncture the dura and enter the cerebrospinal fluid (Figure 1). A low dose of combined local anaesthetic and opioid is then injected directly into the CSF (commonly used examples include 1 millilitre 0.25% plain bupivacaine and 25 mcg fentanyl; or 3 millilitres of the sterile premixed low dose epidural solution). The spinal needle is then withdrawn and the epidural catheter passed into the epidural space as normal. In this way the solution is in direct contact with the nerve roots. Advantages include faster onset of analgesia compared with epidurals, more reliable spread to sacral nerve roots and possibly a reduction in the total dose of local anaesthetic. It is particularly well suited to women in advanced labour and those in excessive amounts of distress. Since the total intrathecal dose of local anaesthetic is significantly lower than that used to induce anaesthesia for caesarean section the resultant effects are quite different – there is minimal motor blockade and change in blood pressure. The choice of procedure lies with the individual anaesthetist, but at present isolated epidurals are by far the most common.

 

Side effects

The combination of inhibition of sympathetic outflow and reduction in circulating catecholamines following effective pain relief results in vasodilatation and associated hypotension in up to 80% of women. Although usually undesirable, this may be of clinical benefit in certain circumstances, for example improving uteroplacental blood flow in pre-eclampsia. These alterations in haemodynamics can be largely avoided by using the low dose local anaesthetic concentrations described above.

 

Motor blockade is another potential side effect, which occurs in a dose-dependent fashion. It was seen more commonly in the past when higher concentrations of local anaesthetic were used. The Comparative Obstetric Mobile Epidural Trial (COMET) published in 2001 clearly demonstrated that low dose epidurals provide effective analgesia and optimise the chances of a spontaneous vaginal delivery. Hence “mobile epidurals” have now become the goal – providing effective sensory blockade with no motor involvement, thus allowing women to mobilise freely (with supervision) in labour. Importantly the doses of local anaesthetic used clinically affect only skeletal muscle activity, therefore do not alter myometrial contractility.

 

In addition to hypotension and leg weakness, potential side effects include pruritus secondary to fentanyl, urinary retention and fever.

 

Risks and contraindications

Like all invasive procedures, epidurals are associated with a number of risks, shown in Table 1. These should be discussed with the patient prior to commencing the procedure, ideally in an antenatal setting. Additional rare risks not easily quantifiable include anaphylaxis and local anaesthetic toxicity (causing seizures and possible cardiac arrest), as well as inadvertent spinal injection leading to loss of consciousness and apnoea. Notably epidurals are not associated with the development of postpartum back pain.

       

Contraindications to neuraxial analgesia include coagulopathy (pathological or therapeutic), thrombocytopenia (usual threshold <80 × 109/litre with no decreasing trend), overlying skin infection, raised intracranial pressure and allergy to local anaesthetics. Use of the technique in women with cardiovascular compromise, particularly fixed cardiac output states, should be undertaken with extreme caution and only by clinicians experienced in such high risk cases.

 

Concerns

Since the introduction of labour epidurals in the 1960s, there have been a number of concerns over potential adverse effects on labour itself, delivery and neonatal outcome. Although many of these have now been answered, evidence remains inconclusive in some areas.

 

Older observational studies postulated an increased rate of caesarean sections among women with epidurals. However, a number of trials have subsequently refuted this. Moreover there is no additional risk even with epidurals placed in early labour (<4 cm cervical dilatation). Similarly, historically it was believed that neuraxial analgesia increased the risk of operative vaginal delivery, however an increasing body of evidence reports no causal association. Neuraxial analgesia can however increase the duration of labour by up to 1 hour. There is also a greater propensity for oxytocin augmentation, though again this may reflect the tendency of women with more complex painful