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Obstetric anaesthesia and analgesia


Obstetric anaesthesia and analgesia involve caring for women during childbirth in three situations:

  • Provision of analgesia for labour, usually by epidural or spinal analgesic techniques

  • Anaesthesia for peripartum operative procedures such as instrumental (e.g. forceps or Ventouse) or caesarean delivery

  • Care of the critically ill parturient

The obstetric anaesthetist is involved in the care of the parturient as part of a multidisciplinary team including obstetricians, midwives, health visitors, physicians and intensive care specialists, necessitating excellent communication skills and record-keeping. Successive reports from the triennial confidential enquiries into maternal mortality currently conducted by the National Perinatal Epidemiology Unit (NPEU), and formerly by the Centre for Maternal and Child Enquiries (CMACE), have highlighted the problems of women with intercurrent medical disease, including obesity, and the importance of the obstetric anaesthetist in their care. This has led to the establishment of obstetric anaesthetic assessment clinics in many hospitals.

Many anaesthetists in training are wary of their obstetric modules. Remote site work in a dynamically changing environment can be challenging, however obstetric anaesthesia offers the opportunity to make a key difference to safety and the overall experience of women around labour and delivery.

Anatomy and physiology of pregnancy

The obstetric anaesthetist must understand maternal adaptation to pregnancy in order to manipulate physiological changes after general anaesthesia or regional analgesia and anaesthesia in such a way that the condition of the neonate at delivery is optimised.

The physiological changes of pregnancy are exaggerated in multiple pregnancy, which is increasing in incidence after the success of assisted conception.

Progesterone

Progesterone is the most important hormone in pregnancy. It is secreted in increasing amounts during the second half of the menstrual cycle to prepare the woman for pregnancy. After conception, the corpus luteum ensures adequate blood concentrations until placental secretion is adequate. The key physiological role of progesterone is its ability to relax smooth muscle. All other physiological changes stem from this pivotal function ( Fig. 43.1 ).

Fig. 43.1, Summary of the main actions of progesterone. It establishes the maternal physiological adaptation to pregnancy. ODC, Oxyhaemoglobin dissociation curve; Pa co 2 , arterial carbon dioxide tension; P 50 , partial pressure of oxygen when haemoglobin is 50% saturated at pH 7.4 and temperature 37°C; bicarbonate.

Haemodynamic changes ( Table 43.1 )

  • Blood volume increases from 65–70 to 80–85 ml kg –1 mainly by expansion of plasma volume (maximal at 30–32 weeks) ( Fig. 43.2 ).

    Fig. 43.2, Changes in blood, plasma and red cell volumes and cardiac output during pregnancy. RBC, Red blood cell.

  • By the third trimester, cardiac output has increased by about 40%–50% as a result of significant increases in heart rate and stroke volume.

  • Pulmonary capillary wedge pressure and central venous pressure do not increase because of the relaxant effect of progesterone on the smooth muscle of arterioles and veins and dilatation of the left ventricle.

  • Systemic and pulmonary vascular resistance are markedly decreased; this allows the increased blood volume to be accommodated at normal vascular pressures.

Table 43.1
Cardiovascular changes in pregnancy
Variable Change Proportional change
Heart rate Increased 20%–30%
Systolic blood pressure Decreased 10%–15% second trimester
Diastolic blood pressure Decreased
Stroke volume Increased 20%–50%
Cardiac output Increased 40%–50% by third trimester
Systemic vascular resistance Decreased 20%
Central venous pressure Unchanged
Pulmonary vascular resistance Decreased 30%
Pulmonary capillary wedge pressure Unchanged

Aortocaval compression

When a pregnant woman lies supine, arterial pressure decreases because the gravid uterus compresses the inferior vena cava, reducing venous return and therefore cardiac output. At term the vena cava is completely occluded in 90% of pregnant women, and stroke volume may only be 30% of that of a non-pregnant woman. The aorta is also often compressed, so femoral arterial pressure may be lower than brachial arterial pressure; this is the main cause of a reduction in uterine blood flow. The combination of both effects is known as aortocaval compression, which becomes clinically significant from around 20 weeks. Physiological compensation occurs via sympathetic stimulation and collateral venous return via the vertebral plexus and azygous veins. The effect of aortocaval compression varies from asymptomatic mild hypotension to cardiovascular collapse and is usually prevented or relieved by left tilt or wedging, although complete lateral position is required in some cases. In the event of cardiac arrest the uterus may be manually displaced to the left if a wedge or tilting table is not present.

Regional blood flow

Blood flow to various organs increases, especially the uterus and placenta, where it rises from 85 to 500 ml min –1 ( Fig. 43.3 ).

Fig. 43.3, Diagrammatic representation of changes in blood flow to various organs during pregnancy, together with percentage changes in cardiac output and blood and plasma volumes.

Blood flow to the nasal mucosa is increased. Nasal intubation may be associated with epistaxis.

There is a considerable increase in blood flow to the skin, resulting in warm, clammy hands and feet. This vasodilatation, together with that in the nasal mucosa, helps dissipate heat from the metabolically active fetoplacental unit.

Respiratory changes ( Table 43.2 )

Respiratory function undergoes several important modifications as a result of the actions of progesterone.

  • The larger airways dilate, and airway resistance decreases.

  • There are increases in tidal volume (from 10–12 weeks’ gestation) and minute volume (by up to 50%).

  • Progesterone exerts a stimulant action on the respiratory centre and carotid body receptors.

  • Alveolar hyperventilation leads to a low arterial carbon dioxide tension ( P a co 2 ) during the second and third trimesters. By the 12th week of pregnancy, P a co 2 may be as low as 4.1 kPa.

  • The respiratory alkalosis is accompanied by a decrease in plasma bicarbonate concentration resulting from renal excretion (base deficit increases from 0 to −3.5 mmol L –1 ). Arterial pH does not change significantly.

  • The oxyhaemoglobin dissociation curve is shifted to the right because the increase in red cell 2,3-diphosphoglycerate (2,3-DPG) concentration outweighs the effects of a low P co 2 , which would normally shift the curve to the left. The P 50 increases from about 3.5 to 4.0 kPa. The oxyhaemoglobin dissociation curve of haemoglobin F (HbF) is to the left of that for HbA. The loading–unloading advantages of HbF are at low oxygen tensions. Placental exchange of oxygen is regulated mainly by a change in oxygen affinities of HbA and HbF caused principally by altered hydrogen ion and carbon dioxide concentrations on both sides of the placenta.

  • The double Bohr and double Haldane effects maintain efficiency of gas transfer.

  • The functional residual capacity (FRC) and residual volume are reduced at term because of the enlarged uterus ( Table 43.2 ). This substantial reduction, combined with the increase in tidal volume, results in large volumes of inspired air mixing with a smaller volume of air in the lungs. The composition of alveolar gas may be altered with unusual rapidity and alveolar and arterial hypoxia develop more quickly than normal during apnoea or airway obstruction. In normal pregnancy, closing volume does not intrude into tidal volume.

  • Oxygen consumption (V̇ o 2 ) increases gradually from 200 to 250 ml min –1 at term (up to 500 ml min –1 in labour). Carbon dioxide production parallels oxygen consumption. In the intervillous space the diffusion gradient for oxygen is approximately 4.0 kPa, and for carbon dioxide is approximately 1.3 kPa.

Table 43.2
Changes in respiratory function in pregnancy
Variable Non-pregnant Term pregnancy
Tidal volume ↑ 450 ml 650 ml
Respiratory rate 16 min –1 16 min –1
Vital capacity 3200 ml 3200 ml
Inspiratory reserve volume 2050 ml 2050 ml
Expiratory reserve volume ↓ 700 ml 500 ml
Functional residual capacity ↓ 1600 ml 1300 ml
Residual volume ↓ 1000 ml 800 ml
P a o 2 slight ↑ 11.3 kPa 12.3 kPa
P a co 2 ↓ 4.7–5.3 kPa 4 kPa
pH slightly ↑ 7.40 7.44
P a o 2 , Arterial oxygen tension; P a co 2 , arterial carbon dioxide tension.

Overall several changes occur in pregnancy that contribute to airway difficulty and an increased rate of development of hypoxaemia during apnoea ( Box 43.1 ).

Box 43.1
Anatomical and physiological changes of pregnancy that increase the risk of hypoxaemia during apnoea

  • Interstitial oedema of the upper airway, especially in pre-eclampsia

  • Enlarged tongue and epiglottis

  • Enlarged, heavy breasts that may impede laryngoscope introduction

  • Increased oxygen consumption

  • Restricted diaphragmatic movement, reducing FRC

FRC, Functional residual capacity.

Renal changes

Renal changes are shown in Table 43.3 .

Table 43.3
Renal changes in pregnancy
Measure Non-pregnant Pregnant
Urea (mmol L −1 ) 2.5–6.7 2.3–4.3
Creatinine (µmol L −1 ) 70–150 50–75
Urate (µmol L −1 ) 200–350 150–350
Bicarbonate (mmol L −1 ) 22–26 18–26
24-h creatinine clearance Increased

Renal blood flow is increased (see Fig. 43.3 ). By 10–12 weeks, glomerular filtration rate (GFR) has increased by 50% and remains at that concentration until delivery. Glycosuria often occurs because of decreased tubular reabsorption and the increased load. The renal pelvis, calyces and ureters dilate as a result of the action of progesterone and intermittent obstruction from the uterus, especially on the right.

Gastrointestinal changes

Gastrointestinal changes also stem from the effects of progesterone on smooth muscle.

A reduction in lower oesophageal sphincter pressure occurs before the enlarging uterus exerts its mechanical effects (an increase in intragastric pressure and a decrease in the gastro-oesophageal angle). These mechanical effects are greater when there is multiple pregnancy, hydramnios or morbid obesity. A history of heartburn denotes a lax gastro-oesophageal sphincter.

Placental gastrin increases gastric acidity. Together with the sphincter pressure changes, this makes regurgitation and inhalation of acid gastric contents more likely to cause pneumonitis in pregnancy.

Gastrointestinal motility decreases but gastric emptying is not delayed during pregnancy. However, it is delayed during labour but returns to normal by 18 h after delivery. Thus women are at risk of regurgitation of gastric contents during this time. Pain, anxiety and systemic opioids (including epidural and subarachnoid administration of opioids) aggravate gastric stasis. Small and large intestinal transit times are increased in pregnancy and may result in constipation.

Changes in liver function and blood tests are summarised in Table 43.4 . Liver blood flow is not increased.

Table 43.4
Liver function and enzyme changes in pregnancy
Measure Change in pregnancy
Albumin Decreased
Alkaline phosphatase Increased (from placenta)
ALT/AST No change
Plasma cholinesterase Decreased
ALT, Alanine aminotransferase; AST, aspartate aminotransferase.

Haematological changes ( Table 43.5 )

  • Red cell volume increases linearly but not as much as plasma volume, which results in decreased haematocrit (physiological anaemia of pregnancy).

  • Haemoglobin concentration decreases from 140 to 120 g L –1 .

  • Decreased haematocrit promotes blood flow by reducing the blood viscosity.

  • Cell-mediated immunity is depressed.

  • There is an increase in platelet production, but the platelet count falls because of increased activity and consumption. Platelet function remains normal.

  • Haematological changes return to normal by the sixth day after delivery.

Table 43.5
Haematological changes associated with pregnancy
Variable Non-pregnant Pregnant
Haemoglobin (g dl –1 ) 140 120
Haematocrit 0.40–0.42 0.31–0.34
Red cell count (L –1 ) 4.2 × 10 12 3.8 × 10 12
White cell count (L –1 ) 6.0 × 10 9 9.0 × 10 9
Erythrocyte sedimentation rate 10 58–68
Platelets (L –1 ) 150–400 × 10 9 120–400 × 10 9

Coagulation

Pregnancy induces a hypercoagulable state. Coagulation and fibrinolysis generally return to pre-pregnant levels 3–4 weeks postpartum. These changes are summarised in Box 43.2 .

  • There is an increase in the majority of clotting factors, a decrease in the quantity of natural anticoagulants and a reduction in fibrinolytic activity.

  • Fibrinolysis decreases as a result of decreased tissue plasminogen activator (t-PA) activity because of inhibitors produced by the placenta.

  • Bleeding time, prothrombin time and partial thromboplastin time remain within normal limits. Thrombo­elastography may be useful to assess platelet function and clot stability, but its use in pregnancy is unproven.

  • The increase in clotting activity is greatest at the time of delivery, with placental expulsion releasing thromboplastic substances. These substances stimulate clot formation to stop maternal blood loss.

Box 43.2
Coagulation changes in late pregnancy

  • Fibrinogen increased from 2.5 (non-pregnant value) to 4.6–6.0 g L –1

  • Factor II slightly increased

  • Factor V slightly increased

  • Factor VII increased 10-fold

  • Factor VIII increased – twice non-pregnant state

  • Factor IX increased

  • Factor X increased

  • Factor XI decreased 60%–70%

  • Factor XII increased 30%–40%

  • Factor XIII decreased 40%–50%

  • Antithrombin IIIa decreased slightly

  • Plasminogen unchanged

  • Plasminogen activator reduced

  • Plasminogen inhibitor increased

  • Fibrinogen-stabilising factor decreases gradually to 50% of non-pregnant value

The epidural and subarachnoid spaces

The epidural space in pregnancy

In pregnancy the epidural veins are dilated by the action of progesterone. These valveless veins of Batson form collaterals and become engorged as a result of aortocaval compression during a uterine contraction or secondary to raised intrathoracic or intra-abdominal pressure (e.g. coughing, sneezing or expulsive efforts of parturition). The dose of local anaesthetic for epidural analgesia or epidural/subarachnoid anaesthesia is reduced by about one third for the following reasons:

  • Spread of local anaesthetic in either the subarachnoid or epidural space is more extensive as a result of the reduced volume.

  • Progesterone-induced hyperventilation leads to a low P a co 2 and a reduced buffering capacity; thus local anaesthetic drugs remain as free salts for longer periods.

  • Pregnancy itself produces antinociceptive effects. The onset of nerve block is more rapid, and human peripheral nerves have been shown to be more sensitive to lidocaine during pregnancy. Increased plasma and CSF progesterone concentrations may contribute towards the reduced excitability of the nervous system.

  • Increased pressure in the epidural space facilitates diffusion across the dura and produces higher concentrations of local anaesthetic in CSF.

  • Venous congestion of the lateral foramina decreases loss of local anaesthetic along the dural sleeves.

During contractions, particularly in the second stage, the pressure in the subarachnoid and epidural space becomes very high. Consequently, it is advised not to advance an epidural needle, insert epidural catheters or administer epidural top-ups at that time.

Even if precautions are taken to prevent it, intermittent aortocaval compression always occurs in association with maternal movement. Consequently the epidural veins become intermittently and unpredictably engorged.

Pain pathways in labour and caesarean section

The afferent nerve supply of the uterus and cervix is via Aδ and C fibres, which accompany the thoracolumbar and sacral sympathetic outflows. The pain of the first stage of labour is referred to the spinal cord segments associated with the uterus and the cervix, namely T10–12 and L1. Pain of distension of the birth canal and perineum is conveyed via S2–4 nerves ( Fig. 43.4 ). When anaesthesia is required for caesarean section, all the layers between the skin and the uterus must be anaesthetised. It is important to remember that the most sensitive layer is the peritoneum, and therefore the block should extend up to at least T4 and also include the sacral roots (S1–5) to cold and T5 to touch.

Fig. 43.4, Nerve supply to the uterus and birth canal.

The placenta

The placenta is both a barrier and link between the fetal and maternal circulations. It consists of both maternal and fetal tissue – the basal and chorionic plates, separated by the intervillous space.

The two circulations are separated by two layers of cells – the cytotrophoblast and the syncytiotrophoblast. Fetal well-being depends on placental blood flow. Placental blood flow depends on the perfusion pressure across the intervillous space and the resistance of the spiral arteries. The spiral and uterine arteries possess α-adrenergic receptors. Placental perfusion is reduced by a reduction in cardiac output (e.g. haemorrhage) or uterine hypertonicity (e.g. overstimulation with Syntocinon).

Functions of the placenta

Transport of respiratory gases

Transport of respiratory gases is the most important function of the placenta and was described earlier.

Hormone production

Human chorionic gonadotrophin (hCG) is secreted by placental syncytiotrophoblasts. Production commences very early in pregnancy and peaks at 8–10 weeks. It stimulates the corpus luteum to secrete progesterone. The hCG concentrations increase again near term gestation, but its role in late pregnancy is unclear.

Human placental lactogen (hPL) has similar effects to growth hormone and causes maternal insulin resistance.

Oestrogens are secreted by the placenta and have a role in breast and uterus development. Progesterone is secreted by the placenta (see earlier).

Immunological

The placenta modifies the fetal and maternal immune system so that the fetus is not rejected.

Immunoglobulin G (IgG) is transferred across the placenta and confers some passive immunity but may also produce disease.

There is a reduction in cell-mediated immunity.

Placental transfer of drugs

The barrier between maternal and fetal blood is a single layer of chorion united with fetal endothelium. The surface area of this is vastly increased by the presence of microvilli. Placental transfer of drugs occurs, therefore, by passive diffusion through cell membranes, which are lipophilic. However, this membrane appears to be punctuated by channels that allow transfer of hydrophilic molecules at a rate that is around 100,000 times lower.

Drugs cross the placenta by simple diffusion of unionised lipophilic molecules. Fick's law of diffusion applies. The rate is directly proportional to the materno–fetal concentration gradient and the area of the placenta available for transfer, and inversely proportional to placental thickness.

Factors determining placental transfer

Materno–fetal concentration gradient

Drug transfer occurs down a concentration gradient in either direction. The maternal drug concentration depends on the route of administration, dose, volume of distribution, drug clearance and metabolism. The highest concentration is achieved after intravenous administration, although epidural and intramuscular administration result in similar concentrations. Fetal drug concentration depends on the usual factors of redistribution, metabolism and excretion. The fetus eliminates drugs less effectively because its enzyme systems are immature. The distribution differs because of the anatomical and physiological organisation of the fetal circulation; for example, drugs accumulate in the liver because of the umbilical venous flow to the liver and are metabolised before distribution. The relatively high extracellular fluid volume explains the large volumes of distribution of local anaesthetics and muscle relaxants.

Molecular weight and lipid solubility

The placental membrane is freely permeable to lipid-soluble substances, which undergo flow-dependent transfer. The majority of anaesthetic drugs are small (molecular weights of less than 500 Da) and lipid soluble and so cross the placenta readily. The main exceptions are the neuromuscular blocking drugs.

Protein binding

A dynamic equilibrium exists between bound (unavailable) and unbound (available) drug. Reduced albumin concentration increases the proportion of unbound drug. Many basic drugs are bound to α 1 -glycoprotein, which is present in much lower concentrations in the fetus than in the adult.

Degree of ionisation

The placental membrane carries an electrical charge; ionised molecules with the same charge are repelled, whereas those with the opposite charge are retained within the membrane. The rate of this permeability-dependent transfer is inversely proportional to molecular size. Size limitation for polar substances begins at molecular weights between 50 and 100 Da. Ions diffuse much more slowly. Factors affecting the degree of ionisation alter the rate of transfer.

Maternal and fetal pH

Changes in maternal or fetal pH alter the degree of ionisation and protein binding of a drug and thus its availability for transfer. This has most significance if the p K a is close to physiological pH (local anaesthetics) and is clinically relevant in the acidotic fetus. Fetal acidosis increases the ionisation of the transferred drug, which is then unable to equilibrate with the maternal circulation, resulting in accumulation of the drug. This is known as ion trapping.

The degree of ionisation of acidic drugs is greater on the maternal side and lower on the fetal side. The converse applies for basic drugs.

Placental factors and uteroplacental blood flow

Placental drug transfer depends on the area of the placenta available for transfer. Physiological shunting occurs, and in pre-eclampsia the placenta itself may present an increased barrier to transfer.

Effects of drugs on the fetus

Drugs may have a harmful effect on the fetus at any time during pregnancy. In the early stages of pregnancy (at a stage when the woman may be unaware that she is pregnant), the conceptus is a rapidly dividing group of cells and the effect of drugs at that stage tends to be an all-or-nothing phenomenon, either slowing cell division if no harm is done or causing death of the embryo. Drugs may produce congenital malformations (teratogenesis), and the period of greatest risk is from weeks 3–11. In the second and third trimesters, drugs may affect the functional development of the fetus or have toxic effects on fetal tissues. Drugs given in labour or near delivery may adversely affect the neonate after delivery. Hence, drugs should be prescribed in pregnancy only if the perceived benefit of the therapy to the mother outweighs the possible detrimental effects on the fetus.

Effects of drugs on the neonate

The ratio of maternal vein to umbilical vein concentration is commonly quoted but indicates the situation at delivery only and gives little information about the effects or distribution of the drug in the neonate.

  • Inhalational anaesthetics. Provided that the induction–delivery interval is short, the fetus is minimally affected. Neonatal elimination is dependent on ventilation.

  • Neuromuscular blocking drugs. These cross the placenta very slowly. Bolus doses of suxamethonium and rocuronium are safe.

  • Thiopental. Crosses the placenta rapidly, with umbilical vein concentration closely following the relatively rapid decrease in maternal blood concentration. Fetal plasma concentration continues to increase for around 40 min after single exposure. However, because of the relatively large fetal volume of distribution, fetal and neonatal tissue concentrations are lower than maternal. Doses of thiopental greater than 8 mg kg –1 have been shown to produce neonatal depression. Lower inductions doses do not affect Apgar score or umbilical cord gas tensions but may produce subtle changes in the neuroadaptive capacity score (NACS), such as reduction in muscular tone, decreased excitability and a predominant sleep state in the first day of life.

  • Propofol. There is conflicting evidence concerning the effects of propofol on the neonate. Induction doses as low as 2–3 mg kg –1 and maintenance doses as low as 5 mg kg –1 h –1 have been found to cause significant neonatal depression. Neonatal elimination of propofol is slower than that in adults. Several comparative studies of propofol and thiopental have shown no difference in neonatal outcome.

  • Diazepam. Should be avoided if possible. The neonate may suffer from respiratory depression, hypotonia, poor thermoregulation and raised bilirubin concentrations.

  • Opioids. Opioids or other sedative drugs may cause a flat cardiotocograph (CTG) trace with loss of beat-to-beat variability. Meperidine and its metabolite norpethidine depress all aspects of neurobehaviour in the neonate. Neonatal elimination is slow, resulting in prolongation of the effects. Transfer of meperidine is increased in the presence of fetal acidosis. Depressant effects are maximum if administration to delivery time is 2–3 h. Fentanyl rapidly crosses the placenta. Apgar scores are low after administration of i.v. fentanyl. Epidural administration of fentanyl in doses of less than 200 µg is not associated with any adverse effect on the fetus. Theoretically, Apgar and neurobehavioural scores should be less affected with alfentanil.

  • Remifentanil crosses the placenta readily but appears to have few adverse effects on the fetus/neonate because it is rapidly metabolised. It can be used for PCA in labour (see later).

  • NSAIDs should be avoided in pregnancy because they can result in premature closure of the ductus arteriosus and premature birth.

Lactation and drugs in obstetric anaesthesia

Many women wish to suckle their infant immediately after delivery and are encouraged to do so.

The effects of a drug administered to the mother on a breastfeeding neonate are determined by peak plasma concentration of the drug, its transfer into milk, composition of milk, volume ingested, metabolism (including first-pass metabolism by the neonate), pharmacokinetics and action in the neonate. Colostrum is more likely to be contaminated by water-soluble drugs, whereas lipid-soluble drugs are secreted into mature milk. The pH of mature human milk is 7.09. Therefore weak acids are less easily transferred than weak bases.

The pharmacokinetics of drugs in the neonate may differ markedly from those in adults. Lipophilic and acidic drugs are bound to albumin and may displace unconjugated bilirubin. Metabolic and excretory pathways are immature, so elimination may be delayed.

  • Opioids. Morphine appears safe with conventional administration. Patient-controlled analgesia may increase maternal plasma concentration. It is transferred readily to breast milk but does not appear to cause neonatal depression, possibly because of first-pass metabolism. A European review of the safety of codeine-containing medicines licensed for pain relief in children began after cases of respiratory depression in children given codeine after adenoidectomy and tonsillectomy. As a result codeine has been restricted in its use in children and is contraindicated in breastfeeding mothers because of the potential harm to babies. Meperidine is associated with neurobehavioural depression of the neonate. Short-acting opioids such as fentanyl and alfentanil are safe, even by continuous epidural infusion.

  • Non-steroidal anti-inflammatory drugs. The NSAIDs ibuprofen, ketorolac and diclofenac are safe. The neonate has immature biotransformation and excretory pathways. Aspirin should be avoided because high concentrations have been observed after a single oral dose. Neonates may be at risk of developing Reye's syndrome.

  • Paracetamol. Paracetamol is minimally secreted into breast milk. However, it is cleared by the neonatal liver more slowly than in adults. It is considered safe.

  • Thiopental and propofol. These drugs are detectable in milk and colostrum. However, the dose received by the neonate after a single induction dose is insignificant.

  • Diazepam. Diazepam and its metabolites are excreted in breast milk. As with placental transfer, there is the possibility of adverse effects on the neonate, especially with continuous administration.

  • Lidocaine and bupivacaine. The amounts excreted in breast milk are small or undetectable.

Pharmacology of relevant drugs

The detailed pharmacology of the drugs used during pregnancy is covered elsewhere, but the following are of particular relevance to the obstetric anaesthetist.

Uterotonic drugs

Syntocinon (oxytocin)

Syntocinon is a synthetic analogue of the posterior pituitary hormone oxytocin, which is responsible for effective uterine muscle contraction. It is used during labour to augment progress, at delivery to aid placental delivery and closure of uterine vasculature and in the postpartum period to reduce postpartum haemorrhage. For augmentation or induction of labour, Syntocinon is usually administered via a syringe or volumetric pump using an increasing dose. The usual dose at delivery is 5 IU, and 40 IU may be infused over 4 h to maintain myometrial contraction and reduce bleeding.

Syntocinon may cause vasodilatation and tachycardia and so boluses should be administered cautiously in the presence of hypovolaemia and in patients with significant cardiac disease. Lower bolus doses (0.3–1 IU) may be equally effective with fewer side effects. Syntocinon also has an antidiuretic hormone effect, so care should be taken if infused in dilute dextrose solution, as hyponatraemia may occur.

Carbetocin

Carbetocin is a long-acting oxytocin analogue that can be given as a single dose to prevent postpartum haemorrhage as an alternative to an infusion of Syntocinon. The optimal dose is probably 100 µg intravenously at caesarean section. It has a plasma half-life between four and ten times that of Syntocinon.

Ergometrine

Ergometrine is also given to stimulate uterine contraction, usually in a dose of 500 µg. Ergometrine causes peripheral vasoconstriction, which may be severe, leading to hypertension and pulmonary oedema; thus it should be avoided in women with hypertensive disease. It can cause nausea and vomiting as a result of its action on other types of smooth muscle, and it is usually reserved for more severe cases of uterine atony.

Syntometrine

Syntometrine is a combination of ergometrine 500 µg and Syntocinon 5 units. Until recently, it was administered routinely by intramuscular injection at the delivery of the anterior shoulder to assist in placental separation and to reduce postpartum haemorrhage; however, Syntocinon alone is now favoured because of its reduced side effect profile.

Prostaglandins

Prostaglandins are a group of endogenous short polypeptides with a wide diversity of physiological functions. Prostaglandins are commonly used to ‘ripen’ the cervix on induction of labour but may cause bronchospasm and hypertension.

Carboprost

Carboprost is prostaglandin F 2 α. It has an important role in the treatment of severe uterine atony unresponsive to Syntocinon or ergometrine. It is administered intramuscularly (250 µg) at 15 min intervals to a maximum dose of 2 mg. It should not be given intravenously or intramyometrially. It may induce bronchospasm and hypertension and should be avoided in patients with asthma.

Misoprostol

Misoprostol is a prostaglandin E 1 analogue. It may be used to induce labour and is given vaginally. It may be given as third or fourth line treatment of postpartum haemorrhage (600 µg p.r.). It produces pyrexia, shivering, nausea and vomiting and diarrhoea.

Dinoprostone

Dinoprostone is prostaglandin E 2 given as a gel, tablets or pessary to induce labour by ripening the cervix before rupture of membranes and intravenous infusion of Syntocinon.

Mifepristone (RU486)

Mifepristone is a prostaglandin antagonist that causes luteolysis and trophoblastic separation. It is given orally with prostaglandins to induce labour after intrauterine death of the fetus and when labour is induced for a non-viable fetus. It is associated with headache, dizziness and gastrointestinal upset.

Tocolytic drugs

β 2 -adrenergic receptor agonists (terbutaline, salbutamol, ritodrine)

β 2 -Adrenergic agonists act on uterine β 2 -receptors, causing relaxation of the myometrium. They can be given orally, subcutaneously or by intravenous infusion for premature labour. The effects should be monitored carefully because severe tachycardia, hypotension, pulmonary oedema, hypokalaemia and hyperglycaemia may occur.

The drugs may also be given by slow i.v. bolus injection (salbutamol or terbutaline 100–250 µg) as part of an in utero fetal resuscitation regimen before emergency caesarean section.

Oxytocin antagonists (atosiban)

Atosiban is an oxytocin antagonist used to decrease uterine contractions; it has few adverse effects but it is expensive.

Glyceryl trinitrate

Glyceryl trinitrate (GTN) acts directly on uterine smooth muscle and can be given intravenously (50 µg) or sub­lingually (200–400 µg) to produce rapid but short-term uterine relaxation. It can be used as part of intrauterine resuscitation, or in cases of uterine hypertonicity, retained placenta and uterine inversion. It causes hypotension and headache.

Indomethacin

Indomethacin is an NSAID and a prostaglandin synthetase inhibitor. It may be given orally or rectally to inhibit contractions after cervical cerclage. It can cause premature closure of the fetal ductus arteriosus and therefore should not be used after 32 weeks’ gestation.

Basic obstetrics

Labour

A large number of pregnant women are assessed as being low risk and are predicted to have an uncomplicated labour, though this can only be confirmed in retrospect. The features of good progress in labour are:

  • contractions occurring every 3 min and lasting 45 s;

  • progressive dilatation of the cervix (approximately 1 cm h –1 );

  • progressive descent of the presenting part;

  • vertex presenting with the head flexed and the occiput anterior;

  • labour not less than 4 h (precipitate) or more than 18 h (prolonged);

  • delivery of a live healthy baby;

  • delivery of a complete placenta and membranes; and

  • no complications.

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