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REVIEW ARTICLE

Thrombocytopenia in the parturient

P. C. A. Kam,1 S. A. Thompson2 and A. C. S. Liew3

1 Professor of Anaesthesia, Department of Anaesthesia, University of NSW at St. George Hospital, 2 Fellow in

Anaesthesia, Department of Anaesthesia, St. George Hospital, 3 Staff Specialist Anaesthetist, Department of

Anaesthesia, University of NSW at St. George Hospital, Belgrave Street, Kogarah, NSW 2217, Australia

Summary

Thrombocytopenia in pregnant women can be associated with substantial maternal and neonatal

morbidity. It may result from a range of conditions and early implementation of some specific

treatment may improve both maternal and neonatal outcome. In this review we discuss the clinical

features of the more common causes of thrombocytopenia associated with pregnancy, and provide

an overview of the anaesthetic considerations.

Keywords Pregnancy. Thrombocytopenia; gestational thrombocytopenia, pre-eclampsia, HELLP,

thrombotic thrombocytopenic purpura, immune thrombocytopenic purpura.

........................................................................................................

Correspondence to: Dr P. C. A. Kam

E-mail: [email protected]

Accepted: 26 October 2003

Thrombocytopenia occurs in approximately 10% of

pregnant women and may be caused by a variety

of obstetric conditions (Table 1) [1]. Although some of

these diseases are not associated with adverse effects

or outcomes of pregnancy, others can be associated with

serious maternal as well as fetal ⁄ neonatal morbidity and

mortality. A multidisciplinary team approach involving

obstetrician, haematologists, paediatricians and anaesthet-

ists is essential for the optimal management of pregnant

women with thrombocytopenia. Thrombocytopenia in

the obstetric patient may be the result of a range of

conditions, from benign disorders such as incidental

gestational thrombocytopenia to life-threatening syn-

dromes such as the ‘haemolysis, elevated liver enzymes,

low platelets’ syndrome (HELLP) [2]. The diagnosis of

specific disorders is often difficult because the time of

onset of these disorders during pregnancy and their

clinical manifestations often overlap.

The aim of this article is to review the differential

diagnosis of thrombocytopenia in pregnancy and high-

light the clinical features and management of the various

diseases that cause thrombocytopenia, and to summarise

the anaesthetic considerations in the management of

thrombocytopenia in the parturient.

Method

Sources for this review include Medline 1980–2003

searched under the following Medical Subject Headings:

thrombocytopenia, pregnancy, platelets, pre-eclampsia,

HELLP, and thrombotic thrombocytopenic purpura

(TTP). The bibliographies of the included studies were

scanned for additional references (reference dredging).

The National Library of Medicine Pub Medical internet

site was also used.

Haemostatic changes in normal pregnancy

During normal pregnancy, major changes in haemostasis

include increasing concentrations of most clotting factors,

decreasing concentrations of some natural anticoagulants

and diminishing fibrinolytic activity [3]. These changes

create a state of hypercoagulability that is most marked

around term and the immediate postpartum period,

thereby decreasing bleeding complications that may be

associated with delivery. The most important initial

factors for haemostasis at delivery, however, are uterine

muscle contractions and constriction of the spiral arteries

that interrupt blood flow.

Anaesthesia, 2004, 59, pages 255–264.....................................................................................................................................................................................................................

� 2004 Blackwell Publishing Ltd 255

All blood coagulation factors except XI and XIII

increase during normal pregnancy [4, 5]. The plasma

fibrinogen concentration increases from non-pregnant

levels of 2.5–4 g.l)1 to 6 g.l)1 in late pregnancy and

labour. The increase in the concentration of the two

components of the factor VIII complex, Factor VIII and

von Willebrand factor (VWF) antigen, occur in parallel in

the first half of pregnancy, but then diverge because of

a two-fold increase in von Willebrand factor antigen.

Factor XI concentrations decrease to approximately 60%

of the non-pregnant values. Factor XIII concentrations

fall to about 50% of the normal non-pregnant value at

term. The increase in factors VII and X is highest in mid-

pregnancy and remains high in the third trimester.

Most blood coagulation inhibitors are unchanged.

Antithrombin and protein C levels are normal during

pregnancy. However, the plasma concentration of free

protein S decreases markedly during pregnancy and may

contribute to the hypercoagulable state [6, 7]. The level of

tissue factor pathway inhibitor increases in pregnancy.

Plasma fibrinolytic activity is reduced during pregnancy

and labour, and returns to normal within 1 h after

placental delivery. The diminished fibrinolysis is caused

by increased concentrations of plasminogen activator-1

derived from endothelial cells and plasminogen activator

inhibitor-2 derived from the placenta.

The normal platelet count range in non-pregnant

women is 150–400 · 109.l)1. In uncomplicated preg-

nancies, recent studies have reported that the platelet

count decreases by an average of 10% during the third

trimester as a result of haemodilution or accelerated

destruction leading to younger and larger platelets [8].

Incidental thrombocytopenia in pregnancy is usually

benign. The mean platelet volume increases, suggesting

that a compensated state of progressive platelet destruc-

tion occurs during the third trimester [9, 10]. The

concentration of plasma b-thromboglobulin (a specific

protein in the a-granules that is secreted during platelet

activation) increases in the second and third trimesters of

pregnancy [11].

Platelet activation, coagulation and fibrinolytic activity

are enhanced during delivery [7]. Significant increases in

fibrinogen degradation products occur in 21% of partu-

rients during labour, with 32% showing the similar

increases in the immediate postpartum period. At 24–72 h

after delivery, fibrinogen degradation remains elevated in

only 10% of women. Platelet count returns to normal

24–72 h postpartum [12, 13], and fibrinolytic activity

decreases rapidly [7]. During placental separation, the

clotting mechanism is activated and factor VIII activity

transiently increases after delivery, shortening coagulation

times [14].

In the pregnant women, thrombocytopenia is defined

as a platelet count of less than 150 · 109.l)1; counts of

100–150 · 109.l)1 are defined as mild thrombocytopenia,

counts of 50–100 · 109.l)1 as moderate thrombocyto-

penia, and counts of less than 50 · 109.l)1 as severe

thrombocytopenia. Thrombocytopenia is caused either

by increased platelet destruction or decreased platelet

production. In pregnancy, increased platelet destruction

may be mediated by immunological mechanisms, abnor-

mal platelet activation, or platelet consumption [15].

Increased destruction or utilisation of platelets during

pregnancy occurs in microangiopathies (exposure to

abnormal blood vessels) such as thrombotic thrombo-

cytopenic purpura, haemolytic uraemic syndrome, hae-

molysis, elevated liver enzymes, low platelet (HELLP)

syndrome, and pre-eclampsia.

Gestational or incidental thrombocytopenia

Gestational or incidental thrombocytopenia, the most

common cause of thrombocytopenia during pregnancy,

occurs in 5–8% of all pregnant women and accounts for

75% of pregnancy-associated thrombocytopenia. The

decreased platelet count may be related to haemodilution

and ⁄ or accelerated platelet turnover with increased

platelet production in the bone marrow, and increased

trapping or destruction at the placenta [16]. The quan-

titative decrease in platelet count is balanced by enhanced

platelet reactivity [17]. Some authors, however, have

described decreased platelet activation mediated by a

plasma factor that selectively inhibits prostaglandin-

dependent activation during pregnancy [18].

The features of gestational thrombocytopenia include a

platelet count usually below 70 · 109.l)1 which returns to

Table 1 Causes of thrombocytopenia in pregnancy.

NormalIncidental or gestational thrombocytopeniaPseudothrombocytopenia (laboratory artefact with EDTAanticoagulant)

Disorders with increased platelet consumptionImmune thrombocytopenic purpuraPregnancy induced hypertension ⁄ HELLP syndromeThrombotic thrombocytopenic purpuraHaemolytic uraemic syndromeInfection-associated (HIV, malaria)Drug-induced (heparin, sulphonamides, penicillin, rifampicin,quinine)

Systemic lupus erythematosusAntiphospholipid syndromeDisseminated intravascular coagulationAmniotic embolismDisorders with reduced platelet productionCongenital thrombocytopeniaAplastic anaemiaLeukaemiaDrug-inducedMyelodysplasia

P. C. A. Kam et al. Æ Thrombocytopenia in the parturient Anaesthesia, 2004, 59, pages 255–264......................................................................................................................................................................................................................

256 � 2004 Blackwell Publishing Ltd

a normal level following delivery within 12 weeks. The

women are asymptomatic with no history of bleeding and

thrombocytopenia is usually detected as part of antenatal

screening. The women have no history of thrombocyto-

penia prior to pregnancy but may have thrombocytopenia

in previous pregnancies. Gestational thrombocytopenia is a

diagnosis of exclusion. However, when a platelet count is

below 70 · 109.l)1, a pathological cause of thrombo-

cytopenia becomes substantially more likely. Gestational

thrombocytopenia usually occurs in the late second or third

trimester. There is an extremely low risk of fetal or neonatal

thrombocytopenia [19]. In non-hypertensive pregnant

women, investigations are only required when thrombo-

cytopenia occurs early in pregnancy or progressively

decreases during the pregnancy or when the platelet count

is less than 70 · 109.l)1. Further investigations must be

undertaken in pregnant women who are symptomatic or

who do not regain a normal postpartum platelet count. If a

thrombocytopenic but otherwise healthy pregnant woman

has a platelet count >70 · 109.l)1 and no history of

previous thrombocytopenia, a meticulous physical exam-

ination, careful blood pressure assessment and monitoring

and a peripheral blood film examination should be

undertaken. The confirmation of normal platelet count

prior to pregnancy decreases the probability of an under-

lying immune thrombocytopenic purpura [20]. Anti-

platelet antibody tests do not differentiate gestational

thrombocytopenia from idiopathic thrombocytopenia. In

a study of 250 pregnant women with thrombocytopenia

(90 with idiopathic thrombocytopenia, 160 with presumed

gestational thrombocytopenia) that evaluated eight differ-

ent platelet antibodies, platelet-associated IgG was elevated

in 69.5% of women with gestational thrombocytopenia

and in 64.6% of women with idiopathic thrombocytopenia

(p = 0.24). Although 85.9% of women with idiopathic

thrombocytopenia had indirect IgG compared with 60.3%

women with gestational thrombocytopenia (p < 0.001),

significant overlap existed and limited its clinical value [21].

It appears that there are no specific diagnostic tests that can

distinguish gestational thrombocytopenia from mild idio-

pathic thrombocytopenia. Therefore, the only means of

differentiation is to monitor platelet counts closely, to

detect levels that decrease below the 50–70 · 109.l)1

range, to document a normal neonatal platelet count and a

restoration of a normal maternal platelet count after

delivery. Women with gestational thrombocytopenia are

not at a risk of either maternal haemorrhage or fetal

haemorrhage.

Immune thrombocytopenic purpura (ITP)

ITP is characterised by immunologically mediated platelet

destruction and an increase in circulating megathrombo-

cytes. The patient produces IgG antiplatelet antibodies

that recognise platelet membrane glycoproteins. The

antibody-coated platelets are then destroyed by the

reticuloendothelial system (primarily the spleen) at a rate

that exceeds the capacity of the bone marrow to produce

new platelets. However, antiplatelet antibodies are pre-

sent in only 80% of cases.

ITP occurs in approximately one case of thrombo-

cytopenia per 1000 pregnancies and accounts for 5% of

cases of pregnancy-associated thrombocytopenia [22]. It is

the most common cause of significant thrombocytopenia

in the first trimester. ITP is a diagnosis of exclusion

because there are no pathognomonic signs, symptoms or

laboratory tests. The four consistent features that are

associated with the condition are persistent thrombo-

cytopenia (platelet count <100 · 109.l)1) with or with-

out peripheral megathrombocytes; normal or increased

number of megakaryocytes detected by bone marrow

aspiration; absence of splenomegaly; and exclusion of

systemic diseases or drugs that are known to cause

thrombocytopenia.

Most women with ITP have a history of bruising easily,

petechiae, epistaxis, and gingival bleeding preceding

pregnancy, although some may be asymptomatic. Symp-

toms of haemorrhage are rare unless the platelet count is

<20 · 109.l)1. A history of prior thrombocytopenia,

underlying autoimmune disease or a platelet count

<50 · 109.l)1 makes the diagnosis of ITP more likely.

In patients with mildly decreased platelet count and with

no prior history of thrombocytopenia, it can be difficult

to distinguish ITP from gestational thrombocytopenia,

because platelet-associated IgG may be elevated in both

diseases [21]. An immunological test that measures

antibodies that react with specific platelet glycoproteins

(monoclonal antibody immobilisation of platelets) cannot

differentiate these two syndromes consistently [23]. From

a clinical view, in the absence of a platelet count prior to

pregnancy, a platelet count <100 · 109.l)1 in the first

trimester that declines progressively as the pregnancy

progresses is consistent with ITP. In contrast, mild

thrombocytopenia occurring in the second or third

trimester and not associated with proteinuria or hyper-

tension indicates incidental or gestational thrombocy-

topenia [24]. ITP is an insidious disease with initial

symptoms such as easy bruising and petechiae. Pregnancy

does not alter the clinical course of ITP. However, there

are anecdotal reports of deterioration of symptoms during

pregnancy and improvement postpartum [2].

Patients with platelet counts >30 · 109.l)1 and no

bleeding do not usually require immediate treatment.

Platelet transfusion is indicated if bleeding occurs or if the

platelet count is <30 · 109.l)1 [9, 23]. More aggressive

measures may be required to increase the platelet count to

Anaesthesia, 2004, 59, pages 255–264 P. C. A. Kam et al. Æ Thrombocytopenia in the parturient......................................................................................................................................................................................................................


a level to allow epidural analgesia for labour and adequate

haemostasis during delivery. A platelet count >50 ·109.l)1 is usually adequate in this regard, although some

authors recommend a platelet count >100 · 109.l)1 [25].

Drug therapy usually commences with oral prednisone

(1–2 mg.kg)1.day)1), with reduction of doses until the

platelet count stabilises at 75–100 · 109.l)1. However,

steroid therapy increases the incidence of gestational

diabetes, pregnancy-induced hypertension and premature

rupture of placental membranes. Patients with low

platelet counts should receive steroids at around 37 weeks

of gestation in order to increase maternal and foetal

platelet counts. Betamethasone or dexamethasone is

preferred because placental enzymes inactivate a major

portion of the prednisone dose that is presented to the

placental circulation.

High doses of intravenous immunoglobulin (2 mg.kg)1)

have been recommended for pregnancy-associated ITP

[24]. However, the responses are often transient and

multiple courses of treatment may be required.

Splenectomy may be required during pregnancy to

decrease platelet destruction in patients who are refractory

to steroid or IgG therapy. It should be performed in the

second trimester because surgery can cause premature

labour in the first trimester and may be more difficult in

the third trimester due to the large gravid uterus.

The maternal consequence of ITP is haemorrhage.

Bleeding complications are usually associated with surgi-

cal incisions (such as episiotomy) and lacerations of the

birth canal. The mother is not at a greater risk of abruptio

placentae or placenta praevia than the general pregnant

population [26]. They are not at higher risk for postpar-

tum uterine bleeding because myometrial contractions

produce mechanical haemostasis without a significant

contribution from platelets. Platelet numbers should be

maintained above 50 · 109.l)1 for delivery. Platelet

counts below 20 · 109.l)1 should be augmented using

platelet transfusions.

The neonate of a mother with ITP may develop ITP as

a result of the transplacental transfer of maternal anti-

platelet IgG [24]. At delivery, 10–20% of these neonates

have platelet counts below 50 · 109.l)1 and, in 5%,

platelet counts may be <20 · 109.l)1 [27]. The major

fetal risk is intracranial haemorrhage causing neurological

sequelae or death, but this is rare [28]. There is no

consistent and reliable correlation between the fetal

platelet numbers at delivery and the severity of maternal

thrombocytopenia or the concentration of maternal

antiplatelet IgG [21, 27]. The most reliable predictor of

fetal thrombocytopenia is the presence of thrombo-

cytopenia at delivery of a prior sibling [29]. Determin-

ation of fetal platelet count can only be achieved by fetal

scalp sampling during labour or percutaneous umbilical

blood sampling, although the latter is associated with

bleeding and fetal bradycardia (� 1%) [30].

In 1977, a case report of intracranial haemorrhage after

a vaginal delivery of a thrombocytopenic infant to a

mother with ITP led to the recommendation that women

with ITP should be delivered by Caesarean section.

However, this approach has not been subjected to

randomised controlled studies and has been recently been

questioned [31, 32]. Cook and colleagues reviewed

literature that included 474 pregnant women with ITP

and reported that the incidence of intracranial haemor-

rhage among neonates with severe thrombocytopenia

(<50 · 109.l)1) was 4% after Caesarean delivery and

5% after vaginal delivery [31]. A literature review of

18 studies on maternal ITP that involved 601 neonates

showed that 12% of neonates had severe thrombo-

cytopenia, but that intracranial haemorrhage only

occurred in 1% (6 ⁄ 601) of neonates and was not related

to the mode of delivery [33]. It is currently recommended

that fetal platelet count using percutaneous umbilical

blood samples should be measured first, and delivery by

Caesarean section undertaken if the fetal platelet count is

<50 · 109.l)1 [34].

Umbilical cord platelet counts should be measured

from umbilical blood obtained at delivery regardless of

the method of delivery. Daily monitoring of platelet

numbers in the neonate is necessary because neonatal

platelet count can decrease for 4–5 days post delivery.

The neonate’s platelet count is usually normal by

1 month of age.

Pre-eclampsia and HELLP syndrome

Pre-eclampsia is characterised by hypertension and pro-

teinuria (> 300 mg.24 h)1) developing after 20 weeks of

gestation, and occurs in 6% of all pregnancies [35]. The

pathological lesions of pre-eclampsia involve deficient

remodelling of the maternal uterine vasculature by the

placental trophoblast early in pregnancy [36]. Abnormal

expression of cell adhesion molecules, and vascular

endothelial cell growth factor and its receptor by

trophoblasts in pre-eclampsia have been reported

[37, 38]. This causes uteroplacental vascular insufficiency

leading to abnormal release and metabolism of nitric

oxide, prostaglandins and endothelin by placental tissues.

These changes lead to platelet activation, generalised

endothelial dysfunction and hypertension [39]. Circula-

ting platelets adhere to damaged or activated endothe-

lium, causing enhanced platelet clearance. Although

increased levels of platelet-associated IgG are detected in

patients with pregnancy-induced hypertension (PIH), this

finding is not specific and does not provide an immuno-

logical basis for the thrombocytopenia [40]. Clearance of



IgG-coated platelets may be further increased by the

reticulo-endothelial system and platelet activation due to

thrombin generation [2]. Platelet function may also be

impaired in women with pre-eclampsia even if their

platelet count is normal.

Pre-eclampsia is present in 21% of cases of maternal

thrombocytopenia [28]. Thrombocytopenia occurs in

50% of pre-eclamptic patients and occasionally precedes

other manifestations of the disease. The thrombocyto-

penia is usually moderate and clinical haemorrhage is

uncommon unless the patient develops disseminated

intravascular coagulopathy. A decreasing maternal platelet

count is considered as an early sign of worsening of pre-

eclampsia and may occur even before other clinical

manifestations of the disease are apparent. The patho-

genesis of thrombocytopenia in women with severe pre-

eclampsia is unknown, although vascular endothelial

damage, impaired prostacyclin production and increased

deposition of fibrin within the vascular bed have been

suggested. Accelerated platelet destruction, platelet acti-

vation, increased platelet volume and increased mega-

karyocyte production have been observed [2]. An

increased response of platelet calcium to arginine vaso-

pressin preceding thrombocytopenia as early as in the first

trimester has been reported and has been proposed as a

possible predictor of the development of the disease [41].

Activation of the coagulation cascade occurs in most pre-

eclamptic patients, but routine tests such as activated

partial thromoboplastin time, prothrombin time and

fibrinogen concentrations are normal. However, fibrin-

ogen D-dimers and thrombin-antithrombin complexes

are elevated in most cases.

Only neonates born prematurely are at risk of neonatal

thrombocytopenia, and especially those with intrauterine

growth retardation [15]. The platelet count in neonatal

thrombocytopenia associated with pre-eclampsia is rarely

below 20 · 109.l)1 and does not cause fetal bleeding

complications [28]. Term infants of mothers with PIH are

no more likely to be thrombocytopenic than those of

normal mothers.

The HELLP (haemolysis, elevated liver enzymes,

low platelets) syndrome, a variant of pre-eclampsia, is

characterised by microangiopathic anaemia, SGOT

> 70 units.l)1, and thrombocytopenia (<100 · 109.l)1)

and is associated with a maternal mortality of about 3.3%.

Severe epigastric or right upper quadrant abdominal pain,

which need not be associated by proteinuria and hyper-

tension, are common symptoms. It is more common in

multiparae, occurs in a slightly younger age group

(19 years vs 25 years), and can manifest in approximately

30% of cases postpartum [42, 43]. It has been suggested

that the underlying primary pathological lesion in the

HELLP syndrome might be endothelial dysfunction and

damage, which leads to platelet aggregation, consumption

and eventually thrombocytopenia. Microthrombi depos-

ited in the liver sinusoids cause obstruction to hepatic

blood flow, consequently leading to liver distension and

elevations of liver enzymes [42]. Although platelet acti-

vation has been suggested in the pathogenesis of pre-

eclampsia or HELLP syndrome, prophylactic treatment of

high-risk pregnant women with low-dose aspirin does not

significantly decrease the incidence of pre-eclampsia [44].

The HELLP syndrome is associated with disseminated

intravascular coagulation, placental abruption, acute renal

failure, adult respiratory distress syndrome and intra-

uterine death. The perinatal mortality is about 22% and is

caused by placental abruption, intrauterine asphyxia, and

prematurity. Approximately 60% of babies die in utero.

Thirty percent of the infants (average gestational

age 32 weeks) are small for gestational age, and thromb-

ocytopenia is present in 25% of these.

The management of pre-eclampsia and HELLP is

focussed on stabilising the mother until fetal maturity is

more favourable. Fetal monitoring is mandatory, and will

help to decide whether early delivery of the fetus is

warranted. Early delivery of the fetus is warranted if there

are threats to fetal or maternal life or if the syndrome

develops beyond 34 weeks of gestation. Caesarean section

is required in 60% of cases [42].

Platelet transfusions increase the platelet count prior to

Caesarean section. However, the lifespan of the transfused

platelets is shortened. Coagulopathy associated with

PIH-related disseminated intravascular coagulation should

be treated with fresh frozen plasma or cryoprecipitate if

fibrinogen levels are low. If pre-eclamptic patients

deteriorate or remain thrombocytopenic after delivery,

plasma exchange and ⁄ or corticosteroids should be con-

sidered to reverse the abnormalities [6, 45].

Thrombotic thrombocytopenic purpura (TTP)

and haemolytic uraemic syndrome (HUS)

Thrombotic thrombocytopenic purpura is characterised

by microangiopathic haemolytic anaemia, thrombo-

cytopenia, central neurological abnormalities, fever and

renal dysfunction. In some series, up to 10% of all cases of

TTP occurred in pregnant patients, and pregnancy is

considered to be a predisposing factor for this disease [47].

A deficiency of a VWF-cleaving protease, ADAMTS 13,

has been identified as a causative factor in the patho-

genesis of TTP [48]. This deficiency may be caused by

mutations in ADAMTS 13 gene in the congenital variant

[49] or may result from antibodies against the protease in

the acquired form of the disease. TTP usually occurs

in the second trimester, with a mean onset of 23 weeks

[50]. The clinical manifestations of haemolytic uremic

syndrome are similar to that of TTP except that renal



dysfunction is more severe in HUS whereas neurological

abnormalities are more pronounced in TTP. Ninety

percent of cases of HUS occur in the postpartum period

(mean = 26 days after delivery) [50]. In most patients with

TTP and HUS, plasma antithrombin concentrations are

normal, whereas reduced antithrombin concentrations are

present in patients with pre-eclampsia or HELLP. As in

the HELLP syndrome, features of microangiopathic

haemolysis such as anaemia, increased bilirubin and

lactate dehydrogenase, decreased haptoglobin, Burr cells,

schistocytes, helmet cells, reticulocytosis and polychrom-

asia, are present in TTP and HUS. The course of TTP

and HUS does not improve following delivery of the

fetus. Remission can be achieved by plasma exchange in

75% of pregnant and non-pregnant patients with TTP.

However plasma exchange is less effective in reversal of

renal dysfunction for pregnancy-associated HUS. Chro-

nic renal failure and hypertension are long-term compli-

cations associated with HUS (Table 2).

Acute fatty liver of pregnancy

Mild microangiopathic haemolysis and thrombocytopenia

are observed in acute fatty liver of pregnancy (AFLP) [50].

AFLP is most common in primiparae and affects one of

5000–10 000 pregnancies. These women present with

malaise, nausea, epigastric and right upper quadrant pain,

dyspnoea, cholestatic liver abnormalities, hypoglycaemia

and decreased levels of fibrinogen and antithrombin. In

75% of these patients, there is laboratory evidence of

disseminated intravascular coagulation caused by decreased

hepatic synthesis of antithrombin. Management of patients

with AFLP is supportive with emphasis of correction of

hypoglycaemia, coagulopathy and electrolyte imbalances.

Other causes of thrombocytopenia in pregnancy

Disseminated intravascular coagulation can be associated

with obstetric disorders such as placental abruption,

amniotic fluid embolism, uterine rupture and intrauterine

fetal death and may cause thrombocytopenia. In systemic

lupus erythematosus (SLE) about 14–25% of patients

develop thrombocytopenia caused by antiplatelet auto-

antibodies or circulating immune complexes [51]. Mater-

nal autoantibodies can cross the placenta and cause fetal

thrombocytopenia, especially in the presence of Ro- and

La-antibodies [52].

Pregnant women suffering from antiphospholipid syn-

drome may have thrombocytopenia secondary to throm-

bosis, fetal loss or associated pre-eclampsia [53].

Approximately 28–42% of SLE patients have antiphosp-

holipid and ⁄ or lupus anticoagulant, and have an increased

risk of thromboembolism compared with those who lack

these antibodies. The high fetal loss associated with the

antiphospholipid syndrome is caused by recurrent throm-

bosis of the placental and decidual blood vessels.

Drug-induced thrombocytopenia occurs in pregnant as

well as non-pregnant women. Quinidine and sulphona-

mides are among the most common drugs associated with

acute thrombocytopenia [54].

Pregnant women with Type IIb von Willebrand

disease may develop thrombocytopenia, which is caused

by the enhanced clearance of platelets that bind to

abnormal von Willebrand Factor molecule. HIV infection

should be considered in any thrombocytopenic patient

with risk factor [55].

Anaesthetic considerations

The choice of anaesthetic technique in the pregnant

women with thrombocytopenia largely depends on the

proposed method of delivery, gestational age of the fetus,

coagulation status, associated obstetric complications,

history of recent or current bleeding and other significant

medical history. The risk of epidural haematoma in the

general population is estimated to be 1 in 150 000 after

epidural analgesia [56]. There are eight reports of spinal

haematomas following obstetric epidural analgesia ⁄ anaes-

thesia in the literature but some of these are questionable

[9, 57]. The incidence of epidural haematoma is 0.2–3.7

in 100 000 obstetric epidural blocks [59].

Circulating platelet numbers and their function deter-

mine the safety of regional anaesthesia. A lower limit of

100 · 109.l)1 for platelet count is suggested as ‘safe’ for

performing an epidural blockade, although there are no

supporting data [60]. Several studies have attempted to

address the issue of the risk of epidural haematoma when

the platelet count is between 50 and 100 · 109.l)1. Two

Table 2 Clinical and laboratory features of HELLP, TTP, HUS.

Feature HELLP TTP HUS

Time of presentation >37 weeks mid-trimester postpartumCNS signs variable severe rareRenal failure variable mild severeHepatic dysfunction definite nil nilFever nil present nil usuallyPurpura nil severe nil usuallyDecreased platelets mild–moderate severe moderateCreatinine increase mild mild largeAST ⁄ ALT increase increase no change no changeLDH increase mild marked markedHyaline thrombi +– ++ ++Post-partumimprovement

yes nil nil

HELLP = ‘Haemolysis, Elevated Liver enzymes, Low Platelets’. TTP =thrombotic thrombocytopenic purpura. HUS = haemolytic uraemicsyndrome. AST = aspartate aminotransferase. ALT = alanine amino-transferase.



retrospective studies have suggested that epidural anaes-

thesia may be safely undertaken when the platelet count is

<100 · 109.l)1 [2, 61]. In a study of 2929 parturients, no

complications associated with regional anaesthesia were

recorded in the 24 women who had a platelet count

<100 · 109.l)1 [62]. Beilin and colleagues reported that,

over a 3-year period, 30 parturients who had platelet

counts ranging from 69 to 98 · 109.l)1 safely received

epidural anaesthesia [63]. A survey of American anaes-

thetists reported that 66% in academic practice and 55% of

those in private practice would place an epidural anaes-

thetic when the platelet count is between 80 · 109.l)1

and 100 · 109.l)1 [64]. Most haematologists suggest that a

platelet count >50 · 109.l)1 is safe for surgery and

neuraxial blockade, provided platelet function is normal

[5, 24].

Before carrying out further investigations to determine

the cause of thrombocytopenia, factitious platelet counts

due to laboratory artefacts must be ruled out by reviewing

the peripheral blood film using a citrated blood sample.

This artefact, termed as pseudo-thrombocytopenia, is

caused by in vitro platelet clumping when EDTA is used

as the anticoagulant, and is due to adhesion of platelets to

the periphery of neutrophils in the presence of platelet

agglutinins (IgG or IgM) [65].

The bleeding time test, a simple bedside test that

evaluates the quality and quantity of platelets, is not

considered to be reliable to determine the safety of

epidural catheter placement because of wide observer

variation. It is affected by technical (length and size of

cut, occlusion pressure) and patient (ethnicity, diabetes,

hypercholesterolaemia, etc.) factors [66].

Coagulation tests performed several weeks before

delivery are not reliable in predicting coagulation abnor-

malities during labour [67]. In a study of 797 women,

prothrombin time and the activated partial thrombo-

plastin time were normal in all patients including those

with low platelets and plasma fibrinogen concentrations

(<2.9 gl)1) and it was concluded that these tests are

unnecessary in clinically normal parturients. The authors

also reported that the percentage of women with

platelet count values <100 · 109.l)1 increased from

0.5% (3 ⁄ 797) to 1.4% (11 ⁄ 797) between blood sampled

during the 9th month of pregnancy and that obtained

in labour.

The thromboelastogram (TEG) measures whole blood

clotting, and the interactions between the coagulation

cascade, fibrinogen, and platelets. However, TEG does

not measure initial platelet adhesion to exposed collagen

in the damaged vessel wall. Orlikowski measured platelet

count, TEG variables and bleeding time in 49 parturients

with pre-eclampsia. The thromboelastography variables,

k time and maximal amplitude (MA) have a strong

correlation with platelet count (k time ) platelet count

<100 · 109.l)1, r = )0.84, p = 0.02; MA ) platelet

count <100 · 109.l)1, r = )0.78, p = 0.04). An MA of

53 mm correlated with a platelet count of 54 · 109.l)1

(95% confidence limits, 40–75 · 109.l)1) and was asso-

ciated with adequate clot formation produced by throm-

boelastography. The authors suggested that patients with

platelet counts greater than 75 · 109.l)1 should not be

denied regional anaesthesia [68]. In another study of TEG

in normal pregnant women and in women with pre-

eclampsia, all patients with a platelet count >75 · 109.l)1

had a normal MA, which indicated a normal clot [69].

It is difficult to draw firm conclusions about the reliability

of TEG to predict which patients might develop epidural

haematoma from these studies because few patients

with platelet counts <75 · 109.l)1 received epidural

anaesthesia.

Aggregometry (measures platelet aggregation in

response to specific agonist such as ADP and epinephrine)

and flow cytometry (measures platelet activation and

aggregation) are not practical clinical tests because they

are time-consuming and require technical expertise.

The Platelet Function Analyser (PFA-100) may offer a

rapid, simple point of care assessment of platelet aggre-

gation. The PFA-100 platelet function analyser evaluates

primary coagulation under high shear stress by measuring

the time required for whole blood to occlude an aperture

in a membrane coated with collagen and the platelet

agonists, epinephrine (PFA-EPI), or adenosine diphos-

phate (PFA-ADP), called ‘closure time’. A 800-ll sample

of citrated blood, maintained at 37 �C, is aspirated into

stainless steel capillaries, through which a central aperture

is cut into the membrane covered with collagen and

epinephrine or collagen-ADP. Platelet activation and

aggregation occurs on the membrane, resulting in the

occlusion of the aperture and interruption of blood flow

[70]. The test takes approximately 7 min. In a study of

platelet function during pregnancy using the PFA-100 in

patients with thrombocytopenia associated with pre-

eclampsia, there was a correlation between platelet

numbers and PFA-ADP closure time (normal range

71–118 s) particularly when the platelet count was less

than 50 · 109.l)1 [71]. The PFA-ADP closure times were

normal in healthy patients. However, the PFA-EPI

closure times increased in six otherwise healthy patients,

suggesting that PFA-EPI may give false positive values.

Further evaluation of the PFA-100 in pregnant women

with platelet counts of less than 50 · 109.l)1 is required

[71]. Haemostasis is initiated by platelet adhesion to

damaged vessel wall and the main disadvantage of all

laboratory platelet function tests is that they do not

measure the interaction between platelet and the vascular

endothelium.



Large prospective studies with an estimated sample size

of >200 000 patients are required to definitively

determine whether it is safe to place an epidural or

spinal anaesthetic in patients with a platelet count

<100 · 109.l)1 [63]. The entire clinical presentation of

the patient must be considered when deciding on the

appropriate choice of anaesthesia. It is important to ensure

that there is no clinical evidence of bleeding and that the

platelet count is not decreasing when epidural catheter

placement is contemplated. A decreasing platelet count is

considered a contraindication to neuraxial blockade,

especially in dynamic conditions such as pre-eclampsia

and ITP [63]. Pseudo-thrombocytopenia must be exclu-

ded. A manual platelet count is more accurate in patients

with recent thrombocytopenia because automated coun-

ters are not reliable at low platelet counts. Specific

questions about medications that might interfere with

platelet numbers and function should be asked. A physical

examination of the patient should include looking for

evidence of bruising and bleeding at venepuncture sites or

petechiae at the blood pressure cuff site. Consumptive

coagulopathy associated with placental abruption and

other conditions must be ruled out. When considering

regional anaesthesia in patients with thrombocytopenia,

spinal anaesthesia may be safer. A soft flexible catheter that

is less likely to puncture blood vessels is preferred if an

epidural anaesthetic is undertaken [66]. Careful monitor-

ing of the patient in the postpartum period to detect early

signs and symptoms of an epidural haematoma should be

undertaken. General anaesthesia for urgent Caesarean

section becomes necessary if coagulation is abnormal or

there is bleeding.

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REVIEW ARTICLE

Human Immunodeficiency Virus: Anesthetic andObstetric ConsiderationsShmuel Evron, MD*, Marek Glezerman, MD†, Ethan Harow, DO‡, Oscar Sadan, MD§, andTiberiu Ezri, MD�

From the *Obstetric Anesthesia Unit, the †Department of Obstetrics and Gynecology, the ‡Ambulatory Surgical Unit,§Delivery Ward, �Department of Anesthesia, The Edith Wolfson Medical Center, Holon (Israel), Sackler School ofMedicine, Tel Aviv University, Tel Aviv, Israel

The pandemic of acquired immune deficiency syn-drome (AIDS) is on the threshold of its third decade ofexistence. The World Health Organization-United Na-tions statistics show that human immunodeficiency vi-rus (HIV)/AIDS pandemia is set to get much worse.Women of reproductive age are the fastest growingpopulation with HIV. Common signs and symptomshave become more moderate or subclinical, and newclinical presentations have emerged. It is quite appar-ent that HIV-disease affects multiple organ systems.Advances have been made in elucidating the pathogen-esis of HIV. In addition, the molecular technique of viralload determination and the CD � 4 T-lymphocytecount enable evaluation of the disease, its prognosis,and its response to therapy. There is limited specificinformation concerning the overall risk of anesthesiaand surgery of HIV/AIDS patients. However, as far as

can be determined, surgical interventions do not in-crease the postoperative risk for complications or deathand should therefore not be withheld. There is also littleevidence to suggest that HIV or antiretroviral drugs in-crease the rate of pregnancy complications or that preg-nancy may alter the course of HIV infection. Generalanesthesia is considered safe, but drug interactions andtheir impact on various organ systems should be con-sidered preoperatively. Regional anesthesia is often thetechnique of choice. Yet, one must take into consider-ation the presence of neuropathies, local infection, orblood clotting abnormalities. It should be emphasizedthat all practicing anesthesiologists should be familiarwith the disease and should use prenatal anesthesiaconsultations and a team approach to assure optimaltreatment for HIV patients.

(Anesth Analg 2004;98:503–11)

A cquired immune deficiency syndrome (AIDS)was first recognized more than 20 years ago,and since then it has reached pandemic propor-

tions. Within 2 decades, more than 50 million peoplehave been infected with the human immunodeficiencyvirus (HIV) and 20 million have died. Worldwide,two-thirds of the 36 million known carriers of HIV areliving in sub-Saharan Africa (1). In the United States(US), 950,000 people have HIV/AIDS. In the year 2001,15,000 of those people died from the disease (1). Newinfections occur at approximately 40,000 per year (2).Young women are the fastest growing populationwith HIV in the US. Almost 30% of new HIV infectionsin the year 2000 were among women. Eighty-two per-cent of the new infections occurred in ethnic/racial

minorities, predominantly among African Americans.The parturient transmits the HIV perinatally; thus theepidemic in children parallels the epidemic amongwomen (2,3). The transmission of the disease innonbreast-fed infants occurs 30% of the time in uteroand 70% during labor and delivery (4).

The overall risk of anesthesia and surgery in HIVpositive patient needs further study. Twenty to 25percent of HIV-positive patients will require surgeryduring their illness (5). Anesthesiologists need to beaware of the disease when deciding on the course ofanesthesia. This multiorgan disease may be compli-cated either by opportunistic infections, tumors, sub-stance abuse, or antiretroviral therapeutic drugs,which all can have an impact on anesthesia.

HIV is a member of the lentivirus family, a subtypeof human retroviruses. It is characterized by a cyto-pathic action, a long latency period, and persistentviremia. As a result of impaired cell-mediated immu-nity, the infected person is more susceptible to viral,bacterial, mycobacterial, and malignant disease (6). Ofthe untreated patients, 10% will develop symptomatic

Accepted for publication September 8, 2003.Address correspondence and reprint requests to M. Glezerman

MD, Professor and Chairman, Department of Obstetrics and Gyne-cology, The Edith Wolfson Medical Center, Holon, Israel. Addressemail to [email protected].

DOI: 10.1213/01.ANE.0000097193.91244.50

©2004 by the International Anesthesia Research Society0003-2999/04 Anesth Analg 2004;98:503–11 503

AIDS in the first 2–3 yr of infection. The remainderwill develop the disease over a 10-yr time period (7).

Diagnosis of HIV Infection

As the viral envelope is composed of different glyco-proteins, antibodies to these proteins or to the p24antigenic core can be detected. The diagnostic tech-niques include serologic tests, viral culture, genomicdetection, and amplification of viral ribonucleic acid(RNA) or proviral deoxyribonucleic acid (DNA).

Specific HIV antibodies can be detected serologi-cally 2–8 wk (usually within 3 wk) after infection. Thefirst antibodies to appear are immunoglobulin (Ig) Mto the viral envelope glycoprotein. After a few daysthe IgG to p24 core antigen and gycoprotein-gp120appear. Antibody detection tests are the enzyme-linked immunosorbent assay (ELISA) and the morespecific Western blot test (8).

HIV diagnosis can be made by direct detection ofHIV using the ELISA test for p24 core antigen or byamplification and detection of proviral DNA or HIVRNA using polymerase chain reaction. This can beimportant for the monitoring of HIV treatment fordetection of HIV in neonates of infected mothers (9).Viral load determination is used for diagnostic quan-tification and monitoring of HIV treatment (10). Theseviral load levels usually correlate with CD4

� T celllymphocyte count. A successful anti-HIV therapymeans viral load suppression to an undetectable bloodlevel.

Clinical Manifestations of HIV Infection

Over time, antiretroviral therapy has changed the ep-idemiologic, demographic and clinical characteristicsof AIDS. The signs and symptoms can be caused bythe HIV infection, opportunistic infections, neoplasm,or by the antiretroviral drugs. As the highly activeantiretroviral therapy (HAART) became more effec-tive, life expectancy and the clinical appearance hasbecome moderated or subclinical.

Central and Peripheral Nervous System. Some 30% ofadults and 50% of children suffering from AIDS willdevelop neurological disorders (11). In the early stageof infection, headaches, photophobia, meningoen-cephalitis, depression, irritability, Guillain-Barre-likesyndromes, or cranial and peripheral neuropathy canbe observed. The latent phase of the disease is associ-ated with demyelinating neuropathy and cerebrospi-nal fluid pathology. The late period of HIV infection isassociated with meningitis, focal or diffused enceph-alopathy, myelopathy, myopathy, and peripheralneuropathy.

As the central nervous system (CNS) is the firstcrucial organ to be affected by anesthetic drugs, early

diagnosis of HIV deserves careful evaluation of cog-nitive and neurologic dysfunction. Patients with AIDSare more sensitive to opioids and benzodiazepines,which also reflects the extent of neurological involve-ment. The probable mechanism is based on increasedinterleukin-1 levels causing an increased � aminobu-tyric acid-mediator production (12). HIV infection, in-tracranial masses, or opportunistic infections maycause cerebral edema, cerebral hemodynamic distur-bances, and increased intracranial pressure (ICP).These deserve anesthetic consideration and measuresfor reducing ICP and generally preclude the use ofneuraxial anesthesia in patients with increased ICP.Peripheral neuropathy is the most frequent neurolog-ical complication in HIV patients (13). It affects ap-proximately 35% of patients with AIDS and manifestsclinically as a polyneuropathy and myopathy.

An autonomic dysfunction in the HIV-infected per-son may appear with or without CNS abnormalities.AIDS patients may present with uncommon auto-nomic disturbances, such as orthostatic syncope, hy-potension, and diarrhea (14).

Pulmonary Abnormalities. The pulmonary manifes-tations of patients infected with HIV are causedmainly by opportunistic infections. The most commonof these, Pneumocystis carinii infection, has becomerarer with the use of HAART and prophylactic drugtherapy (15). An immunocompromised person with aCD4

� lymphocyte count of �200 cells/mm3 is at in-creased risk for developing P. carinii pneumonia. Thedisease may present as adult respiratory distress syn-drome and may be complicated by pneumatoceles,pneumothorax, or respiratory failure (16). Computedtomography of the chest in the early stages of thedisease may reveal bilateral haziness of both lungs,whereas chest radiograph appears normal (17).

Tuberculosis (TB) is another concern in AIDS pa-tients. The incidence of HIV-associated TB has beenincreasing, especially among women of childbearingage (18). Patients with both infections may presentwith atypical manifestations of TB that causes diffi-culty in making a diagnosis. Other pathologies thatmay affect the lungs are Kaposi’s sarcoma, lympho-mas, and cavitary lung disease caused either by fungalpathogens or Nocardia.

Cardiac Manifestations. Advances in the treatmentof HIV infection have improved longevity of HIVpatients, thereby they develop more cardiac involve-ment (Table 1) (19). In the advanced stage of thedisease, myocarditis is more common and is caused byopportunistic infections or neoplasm-like lymphomasand Kaposi’s sarcoma (20).

There are reports of various abnormalities associ-ated with a hypercoagulable state (21). These includepulmonary hypertension, accelerated coronary arte-riosclerosis, a decrease in left ventricular contractility

504 REVIEW ARTICLE EVRON ET AL. ANESTH ANALGHUMAN IMMUNODEFICIENCY VIRUS: ANESTHETIC AND OBSTETRIC CONSIDERATIONS 2004;98:503–11

and myocardial infarction in young HIV patients. Pre-operative cardiac evaluation is therefore mandatoryand appropriate perioperative cardiovascular moni-toring of these patients is of crucial importance (22).

Gastrointestinal Abnormalities. Gastrointestinal ab-normalities are commonly encountered in patientswith AIDS (Table 1). Signs and symptoms may origi-nate from the oropharynx, esophagus, stomach, andhepatobiliary system (23). The main cause of dyspha-gia is Candida albicans esophagitis. Other commonpathogens are cytomegalovirus (CMV), herpes virus,Kaposi’s sarcoma, histoplasmosis, and squamous cellcarcinoma. In advanced AIDS, esophageal reflux iscommon, which may increase the risk for pulmonaryaspiration on induction of general anesthesia (24). Ab-normal liver function tests are also common in ad-vanced AIDS and reflect the decreased metabolic andsecretory ability of the liver in addition to coagulationabnormalities. Finally, electrolyte abnormalities arecaused by diarrhea and decreased oral intake resultingfrom dysphagia or nausea.

Hematological Abnormalities. A wide spectrum ofhematologic abnormalities in HIV patients is verycommon and may appear at any stage of the disease(Table 1). Bone marrow involvement and coagulationabnormalities may result from HIV infection, anti-HIVdrugs, nutritional factors, and bone marrow infiltra-tion by opportunistic infection or neoplastic diseases(25).

The literature contains reports of thrombotic epi-sodes and various predisposing abnormalities related

to a hypercoagulable state that correlate with the se-verity of HIV disease (26). The coexistence of HIV-related illness, such as malignancies and autoimmunedisease, as well as antiretroviral drug therapy itself,may also predispose these patients to thromboembolicevents (26).

Another coagulation abnormality seen in the HIVpatients is idiopathic thrombocytopenic purpura thatis caused by platelet serum immunoglobulin, or directadverse effects of HIV infection on the megakaryo-cytes (25). Some of the antiretroviral (zidovudine) orantiopportunistic drugs (ganciclovir) may contributeto these hematologic abnormalities as a result of bonemarrow suppression (25).

Renal Abnormalities. HIV patients are at risk fordeveloping various renal diseases caused by HIV in-fection, viral hepatitis, drug abuse, antiretroviraldrugs, and dehydration (27). The HIV-associated ne-phropathy is a distinct clinico-pathological syndromepresenting as a nephrotic syndrome. The use ofangiotensin-converting enzyme inhibitors, steroids,and antiretroviral treatment may slow down its pro-gression to end-stage renal failure (28). The use of anantiretroviral drug, such as adefovir, may cause acutetoxic tubular necrosis (29). Indinavir, which is alsocommonly used, is associated with a 3% incidence ofnephrolithiasis (30).

Endocrinologic and Metabolic Abnormalities. Thecourse of HIV infection or AIDS can be complicated bya variety of endocrine and metabolic abnormalities.This may be a direct effect of HIV on the respectiveglands, by opportunistic infections, neoplasm, or an-tiretroviral drugs. Primary or secondary adrenal insuf-ficiency is still the most serious endocrine complica-tion in HIV patients (31). Thyroid function tests inAIDS patients may be abnormal, although clinical hy-pothyroidism is rare.

Hypoglycemia is another metabolic abnormalitythat may be caused by islet cell damage resulting frompentamidine treatment. Hyperinsulinemic hypoglyce-mia may be associated with hypopituitarism in anAIDS patient or as a complication of protease inhibitortreatment (22).

HIV and Pregnancy

One-third of new HIV positive patients in 2000 werewomen (1). In the US, the nationwide seroprevalenceof HIV during pregnancy has been reported as 1.7 per1000 pregnancies (32). The majority of pediatric HIVinfections resulted from vertical transmission of thevirus from mother to infant. This occurred 4.4% of thetime during pregnancy, 60% of the time during deliv-ery, and 35.6% of the time during breastfeeding (33).

A meta-analysis of the International Perinatal HIVgroup included 15 prospective European and NorthAmerican studies of 8500 parturients. A reduction of

Table 1. Manifestations of Human ImmunodeficiencyVirus Infection

CardiovascularPericardial effusionMyocarditis (opportunistic infections, neoplasms)Dilated cardiomyopathyEndocarditisPulmonary hypertensionDrug-related cardiotoxicityThromboembolic complicationsRheological impairment (increase of tumor necrosis

factor and interleukin 1-alpha)Decreased left ventricular contractilityMyocardial infarction

GastrointestinalEsophagitis, dysphagia, odynophagiaDiarrhea, gastrointestinal bleeding, abdominal painHepatitisBiliary disease (acalculous cholangitis)

HematologicAnemiaLeukopenia, lymphopeniaThrombocytopeniaBone marrow suppression (infections, drugs, neoplasms)HypercoagulabilityAcquired immune deficiency syndrome-related

lymphoma (Hodgkin’s disease)

ANESTH ANALG REVIEW ARTICLE EVRON ET AL. 5052004;98:503–11 HUMAN IMMUNODEFICIENCY VIRUS: ANESTHETIC AND OBSTETRIC CONSIDERATIONS

vertical transmission by more than 50% was observedwhen elective cesarean delivery was performed (34).More recently, elective cesarean delivery combined withantiretroviral therapy has reduced vertical transmissionto �5% (35). The American College of Obstetricians andGynecologists (ACOG) committee opinion of May 2000stated that when viral loads are more than 1000 copiesper milliliter, the benefit from elective cesarean deliveryis beyond that achieved by antiretroviral therapy alone(36). It has been further noted that the mode of deliveryshould be individually assessed and that the viral loadtesting has to be followed every 3 mo. Many practitio-ners do not recommend elective cesarean delivery forHIV-infected women who are compliant with antiretro-viral therapy and have undetectable HIV viral loads (37).The revised ACOG Committee Opinion also considersroutine delivery by cesarean section to be problematicand potentially dangerous, especially in rural hospitalsin Africa where maternal mortality approximates 230per 100,000 (36). The incidence of complications is sig-nificantly increased when the CD4

� count is �200 mm�3

(38,39). Routine HIV testing should be offered to everypregnant person at risk of HIV infection.

The percentage of women diagnosed before deliveryin the US has improved from 51% in 1993 to 80% in 1996(40). The European Collaborative study has shown that14% of HIV-infected pregnant women are immunocom-promised, and there is no evidence to suggest that preg-nancy alters the course of HIV infection (41).

Intrauterine growth retardation and premature de-livery were reported among infants of HIV-infectedwomen regardless of their infectious condition (41).

HIV Therapy Interaction with Anesthesia andObstetrics

Combined HAART has dramatically improved survivalof HIV-diseased patients, has delayed the progress of the

disease, and has caused a decline in AIDS incidence anddeath. More than 14 drugs have been used. Most of themproduce side effects that interact with anesthetic drugs.Some of these adverse effects may mimic signs andsymptoms of the HIV disease itself. Side effects may alsoresult from drugs used for prevention or treatment ofopportunistic infections.

Pregnancy may affect timing and choice of therapy,but it is not considered a contraindication or a reason topostpone treatment, although dosing must take into con-sideration blood volume and volume of distributionchanges during pregnancy. In addition, there are poten-tial toxic drug effects on the fetus and the newborn(42,43). New guidelines suggest that pregnant womenshould continue or start with combined HAART therapyat a maximally suppressive regimen, although little dataon animal and human toxicity support these recommen-dations (43). Additional information is available athttp://www.aidsinfo.nih.gov.

Antiretroviral Drugs

Three classes of antiretroviral drugs have gained Foodand Drug Administration approval and are currentlyused in the management of HIV disease (44) (Tables2–4).

1. Nucleosides analog reverse transcriptase inhibi-tors. These drugs inhibit the completion of re-verse transcription by binding to the viral DNA.Side effects commonly reported with zidovudinetreatment include headache, insomnia, nausea,and vomiting. Prolonged therapy can lead toneuropathy, malaise, myalgia and myopathywith increased creatinine-phosphokinase, andpancytopenia. Peripheral neuropathy is the mostcommon side effect of zalcitabine. It correlateswith the severity of HIV infection and may affect

Table 2. Antiretroviral Drugs [Nucleoside Analogue Reverse Transcriptase Inhibitors (NRTIs)] and Side Effects

Generic Name Trade NameFDA Pregnancy

Category Dose Adverse Side Effects

Zidovudine (AZT) Retrovir* C 100 mg 6�/day Anemia, neutropenia, pancytopenia, headache,neuropathy, myopathy

Didanosine (ddi) Videx† B 200 mg b.i.d. Peripheral neuropathy, pancreatitis,gastrointestinal disturbances

Stavudine (d4T) Zerit† C 40 mg b.i.d. Peripheral neuropathy, pancreatitisZalcitabine (ddC) Hivid‡ C 0.75 mg t.i.d. Peripheral neuropathy, pancreatitisAbacavir Ziagen* C 300 mg t.i.d. Gastrointestinal disturbances, skin rash, myalgiaLamivudine (3Tc) Epivir* C 300 mg b.i.d. Peripheral neuropathy, skin rash,

gastrointestinal disturbancesZidovudine plus

LamivudineCombivir* C 300 mg b.i.d. Peripheral neuropathy, pancreatitis

Adefovir Hepsera§ C 120 mg/day Gastrointestinal disturbances, increased liverenzymes, renal toxicity

Food and Drug Administration (FDA) Pregnancy Category � “B” (animal reproduction studies failed to demonstrate a risk to the fetus); “C” (safety in humanpregnancy has not been determined).

* Manufactured by GlaxoSmithKline, Research Triangle Park, NC; † manufactured by Bristol-Myers Squibb, New York, NY; ‡ manufactured by RochePharmaceuticals, Basel, Switzerland; § manufactured by Gilead Sciences, Foster City, CA.


30% of patients treated (45). Lamivudine is theleast neurotoxic of the currently used nucleosideanalogues. It may exacerbate preexisting neurop-athy (46). However, combined antiretroviral ther-apy was shown to improve HIV-related periph-eral neuropathy (47). Peripheral neuropathy isgenerally reversible on cessation of therapy.

2. Non-nucleotide reverse transcriptase inhibitors(NNRTIs). These drugs inhibit the enzyme reversetranscriptase by direct binding. Because they bindonly to the HIV-1, resistance to them develops rap-idly when given as a single drug. The recommen-dations are to use NNRTIs in combination withthree or more drugs to enhance their effectiveness(48). The NNRTIs most commonly used are nevi-rapine, delavirdine, and efavirenz (Table 3). Theirmajor side effect is skin rash, including Stevens-Johnson’s syndrome. Nevirapine causes cyto-chrome P450 enzyme induction (CYP3 A3/4) andmay decrease serum levels of some anesthetic orsedative drugs (i.e., midazolam, fentanyl) (49).

3. Protease inhibitors (PIs) (Table 4). These drugsinhibit the HIV protease by binding to the activecleavage site. The most commonly used PIs aresaquinavir, ritonavir, indinavir, and nelfinavir.

Side effects are gastrointestinal symptoms, hy-perglycemia, peripheral neuropathy, obstructiveuropathy (30), increased liver enzymes, and hy-pertriglyceridemia (50). Efavirenz is a potent ter-atogenic drug that should be avoided during thefirst trimester of pregnancy (45). Indinavir maybe associated with mild hyperbilirubinemia, he-maturia, and renal failure resulting from obstruc-tive uropathy (30). The PIs are metabolized bythe cytochrome P450 isoenzyme cytochromeP3A4(CYP3A4). They competitively inhibit the enzymeand may increase the effects of drugs metabo-lized by cytochrome P450. Therefore, these anes-thetic drugs should be titrated carefully (49).Ritonavir is the most potent inhibitor of CYP3A4and CYP2D6 and is a less potent inhibitor ofCYP2C9/10 (51). Fentanyl, a synthetic opioid an-algesic, is metabolized mainly by CYP3A4 (51)and to a lesser extent by other CYPs (52).

Anesthetic Management

Assessment of risk and coexisting diseases during pre-operative evaluation should focus on the patient’s sta-tus, type of surgery, and anesthesia, which, combined

Table 3. Antiretroviral Drugs (Non-Nucleoside Reverse Transcriptase Inhibitors) and Side Effects

GenericName Trade Name

FDA PregnancyCategory Dose Adverse Side Effects

Nevirapine Viramune* C 200 mg q.d. Gastrointestinal disturbances, increased liver enzymes,skin rash, P-450 enzyme induction

Efavirenz** Sustiva† C 600 mg q.d. Skin rash, gastrointestinal disturbances, increased liverenzymes

Delavirdine Rescriptor C 400 mg t.i.d. Skin rash, gastrointestinal disturbances, increased liverenzymes

Food and Drug Administration (FDA) Pregnancy Category � “C” (safety in human pregnancy has not been determined).* Manufactured by Boehringer Ingelheim, Ridgefield, CT; † manufactured by Bristol-Myers Squibb, New York, NY; ‡ manufactured by Pfizer, New York, NY.** Efavirenz should be avoided during the first trimester of pregnancy.

Table 4. Antiretroviral Drugs (Protease Inhibitors) and Side Effects

GenericName Trade Name

FDA PregnancyCategory Dose Adverse Side Effects

Saquinavir Invirase fortovase* C 600 mg t.i.d. Gastrointestinal disturbances, hyperglycemia,lipodystrophy, inhibits cytochrome P-450-isoenzyme(CYP3A)

Indinavir Crixivan† B 800 mg t.i.d. Gastrointestinal disturbances, hyperglycemia, skin rash,nephrolithiasis, renal failure, unusual distribution offat, inhibits cytochrome P-450

Ritonavir Norvir‡ B 600 mg b.i.d. Gastrointestinal disturbances, hyperglycemia, increasedliver enzymes, lipodystrophy, inhibits cytochromeP-450

Nelfinavir Viracept§ C 750 mg t.i.d. Gastrointestinal disturbances, hyperglycemia,lipodystrophy, inhibits cytochrome P-450

Amprenavir Agenerase� C 1200 mg b.i.d. Skin rash, inhibits cytochrome P-450

Food and Drug Administration (FDA) Pregnancy Category � “B” (animal reproduction studies failed to demonstrate a risk to the fetus); “C” (safety in humanpregnancy has not been determined).

* Manufactured by Roche Pharmaceuticals, Basel, Switzerland; † manufactured by Merck, Whitehouse Station, NJ; ‡ manufactured by Abbott Laboratories,North Chicago, IL; § manufactured by Pfizer, New York, NY; � manufactured by GlaxoSmithKline, Research Triangle Park, NC.


with the Centers for Disease Control stage of HIVinfection, the immunologic status (CD4

� cell count),and the coexistence of opportunistic infections andmalignancies, should allow a good prediction for theperioperative risk of the HIV-patient to be construed.Advanced HIV infection, when accompanied with op-portunistic infections or malignancies, may complicatethe perioperative course and management. The CD4

�

count/mortality relationship is useful in risk assess-ment. Regardless of surgical procedure, there is a13.3% mortality rate 6 mo postoperatively when theCD4

� count is �50 mm�3 and a 0.8% mortality ratewhen the CD4

� count is more than 200 mm�3 (53).Preoperative assessment consists of the history,

physical examination, and laboratory studies. The his-tory should include evaluation of opportunistic infec-tions and malignancy and concurrent treatments withantiretroviral or antiopportunistic drugs. The labora-tory work-up should include complete blood count,clotting functions, and glucose, liver, and renal func-tion tests. Verification of the immunological status,i.e., the CD4

� lymphocyte cell count and viral loadduring the previous 3 mo, is important. Chest radio-graph and electrocardiogram should be performed inall patients. Patients with a history or signs of cardiacor pulmonary dysfunction should undergo a morethorough evaluation (blood gases, pulmonary func-tion tests, echocardiography, cardiac effort test, andradioactive cardiac scanning or even cardiac catheter-ization). One must remember that these patients haveoften been subjected to cardiotoxic antiretroviraldrugs, may be in a hypercoagulable state, may haveaccelerated coronary arteriosclerosis, and often havedecreased left ventricular contractility (19–22). Theywill require appropriate preoperative work-up andtherapy before any anesthetic or surgical procedure.

Anesthetic Techniques

Factors that need to be considered when administer-ing general anesthesia include the possible effects ofanesthesia and opioids on the immune system, thepulmonary and neurologic status of the HIV patient,and possible interactions with anti-HIV medications.Laboratory data suggest a detrimental effect of opi-oids on immune function (54). However, the clinicalsignificance of short-term opioid administration dur-ing general anesthesia is unclear and there are notenough clinical data available to justify its avoidance.The presence of neurologic manifestations, such asovert dementia, may impair the ability of the patientto provide preoperative consent (55) and may increasebrain sensitivity to sedative or psychoactive drugs(opioids, benzodiazepines, and neuroleptics). Oppor-tunistic infections may be associated with increasedICP, predominantly with toxoplasmosis. Becausethese infections respond rapidly to medical therapy,

surgery should be postponed whenever possiblewhen they are present. Increased ICP and CNS infec-tions (meningitis, encephalopathy, or myelopathy) arecontraindications to neuraxial anesthesia (56).

The diagnostic approach to patients with HIV infec-tion and neuropathy, myopathy, or other neurologicaldeficit consists of taking a comprehensive neurologi-cal history and physical examination. Blood studiesare needed to exclude diabetes mellitus, vitamin defi-ciencies, alcoholism, hereditary diseases, and infec-tious diseases such as CMV or Lyme disease. Cerebro-spinal fluid analysis and nerve or muscle biopsy maybe required. Radiological studies of the spinal cordshould be performed as part of the neurological eval-uation to exclude compressive lesions in symptomaticpatients. This is particularly important in a patientscheduled for a surgical procedure under regionalanesthesia (57).

The complications associated with the use of succi-nylcholine, such as hyperkalemia or hyperpyrexia, areonly a potential risk to be considered in the HIVpatient with progressive neuropathy, myopathy, andmuscle wasting. No such complication in HIV patientshas been reported in the literature; hence, the use ofsuccinylcholine is not absolutely contraindicated (58).

Pulmonary complications can occur as a conse-quence of opportunistic infections. This may lead torespiratory distress and hypoxemia, aggravated by adecrease in functional residual capacity seen duringpregnancy. Regional anesthesia may be a preferabletechnique in these patients. However, a high motorblock with intercostal muscle paralysis may not betolerated. Regional anesthesia was shown to be asso-ciated with reduced morbidity and mortality in a widerange of patients, including treated HIV parturientshaving cesarean delivery under spinal anesthesia (59).

Toxic Side Effects and Drug Interaction withAnesthesia

Before administration of any anesthetics, the anesthe-siologist should be aware of the possible toxic sideeffects or to the possible interaction of antiretroviraldrugs with the anesthetics. For example, neuropathyor myopathy may dictate change of anesthetic tech-niques. Anemia and thrombocytopenia are major toxicside effects of zidovudine. PIs can affect glucose me-tabolism. Foscarnet and PIs can cause renal toxicity.Foscarnet can also alter calcium and magnesium bal-ance. Other side effects include increased liver en-zymes (trimethoprim-sulfamethoxazole), broncho-spasm (aerosolized pentamidine), and ventriculararrhythmias (IV pentamidine).

Pis, such as ritonavir, are inhibitors of CYP450,which impair the metabolism of multiple anestheticsand analgesics, such as midazolam and fentanyl, andcardiac drugs, such as amiodarone and quinidine (51).


Nevirapine is an inducer of CYP450 and therefore in-creasing doses of anesthetic drugs may be required inpatients receiving the drug (60). Etomidate, atra-curium, remifentanil and desflurane are not depen-dent on CYP450 hepatic metabolism, and therefore, arepreferable drugs.

When considering the type of anesthesia, regional an-esthesia has the advantage of not interfering with theimmune system or with antiretroviral drugs. Contrain-dications to regional anesthesia in these patients aresepsis and platelet abnormalities. The presence of neu-ropathy may reduce the appeal of regional anesthesiabut there are no data to contradict its use. In a review of96 HIV positive parturients, of whom 36 delivered underregional anesthesia, the advantages of regional anesthe-sia were confirmed (61). In a recent article (59), the effectof spinal anesthesia was studied in 45 HIV-treated par-turients who underwent cesarean delivery. There wereno perioperative complications or changes in immunefunction or viral load. The American Medical Associa-tion addressed the issue of providing care for patientswith HIV and stated that physicians have an ethical dutyto provide any treatment needed to HIV patients andavoid discrimination against such patients (62).

Postdural puncture headache may occur after regionalanesthesia and may necessitate epidural blood patch.Tom et al. (63) found no increase in neurologic abnor-malities in 6 HIV patients receiving an epidural bloodpatch during a follow-up period of 2 yr. There is noevidence to contraindicate the use of blood patch inHIV-positive patients. However, the small numbers re-ported may justify a conservative management as a firstchoice (64).

Magnetic resonance imaging (MRI) studies of the spi-nal cord in 55 symptomatic HIV patients showed neu-rologic involvement of the spinal cord in 49 patients,mostly of infectious origin (57). Currently, MRI is notoften done in the preoperative HIV patient presentingwith neurologic involvement, but is considered in a com-prehensive neurological work-up or for neurosurgicalindications to verify soft tissue pathology. There areincreasing numbers of compromised HIV patients whoare drug abusers, diabetics, postorgan transplantationrecipients, and on long-term steroid treatment develop-ing spinal infections. They are often diagnosed too late,mostly presenting with back pain or other neurologicsigns or symptoms (65). Prolonged epidural catheteriza-tion in such severely compromised patients may be con-traindicated (66). However, a series of 350 cancer pa-tients who had prolonged epidural catheterization andwere monitored closely for possible infection andpromptly treated had no adverse sequelae (67).

ConclusionsThe pandemic of AIDS is on the threshold of its thirddecade of existence. The World Health Organization

and United Nations statistics indicate that HIV/AIDSpandemia will get much worse. Women of reproduc-tive age are the fastest growing population with HIV.Common signs and symptoms have become moremoderate or subclinical, and new clinical presenta-tions have emerged. It is quite apparent that HIVdisease affects multiple organ systems. Advances havebeen made in elucidating the pathogenesis of HIV. Inaddition, the molecular technique of viral load deter-mination and the CD�

4 T-lymphocyte count enablethe evaluation of the disease, its prognosis, and itsresponse to therapy. There is limited specific informa-tion concerning the overall risk of anesthesia and sur-gery on HIV/AIDS patients. However, as far as can bedetermined, surgical interventions do not increase thepostoperative risk for complications or death andshould therefore not be withheld. There is also littleevidence to suggest that HIV or antiretroviral drugsincrease the rate of pregnancy complications or thatpregnancy may alter the course of HIV infection. Gen-eral anesthesia is considered safe, but drug interac-tions and their impact on various organ systemsshould be considered preoperatively. Regional anes-thesia is often the technique of choice. Yet, one mustconsider the presence of neuropathies, local infectionor blood clotting abnormalities.

Anesthesiologists must be familiar with this disease,and prenatal anesthesia consultations and a team ap-proach will optimize treatment for the pregnantwoman with HIV.

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59. Avidan MS, Groves P, Blott N, et al. Low complication rateassociated with cesarean section under spinal anesthesia forHIV-1 infected women on antiretroviral therapy. Anesthesiol-ogy 2002;97:320–4.

60. Sahai J. Risks and synergies from drug interaction. AIDS 1996;10(Suppl 1):S21–5.

61. Gershon RY, Manning-Williams D. Anesthesia and the HIV-infected parturients: a retrospective study. Int J Obstet Anesth1997;6:76–81.

62. Kern JMcD, Gray BB. AIDS litigation for the primary care phy-sician. In: Sade MA, Volberding PA, eds. The medical manage-ment of AIDS. 3rd ed. Philadelphia: WB Saunders, 1992:477–83.

63. Tom DJ, Gulevich SJ, Shapiro HM, et al. Epidural blood patch inthe HIV positive patient: review of clinical experience. Anesthe-siology 1992;76:943–7.

64. Wlody DJ. Human immunodeficiency virus. In: Chestnut DH(ed). Obstetric anesthesia principles and practice. 2nd ed. StLouis: Mosby, 1999:860–74.

65. Broner FA, Garland DE, Zigler JE. Spinal infections in the im-munocompromised host. Orthop Clin North Am 1996;27:37–46.

66. Savioz D, Chilcott M, Ludwig C, et al. Preoperative counts ofCD4 T-lymphocytes and early post-operative infective compli-cations in HIV-positive patients. Eur J Surg 1998;161:483–7.

67. Du Pen SL, Peterson DG, Williams A, Bogosian AJ. Infectionduring chronic epidural catheterization: diagnosis and treat-ment. Anesthesiology 1990;73:905–9.


Best Practice & Research Clinical Obstetrics and GynaecologyVol. 19, No. 2, pp. 169–183, 2005

1

Management of human immunodeficiency

virus infection in pregnancy

J. Moodley* MBChB, FRCOG, FCOG, MD

Head of Department

D. Moodley MMedSci, PhD

Scientist

MRC/UKZN Pregnancy Hypertension Research Unit, Department of Obstetrics and Gynaecology,

Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

The HIV global epidemic is having a devastating effect on women of reproductive age; women aged15–24 years are 2.5 times more likely to be infected than young men in the same age group. Further,mother-to-child transmission (MTCT) accounts for almost two-thirds of the new infections thatoccur in children world-wide, annually. MTCTof HIV-1 varies widely and is dependent on obstetricpractices, mode of delivery, breastfeeding, and the level of the viral load in the mother.Antiretroviral therapy (ARV) in pregnancy is prescribed for two main reasons: (i) women whoneed ARV medication for their own health; (ii) women who do not need treatment, or do nothave access to treatment are offered prophylaxis to prevent MTCT, using one of a number of ARVregimens known to be effective.HIV infection is also associated with significant maternal morbidity and mortality. Clinicians caringfor HIV-infected women need to update their knowledge continuously to provide optimal care.

Key words: pregnancy; HIV; mother-to-child transmission; antiretroviral management.

An estimated 40 million people are living with HIV worldwide. Every day in 2003, anestimated 14 000 people were newly infected with HIV.1 More than 95% of these live inlow- or middle-income countries, where women and children are most vulnerable. Theepidemic is devastating for women, particularly in sub-Saharan Africa, where womenare more likely to be infected with HIV than men. Among young people, thisdiscrepancy is particularly high; women aged 15–24 years are up to 2.5 times morelikely to be infected than young men in the same age group. It is therefore not surprising

doi:10.1016/j.bpobgyn.2004.10.007available online at http://www.sciencedirect.com

1521-6934/$ - see front matter Q 2004 Elsevier Ltd. All rights reserved.

* Corresponding author. Address: Department of Obstetrics and Gynaecology, Nelson R Mandela School of

Medicine, Private Bag 7, Congella 4013, South Africa. Tel.: C27 31 260 4250; Fax: C27 31 260 4427.

E-mail address: [email protected] (J. Moodley).

http://www.sciencedirect.com

170 J. Moodley and D. Moodley

that of the 630 000 children infected with HIV annually worldwide, the great majorityare infected by mother-to-child transmission (MTCT).1

In the absence of an intervention, the risk of MTCT of HIV varies between 15 and20% in non-breastfeeding women in Europe, and between 25 and 40% in breastfeedingAfrican populations.2 The principal risks of transmission are related to maternal plasmaviral load, obstetric factors and infant feeding. MTCT is therefore largely preventablewhere antenatal HIV screening is available, feeding exclusively by artificial formula isfeasible, and where there is provision for antiretroviral (ARV) therapy and delivery bycaesarean section (C/S).

HIV infection in pregnancy is associated with significant maternal morbidity andmortality.3 Maternal deaths due to HIV and AIDS are now the leading cause of maternalmortality in South Africa, accounting for 23% of all maternal deaths.3 Clinicians whocare for HIV-infected women of reproductive age therefore need to keep abreast of theliterature to provide optimal care, including counselling, to allow women to balance therisks and benefits while deciding on therapeutic or prophylactic options for themselves,and their children, respectively. Moreover, clinicians should be strong advocates forpreventing new infections (HIV and other sexually transmitted infections), by providingappropriate counselling on safe sexual practices.

INTERACTIONS BETWEEN HIV AND PREGNANCY

Effect of pregnancy on HIV-disease progression

Studies in the USA and Europe have not shown pregnancy to have any effect on theprogression of HIV disease.4,5 Reports from resource-poor countries, however, suggestthat progression accelerates with pregnancy, but it is difficult to interpret such reportsbecause the sample sizes are small and the studies are subject to selection bias relatedto the indications for testing.6

Effect of HIV on pregnancy outcomes

Controversies about the outcomes of pregnancy in HIV-infected women still exist. Inrich countries, reports do not suggest an increase in the frequency of preterm birth,low birth weight babies, intrauterine growth retardation and stillbirths in comparisonwith similar groups of HIV non-infected women.6 Higher rates of perinatal mortality,however, are reported in HIV-infected women from poor countries, with advanced HIVinfections being associated with the highest neonatal death rates.6 The theory thatthere is a syndrome of malformation-related HIV infection has not been proven.Similarly, no studies have indicated that there is an increase in the frequency of birthdefects related to HIV infection.6–8

ANTENATAL CARE IN THE HIV-INFECTED

HIV testing

Among pregnant women, knowing one’s HIV status is the key to the preventionof MTCT. In countries where voluntary counselling and testing (VCT) for HIVand prevention of MTCT programmes are not an integral part of existing healthservices, it is common for women not to know their HIV status prior to pregnancy.

Management of HIV infection in pregnancy 171

Therefore, it is the responsibility of all health care workers providing care for pregnantwomen to make sure that they are offered voluntary counselling and HIV testingoptions as early in pregnancy as possible. Counselling and options for testing for HIVshould also accompany family planning and gynaecological consultations.

Concerns about the ethical issues of testing for HIVare discussed in Chapter 7. In brief,in the USA, the HIV test is offered with patient notification and the right to refuse. Thisapproach is simple and practical but maintains the patient’s autonomy. It recommends HIVtesting and offers more consideration than that applied to the battery of routine antenataltests for which the ‘general care’ consent suffices. Furthermore, the process is not soonerous as to dissuade clinicians from offering it, or the patient to perceive that she is atspecial risk. Mandatory testing without the right of refusal and VCT are other methodsused for establishing the HIV status of the woman. The former is regarded as time-consuming and impractical by clinicians, while the latter impinges on the patient’s rights.

Despite the practical approach recommended for HIV testing in the USA, there are anumber of women, particularly in poor countries, who do not initiate antenatal careuntil late pregnancy, or even early labour. This is a particularly vulnerable group, and ithas been reported that the prevalence of HIV infection in this group is much greaterthan in women who begin antenatal care early in pregnancy.9 There are, however,robust data indicating that initiating ARV therapy in late pregnancy and/or intrapartum,and neonatal prophylaxis, can reduce the risk of MTCT.10 Efforts should therefore bemade to give counselling and use rapid tests, with informed consent, in late pregnancyor early labour, to discern the serostatus of such women.

All algorithms for testing for HIV do include individual post-test counselling by anappropriately trained health professional. Women diagnosed with HIV in pregnancyshould be informed that interventions (such as ARVs, C/S, and avoidance ofbreastfeeding) can reduce the risk of MTCT from 30 to less than 2%.11,12 In addition,there should also be a clear referral pathway for women who are HIV infected and theyshould be managed by a team comprising a counsellor, HIV physician, an obstetrician, amidwife, a paediatrician and support groups.

Specific considerations during antenatal care

Other sexually transmitted infections

All pregnant women should be screened for genital infections, in view of the fact thatincreased HIV genital tract replication may occur due to other local infections. Viralload in cervical vaginal secretions has been shown to correlate with MTCT.13 Usually,genital tract viral load mirrors the plasma load14 but discordance may occur15, notablyin the presence of genital infections or ulceration.16 This therefore warrants testing forChlamydia trachomatis, Neisseria gonorrhoea and bacterial vaginosis. Furthermore,screening for hepatitis B and C should also be performed.

PRESCRIBING ANTIRETROVIRAL THERAPY IN PREGNANCY

Effect of antiretroviral therapy on pregnancy outcome

It has been suggested that ARV therapy may increase the adverse outcomes ofpregnancy. The rate of preterm labour has been reported to be increased with the useof highly active antiretroviral therapy (HAART).7 Data from the USA have not shownan increase in the rate of preterm birth with the use of dual nucleoside and


a protease-inhibitor regimen10, but data from a European cohort study have shownhigher rates of preterm birth as the number of ARV agents used has increased.8

The effect of first trimester exposure to ARVs and folate antagonists used forprophylaxis against Pneumocystitis carinii pneumonia (PCP) should alert clinicians to theneed to offer detailed fetal anomaly ultrasound scans, although there is no robustevidence that most ARVs are teratogenic or that preconceptual folic acid reducesneural tube defects in those HIV-infected women taking folate antagonists such as co-trimoxazole for the prevention of PCP.

There is preliminary evidence that pre-eclampsia is more common amongst thosetreated with ARV, compared with controls.17 The toxic effects of ARVs, however,overlap the clinical signs of severe pre-eclampsia, e.g. lactic acidosis is a recognisedcomplication of certain ARVs and may mimic signs of pre-eclampsia. The ARV drugsstavudine and didanosine have been suspected of causing this problem, and pregnantwomen are stated to be particularly susceptible to lactic acidosis.18 Thus, if thiscomplication is suspected, liver function tests and blood lactate should be monitored.The presenting symptoms of lactic acidosis are often non-specific but may includegastrointestinal disturbance, fatigue, fever and breathlessness.17,18

HAART has been shown to be very effective in keeping viral loads at low levels and indramatically improving the health of HIV-infected people, in spite of serious side effects.Pregnancy should not be regarded as a barrier to their use. ARV therapy is provided fortwo main reasons during pregnancy: first, for prevention of MTCT (therapy usuallydiscontinued at, or soon after, delivery), and second, for treatment of maternal health(treatment continued indefinitely).

Prevention of MTCT

Perinatal transmission is the most common cause of HIV infection in infants andchildren worldwide.1 In the absence of interventions, the frequency of MTCT varieswidely, with rates ranging from 15 to 40%. The wide range of these rates is possibly dueto differences in patterns of breastfeeding, maternal viral load and obstetric practices.Most transmissions occur during the last 2 weeks of pregnancy, in labour, and duringdelivery. Although the actual mechanisms of vertical transmission have not beenidentified, possible reasons include microtransfusions during Braxton Hicks contrac-tions, labour contractions, ascent of the virus through the vagina and cervix oncemembranes have ruptured, and absorption of the virus through the infant’s digestivetract during parturition. These possible mechanisms of transmission are supported bystudies demonstrating reduced transmission following elective C/S, and increasedinfection with prolonged duration of ruptured membranes.19,20 Although there is verylittle evidence of the risks of antenatal procedures such as amniocentesis,cordocentesis and chorionic villus sampling, most clinicians advise that prophylacticARV therapy may be necessary if these procedures are going to be performed.

For women who are HIV-infected but not taking HAART during pregnancy, and forwomen with a detectable viral load, scheduled planned caesarean delivery is of benefitin reducing MTCT.6 A meta-analysis of 15 prospective cohort studies, which included8533 mother–child pairs, found a 50% reduction in transmission rates in women whounderwent a scheduled C/S before the onset of labour or rupture of membranes.20

In women with a viral load undetectable by current laboratory techniques, the benefitof C/S is uncertain.21,22 Delivery by C/S is associated with anaesthetic, intraoperativeand post-operative complications. Reports on morbidity and mortality related to C/S in


HIV-infected women are not consistent. Some studies indicate that sepsis rates areincreased in HIV-infected women in comparison with those who are uninfected, and thecomplication rates are related to the level of immunocompromise.23,12 In poorlyresourced countries the picture may be worse. The Saving Mothers Report3 shows thatthe commonest cause of maternal deaths in South Africa between 1999 and 2001 wasnon-pregnancy-related sepsis; the great majority of the women were HIV-infected and aconsiderable proportion of them had a C/S. However, other studies have found nodifferences in post-C/S complications between HIV-infected and non-infected women.In the European Randomised Mode of Delivery Trial, elective C/S was not associatedwith increased morbidity or mortality compared with vaginal delivery.12

Women who opt for vaginal delivery should accept obstetric practices minimisingMTCT. These practices include avoiding fetal scalp electrodes, fetal blood sampling, theuse of the ventouse in the second stage of labour, episiotomies, and most importantly,keeping the fetal membranes intact for as long as possible in the first stage of labour.

Maternal markers of MTCT (Table 1)

The factor which best predicts the likelihood of infection in the neonate is maternalviral load.21,22 It is well established that, in the majority of women, a high plasma viralload and an associated low antenatal CD4 T-lymphocyte count mean an increased riskof MTCT.21 Two large studies demonstrated that perinatal transmission wassignificantly associated with maternal viral load.21,22 These studies also showed thatno transmission occurred where plasma load was !100011 and !500 copies/ml.22

Current plasma viral load assays have lower limits of detection than those used in theabove studies21,22, and a meta-analysis of seven prospective studies demonstrated44 cases of perinatal transmission among 1202 women with viral loads !1000 copies/ml at, or near the time of, delivery.22 Thus, the highest rate of transmission is found inthose women with HIV plasma viral loads O100 000 copies/ml. Conversely,transmission rates are low when viral loads are undetectable, but there is insufficientevidence for a viral load threshold below which transmission never occurs. However,the more effective a drug regimen, the greater the likelihood it will preventtransmission (Table 1).

Antiretroviral regimens to prevent MTCT (Table 2)

There is now good evidence, substantiated by the AIDS Clinical Trials Groups (ACTG)protocol 076, that zidovudine given as monotherapy, administered 5 times a day andinitiated between 14 and 34 weeks of pregnancy, intravenously during delivery, and toinfants for 6 weeks, reduces the risk of vertical transmission of HIV in non-breastfeeding populations by two-thirds, from 25 to 7.6%.19 These findings have beensupported by a number of observational studies, and zidovudine monotherapy is oneoption currently used to prevent perinatal transmission in HIV-infected women whoare not on ARV therapy for their own health. Maximum benefit in respect to this optionis gained by recommending elective C/S as the mode of delivery and exclusively formulafeeding.19 Viral resistance, like any other course of monotherapy, can occur withzidovudine if this antiretroviral does not suppress viral loads to undetectable levels, mayallow the emergence of a resistant virus compromising the use of ARV therapy in thefuture (Table 2).

An alternative option is a short-term antiretroviral therapy (START) regimen, wherehighly active antiretroviral drugs are taken for the duration of the pregnancy and

Table 1. Use of maternal markers for PMTCT and delaying maternal disease progression.

HIV-disease stage

(CD4 count) !200 200–500 O500

Predicted viral load High Moderate to low Low

Risk of maternal

AIDS/death

High Low Low

Risk of MTCT High Moderate Low

Recommended PMTCT

interventions for

non-breastfeeding

populations

HAART HAART/short-course

MTCT prophylaxis dual

or triple ARV regimen

Short-course MTCT

prophylaxis dual or triple

ARV regimen

– Lack of scientific

evidence

– Balance PMTCT benefits

against maternal side

effects

Recommended PMTCT

ART for breastfeeding

populations

HAART HAART/short-course

MTCT prophylaxis dual

or triple ARV regimen

Short-course MTCT

prophylaxis dual or triple

ARV regimen and

counselling on safe infant

feeding practices

– Lack of scientific

evidence

– Balance PMTCT benefits

against maternal side

effects

AIDS, autoimmune deficiency syndrome; MTCT, mother to child transmission; ARV, antiretroviral;

PMTCT, prevention of mother to child transmission; HAART, highly active antiretroviral therapy


discontinued shortly after delivery, provided the maternal viral load is undetectable.23 Itis recommended that zidovudine be included in any combination ARV because of itsdemonstrated efficacy in preventing MTCT and its relative safety. In addition,zidovudine’s passage through the placenta is excellent, while that of other ARVs isvariable. The passage through the placenta allows inhibitory levels of the drug in thefetus, ensuring pre-exposure prophylaxis.

The majority of HIVoccurs in resource-poor countries, thus complex and prolongedregimens are costly and logistically difficult to implement. Several studies have thereforereported on short-course regimens in order to determine if affordable regimens couldbe utilised. The first report of such a successful course, from Thailand, showed that therate of perinatal transmission of the participants in the study, given a twice-daily dose ofzidovudine beginning at 36 weeks, and during labour, was reduced by 50%.24

Slightly lower efficacy rates were observed in breastfeeding populations in tworandomised trials, one in Cote d’Ivoire (37% reduction in transmission at 12 weeks’neonatal age) and the other in Cote d’Ivoire/Burkina Faso (38% reduction by 6 monthsof age).25,26 Supporting evidence of the efficacy of abbreviated regimens of ARVs forprevention of HIV-1 from Wade et al10 indicates that rates of transmission varieddepending on when zidovudine prophylaxis began. Respective rates of transmission forthe prenatal and intrapartum periods and the first 48 hours of neonatal life were 6, 10and 9.3%. In the absence of zidovudine prophylaxis, the transmission rates were 26%.

Nevirapine has also been used as a short-course therapy. Its low price, rapid onset ofaction, and the rapid fall in viral load that occurs after its use, make it attractive for

Table 2. ART options for prevention of mother-to-child transmission of HIV.

Antepartum Intrapartum Post-partum mother Post-partum infant Perinatal transmission

US (PACTG 076)19 Starting at 14–34 weeks ZDV intravenous

infusion

No ARV Formula feeding 18 months

ZDV only ZDV 100 mg 5!/day ZDV 2 mg/kg qid!6 weeks 7.6% (68% efficacy)

Thailand (CDC)38 Starting at 36 weeks ZDV 300 mg q

3 hours

No ARV Formula feeding 6 months

ZDV only ZDV 300 mg bid No ARV 9.4% (50% efficacy)

Ivory Coast (CDC)26 Starting at 36 weeks ZDV 300 mg q

3 hours

No ARV Breast feeding 3 months

ZDV only ZDV 300 mg bid No ARV 16.5% (37% efficacy)

24 months

22.5% (26% efficacy)

South Africa, Uganda,

Tanzania (PETRA)29Starting at 36 weeks ZDV 300 mg q

3 hours plus 3TC

150 mg q 12 hours

ZDV 300 mg bidC3TC

150 mg bid!7 days

Breast feeding 6 weeks

ZDV/3TC ZDV 300 mg bid plus

3TC 150 mg bid

ZDV 4 mg/kg bid plus 3TC

2 mg/kg bid!7 days

5.7% (63% efficacy)

18 months

14.9%

No ARV ZDV 300 mg q

3 hours plus 3TC

150 mg q 12 hours

ZDV 300 mg bidC3TC

150 mg bid!7 days

Breast feeding 6 weeks

ZDV 4 mg/kg bid plus 3TC

2 mg/kg bid!7 days

8.9% (42% efficacy)

18 months

18.1%

Uganda (HIVNET 012)27 No ARV NVP 200 mg!1 Breast feeding 14–16 weeks

NVP vs ZDV NVP 2 mg/kg!1 at

48–72 hours


18 months


No ARV ZDV 300 mg q

3 hours

Breast feeding 14–16 weeks

ZDV 4 mg/kg bid!7 days 25.1%

18 months

25.8%

US/Europe/Brazil/Baha-

mas (PACTG 316)39Non-study ARV (23%

ZDV alone, 36% combo

without PI, 41% combo

with PI)

Standard intrave-

nous ZDV

Non-study ARV Formula feeding 6 months

NVP vs placebo NVP 200 mg!1 Standard ZDV (with or

without other ARV)!6

weeks

1.4% (with NVP)

(continued on next page)

Man

agemen

tofH

IVin

fection

inpregn

ancy

175

Table 2 (continued)

Antepartum Intrapartum Post-partum mother Post-partum infant Perinatal transmission

Women and infants on

standard ARV

NVP 2 mg/kg!1

at 48–72 hours

1.6% (without NVP)

South Africa (SAINT) 28 No ARV NVP 200 mg!1 NVP 200 mg!1 at

24–48 hours

Breast feeding (42%) 8 weeks

NVP vs ZDV/3TC NVP 6 mg!1 at

24–48 hours (O2 kg)

12.3%

No ARV ZDV 600 mg then

300 mg q 3 hours

plus 3TC 150 mg q

12 hours

ZDV 300 mg bid plus

3TC 150 mg bid!7

days

ZDV 12 mg bid plus 3TC

6 mg bid!7 days (O2 kg)

8 weeks

9.3%

Thailand/PHPT

(Harvard)30Starting at 28 weeks ZDV 300 mg q

3 hours

No ARV Formula feeding 6 weeks

ZDV with/without NVP ZDV 300 mg bid ZDV 2 mg/kg qid!7 days 6.3%

ZDV 300 mg bid ZDV 300 mg q

3 hours plus NVP

200 mg!1

No ARV ZDV 2 mg/kg qid!7 days 6 weeks

2.8%

ZDV 300 mg bid ZDV 300 mg q

3 hours plus NVP

200 mg!1

No ARV ZDV 2 mg/kg qid!7 days

plus NVP 6 mg!1 at

48–72 hours

6 weeks

2%

US, United States; PACTG, pediatric AIDS clinical trails group; ZDV, zidovudine; NVP, nevirapine; HIVNET 012, HIVNET 012 trial27; ARV, antiretroviral; PETRA, The

Perinatal Transmission Study

176

J.M

oodley

and

D.

Moodley


prophylaxis, particularly in poor countries. Two studies from Africa, HIVNET 012, andthe South African Intrapartum Nevirapine Trial (SAINT) have reported significantreductions with the use of short doses of nevirapine to mother and baby.27,28 Inaddition, the Perinatal Transmission Trial (PETRA) reported on a short course ofzidovudine and lamivudine in a predominantly breastfeeding population. This trialenrolled 1823 women into four arms: (1) zidovudine–lamivudine given at 36 weeks andcontinued through labour and for 1 week after delivery; (2) zidovudine–lamivudinegiven intrapartum and 1 week post-delivery; (3) zidovudine–lamivudine givenintrapartum only; and (4) placebo. There were significant reductions for HIV-1transmission when compared to placebo for arms 1 and 2 but not 3.29

More recently, an observational study from Thailand showed that zidovudine, fromthe 28th week of pregnancy, plus ‘a booster dose’ of nevirapine given to the mother inlabour and to the baby as soon as possible after birth, was much more effective than ashort course of zidovudine alone started at 28 weeks. The authors conclude that asingle dose of nevirapine given to the mother at delivery and a dose to the baby as soonas possible after birth, added to oral zidovudine initiated at 28 weeks’ gestation, resultsin very low transmission rates (1.1%), with minimal medical and financial burdens.These low rates of transmission are very similar to those achieved with very complex,expensive and potentially toxic multi-drug maternal regimens.30 It is therefore notsurprising that, in recently updated guidelines, the World Health Organization (WHO)recommends this regimen for the prevention of MTCT of HIV-1 for pregnant womenwho do not require ARVs for their own health.31

Monotherapy and viral resistance

There are concerns regarding the use of monotherapy, and of the combination of drugsfor prevention of MTCT only. Fewer transmissions are likely to occur withcombinations, and viral resistance may be lower, but these factors must be balancedagainst the exposure of the mother and fetus to a number of potentially toxic drugs.There have also been recent concerns regarding the development of viral resistancewith the use of single-dose nevirapine (NVP) in resource-poor countries. Whilst single-dose NVP has been successful in limiting transmission rates of HIV, as proven by theHIV-NET 012 study27, the emergence of resistant mutations after a single dose of NVP,owing to its long half-life, is worrying. In a sub-study from HIV-NET 012, it was reportedthat in a subset of 140 women with subtypes A and D, the rate of NVP resistanceincreased from 7 days to 8 weeks. The mutations 7181C and K103N were found, andthe study confirmed that there is a correlation between subtype and the selection anddecay of NVP-related resistance.32

In a study by Jourdain et al33, resistance mutations to nucleoside reversetranscriptase inhibitors were detected 10 days after delivery in 5% of mothers, andamong the women who received intrapartum nevirapine, 32% had at least one mutationthat conferred resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs).This group of researchers also addressed the question whether ARVs given to preventMTCT might compromise the efficacy of ARV drugs subsequently administered for HIV-1 treatment in the mother. Their findings suggest that those who receive single-dosenevirapine alone, or combination regimens for the prevention of MTCT, and in whommutant variants develop, may be less likely than women who do not receive intrapartumnevirapine, or have resistance mutations, to have maximal viral suppression whenNNRTI-based treatment is initiated soon after delivery.33 The actual significance ofthese data still requires clarification, as ARVs were initiated within 6 months of delivery,


and it has been reported that HIV viral mutant strains fade with time.32 Delay ininitiating treatment, therefore, may not result in similar findings. Given that access totreatment remains scarce in resource-poor settings, these studies do not so muchcaution against the use of NVP treatment, as stress the urgent need to explore moreviable options that prevent transmission but do not compromise treatment duringsubsequent pregnancies, or treatment for children.

WOMEN TREATED WITH ARV THERAPY FOR THEIR OWN HEALTH

These women are likely to have advanced disease with high viral loads (O10 000–20 000 copies/ml, and/or decreasing, or low CD4 counts !350!106/l). Treatmentwith ARV therapy should be avoided in the first trimester, but treatment whichsuppresses plasma viraemia is targeted, to improve both maternal morbidity andmortality and to prevent perinatal transmission.

Studies have found that membranes ruptured for more than 4 hours wereassociated with double the risk of HIV transmission.34,35 The relevance of thesestudies for women with undetectable viral loads is uncertain.

Preventing progression of HIV disease in pregnancy in resource-limitedcountries

Preventing the progression of HIV-1 disease using low-cost immunomodulatinginterventions in poorly resourced countries has been proposed. Recently, multivitaminsupplements (vitamins A, B, C and E) have been shown to delay the progression of HIVdisease, in a randomised trial which enrolled 1078 pregnant women with HIV in adouble-blind, placebo-controlled trial in Dar Es Salaam, Tanzania.36 The authorsindicate that multivitamin supplements provide an effective, low-cost method ofdelaying the progression of HIV disease and thereby delaying the initiation of ARVtherapy in HIV-infected women.36

Post-partum management

It is estimated that breastfeeding increases the overall MTCT rate by 14% for womeninfected with HIV before birth and by 30% in mothers infected post-natally.37

Breastfeeding in industrialised countries is therefore avoided. In resource-poorsettings, it may be difficult to balance the need for babies to receive breast milk with theneed to avoid breast milk transmission of HIV. Advice may need to change as newinformation and options become available. In poor countries, therefore, adviceregarding breastfeeding should remain that breast milk will always be the best, cheapest,and only food and drink needed by most young babies.

Management of the neonate

Early diagnosis of positive infants, preferably at 6 weeks after they are born, and 4weeks after any breastfeeding ends, is important for the families, so that clinicalresources can be used where they are most needed.

Maternal antibodies crossing the placenta are detectable in most neonates ofmothers who are HIV positive. For this reason, polymerase chain reaction is used for


the diagnosis of infant infections at birth, 3 weeks, 6 weeks and 6 months. The definitivetest is the HIV antibody test—a negative result at 18 months of age confirms that thechild is uninfected.

SOME ASPECTS OF THE USE OF ANTIRETROVIRALDRUGS IN PREGNANCY

Monitoring virological and immunological status

The cornerstones of monitoring are viral loads and CD4 counts. Treatment in the non-pregnant is generally indicated when the CD4 counts falls to !200 mm3 or whenplasma ribonucleic acid (RNA) levels are O55 000 copies/ml. Controversy existswhether the treatment should be initiated at CD4 counts !350 mm3. These guidelinesare also recommended for pregnant women. Implementation of these recommen-dations should be individualised and is dependent on factors such as the woman’swillingness and readiness to commit to take lifelong therapy; the benefits and risks inasymptomatic individuals; and of adherence to the treatment. Adherence to therapy isthe sine qua non of successful therapy. Haphazard or intermittent therapy complianceleads to drug resistance.

Once therapy is initiated, success is based on monitoring viral loads. This shouldoccur on a regular basis. The speed at which viral loads fall varies with the baseline level,but a fall in levels should be seen within a month and undetectable levels are reached by6 months with a highly active antiviral drug regimen. If this goal is not achieved, or thereis a re-emergence of detectable levels of virus, then failure of the drug therapy, orresistance to the virus has occurred. A decision as to a new therapy regimen must beconsidered following resistance testing.

Drug therapy

There are a number of HAART regimens used, and they are classified into nucleosidereverse transcriptase inhibitors, protease inhibitors and NNRTIs. A large number ofchoices exist within these categories. In general terms, dual nucleoside reversetranscriptase inhibitors and a protease inhibitor or a NNRTI have been recommended.However, certain medications should not be used in combination; zidovudine andstavudine have overlapping toxicities; didanosine and stavudine have recently beenlinked to several cases of mitochondrial toxicity in pregnancy; and didanosine andzalcitabine in combination have diminished efficacy.18

In the mother, clinical disorders associated with mitochondrial toxicity includeneuropathy, myopathy, cardiomyopathy, pancreatitis, hepatic steatosis and lacticacidosis. Although these disorders are rare, clinicians must be aware of theseserious morbidities in pregnant HIV-infected women receiving nucleoside reversetranscriptase inhibitors, and investigate all new symptoms thoroughly. Alternatively,liver enzyme tests should be performed routinely in the last trimester of pregnancy.

Amongst the NNRTIs, efavirenz should not be used because of reported teratogeniceffects in monkey models. Protease inhibitors have been linked to abnormal glucosemetabolism, nephrolithiasis and hyperbilirubinaemia. Despite concerns about toxicity,pregnant women should be provided with ARV therapy, as the benefits to baby andmother outweigh any harm. Nonetheless, all pregnant women on ARVs should have


regular monitoring of liver function tests and blood counts to detect toxicity as early aspossible.

CONCLUSION

The management of HIV-infected women in pregnancy should be undertaken by amultidisciplinary team consisting of an obstetrician, neonatologist, HIV expert andsupport staff. Women who need ARV treatment for their own health should receive it,to improve their health and decrease HIV transmission to their babies. Asymptomaticwomen, or those who do not require ARV therapy for their own health, should receivethe most efficacious regimen to reduce MTCT to a minimum.

SUMMARY

The management of HIV in pregnancy focuses on caring for those already infected andpreventing the transmission of HIV to the baby. A holistic approach to these goalsshould involve a multidisciplinary team consisting of an obstetrician, neonatologist, HIVphysician and support team.

ARV therapeutic regimens are complex and potentially harmful and require strictadherence to therapy if the development of viral mutant strains is to be avoided. ARVregimens are given either to prevent MTCTor to improve maternal health. In the latterinstance, indications for ARV therapy follow those for the non-pregnant adult.

Clinicians managing the HIV-infected pregnant woman must update their knowledgecontinuously and be aware of any drug toxicity associated with ARV regimens so thatany new symptom may be investigated aggressively. Monitoring of response to drugs isdone by performing regular estimations of viral loads, as the aim of the ARV regimen isto achieve a state in which the viral load is undetectable.

Prevention of MTCT includes not only the use of ARV as prophylaxis but alsoappropriate obstetric practices such as avoiding episiotomies, keeping the fetalmembranes intact, avoiding the use of the ventouse and advising against breastfeeding,where feasible.

Practice points

† testing for HIV status should be offered to all pregnant women, utilising apractical protocol, without infringing human rights

† pregnant women should have access to all of the same therapies as non-pregnant women, except that (i) efavirenz, (ii) hydroxyurea, and (iii) acombination of stavudine and didanosine, should not be issued

† all pregnant women should receive ARV, either for their own health, or for theprevention of MTCT of HIV, using appropriate regimens

† C/S should be recommended to all women with viral loads O1000 copies/ml

*

*

Research agenda

† establish the appropriate approach for interventions in HIV-infected womenwho do not require treatment for their own health

† role of elective C/S for HIV-infected pregnant women with good viralsuppression

† research into the pharmacokinetics of ARV drugs in pregnancy† to investigate further the issues of drug resistance and its effects on the use of

ARV therapy in the future† issues surrounding breastfeeding in resource-poor countries, which bear the

burden of disease† to establish cheap, but technically easy methods to diagnose HIV infections in

babies, as soon as possible following birth† to establish potential short- and long-term complications of ARV drugs in

pregnancy† to evaluate the effect on MTCTand maternal health of planned C/S for women

who are taking HAART, or who have very low viral loads


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REVIEW ARTICLE

Obesity and obstetric anaesthesia

K. Saravanakumar,1 S. G. Rao1 and G. M. Cooper2

1 Specialist Registrar, 2 Consultant Anaesthetist, Department of Anaesthetics, Birmingham Women’s Hospital,

Metchley Park Road, Edgbaston, Birmingham B15 2TG, UK

Summary

The prevalence of obesity continues to increase despite preventive strategies. Obese parturients are

at increased risk of having either concurrent medical problems or superimposed antenatal diseases

such as pre-eclampsia and gestational diabetes. Moreover, they have a tendency to labour abnor-

mally contributing to increased instrumental delivery and Caesarean section. Obesity is a risk factor

for anaesthesia related maternal mortality. Morbidly obese women must be considered as high-risk

and deserve an anaesthetic consultation during their antenatal care. The significant difficulty in

administering epidural analgesia should not preclude their use in labour. A more liberalised use of

regional techniques may be a means to further reduce anaesthesia-related maternal mortality in the

obese population. The mother’s life should not be jeopardised to save a compromised fetus.

Prophylactic placement of an epidural catheter when not contraindicated in labouring morbidly

obese women would potentially decrease anaesthetic and perinatal complications associated with

attempts at emergency provision of regional or general anaesthesia. Early mobilisation, aggressive

chest physiotherapy and adequate pain control are essential components of effective postoperative

care.

........................................................................................................

Correspondence to: K. Saravanakumar


Accepted: 18 September 2005

Obesity is a global health problem whose prevalence is

increasing. The World Health Organization (WHO)

characterised obesity as a pandemic issue whose preval-

ence is higher in women than in men [1]. Consequently,

the anaesthetist is increasingly confronted with the

problems of anaesthetising obese patients, and even

more so the obstetric anaesthetist. Adding to the

spectrum of medical and surgical pathologies, obesity is

also associated with an increased incidence of antenatal

disorders. A thorough understanding of physiology,

pathophysiology, associated conditions, their complica-

tions and the implications for analgesia and anaesthesia

should place the anaesthetist in a better position to care

for these patients.

Definition

Obesity is often defined simply as a condition of abnormal

or excessive fat accumulation in adipose tissue to the

extent that health may be impaired [2]. The underlying

process is positive energy balance and weight gain.

Obesity is often expressed with reference to body mass

index (BMI).

Body mass index ¼ weight ðin kgÞ=height2 ðin mÞ:

Though BMI is a useful measure of prevalence and

associated health risks of obesity, it does not account for

the wide variation in the distribution of fat and may not

correspond to the same degree of fatness in different

individuals. WHO classifies obesity primarily based on the

association between BMI and mortality (Table 1) [1].

Epidemiology

The prevalence of obesity is increasing at an alarming rate

in both developed and developing countries. In pregnant

women in the United States at the end of the last century,

the prevalence ranged from 18.5% to 38.3% according to

the cohort studied and the cut-off point used to define

overweight [3]. A Brazilian study at a similar time

reported the prevalence of obesity in pregnancy to be

5.5% [4]. The Health Survey of England published in

Anaesthesia, 2006, 61, pages 36–48 doi:10.1111/j.1365-2044.2005.04433.x.....................................................................................................................................................................................................................

� 2006 The Authors

36 Journal compilation � 2006 Blackwell Publishing Ltd

2002 gives us data about the prevalence of obesity in

England. Females in the reproductive age group (16–

44 years) have shown a dramatic increase in BMI (Fig. 1).

The percentage of women with BMI above 30 increased

from 12% in 1993 to 18.3% in 2002. Even more alarming

is that the percentage of morbidly obese women has

doubled in the last decade [5]. This illustrates the problem

we are facing.

Physiological changes in obesity and pregnancy

Physiological changes associated with pregnancy are

significant enough to have serious anaesthetic implica-

tions. When these are compounded by obesity, the

anaesthetist may have to deal with a patient with seriously

limited physiological reserve. Often, obesity has associ-

ated co-morbidities and pathological changes in different

organ systems.

Respiratory system

All aspects of oxygenation and ventilation are affected

in pregnancy. The physical, mechanical and hormonal

changes influence the respiratory system. Table 2 sum-

marises these changes in pregnancy, obesity and the

combined effect of pregnancy with obesity [6–10].

Fortunately, not all changes associated with pregnancy

in obese women are detrimental. In fact, there may be

some improvement in respiratory function in an obese

patient who becomes pregnant; especially the functional

residual capacity, which usually improves [6]. Hormonal

changes, through the relaxing effect of progesterone on

smooth muscle, decreases airway resistance, thus reducing

some of the negative effects of obesity on the respiratory

system [8, 9]. Studies that have shown the respiratory

effects of obesity in pregnancy to be minimal were carried

out in the sitting position, whereas the supine position

may alter the volume, flow and mechanical properties of

breathing.

Obstructive sleep apnoea (OSA) is not uncommon

in obese women who become pregnant. Pregnancy has

some protective effects on sleep apnoea, despite the

hyperaemia of nasal passages. Early in pregnancy, the

increased sensitivity of the respiratory centre decreases

apnoeic episodes and, in the later part of pregnancy,

women tend to sleep on their side, thereby decreasing

the likelihood of airway obstruction. Chronic hyp-

oxia, hypercapnia and pulmonary hypertension increase

Table 1 WHO classification of obesity.

Classification BMI; kg.m)2 Risk of co-morbidities

Normal 18.5–24.9 AverageOverweight ‡25Pre-obese 25–29.9 IncreasedObese class 1 30–34.9 ModerateObese class 2 35–39.9 SevereObese class 3 ‡40 Very severe

WHO, World Health Organization; BMI, Body Mass Index.

0

2

4

6

8

10

12

14

16

18

20

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

Year

% o

f to

tal p

op

ula

tio

n

BM

I >30

0

0.5

1

1.5

2

2.5

BM

I > 4

0

BMI over 30BMI over 40

Figure 1 Prevalence of obesity among females aged 16–44 inEngland as measured by BMI (source: Health survey for England2002).

Table 2 Changes in the respiratory system (changes represent ageneral trend rather than absolute values).

Parameter Pregnancy Obesity Combined

Progesterone level › « ›Sensitivity to CO2 › fl ›Tidal volume › fl ›Respiratory rate › « or › ›Minute volume › fl or « ›Inspiratory capacity › fl ›Inspiratory reserve volume › fl ›Expiratory reserve volume fl flfl flResidual volume fl fl or « ›Functional residual capacity flfl flflfl flflVital capacity « fl flFEV1 « fl or « «FEV1 ⁄ VC « « «Total lung capacity fl flfl flCompliance « flfl flWork of breathing › ›› ›Resistance fl › flV ⁄ Q mismatch › › ››DLco › or « « «PaO2 fl flfl flPaCO2 fl › fl

› ¼ increase; fl ¼ decrease; « ¼ No change (multiple arrows repre-sent the degree of intensity).CO2 ¼ carbon dioxide; FEV1 ¼ forced expiratory volume in 1 s; VC ¼vital capacity; V ⁄ Q ¼ ratio of ventilation to perfusion; DLco ¼ diffu-sion capacity of lung for carbon monoxide; PaO2 ¼ Partial pressure ofoxygen; PaCO2 ¼ partial pressure of carbon dioxide.

Anaesthesia, 2006, 61, pages 36–48 K. Saravanakumar et al. Æ Obesity and obstetric anaesthesia......................................................................................................................................................................................................................


Journal compilation � 2006 Blackwell Publishing Ltd 37

maternal morbidity and mortality significantly [11, 12].

Caesarean section, despite being lower abdominal sur-

gery, potentially leads to reduced lung volume and

capacities compared to non-obese patients [13].

Cardiovascular system

Pregnancy is associated with wide-ranging cardiovascular

changes in line with increased oxygen demand. Obesity

induced pathological changes have profound effects on

cardiac, endothelial and vascular function. Unlike the

respiratory system, where pregnancy offers some favour-

able effects in obese patients, the cardiovascular system is

further stressed. The endocrinological, inflammatory and

microvascular changes associated with obesity remain and

are further augmented in pregnancy [14–16]. Table 3

summarises the changes in normal pregnancy, obese

patients and obese pregnant women [14–20].

The extent of cardiovascular pathological changes

secondary to obesity is dependent on the duration of

obesity and its severity [18]. Any extra amount of fat

deposited in the body demands its share of cardiac output.

Every 100 g of fat deposited increases the cardiac output

by 30–50 ml.min)1. This is also accompanied by an

increase in blood volume. Volume load initially brings

about left ventricular hypertrophy and then subsequently

the myocardium starts to dilate against the increased

pressure overload. The pressure overload is secondary to

increased sympathetic activity due to the potentiating

effects of hormones such as leptin, insulin and some

inflammatory mediators. The heart rate increases in line

with elevated cardiac output, thereby decreasing the

diastolic interval and thus the time for myocardial

perfusion. Impaired myocardial diastolic relaxation leads

to diastolic dysfunction. If fat deposition occurs in

myocardial tissue, then conduction and contractility can

be seriously affected [18, 19]. Hence, it is not uncommon

to see systolic, diastolic or both systolic and diastolic

dysfunction of the left ventricle. Right ventricular failure

can be present in patients with pulmonary hypertension

and OSA. Congestive heart failure is a consequence in the

presence of any additional stress [9, 10, 16, 18, 19].

Insulin resistance and dyslipidaemias affect the vascular

tree and increased inflammatory mediators such as

C-reactive protein, IL-6, and TNF-a affect endothelial

function. This endothelial dysfunction in pregnant

women may predispose to the development of preg-

nancy-induced hypertension [15, 16, 19, 21]. The

well-known effect of an enlarged uterus compressing

abdominal major vessels and causing supine hypotension

syndrome (SHS) can also be seen in obese patients. This

can be greatly exacerbated in obese parturients where a

large panniculus adds to the uterine compression. The

problem may extend postoperatively if the panniculus is

large enough to cause compression of the vessels by itself.

Tseuda et al. reported two cases of sudden death on

assuming the supine position in morbidly obese patients,

which they attributed to circulatory changes brought

about by changes in their position [22]. Drenick & Fisler

also reported cases of postoperative cardiac arrest in obese

surgical patients. There was no pathology found at

autopsy to explain the cardiac arrest [23].

Gastrointestinal changes

Both anatomical and hormonal changes increase the

incidence and severity of gastric reflux in pregnant women.

Hiatus hernia is more common in obese patients and

obesity itself increases the risk of aspiration under anaes-

thesia. When pregnancy is associated with obesity, the

likelihood of regurgitation and aspiration substantially

increases. Roberts and Shirley studied obese and non-obese

pregnant women in labour; the gastric volume in obese

parturients was five times greater than in controls [24].

Endocrine and reproduction

Because obese girls reach critical mass earlier than normal

weight girls, they tend to reach menarche earlier. An

ob protein called leptin is implicated in the mechanism.

Obesity-induced changes in the reproductive system

mean there is a reduced likelihood that these women

will become pregnant [25]. Despite the potential

Table 3 Changes in the cardiovascular system. Table shows thegeneral trend. Extent of variability in each parameter depends onduration, degree of obesity and associated co-morbid states.

Parameter Pregnancy Obesity Combined

Heart rate › ›› ››Stroke volume ›› › ›Cardiac Output ›› ›› ›››Cardiac Index › or « « « or flHaematocrit flfl › flBlood volume ›› › ›Systemic vascularresistance

flfl › « or fl

Mean arterial pressure › ›› ››Supine hypotension Present Present ››Left ventricularmorphology

Hypertrophy Hypertrophyand dilation

Hypertrophyand dilation

Sympathetic activity › ›› ›››Systolic function « « or fl « or flDiastolic function « fl flCentral venous pressure « › ››Pulmonary wedgepressure

« ›› ››

Pulmonaryhypertension

Absent May bepresent

May bepresent

Pre-eclampsia « n ⁄ a ››

› ¼ increase, fl ¼ decrease, « ¼ no change (multiple arrows repre-sent the degree of intensity). n ⁄ a ¼ not applicable.

K. Saravanakumar et al. Æ Obesity and obstetric anaesthesia Anaesthesia, 2006, 61, pages 36–48......................................................................................................................................................................................................................



anatomical difficulties of intercourse, pregnancy is by no

means uncommon. Onset of menopause is earlier by an

average of 4 years [25]. Obese parturients exhibit insulin

resistance [21] and are more prone to develop gestational

diabetes, which may persist even after pregnancy [26].

Perinatal outcomes of obesity

Maternal morbidity

The major maternal complications reported to be asso-

ciated with obesity during pregnancy include hyperten-

sive disease (chronic hypertension and pre-eclampsia),

diabetes mellitus (pregestational and gestational), respir-

atory disorders (asthma and sleep apnoea), thromboem-

bolic disease, Caesarean section and infections (primarily

urinary tract infections, wound infections and endome-

tritis) [27]. Association between obesity and hypertensive

disorders of pregnancy, diabetes, delivery by Caesarean

section (both primary and repeat) are well documented

[28–30]. Although obese parturients are at significant risk

of pre-eclampsia, they do not seem to be at increased risk

of HELLP (Haemolysis, Elevated Liver enzymes, Low

Platelets) syndrome [31]. As discussed before, dyslipidae-

mias, lipid peroxidation, endothelial damage, platelet

aggregation and inflammatory mediators make direct and

indirect contributions towards the pathophysiology of the

hypertensive disorders of pregnancy [21]. Complications

during labour such as intrapartum fetal distress, meconium

aspiration, failure to progress, abnormal presentation,

shoulder dystocia and an increased rate of instrumental

delivery are more common [28, 32, 33]. Moreover, the

success of vaginal birth after Caesarean section has been

shown to decrease stepwise with increasing maternal BMI

[32, 34]. Postoperative endometritis and wound infection

are significantly higher in obese women [33–35] Obesity

is an intrinsic risk factor for both increased operative

blood loss and postpartum haemorrhage [36]. Carter et al.

have demonstrated a significant association between BMI,

eating attitudes and symptoms of anxiety and depression

in the postpartum period that are not present during

pregnancy [37]. Overall, the literature suggests that obese

pregnant women have a 14–25% incidence of pre-

eclampsia, a 6–14% incidence of gestational diabetes and a

30–47% likelihood of Caesarean delivery [27, 28].

Fetal morbidity

Maternal obesity is associated with fetal macrosomia,

increased risk of birth defects and fetal deaths [38–40].

Various studies have revealed an increased risk of a variety

of conditions such as neural tube defects, especially spina

bifida, omphalocoele and heart defects, in particular

ventricular outflow tract defects or multiple anomalies

[39]. Moreover, increasing maternal size represents a

major risk factor for failure of ultrasound to diagnose fetal

anomalies [41]. Chauhan et al. reported a higher inci-

dence of umbilical arterial acidosis (pH < 7.10) among

obese women regardless of whether they had a trial of

labour or repeat Caesarean delivery [29]. The higher

incidence of fetal compromise in morbidly obese women

could be the result of an inability to assess the fetus

adequately because of size, underlying medical compli-

cations such as chronic hypertension, pregestational

diabetes or that traditional intrauterine resuscitative efforts

are inadequate in overweight patients. Obese women face

difficulties with both lactogenesis and initiation of breast-

feeding because of a decreased prolactin response to

suckling [42, 43]. Breast-feeding is protective of child-

hood obesity [44]. The worries about propagation of a

vicious circle are being confirmed by the longitudinal

study of British cohort from 1958 that concludes maternal

weight rather than birth weight as an important risk factor

for childhood obesity and adult BMI [45].

Weight gain and changes

Pregnancy is normally associated with weight gain that

consists of the growing fetus and enlarging maternal-fluid

and soft-tissue compartments including fat. On average, a

3.5 kg weight gain is mostly due to maternal storage of fat

during pregnancy [46]. Ledermann et al. showed that

women who are overweight or obese and gain weight as

recommended during pregnancy appear to have a small

or negligible increase in total body fat [17]. The main

components of weight gain in these heavier women are

fluid and non-fat soft tissues. Community based studies

have also reported that maternal obesity is not associated

with increased weight gain after pregnancy, though they

are generally at risk of gaining more weight [47].


Obesity has been identified as a significant risk factor

for anaesthesia related maternal mortality [48, 49]. The

increased incidence of operative procedures, both elective

and emergency, and the concurrent medical and ante-

natal problems may contribute to the risk. Postopera-

tive complications such as wound infection, deep vein

thrombosis, atelectasis and chest infection are more

prevalent [49–51]. In addition to the associated medical

problems, the anaesthetist is challenged by these patients

with technical difficulties of airway management and

insertion of regional blocks. No anaesthetic technique is

without special hazards in grossly obese patients.

Airway

The incidence of failed tracheal intubation is approxi-

mately 1 in 280 in the obstetric population compared to 1

in 2230 in the general surgical population [52–54]. This




contrasts with an incidence of difficult intubation in an

obese population as high as 15.5% [55]. In his institutional

experience, Dewan [7] reports the incidence as high as

33% in morbidly obese parturients. Interestingly, a 6-year

review of failed intubations in obstetric patients in a UK

region reported 36 cases of failed intubation and the

average BMI of these women was found to be 33 [53]. So

it is evident that difficult or failed tracheal intubation in

obese parturients is very high and optimal assessment and

management of the airway cannot be overemphasised in

this population.

Though there are no bony differences between the

pregnant and non-pregnant population, obese and non-

obese patients, fat deposition in obese and soft tissue

changes during pregnancy do influence the airway.

Operational factors such as poor head positioning, cricoid

pressure [56] and anxiety contribute to the difficulty on

occasion. In addition, pregnancy induced hypertension,

upper respiratory tract infection, stridor and voice

changes may suggest the presence of airway oedema.

Weight gain in excess of 15 kg during pregnancy has

been shown to be associated with an increase in

suboptimal laryngoscopic views [57].

Although not totally reliable, assessment of oropharyn-

geal structures using the Mallampatti classification has

been shown to strongly correlate with the prediction of

difficult intubation in obstetric anaesthesia [58, 59]. Other

features shown to be significant include short neck,

receding mandible and protruding maxillary incisors [58].

The combination of two tests (Mallampatti and thyro-

mental distance), albeit in a small study of 80 obstetric

patients receiving general anaesthesia, has been shown to

be 100% sensitive with 70% positive predictor value [59].

These tests can be done in less than 1 min; hence they

are also useful in an emergency scenario. A previous

uneventful general anaesthetic for either obstetric or non-

obstetric reasons may not be helpful because of weight

gain. However, previous anaesthetic charts inform of

laryngoscopic view. In cases of documented difficult

intubation, further airway imaging (X-ray and compu-

terised tomography) is questionable as the combined

clinical and radiological measurements only improve

predictability of a difficult airway by 0.04% compared

to clinical assessments alone [60]. Anaesthesia for both

emergency and elective scenarios should be planned in

advance. It is appropriate to involve patients in the

decision-making process for safe delivery of the fetus.

Respiratory system

The likelihood of OSA has been alluded to, but it is often

under-diagnosed in women of childbearing age [11].

Normal women in late pregnancy have difficulty with

sleep maintenance and spend less time in the supine

position. It is possible that, inasmuch as complaints of

difficulty in sleeping and daytime fatigue are common,

women suffering from OSA are not identified. Careful

history taking may help diagnose OSA. Prompt diagnosis

by polysomnography and treatment with continuous

positive airway pressure may be beneficial. Pulmonary

hypertension and right heart failure need to be excluded

in parturients with OSA [12, 61]. Measurement of

oxygen saturation by pulse oximetry, both in sitting and

supine positions, may provide evidence of airway closure

during normal tidal volume ventilation, thereby identi-

fying candidates for postoperative oxygen administration.

Pre-operative arterial blood gas examination provides

information regarding the current status of ventilation and

oxygenation. Detailed pulmonary investigations including

chest X-ray should be reserved for those with more severe

respiratory disease. Pre-operative antibiotics and chest

physiotherapy are ideally reserved for patients with

concurrent chest infection.

Cardiovascular system

Cardiovascular co-morbidities such as hypertension,

ischaemic heart disease and heart failure dominate the

clinical picture in the obese population and these can

co-exist in obese parturients. Nearly 40% of the obese

population experience angina without demonstrable

coronary artery disease [62]. Hence, routine electrocar-

diograph recording may be useful. Cardiologists should be

involved early in the care of symptomatic morbidly obese

parturients to investigate and optimise the disease status

wherever appropriate.

Gastrointestinal and endocrine systems

Gastro-oesophageal reflux and diabetes mellitus are the

most commonly seen disorders [28]. Any previous

laboratory investigations such as fasting blood glucose

concentration and liver function tests should be noted. If

there is any abnormality of liver function, HELLP

syndrome should be ruled out.

Though aggressive prophylaxis against acid aspiration is

advocated for all obese mothers undergoing Caesarean

section [24, 63], there is a lack of conclusive evidence for

starvation policies and prophylaxis during labour. Current

evidence suggests avoiding solids and semisolids once a

woman is in active labour or requests analgesia [64].

Sodium citrate and ranitidine remain the most commonly

used drugs for acid aspiration prophylaxis in the UK [65].

Practical considerations

Obese parturients share a battery of technical difficulties

along with their non-pregnant counterparts. Blood

pressure measurement will require an appropriate sized

cuff; otherwise both systolic and diastolic readings will be




overestimated. There is a strong argument in favour of

invasive blood pressure monitoring peri-operatively if

there are difficulties in getting the appropriate size cuff

and positioning of the arm, as commonly used regional

blocks demand frequent monitoring of blood pressure

[66]. Venous access can be difficult and extravasation may

not be immediately apparent. Patients should be warned

about the difficulties and the possible need for central

venous access and arterial cannulation in the peri-

operative period. When regional anaesthesia is contem-

plated, examination of needle insertion sites and spinal

bony landmarks might predict difficulty [67].

Many of the other vital accessories are related to the

physical size of parturients and need to be considered well

in advance of the delivery. The weight bearing capacity of

delivery beds and operating tables should be adequate to

accommodate super-morbidly obese parturients. Suit-

able equipment (trapezes, lifters and hoover matts) and

sufficient numbers of personnel for safe transfer of women

within the hospital must be available. Sufficiently large

blood pressure cuffs should be made available wherever

blood pressure readings might be taken, including clinics,

wards and the delivery suite. Mechanical devices for

thrombo-prophylaxis such as stockings of appropriate size

and sequential compression devices are other requisites for

these patients.

Anaesthetic management

Analgesia for labour

Analgesia during labour is of significant importance for

the positive experience of childbirth for many mothers.

Increased prepregnancy weight is associated with an

increased incidence of fetal macrosomia and labour

abnormalities such as shoulder dystocia. Each of these is

a known risk factor for more painful contractions and

complicated labour. Melzack et al. reported a positive

correlation of BMI with the severity of labour pain

[68]; however, this has been questioned by Ranta et al.

[69]. Although there are various modalities of pain

relief, analgesia using neuroaxial blockade has been

shown to be the most effective [70]. The anticipated

technical difficulties should not preclude the use of

epidural analgesia in obese parturients. Effective pain

relief during labour can improve maternal respiratory

function and attenuate sympathetically mediated cardio-

vascular responses [71, 72]. Available evidence shows

that the rate of Caesarean delivery does not increase

with epidural analgesia during labour [70], though

obesity increases the need for Caesarean section. Hence,

placing a functional epidural catheter is advantageous

should any operative intervention be required. In

addition, epidural analgesia can be extended into the

postoperative period where adequate pain relief can

optimise care.

The challenges for the anaesthetist should not be

underestimated. Technical difficulties include positioning

the patient correctly, identification of the midline,

identification of the epidural space, and dislodgement of

catheters [51, 66, 73]. The initial failure rate for epidural

catheter placement can be very high (42%) [51] and

multiple attempts of catheter placement are common.

Jordan et al. noted 74.4% of massively obese parturients

needed more than a single attempt and 14% needed more

than three attempts for successful epidural placement [50].

The knee–chest position required for siting epidurals in

the lateral position is difficult to obtain in the obese. One

study found that cardiac output decreased more in the

lateral decubitus position with maximal lumbar flexion

compared with the sitting position [74]. Moreover, in the

lateral position, gravity can drag down the pad of fat

obscuring the midline. Another study found the depth of

the epidural space from skin to be greater in patients

where the epidural was inserted in the lateral decubitus

position [75]. Overall, the sitting position is preferable.

Various techniques have been reported to identify the

midline in difficult scenarios. They include using

the prominence of the seventh cervical vertebrae and

the gluteal cleft to identify the midline and using a 26-G

8.5 cm spinal needle to probe subcutaneous tissue and

delineate the position of a posterior process above and

below a lumbar interspace [76]. Where it is difficult to

identify the space, parturients can assist verbally in

directing needle to the midline [66] and tilting the table

towards the anaesthetist can encourage opening of

interspinous spaces by forcing the parturient to bend

forwards. The difficulty in location of the midline

increases the likelihood of lateral projection of the needle

apparently increasing the depth of the space and mal-

positioning of the catheter [77]. The paramedian

approach to identify the epidural space is sometimes

popular in difficult cases. With the back pad of fat and

pregnancy induced softening of the tissues, there is a

higher incidence of false positives in identifying the

epidural space. It has been argued that the loss of

resistance technique is more reliable than the techniques

that are dependent on subatmospheric pressure in the

obese. The depth of epidural space at the L3–4 interface

positively correlates with BMI [75, 78].

Some of the difficulties can be circumvented by using

ultrasound to identify the epidural space and calculate its

depth [79, 80]. Ultrasound studies have confirmed the

significant changes in spinal anatomy in pregnancy and

found the skin–epidural distance to be greater in preg-

nancy. They have also revealed that the safety zone

between transfixation of the ligamentum flavum and




inadvertent dural puncture is smaller [81]. Although the

epidural space may be deeper in overweight people, the

majority of studies report that only a few have an epidural

space deeper than 8 cm [75, 78]. Hence it seems

appropriate to use a standard needle to identify the

epidural space on the first attempt. A successfully placed

catheter can easily be dislodged by the drag of the back

pad of fat when parturients move around in bed. Wasson

postulates that a 6 cm lateral movement of skin site

relative to the spine would drag 2 cm of catheter out of

the epidural space [82]. Moreover, the catheter is

subjected to a drag when the flexed back is relaxed

immediately after a successful placement. These should be

taken into consideration when deciding the length of

catheter to be left in the space for a successful working

epidural. The other common reasons for a successfully

placed catheter to fail include inadequate dose of local

anaesthetic, poor drug spread, misplacement of the

catheter, septae within the epidural space and fetal

malpositioning leading to more stimulation. With

increased operative intervention in obese parturients, it

is prudent to make sure that the epidural is working well

and, if not, to replace the catheter at the earliest possible

opportunity. Hodgkinson et al. have shown that BMI and

weight are the major determinants of cephalad spread of

epidural anaesthesia and that in obese patients the sitting

position reduced cephalad spread [83, 84]. However,

Milligan et al. showed no difference in the spread of

epidural analgesia between obese and non-obese patients

requesting labour analgesia, either in the sitting or in the

lateral position [85].

Entonox can be a useful adjunct. Other forms of

inhalational analgesia involving isoflurane and desflurane

provide better analgesia when compared to nitrous oxide

alone but cause more sedation and amnesia. Whereas

intramuscular opioid injections may be unreliable, patient

controlled intravenous analgesia has been used success-

fully in obese patients. However, opioids in labour have

been associated with maternal and fetal side-effects [86].

All these methods potentially cause maternal drowsiness

and lead to airway obstruction, thus inherently carrying a

risk to the obese parturients.

Anaesthesia for Caesarean section

Obesity and Caesarean section have been identified as

independent risk factors for maternal morbidity and

mortality [28]. In Why Mothers Die 2000–02, 35% of all

the women who died were obese, 50% more than in the

general population [49]. Analysis of direct maternal deaths

due to anaesthesia reported in the confidential enquiries

from 1979 to 2002 reveals the dominance of deaths under

general compared to regional anaesthesia (Table 4 [49,

87–93]). Hawkins, in her analysis of maternal deaths in

the United States, also reported that the absolute number

of deaths due to complications of general anaesthesia,

although small, is not decreasing over time [94] (Fig. 2).

Regional anaesthesia is a safer option than general

anaesthesia for delivery of the fetus [49, 94]. The

principles in the anaesthetic management of these patients

include

• regional anaesthesia unless contraindicated;

• care provided by experienced medical personnel (both

anaesthetist and obstetrician);

• anticipation of problems and effective preparation in

terms of equipment, monitoring and personnel;

• general anaesthesia, if required should be delivered

with tracheal intubation and controlled ventilation;

• postoperative care that includes close monitoring, early

mobilisation, and physiotherapy; a high dependency

setting may achieve this most appropriately;

• judicious use of neuraxial, oral and intravenous opioids

for postoperative pain relief.

Table 4 Direct maternal deaths due to anaesthesia by types ofanaesthesia in United Kingdom 1979–2002. Derived fromCEMD reports. Since 1979, maternal deaths are reported asdirect and indirect.

Year Total (n) GA (n) RA (n)

2000–02 6 6 01997–99 3 2 11994–96 1 0 11991–93 8 7 11988–90 4 3 11985–87 8 7 11982–84 18 17 11979–81 22 22 0

GA, general anaesthesia; RA, regional anaesthesia.

Figure 2 Anaesthesia-related maternal deaths by types ofanaesthesia, United States 1979–90 [94]. Reprinted with per-mission from Anesthesiology.




It is not surprising that obese parturients undergoing

Caesarean section are at increased risk of bleeding [36, 50]

and require longer operating time [50, 51]. Panniculus

retraction is another issue in morbidly obese parturients.

Cephalad retraction of the panniculus can cause severe

cardiovascular compromise. There has been at least one

report of fetal death attributed to severe hypotension

following panniculus retraction [95]. The dense regional

block up to the fourth thoracic dermatome required for

Caesarean section can compound cardiovascular compro-

mise. Paralysis of intercostal muscles along with the

supine position and cephalad retraction of the panniculus

has the potential to increase the work of breathing

substantially and provoke respiratory failure in this

susceptible population. Suspending the abdominal panni-

culus vertically may alleviate some of these problems [95].

Regional anaesthesia

Single shot spinal anaesthesia remains the most common

type of anaesthesia employed for delivery of the fetus by

Caesarean section. The advantage of using subarachnoid

block includes a dense reliable block of rapid onset.

However, relevant issues include technical difficulties,

potential for high spinal blockade, profound dense

thoracic motor blockade leading to cardiorespiratory

compromise and inability to prolong the blockade.

Technical difficulties are the same as those for locating

the epidural space. However, it is often easier to identify

the epidural space with a large gauge stiff epidural needle

than with a smaller gauge flexible spinal needle. Many

anaesthetists use an epidural needle as an introducer for a

spinal needle in difficult cases. It is widely believed that

local anaesthetic requirements are less in pregnant

patients, more so in obese patients. Proposed mechanisms

for the enhanced neural blockade in pregnancy include

hormone-related changes in the action of spinal cord

neurotransmitters, potentiation of the analgesic effect of

endogenous analgesic systems, increased permeability of

the neural sheath or other pharmacokinetic ⁄ dynamic

differences [96]. Both pregnancy and obesity increase

intra-abdominal pressure and cause compression of the

inferior vena cava, which leads to engorgement of the

epidural venous plexus and increased epidural space

pressure. This in turn reduces the volume of cerebrospinal

fluid in the subarachnoid space. Magnetic resonance

imaging has confirmed the decreased cerebrospinal fluid

volume in obese parturients [97]. Greene suggests that

obesity per se does not decrease local anaesthetic require-

ments, rather the larger buttocks of obese patients place

the vertebral column in the Trendelenburg position,

exaggerating the spread of spinal anaesthesia [98]. There is

little evidence in the literature to suggest an exaggerated

spread in obese patients for a given amount of local

anaesthetic agent [99–102]. Whatever the mechanism, the

consequences of extensive blockade in the presence of a

potentially difficult airway dictate the amount of local

anaesthetic agent given intrathecally. Duration of surgery

may extend beyond the duration of single-shot spinal

anaesthesia and in such cases intra-operative induction of

general anaesthesia is undesirable and potentially hazard-

ous. Although continuous spinal anaesthesia represents an

alternative [103], the merit of using it routinely for

Caesarean section is yet to be proved. Hence, while

choosing single-shot spinal anaesthesia, the consequences

of extensive blockade and prolonged surgery must be

borne in mind.

Compared with spinal anaesthesia, epidural anaesthesia

offers several advantages, including an easily titratable

local anaesthetic dose and level of anaesthesia, ability to

extend the block for prolonged surgery, slower and more

easily controllable haemodynamic changes, a decreased

potential for excess motor blockade and its utilisation for

postoperative analgesia. Hodgkinson and Hussain demon-

strated that height of blockade for a given volume of local

anaesthetic agent is proportional to BMI and weight but

not height [83]. The decreased volume of the epidural

space, for reasons discussed above, may contribute to

excessive spread of local anaesthetic agents in obese

parturients. However, incremental injection of local

anaesthetic doses reduces the effect of obesity on the

spread of epidural anaesthesia. Extending labour epidural

analgesia for Caesarean section requires additional local

anaesthetic agent at higher concentrations. An optimum

dose for this remains undetermined.

A combined spinal-epidural technique represents an

attractive alternative [104], combining the advantages of

rapid onset and dense block with the ability to prolong

the block and use postoperatively. Furthermore, use of

less local anaesthetic agent intrathecally may circumvent

the problems of sudden onset of hypotension. However,

the technical challenge of correctly placing an epidural

catheter remains.

General anaesthesia

In England, 5–19% of Caesarean sections are done under

general anaesthesia in the majority of the units [105]. The

anatomical and physiological changes caused by both

obesity and pregnancy are less favourable to anaesthetists,

resulting in an increased incidence of difficult intubation

and rapid desaturation during the apnoeic phase. The

potential for an unanticipated difficult airway, difficult

mask ventilation and rapid desaturation emphasises the

need for an additional pair of experienced hands when

administering general anaesthesia. In known cases of

difficulty, awake intubation by direct laryngoscopy, fiber

optic bronchoscope or Bullard laryngoscope [106] is




an alternative method of securing the airway. Awake

intubation poses its own problems. The nasal route is not

recommended because of the characteristic engorgement

of nasal mucosa during pregnancy. Hypertension and

catecholamine release during the procedure could

adversely affect uterine blood flow. Moreover, it is

difficult to perform in urgent scenarios such as maternal

haemorrhage or fetal distress [7]. In any of these

circumstances, the mother’s life should not be endangered

to save a compromised fetus.

In an otherwise normal airway, administration of

general anaesthesia begins with effective denitrogenation

of the lungs, as obese parturients desaturate rapidly

compared to normal patients. Denitrogenation can be

performed by either 3 min of tidal breathing with 100%

oxygen or by four maximal breaths with 100% oxygen.

There is little evidence to support one technique over the

other [107, 108]. Hence, it is reasonable that urgency of

Caesarean section dictates the technique of denitrogena-

tion. The choice of intravenous induction agent is

relatively unimportant if there are no co-existing medical

problems. Dewan suggests that at least 4 mg.kg)1 of

thiopental (up to a maximum dose of 500 mg) should be

used if chosen, to avoid the risk of maternal awareness,

hypertension and decreased uterine blood flow during

light anaesthesia [7]. Administration of a larger dose may

be associated with delayed arousal in the event of failed

intubation. Succinylcholine remains the muscle relaxant of

choice for intubation. Bentley et al. observed increased

pseudo-cholinesterase activity in obese non-pregnant

patients. They recommended that anaesthetists should

administer succinylcholine on the basis of total rather than

lean body weight in adult patients [109]. However,

pregnancy reduces pseudo-cholinesterase activity. Hence

the dose of succinylcholine 1.0–1.5 mg.kg)1 up to a

maximum of 200 mg is reasonable [7]. Tracheal intuba-

tion should be confirmed by the repetitive and character-

istic waveform of capnography in addition to auscultation.

Endobronchial intubation should also be promptly rec-

ognised and corrected to avoid intra- and postoperative

pulmonary complications. In the event of failure to

intubate the trachea after rapid sequence induction, it is

imperative to institute a failed intubation drill without

delay. Repeated attempts and a second dose of succinyl-

choline are seldom beneficial and often detrimental. The

primary objective in the management of failed intubation

is to ensure adequate maternal oxygenation despite the

concerns of fetal well-being or risk of regurgitation.

In morbidly obese patients, a relatively high-inspired

oxygen concentration may be necessary compared to

non-obese counterparts, necessitating use of high con-

centrations of volatile agents. Under general anaesthesia,

functional residual capacity (FRC) decreases because of

the supine position, use of volatile agents, muscle

relaxants and cephalad retraction of a panniculus, leading

to early closure of small airways, exaggerating hypoxae-

mia. Various techniques such as higher tidal volumes,

high inspired oxygen and the use of positive end-

expiratory pressure (PEEP) have been used to maintain

adequate oxygenation. In high-risk cases, emptying of the

stomach and administration of sodium citrate via an

orogastric tube before extubation may be helpful. Extu-

bation should be attempted only in awake patients with

adequate reversal of neuromuscular blockade, as there

have been incidences of failed extubation in obese

parturients [50, 51]. A 30� head-up tilt is a more

favourable position for extubation than supine in the

obese population [110].

Postoperative care

Obese parturients are at increased risk of postoperative

complications such as hypoxaemia, atelectasis and pneu-

monia, deep vein thrombosis and pulmonary embolism,

pulmonary oedema, postpartum cardiomyopathy, post-

operative endometritis and wound complications such as

infection and dehiscence [50, 51]. Early mobilisation,

thromboprophylaxis, aggressive chest physiotherapy and

adequate pain control are the key to the success of

effective postoperative care.

In the recovery room, critical respiratory events

(desaturation, hypoventilation and airway obstruction)

occur twice as commonly in the obese compared to non-

obese [111]. Computerised tomography has demonstrated

that obesity predisposes to the formation of pulmonary

atelectasis per se and even more so under general

anaesthesia, persisting into the postoperative period

[112]. Moreover, even after spinal anaesthesia, there is a

BMI dependent decrease in respiratory function [113].

Hence, these critical respiratory events may not be benign

and can lead to postoperative pulmonary morbidity.

Nursing in the reclined position and oxygen supplemen-

tation can potentially reduce critical respiratory events.

Early mobilisation has been shown to improve the

respiratory volumes in the immediate postoperative phase

[113]. Interestingly, Hood and Dewan found that, in

morbidly obese women, all postpartum complications

occurred in those undergoing Caesarean section and not

in those having vaginal delivery [51]. In general surgical

patients, pre-operative pulmonary function tests have

been shown to predict postoperative pulmonary compli-

cations in obese patients [77] and an extrapolation for

obese parturients may be true.

Pain control should be adequate in the postoperative

period to facilitate mobilisation and chest physiotherapy,

as it is one of the determinants of postoperative maternal

morbidity. Epidural analgesia has been shown to improve




postoperative respiratory function in patients undergoing

abdominal surgery [114]. Epidural infusion of local

anaesthetic with opioids improves the quality of dynamic

postoperative pain relief [115]. Patient controlled intra-

venous opioids have also been successfully used for

postoperative pain relief in the morbidly obese [116].

Thrombo-embolic episodes remain the leading cause of

direct maternal deaths in the UK. Obesity is a known

independent risk factor for deep vein thrombosis. Both

pharmacological and mechanical strategies are used for

thromboprophylaxis and an adequate dose of an anti-

coagulant for an appropriate duration is recommended

[117]. Obesity cardiomyopathy is a well-recognised

clinical entity and at least three cases of peripartum

cardiomyopathy in obese patients have been reported

[51, 118, 119]. Although not established yet, obesity may

well be a risk factor for peripartum cardiomyopathy [119].

Wound complications occur more frequently in obese

than in non-obese patients and often lead to prolonged

recovery. They have been found to be increased with

midline abdominal incision compared to a Pfannenstiel

incision [120]. An increased incidence of postoperative

complications and antepartum medical disease probably

contributes significantly to longer hospitalisation for the

morbidly obese. Hospital stay and costs have been found

to be increased for morbidly obese patients after both

vaginal delivery and Caesarean section [121].

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Anesthesiology 2007; 106:843–63 Copyright © 2007, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Practice Guidelines for Obstetric Anesthesia

An Updated Report by the American Society of Anesthesiologists Task Force onObstetric Anesthesia*

PRACTICE guidelines are systematically developed rec-ommendations that assist the practitioner and patient inmaking decisions about health care. These recommen-dations may be adopted, modified, or rejected accordingto clinical needs and constraints and are not intended toreplace local institutional policies. In addition, practiceguidelines are not intended as standards or absoluterequirements, and their use cannot guarantee any spe-cific outcome. Practice guidelines are subject to revisionas warranted by the evolution of medical knowledge,technology, and practice. They provide basic recommen-dations that are supported by a synthesis and analysis ofthe current literature, expert opinion, open forum com-mentary, and clinical feasibility data.

This update includes data published since the “Prac-tice Guidelines for Obstetrical Anesthesia” were adoptedby the American Society of Anesthesiologists in 1998; italso includes data and recommendations for a widerrange of techniques than was previously addressed.

Methodology

A. Definition of Perioperative Obstetric AnesthesiaFor the purposes of these Guidelines, obstetric anes-

thesia refers to peripartum anesthetic and analgesic ac-

tivities performed during labor and vaginal delivery, ce-sarean delivery, removal of retained placenta, andpostpartum tubal ligation.

B. Purposes of the GuidelinesThe purposes of these Guidelines are to enhance the

quality of anesthetic care for obstetric patients, improvepatient safety by reducing the incidence and severity ofanesthesia-related complications, and increase patientsatisfaction.

C. FocusThese Guidelines focus on the anesthetic management

of pregnant patients during labor, nonoperative delivery,operative delivery, and selected aspects of postpartumcare and analgesia (i.e., neuraxial opioids for postpartumanalgesia after neuraxial anesthesia for cesarean deliv-ery). The intended patient population includes, but isnot limited to, intrapartum and postpartum patients withuncomplicated pregnancies or with common obstetricproblems. The Guidelines do not apply to patients un-dergoing surgery during pregnancy, gynecologic pa-tients, or parturients with chronic medical disease (e.g.,severe cardiac, renal, or neurologic disease). In addition,these Guidelines do not address (1) postpartum analge-sia for vaginal delivery, (2) analgesia after tubal ligation,or (3) postoperative analgesia after general anesthesia(GA) for cesarean delivery.

D. ApplicationThese Guidelines are intended for use by anesthesiol-

ogists. They also may serve as a resource for otheranesthesia providers and healthcare professionals whoadvise or care for patients who will receive anestheticcare during labor, delivery, and the immediate postpar-tum period.

E. Task Force Members and ConsultantsThe American Society of Anesthesiologists (ASA) ap-

pointed a Task Force of 11 members to (1) review thepublished evidence, (2) obtain the opinion of a panel ofconsultants including anesthesiologists and nonanesthe-siologist physicians concerned with obstetric anesthesiaand analgesia, and (3) obtain opinions from practitionerslikely to be affected by the Guidelines. The Task Forceincluded anesthesiologists in both private and academicpractices from various geographic areas of the UnitedStates and two consulting methodologists from the ASACommittee on Standards and Practice Parameters.

The Task Force developed the Guidelines by means of

This article is featured in “This Month in Anesthesiology.”Please see this issue of ANESTHESIOLOGY, page 5A.�

Additional material related to this article can be found on theANESTHESIOLOGY Web site. Go to http://www.anesthesiology.org, click on Enhancements Index, and then scroll down tofind the appropriate article and link. Supplementary materialcan also be accessed on the Web by clicking on the “Arti-clePlus” link either in the Table of Contents or at the top ofthe HTML version of the article.

�

* Developed by the American Society of Anesthesiologists Task Force onObstetric Anesthesia: Joy L. Hawkins, M.D. (Chair), Denver, Colorado; James F.Arens, M.D., Houston, Texas; Brenda A Bucklin, M.D., Denver, Colorado; RichardT. Connis, Ph.D., Woodinville, Washington; Patricia A. Dailey, M.D., Hillsbor-ough, California; David R. Gambling, M.B.B.S., San Diego, California; David G.Nickinovich, Ph.D., Bellevue, Washington; Linda S. Polley, M.D., Ann Arbor,Michigan; Lawrence C. Tsen, M.D., Boston, Massachusetts; David J. Wlody, M.D.,Brooklyn, New York; and Kathryn J. Zuspan, M.D., Stillwater, Minnesota.

Submitted for publication October 31, 2006. Accepted for publication Octo-ber 31, 2006. Supported by the American Society of Anesthesiologists under thedirection of James F. Arens, M.D., Chair, Committee on Standards and PracticeParameters. Approved by the House of Delegates on October 18, 2006. A list ofthe references used to develop these Guidelines is available by writing to theAmerican Society of Anesthesiologists.

Address reprint requests to the American Society of Anesthesiologists: 520North Northwest Highway, Park Ridge, Illinois 60068-2573. This Practice Guide-line, as well as all published ASA Practice Parameters, may be obtained at no costthrough the Journal Web site, www.anesthesiology.org.

Anesthesiology, V 106, No 4, Apr 2007 843

a seven-step process. First, they reached consensus onthe criteria for evidence. Second, original published re-search studies from peer-reviewed journals relevant toobstetric anesthesia were reviewed. Third, the panel ofexpert consultants was asked to (1) participate in opin-ion surveys on the effectiveness of various peripartummanagement strategies and (2) review and comment ona draft of the Guidelines developed by the Task Force.Fourth, opinions about the Guideline recommendationswere solicited from active members of the ASA whoprovide obstetric anesthesia. Fifth, the Task Force heldopen forums at two major national meetings† to solicitinput on its draft recommendations. Sixth, the consult-ants were surveyed to assess their opinions on the fea-sibility of implementing the Guidelines. Seventh, allavailable information was used to build consensuswithin the Task Force to finalize the Guidelines (appen-dix 1).

F. Availability and Strength of EvidencePreparation of these Guidelines followed a rigorous

methodologic process (appendix 2). To convey the find-ings in a concise and easy-to-understand fashion, theseGuidelines use several descriptive terms. When suffi-cient numbers of studies are available for evaluation, thefollowing terms describe the strength of the findings.

Support: Meta-analysis of a sufficient number of random-ized controlled trials‡ indicates a statistically signifi-cant relationship (P � 0.01) between a clinical inter-vention and a clinical outcome.

Suggest: Information from case reports and observationalstudies permits inference of a relationship between anintervention and an outcome. A meta-analytic assess-ment of this type of qualitative or descriptive informa-tion is not conducted.

Equivocal: Either a meta-analysis has not found signifi-cant differences among groups or conditions, or thereis insufficient quantitative information to conduct ameta-analysis and information collected from case re-ports and observational studies does not permit infer-ence of a relationship between an intervention and anoutcome.

The lack of scientific evidence in the literature isdescribed by the following terms.

Silent: No identified studies address the specified rela-tionship between an intervention and outcome.

Insufficient: There are too few published studies to in-

vestigate a relationship between an intervention andoutcome.

Inadequate: The available studies cannot be used toassess the relationship between an intervention and anoutcome. These studies either do not meet the criteriafor content as defined in the Focus section of theseGuidelines, or do not permit a clear causal interpreta-tion of findings due to methodologic concerns.

Formal survey information is collected from consult-ants and members of the ASA. The following termsdescribe survey responses for any specified issue. Re-sponses are solicited on a five-point scale ranging from 1(strongly disagree) to 5 (strongly agree), with a score of3 being equivocal. Survey responses are summarizedbased on median values as follows:

Strongly Agree: Median score of 5 (at least 50% of theresponses are 5)

Agree: Median score of 4 (at least 50% of the responsesare 4 or 4 and 5)

Equivocal: Median score of 3 (at least 50% of the re-sponses are 3, or no other response category or com-bination of similar categories contain at least 50% ofthe responses)

Disagree: Median score of 2 (at least 50% of the re-sponses are 2 or 1 and 2)

Strongly Disagree: Median score of 1 (at least 50% of theresponses are 1)

Guidelines

I. Perianesthetic EvaluationHistory and Physical Examination. Although com-

parative studies are insufficient to evaluate the peripar-tum impact of conducting a focused history (e.g., review-ing medical records) or a physical examination, theliterature reports certain patient or clinical characteris-tics that may be associated with obstetric complications.These characteristics include, but are not limited to,preeclampsia, pregnancy-related hypertensive disorders,HELLP syndrome, obesity, and diabetes.

The consultants and ASA members both strongly agreethat a directed history and physical examination, as wellas communication between anesthetic and obstetric pro-viders, reduces maternal, fetal, and neonatal complica-tions.

Recommendations. The anesthesiologist should con-duct a focused history and physical examination be-fore providing anesthesia care. This should include,but is not limited to, a maternal health and anesthetichistory, a relevant obstetric history, a baseline bloodpressure measurement, and an airway, heart, and lungexamination, consistent with the ASA “Practice Advi-sory for Preanesthesia Evaluation.”§ When a neuraxialanesthetic is planned or placed, the patient’s backshould be examined.

† International Anesthesia Research Society, 80th Clinical and Scientific Con-gress, San Francisco, California, March 25, 2006; and Society of Obstetric Anes-thesia and Perinatology 38th Annual Meeting, Hollywood, Florida, April 29, 2006.

‡ A prospective nonrandomized controlled trial may be included in a meta-analysis under certain circumstances if specific statistical criteria are met.

§ American Society of Anesthesiologists Task Force on Preanesthesia Evaluation:Practice advisory for preanesthesia evaluation. ANESTHESIOLOGY 2002; 96:485–96.

844 PRACTICE GUIDELINES

Anesthesiology, V 106, No 4, Apr 2007

Recognition of significant anesthetic or obstetric riskfactors should encourage consultation between the ob-stetrician and the anesthesiologist. A communicationsystem should be in place to encourage early and ongo-ing contact between obstetric providers, anesthesiolo-gists, and other members of the multidisciplinary team.

Intrapartum Platelet Count. The literature is insuf-ficient to assess whether a routine platelet count canpredict anesthesia-related complications in uncompli-cated parturients. The literature suggests that a plateletcount is clinically useful for parturients with suspectedpregnancy-related hypertensive disorders, such as pre-eclampsia or HELLP syndrome, and for other disordersassociated with coagulopathy.

The ASA members are equivocal, but the consultantsagree that obtaining a routine intrapartum platelet countdoes not reduce maternal anesthetic complications.Both the consultants and ASA members agree that, forpatients with suspected preeclampsia, a platelet countreduces maternal anesthetic complications. The consult-ants strongly agree and the ASA members agree that aplatelet count reduces maternal anesthetic complica-tions for patients with suspected coagulopathy.

Recommendations. A specific platelet count predic-tive of neuraxial anesthetic complications has not beendetermined. The anesthesiologist’s decision to order orrequire a platelet count should be individualized andbased on a patient’s history, physical examination, andclinical signs. A routine platelet count is not necessary inthe healthy parturient.

Blood Type and Screen. The literature is insufficientto determine whether obtaining a blood type and screenis associated with fewer maternal anesthetic complica-tions. In addition, the literature is insufficient to deter-mine whether a blood cross-match is necessary forhealthy and uncomplicated parturients. The consultantsand ASA members agree that an intrapartum blood sam-ple should be sent to the blood bank for all parturients.

Recommendations. A routine blood cross-match is notnecessary for healthy and uncomplicated parturients forvaginal or operative delivery. The decision whether toorder or require a blood type and screen, or cross-match,should be based on maternal history, anticipated hemor-rhagic complications (e.g., placenta accreta in a patientwith placenta previa and previous uterine surgery), andlocal institutional policies.

Perianesthetic Recording of the Fetal Heart Rate.The literature suggests that anesthetic and analgesicagents may influence the fetal heart rate pattern. There isinsufficient literature to demonstrate that perianestheticrecording of the fetal heart rate prevents fetal or neona-tal complications. Both the consultants and ASA mem-

bers agree, however, that perianesthetic recording of thefetal heart rate reduces fetal and neonatal complications.

Recommendations. The fetal heart rate should bemonitored by a qualified individual before and after ad-ministration of neuraxial analgesia for labor. The TaskForce recognizes that continuous electronic recordingof the fetal heart rate may not be necessary in everyclinical setting and may not be possible during initiationof neuraxial anesthesia.

II. Aspiration PreventionClear Liquids. There is insufficient published evi-

dence to draw conclusions about the relationship be-tween fasting times for clear liquids and the risk ofemesis/reflux or pulmonary aspiration during labor. Theconsultants and ASA members both agree that oral intakeof clear liquids during labor improves maternal comfortand satisfaction. Although the ASA members are equiv-ocal, the consultants agree that oral intake of clear liq-uids during labor does not increase maternal complica-tions.

Recommendations. The oral intake of modestamounts of clear liquids may be allowed for uncompli-cated laboring patients. The uncomplicated patient un-dergoing elective cesarean delivery may have modestamounts of clear liquids up to 2 h before induction ofanesthesia. Examples of clear liquids include, but are notlimited to, water, fruit juices without pulp, carbonatedbeverages, clear tea, black coffee, and sports drinks.�The volume of liquid ingested is less important than thepresence of particulate matter in the liquid ingested.However, patients with additional risk factors for aspira-tion (e.g., morbid obesity, diabetes, difficult airway) orpatients at increased risk for operative delivery (e.g.,nonreassuring fetal heart rate pattern) may have furtherrestrictions of oral intake, determined on a case-by-casebasis.

Solids. A specific fasting time for solids that is predic-tive of maternal anesthetic complications has not beendetermined. There is insufficient published evidence toaddress the safety of any particular fasting period forsolids in obstetric patients. The consultants and ASAmembers both agree that the oral intake of solids duringlabor increases maternal complications. They bothstrongly agree that patients undergoing either electivecesarean delivery or postpartum tubal ligation shouldundergo a fasting period of 6–8 h depending on the typeof food ingested (e.g., fat content).� The Task Forcerecognizes that in laboring patients the timing of deliv-ery is uncertain; therefore, compliance with a predeter-mined fasting period before nonelective surgical proce-dures is not always possible.

Recommendations. Solid foods should be avoided inlaboring patients. The patient undergoing elective sur-gery (e.g., scheduled cesarean delivery or postpartumtubal ligation) should undergo a fasting period for solids

� American Society of Anesthesiologists Task Force on Preoperative Fasting:Practice guidelines for preoperative fasting and the use of pharmacologic agentsto reduce the risk of pulmonary aspiration. ANESTHESIOLOGY 1999; 90:896–905.

845PRACTICE GUIDELINES


of 6–8 h depending on the type of food ingested (e.g., fatcontent).�

Antacids, H2 Receptor Antagonists, and Metoclo-pramide. The literature does not sufficiently examinethe relationship between reduced gastric acidity and thefrequency of emesis, pulmonary aspiration, morbidity, ormortality in obstetric patients who have aspirated gastriccontents. Published evidence supports the efficacy ofpreoperative nonparticulate antacids (e.g., sodium ci-trate, sodium bicarbonate) in decreasing gastric acidityduring the peripartum period. However, the literature isinsufficient to examine the impact of nonparticulateantacids on gastric volume. The literature suggests thatH2 receptor antagonists are effective in decreasing gas-tric acidity in obstetric patients and supports the efficacyof metoclopramide in reducing peripartum nausea andvomiting. The consultants and ASA members agree thatthe administration of a nonparticulate antacid beforeoperative procedures reduces maternal complications.

Recommendations. Before surgical procedures (i.e.,cesarean delivery, postpartum tubal ligation), practitio-ners should consider the timely administration of non-particulate antacids, H2 receptor antagonists, and/ormetoclopramide for aspiration prophylaxis.

III. Anesthetic Care for Labor and Vaginal DeliveryOverview. Not all women require anesthetic care dur-

ing labor or delivery. For women who request pain relieffor labor and/or delivery, there are many effective anal-gesic techniques available. Maternal request representssufficient justification for pain relief. In addition, mater-nal medical and obstetric conditions may warrant theprovision of neuraxial techniques to improve maternaland neonatal outcome.

The choice of analgesic technique depends on themedical status of the patient, progress of labor, andresources at the facility. When sufficient resources (e.g.,anesthesia and nursing staff) are available, neuraxialcatheter techniques should be one of the analgesic op-tions offered. The choice of a specific neuraxial blockshould be individualized and based on anesthetic riskfactors, obstetric risk factors, patient preferences,progress of labor, and resources at the facility.

When neuraxial catheter techniques are used for anal-gesia during labor or vaginal delivery, the primary goal isto provide adequate maternal analgesia with minimalmotor block (e.g., achieved with the administration oflocal anesthetics at low concentrations with or withoutopioids).

When a neuraxial technique is chosen, appropriateresources for the treatment of complications (e.g., hypo-tension, systemic toxicity, high spinal anesthesia) shouldbe available. If an opioid is added, treatments for relatedcomplications (e.g., pruritus, nausea, respiratory depres-sion) should be available. An intravenous infusion shouldbe established before the initiation of neuraxial analgesia

or anesthesia and maintained throughout the duration ofthe neuraxial analgesic or anesthetic. However, admin-istration of a fixed volume of intravenous fluid is notrequired before neuraxial analgesia is initiated.

Timing of Neuraxial Analgesia and Outcome ofLabor. Meta-analysis of the literature determined thatthe timing of neuraxial analgesia does not affect thefrequency of cesarean delivery. The literature also sug-gests that other delivery outcomes (i.e., spontaneous orinstrumented) are also unaffected. The consultantsstrongly agree and the ASA members agree that earlyinitiation of epidural analgesia (i.e., at cervical dilationsof less than 5 cm vs. equal to or greater than 5 cm)improves analgesia. They both disagree that motor blockor maternal, fetal, or neonatal side effects are increasedby early administration.

Recommendations. Patients in early labor (i.e., � 5 cmdilation) should be given the option of neuraxial analge-sia when this service is available. Neuraxial analgesiashould not be withheld on the basis of achieving anarbitrary cervical dilation, and should be offered on anindividualized basis. Patients may be reassured that theuse of neuraxial analgesia does not increase the inci-dence of cesarean delivery.

Neuraxial Analgesia and Trial of Labor after Pre-vious Cesarean Delivery. Nonrandomized compara-tive studies suggest that epidural analgesia may be usedin a trial of labor for previous cesarean delivery patientswithout adversely affecting the incidence of vaginal de-livery. Randomized comparisons of epidural versusother anesthetic techniques were not found. The con-sultants and ASA members agree that neuraxial tech-niques improve the likelihood of vaginal delivery forpatients attempting vaginal birth after cesarean delivery.

Recommendations. Neuraxial techniques should beoffered to patients attempting vaginal birth after previ-ous cesarean delivery. For these patients, it is also ap-propriate to consider early placement of a neuraxialcatheter that can be used later for labor analgesia, or foranesthesia in the event of operative delivery.

Early Insertion of a Spinal or Epidural Catheterfor Complicated Parturients. The literature is insuffi-cient to assess whether, when caring for the compli-cated parturient, the early insertion of a spinal or epi-dural catheter, with later administration of analgesia,improves maternal or neonatal outcomes. The consult-ants and ASA members agree that early insertion of aspinal or epidural catheter for complicated parturientsreduces maternal complications.

Recommendations. Early insertion of a spinal or epi-dural catheter for obstetric (e.g., twin gestation or pre-eclampsia) or anesthetic indications (e.g., anticipateddifficult airway or obesity) should be considered to re-duce the need for GA if an emergent procedure becomesnecessary. In these cases, the insertion of a spinal or



epidural catheter may precede the onset of labor or apatient’s request for labor analgesia.

Continuous Infusion Epidural Analgesia.CIE Compared with Parenteral Opioids. The literature

suggests that the use of continuous infusion epidural(CIE) local anesthetics with or without opioids providesgreater quality of analgesia compared with parenteral(i.e., intravenous or intramuscular) opioids. The consult-ants and ASA members strongly agree that CIE localanesthetics with or without opioids provide improvedanalgesia compared with parenteral opioids.

Meta-analysis of the literature indicates that there is alonger duration of labor, with an average duration of 24min for the second stage, and a lower frequency ofspontaneous vaginal delivery when continuous epidurallocal anesthetics are administered compared with intra-venous opioids. Meta-analysis of the literature deter-mined that there are no differences in the frequency ofcesarean delivery. Neither the consultants nor ASA mem-bers agree that CIE local anesthetics compared withparenteral opioids significantly (1) increase the durationof labor, (2) decrease the chance of spontaneous deliv-ery, (3) increase maternal side effects, or (4) increasefetal and neonatal side effects.

CIE Compared with Single-injection Spinal. There isinsufficient literature to assess the analgesic efficacy ofCIE local anesthetics with or without opioids comparedto single-injection spinal opioids with or without localanesthetics. The consultants are equivocal, but the ASAmembers agree that CIE local anesthetics improve anal-gesia compared with single-injection spinal opioids; boththe consultants and ASA members are equivocal regard-ing the frequency of motor block. The consultants areequivocal, but the ASA members disagree that the use ofCIE compared with single-injection spinal opioids in-creases the duration of labor. They both disagree thatCIE local anesthetics with or without opioids comparedto single-injection spinal opioids with or without localanesthetics decreases the likelihood of spontaneous de-livery or increases maternal, fetal, or neonatal side ef-fects.

CIE with and without Opioids. The literature supportsthe induction of analgesia using epidural local anesthet-ics combined with opioids compared with equal con-centrations of epidural local anesthetics without opioidsfor improved quality and longer duration of analgesia.The consultants strongly agree and the ASA membersagree that the addition of opioids to epidural local anes-thetics improves analgesia; they both disagree that fetalor neonatal side effects are increased. The consultantsdisagree, but the ASA members are equivocal regarding

whether the addition of opioids increases maternal sideeffects.

The literature is insufficient to determine whether in-duction of analgesia using local anesthetics with opioidscompared with higher concentrations of epidural localanesthetics without opioids provides improved qualityor duration of analgesia. The consultants and ASA mem-bers are equivocal regarding improved analgesia, andthey both disagree that maternal, fetal, or neonatal sideeffects are increased using lower concentrations of epi-dural local anesthetics with opioids.

For maintenance of analgesia, the literature suggeststhat there are no differences in the analgesic efficacy oflow concentrations of epidural local anesthetics withopioids compared with higher concentrations of epi-dural local anesthetics without opioids. The Task Forcenotes that the addition of an opioid to a local anestheticinfusion allows an even lower concentration of localanesthetic for providing equally effective analgesia.However, the literature is insufficient to examinewhether a bupivacaine infusion concentration of lessthan or equal to 0.125% with an opioid provides com-parable or improved analgesia compared with a bupiva-caine concentration greater than 0.125% without anopioid.# Meta-analysis of the literature determined thatlow concentrations of epidural local anesthetics withopioids compared with higher concentrations of epi-dural local anesthetics without opioids are associatedwith reduced motor block. No differences in the dura-tion of labor, mode of delivery, or neonatal outcomes arefound when epidural local anesthetics with opioids arecompared with epidural local anesthetics without opi-oids. The literature is insufficient to determine the ef-fects of epidural local anesthetics with opioids on othermaternal outcomes (e.g., hypotension, nausea, pruritus,respiratory depression, urinary retention).

The consultants and ASA members both agree thatmaintenance of epidural analgesia using low concentra-tions of local anesthetics with opioids provides im-proved analgesia compared with higher concentrationsof local anesthetics without opioids. The consultantsagree, but the ASA members are equivocal regarding theimproved likelihood of spontaneous delivery whenlower concentrations of local anesthetics with opioidsare used. The consultants strongly agree and the ASAmembers agree that motor block is reduced. They agreethat maternal side effects are reduced with this drugcombination. They are both equivocal regarding a reduc-tion in fetal and neonatal side effects.

Recommendations. The selected analgesic/anesthetictechnique should reflect patient needs and preferences,practitioner preferences or skills, and available re-sources. The continuous epidural infusion techniquemay be used for effective analgesia for labor and deliv-ery. When a continuous epidural infusion of local anes-thetic is selected, an opioid may be added to reduce the

# References to bupivacaine are included for illustrative purposes only, andbecause bupivacaine is the most extensively studied local anesthetic for contin-uous infusion epidural analgesia. The Task Force recognizes that other localanesthetics are appropriate for continuous infusion epidural analgesia.



concentration of local anesthetic, improve the quality ofanalgesia, and minimize motor block.

Adequate analgesia for uncomplicated labor and deliv-ery should be administered with the secondary goal ofproducing as little motor block as possible by usingdilute concentrations of local anesthetics with opioids.The lowest concentration of local anesthetic infusionthat provides adequate maternal analgesia and satisfac-tion should be administered. For example, an infusionconcentration greater than 0.125% bupivacaine is unnec-essary for labor analgesia in most patients.

Single-injection Spinal Opioids with or withoutLocal Anesthetics. The literature suggests that spinalopioids with or without local anesthetics provide effec-tive analgesia during labor without altering the incidenceof neonatal complications. There is insufficient literatureto compare spinal opioids with parenteral opioids. Thereis also insufficient literature to compare single-injectionspinal opioids with local anesthetics versus single-injec-tion spinal opioids without local anesthetics.

The consultants strongly agree and the ASA membersagree that spinal opioids provide improved analgesiacompared with parenteral opioids. They both disagreethat, compared with parenteral opioids, spinal opioidsincrease the duration of labor, decrease the chance ofspontaneous delivery, or increase fetal and neonatal sideeffects. The consultants are equivocal, but the ASA mem-bers disagree that maternal side effects are increasedwith spinal opioids.

Compared with spinal opioids without local anesthet-ics, the consultants and ASA members both agree thatspinal opioids with local anesthetics provide improvedanalgesia. They both disagree that the chance of sponta-neous delivery is decreased and that fetal and neonatalside effects are increased. They are both equivocal re-garding an increase in maternal side effects. However,they both agree that motor block is increased when localanesthetics are added to spinal opioids. Finally, the con-sultants disagree, but the ASA members are equivocalregarding an increase in the duration of labor.

Recommendations. Single-injection spinal opioidswith or without local anesthetics may be used to provideeffective, although time-limited, analgesia for labor whenspontaneous vaginal delivery is anticipated. If labor isexpected to last longer than the analgesic effects of thespinal drugs chosen or if there is a good possibility ofoperative delivery, a catheter technique instead of asingle injection technique should be considered. A localanesthetic may be added to a spinal opioid to increaseduration and improve quality of analgesia. The TaskForce notes that the rapid onset of analgesia provided bysingle-injection spinal techniques may be advantageousfor selected patients (e.g., those in advanced labor).

Pencil-point Spinal Needles. The literature supportsthe use of pencil-point spinal needles compared withcutting-bevel spinal needles to reduce the frequency of

post–dural puncture headache. The consultants and ASAmembers both strongly agree that the use of pencil-pointspinal needles reduces maternal complications.

Recommendations. Pencil-point spinal needles shouldbe used instead of cutting-bevel spinal needles to mini-mize the risk of post–dural puncture headache.

Combined Spinal–Epidural Analgesia. The litera-ture supports a faster onset time and equivalent analgesiawith combined spinal–epidural (CSE) local anestheticswith opioids versus epidural local anesthetics with opioids.The literature is equivocal regarding the impact of CSEversus epidural local anesthetics with opioids on maternalsatisfaction with analgesia, mode of delivery, hypotension,motor block, nausea, fetal heart rate changes, and Apgarscores. Meta-analysis of the literature indicates that thefrequency of pruritus is increased with CSE.

The consultants and ASA members both agree that CSElocal anesthetics with opioids provide improved earlyanalgesia compared with epidural local anesthetics withopioids. They are equivocal regarding the impact of CSEwith opioids on overall analgesic efficacy, duration oflabor, and motor block. The consultants and ASA mem-bers both disagree that CSE increases the risk of fetal orneonatal side effects. The consultants disagree, but theASA members are equivocal regarding whether CSE in-creases the incidence of maternal side effects.

Recommendations. Combined spinal–epidural tech-niques may be used to provide effective and rapid onsetof analgesia for labor.

Patient-controlled Epidural Analgesia. The litera-ture supports the efficacy of patient-controlled epiduralanalgesia (PCEA) versus CIE in providing equivalent an-algesia with reduced drug consumption. Meta-analysis ofthe literature indicates that the duration of labor islonger with PCEA compared with CIE for the first stage(e.g., an average of 36 min) but not the second stage oflabor. Meta-analysis of the literature also determined thatmode of delivery, frequency of motor block, and Apgarscores are equivalent when PCEA administration is com-pared with CIE. The literature supports greater analgesicefficacy for PCEA with a background infusion comparedwith PCEA without a background infusion; meta-analysisof the literature also indicates no differences in the modeof delivery or frequency of motor block. The consultantsand ASA members agree that PCEA compared with CIEimproves analgesia and reduces the need for anestheticinterventions; they also agree that PCEA improves ma-ternal satisfaction. The consultants and ASA members areequivocal regarding a reduction in motor block, an in-creased likelihood of spontaneous delivery, or a decreasein maternal side effects with PCEA compared with CIE.They both agree that PCEA with a background infusionimproves analgesia, improves maternal satisfaction, andreduces the need for anesthetic intervention. The ASAmembers are equivocal, but the consultants disagree thata background infusion decreases the chance of sponta-



neous delivery or increases maternal side effects. Theconsultants and ASA members are equivocal regardingthe effect of a background infusion on the incidence ofmotor block.

Recommendations. Patient-controlled epidural analge-sia may be used to provide an effective and flexibleapproach for the maintenance of labor analgesia. TheTask Force notes that the use of PCEA may be preferableto fixed-rate CIE for providing fewer anesthetic interven-tions and reduced dosages of local anesthetics. PCEAmay be used with or without a background infusion.

IV. Removal of Retained PlacentaAnesthetic Techniques. The literature is insufficient

to assess whether a particular type of anesthetic is moreeffective than another for removal of retained placenta.The consultants strongly agree and the ASA membersagree that, if a functioning epidural catheter is in placeand the patient is hemodynamically stable, epidural an-esthesia is the preferred technique for the removal ofretained placenta. The consultants and ASA membersboth agree that, in cases involving major maternal hem-orrhage, GA is preferred over neuraxial anesthesia.

Recommendations. The Task Force notes that, in gen-eral, there is no preferred anesthetic technique for re-moval of retained placenta. However, if an epidural cath-eter is in place and the patient is hemodynamicallystable, epidural anesthesia is preferable. Hemodynamicstatus should be assessed before administering neuraxialanesthesia. Aspiration prophylaxis should be considered.Sedation/analgesia should be titrated carefully due to thepotential risks of respiratory depression and pulmonaryaspiration during the immediate postpartum period. Incases involving major maternal hemorrhage, GA with anendotracheal tube may be preferable to neuraxial anes-thesia.

Uterine Relaxation. The literature suggests that ni-troglycerin is effective for uterine relaxation during theremoval of retained placenta. The consultants and ASAmembers both agree that the administration of nitroglyc-erin for uterine relaxation improves success in removinga retained placenta.

Recommendations. Nitroglycerin may be used as analternative to terbutaline sulfate or general endotrachealanesthesia with halogenated agents for uterine relax-ation during removal of retained placental tissue. Initiat-ing treatment with incremental doses of intravenous orsublingual (i.e., metered dose spray) nitroglycerin mayrelax the uterus sufficiently while minimizing potentialcomplications (e.g., hypotension).

V. Anesthetic Choices for Cesarean DeliveryEquipment, Facilities, and Support Personnel.

The literature is insufficient to evaluate the benefit ofproviding equipment, facilities and support personnel inthe labor and delivery operating suite comparable to that

available in the main operating suite. The consultantsand ASA members strongly agree that the availableequipment, facilities, and support personnel should becomparable.

Recommendations. Equipment, facilities, and sup-port personnel available in the labor and deliveryoperating suite should be comparable to those avail-able in the main operating suite. Resources for thetreatment of potential complications (e.g., failed intu-bation, inadequate analgesia, hypotension, respiratorydepression, pruritus, vomiting) should also be avail-able in the labor and delivery operating suite. Appro-priate equipment and personnel should be available tocare for obstetric patients recovering from majorneuraxial anesthesia or GA.

General, Epidural, Spinal, or Combined Spinal–Epidural Anesthesia. The literature suggests that in-duction-to-delivery times for GA are lower comparedwith epidural or spinal anesthesia and that a higherfrequency of maternal hypotension may be associatedwith epidural or spinal techniques. Meta-analysis of theliterature found that Apgar scores at 1 and 5 min arelower for GA compared with epidural anesthesia andsuggests that Apgar scores are lower for GA versus spinalanesthesia. The literature is equivocal regarding differ-ences in umbilical artery pH values when GA is com-pared with epidural or spinal anesthesia.

The consultants and ASA members agree that GA re-duces the time to skin incision when compared witheither epidural or spinal anesthesia; they also agree thatGA increases maternal complications. The consultantsare equivocal and the ASA members agree that GA in-creases fetal and neonatal complications. The consult-ants and ASA members both agree that epidural anesthe-sia increases the time to skin incision and decreases thequality of anesthesia compared with spinal anesthesia.They both disagree that epidural anesthesia increasesmaternal complications.

When spinal anesthesia is compared with epiduralanesthesia, meta-analysis of the literature found that in-duction-to-delivery times are shorter for spinal anesthe-sia. The literature is equivocal regarding hypotension,umbilical pH values, and Apgar scores. The consultantsand ASA members agree that epidural anesthesia in-creases time to skin incision and reduces the quality ofanesthesia when compared with spinal anesthesia. Theyboth disagree that epidural anesthesia increases maternalcomplications.

When CSE is compared with epidural anesthesia, meta-analysis of the literature found no differences in thefrequency of hypotension or in 1-min Apgar scores; theliterature is insufficient to evaluate outcomes associatedwith the use of CSE compared with spinal anesthesia.The consultants and ASA members agree that CSE anes-thesia improves anesthesia and reduces time to skinincision when compared with epidural anesthesia. The



ASA members are equivocal, but the consultants disagreethat maternal side effects are reduced. The consultantsand ASA members both disagree that CSE improves an-esthesia compared with spinal anesthesia. The ASAmembers are equivocal, but the consultants disagree thatmaternal side effects are reduced. The consultantsstrongly agree and the ASA members agree that CSEcompared with spinal anesthesia increases flexibility ofprolonged procedures, and they both agree that the timeto skin incision is increased.

Recommendations. The decision to use a particularanesthetic technique for cesarean delivery should beindividualized, based on several factors. These includeanesthetic, obstetric, or fetal risk factors (e.g., elective vs.emergency), the preferences of the patient, and thejudgment of the anesthesiologist. Neuraxial techniquesare preferred to GA for most cesarean deliveries. Anindwelling epidural catheter may provide equivalent on-set of anesthesia compared with initiation of spinal an-esthesia for urgent cesarean delivery. If spinal anesthesiais chosen, pencil-point spinal needles should be usedinstead of cutting-bevel spinal needles. However, GAmay be the most appropriate choice in some circum-stances (e.g., profound fetal bradycardia, ruptureduterus, severe hemorrhage, severe placental abruption).Uterine displacement (usually left displacement) shouldbe maintained until delivery regardless of the anesthetictechnique used.

Intravenous Fluid Preloading. The literature sup-ports and the consultants and ASA members agree thatintravenous fluid preloading for spinal anesthesia re-duces the frequency of maternal hypotension whencompared with no fluid preloading.

Recommendations. Intravenous fluid preloading maybe used to reduce the frequency of maternal hypoten-sion after spinal anesthesia for cesarean delivery. Al-though fluid preloading reduces the frequency of mater-nal hypotension, initiation of spinal anesthesia shouldnot be delayed to administer a fixed volume of intrave-nous fluid.

Ephedrine or Phenylephrine. The literature sup-ports the administration of ephedrine and suggests thatphenylephrine is effective in reducing maternal hypoten-sion during neuraxial anesthesia for cesarean delivery.The literature is equivocal regarding the relative fre-quency of patients with breakthrough hypotensionwhen infusions of ephedrine are compared with phen-ylephrine; however, lower umbilical cord pH values arereported after ephedrine administration. The consultantsagree and the ASA members strongly agree that ephed-rine is acceptable for treating hypotension duringneuraxial anesthesia. The consultants strongly agree andthe ASA members agree that phenylephrine is an accept-able agent for the treatment of hypotension.

Recommendations. Intravenous ephedrine and phen-ylephrine are both acceptable drugs for treating hypo-

tension during neuraxial anesthesia. In the absence ofmaternal bradycardia, phenylephrine may be preferablebecause of improved fetal acid–base status in uncompli-cated pregnancies.

Neuraxial Opioids for Postoperative Analgesia.For improved postoperative analgesia after cesarean de-livery during epidural anesthesia, the literature supportsthe use of epidural opioids compared with intermittentinjections of intravenous or intramuscular opioids. How-ever, a higher frequency of pruritus was found withepidural opioids. The literature is insufficient to evaluatethe impact of epidural opioids compared with intrave-nous PCA. In addition, the literature is insufficient toevaluate spinal opioids compared with parenteral opi-oids. The consultants strongly agree and the ASA mem-bers agree that neuraxial opioids for postoperative anal-gesia improve analgesia and maternal satisfaction.

Recommendations. For postoperative analgesia afterneuraxial anesthesia for cesarean delivery, neuraxial opi-oids are preferred over intermittent injections of paren-teral opioids.

VI. Postpartum Tubal LigationThere is insufficient literature to evaluate the benefits

of neuraxial anesthesia compared with GA for postpar-tum tubal ligation. In addition, the literature is insuffi-cient to evaluate the impact of the timing of a postpar-tum tubal ligation on maternal outcome. The consultantsand ASA members both agree that neuraxial anesthesiafor postpartum tubal ligation reduces complicationscompared with GA. The ASA members are equivocal butthe consultants agree that a postpartum tubal ligationwithin 8 h of delivery does not increase maternal com-plications.

Recommendations. For postpartum tubal ligation,the patient should have no oral intake of solid foodswithin 6 – 8 h of the surgery, depending on the type offood ingested (e.g., fat content).� Aspiration prophy-laxis should be considered. Both the timing of theprocedure and the decision to use a particular anes-thetic technique (i.e., neuraxial vs. general) should beindividualized, based on anesthetic risk factors, obstet-ric risk factors (e.g., blood loss), and patient prefer-ences. However, neuraxial techniques are preferred toGA for most postpartum tubal ligations. The anesthe-siologist should be aware that gastric emptying will bedelayed in patients who have received opioids duringlabor, and that an epidural catheter placed for labormay be more likely to fail with longer postdeliverytime intervals. If a postpartum tubal ligation is to beperformed before the patient is discharged from thehospital, the procedure should not be attempted at atime when it might compromise other aspects of pa-tient care on the labor and delivery unit.



VII. Management of Obstetric and AnestheticEmergenciesResources for Management of Hemorrhagic

Emergencies. Observational studies and case reportssuggest that the availability of resources for hemorrhagicemergencies may be associated with reduced maternalcomplications. The consultants and ASA members bothstrongly agree that the availability of resources for man-aging hemorrhagic emergencies reduces maternal com-plications.

Recommendations. Institutions providing obstetriccare should have resources available to manage hemor-rhagic emergencies (table 1). In an emergency, the useof type-specific or O negative blood is acceptable. Incases of intractable hemorrhage when banked blood isnot available or the patient refuses banked blood, intra-operative cell-salvage should be considered if available.

Central Invasive Hemodynamic Monitoring.There is insufficient literature to examine whether pulmo-nary artery catheterization is associated with improved ma-ternal, fetal, or neonatal outcomes in patients with preg-nancy-related hypertensive disorders. The literature is silentregarding the management of obstetric patients with cen-tral venous catheterization alone. The consultants and ASAmembers agree that the routine use of central venous orpulmonary artery catheterization does not reduce maternalcomplications in severely preeclamptic patients.

Recommendations. The decision to perform invasivehemodynamic monitoring should be individualized andbased on clinical indications that include the patient’smedical history and cardiovascular risk factors. The TaskForce recognizes that not all practitioners have access toresources for use of central venous or pulmonary arterycatheters in obstetric units.

Equipment for Management of Airway Emergen-cies. Case reports suggest that the availability of equip-ment for the management of airway emergencies may beassociated with reduced maternal, fetal, and neonatalcomplications. The consultants and ASA members both

strongly agree that the immediate availability of equip-ment for the management of airway emergencies re-duces maternal, fetal, and neonatal complications.

Recommendations. Labor and delivery units shouldhave personnel and equipment readily available to man-age airway emergencies, to include a pulse oximeter andqualitative carbon dioxide detector, consistent with theASA Practice Guidelines for Management of the DifficultAirway.** Basic airway management equipment shouldbe immediately available during the provision ofneuraxial analgesia (table 2). In addition, portable equip-ment for difficult airway management should be readilyavailable in the operative area of labor and delivery units(table 3). The anesthesiologist should have a preformu-lated strategy for intubation of the difficult airway. Whentracheal intubation has failed, ventilation with mask andcricoid pressure, or with a laryngeal mask airway orsupraglottic airway device (e.g., Combitube®, Intubating

** American Society of Anesthesiologists Task Force on Management of theDifficult Airway: Practice guidelines for management of the difficult airway: Anupdated report. ANESTHESIOLOGY 2003; 98:1269–77.

Table 1. Suggested Resources for Obstetric HemorrhagicEmergencies

● Large-bore intravenous catheters● Fluid warmer● Forced-air body warmer● Availability of blood bank resources● Equipment for infusing intravenous fluids and blood products

rapidly. Examples include, but are not limited to, hand-squeezed fluid chambers, hand-inflated pressure bags, andautomatic infusion devices

The items listed represent suggestions. The items should be customized tomeet the specific needs, preferences, and skills of the practitioner and health-care facility.

Table 2. Suggested Resources for Airway Management duringInitial Provision of Neuraxial Anesthesia

● Laryngoscope and assorted blades● Endotracheal tubes, with stylets● Oxygen source● Suction source with tubing and catheters● Self-inflating bag and mask for positive-pressure ventilation● Medications for blood pressure support, muscle relaxation, and

hypnosis● Qualitative carbon dioxide detector● Pulse oximeter


Table 3. Suggested Contents of a Portable Storage Unit forDifficult Airway Management for Cesarean Delivery Rooms

● Rigid laryngoscope blades of alternate design and size fromthose routinely used

● Laryngeal mask airway● Endotracheal tubes of assorted size● Endotracheal tube guides. Examples include, but are not limited

to, semirigid stylets with or without a hollow core for jetventilation, light wands, and forceps designed to manipulate thedistal portion of the endotracheal tube

● Retrograde intubation equipment● At least one device suitable for emergency nonsurgical airway

ventilation. Examples include, but are not limited to, a hollow jetventilation stylet with a transtracheal jet ventilator, and asupraglottic airway device (e.g., Combitube®, Intubating LMA[Fastrach™])

● Fiberoptic intubation equipment● Equipment suitable for emergency surgical airway access (e.g.,

cricothyrotomy)● An exhaled carbon dioxide detector● Topical anesthetics and vasoconstrictors


Adapted from Practice guidelines for management of the difficult airway: Anupdated report by the American Society of Anesthesiologists Task Force onManagement of the Difficult Airway. ANESTHESIOLOGY 2003; 98:1269–77.



LMA [Fastrach™]) should be considered for maintainingan airway and ventilating the lungs. If it is not possible toventilate or awaken the patient, an airway should becreated surgically.

Cardiopulmonary Resuscitation. The literature isinsufficient to evaluate the efficacy of cardiopulmonaryresuscitation in the obstetric patient during labor anddelivery. In cases of cardiac arrest, the American HeartAssociation has stated that 4–5 min is the maximum timerescuers will have to determine whether the arrest canbe reversed by Basic Life Support and Advanced CardiacLife Support interventions.†† Delivery of the fetus mayimprove cardiopulmonary resuscitation of the mother byrelieving aortocaval compression. The American HeartAssociation further notes that “the best survival rate forinfants �24 to 25 weeks in gestation occurs when thedelivery of the infant occurs no more than 5 min afterthe mother’s heart stops beating. This typically requiresthat the provider begin the hysterotomy about 4 minafter cardiac arrest.”†† The consultants and ASA mem-bers both strongly agree that the immediate availabilityof basic and advanced life-support equipment in thelabor and delivery suite reduces maternal, fetal, andneonatal complications.

Recommendations. Basic and advanced life-supportequipment should be immediately available in the oper-ative area of labor and delivery units. If cardiac arrestoccurs during labor and delivery, standard resuscitativemeasures should be initiated. In addition, uterine dis-placement (usually left displacement) should be main-tained. If maternal circulation is not restored within 4min, cesarean delivery should be performed by the ob-stetrics team.

Appendix 1: Summary of Recommendations

I. Perianesthetic Evaluation

● Conduct a focused history and physical examination before provid-ing anesthesia care

- Maternal health and anesthetic history- Relevant obstetric history- Airway and heart and lung examination- Baseline blood pressure measurement- Back examination when neuraxial anesthesia is planned or

placed

● A communication system should be in place to encourage early andongoing contact between obstetric providers, anesthesiologists, andother members of the multidisciplinary team

● Order or require a platelet count based on a patient’s history, phys-ical examination, and clinical signs; a routine intrapartum plateletcount is not necessary in the healthy parturient

● Order or require an intrapartum blood type and screen or cross-match based on maternal history, anticipated hemorrhagic complica-tions (e.g., placenta accreta in a patient with placenta previa and

previous uterine surgery), and local institutional policies; a routineblood cross-match is not necessary for healthy and uncomplicatedparturients

● The fetal heart rate should be monitored by a qualified individualbefore and after administration of neuraxial analgesia for labor; con-tinuous electronic recording of the fetal heart rate may not benecessary in every clinical setting and may not be possible duringinitiation of neuraxial anesthesia

II. Aspiration Prophylaxis

● Oral intake of modest amounts of clear liquids may be allowed foruncomplicated laboring patients

● The uncomplicated patient undergoing elective cesarean deliverymay have modest amounts of clear liquids up to 2 h before inductionof anesthesia

● The volume of liquid ingested is less important than the presence ofparticulate matter in the liquid ingested

● Patients with additional risk factors for aspiration (e.g., morbid obe-sity, diabetes, difficult airway) or patients at increased risk for oper-ative delivery (e.g., nonreassuring fetal heart rate pattern) may havefurther restrictions of oral intake, determined on a case-by-case basis

● Solid foods should be avoided in laboring patients● Patients undergoing elective surgery (e.g., scheduled cesarean deliv-

ery or postpartum tubal ligation) should undergo a fasting period forsolids of 6–8 h depending on the type of food ingested (e.g., fatcontent)

● Before surgical procedures (i.e., cesarean delivery, postpartum tuballigation), practitioners should consider timely administration of non-particulate antacids, H2 receptor antagonists, and/or metoclopramidefor aspiration prophylaxis

III. Anesthetic Care for Labor and Delivery

Neuraxial Techniques: Availability of Resources.

● When neuraxial techniques that include local anesthetics are chosen,appropriate resources for the treatment of complications (e.g., hypo-tension, systemic toxicity, high spinal anesthesia) should be available

● If an opioid is added, treatments for related complications (e.g.,pruritus, nausea, respiratory depression) should be available

● An intravenous infusion should be established before the initiation ofneuraxial analgesia or anesthesia and maintained throughout theduration of the neuraxial analgesic or anesthetic

● Administration of a fixed volume of intravenous fluid is not requiredbefore neuraxial analgesia is initiated

Timing of Neuraxial Analgesia and Outcome of Labor.

● Neuraxial analgesia should not be withheld on the basis of achievingan arbitrary cervical dilation, and should be offered on an individu-alized basis when this service is available

● Patients may be reassured that the use of neuraxial analgesia does notincrease the incidence of cesarean delivery

Neuraxial Analgesia and Trial of Labor after Previous Cesar-ean Delivery.

● Neuraxial techniques should be offered to patients attempting vagi-nal birth after previous cesarean delivery

● For these patients, it is also appropriate to consider early placementof a neuraxial catheter that can be used later for labor analgesia or foranesthesia in the event of operative delivery

Early Insertion of Spinal or Epidural Catheter for Compli-cated Parturients.

● Early insertion of a spinal or epidural catheter for obstetric (e.g., twingestation or preeclampsia) or anesthetic indications (e.g., anticipated

†† 2005 American Heart Association guidelines for cardiopulmonary resusci-tation and emergency cardiovascular care. Circulation 2005; 112(suppl):IV1–203.



difficult airway or obesity) should be considered to reduce the needfor general anesthesia if an emergent procedure becomes necessary

- In these cases, the insertion of a spinal or epidural catheter mayprecede the onset of labor or a patient’s request for labor analgesia

Continuous Infusion Epidural (CIE) Analgesia.

● The selected analgesic/anesthetic technique should reflect patientneeds and preferences, practitioner preferences or skills, and avail-able resources

● CIE may be used for effective analgesia for labor and delivery● When a continuous epidural infusion of local anesthetic is selected,

an opioid may be added to reduce the concentration of local anes-thetic, improve the quality of analgesia, and minimize motor block

● Adequate analgesia for uncomplicated labor and delivery should beadministered with the secondary goal of producing as little motorblock as possible by using dilute concentrations of local anestheticswith opioids

● The lowest concentration of local anesthetic infusion that providesadequate maternal analgesia and satisfaction should be administered

Single-injection Spinal Opioids with or without Local Anes-thetics.

● Single-injection spinal opioids with or without local anesthetics maybe used to provide effective, although time-limited, analgesia forlabor when spontaneous vaginal delivery is anticipated

● If labor is expected to last longer than the analgesic effects of thespinal drugs chosen or if there is a good possibility of operativedelivery, a catheter technique instead of a single injection techniqueshould be considered

● A local anesthetic may be added to a spinal opioid to increaseduration and improve quality of analgesia

Pencil-point Spinal Needles.

● Pencil-point spinal needles should be used instead of cutting-bevelspinal needles to minimize the risk of post–dural puncture headache

Combined Spinal–Epidural (CSE) Anesthetics.

● CSE techniques may be used to provide effective and rapid analgesiafor labor

Patient-controlled Epidural Analgesia (PCEA).

● PCEA may be used to provide an effective and flexible approach forthe maintenance of labor analgesia

● PCEA may be preferable to CIE for providing fewer anesthetic inter-ventions, reduced dosages of local anesthetics, and less motor block-ade than fixed-rate continuous epidural infusions

● PCEA may be used with or without a background infusion

IV. Removal of Retained Placenta

● In general, there is no preferred anesthetic technique for removal ofretained placenta

- If an epidural catheter is in place and the patient is hemodynam-ically stable, epidural anesthesia is preferable

● Hemodynamic status should be assessed before administeringneuraxial anesthesia

● Aspiration prophylaxis should be considered● Sedation/analgesia should be titrated carefully due to the potential

risks of respiratory depression and pulmonary aspiration during theimmediate postpartum period

● In cases involving major maternal hemorrhage, general anesthesiawith an endotracheal tube may be preferable to neuraxial anesthesia

● Nitroglycerin may be used as an alternative to terbutaline sulfate or

general endotracheal anesthesia with halogenated agents for uterinerelaxation during removal of retained placental tissue

- Initiating treatment with incremental doses of intravenous orsublingual (i.e., metered dose spray) nitroglycerin may relax theuterus sufficiently while minimizing potential complications(e.g., hypotension)

V. Anesthetic Choices for Cesarean Delivery

● Equipment, facilities, and support personnel available in the laborand delivery operating suite should be comparable to those availablein the main operating suite

- Resources for the treatment of potential complications (e.g.,failed intubation, inadequate analgesia, hypotension, respiratorydepression, pruritus, vomiting) should be available in the laborand delivery operating suite

- Appropriate equipment and personnel should be available tocare for obstetric patients recovering from major neuraxial orgeneral anesthesia

● The decision to use a particular anesthetic technique should beindividualized based on anesthetic, obstetric, or fetal risk factors (e.g.,elective vs. emergency), the preferences of the patient, and thejudgment of the anesthesiologist

- Neuraxial techniques are preferred to general anesthesia for mostcesarean deliveries

● An indwelling epidural catheter may provide equivalent onset ofanesthesia compared with initiation of spinal anesthesia for urgentcesarean delivery

● If spinal anesthesia is chosen, pencil-point spinal needles should beused instead of cutting-bevel spinal needles

● General anesthesia may be the most appropriate choice in somecircumstances (e.g., profound fetal bradycardia, ruptured uterus, se-vere hemorrhage, severe placental abruption)

● Uterine displacement (usually left displacement) should be main-tained until delivery regardless of the anesthetic technique used

● Intravenous fluid preloading may be used to reduce the frequency ofmaternal hypotension after spinal anesthesia for cesarean delivery

● Initiation of spinal anesthesia should not be delayed to administer afixed volume of intravenous fluid

● Intravenous ephedrine and phenylephrine are both acceptable drugsfor treating hypotension during neuraxial anesthesia

- In the absence of maternal bradycardia, phenylephrine may bepreferable because of improved fetal acid–base status in uncom-plicated pregnancies

● For postoperative analgesia after neuraxial anesthesia for cesareandelivery, neuraxial opioids are preferred over intermittent injectionsof parenteral opioids

VI. Postpartum Tubal Ligation

● For postpartum tubal ligation, the patient should have no oral intakeof solid foods within 6–8 h of the surgery, depending on the type offood ingested (e.g., fat content)

● Aspiration prophylaxis should be considered● Both the timing of the procedure and the decision to use a particular

anesthetic technique (i.e., neuraxial vs. general) should be individu-alized, based on anesthetic risk factors, obstetric risk factors (e.g.,blood loss), and patient preferences

● Neuraxial techniques are preferred to general anesthesia for mostpostpartum tubal ligations

- Be aware that gastric emptying will be delayed in patients who havereceived opioids during labor and that an epidural catheter placed



for labor may be more likely to fail with longer postdelivery timeintervals

● If a postpartum tubal ligation is to be performed before the patient isdischarged from the hospital, the procedure should not be attemptedat a time when it might compromise other aspects of patient care onthe labor and delivery unit

VII. Management of Obstetric and AnestheticEmergencies

● Institutions providing obstetric care should have resources availableto manage hemorrhagic emergencies

- In an emergency, the use of type-specific or O negative blood isacceptable

- In cases of intractable hemorrhage when banked blood is notavailable or the patient refuses banked blood, intraoperativecell-salvage should be considered if available

- The decision to perform invasive hemodynamic monitoringshould be individualized and based on clinical indications thatinclude the patient’s medical history and cardiovascular riskfactors

● Labor and delivery units should have personnel and equipmentreadily available to manage airway emergencies, to include a pulseoximeter and qualitative carbon dioxide detector, consistent with theASA Practice Guidelines for Management of the Difficult Airway

- Basic airway management equipment should be immediatelyavailable during the provision of neuraxial analgesia

- Portable equipment for difficult airway management should bereadily available in the operative area of labor and delivery units

- The anesthesiologist should have a preformulated strategy forintubation of the difficult airway

- When tracheal intubation has failed, ventilation with mask andcricoid pressure, or with a laryngeal mask airway or supraglotticairway device (e.g., Combitube®, Intubating LMA [Fastrach™])should be considered for maintaining an airway and ventilatingthe lungs

- If it is not possible to ventilate or awaken the patient, an airwayshould be created surgically

● Basic and advanced life-support equipment should be immediatelyavailable in the operative area of labor and delivery units

● If cardiac arrest occurs during labor and delivery, standard resuscita-tive measures should be initiated

- Uterine displacement (usually left displacement) should be main-tained

- If maternal circulation is not restored within 4 min, cesareandelivery should be performed by the obstetrics team

Appendix 2: Methods and AnalysesThe scientific assessment of these Guidelines was based on evidence

linkages or statements regarding potential relationships between clin-ical interventions and outcomes. The interventions listed below wereexamined to assess their impact on a variety of outcomes related toobstetric anesthesia.‡‡

1. Perianesthetic Evaluationi. A directed history and physical examinationii. Communication between anesthetic and obstetric providersiii. A routine intrapartum platelet count does not reduce maternal

anesthetic complicationsiv. For suspected preeclampsia or coagulopathy an intrapartum

platelet countv. An intrapartum blood type and screen for all parturients reduces

maternal complicationsvi. For healthy and uncomplicated parturients, a blood cross-match

is unnecessaryvii. Perianesthetic recording of the fetal heart rate reduces fetal and

neonatal complications

2. Aspiration Prophylaxis in the Obstetric Patienti. Oral intake of clear liquids during labor improves patient comfort

and satisfaction but does not increase maternal complicationsii. Oral intake of solids during labor increases maternal complica-

tionsiii. A fasting period for solids of 6–8 h before an elective cesarean

reduces maternal complicationsiv. Nonparticulate antacids versus no antacids before operative pro-

cedures (excluding operative vaginal delivery) reduces maternalcomplications

3. Anesthetic Care for Labor and Delivery§§i. Neuraxial techniques

a. Prophylactic spinal or epidural catheter insertion for compli-cated parturients reduces maternal complications

b. Continuous epidural infusion of local anesthetics with orwithout opioids versus parenteral opioids

c. Continuous epidural infusion of local anesthetics with orwithout opioids versus spinal opioids with or without localanesthetics

d. Induction of epidural analgesia using local anesthetics withopioids versus equal concentrations of epidural local anes-thetics without opioids

e. Induction of epidural analgesia using local anesthetics withopioids versus higher concentrations of epidural local anes-thetics without opioids

f. Maintenance of epidural infusion of lower concentrations oflocal anesthetics with opioids versus higher concentrationsof local anesthetics without opioids (e.g., bupivacaine con-centrations � 0.125% with opioids vs. concentrations �0.125% without opioids)

g. Single-injection spinal opioids with or without local anesthet-ics versus parenteral opioids

h. Single-injection spinal opioids with local anesthetics versusspinal opioids without local anesthetics

ii. Combined spinal–epidural (CSE) techniquesa. CSE local anesthetics with opioids versus epidural local an-

esthetics with opioidsiii. Patient-controlled epidural analgesia (PCEA)

a. PCEA versus continuous infusion epiduralsb. PCEA with a background infusion versus PCEA without a

background infusioniv. Neuraxial analgesia, timing of initiation, and progress of labor

a. Administering epidural analgesia at cervical dilations of � 5cm (vs. � 5 cm)

b. Neuraxial techniques for patients attempting vaginal birthafter previous cesarean delivery

4. Removal of Retained Placentai. If an epidural catheter is in situ and the patient is hemodynamically

stable, epidural anesthesia is preferred over general or spinal anes-thesia to improve the success at removing retained placenta

‡‡ Unless otherwise specified, outcomes for the listed interventions refer tothe reduction of maternal, fetal, and neonatal complications.

§§ Additional outcomes include improved analgesia, analgesic use, maternalcomfort, and satisfaction.



ii. In cases involving major maternal hemorrhage, general anes-thesia is preferred over neuraxial anesthesia to reduce maternalcomplications

iii. Administration of nitroglycerin for uterine relaxation improvessuccess at removing retained placenta

5. Anesthetic Choices for Cesarean Deliveryi. Equipment, facilities, and support personnel available in the

labor and delivery suite should be comparable to that availablein the main operating suite

ii. General anesthesia versus epidural anesthesiaiii. General anesthesia versus spinal anesthesiaiv. Epidural anesthesia versus spinal anesthesiav. CSE anesthesia versus epidural anesthesiavi. CSE anesthesia versus spinal anesthesiavii. Use of pencil-point spinal needles versus cutting-bevel spinal

needles reduces maternal complicationsviii. Intravenous fluid preloading versus no intravenous fluid pre-

loading for spinal anesthesia reduces maternal hypotensionix. Ephedrine or phenylephrine reduces maternal hypotension dur-

ing neuraxial anesthesiax. Neuraxial opioids versus parenteral opioids for postoperative

analgesia after neuraxial anesthesia for cesarean delivery

6. Postpartum Tubal Ligationi. Neuraxial anesthesia versus general anesthesia

ii. A postpartum tubal ligation within 8 h of delivery does notincrease maternal complications

7. Management of Complicationsi. Availability of resources for management of hemorrhagic emer-

genciesii. Immediate availability of equipment for management of airway

emergenciesiii. Immediate availability of basic and advanced life-support equip-

ment in the labor and delivery suiteiv. Invasive hemodynamic monitoring for severely preeclamptic

patientsScientific evidence was derived from aggregated research literature,

and opinion-based evidence was obtained from surveys, open presen-tations, and other activities (e.g., Internet posting). For purposes ofliterature aggregation, potentially relevant clinical studies were identi-fied via electronic and manual searches of the literature. The elec-tronic and manual searches covered a 67-yr period from 1940 through2006. More than 4,000 citations were initially identified, yielding a totalof 2,986 nonoverlapping articles that addressed topics related to theevidence linkages. After review of the articles, 2,549 studies did notprovide direct evidence and were subsequently eliminated. A total of437 articles contained direct linkage-related evidence.

Initially, each pertinent outcome reported in a study was classified assupporting an evidence linkage, refuting a linkage, or equivocal. Theresults were then summarized to obtain a directional assessment foreach evidence linkage before conducting a formal meta-analysis. Liter-ature pertaining to 11 evidence linkages contained enough studieswith well-defined experimental designs and statistical information suf-ficient for meta-analyses. These linkages were (1) nonparticulate ant-acids versus no antacids, (2) continuous epidural infusion of localanesthetics with or without opioids versus parenteral opioids, (3)induction of epidural analgesia using local anesthetics with opioidsversus equal concentrations of epidural local anesthetics without opi-oids, (4) maintenance of epidural infusion of lower concentrations oflocal anesthetics with opioids versus higher concentrations of localanesthetics without opioids, (5) CSE local anesthetics with opioidsversus epidural local anesthetics with opioids, (6) PCEA versus con-

tinuous infusion epidurals, (7) general anesthesia versus epidural an-esthesia for cesarean delivery, (8) CSE anesthesia versus epidural an-esthesia for cesarean delivery, (9) use of pencil-point spinal needlesversus cutting-bevel spinal needles, (10) ephedrine or phenylephrinereduces maternal hypotension during neuraxial anesthesia, and (11)neuraxial opioids versus parenteral opioids for postoperative analgesiaafter neuraxial anesthesia for cesarean delivery.

General variance-based effect-size estimates or combined probabilitytests were obtained for continuous outcome measures, and Mantel-Haenszel odds ratios were obtained for dichotomous outcome measures.Two combined probability tests were used as follows: (1) the Fishercombined test, producing chi-square values based on logarithmic trans-formations of the reported P values from the independent studies, and (2)the Stouffer combined test, providing weighted representation of thestudies by weighting each of the standard normal deviates by the size ofthe sample. An odds ratio procedure based on the Mantel-Haenszelmethod for combining study results using 2 � 2 tables was used withoutcome frequency information. An acceptable significance level was setat P � 0.01 (one-tailed). Tests for heterogeneity of the independentstudies were conducted to assure consistency among the study results.DerSimonian-Laird random-effects odds ratios were obtained when signif-icant heterogeneity was found (P � 0.01). To control for potential pub-lishing bias, a “fail-safe n” value was calculated. No search for unpublishedstudies was conducted, and no reliability tests for locating research resultswere done.

Meta-analytic results are reported in table 4. To be accepted assignificant findings, Mantel-Haenszel odds ratios must agree with com-bined test results whenever both types of data are assessed. In theabsence of Mantel-Haenszel odds ratios, findings from both the Fisherand weighted Stouffer combined tests must agree with each other tobe acceptable as significant.

Interobserver agreement among Task Force members and two meth-odologists was established by interrater reliability testing. Agreementlevels using a � statistic for two-rater agreement pairs were as follows:(1) type of study design, � � 0.83–0.94; (2) type of analysis, � �0.71–0.93; (3) evidence linkage assignment, � � 0.87–1.00; and (4)literature inclusion for database, � � 0.74–1.00. Three-rater chance-corrected agreement values were (1) study design, Sav � 0.884, Var(Sav) � 0.004; (2) type of analysis, Sav � 0.805, Var (Sav) � 0.009; (3)linkage assignment, Sav � 0.911, Var (Sav) � 0.002; and (4) literaturedatabase inclusion, Sav � 0.660, Var (Sav) � 0.024. These valuesrepresent moderate to high levels of agreement.

Consensus was obtained from multiple sources, including (1) surveyopinion from consultants who were selected based on their knowledgeor expertise in obstetric anesthesia or maternal and fetal medicine, (2)survey opinions solicited from active members of the ASA, (3) testi-mony from attendees of publicly held open forums at two nationalanesthesia meetings, (4) Internet commentary, and (5) Task Forceopinion and interpretation. The survey rate of return was 75% (n � 76of 102) for the consultants, and 2,326 surveys were received fromactive ASA members. Results of the surveys are reported in tables 5 and6 and in the text of the Guidelines.

The consultants were asked to indicate which, if any, of the evi-dence linkages would change their clinical practices if the Guidelineswere instituted. The rate of return was 35% (n � 36). The percent ofresponding consultants expecting no change associated with eachlinkage were as follows: perianesthetic evaluation—97%; aspirationprophylaxis—83%; anesthetic care for labor and delivery—89%; re-moval of retained placenta—97%; anesthetic choices for cesarean de-livery—97%; postpartum tubal ligation—97%; and management ofcomplications—94%. Ninety-seven percent of the respondents indi-cated that the Guidelines would have no effect on the amount of timespent on a typical case. One respondent indicated that there would bean increase of 5 min in the amount of time spent on a typical case withthe implementation of these Guidelines.



Table 4. Meta-analysis Summary

Heterogeneity

Linkages n

FisherChi-

square P

WeightedStouffer

Zc PEffectSize

Mantel-Haenszel

OR CI SignificanceEffectSize

Aspiration Prophylaxis

Nonparticulate antacids vs. no antacids

Gastric pH* 5 66.80 0.001 9.78 0.001 0.88 — — 0.001 0.001

Metoclopramide vs. no metoclopramide

Nausea 6 — — — — — 0.25 0.14–0.46 — NS

Vomiting 6 — — — — — 0.36 0.19–0.68 — NS

Anesthetic Care for Labor and Vaginal Delivery

CIE local anesthetics � opioids vs. IV opioids

Duration of labor 1st stage 5 50.19 0.001 5.42 0.001 0.15 — — NS NS

Duration of labor 2nd stage 7 67.53 0.001 4.84 0.001 0.21 — — NS 0.001

Spontaneous delivery 8 — — — — — 0.53 0.42–0.68 — NS

Cesarean delivery† 8 — — — — — 0.88 0.50–1.47 — 0.01

Fetal acidosis 5 — — — — — 0.71 0.51–0.98 — NS

1-min Apgar 5 — — — — — 1.62 1.03–2.54 — NS

5-min Apgar 5 — — — — — 1.17 0.41–3.32 — NS

Epidural induction LA�O vs. equal LA doses

Analgesia (mean, SD) 6 91.21 0.001 17.70 0.001 0.99 — — 0.001 0.001

Analgesia (pain relief) 5 — — — — — 4.03 2.14–7.56 — NS

Duration of labor 5 38.62 0.001 0.04 0.480 0.01 — — 0.001 0.001


Hypotension 8 — — — — — 0.79 0.44–1.44 — NS

Motor block* 5 — — — — — 0.44 0.24–0.81 — NS

Pruritus 7 — — — — — 6.15 3.22–11.74 — NS

1-min Apgar 6 — — — — — 0.82 0.45–1.51 — NS

Epidural maintenance LA�O vs. higher LA doses

Duration of labor 5 19.82 0.030 1.99 0.020 0.05 — — NS NS


Motor block 6 — — — — — 0.29 0.21–0.40 — NS

1-min Apgar 6 — — — — — 0.94 0.60–1.47 — NS

Pencil-point vs. cutting-bevel spinal needles

Post–dural puncture headache 5 — — — — — 0.34 0.18–0.63 — NS

CSE LA�O vs. epidural LA�O

Analgesia (pain relief)† 7 — — — — — 1.16 0.62–1.85 — 0.010

Satisfaction with analgesia 5 — — — — — 1.45 0.89–2.34 — NS

Analgesia (time to onset) 5 57.80 0.001 �13.33 0.001 0.90 — — 0.001 0.001


Hypotension 6 — — — — — 1.76 0.73–4.26 — NS

Motor block 7 — — — — — 1.20 0.90–1.60 — NS

Nausea 5 — — — — — 1.22 0.63–2.36 — NS

Pruritus† 9 — — — — — 4.86 1.63–14.65 — 0.001

Motor block 7 — — — — — 1.20 0.90–1.60 NS

Fetal heart rate changes 6 — — — — — 1.25 0.92–1.70 — NS

1-min Apgar 6 — — — — — 1.16 0.76–1.78 — NS

5-min Apgar 6 — — — — — 1.36 0.52–3.56 — NS

PCEA vs. CIE

Pain relief/score 5 21.78 0.020 0.17 0.433 0.04 — — NS NS

Analgesic use 7 84.98 0.001 10.74 0.001 0.85 — — 0.001 0.001

Duration of labor 1st stage 5 42.42 0.001 5.24 0.001 0.44 — — 0.008 0.001

Duration of labor 2nd stage 6 43.08 0.001 2.01 0.022 0.18 — — 0.001 0.001


Motor block† 7 — — — — — 0.52 0.15–3.44 — 0.010

1-min Apgar 6 — — — — — 0.63 0.27–1.50 — NS

PCEA with background infusion vs. PCEA

Analgesia (pain relief) 5 — — — — — 3.33 1.87–5.92 — NS


Motor block 5 — — — — — 1.18 0.47–2.97 — NS

(continued)



Table 4. Continued

Heterogeneity

Linkages n

FisherChi-

square P

WeightedStouffer

Zc PEffectSize

Mantel-Haenszel

OR CI SignificanceEffectSize

Early vs. late epidural

Cesarean delivery 5 — — — — — 0.95 0.67–1.35 — NS

Anesthetic Choices for Cesarean Delivery

GA vs. epidural

Umbilical pH 5 49.04 0.001 0.52 0.300 0.37 — — 0.001 0.001

1-min Apgar 5 49.04 0.001 �2.72 0.003 0.01 — — 0.010 0.010

5-min Apgar 5 28.40 0.005 �2.95 0.002 0.08 — — NS NS

CSE vs. epidural

Hypotension 5 — — — — — 0.92 0.44–1.94 — NS

Umbilical pH 5 55.91 0.001 1.80 0.036 0.11 — — 0.001 0.001

1-min Apgar 5 — — — — — 0.55 0.22–1.52 — NS

Fluid preloading vs. no preloading

Hypotension* 6 — — — — — 0.46 0.29–0.73 — NS

Ephedrine vs. placebo

Hypotension 7 — — — — — 0.26 0.14–0.48 — NS

Ephedrine vs. phenylephrine

Hypotension 6 — — — — — 1.74 0.97–3.12 — NS

Umbilical pH 6 59.68 0.001 �7.55 0.001 0.71 — — 0.001 0.001

Neuraxial vs. parenteral O for postoperative analgesia

Analgesia 7 75.12 0.001 5.82 0.001 0.61 — — 0.001 0.001

Nausea 9 — — — — — 1.13 0.57–2.22 — NS

Vomiting 5 — — — — — 1.02 0.36–2.87 — NS

Pruritus 9 — — — — — 6.23 3.32–11.68 — NS

* Nonrandomized comparative studies included in analysis. † DerSimonian-Laird random effects odds ratio (OR).

CI � confidence interval; CIE � continuous infusion epidural; CSE � combined spinal–epidural; GA � general anesthesia; IV � intravenous; LA � localanesthetics; LA�O � local anesthetics with opioids; NS � not significant; O � opioids; PCEA � patient-controlled epidural analgesia.



Table 5. Consultant Survey Responses

Percent Responding to Each Item

nStronglyAgree Agree Uncertain Disagree

StronglyDisagree

Perianesthetic Evaluation

1. Directed history and physical examination reduces maternal, fetal, and neonatal complications 76 72.4* 26.3 1.3 0.0 0.0

2. Communication between anesthetic and obstetric providers reduces maternal, fetal, and neonatal

complications

76 89.5* 10.5 0.0 0.0 0.0

3. A routine intrapartum platelet count does not reduce maternal anesthetic complications 75 36.0 44.0* 8.0 10.7 1.3

4. An intrapartum platelet count reduces maternal anesthetic complications:

For suspected preeclampsia 76 46.1 36.8* 9.2 7.9 0.0

For suspected coagulopathy 76 59.2* 32.9 5.3 2.6 0.0

5. All parturients should have an intrapartum blood sample sent to the blood bank to reduce maternal

complications

76 21.1 32.9* 17.1 26.3 2.6

6. Perianesthetic recording of the fetal heart rate reduces fetal and neonatal complications 76 18.4 59.2* 13.2 9.2 0.0


7a. Oral intake of clear liquids during labor improves patient comfort and satisfaction 76 32.9 60.5* 1.3 3.9 1.3

7b. Oral intake of clear liquids during labor does not increase maternal complications 75 16.0 45.3* 22.7 12.0 4.0

8a. Oral intake of solids during labor increases maternal complications 76 47.4 32.9* 10.5 5.3 3.9

8b. The patient undergoing elective cesarean delivery should undergo a fasting period for solids of 6–8 h

depending on the type of food ingested (e.g., fat content)

76 65.8* 30.3 3.9 0.0 0.0

8c. The patient undergoing elective postpartum tubal ligation should undergo a fasting period for solids of

6–8 h depending on the type of food ingested (e.g., fat content)

76 56.6* 27.6 9.2 5.3 1.3

9. Administration of a nonparticulate antacid before operative procedures reduces maternal complications 75 29.3 45.3* 18.7 5.3 1.3

Anesthetic Care for Labor and Delivery

Neuraxial techniques:

10. Prophylactic spinal or epidural catheter insertion for complicated parturients reduces maternal

complications

75 42.7 40.0* 16.0 1.3 0.0

11. Continuous epidural infusion using local anesthetics with or without opioids vs. parenteral opioids:

Improves analgesia 75 84.0* 16.0 0.0 0.0 0.0

Increases the duration of labor 75 4.0 24.0 21.3 36.0* 14.7

Decreases the chance of spontaneous delivery 74 4.1 16.2 12.2 41.9* 25.7

Increases maternal side effects 75 1.3 8.0 14.7 42.7* 33.3

Increases fetal and neonatal side effects 75 0.0 4.0 6.7 46.7* 42.7

12. Continuous epidural infusion using local anesthetics with or without opioids vs. spinal opioids with or

without local anesthetics:

Improves analgesia 74 12.2 25.7 20.3* 35.1 6.8

Increases the duration of labor 75 0.0 16.0 37.3* 34.7 12.0


Increases maternal motor block 74 5.4 41.9 17.6* 28.4 6.8



13a. Induction of epidural analgesia using local anesthetics with opioids vs. epidural analgesia with equal

concentrations of local anesthetics without opioids:




13b. Induction of epidural analgesia using low-dose local anesthetics with opioids vs. higher concentrations of

epidural local anesthetics without opioids:

Improves analgesia 74 23.0 21.6 21.6* 32.4 1.4



14a. Maintenance of epidural infusion of lower concentrations of local anesthetics with opioids vs. higher


Improves analgesia 74 21.6 28.4* 27.0 23.0 0.0

Reduces the duration of labor 74 4.1 35.1 40.5* 17.6 2.7

Improves the chance of spontaneous delivery 74 12.2 60.8* 14.9 10.8 1.4

Reduces maternal motor block 74 51.4* 43.2 5.4 0.0 0.0

Reduces maternal side effects 74 16.2 44.6* 23.0 16.2 0.0

Reduces fetal and neonatal side effects 74 8.1 24.3 32.4* 32.4 2.7

14b. Maintenance of epidural analgesia using bupivacaine < 0.125% with opioids vs. bupivacaine

concentrations > 0.125% without opioids:



Improves the chance of spontaneous delivery 74 14.9 52.7* 24.3 8.1 0.0

Reduces maternal motor block 74 40.5 51.4* 5.4 2.7 0.0

Reduces maternal side effects 74 14.9 41.9* 25.7 17.6 0.0

Reduces fetal and neonatal side effects 74 4.1 31.1 35.1* 28.4 1.4

(continued)



Table 5. Continued



StronglyDisagree

15. Single-injection spinal opioids with or without local anesthetics vs. parenteral opioids:

Improve analgesia 74 68.9* 28.4 2.7 0.0 0.0

Increase the duration of labor 74 1.4 5.4 20.3 51.4* 21.6

Decrease the chance of spontaneous delivery 74 1.4 8.1 10.8 54.1* 25.7

Increase maternal side effects 74 0.0 25.7 25.7* 36.5 12.2

Increase fetal and neonatal side effects 74 0.0 9.5 16.2 51.4* 23.0

16. Single-injection spinal opioids with local anesthetics vs. spinal opioids without local anesthetics:

Improve analgesia 74 44.6 44.6* 4.1 5.4 1.4

Increase the duration of labor 74 2.7 6.8 25.7 51.4* 13.5


Increase maternal motor block 74 13.5 54.1* 9.5 21.6 1.4

Increase maternal side effects 74 1.4 27.0 23.0* 40.5 8.1


Combined spinal–epidural (CSE) techniques:

17. CSE local anesthetics with opioids vs. epidural local anesthetics with opioids:

Improve early analgesia 74 48.6 35.1* 5.4 10.8 0.0

Improve overall analgesia 74 18.9 31.1 23.0* 25.7 1.4

Decrease the duration of labor 74 4.1 18.9 47.3* 29.7 0.0


Reduce maternal motor block 74 5.4 37.8 24.3* 32.4 0.0

Increase maternal side effects 74 0.0 18.9 24.3 54.1* 2.7


Patient-controlled epidural analgesia (PCEA):

18. PCEA vs. continuous infusion epidurals:


Improves maternal satisfaction 75 41.3 46.7* 8.0 2.7 1.3

Reduces the need for anesthetic interventions 75 42.7 36.0* 10.7 9.3 1.3

Increases the chance of spontaneous delivery 74 4.1 13.5 45.9* 33.8 2.7

Reduces maternal motor block 75 9.3 38.7 24.0* 26.7 1.3

Decreases maternal side effects 75 5.3 28.0 30.7* 34.7 1.3

19. PCEA with a background infusion vs. PCEA without a background infusion:


Improves maternal satisfaction 74 24.3 43.2* 23.0 9.5 0.0

Reduces the need for anesthetic interventions 74 21.6 56.8* 12.2 9.5 0.0


Increases maternal motor block 74 1.4 39.2 25.7* 32.4 1.4


Neuraxial Analgesia, Timing of Initiation, and Progress of Labor

20. Administering epidural analgesia at cervical dilations of � 5 centimeters (vs. � 5 cm):



Improves the chance of spontaneous delivery 74 0.0 10.8 48.6* 32.4 8.1

Increases maternal motor block 75 1.3 28.0 17.3 42.7* 10.7



21. Neuraxial techniques improve the likelihood of vaginal delivery for patients attempting vaginal birth after

previous cesarean delivery

75 21.3 36.0* 33.3 8.0 1.3

Removal of Retained Placenta

22. If an epidural catheter is in situ and the patient is hemodynamically stable, epidural anesthesia is the

preferred technique

75 66.7* 30.7 2.7 0.0 0.0

23. In cases involving major maternal hemorrhage, a general endotracheal anesthetic is preferred over

neuraxial anesthesia

75 30.7 48.0* 12.0 6.7 2.9

24. Administration of nitroglycerin for uterine relaxation improves success at removing retained placenta 75 34.7 48.0* 9.3 6.7 1.3


25. Equipment, facilities, and support personnel available in the labor and delivery operating suite should be

comparable to that available in the main operating suite

74 82.4* 16.2 1.4 0.0 0.0

26. General anesthesia vs. epidural anesthesia:

Reduces time to skin incision 74 40.5 37.8* 8.1 9.5 4.1

Increases maternal complications 74 37.8 47.3* 9.5 5.4 0.0

Increases fetal and neonatal complications 74 14.9 28.4 24.3* 29.7 2.7

27. General anesthesia vs. spinal anesthesia:


Increases maternal complications 74 33.8 50.0* 6.8 8.1 1.4

Increases fetal and neonatal complications 74 12.2 28.4 23.0* 33.8 2.7

(continued)



Table 5. Continued



StronglyDisagree

28. Epidural anesthesia vs. spinal anesthesia:

Increases time to skin incision 74 43.2 43.2* 8.1 5.4 0.0

Reduces quality of anesthesia 74 12.2 56.8* 9.5 17.6 4.1

Increases maternal complications 74 1.4 13.5 28.4 48.6* 8.1

29. CSE anesthesia vs. epidural anesthesia:

Improves anesthesia 73 20.5 47.9* 20.5 11.0 0.0


Reduces maternal side effects 73 2.7 12.3 30.1 52.1* 2.7

30. CSE anesthesia vs. spinal anesthesia:

Improves anesthesia 72 1.4 15.3 25.0 52.8* 5.6

Increases flexibility for prolonged procedures 73 61.6* 32.9 4.1 1.4 0.0

Increases time to skin incision 73 6.8 49.3* 17.8 21.9 4.1

Reduces maternal side effects 73 1.4 11.0 37.0 47.9* 2.9

31. Use of pencil-point spinal needles vs. cutting-bevel spinal needles reduces maternal complications 73 75.3* 23.3 1.4 0.0 0.0

32. Intravenous fluid preloading vs. no intravenous fluid preloading for spinal anesthesia reduces maternal

hypotension

73 30.1 46.6* 12.3 9.6 1.4

33a. Intravenous ephedrine is an acceptable agent to treat hypotension during neuraxial anesthesia 75 48.0 49.3* 1.3 1.3 0.0

33b. Intravenous phenylephrine is an acceptable agent to treat hypotension during neuraxial anesthesia 75 50.7* 40.0 6.7 2.7 0.0

34. Neuraxial opioids vs. parenteral opioids for postoperative analgesia after regional anesthesia for cesarean

delivery:


Improves maternal satisfaction 69 52.2* 33.3 8.7 5.8 0.0

Postpartum Tubal Ligation

35. Neuraxial vs. general anesthesia reduces maternal complications 70 24.3 58.6* 12.9 2.9 1.4

36. An immediate (� 8 h) postpartum tubal ligation does not increase maternal complications 70 14.3 50.0* 22.9 11.4 1.4

Management of Complications

37. Availability of resources for management of hemorrhagic emergencies reduces maternal complications 70 74.3* 25.7 0.0 0.0 0.0

38. Immediate availability of equipment for management of airway emergencies reduces maternal, fetal, and


70 80.0* 20.0 0.0 0.0 0.0

39. Immediate availability of basic and advanced life-support equipment in the labor and delivery suite

reduces maternal, fetal, and neonatal complications

70 78.6* 21.4 0.0 0.0 0.0

40. Routine use of central venous or pulmonary artery catheterization reduces maternal complications in

severely preeclamptic patients

70 0.0 10.0 12.9 55.7* 21.4

* Median.

n � number of consultants who responded to each item.



Table 6. ASA Membership Survey Responses



StronglyDisagree

Perianesthetic Evaluation

1. Directed history and physical examination reduces maternal, fetal, and neonatal complications 2,324 57.5* 38.3 3.0 1.0 0.1

2. Communication between anesthetic and obstetric providers reduces maternal, fetal, and neonatal

complications

2,321 77.9* 21.3 0.6 0.2 0.1

3. A routine intrapartum platelet count does not reduce maternal anesthetic complications 2,320 11.9 36.2 22.3* 23.6 6.0

4. An intrapartum platelet count reduces maternal anesthetic complications:

For suspected preeclampsia 2,326 35.8 47.9* 11.4 4.3 0.6

For suspected coagulopathy 2,323 46.8 43.5* 6.2 2.8 0.6

5. All parturients should have an intrapartum blood sample sent to the blood bank to reduce maternal

complications

2,317 22.1 34.3* 19.0 21.9 2.7

6. Perianesthetic recording of the fetal heart rate reduces fetal and neonatal complications 2,319 25.0 38.5* 25.2 9.9 1.6


7a. Oral intake of clear liquids during labor improves patient comfort and satisfaction 2,283 15.4 65.5* 12.1 6.2 0.8

7b. Oral intake of clear liquids during labor does not increase maternal complications 2,285 6.7 40.2 23.6* 23.5 6.0

8a. Oral intake of solids during labor increases maternal complications 2,284 48.2 38.0* 9.9 2.8 1.1

8b. The patient undergoing elective cesarean delivery should undergo a fasting period for solids of 6–8 h

depending on the type of food ingested (e.g., fat content)

2,283 66.8* 30.3 1.1 1.3 0.5

8c. The patient undergoing elective postpartum tubal ligation should undergo a fasting period for solids of

6–8 h depending on the type of food ingested (e.g., fat content)

2,281 66.9* 30.2 1.1 1.4 0.4

9. Administration of a nonparticulate antacid before operative procedures reduces maternal complications 2,281 24.5 43.3* 24.0 7.2 1.1

Anesthetic Care for Labor and Delivery

Neuraxial techniques:

10. Prophylactic spinal or epidural catheter insertion for complicated parturients reduces maternal

complications

2,071 17.6 42.4* 26.9 11.8 1.2

11. Continuous epidural infusion using local anesthetics with or without opioids vs. parenteral opioids:

Improves analgesia 2,170 73.6* 25.1 0.8 0.4 0.1

Increases the duration of labor 2,174 1.2 14.4 19.0 51.7* 13.8

Decreases the chance of spontaneous delivery 2,171 0.8 7.4 16.9 53.3* 21.6

Increases maternal side effects 2,169 0.6 12.0 9.8 58.9* 18.7

Increases fetal and neonatal side effects 2,168 0.3 3.0 7.5 61.3* 27.9

12. Continuous epidural infusion using local anesthetics with or without opioids vs. spinal opioids with or

without local anesthetics:

Improves analgesia 2,160 17.4 36.5* 24.8 20.2 1.2

Increases the duration of labor 2,161 0.8 8.9 31.8 49.7* 8.8

Decreases the chance of spontaneous delivery 2,158 0.6 5.8 27.7 53.7* 12.3

Increases maternal motor block 2,149 3.7 36.0 16.1* 38.7 5.4



13a. Induction of epidural analgesia using local anesthetics with opioids vs. epidural analgesia with equal



Increases maternal side effects 2,150 2.6 38.0 12.8* 40.4 6.2


13b. Induction of epidural analgesia using low-dose local anesthetics with opioids vs. higher concentrations

of epidural local anesthetics without opioids:

Improves analgesia 2,155 13.1 31.7 26.9* 26.6 1.7



14a. Maintenance of epidural infusion of lower concentrations of local anesthetics with opioids vs. higher



Reduces the duration of labor 1,980 3.9 28.0 44.9* 21.6 1.6

Improves the chance of spontaneous delivery 1,977 6.9 41.1 35.9* 15.1 1.0

Reduces maternal motor block 1,977 31.3 63.0* 2.9 2.4 0.4

Reduces maternal side effects 1,971 11.4 47.1* 26.8 14.0 0.9

Reduces fetal and neonatal side effects 1,972 7.4 34.4 38.1* 18.6 1.5

14b. Maintenance of epidural analgesia using bupivacaine < 0.125% with opioids vs. bupivacaine

concentrations > 0.125% without opioids:




Reduces maternal motor block 1,967 23.4 63.7* 5.3 6.5 1.1

Reduces maternal side effects 1,960 9.2 44.7* 27.0 18.1 1.0

Reduces fetal and neonatal side effects 1,957 6.3 31.3 39.0* 21.6 1.8

(continued)



Table 6. Continued



StronglyDisagree

15. Single-injection spinal opioids with or without local anesthetics vs. parenteral opioids:

Improve analgesia 1,966 36.9 50.2* 8.9 3.6 0.5

Increase the duration of labor 1,963 0.4 2.7 31.5 55.8* 9.6

Decrease the chance of spontaneous delivery 1,967 0.4 2.8 27.9 58.3* 10.7

Increase maternal side effects 1,958 2.1 23.7 23.1 45.1* 5.8

Increase fetal and neonatal side effects 1,960 0.7 7.7 25.6 55.9* 10.2

16. Single-injection spinal opioids with local anesthetics vs. spinal opioids without local anesthetics:

Improve analgesia 1,961 29.2 55.6* 9.4 5.5 0.4

Increase the duration of labor 1,960 1.1 10.2 43.0* 41.2 4.6


Increase maternal motor block 1,955 12.5 59.0* 11.6 15.4 1.4

Increase maternal side effects 1,951 2.5 33.1 28.9* 33.1 2.4


Combined spinal–epidural (CSE) techniques:

17. CSE local anesthetics with opioids vs. epidural local anesthetics with opioids:

Improve early analgesia 1,887 31.1 44.6* 11.7 11.2 1.5

Improve overall analgesia 1,884 14.0 26.8 27.1* 28.7 3.5

Decrease the duration of labor 1,884 1.5 8.8 48.2* 38.2 3.4


Reduce maternal motor block 1,880 4.0 23.8 27.6* 41.0 3.5

Increase maternal side effects 1,877 2.0 28.2 33.0* 34.2 2.6


Patient-controlled epidural analgesia (PCEA):

18. PCEA vs. continuous infusion epidurals:


Improves maternal satisfaction 1,848 27.8 46.5* 19.6 5.6 0.5

Reduces the need for anesthetic interventions 1,849 22.4 42.9* 21.4 12.1 1.1

Increases the chance of spontaneous delivery 1,845 2.6 12.1 56.9* 26.4 2.1

Reduces maternal motor block 1,846 4.3 34.1 40.4* 20.5 0.8

Decreases maternal side effects 1,838 3.8 27.0 46.5* 21.9 0.9

19. PCEA with a background infusion vs. PCEA without a background infusion:



Reduces the need for anesthetic interventions 1,829 22.4 46.0* 24.7 6.6 0.3

Decreases the chance of spontaneous delivery 1,831 0.8 4.3 48.6* 41.6 4.8

Increases maternal motor block 1,837 1.0 27.3 40.8* 28.6 2.2

Increases maternal side effects 1,828 0.8 12.8 43.5* 39.6 3.3

Neuraxial Analgesia, Timing of Initiation, and Progress of Labor

20. Administering epidural analgesia at cervical dilations of � 5 centimeters (vs. � 5 cm):




Increases maternal motor block 1,819 0.9 20.5 21.2 53.4* 4.0



21. Neuraxial techniques improve the likelihood of vaginal delivery for patients attempting vaginal birth after

previous cesarean delivery

1,816 8.7 41.6* 37.9 10.1 1.7

Removal of Retained Placenta

22. If an epidural catheter is in situ and the patient is hemodynamically stable, epidural anesthesia is the

preferred technique

1,821 30.8 59.5* 4.3 4.4 1.0

23. In cases involving major maternal hemorrhage, a general endotracheal anesthetic is preferred over

neuraxial anesthesia

1,823 36.0 48.8* 6.9 7.5 0.9

24. Administration of nitroglycerin for uterine relaxation improves success at removing retained placenta 1,812 15.6 54.1* 26.4 3.5 0.4


25. Equipment, facilities, and support personnel available in the labor and delivery operating suite should be

comparable to that available in the main operating suite

1,815 78.3* 20.3 0.5 0.9 0.1

26. General anesthesia vs. epidural anesthesia:

Reduces time to skin incision 1,826 30.9 46.3* 6.8 14.3 1.6

Increases maternal complications 1,824 27.3 50.1* 10.9 9.6 2.0

Increases fetal and neonatal complications 1,825 13.9 37.5* 23.2 22.8 2.6

27. General anesthesia vs. spinal anesthesia:


Increases maternal complications 1,815 23.8 49.6* 10.7 13.8 2.0

Increases fetal and neonatal complications 1,803 13.6 37.2* 21.9 24.6 2.8

(continued)



Table 6. Continued



StronglyDisagree

28. Epidural anesthesia vs. spinal anesthesia:

Increases time to skin incision 1,823 32.1 54.3* 3.8 8.7 1.0

Reduces quality of anesthesia 1,821 15.0 51.0* 8.8 21.5 3.6

Increases maternal complications 1,816 1.2 8.8 24.5 59.1* 6.4

29. CSE anesthesia vs. epidural anesthesia:

Improves anesthesia 1,794 18.7 45.4* 22.6 12.5 0.9


Reduces maternal side effects 1,791 2.6 9.4 42.4* 43.3 2.4

30. CSE anesthesia vs. spinal anesthesia:

Improves anesthesia 1,800 4.4 14.3 28.5 48.2* 4.6

Increases flexibility for prolonged procedures 1,808 32.1 54.8* 10.2 2.5 0.4

Increases time to skin incision 1,804 9.9 48.7* 17.7 22.1 1.7

Reduces maternal side effects 1,802 0.9 7.7 41.6* 46.1 3.7

31. Use of pencil-point spinal needles vs. cutting-bevel spinal needles reduces maternal complications 1,819 51.7* 39.4 5.7 2.9 0.4

32. Intravenous fluid preloading vs. no intravenous fluid preloading for spinal anesthesia reduces maternal

hypotension

1,817 40.0 43.0* 9.0 6.5 1.4

33a. Intravenous ephedrine is an acceptable agent to treat hypotension during neuraxial anesthesia 1,819 50.7* 47.3 0.9 1.0 0.1

33b. Intravenous phenylephrine is an acceptable agent to treat hypotension during neuraxial anesthesia 1,820 31.9 52.8* 6.0 8.0 1.3

34. Neuraxial opioids vs. parenteral opioids for postoperative analgesia after regional anesthesia for cesarean

delivery:



Postpartum Tubal Ligation

35. Neuraxial vs. general anesthesia reduces maternal complications 1,812 28.8 45.0* 15.2 9.4 1.6

36. An immediate (� 8 h) postpartum tubal ligation does not increase maternal complications 1,814 6.4 34.1 32.3* 23.0 4.2

Management of Complications

37. Availability of resources for management of hemorrhagic emergencies reduces maternal complications 1,823 67.9* 30.8 1.0 0.3 0.0

38. Immediate availability of equipment for management of airway emergencies reduces maternal, fetal, and


1,817 77.2* 22.1 0.6 0.2 0.0

39. Immediate availability of basic and advanced life-support equipment in the labor and delivery suite

reduces maternal, fetal, and neonatal complications

1,812 73.4* 24.8 1.6 0.2 0.0

40. Routine use of central venous or pulmonary artery catheterization reduces maternal complications in

severely preeclamptic patients

1,822 3.2 13.3 33.0 40.8* 9.6

* Median.

ASA � American Society of Anesthesiologists; n � number of members who responded to each item.



Spinal Hypotension During Elective Cesarean Delivery:Closer to a SolutionRobert A. Dyer, FCA (SA), PhD, and Anthony R. Reed, FRCA

Hypotension during spinal anesthesia for cesareandelivery should be minimized, both for maternalsafety and comfort, and fetal wellbeing. Traditional

teaching is that aortocaval compression predisposes the par-turient to decreased venous return and hence cardiac outputand blood pressure during spinal anesthesia for cesareandelivery. However, a variety of measures to improve venousreturn, including lateral tilt and numerous fluid administra-tion regimens, have failed to eliminate hypotension.1 Recentstudies focusing on the arterial circulation as a source forhypotension suggest that in the fluid-replete parturient un-dergoing elective cesarean delivery, moderate spinal hypoten-sion (20% decrease from baseline) primarily reflects decreasedsystemic vascular resistance.2–4 In most cases, venous returnis initially maintained and consequently there is a partialcompensatory increase in cardiac output, mediated by anincrease in stroke volume and heart rate. In this situa-tion, the rapidly acting �-agonist phenylephrine seems tobe the best option to restore baseline hemodynamicsrapidly. Although ephedrine has traditionally been usedto treat spinal anesthesia–induced hypotension, recent evi-dence suggests that ephedrine causes neonatal acidosis,and large doses may be harmful in a compromised fetus, byincreasing oxygen demand and anaerobic metabolism.5,6

Ephedrine is also associated with a higher incidence ofnausea and vomiting than phenylephrine.

The dose and method of administration of phenyleph-rine have been the subject of extensive investigation.7–12 Inthis issue of Anesthesia & Analgesia, 2 articles address thissubject. First, Allen et al.13 compared placebo with the useof 4 different infusion rates of phenylephrine, in combina-tion with a crystalloid coload, and assessed “hemodynamicstability” by heart rate and blood pressure. The aim was tomaintain blood pressure within 20% of baseline values.They demonstrated that infusing phenylephrine at a fixedrate of 75 or 100 �g/min is associated with more episodesof hypertension than placebo, or the lower infusion rates of

25 or 50 �g/min, respectively. Seven patients in the groupreceiving 100 �g/min developed sinus bradycardia andwere given glycopyrrolate. It may be more appropriate totreat baroreceptor-mediated bradycardia associated with awell-maintained blood pressure by discontinuing the infu-sion than by the administration of an anticholinergic. Thiswould avert the reactive hypertension reported by theauthors. This work suggests that to reduce hypotensionand avoid hypertension and bradycardia, slower infusionrates of phenylephrine are a better starting point, withsupplementary boluses as necessary, in keeping with thepharmacokinetic principle of the use of a bolus followed byan infusion to increase steady-state concentrations. Alter-natively, the authors speculate, varying infusion ratescould be used. The fact that some patients experiencedbradycardia and hypertension even at the slower infusionrates suggests that bolus administration of phenylephrine,titrated as required in the individual case, may be a betteroption than prophylactic infusions.

In the second important contribution, Stewart et al.,14

using a suprasternal Doppler flow technique, describedcardiac output changes associated with infusions of 25, 50,and 100 �g/min phenylephrine, respectively, after theadministration of a rapid crystalloid preload, during spinalanesthesia for elective cesarean delivery. The aim was tomaintain baseline blood pressure. The infusion of phenyl-ephrine at 100 �g/min for 20 minutes was associated witha reduction in heart rate from 80 to 58 bpm and a reductionin cardiac output from 5.1 to 4.0 L/min. Neonatal outcomeswere similar among groups. This is in agreement with arecent investigation of the hemodynamic effects of bolusesof ephedrine and phenylephrine using pulse power analy-sis. Bolus administration of phenylephrine in response tohypotension (20% decrease from baseline blood pressure)was shown to reduce maternal cardiac output to close tobaseline values (an effect strongly correlated with maternalheart rate) and restore blood pressure.2

In the non-obstetric population, phenylephrine (1:20,000)added to epidural lidocaine,15 and IV methoxamine admin-istered during spinal anesthesia,16 have been shown toreduce cardiac output. The studies published in this issueexamining the effects of phenylephrine infusions duringspinal anesthesia for cesarean delivery suggest that the useof phenylephrine in doses that cause hypertension andsinus bradycardia is inappropriate.

How does phenylephrine influence cardiac output? Theeffect of �-agonists on venous return is controversial.17 It is

From the Department of Anaesthesia, University of Cape Town and NewGroote Schuur Hospital, Cape Town, South Africa.

Accepted for publication May 24, 2010.

Disclosure: Neither author has any conflict of interest in the writing of thiseditorial.

Address correspondence and reprint requests to Robert A. Dyer, FCA (SA),PhD, D23, Department of Anaesthesia, University of Cape Town and NewGroote Schuur Hospital, Anzio Rd., Observatory 7925, Cape Town, SouthAfrica. Address e-mail to [email protected].

Copyright © 2010 International Anesthesia Research SocietyDOI: 10.1213/ANE.0b013e3181ea5f77

November 2010 • Volume 111 • Number 5 www.anesthesia-analgesia.org 1093

EDITORIAL

likely that low doses of phenylephrine increase venousreturn, and thus cardiac output, by causing some degree ofincrease in splanchnic venous tone,18 particularly in theparturient at term, with her expanded blood volume. Bycontrast, high doses of phenylephrine cause a baroreceptor-mediated reduction in heart rate and dilation of splanchnicveins and a shift of blood into the splanchnic vasculaturewith a decrease in venous return.19 Although the indirectbaroreceptor reflex-mediated sympathetic effects on thesplanchnic circulation are blocked under spinal anesthesia,the heart rate- and direct receptor-mediated effects ofhigh-dose phenylephrine persist. The latter may cause asignificant increase in splanchnic arterial resistance, result-ing in a decrease in splanchnic blood flow.20 Hepatic veinresistance may also be increased. Both effects would reducevenous return. It was interesting that Stewart et al. notedthat larger doses of phenylephrine were required to main-tain equivalent control of the blood pressure when theinfusion rate was 100 �g/min. This would be in keepingwith a dose-related decrease in venous return. Because theCorrected Flow Time Index is a measure of ventricularfilling, the suprasternal Doppler flow technique, whichincorporates this technology, could be used in future re-search to study a surrogate marker of cardiac filling andhence changes in venous return.

High-dose phenylephrine may also reduce cardiac out-put by decreasing stroke volume. Stroke volume maydecrease in response to a marked increase in systemicvascular resistance and afterload. This decrease in strokevolume was not shown in the study by Stewart et al.,because the effect is best demonstrated after bolus admin-istration, using beat-by-beat measurements.2 A compensa-tory increase in stroke volume may occur via the Anrepeffect,2,21 postulated to be the recovery from subendocar-dial ischemia induced by the increase in afterload, andsubsequent correction by autoregulation of the coronaryvascular bed.22 This effect would be undesirable if there iseither coronary artery disease or ventricular dysfunction.

Animal studies have shown that under normal physio-logical conditions, uterine blood flow is higher than re-quired for fetal oxygen demand,23 thus conferring a marginof safety under conditions of rapid changes in uterine flow.This could explain the lack of neonatal acidosis observedduring the administration of large doses of phenylephrine,even in the face of decreases in cardiac output.7–9 However,as Stewart et al. rightly pointed out, significant reductionsin maternal cardiac output could have deleterious effectson the outcome of a compromised fetus.14

In the absence of cardiac output monitoring in everydaypractice, heart rate is a good surrogate marker of cardiacoutput. Usually, the initial response to spinal anesthesia forelective cesarean delivery is an increase in heart rate and awell-maintained or increased cardiac output.2,4 In thissituation, restoring the heart rate to the baseline value usingphenylephrine in conjunction with a rapid fluid coloadshould be the primary goal. Because a small proportion ofpatients respond to spinal anesthesia with hypotension andbradycardia,24 which usually reflects a decrease in cardiacoutput, anticholinergics and ephedrine (and occasionallyepinephrine) do have a role to play, together with increas-ing lateral tilt and fluid administration.

The primary goal should thus be the maintenance of thebaseline heart rate. In many cases, this can be achieved bysimply using boluses of phenylephrine.25 Alternatively,variable rate infusions may be used, with supplementaryboluses of phenylephrine (either administered as prophy-laxis or in response to modest hypotension). These inter-ventions will correct blood pressure and cardiac outputsimultaneously, and maintain the baseline resting physio-logical hemodynamics. This, after all, is what we aresupposed to do as anesthesiologists.

Further research should explore the exact dose-relatedeffects of phenylephrine on venous return in the termparturient. This would enable the anesthesiologist to fine-tune what is now a well-understood clinical scenario. Themore difficult issue of establishing predictors for the rarerpresentation of acute bradycardia and hypotension is farfrom resolved and requires further investigation.26

REFERENCES1. Sharwood-Smith G, Drummond GB. Hypotension in obstetric

spinal anaesthesia: a lesson from pre-eclampsia. Br J Anaesth2009;102:291–4

2. Dyer RA, Reed AR, van Dyk D, Arcache MJ, Hodges O,Lombard CJ, Greenwood J, James MF. Hemodynamic effects ofephedrine, phenylephrine and phenylephrine co-administeredwith oxytocin, during spinal anesthesia for elective cesareandelivery. Anesthesiology 2009;111:753–65

3. Dyer RA, Piercy JL, Reed AR, Lombard CJ, Schoeman LK,James MF. Hemodynamic changes associated with spinalanesthesia for cesarean delivery in severe preeclampsia. Anes-thesiology 2008;108:802–11

4. Langesaeter E, Rosseland LA, Stubhaug A. Continuous inva-sive blood pressure and cardiac output monitoring duringcesarean delivery: a randomized, double-blind comparison oflow-dose versus high-dose spinal anesthesia with intravenousphenylephrine or placebo infusion. Anesthesiology 2008;109:856–63

5. Macarthur A, Riley ET. Obstetric anesthesia controversies:vasopressor choice for postspinal hypotension during cesareandelivery. Int Anesthesiol Clin 2007;45:115–32

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Spinal Hypotension at Cesarean Delivery

November 2010 • Volume 111 • Number 5 www.anesthesia-analgesia.org 1095

REVIEW ARTICLE

Thrombocytopenia in the parturient

P. C. A. Kam,1 S. A. Thompson2 and A. C. S. Liew3

1 Professor of Anaesthesia, Department of Anaesthesia, University of NSW at St. George Hospital, 2 Fellow in

Anaesthesia, Department of Anaesthesia, St. George Hospital, 3 Staff Specialist Anaesthetist, Department of

Anaesthesia, University of NSW at St. George Hospital, Belgrave Street, Kogarah, NSW 2217, Australia

Summary

Thrombocytopenia in pregnant women can be associated with substantial maternal and neonatal

morbidity. It may result from a range of conditions and early implementation of some specific

treatment may improve both maternal and neonatal outcome. In this review we discuss the clinical

features of the more common causes of thrombocytopenia associated with pregnancy, and provide

an overview of the anaesthetic considerations.

Keywords Pregnancy. Thrombocytopenia; gestational thrombocytopenia, pre-eclampsia, HELLP,

thrombotic thrombocytopenic purpura, immune thrombocytopenic purpura.

........................................................................................................

Correspondence to: Dr P. C. A. Kam


Accepted: 26 October 2003

Thrombocytopenia occurs in approximately 10% of

pregnant women and may be caused by a variety

of obstetric conditions (Table 1) [1]. Although some of

these diseases are not associated with adverse effects

or outcomes of pregnancy, others can be associated with

serious maternal as well as fetal ⁄ neonatal morbidity and

mortality. A multidisciplinary team approach involving

obstetrician, haematologists, paediatricians and anaesthet-

ists is essential for the optimal management of pregnant

women with thrombocytopenia. Thrombocytopenia in

the obstetric patient may be the result of a range of

conditions, from benign disorders such as incidental

gestational thrombocytopenia to life-threatening syn-

dromes such as the ‘haemolysis, elevated liver enzymes,

low platelets’ syndrome (HELLP) [2]. The diagnosis of

specific disorders is often difficult because the time of

onset of these disorders during pregnancy and their

clinical manifestations often overlap.

The aim of this article is to review the differential

diagnosis of thrombocytopenia in pregnancy and high-

light the clinical features and management of the various

diseases that cause thrombocytopenia, and to summarise

the anaesthetic considerations in the management of

thrombocytopenia in the parturient.

Method

Sources for this review include Medline 1980–2003

searched under the following Medical Subject Headings:

thrombocytopenia, pregnancy, platelets, pre-eclampsia,

HELLP, and thrombotic thrombocytopenic purpura

(TTP). The bibliographies of the included studies were

scanned for additional references (reference dredging).

The National Library of Medicine Pub Medical internet

site was also used.

Haemostatic changes in normal pregnancy

During normal pregnancy, major changes in haemostasis

include increasing concentrations of most clotting factors,

decreasing concentrations of some natural anticoagulants

and diminishing fibrinolytic activity [3]. These changes

create a state of hypercoagulability that is most marked

around term and the immediate postpartum period,

thereby decreasing bleeding complications that may be

associated with delivery. The most important initial

factors for haemostasis at delivery, however, are uterine

muscle contractions and constriction of the spiral arteries

that interrupt blood flow.

Anaesthesia, 2004, 59, pages 255–264.....................................................................................................................................................................................................................


All blood coagulation factors except XI and XIII

increase during normal pregnancy [4, 5]. The plasma

fibrinogen concentration increases from non-pregnant

levels of 2.5–4 g.l)1 to 6 g.l)1 in late pregnancy and

labour. The increase in the concentration of the two

components of the factor VIII complex, Factor VIII and

von Willebrand factor (VWF) antigen, occur in parallel in

the first half of pregnancy, but then diverge because of

a two-fold increase in von Willebrand factor antigen.

Factor XI concentrations decrease to approximately 60%

of the non-pregnant values. Factor XIII concentrations

fall to about 50% of the normal non-pregnant value at

term. The increase in factors VII and X is highest in mid-

pregnancy and remains high in the third trimester.

Most blood coagulation inhibitors are unchanged.

Antithrombin and protein C levels are normal during

pregnancy. However, the plasma concentration of free

protein S decreases markedly during pregnancy and may

contribute to the hypercoagulable state [6, 7]. The level of

tissue factor pathway inhibitor increases in pregnancy.

Plasma fibrinolytic activity is reduced during pregnancy

and labour, and returns to normal within 1 h after

placental delivery. The diminished fibrinolysis is caused

by increased concentrations of plasminogen activator-1

derived from endothelial cells and plasminogen activator

inhibitor-2 derived from the placenta.

The normal platelet count range in non-pregnant

women is 150–400 · 109.l)1. In uncomplicated preg-

nancies, recent studies have reported that the platelet

count decreases by an average of 10% during the third

trimester as a result of haemodilution or accelerated

destruction leading to younger and larger platelets [8].

Incidental thrombocytopenia in pregnancy is usually

benign. The mean platelet volume increases, suggesting

that a compensated state of progressive platelet destruc-

tion occurs during the third trimester [9, 10]. The

concentration of plasma b-thromboglobulin (a specific

protein in the a-granules that is secreted during platelet

activation) increases in the second and third trimesters of

pregnancy [11].

Platelet activation, coagulation and fibrinolytic activity

are enhanced during delivery [7]. Significant increases in

fibrinogen degradation products occur in 21% of partu-

rients during labour, with 32% showing the similar

increases in the immediate postpartum period. At 24–72 h

after delivery, fibrinogen degradation remains elevated in

only 10% of women. Platelet count returns to normal

24–72 h postpartum [12, 13], and fibrinolytic activity

decreases rapidly [7]. During placental separation, the

clotting mechanism is activated and factor VIII activity

transiently increases after delivery, shortening coagulation

times [14].

In the pregnant women, thrombocytopenia is defined

as a platelet count of less than 150 · 109.l)1; counts of

100–150 · 109.l)1 are defined as mild thrombocytopenia,

counts of 50–100 · 109.l)1 as moderate thrombocyto-

penia, and counts of less than 50 · 109.l)1 as severe

thrombocytopenia. Thrombocytopenia is caused either

by increased platelet destruction or decreased platelet

production. In pregnancy, increased platelet destruction

may be mediated by immunological mechanisms, abnor-

mal platelet activation, or platelet consumption [15].

Increased destruction or utilisation of platelets during

pregnancy occurs in microangiopathies (exposure to

abnormal blood vessels) such as thrombotic thrombo-

cytopenic purpura, haemolytic uraemic syndrome, hae-

molysis, elevated liver enzymes, low platelet (HELLP)

syndrome, and pre-eclampsia.

Gestational or incidental thrombocytopenia

Gestational or incidental thrombocytopenia, the most

common cause of thrombocytopenia during pregnancy,

occurs in 5–8% of all pregnant women and accounts for

75% of pregnancy-associated thrombocytopenia. The

decreased platelet count may be related to haemodilution

and ⁄ or accelerated platelet turnover with increased

platelet production in the bone marrow, and increased

trapping or destruction at the placenta [16]. The quan-

titative decrease in platelet count is balanced by enhanced

platelet reactivity [17]. Some authors, however, have

described decreased platelet activation mediated by a

plasma factor that selectively inhibits prostaglandin-

dependent activation during pregnancy [18].

The features of gestational thrombocytopenia include a

platelet count usually below 70 · 109.l)1 which returns to

Table 1 Causes of thrombocytopenia in pregnancy.

NormalIncidental or gestational thrombocytopeniaPseudothrombocytopenia (laboratory artefact with EDTAanticoagulant)

Disorders with increased platelet consumptionImmune thrombocytopenic purpuraPregnancy induced hypertension ⁄ HELLP syndromeThrombotic thrombocytopenic purpuraHaemolytic uraemic syndromeInfection-associated (HIV, malaria)Drug-induced (heparin, sulphonamides, penicillin, rifampicin,quinine)

Systemic lupus erythematosusAntiphospholipid syndromeDisseminated intravascular coagulationAmniotic embolismDisorders with reduced platelet productionCongenital thrombocytopeniaAplastic anaemiaLeukaemiaDrug-inducedMyelodysplasia



a normal level following delivery within 12 weeks. The

women are asymptomatic with no history of bleeding and

thrombocytopenia is usually detected as part of antenatal

screening. The women have no history of thrombocyto-

penia prior to pregnancy but may have thrombocytopenia

in previous pregnancies. Gestational thrombocytopenia is a

diagnosis of exclusion. However, when a platelet count is

below 70 · 109.l)1, a pathological cause of thrombo-

cytopenia becomes substantially more likely. Gestational

thrombocytopenia usually occurs in the late second or third

trimester. There is an extremely low risk of fetal or neonatal

thrombocytopenia [19]. In non-hypertensive pregnant

women, investigations are only required when thrombo-

cytopenia occurs early in pregnancy or progressively

decreases during the pregnancy or when the platelet count

is less than 70 · 109.l)1. Further investigations must be

undertaken in pregnant women who are symptomatic or

who do not regain a normal postpartum platelet count. If a

thrombocytopenic but otherwise healthy pregnant woman

has a platelet count >70 · 109.l)1 and no history of

previous thrombocytopenia, a meticulous physical exam-

ination, careful blood pressure assessment and monitoring

and a peripheral blood film examination should be

undertaken. The confirmation of normal platelet count

prior to pregnancy decreases the probability of an under-

lying immune thrombocytopenic purpura [20]. Anti-

platelet antibody tests do not differentiate gestational

thrombocytopenia from idiopathic thrombocytopenia. In

a study of 250 pregnant women with thrombocytopenia

(90 with idiopathic thrombocytopenia, 160 with presumed

gestational thrombocytopenia) that evaluated eight differ-

ent platelet antibodies, platelet-associated IgG was elevated

in 69.5% of women with gestational thrombocytopenia

and in 64.6% of women with idiopathic thrombocytopenia

(p = 0.24). Although 85.9% of women with idiopathic

thrombocytopenia had indirect IgG compared with 60.3%

women with gestational thrombocytopenia (p < 0.001),

significant overlap existed and limited its clinical value [21].

It appears that there are no specific diagnostic tests that can

distinguish gestational thrombocytopenia from mild idio-

pathic thrombocytopenia. Therefore, the only means of

differentiation is to monitor platelet counts closely, to

detect levels that decrease below the 50–70 · 109.l)1

range, to document a normal neonatal platelet count and a

restoration of a normal maternal platelet count after

delivery. Women with gestational thrombocytopenia are

not at a risk of either maternal haemorrhage or fetal

haemorrhage.

Immune thrombocytopenic purpura (ITP)

ITP is characterised by immunologically mediated platelet

destruction and an increase in circulating megathrombo-

cytes. The patient produces IgG antiplatelet antibodies

that recognise platelet membrane glycoproteins. The

antibody-coated platelets are then destroyed by the

reticuloendothelial system (primarily the spleen) at a rate

that exceeds the capacity of the bone marrow to produce

new platelets. However, antiplatelet antibodies are pre-

sent in only 80% of cases.

ITP occurs in approximately one case of thrombo-

cytopenia per 1000 pregnancies and accounts for 5% of

cases of pregnancy-associated thrombocytopenia [22]. It is

the most common cause of significant thrombocytopenia

in the first trimester. ITP is a diagnosis of exclusion

because there are no pathognomonic signs, symptoms or

laboratory tests. The four consistent features that are

associated with the condition are persistent thrombo-

cytopenia (platelet count <100 · 109.l)1) with or with-

out peripheral megathrombocytes; normal or increased

number of megakaryocytes detected by bone marrow

aspiration; absence of splenomegaly; and exclusion of

systemic diseases or drugs that are known to cause

thrombocytopenia.

Most women with ITP have a history of bruising easily,

petechiae, epistaxis, and gingival bleeding preceding

pregnancy, although some may be asymptomatic. Symp-

toms of haemorrhage are rare unless the platelet count is

<20 · 109.l)1. A history of prior thrombocytopenia,

underlying autoimmune disease or a platelet count

<50 · 109.l)1 makes the diagnosis of ITP more likely.

In patients with mildly decreased platelet count and with

no prior history of thrombocytopenia, it can be difficult

to distinguish ITP from gestational thrombocytopenia,

because platelet-associated IgG may be elevated in both

diseases [21]. An immunological test that measures

antibodies that react with specific platelet glycoproteins

(monoclonal antibody immobilisation of platelets) cannot

differentiate these two syndromes consistently [23]. From

a clinical view, in the absence of a platelet count prior to

pregnancy, a platelet count <100 · 109.l)1 in the first

trimester that declines progressively as the pregnancy

progresses is consistent with ITP. In contrast, mild

thrombocytopenia occurring in the second or third

trimester and not associated with proteinuria or hyper-

tension indicates incidental or gestational thrombocy-

topenia [24]. ITP is an insidious disease with initial

symptoms such as easy bruising and petechiae. Pregnancy

does not alter the clinical course of ITP. However, there

are anecdotal reports of deterioration of symptoms during

pregnancy and improvement postpartum [2].

Patients with platelet counts >30 · 109.l)1 and no

bleeding do not usually require immediate treatment.

Platelet transfusion is indicated if bleeding occurs or if the

platelet count is <30 · 109.l)1 [9, 23]. More aggressive

measures may be required to increase the platelet count to



a level to allow epidural analgesia for labour and adequate

haemostasis during delivery. A platelet count >50 ·109.l)1 is usually adequate in this regard, although some

authors recommend a platelet count >100 · 109.l)1 [25].

Drug therapy usually commences with oral prednisone

(1–2 mg.kg)1.day)1), with reduction of doses until the

platelet count stabilises at 75–100 · 109.l)1. However,

steroid therapy increases the incidence of gestational

diabetes, pregnancy-induced hypertension and premature

rupture of placental membranes. Patients with low

platelet counts should receive steroids at around 37 weeks

of gestation in order to increase maternal and foetal

platelet counts. Betamethasone or dexamethasone is

preferred because placental enzymes inactivate a major

portion of the prednisone dose that is presented to the

placental circulation.

High doses of intravenous immunoglobulin (2 mg.kg)1)

have been recommended for pregnancy-associated ITP

[24]. However, the responses are often transient and

multiple courses of treatment may be required.

Splenectomy may be required during pregnancy to

decrease platelet destruction in patients who are refractory

to steroid or IgG therapy. It should be performed in the

second trimester because surgery can cause premature

labour in the first trimester and may be more difficult in

the third trimester due to the large gravid uterus.

The maternal consequence of ITP is haemorrhage.

Bleeding complications are usually associated with surgi-

cal incisions (such as episiotomy) and lacerations of the

birth canal. The mother is not at a greater risk of abruptio

placentae or placenta praevia than the general pregnant

population [26]. They are not at higher risk for postpar-

tum uterine bleeding because myometrial contractions

produce mechanical haemostasis without a significant

contribution from platelets. Platelet numbers should be

maintained above 50 · 109.l)1 for delivery. Platelet

counts below 20 · 109.l)1 should be augmented using

platelet transfusions.

The neonate of a mother with ITP may develop ITP as

a result of the transplacental transfer of maternal anti-

platelet IgG [24]. At delivery, 10–20% of these neonates

have platelet counts below 50 · 109.l)1 and, in 5%,

platelet counts may be <20 · 109.l)1 [27]. The major

fetal risk is intracranial haemorrhage causing neurological

sequelae or death, but this is rare [28]. There is no

consistent and reliable correlation between the fetal

platelet numbers at delivery and the severity of maternal

thrombocytopenia or the concentration of maternal

antiplatelet IgG [21, 27]. The most reliable predictor of

fetal thrombocytopenia is the presence of thrombo-

cytopenia at delivery of a prior sibling [29]. Determin-

ation of fetal platelet count can only be achieved by fetal

scalp sampling during labour or percutaneous umbilical

blood sampling, although the latter is associated with

bleeding and fetal bradycardia (� 1%) [30].

In 1977, a case report of intracranial haemorrhage after

a vaginal delivery of a thrombocytopenic infant to a

mother with ITP led to the recommendation that women

with ITP should be delivered by Caesarean section.

However, this approach has not been subjected to

randomised controlled studies and has been recently been

questioned [31, 32]. Cook and colleagues reviewed

literature that included 474 pregnant women with ITP

and reported that the incidence of intracranial haemor-

rhage among neonates with severe thrombocytopenia

(<50 · 109.l)1) was 4% after Caesarean delivery and

5% after vaginal delivery [31]. A literature review of

18 studies on maternal ITP that involved 601 neonates

showed that 12% of neonates had severe thrombo-

cytopenia, but that intracranial haemorrhage only

occurred in 1% (6 ⁄ 601) of neonates and was not related

to the mode of delivery [33]. It is currently recommended

that fetal platelet count using percutaneous umbilical

blood samples should be measured first, and delivery by

Caesarean section undertaken if the fetal platelet count is

<50 · 109.l)1 [34].

Umbilical cord platelet counts should be measured

from umbilical blood obtained at delivery regardless of

the method of delivery. Daily monitoring of platelet

numbers in the neonate is necessary because neonatal

platelet count can decrease for 4–5 days post delivery.

The neonate’s platelet count is usually normal by

1 month of age.

Pre-eclampsia and HELLP syndrome

Pre-eclampsia is characterised by hypertension and pro-

teinuria (> 300 mg.24 h)1) developing after 20 weeks of

gestation, and occurs in 6% of all pregnancies [35]. The

pathological lesions of pre-eclampsia involve deficient

remodelling of the maternal uterine vasculature by the

placental trophoblast early in pregnancy [36]. Abnormal

expression of cell adhesion molecules, and vascular

endothelial cell growth factor and its receptor by

trophoblasts in pre-eclampsia have been reported

[37, 38]. This causes uteroplacental vascular insufficiency

leading to abnormal release and metabolism of nitric

oxide, prostaglandins and endothelin by placental tissues.

These changes lead to platelet activation, generalised

endothelial dysfunction and hypertension [39]. Circula-

ting platelets adhere to damaged or activated endothe-

lium, causing enhanced platelet clearance. Although

increased levels of platelet-associated IgG are detected in

patients with pregnancy-induced hypertension (PIH), this

finding is not specific and does not provide an immuno-

logical basis for the thrombocytopenia [40]. Clearance of



IgG-coated platelets may be further increased by the

reticulo-endothelial system and platelet activation due to

thrombin generation [2]. Platelet function may also be

impaired in women with pre-eclampsia even if their

platelet count is normal.

Pre-eclampsia is present in 21% of cases of maternal

thrombocytopenia [28]. Thrombocytopenia occurs in

50% of pre-eclamptic patients and occasionally precedes

other manifestations of the disease. The thrombocyto-

penia is usually moderate and clinical haemorrhage is

uncommon unless the patient develops disseminated

intravascular coagulopathy. A decreasing maternal platelet

count is considered as an early sign of worsening of pre-

eclampsia and may occur even before other clinical

manifestations of the disease are apparent. The patho-

genesis of thrombocytopenia in women with severe pre-

eclampsia is unknown, although vascular endothelial

damage, impaired prostacyclin production and increased

deposition of fibrin within the vascular bed have been

suggested. Accelerated platelet destruction, platelet acti-

vation, increased platelet volume and increased mega-

karyocyte production have been observed [2]. An

increased response of platelet calcium to arginine vaso-

pressin preceding thrombocytopenia as early as in the first

trimester has been reported and has been proposed as a

possible predictor of the development of the disease [41].

Activation of the coagulation cascade occurs in most pre-

eclamptic patients, but routine tests such as activated

partial thromoboplastin time, prothrombin time and

fibrinogen concentrations are normal. However, fibrin-

ogen D-dimers and thrombin-antithrombin complexes

are elevated in most cases.

Only neonates born prematurely are at risk of neonatal

thrombocytopenia, and especially those with intrauterine

growth retardation [15]. The platelet count in neonatal

thrombocytopenia associated with pre-eclampsia is rarely

below 20 · 109.l)1 and does not cause fetal bleeding

complications [28]. Term infants of mothers with PIH are

no more likely to be thrombocytopenic than those of

normal mothers.

The HELLP (haemolysis, elevated liver enzymes,

low platelets) syndrome, a variant of pre-eclampsia, is

characterised by microangiopathic anaemia, SGOT

> 70 units.l)1, and thrombocytopenia (<100 · 109.l)1)

and is associated with a maternal mortality of about 3.3%.

Severe epigastric or right upper quadrant abdominal pain,

which need not be associated by proteinuria and hyper-

tension, are common symptoms. It is more common in

multiparae, occurs in a slightly younger age group

(19 years vs 25 years), and can manifest in approximately

30% of cases postpartum [42, 43]. It has been suggested

that the underlying primary pathological lesion in the

HELLP syndrome might be endothelial dysfunction and

damage, which leads to platelet aggregation, consumption

and eventually thrombocytopenia. Microthrombi depos-

ited in the liver sinusoids cause obstruction to hepatic

blood flow, consequently leading to liver distension and

elevations of liver enzymes [42]. Although platelet acti-

vation has been suggested in the pathogenesis of pre-

eclampsia or HELLP syndrome, prophylactic treatment of

high-risk pregnant women with low-dose aspirin does not

significantly decrease the incidence of pre-eclampsia [44].

The HELLP syndrome is associated with disseminated

intravascular coagulation, placental abruption, acute renal

failure, adult respiratory distress syndrome and intra-

uterine death. The perinatal mortality is about 22% and is

caused by placental abruption, intrauterine asphyxia, and

prematurity. Approximately 60% of babies die in utero.

Thirty percent of the infants (average gestational

age 32 weeks) are small for gestational age, and thromb-

ocytopenia is present in 25% of these.

The management of pre-eclampsia and HELLP is

focussed on stabilising the mother until fetal maturity is

more favourable. Fetal monitoring is mandatory, and will

help to decide whether early delivery of the fetus is

warranted. Early delivery of the fetus is warranted if there

are threats to fetal or maternal life or if the syndrome

develops beyond 34 weeks of gestation. Caesarean section

is required in 60% of cases [42].

Platelet transfusions increase the platelet count prior to

Caesarean section. However, the lifespan of the transfused

platelets is shortened. Coagulopathy associated with

PIH-related disseminated intravascular coagulation should

be treated with fresh frozen plasma or cryoprecipitate if

fibrinogen levels are low. If pre-eclamptic patients

deteriorate or remain thrombocytopenic after delivery,

plasma exchange and ⁄ or corticosteroids should be con-

sidered to reverse the abnormalities [6, 45].

Thrombotic thrombocytopenic purpura (TTP)

and haemolytic uraemic syndrome (HUS)

Thrombotic thrombocytopenic purpura is characterised

by microangiopathic haemolytic anaemia, thrombo-

cytopenia, central neurological abnormalities, fever and

renal dysfunction. In some series, up to 10% of all cases of

TTP occurred in pregnant patients, and pregnancy is

considered to be a predisposing factor for this disease [47].

A deficiency of a VWF-cleaving protease, ADAMTS 13,

has been identified as a causative factor in the patho-

genesis of TTP [48]. This deficiency may be caused by

mutations in ADAMTS 13 gene in the congenital variant

[49] or may result from antibodies against the protease in

the acquired form of the disease. TTP usually occurs

in the second trimester, with a mean onset of 23 weeks

[50]. The clinical manifestations of haemolytic uremic

syndrome are similar to that of TTP except that renal



dysfunction is more severe in HUS whereas neurological

abnormalities are more pronounced in TTP. Ninety

percent of cases of HUS occur in the postpartum period

(mean = 26 days after delivery) [50]. In most patients with

TTP and HUS, plasma antithrombin concentrations are

normal, whereas reduced antithrombin concentrations are

present in patients with pre-eclampsia or HELLP. As in

the HELLP syndrome, features of microangiopathic

haemolysis such as anaemia, increased bilirubin and

lactate dehydrogenase, decreased haptoglobin, Burr cells,

schistocytes, helmet cells, reticulocytosis and polychrom-

asia, are present in TTP and HUS. The course of TTP

and HUS does not improve following delivery of the

fetus. Remission can be achieved by plasma exchange in

75% of pregnant and non-pregnant patients with TTP.

However plasma exchange is less effective in reversal of

renal dysfunction for pregnancy-associated HUS. Chro-

nic renal failure and hypertension are long-term compli-

cations associated with HUS (Table 2).

Acute fatty liver of pregnancy

Mild microangiopathic haemolysis and thrombocytopenia

are observed in acute fatty liver of pregnancy (AFLP) [50].

AFLP is most common in primiparae and affects one of

5000–10 000 pregnancies. These women present with

malaise, nausea, epigastric and right upper quadrant pain,

dyspnoea, cholestatic liver abnormalities, hypoglycaemia

and decreased levels of fibrinogen and antithrombin. In

75% of these patients, there is laboratory evidence of

disseminated intravascular coagulation caused by decreased

hepatic synthesis of antithrombin. Management of patients

with AFLP is supportive with emphasis of correction of

hypoglycaemia, coagulopathy and electrolyte imbalances.

Other causes of thrombocytopenia in pregnancy

Disseminated intravascular coagulation can be associated

with obstetric disorders such as placental abruption,

amniotic fluid embolism, uterine rupture and intrauterine

fetal death and may cause thrombocytopenia. In systemic

lupus erythematosus (SLE) about 14–25% of patients

develop thrombocytopenia caused by antiplatelet auto-

antibodies or circulating immune complexes [51]. Mater-

nal autoantibodies can cross the placenta and cause fetal

thrombocytopenia, especially in the presence of Ro- and

La-antibodies [52].

Pregnant women suffering from antiphospholipid syn-

drome may have thrombocytopenia secondary to throm-

bosis, fetal loss or associated pre-eclampsia [53].

Approximately 28–42% of SLE patients have antiphosp-

holipid and ⁄ or lupus anticoagulant, and have an increased

risk of thromboembolism compared with those who lack

these antibodies. The high fetal loss associated with the

antiphospholipid syndrome is caused by recurrent throm-

bosis of the placental and decidual blood vessels.

Drug-induced thrombocytopenia occurs in pregnant as

well as non-pregnant women. Quinidine and sulphona-

mides are among the most common drugs associated with

acute thrombocytopenia [54].

Pregnant women with Type IIb von Willebrand

disease may develop thrombocytopenia, which is caused

by the enhanced clearance of platelets that bind to

abnormal von Willebrand Factor molecule. HIV infection

should be considered in any thrombocytopenic patient

with risk factor [55].


The choice of anaesthetic technique in the pregnant

women with thrombocytopenia largely depends on the

proposed method of delivery, gestational age of the fetus,

coagulation status, associated obstetric complications,

history of recent or current bleeding and other significant

medical history. The risk of epidural haematoma in the

general population is estimated to be 1 in 150 000 after

epidural analgesia [56]. There are eight reports of spinal

haematomas following obstetric epidural analgesia ⁄ anaes-

thesia in the literature but some of these are questionable

[9, 57]. The incidence of epidural haematoma is 0.2–3.7

in 100 000 obstetric epidural blocks [59].

Circulating platelet numbers and their function deter-

mine the safety of regional anaesthesia. A lower limit of

100 · 109.l)1 for platelet count is suggested as ‘safe’ for

performing an epidural blockade, although there are no

supporting data [60]. Several studies have attempted to

address the issue of the risk of epidural haematoma when

the platelet count is between 50 and 100 · 109.l)1. Two

Table 2 Clinical and laboratory features of HELLP, TTP, HUS.

Feature HELLP TTP HUS

Time of presentation >37 weeks mid-trimester postpartumCNS signs variable severe rareRenal failure variable mild severeHepatic dysfunction definite nil nilFever nil present nil usuallyPurpura nil severe nil usuallyDecreased platelets mild–moderate severe moderateCreatinine increase mild mild largeAST ⁄ ALT increase increase no change no changeLDH increase mild marked markedHyaline thrombi +– ++ ++Post-partumimprovement

yes nil nil

HELLP = ‘Haemolysis, Elevated Liver enzymes, Low Platelets’. TTP =thrombotic thrombocytopenic purpura. HUS = haemolytic uraemicsyndrome. AST = aspartate aminotransferase. ALT = alanine amino-transferase.



retrospective studies have suggested that epidural anaes-

thesia may be safely undertaken when the platelet count is

<100 · 109.l)1 [2, 61]. In a study of 2929 parturients, no

complications associated with regional anaesthesia were

recorded in the 24 women who had a platelet count

<100 · 109.l)1 [62]. Beilin and colleagues reported that,

over a 3-year period, 30 parturients who had platelet

counts ranging from 69 to 98 · 109.l)1 safely received

epidural anaesthesia [63]. A survey of American anaes-

thetists reported that 66% in academic practice and 55% of

those in private practice would place an epidural anaes-

thetic when the platelet count is between 80 · 109.l)1

and 100 · 109.l)1 [64]. Most haematologists suggest that a

platelet count >50 · 109.l)1 is safe for surgery and

neuraxial blockade, provided platelet function is normal

[5, 24].

Before carrying out further investigations to determine

the cause of thrombocytopenia, factitious platelet counts

due to laboratory artefacts must be ruled out by reviewing

the peripheral blood film using a citrated blood sample.

This artefact, termed as pseudo-thrombocytopenia, is

caused by in vitro platelet clumping when EDTA is used

as the anticoagulant, and is due to adhesion of platelets to

the periphery of neutrophils in the presence of platelet

agglutinins (IgG or IgM) [65].

The bleeding time test, a simple bedside test that

evaluates the quality and quantity of platelets, is not

considered to be reliable to determine the safety of

epidural catheter placement because of wide observer

variation. It is affected by technical (length and size of

cut, occlusion pressure) and patient (ethnicity, diabetes,

hypercholesterolaemia, etc.) factors [66].

Coagulation tests performed several weeks before

delivery are not reliable in predicting coagulation abnor-

malities during labour [67]. In a study of 797 women,

prothrombin time and the activated partial thrombo-

plastin time were normal in all patients including those

with low platelets and plasma fibrinogen concentrations

(<2.9 gl)1) and it was concluded that these tests are

unnecessary in clinically normal parturients. The authors

also reported that the percentage of women with

platelet count values <100 · 109.l)1 increased from

0.5% (3 ⁄ 797) to 1.4% (11 ⁄ 797) between blood sampled

during the 9th month of pregnancy and that obtained

in labour.

The thromboelastogram (TEG) measures whole blood

clotting, and the interactions between the coagulation

cascade, fibrinogen, and platelets. However, TEG does

not measure initial platelet adhesion to exposed collagen

in the damaged vessel wall. Orlikowski measured platelet

count, TEG variables and bleeding time in 49 parturients

with pre-eclampsia. The thromboelastography variables,

k time and maximal amplitude (MA) have a strong

correlation with platelet count (k time ) platelet count

<100 · 109.l)1, r = )0.84, p = 0.02; MA ) platelet

count <100 · 109.l)1, r = )0.78, p = 0.04). An MA of

53 mm correlated with a platelet count of 54 · 109.l)1

(95% confidence limits, 40–75 · 109.l)1) and was asso-

ciated with adequate clot formation produced by throm-

boelastography. The authors suggested that patients with

platelet counts greater than 75 · 109.l)1 should not be

denied regional anaesthesia [68]. In another study of TEG

in normal pregnant women and in women with pre-

eclampsia, all patients with a platelet count >75 · 109.l)1

had a normal MA, which indicated a normal clot [69].

It is difficult to draw firm conclusions about the reliability

of TEG to predict which patients might develop epidural

haematoma from these studies because few patients

with platelet counts <75 · 109.l)1 received epidural

anaesthesia.

Aggregometry (measures platelet aggregation in

response to specific agonist such as ADP and epinephrine)

and flow cytometry (measures platelet activation and

aggregation) are not practical clinical tests because they

are time-consuming and require technical expertise.

The Platelet Function Analyser (PFA-100) may offer a

rapid, simple point of care assessment of platelet aggre-

gation. The PFA-100 platelet function analyser evaluates

primary coagulation under high shear stress by measuring

the time required for whole blood to occlude an aperture

in a membrane coated with collagen and the platelet

agonists, epinephrine (PFA-EPI), or adenosine diphos-

phate (PFA-ADP), called ‘closure time’. A 800-ll sample

of citrated blood, maintained at 37 �C, is aspirated into

stainless steel capillaries, through which a central aperture

is cut into the membrane covered with collagen and

epinephrine or collagen-ADP. Platelet activation and

aggregation occurs on the membrane, resulting in the

occlusion of the aperture and interruption of blood flow

[70]. The test takes approximately 7 min. In a study of

platelet function during pregnancy using the PFA-100 in

patients with thrombocytopenia associated with pre-

eclampsia, there was a correlation between platelet

numbers and PFA-ADP closure time (normal range

71–118 s) particularly when the platelet count was less

than 50 · 109.l)1 [71]. The PFA-ADP closure times were

normal in healthy patients. However, the PFA-EPI

closure times increased in six otherwise healthy patients,

suggesting that PFA-EPI may give false positive values.

Further evaluation of the PFA-100 in pregnant women

with platelet counts of less than 50 · 109.l)1 is required

[71]. Haemostasis is initiated by platelet adhesion to

damaged vessel wall and the main disadvantage of all

laboratory platelet function tests is that they do not

measure the interaction between platelet and the vascular

endothelium.



Large prospective studies with an estimated sample size

of >200 000 patients are required to definitively

determine whether it is safe to place an epidural or

spinal anaesthetic in patients with a platelet count

<100 · 109.l)1 [63]. The entire clinical presentation of

the patient must be considered when deciding on the

appropriate choice of anaesthesia. It is important to ensure

that there is no clinical evidence of bleeding and that the

platelet count is not decreasing when epidural catheter

placement is contemplated. A decreasing platelet count is

considered a contraindication to neuraxial blockade,

especially in dynamic conditions such as pre-eclampsia

and ITP [63]. Pseudo-thrombocytopenia must be exclu-

ded. A manual platelet count is more accurate in patients

with recent thrombocytopenia because automated coun-

ters are not reliable at low platelet counts. Specific

questions about medications that might interfere with

platelet numbers and function should be asked. A physical

examination of the patient should include looking for

evidence of bruising and bleeding at venepuncture sites or

petechiae at the blood pressure cuff site. Consumptive

coagulopathy associated with placental abruption and

other conditions must be ruled out. When considering

regional anaesthesia in patients with thrombocytopenia,

spinal anaesthesia may be safer. A soft flexible catheter that

is less likely to puncture blood vessels is preferred if an

epidural anaesthetic is undertaken [66]. Careful monitor-

ing of the patient in the postpartum period to detect early

signs and symptoms of an epidural haematoma should be

undertaken. General anaesthesia for urgent Caesarean

section becomes necessary if coagulation is abnormal or

there is bleeding.

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