analgesia de parto en feto

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The effects of maternal labour analgesia on the fetus

Felicity Reynolds, MBBS, MD, FRCA, FRCOG, ad eundem Emeritus Professor ofObstetric Anaesthesia a

Anaesthetic Department, St Thomas Hospital, London SE1 7EH, UK

Keywords:

labour analgesia

pethidine

opioids

neuraxial analgesia

epidural analgesia

local anaesthetics

neonatal welfare

umbilical artery acid-base balance

breast feeding

Maternal labour pain and stress are associated with progressive

fetal metabolic acidosis. Systemic opioid analgesia does little to

mitigate this stress, but opioids readily cross the placenta and

cause fetal-neonatal depression and impair breast feeding. Pethi-

dine remains the most widely used, but alternatives, with the

possible exception of remifentanil, have little more to offer. Inha-

lational analgesia using Entonox is more effective and, being

rapidly exhaled by the newborn, is less likely to produce lasting

depression. Neuraxial analgesia has maternal physiological andbiochemical effects, some of which are potentially detrimental and

some favourable to the fetus. Actual neonatal outcome, however,

suggests that benefits outweigh detrimental influences. Meta-

analysis demonstrates that Apgar score is better after epidural than

systemic opioid analgesia, while neonatal acid-base balance is

improved by epidural compared to systemic analgesia and even

compared to no analgesia. Successful breast feeding is dependent

on many factors, therefore randomized trials are required to

elucidate the effect of labour analgesia.

2009 Elsevier Ltd. All rights reserved.

Introduction

A number of widely held misconceptions about the effects of maternal anaesthesia and analgesia on

the fetus have for many years hampered best practice in the UK. For example, despite old and new

evidence to the contrary, it is commonly believed that:

E-mail address: [email protected] Of the on-time United Medical and Dental Schools of Guys and St Thomas Hospitals, now no longer in existence and

swallowed up by Kings College London.

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Obstetrics and Gynaecologyj o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / b p o b g y n

1521-6934/$ see front matter 2009 Elsevier Ltd. All rights reserved.

doi:10.1016/j.bpobgyn.2009.11.003

Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289302
mailto:[email protected]://www.sciencedirect.com/science/journal/15216934http://www.elsevier.com/locate/bpobgynhttp://www.elsevier.com/locate/bpobgynhttp://www.sciencedirect.com/science/journal/15216934mailto:[email protected]


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1. Unmodified labour is relatively harmless to the baby, and any pharmacological form of analgesia

must have adverse effects.

2. Epidural analgesia, the most invasive form of pain relief in labour, must also be the most damaging

to the fetus.

3. Pethidine should be avoided in the last hour of labour, to avoid neonatal sedation.

I cannot stress too strongly: these are indeed misconceptions, but they die hard. One common

problem is that, instead of examining the effect of any procedure on the newborn, various surrogate

outcomes such as maternal blood pressure, fetal heart rate, duration of labour, need for oxytocin,

delivery type and even maternal fever are assumed to equate with fetal/neonatal welfare. This is

erroneous. Another surrogate outcome that has in the past received too much attention is measure-

ment of drug concentration rather than drug effect. There are several genuine yardsticks of neonatal

welfare, for example: Apgar score, neurobehavioural score, acid-base balance and feeding. Although of

variable reliability, all merit attention. Sadly, many studies of labour analgesia fail to include any

measures of neonatal outcome.

Maternal analgesia in and around parturition may have directpharmacological effects on the baby,

because of placental transfer of maternally administered drugs, or indirect effects secondary to phys-iological or biochemical changes in the mother. These disparate means of affecting the fetus must be

borne in mind when considering each type of procedure.

It is important that all those wishing to keep mothers correctly informed should be fully conversant

with the evidence, so as to be competent to disabuse both fellow care-givers and lay consumers of their

misconceptions.

Effects of labour pain on the baby

Labour induces a massive catecholamine surge in the fetus, particularly in the second stage, which

helps to preserve blood flow to brain, heart and adrenal and to promote post-natal adaptive circulatory

changes and surfactant release. While this fetal stress response is favourable to the fetus, unmodified

natural labour produces maternal changes that are far from innocuous. Maternal hyperventilation in

response to pain has long been known to have adverse fetal effects.1,2 It leads to:

respiratory alkalosis and a left shift in the oxygen dissociation curve (potentially disadvantageous

to placental transfer of oxygen).

a compensatory metabolic acidosis, which becomes progressively more severe as labour advances

and is also conveyed to the fetus.3

Episodes of hypoventilation, hence haemoglobin desaturation, between contractions.4

Uterine vasoconstriction.1

Meanwhile the stress of labour also leads to release of maternal cortisol and catecholamines, which

may prolong labour and impair placental flow.5-7 Stress hormones also bring about lypolysis with

release of free fatty acids (readily transferable across the placenta) and hyperglycaemia, which will

exacerbate fetal hypoxia. All these changes tend to intensify fetal metabolic acidosis, which indeed

becomes progressively more severe as labour advances.3

Effects of systemic labour analgesia on fetus and neonate

Any drug that depends for its effect on its presence in maternal blood and central nervous system

must readily cross the blood-brain barrier and therefore also the placenta. 8 Hence, given time, such

a drug has a direct affect on the baby. Snow himself observed that excessive chloroform could producea sleepy baby, and advocated careful control of dosage.9 Nevertheless, in the next century, deep

sedation using hyoscine (twilight sleep) and then barbiturates became popular, to the detriment of

both mother and baby. In the mid 20th century it was acknowledged that analgesia might be preferable

to sedation, and nitrous oxide and pethidine were adopted in the UK.

F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289302290


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Inhalational analgesia

Nitrous oxide was initially used in labour as a hypoxic mixture of gas and air and, thanks to the

development by Tunstall in 1961 of Entonox (a 5050 mixture with oxygen in a single cylinder),10 and

despite the contribution of nitrous oxide to greenhouse gases, it became and remains the most popular

analgesic for labour in the UK. Although nitrous oxide passes readily across the placenta, it is rapidlyexcreted by the newborn lungs, and though maternal hypoxaemic episodes occur after hyperventi-

lation during contractions, these are offset by the increased FiO 2 in Entonox and have little apparent

effect on Apgar score, neurologic and adaptive capacity scores or acid-base balance.11

All the modern volatile anaesthetic agents have been used as alternatives or adjuncts to nitrous

oxide at various times.11 The more prolonged and profound the maternal effect, the greater the

potential sedation in the newborn, but again, these modern and poorly soluble agents are rapidly

excreted by the newborn lungs in the usual way.

Systemic opioids

Opioids given to provide systemic analgesia in labour have extensive dose-dependent direct fetaland neonatal effects, but as pain relief is less effective than with neuraxial analgesia, they are less able

to mitigate the adverse effects of labour pain. Therefore any indirect benefit is small, but direct

pharmacological effects on the baby readily occur.

Pethidine

In twilight sleep, a combination of morphine and hyoscine, the morphine element was kept to

a minimum, as it was perceived to endanger the fetus. Then in 1950 pethidine was made available to

midwives, in the belief that it had the analgesic effect of morphine, but without its side effects. It was

also widely believed to be a more powerful analgesic than nitrous oxide. Wrong on both counts! Quite

quickly the ineffectiveness of pethidine 12 and it adverse effects on the newborn 13 began to emerge,

but these findings are often ignored.In the fetus, breathing movements, muscular activity, oxygen saturation, and short-term heart rate

variability are all reduced following maternal pethidine.14 The impact of these changes on outcome is

unclear, but there is no doubt that numerous adverse effects are observed also in the newborn.

Neonatal sequelae of pethidine are prolonged. Respiratory depression has been extensively docu-

mented and is at its worst if pethidine is given repeatedly and three hours or more before delivery, least

if given only within the last hourof labour.15,16 Large doses of pethidine depress the Apgar score,13 but

though smaller doses may not, it must be remembered that Apgar score is only applicable to the first

few minutes of life, a stimulating time for the newborn, who may later become severely depressed.

Indeed reduced oxygen saturation, increased carbon dioxide levels and metabolic acidosis have been

observed in the first few hours of life, even after small doses of pethidine.3,14,17 A placebo-controlled

trial of pethidine in over 400 women found that umbilical artery respiratory and metabolic acidosiswere more severe with pethidine than placebo.18 The incidence of acidosis was highest when pethidine

was given 5 h before birth. Various neurobehavioural studies have found that babies whose mothers

had pethidine are sleepy, less good at suckling 19 and slow to establish breast feeding 20; thermo-

regulation may also be impaired.21 Observational studies support an adverse effect of maternal

pethidine 20,22-24 and indeed of other opioids 25,26 on breast feeding.

The prolonged effects of pethidine on the baby may largely be attributed to the presence of its long-

acting active metabolite norpethidine.16 All the effects may be rapidly and apparently permanently

reversed by giving the newborn intramuscular naloxone in a dose of 60100 mg/kg.19,27 This practice,

however, appears to have gone out of favour.

Alternatives to pethidineVarious substitutes for pethidine have been introduced, with the intent of producing superior

labour analgesia without neonatal depression w a forlorn hope. Unfortunately, fetal and neonatal

outcomes for these alternative drugs have been even less thoroughly studied than those of pethidine,

surely an omission, in view of its many know adverse neonatal effects.

F. Reynolds / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 289302 291


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Older agents. In the 1980s various alternatives were investigated and compared with pethidine. The

findings have been summarised by Scrutton.14 Meptazinol was used in some centres, but any neonatal

benefit that was sometimes noted was offset by a greater tendency to maternal side effects. Pentazo-

cine, likewise, was sometimes found to produce less neonatal detriment than pethidine, but the

balance between maternal analgesia, tachyphylaxis and side effects was not favourable. Nalbuphine

produced apparently even more sedation than did pethidine, and a less good neonatal outcome. Bothpentazocine and nalbuphine have been found to cause significant fetal metabolic acidosis. 28 Another

agent, butorphanol, not used in the UK though popular in the US, is apparently a superior analgesic with

milder fetal effects.28,29

In the belief that morphine itself might produce better labour analgesia than pethidine, Swedish

investigators conducted a randomized comparison of the two, both given intravenously in repeated

doses up to 0.15 mg/kg for morphine and 1.5 mg/kg for pethidine.30 Both produced maternal sedation,

neither lowered the pain score and there was no difference in Apgar scores between the two drugs.

In the UK, however, particularly in Scotland, diamorphine has received more attention than

morphine. One randomized study of intramuscular administration showed slightly better analgesia but

fewer low Apgar scores with diamorphine 7.5 mg than with pethidine 150 mg.31 Meanwhile, neonatal

sedation with a 10-mg dose, inadequate analgesia with 5 mg and an apparently increased need forneonatal resuscitation led Rawal et al. 32 to study the transplacental disposition of diamorphine

metabolites following a single 7.5-mg maternal dose in labour. They found that the concentration in

cord blood of free morphine, the principle active metabolite, was significantly associated with the need

for neonatal resuscitation. Diamorphine, being more lipid soluble than morphine, can more readily

cross the placenta, during which process it undergoes hydrolysis to morphine. It is no magic bullet for

systemic labour analgesia.

The fentanyl family. Fentanyl, alfentanil and remifentanil have been used to provide systemic, usually

patient-controlled intravenous analgesia (PCIA) during labour.

In a randomized open study, women in labour received either intravenous fentanyl 50100 mg/h orpethidine 2550 mg every 23 h.33 Analgesia was equivalent but maternal side effects were more severe

andneonatal naloxonewas neededmore frequently in thepethidinegroup. Thesefindings areunexpected

and have not been reproduced. A study comparing fentanyl with alfentanil by PCIA found no difference in

Apgar or neurologic and adaptive capacity score (NACS), umbilical vein pH or naloxone requirements.34

Remifentanil appears to offer better hope of advantage. Apgar scores and NACS have been found

better with remifentanil than with pethidine, when used for PCIA,35,36 although the drug has not

always lived up to early promise and low umbilical base excess values have been reported. 37 When

neuraxial analgesia is contraindicated, PCIA remifentanil may currently be the best option, but

monitoring both maternal and neonatal respiration has been advised. One wonders why no such

precautions are recommended for pethidine.

Tramadol. Several studies have compared intramuscular tramadol and pethidine, producing variable

results and little information about the newborn. In one randomized trial from Singapore, tramadol

100 mg and pethidine 75 mg produced equivalent analgesia but pethidine produced more maternal

side effects and a lower respiratory rate in the newborn.38 In another from Iran, comparing tramadol

100 mg with pethidine 50 mg, women given pethidine had longer labours, lower pain scores in the

second stage and more side effects, but no difference in Apgar scores.39 A third from Turkey comparing

the two drugs both in 100-mg doses, found greater pain relief with pethidine, more side effects with

tramadol and no difference in duration of labour or Apgar scores.40

Adjuncts

Systemic opioids should be combined with anti-emetics, as nausea, exacerbated by opioids, is such

a problem in labour, but more information is needed about their fetal/neonatal effects. Vella et al. found

that the addition of promethazine or metoclopramide to pethidine had no effect on Apgar scores

compared to placebo.41 Promethazine, however, though effective as an antiemetic, produces severe

maternal sedation and an anti-analgesic effect, so should not be used in this context.



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To gain a true comparative picture of the various opioids and adjuncts that are given systemically,

randomized studies that assess maternal and neonatal respiratory status, neonatal neurobehavioural

status, acid-base balance and breast feeding, and that use PCIA to ensure analgesic equivalence, are

needed.

Effects of neuraxial analgesia on fetus and neonate

The following sections describes findings in relation to neuraxial analgesia in general. Evidence for

variation in neonatal effects due to different drug combinations and routes of delivery will be

addressed in a later section.

Direct effects of neuraxial analgesia

Neuraxial analgesia does not depend for its effect on the presence of drug in maternal blood, so

adverse direct fetal drug effects are likely only if maternal systemic effects of the drugs given neu-

raxially reach a detectable threshold. Thus when lidocaine was used to provide continuous epidural

analgesia, drowsiness was observed in both mother and baby. Longer-acting local anaesthetics(bupivacaine, ropivacaine, levobupivacaine), correctly sited, are more slowly absorbed, and systemic

effects are usually observed only after accidental i.v. administration. Although opioids are well rec-

ognised to produce direct fetal and neonatal depression and to impair breast-feeding when used

systemically, their potential to do so when used for neuraxial analgesia is less, 42 though still present

with large dose.43,44

Indirect effects of neuraxial analgesia

Neuraxial analgesia does not obtund the valuable fetal stress response to labour. While direct fetal

effects are also unlikely, indirect effects resulting from maternal physiological and biochemical changes

are on the cards. It is often believed that, because neuraxial analgesia may have potentially adversematernal effects,45,46 it must be bad for the baby, but it also has beneficial effects 4754 (Table 1). Not

least of these is the fact that effective neuraxial analgesia can reverse the adverse maternal effects on

the baby of labour itself (see above, Effects of labour pain). Outcome depends on the balance between

the two opposing forces; no assumptions should therefore be made as to overall neonatal effect

without direct neonatal assessment. Assessment of the fetus, though less crucial because it can be

misleading, has also been a focus of attention.

Fetal assessment

Cardiotocography

Cardiotocography during labour is not a reliable predictor of neonatal welfare. Despite its short-comings, however, it is often considered mandatory for mothers receiving neuraxial analgesia. In

consequence loss of short-term variability, decelerations and major bradycardia may be noted,

although meta-analysis of controlled trials shows that fetal heart rate abnormalities are not increased

by epidural compared with systemic opioid analgesia 55 or by epidural fentanyl,56 though they are

increased by intrathecal opioids,57 but without increasing the caesarean section rate. Interestingly,

Table 1

Maternal changes produced by neuraxial analgesia that may affect the baby.

Potentially unfavourable maternal effects [45] Potentially favourable maternal effects

Hypotension

FeverIncreased need for oxytocin

Prolonged second stage

Increased need for instrumental delivery

Reduced maternal stress hormones 47-50

Reduces hyperventilation3

Uterine vasodilatation due to sympathetic blockade 51

Fewer episodes of Hb desaturation 52-54

Analgesic effect not dependent on presence of drug

in the blood, so placental transfer is not an issue



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caesarean section rate rather than actual neonatal wellbeing has always been of the focus of concern

another surrogate outcome!

Various explanations have been put forward for these episodes of fetal bradycardia. They may be

associated with the rapid onset of analgesia, with a reduction in epinephrine allowing the unopposed

action of norepinephrine to provoke uterine vasoconstriction and hypertonus,7 reduced maternal

blood pressure and cardiac output, omission of local anaesthetic, which would otherwise blocksympathetic fibres and cause uterine vasodilatation, and omission of fluid preload, which would inhibit

uterine contractions and reduce the incidence of fetal heart rate decelerations. A combination of

ruptured membranes, an unengaged head and variable decelerations (signalling cord compression)

may be a predictor of fetal bradycardia.58 Provided the changes are brief and do not reflect poor

placental perfusion resulting from uterine hypertonus or vasoconstriction, maternal hypotension or

aortocaval compression, their presence appears to be irrelevant to fetal outcome.57

Logic dictates that oxytocin administration must be discontinued before siting a neuraxial block and

the external tocodynamometer belt must be replaced as soon as the procedure is completed, otherwise

once analgesia is achieved uterine contractions may be undetected.

Fetal blood flowWhile uterine blood flow can be said to influence fetal wellbeing, umbilical flow may reflect it.

Current Doppler flow technology has generated many studies encompassing flow characteristics of

both sets of vessels. Most suggest that epidural analgesia has little impact on uterine 5961 or umbilical6062 vessels, although a fall in resistance in preeclampsia has been recorded in both.59,62 No studies

demonstrated any correlation with neonatal outcome.

Fetal oxygenation

Normal fetal oxygen saturation during labour varies between 30 and 70%. With such built-in

variability, uncontrolled studies over short periods with small numbers of subjects, that purport to

show the effect of neuraxial analgesia, are valueless. Most, however, show no significant change in

saturation before and after the block.63

In a controlled study continued throughout active labour in 150women, no significant difference in fetal oxygen saturation between the epidural and no-epidural

groups was detected.64

Neonatal assessment

Apgar score

Meta-analysis of randomized controlled trials showed that there were significantly fewer low Apgar

scores at one and five minutes with epidural than with systemic opioid analgesia.45 The epidurals were

of various types. A more recent multicentre comparison of PCIA fentanyl with patient-controlled

epidural analgesia (PCEA) using a bupivacaine-fentanyl combination found lower 1-minute Apgarscores and greater need for active resuscitation and naloxone in the PCIA group. 65

Neurobehavioural assessments

Over the years various neurobehavioural tests have been developed in an attempt to assess the

newborn further into the post-natal period. The most used by anaesthetists, the neurological and

adaptive capacity score (NACS) was designed to discriminate between drug effects and neonatal

asphyxia.66 It may not be very sensitive or reliable, but it does correlate with breast feeding. Meta-

analyses of randomized trials revealed no significant difference in NACS between epidural and systemic

opioid analgesia.45

Acid-base balanceWhile fetal assessments and Apgar and neurobehavioural scores have serious shortcomings,

umbilical artery acid-base balance is a generally considered reliable. Since neuraxial analgesia does not

depend for its effect on the presence of drug in maternal blood, it is most likely to affect the fetus

indirectly, via maternal changes. The acid-base status of umbilical arterial blood reflects the quality of



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the recent in utero environment and the efficiency of transplacental exchange. It is therefore an

appropriate yardstick for the potential effects of neuraxial analgesia.

Arterial pH reflects both respiratory and metabolic changes, thus during labour both maternal and

fetal values are influenced by the extent to which maternal pain stimulates hyperventilation. Base

excess therefore better reflects metabolic acidosis, which itself is an index of hypoxia. Once born, a baby

can no longer rely on maternal ventilation to maintain acid-base balance, and neonatal respiration may

be depressed following maternal opioid analgesia. The presence of adequate buffer base is therefore

important to the newborn.In 1974, three studies found that, whereas normal labour was associated with a progressive dete-

rioration in base excess in mothers and babies, epidural analgesia appeared to mitigate this adverse

effect,3,67,68 and indeed protected the fetus from the adverse effects of a prolonged second stage of

labour. These consistent findings were widely ignored. Towards the end of the last century, accusations

that epidural analgesia increased the need for caesarean section and long-term backache spurred

researchers to conduct randomized trials comparing systemic with various types of neuraxial anal-

gesia, and many remembered to look at the babies. Meta-analysis of umbilical acid-base values from

these trials and some unpublished data 69 showed that both UA pH and base excess were improved

following epidural compared to systemic analgesia. Though the differences between treatment groups

was small, any improvement must represent a potential benefit, particularly to the at risk fetus.

It may be thought that this apparent benefit of neuraxial analgesia is simply due to the detrimentaleffect of systemic opioid analgesia. Researchers from Dallas therefore compared umbilical artery acid-

base status in 110 babies whose mothers had epidural analgesia with babies of a matched cohort of

mothers who had no analgesia.70 They found no difference in pH, but a significantly higher PCO2 in the

epidural group, reflecting the absence of maternal hyperventilation, and lower base deficit (Fig. 1),

confirming a positive beneficial effect of epidural analgesia in reducing fetal metabolic acidosis.

There is no disputing that epidural analgesia in labour is associated with maternal fever, but if this

were of serious consequence to the baby it would be reflected in an increased neonatal acidosis,

whereas the reverse is true.

Breast feeding

There is no doubt of the value of successful breast feeding, and of its importance as a measure ofneonatal welfare. Successful breast feeding depends on intention to breast-feed, parity, age, local

tradition, social class, education, maternal exhaustion, the amount of help and support that is provided

and, probably last of all the type of analgesia given in labour. The many confounding variables make

results of unrandomized trials unreliable. Yet observational studies, many even retrospective, often

4

5

6

7

8

UA pH PCO2 base deficit

no analgesia

epidural*

**

Fig. 1. Umbilical artery acid-base status in babies whose mothers had had epidural analgesia using a low-dose combination,compared with babies of 110 matched pairs who had had no analgesia. Units: PCO 2 kPa; base deficit mEq/L. *P 0.01; **P 0.009.

Data from Schocket et al. 70



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with small numbers, purporting to show the effects of analgesia on breast feeding, are still reported.

Some do not distinguish between different types of analgesia or confuse systemic with neuraxial

routes of administration.7173 Unsurprisingly, therefore, such trials demonstrate variable effects of

neuraxial analgesia on breast feeding 7185 (Table 2), many finding no adverse effect from neuraxial

analgesia.7476,78,82,83,85 Only those purporting to show adverse effects from epidural analgesia receive

much publicity. As Leighton and Halpern point out, some hospitals have policies for the care of womenwho have had neuraxial analgesia that mitigate against establishment of breast feeding; where early

maternal-infant separation is minimized, epidural analgesia has no adverse effect on lactation

success.55

Meanwhile, one observational study and one randomized trial have suggested (perhaps unsur-

prisingly) an adverse effect on breast feeding of large epidural doses of fentanyl.43,44 Opioids even

given epidurally must enter the maternal circulation before they are eliminated. When prolonged

epidural analgesia for labour using a local anaesthetic-opioid combination is extended for emergency

caesarean section, it is unwise for the babys sake to give further opioid epidurally or systemically until

after delivery.

Effect on the baby of variation in routes of delivery and drug combinations

The field of neuraxial analgesia in labour is replete with randomized comparisons of different drugs

and modes of administration, but for neonatal outcome many report only the Apgar score, which is

barely sensitive enough to detect such subtle changes as are likely to arise.

Neuraxial analgesia may be initiated using an epidural bolus or a combined spinal-epidural

approach and may be continued using boluses, infusion or PCEA. None of these variations has been

shown to have an impact on the newborn.86,87 Several randomized studies have been conducted to

explore the suggestion that early initiation of epidural analgesia might increase the caesarean section

rate. All have refuted this, and in so doing also demonstrated that timing of initiation had no impact on

Apgar score 88,89 or funic acid-base status.88

A randomized comparison of single-shot spinal analgesia using low-dose bupivacaine-sufentaniland paracervical block using bupivacaine alone, however, showed that though analgesia was better in

the spinal group, umbilical artery pH was significantly lower.90 This is an interesting finding, consistent

with the significant detrimental effect on funic acid-base balance of spinal compared with general and

epidural anaesthesia for caesarean section.91

Of the local anaesthetics themselves, from the fetal viewpoint there is little difference between

bupivacaine, levobupivacaine and ropivacaine. Lidocaine is unsuitable for the purpose.

The commonest adjunct to local anaesthetics, fentanyl, has been extensively studied. The best

evidence comes from a randomized double-blind comparison of low-dose bupivacaine plus fentanyl

and bupivacaine alone, titrated to produce equal analgesia, in 400 labouring women. 92 There were no

significant differences between the groups in Apgar scores or umbilical artery pH, but 24-h NACS was

significantly less good in the fentanyl group. A mildly depressed NACS with fentanyl has been recordedin other studies 93,94 and would support the finding that larger doses of fentanyl have been associated

with slightly impaired breast feeding.43,44 A double-blind comparison of three loading doses of

epidural fentanyl found no difference in Apgar scores between 50, 75 or 100 mg.95 While epidural

fentanyl may increase the number of episodes of maternal desaturation, such episodes have not been

found to correlate with funic pH or NACS.94 Any differences between epidural sufentanil and fentanyl

are slight.96 Intrathecal sufentanil, on the other hand, is associated with a significantly disturbed fetal

heart trace and uterine hyperactivity,57,97 though again the difference between sufentanil and fentanyl

may be slight.98

Any adverse effects of epidural fentanyl on the baby are mild compared with the outstanding

maternal benefit and increased safety of the low-dose combination. The same cannot be said of some

other agents that may be combined with local anaesthetic for neuraxial analgesia. Adverse neonataleffects of clonidine and epinephrine should not be ignored. Both epidural and intrathecal clonidine

may potentiate analgesia with local anaesthetics, but the addition of clonidine to epidural ropivacaine

was associated with reduce Apgar score and NACS,99 while a 30mg intrathecal dose worsened fetal

heart rate abnormalities and umbilical artery pH.100 In one randomized trial the addition of



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epinephrine 1:800,000 to epidural levobupivacaine and sufentanil was associated with reduced Apgar

scores at 1 and 5 min 101 though in another, the addition of 1:200,000 epinephrine to a bupivacaine

infusion had no significant effect on Apgar score, umbilical artery pH or respiratory gases.102 The

increase in maternal motor block anyway makes the addition of epinephrine to epidural local anaes-

thetic unsuitable during labour.

Summary and conclusions

Systemic opioids, in addition to producing less effective analgesia than neuraxial techniques, also

have a less favourable effect on the newborn. Nitrous oxide in the form of Entonox is not only more

effective than systemic opioids, it is also less likely to depress the newborn.

There is no disputing that epidural analgesia in labour is associated with maternal fever, but if this

were of serious consequence to the baby it would be reflected in an increased neonatal acidosis,

whereas the reverse is true. Expectant mothers should be reassured that, although epidural analgesia

may be associated with some short-term maternal side effects, its effects on the baby, when compared

with systemic analgesia, are more consistently beneficial in terms not only of Apgar score but also of

acid-base status, and it is less likely than systemic opioids to impair breast feeding.

Practice points

Be aware that maternal labour pain and stress are associated with progressive fetal metabolic

acidosis.

Nitrous oxide relieves pain more effectively than pethidine, and if Entonox is found to be

insufficient, it is useless offering pethidine.

Pethidine produces neonatal depression, which is most severe when given 35 hours before

birth, but very slight if given only within an hour of delivery. Logic dictates that oxytocin administration must be discontinued before siting a neuraxial

block and the external tocodynamometer belt must be replaced as soon as the procedure is

completed, otherwise once analgesia is achieved uterine contractions may be undetected.

Expectant mothers should be reassured that, although epidural analgesia may be associated

with some short-term maternal side effects, its effects on the baby, when compared with

systemic analgesia, are more consistently beneficial in terms not only of Apgar score but also

of acid-base status, and it is less likely to impair breast feeding.

When prolonged epidural analgesia for labour using a local anaesthetic-opioid combination

is extended for emergency caesarean section, it is unwise for the babys sake to give further

opioid epidurally or systemically until after birth.

Neuraxial labour analgesia should not be augmented with clonidine or epinephrine, both ofwhich tend to have detrimental neonatal effects.

There is no disputing that epidural analgesia in labour is associated with maternal fever, but if

this were of serious consequence to the baby it would be reflected in an increased neonatal

metabolic acidosis, whereas the reverse is true.

Research agenda

To gain a true comparative picture of the various agents and types of analgesia that are used inlabour, randomized studies that use PCIA (or PCEA) to ensure analgesic equivalence and that

assess maternal and neonatal respiratory status, neonatal neurobehavioural status, acid-base

balance and breast feeding, are needed.



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References

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