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    New developments in obstetric anaesthesia

    Dr Roshan Fernando, Consultant Anaesthetist, University College Hospital, London, UK

    [email protected]

    During this lecture I will concentrate mainly on the following 4 areas:

    1. Phenylephrine and the prevention of hypotension during spinal anaesthesia forcaesarean section.

    2. Breastfeeding and regional anaesthesia3. Epidurals and pyrexia during labour4. Spinal anaesthesia safety issues; CSE anaesthesia


    Historically ephedrine has been recommended as the best vasopressor for the treatment of

    spinal anaesthesia induced hypotension in obstetrics because animal studies showed that

    it caused less reduction in uterine blood flow compared with alpha agonists (1). Howeverephedrine has limited efficacy (2). To effectively maintain blood pressure and prevent

    maternal symptoms, large doses may be needed. Ephedrine also has a slow onset of

    action and a relatively long duration of action. This may make accurate titration of blood

    pressure difficult and when large doses are used to restore blood pressure, sustained

    increases above baseline may occur (3). Increased heart rate and contractility are likely to

    increase myocardial oxygen demand. In fact increases in heart rate have been associatedwith palpitations, atrial / ventricular ectopics and tachyarrhythmias (4). It is now known

    the using ephedrine is associated with a dose dependent depression of fetal pH and base

    excess (3,5-8). The mechanism is not understood. Data from animal studies suggest that a

    reduction in uteroplacental blood flow is unlikely. It could be that there is a directstimulating effect on fetal metabolism. The clinical implication of fetal acidosis induced

    by ephedrine in low risk elective caesarean delivery patients is not certain since there is

    no measurable clinical adverse effect. Although it is known that neonatal outcome isexpected to be good regardless of anaesthetic technique in low risk elective cases, it is

    uncertain how this translates to high risk cases such as patients with compromised babies

    presenting for emergency caesarean delivery. Recently Ngan Kee et al found that there

    were no differences in umbilical cord pH or base excess when ephedrine orphenylephrine were used to treat maternal hypotension during emergency caesareandelivery under spinal anaesthesia, although lower fetal lactate levels were found in

    patients receiving phenylephrine (9).

    Traditionally alpha agonists such as phenylephrine were reserved as second line agentsfor use when ephedrine was ineffective. However recent clinical studies have failed to

    show any evidence of adverse fetal / neonatal effects when such drugs are used in doses

    needed to maintain maternal blood pressure within the normal range (10-12). Unlikeephedrine, phenylephrine is a rapidly acting potent vasoconstrictor with a short duration

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    of action. Physiologically, it makes sense to treat spinal anaesthesia induced vasodilation

    with a vasoconstrictor. A reflex decrease in heart rate is commonly seen withphenylephrine but this rarely needs treatment with an anticholinergic drug.

    Combinations of phenylephrine and ephedrine have also been used, with ephedrine

    counteracting the reductions in heart rate and cardiac output seen with phenylephrine (13).A recent study by Ngan Kee et al demonstrated that there was no advantage of these

    regimens since increasing the dose of ephedrine, in a ephedrine / phenylephrine

    combination, caused more fetal acidosis and less haemodynamic control (14).

    A common phenylephrine regimen is to use 50-100 mcg/min titrated to maintain baselinesystolic blood pressure. Aggressive maintaining blood pressure close to the baseline

    reduces the incidence of maternal nausea and vomiting without causing fetal acidosis

    (11,12). A combination of a crystalloid coload technique with a phenylephrine infusion is

    the only technique which has been shown to virtually eliminate spinal inducedhypotension (10).


    The effect of epidural analgesia on breastfeeding continues to appear in the lay press,

    partly due to conflicting results in the scientific literature. Numerous studies in the past

    have suggested a variable effect on breastfeeding success after epidural labour analgesia.Unfortunately these studies were not randomised and sometimes retrospective (15-

    23).There are many confounding factors including the intention to breast feed, parity, age,

    local tradition, social class, education, delivery type and the amount of help and supportoffered to the mother. These may make the results of unrandomised trials unreliable.

    Jordon et al. were the first to report a dose-response relationship between epidural

    fentanyl and infant feeding in a retrospective cohort study.(24) The authors identified arandom sample of 425 healthy primiparae delivering singleton babies at term from the

    birth register after which they retrieved and analysed the corresponding obstetric /

    midwifery case notes. The main outcome measure was the infant feeding method athospital discharge. A logistic regression model was used for data analysis using 13

    variables including feeding intention, mothers occupation, drugs administered and

    caesarean delivery. This model predicted that, when other established determinants of

    infant feeding were accounted for, the use of intrapartum fentanyl could impedebreastfeeding especially at higher doses. The authors concluded that breastfeeding rates

    could be improved by omitting fentanyl from labour regional analgesic regimens. Apart

    from the retrospective nature of data collection, the study also has problems relating to

    those mothers given epidural fentanyl for intrapartum analgesia. Of the 232 mothers

    (55%) receiving epidural analgesia, 22% also had intramuscular opioid, primarilypethidine. Within this subgroup it is unclear how many epidurals were administered using

    only local anaesthetic or a mixture of opioid and local anaesthetic. Therefore the

    conclusions of this study must be interpreted with caution.

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    Beilin et al. conducted the first randomised double blind trial to evaluate the impact of

    epidural fentanyl on infant breastfeeding based on the results of an initial observationalpilot study.(25) One hundred and eighty-nine women who had previously breastfed a

    child for at least six weeks were assigned to one of three groups, after requesting epidural

    labour analgesia. The groups were based on the total amount of epidural fentanyl to be

    administered during labour: no fentanyl, an intermediate fentanyl dose (1-150 g) or highdose fentanyl (>150 g). All groups received bupivacaine by infusion with the no

    fentanyl group receiving 0.125% bupivacaine compared to 0.0625% bupivacaine in the

    other two groups. At delivery, a blood sample was taken from the umbilical vein and

    analyzed for fentanyl and bupivacaine concentrations. On the first postpartum day, the

    mother and a lactation consultant assessed the infant breastfeeding using structuredquestionnaires and a paediatrician assessed the infants Neurologic and Adaptive

    Capacity Score (NACS). Six weeks later, the mothers were contacted by telephone to

    find out if they were still breastfeeding. Of the 189 women enrolled, 12 were excluded,

    seven because they had a caesarean delivery, leaving approximately 60 women in eachgroup. More than 95% had a spontaneous vaginal delivery and the rest were forceps-

    assisted vaginal deliveries. When the results were analysed by intention to treat, there

    were no significant differences in breastfeeding problems at 24 hours, but at six weekspostpartum, the mothers in the high dose fentanyl group were more likely to have stopped

    breastfeeding (P=0.005). However 15 women received a different amount of fentanyl

    from that planned, with five in the no fentanyl group receiving some fentanyl, one in the

    intermediate-dose group receiving more than 150g fentanyl and nine in the high-dose

    group receiving less than 150 g fentanyl. Therefore when data were reanalyzed based onthe amount of epidural fentanyl actually given, patients receiving >150 g of fentanyl

    were more likely to have difficulty breastfeeding both at 24 hours and six weeks

    postpartum. The most common breastfeeding problems encountered by the mother at 24hours were sleepy infant (55%), inability to latch onto the nipple (23%) and fussy infant

    refusing to feed (19%). If a mother reported a problem at 24 hours, she was more likely

    not to be breastfeeding at six weeks (29%) than if she did not report a problem at 24

    hours (6%) (P=0.004). There was no association between the lactation consultantsassessment at 24 hours and the mothers assessment or breastfeeding success at six weeks.

    The study is not without problems, including 11% of women failing to respond to the sixweek postpartum telephone interview and the failure to measure fentanyl concentrations

    in breast milk. From a pharmacological viewpoint, it is unlikely that fentanyl would be

    present in significant quantities in either the newborn circulation or maternal breast milk

    at 24 hours let alone one six weeks postpartum.(26,27) Bader and colleagues usingcontinuous epidural infusions of 0.125% bupivacaine with fentanyl 2 g/ml for labouranalgesia found that even after many hours, there was no significant drug

    accumulation.(27) The high mean umbilical vein (UV)/maternal vein ratio of 0.94

    suggests that placental transfer of fentanyl, a highly lipid soluble drug, is rapid and that

    UV concentrations equilibrate with those in maternal blood, although the absolute UVfentanyl concentration is low. Steer et al. administered intravenous fentanyl to women

    undergoing caesarean delivery or postpartum tubal ligation and subsequently measured

    the concentration in both maternal plasma and colostrum.(26) Interestingly, fentanylconcentrations in colostrum were always higher than in serum. Colostrum fentanyl

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    concentrations were highest at 45 minutes, but were virtually undetectable 10 hours later.

    More importantly, the work by Desprats et al. suggests that even if the UV fentanyl levelsare low, there is still a chance of drug accumulation in fetal tissues.(28) This group found

    that the fetal extraction ratio, the difference between the umbilical vein and artery

    concentrations, was 53% after fentanyl 100 g combined with local anaesthetic was

    given as a single bolus to provide anaesthesia for caesarean delivery. Possibleexplanations for such a high extraction ratio include rapid fetal metabolism or drug

    accumulation with the latter potentially correlating with Beilin et al.s findings of

    breastfeeding problems at 24 hours postpartum. The effect at 6 weeks could simply

    reflect the known importance of early establishment of breast feeding on its continuation.

    More recently, Torvaldsen et al. conducted a prospective cohort study of 1280 women

    delivering their babies in hospital to determine breastfeeding rates between one and 24

    weeks postpartum.(29) Women delivering vaginally and those undergoing caesarean

    delivery were all included in the cohort. These authors claimed a relationship betweenepidurals and difficulty in breastfeeding during the first week and at 24 weeks postpartum.

    Women who had epidurals, as well as those who had had systemic pethidine, were twice

    as likely to stop breastfeeding in the first 24 weeks postpartum compared to those whohad non-pharmacological methods of labour analgesia. Unfortunately the results are

    difficult to interpret since all women receiving low dose epidural bupivacaine / fentanyl

    for labour analgesia also had intramuscular pethidine beforehand.

    Despite the negative study findings of breastfeeding after epidural fentanyl administration,we should still be cautious about removing fentanyl altogether from epidural infusions

    since this would necessitate increases in local anesthetic concentration to provide

    adequate analgesia with all its attendant risks.Instead as obstetric anaesthesiologists weshould be aware of a potential link between epidural fentanyl and breastfeeding and be

    ready to provide unbiased information to mothers.

    Epidurals and intrapartum fever

    Epidural labour analgesia has been linked to intrapartum temperature elevation (30).Maternal pyrexia has also been correlated with neonatal brain injury, including a four-

    fold increase in the risk of cerebral palsy (31) and neonatal encephalopathy (32,33), as

    well as learning deficits in older children (34). The cause of the rise in temperature is

    unclear. Theories include altered thermoregulation and maternal-fetal inflammation /infection (35). Fusi first reported this association in 1989 when the mean vaginal

    temperatures of mothers receiving labour epidurals increased by 1C during the course of

    labour compared with those receiving intramuscular meperidine (30). At the time theyhypothesized that the fever could be due to an imbalance between heat producing and

    heat dissipating mechanisms. Camann et al measured tympanic temperatures during

    labour and found similar results (36). Other studies have confirmed this association (37-

    40). Studies have also identified nulliparity, prolonged rupture of membranes, prolongedlabour duration, high maternal admission temperature, early chorioamnionitis and

    frequent vaginal examinations as risk factors for maternal temperature (41,42). A recent

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    study has suggested that epidural analgesia is not associated with increased temperature

    in the majority of women, but that the hyperthermia is an abnormal response confined toa minority subset which occurs immediately after exposure (43). Goetzl et al observed

    hourly maternal tympanic temperatures after epidural analgesia in a prospective cohort of

    99 women at term and found that women who later developed intrapartum fever had a

    higher mean temperature within 1 hour after epidural analgesia. In contrast women whoremained afebrile had no increase in core temperature.

    Spinal anaesthesia

    The reduced mortality associated with obstetric anaesthesia for caesarean section in the

    UK has been due to spinal anaesthesia as the preferred way to provide anaesthesia and to

    the administration of safer general anaesthesia. Another important point is that obstetric

    anaesthesia has been developed into a subspecialty and junior anaesthetists are moreclosely supervised. In South Africa, the National Committee for the Confidential

    Enquiries into Maternal Deaths (1999 2001) reported that although more deaths wereassociated with general anaesthesia, there was still significant mortality associated with

    spinal anaesthesia for caesarean section. During this period 25 patients died under spinal

    anaesthesia with little or no co-morbidity in most cases. The experience in South Africa

    is unlikely to be unique. The reasons for the increased morbidity / mortality may include

    inadequate experience and training of the anaesthetist, inappropriate use of spinal

    anaesthesia in patients with significant co-morbidities, a single medical practitionerperforming both anaesthesia and surgery and neonatal resuscitation by the anaesthetist

    compromising care of the mother.

    A single shot spinal technique is a popular choice for caesarean section. It is relatively

    straightforward and provides rapid good quality anaesthesia. Preoperative assessment and

    preparation for spinal anaesthesia are important. Absolute contraindications to spinal

    anaesthesia include the lack of resuscitation drugs or equipment, hypovolaemia (e.g.during ongoing major obstetric haemorrhage), cardiovascular co-morbidity (e.g. mitral or

    aortic stenosis), coagulation abnormalities and severe systemic sepsis.

    Typically for a single shot spinal technique the patient is positioned sitting up and 0.5%

    hyperbaric bupivacaine 10-13 mg with 15mcg fentanyl is injected through a 25-27G

    pencilpoint needle at L3-4 / L4-5. The use of small gauge pencilpoint spinal needles is

    associated with an extremely low incidence of spinal headache.

    Spinal anaesthesia for caesarean section causes extensive sympathetic blockade. Since

    aortocaval compression by the gravid uterus will reduce maternal venous return and

    cardiac output, it must be avoided by tilting the operating table 15 degrees to the left or

    by using a uterine wedge. Spinal anaesthesia in the presence of significant aortocavalcompression may cause catastrophic hypotension since it will impair the normal

    physiological responses to hypotension including the baroreceptor mediated heart rate

    increase and venous and arterial constriction.

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    Management of haemodynamic instability include the use of intravenous fluids (20 ml /

    kg crystalloid) given rapidly at the time of spinal anaesthesia (co-loading) (10,44)through a 14 / 16G cannula, frequent monitoring of blood pressure (every minute

    initially) and the use of vasopressors such as phenylephrine or ephedrine.

    Spinal anaesthesia can be used for preeclamptic patients who have normal coagulationand a platelet count above 75-80 x 10

    9/ L assuming that they have had effective blood

    pressure control treatment before caesarean section. Since these patients have a risk of

    pulmonary oedema, if given excessive fluids, many units restrict perioperativeintravenous fluids to 10ml / kg. Severe preeclamptics may exhibit less hypotension

    during spinal anaesthesia than healthy parturients (45,46). These patients also do not

    show more marked cardiovascular responses to conventional doses of vasopressors than

    normal parturients when these are given during spinal anaesthesia.

    Oxytocin is usually given after delivery of the baby during caesarean section. Sinceoxytocin can cause significant hypotension (47) it is recommended that the initial dose (5

    IU) should be injected slowly in the healthy parturient or by continuous infusion insomeone who is unstable.

    Combined spinal epidural anesthesia (CSE)

    CSE anaesthesia is a common technique used for elective caesarean section. It offers both

    the speed of onset and quality of spinal anaesthesia, with the additional flexibility of an

    epidural catheter, although it is in theory more technically difficult to perform. The spinal

    injection will provide rapid anaesthesia for surgery with the epidural catheter being usedfor intraoperative supplementation or postoperative analgesia. A CSE is usually sited

    utilising a single space needle-through-needle technique using a standard epidural needlesuch as a 16G Tuohy needle through which a longer spinal needle, such as a119mm, 27G

    Whitacre spinal needle, is advanced into the subarachnoid space once the epidural needle

    is correctly located in the epidural space (48). It has been suggested that sequential CSE

    anaesthesia using a small initial spinal dose followed by epidural top-ups may offer

    significant advantages over traditional spinal or epidural techniques by reducing theincidence of hypotension while preserving the quality of analgesia (49,50). Although

    avoidance of hypotension is important for all patients, this technique may be particularly

    advantageous for high-risk parturients with cardiac disease for example, where changes

    in haemodynamic status are less well tolerated.

    A recent review by Roofthooft and Van de Velde summaries the evidence for

    administering low dose spinal bupivacaine for caesarean section to improvehaemodynamic stability (51). Many prospective trials show that lowering the spinal dose

    may indeed improve maternal haemodynamic stability (52-59). Although doses of

    intrathecal bupivacaine between 5 and 7mg are sufficient to provide effective anaesthesia,

    complete motor block is seldom achieved, and the duration of anaesthesia adequate for

    surgery is limited. As a result, an epidural back-up catheter, as part of a CSE, ismandatory. Van de Velde et al compared 6.5mg vs. 9.5mg hyperbaric bupivacaine with

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    sufentanil for elective caesarean section and reported that although the incidence of

    hypotension was lower in the 6.5mg group (16% vs. 68%), intraoperative epiduralsupplementation was 20% vs. 8% respectively (52). Roofthooft and Van de Velde, who

    have extensive experience of such low dose techniques, suggest a spinal bupivacaine

    dose between 5.5 and 6.5 mg combined with opioids (as part of a CSE technique) to

    provide reliable anaesthesia from the start of the spinal injection for 6070 min. If theuterus is not closed after 45 min, an epidural top-up is given to pre-empt intraoperative

    breakthrough pain.

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