07RC1

Pregnancy and neurosurgery

Eberhard F. Kochs
Sabine Himmelseher
Department of Anaesthesia, Technische Universität München, Klinikum rechts der Isar, Munich, Germany

Monday, 13 June 2011 8:30 - 9:15 Room: E108

Injuries to the central nervous system including subarachnoid (SAH) and intracranial haemorrhage (ICH), acute traumatic brain injury,
and primary or metastatic brain tumours constitute a major source of non-obstetric morbidity and mortality during pregnancy [1-7]. For
example, SAH accounts for 5-13% of all maternal deaths and is the third most common non-obstetric cause of maternal mortality [2, 3, 5].
Trauma complicates at least 7% of all pregnancies, and is a significant cause of non-obstetric morbidity and mortality in gravid patients
[6-8].

Subarachnoid haemorrhage resulting from ruptured intracranial arterial aneurysms and arterio-venous malformations (AVM) should
be managed promptly by interventional endovascular treatment or intracranial surgery at any stage of pregnancy [3-5]. However, stable
patients with an intracranial aneurysm or an AVM that is not bleeding can often be allowed to continue to reach term gestation, followed
by elective postpartum excision or coiling. Sometimes a combined procedure involving Caesarean section and subsequent neurosurgery
is performed. If possible, neurosurgery for neoplastic lesions should be deferred until after delivery, but if the clinical course of the brain
tumour is causing deterioration, earlier interventions to improve maternal and foetal outcome may become necessary. Hormonal changes
in pregnancy may accelerate intracranial tumour growth, oedema, and blood vessel engorgement, and increased oestrogen and human
chorionic gonadotropin concentrations appear to lower seizure thresholds [1, 5, 9, 10]. Pregnant patients presenting with CNS trauma,
spinal or epidural lesions or haemorrhages may also require immediate or urgent surgery.

Provision of anaesthesia for neurosurgical patients who need surgical treatment while pregnant is a major challenge. A balance
between competing or even contradictory clinical goals may need to be achieved, for example application of some neuroanaesthetic
techniques or protective interventions may benefit the mother but carry risks for harming the foetus (Figure 1). In general, principles of
anaesthesia for the care of non-pregnant neurosurgical and pregnant patients fully apply in both situations. Unsurprisingly, evidence-
based knowledge from randomised controlled clinical trials to guide planning and management is sparse [5, 6, 8-10]. Neuroanaesthetic
techniques should be designed to avoid foetal hypoxia, hypercarbia, hypotension, teratogenicity, and induction of preterm labour and
acknowledge pregnancy-related changes in maternal physiology. Neuroprotective measures such as hyperventilation or induced hyper-
osmolarity should only be used with caution and to a limited extent, because hypocarbia, reduced uterine perfusion, and foetal hyperos-
molarity or dehydration pose serious threats to the foetus. Neuroanaesthesia must therefore strive to offer optimal care for the mother
and minimise or eliminate risks to the foetus, whilst also ensuring the shortest possible exposure to anaesthetic drugs. All neurosurgical
procedures during pregnancy must be considered major interventions. Accordingly, a multi-disciplinary and well planned strategy and
team approach are advisable in all scenarios [3-11]. If an emergency should develop during pregnancy, initial stabilisation of the mother
should take priority, although assessment and subsequent treatment has to consider mother and child.

- 1 -
 NEUROANAESTHESIA BACKGROUND for PLANNING / MANAGEMENT

Pregnancy-Related Uteroplacental Anaesthetic Drugs-Associated

Physiologic Changes Perfusion Effects on Foetus

APPROACH: PROVIDE BALANCE BETWEEN THERAPY for MOTHER and RISKS for FOETUS
OMPECONTRADICTORY

NEUROANAESTHESIA

RISKS for FOETUS  VENTILATORY / AIRWAY MANAGEMENT

 ANAESTHESIA
 HYPOXEMIA, ASPHYXIA  HAEMODYNAMIC MANAGEMENT
 TERATOGENICITY
 NEUROTOXICITY
 PRE-TERM LABOUR
 REDUCED UTERO-
PLACENTAL PERFUSION

 HYPEROSMOLARITY /
DEHYDRATION NEUROPROTECTIVE
 UTERINE ARTERY MEASURES
VASOCONSTRICTION
 HYPOTHERMIA  HYPEROSMOLAR SOLUTIONS
 HYPERVENTILATION
 HYPOTHERMIA

NEUROANAESTHETIC GOAL

OPTIMAL CARE for MOTHER and MINIMIZATION of HARM for FOETUS

Figure 1. Prudent neuroanaesthetic care may minimize foetal exposure to potentially harmful conditions

Case reports and clinical practice suggest that the complexity of resuscitative, (neuro)anaesthetic, neurosurgical, obstetric, neonatal
and critical care support for mother and foetus increases progressively from elective, to urgent, to emergency situations because of the
reduction in both time available and safety associated with the treatment [6, 7].

- 2 -
Background

Implications of pregnancy related physiological changes

The multiplicity of anatomical and physiological changes that occurs during pregnancy have numerous implications for anaesthetic
care (Table 1) [8]. For example, the plasma volume increases by ~ 50% at the end of the first trimester and results in a relative anaemia
that can mimic haemorrhage in pregnancy. Assessment of intravascular volume and blood loss is complicated by a decrease in peripheral
20
and pulmonary vascular resistance, a reduced blood pressure, and an increase in cardiac output, all of which mask signs of hypovolae-
mia.

Table 1. Physiological changes in pregnancy and their Implications

System Change in pregnancy Implications

Central Nervous
Minimal alveolar concentrations ↓ 25% Initial end-tidal sevoflurane or iso-
for inhalational anaesthetics flurane concentrations of 1-1.5%
are appropriate
Cardiovascular
Cardiac output ↑ 40% Hypovolaemia difficult to detect
Heart rate ↑ 20% as venoconstriction often absent
Systemic vascular resistance ↓ 15%
Central venous pressure ↔ Significant blood loss may occur
Plasma volume ↑ 45% before signs of shock present
Blood volume ↑ 40%
Electrocardiograph nonspecific ST changes, ECG may mimic myocardial
Q in III, aVF, ectopics contusion
Respiratory
Tidal volume ↑ 35% Rapid hypoxemia due to decreased
Respiratory rate ↑ 15% oxygen and respiratory reserve
Functional residual capacity ↓ 25%
Residual volume ↓ 20% Increased uptake of inhaled agents
Oxygen consumption ↑ 20%
PaCO2 ↓ 15% Decreased maternal buffering
Bicarbonate ↓ 15% reserve
Haematological
Haemoglobin ↓ 20% Haemorrhage may be misinterpreted
Coagulation factors ↑≈ 50-100% as physiological anaemia
White cell count ↑25% Increased coagulant activity may
reduce blood loss, but also cause a
prothrombotic state
Renal
Renal blood flow ↑ 60% Naturiesis
Glomerular filtration rate ↓ 30% In case of oliguria: fluid challenge
may be required to differentiate
between pre-renal and renal cause

Gastrointestinal ↑ Cephalad shift of small intestine ↑ Risk of upper abdominal

penetrating injury
↓ Gastro-oesophageal sphincter function ↑ Risk of reflux and aspiration

↑ = increase, ↓ = decrease, ↔ = no significant change (modified from Himmelseher and Kuczkowski [8])

- 3 -
 Typical signs of instability may, therefore, not be reflected in maternal haemodynamic measurements, and blood loss up to 2 litres
may not be clinically apparent. Several factors predispose pregnant patients to early and rapid oxygen desaturation. At term, the pregnant
patient has a 20% increase in oxygen consumption at rest, and the gravid uterus elevates the diaphragm by 5 cm. Weight gain adds to the
decrease in functional residual capacity, which, together with a tendency for small airway collapse and vascular engorgement, results in a
reduced oxygen reserve. Increased minute ventilation decreases the arterial carbon dioxide tension, and increased renal excretion of bi-
carbonate ions limits respiratory alkalosis. Thus, pregnant patients rapidly develop metabolic acidosis during hypoperfusion and hypoxia.
All parturients should be assumed to have full stomachs because gastro-intestinal motility is decreased, gastric acid content is elevated,
and gastro-oesophageal sphincter function is reduced. In combination with intracranial pathology, pregnant neurosurgical patients may
have an especially increased risk of aspiration of gastric contents. Because clotting factors and plasma proteins increase during preg-
nancy, blood becomes hypercoagulable resulting in an increased risk of thrombo-embolism. Following trauma, a coagulopathy may be
present despite a normal fibrinogen level. Because the activity of the plasminogen system is also altered, delayed fibrinolysis may occur.
Placental laceration or traumatic abruption may readily cause disseminated intravascular coagulation.

Maintaining uterine blood flow

Maintenance of maternal systemic arterial blood pressure is of the utmost importance at all times to ensure adequate uterine blood
flow and transplacental delivery of oxygen and nutrients to the foetus. While pre-pregnancy uterine blood flow is about 60 ml/min, uter-
ine blood flow increases to 600 ml/min at term, which accounts for ~ 10% of total maternal cardiac output [12]. Due to vasodilation of
placental vessels, uterine blood flow is maximal in late pregnancy, and because autoregulation is absent, uterine perfusion is related
to maternal mean arterial pressure in a linear fashion. When undergoing neuroanaesthesia, hypovolaemia, anaesthetic (over)doses,
vasodilators, sympathetic blockade from neuraxial anaesthesia, or exaggerated positive pressure ventilation can easily decrease MAP
and uterine blood flow. This has to be strictly avoided or aggressively treated. However, all vasopressors affect uterine blood flow in a
dose-dependent manner (Table 2), and should be carefully titrated to prevent overshooting their vasoconstrictor activity. In advanced
pregnancy, aorto-caval compression due to the gravid uterus when supine may reduce effective cardiac output up to 25%. Uterine dis-
placement or left lateral tilt at a 15-degree angle (if there is uncertainty about spinal cord injury) is mandatory after 20 weeks’ gestation.

Anaesthetic agents and potential drug induced embryotoxicity

Foetal exposure to drugs used in neuroanaesthesia depends on their placental transfer and characteristics of the foetal circulation
that delay equilibration between foetal arterial and venous blood. Most substances administered to the mother during neuroanaesthesia
readily cross the placenta, and reach the foetus via passive diffusion across a concentration gradient (Table 3) [12-14,17]. At Caesarean
section under general anaesthesia the time interval from induction of anaesthesia to the delivery of the foetus is critical as far as neona-
tal drug plasma concentrations of anaesthetic drugs originally given to the mother is concerned. No ‘best’ anaesthetic agent has been
identified for the pregnant patient because virtually every drug has been shown to be teratogenic to certain species at certain times under
certain conditions. High doses or prolonged exposure to all classes of substances should be avoided, because the dosage of anaesthet-
ics reaching the developing embryo determines the degree of teratogenic or ‘toxic’ effects. The time at which drug exposure occurs during
embryogenesis is critical; for instance, a specific drug could kill the blastocyst or allow it to develop entirely normally if exposure occurs
during the first 2 weeks of gestation because the cells are ‘totipotent’ at this time [15]. If exposure occurs 12 weeks after conception, or-
ganogenesis is complete and only organ size or perhaps brain development could be affected. However, to investigate the mechanisms
by which anaesthetics cause developmental neurotoxicity, a research technique using pharmacogenetics or system biology may be help-
ful [16]. Experimental data derived predominantly from rodent animal models (and occasionally primates) cannot be directly extrapolated
to provide advice governing the use or avoidance of specific drugs in the clinical setting at the present time. In summary, despite the
recent debate regarding the effects of anaesthesia on the developing brain, there is a lack of prospective animal studies investigating
the effects of anaesthetics on embryo development and neurotoxicity. It is probable that sample sizes for such studies might need to be
enormous to identify the actual incidence of anaesthetic drug toxicity. During organogenesis, the potential for teratogenicity associated
with anaesthetic drugs is, nevertheless, rather high.

- 4 -
 21

Table 2. Commonly used vasoactive drugs and pregnancy

Drug Teratogenicity Side-effects Recommendations

Epinephrine Not observed Reduction of For vital indications only

uteroplacental As adjuvant drug in regional
perfusion (UPP) anaesthesia without concern
Norepinephrine Not observed As above Strict indications only
Dobutamine Not observed No reduction of UPP Prefer

Cafedrine / Theo- Not observed Dose-dependent

drenalin reduction of UPP
st
Etilefrine So far, not observed Avoid during 1 trimester
Ephedrine With high doses, Dose-dependent As above
Phenylephrine embryotoxic effects reduction of UPP As above
cannot be excluded
ß-Blockers Some reports of Reduced foetal weight Prefer well proved drugs
increased rates of gain, bradycardia and such as metoprolol
deformity after hypoglycemia if used
atenolol until delivery
st
α-Methyldopa Probably no Some reports of 1 Choice drug
teratogenicity hepatotoxic effects
nd
Dihydralazine Not observed As above 2 Choice drug
nd
Calcium channel Not observed Tocolytic effects; 2 Choice drugs, prefer
blockers Verapamil: hyperpro- well proved agents
lactinaemia and such as nifedipine or
galactorrhoea possible verapamil
ACE-Inhibitors,
AT-II-Receptor- Unclear Deficits in placental Contraindicated
Antagonists perfusion
Clonidine Not observed Reserve drug
st
Digoxin Not observed 1 Choice drug for foetal
tachycardia
Nitroglycerine Not observed Tocolytic Limited data on use during
st
1 trimester

UPP = uteroplacental perfusion, ACE = angiotensin converting enzyme; AT = angiotensin (modified from Neindorff [13])

- 5 -
 22

Table 3. Critical components of foetal exposure to drugs used in neuroanaesthesia

Determinants of drug passage across the placenta

Physicochemical drug Concentration gradient Haemodynamic factors
characteristics

Molecular weight Drug dose administered Hypotension

(e.g., blood loss, regional blocks)
Lipid solubility Timing of intravenous Aortocaval compression
administration relative to
uterine contraction
Nonionized versus Use of vasoconstrictors Use of vasoconstrictors
ionized

Characteristics of the foetal circulation

The foetal circulation delays drug equilibration between mother and foetus. The foetal liver is the first
organ perfused by the umbilical vein, and umbilical vein blood is diluted by foetal venous blood from the
gastrointestinal tract, head, and extremities.

(modified from Pedersen et al [17])

From a clinical point of view, the choice of neuroanaesthetic and other drugs should be limited to those with a strong - albeit empiri-
cal – safety record. Among intravenous agents, thiopental and propofol may cause neonatal depression, and need to be carefully titrated
Legends
to avoid maternal hypotension [9, 10]. In haemodynamically compromised patients lower than usual doses of these agents may be ap-
Figure 1to produce the desired effects. Whether propofol offers any advantage or disadvantage over thiopental in pregnant patients is
propriate
controversial. Propofol may be associated with slightly lower initial Apgar scores at the time of Caesarean section, and may cause mild
Prudent neuroanaesthetic care may minimise foetal exposure to potentially harmful conditions
metabolic acidosis in long neurosurgical procedures in pregnant patients [10].

Ketamine has been used in combination with other drugs for induction of anaesthesia in the obstetric setting to prevent hypotension.
Figure 2
When the racemic form is given to the mother at a dose of 1-1.5 mg/kg, hypotension can be prevented providing the patient is not pro-
Timingvolume
foundly of neurosurgery inthe
depleted and relation
drug istoinjected
gestational
slowly.age and tasks
Ketamine is nooflonger
neuroanaesthesia (modified
contra-indicated in the head-injured patient. It does not
increase
from Ngthe ICP
and when combined
Kitchen with a GABA
[5] and Rosen [11]).agonist in mechanically ventilated patients [8]. Ketamine crosses the placenta, but tends
not to produce neonatal depression. Ketamine has been implicated in causing neurotoxic effects at, or slightly above, clinically relevant
doses in whole-animal models [16]. However, this should not be construed to imply that ketamine carries a greater risk of causing neuro-
degeneration than other anaesthetics because to date most preclinical data have been generated with this drug. Whether prevention of
hypotension through the use of ketamine or any other drug is likely to be of greater benefit to the mother and foetus than the avoidance
of the potential to cause long-term drug induced effects on the nervous system is a question that cannot be answered.

Remifentanil and target-controlled propofol infusions have been used in pregnant women [9, 10]. If used for Caesarean section,
personnel skilled in neonatal resuscitation and administration of naloxone are required to be present because of the risk of neonatal
chest wall rigidity and apnoea. All opioids administered to the mother prior to delivery may cause neonatal respiratory depression and
require monitoring of the newborn. This also applies to opioids administered neuraxially because of the potential for systemic absorption.
Benzodiazepines may also cause neonatal depression and induce a ‘floppy infant’ syndrome with reduced muscle tone, hyporeflexia,
and difficulty suckling. Due to limited foetal metabolising capacity, benzodiazepines readily accumulate in foetal tissues, which may lead
to pharmacologically effective plasma concentrations in the neonate days or weeks after administration to the mother. Nevertheless,
carefully titrated use of a benzodiazepine may be suitable for anxiolysis in the second and third trimester, for example to facilitate awake
fiberoptic intubation. For maintenance of balanced general anaesthesia, volatile inhalational anaesthetics such as isoflurane or sevoflu-
rane at 1–2 MAC are effective. Pregnant patients require about 25% lower doses of most volatile anaesthetics. At these concentrations,
only minor increases in uterine blood flow and uterine bleeding are induced, and cerebral autoregulation is preserved. Because all volatile
anaesthetics induce uterine relaxation, concentrations > 1-1.5 MAC should be avoided.

- 6 -
 Nitrous oxide should not be administered in pregnant neurosurgical patients for a variety of reasons. In the mother, it may increase
the ICP and cerebral oxygen metabolic rate, expanding the size of an occult pneumothorax and contributing to postoperative nausea and
vomiting. In the foetus, nitrous oxide may have adverse effects on development because of its propensity to oxidize cobalamin and inhibit
methionine synthase activity, affecting, for example, DNA production and myelin deposition.

Muscle relaxants cross the placenta only in small amounts. Approximately 10% of maternal plasma concentrations can be detected
in the foetus, which is usually not enough to cause foetal muscle relaxation. In view of its short onset, predictable block, and short dura-
tion of action, succinylcholine is the relaxant of choice for rapid sequence induction of anaesthesia in pregnancy. Although there may be
a transient, but in most cases clinically negligible increase in ICP, it should be used when there is urgent need to secure the airway [6,
9, 10]. This seems to be especially valid for the head-injured, pregnant trauma patient with a higher likelihood of difficult intubation, re-
gurgitation and aspiration, and critical oxygen desaturation. Nevertheless, succinylcholine is absolutely contra-indicated in some trauma
settings: after a time interval of ~ 24-48 hours succinylcholine must not be used following spinal cord injury, denervation injuries causing
extremity paralysis, severe muscle crush or burn injuries and cerebral insults associated with paralysis. In such situations the risk of
inducing hyperkalaemia leading to cardiac arrest is too high. Succinylcholine may increase uterine tone, which may be relevant if foetal
hypoxia is present. In the third trimester of pregnancy, plasma cholinesterase is reduced by 25%, which may unmask an inborn plasma
cholinesterase deficiency and lead to prolonged effects of both succinylcholine and mivacurium. In recent years, rocuronium has proven
to be a good alternative to provide acceptable to good intubating conditions in emergencies, especially when used at higher doses of
1-1.5 mg/kg for rapid sequence induction. However, these doses will result in at least 50 minutes of muscle paralysis, and the possibil-
ity of a ‘cannot ventilate, cannot intubate’ scenario. Hopefully, the introduction of sugammadex into clinical practice and its reversal of
rocuronium-induced neuromuscular block will help to prevent such disasters, although there is almost no clinical experience with the use
of sugammadex in pregnant patients. Cholinergic drugs such as neostigmine may be used for antagonizing muscle relaxants, but atten-
tion should be paid not to induce labour prematurely.

Whenever possible, regional anaesthesia should be included in the anaesthetic plan. It provides analgesia without interfering with
labour or producing maternal or foetal depression. Ropivacaine and bupivacaine show less uteroplacental transfer than lidocaine, me-
pivacaine, and prilocaine, and ropivacaine’s lower toxicity increases its margin of safety when applied neuraxially. When typical doses
are employed, no embryotoxic effects from neuraxial local anaesthetics (LA) have been observed, although foetal acidosis may increase
uteroplacental transfer of these drugs. Local anaesthetics may be combined with opioids permitting a dose reduction of the local anaes-
thetic component but adding the possibility of opioid-related side-effects. Paracetamol has been utilised as a first line analgesic agent
during pregnancy, but may cause asthma in the child. Non-steroidal anti-inflammatory drugs should not be used after the 28th gestational
week because they may cause premature closure of the ductus arteriosus. Cyclo-oxygenase inhibitors are usually avoided, because
they carry a potential for inducing foetal renal failure, necrotizing enterocolitis or persistent foetal circulation after birth when used after
32 weeks gestational age [10]. Tramadol may be used, but lowers the seizure threshold. Aspirin and metamizol have been considered
as second-line analgesic agents for pregnant women. However, both should not be given in the third trimester because of concerns of
ductus arteriosus closure, and aspirin’s inhibition of thrombocyte aggregation.

Corticosteroids carry a risk for inducing oro-palatal-mandibular clefts, and should be avoided during the first trimester. The administra-
tion of a single dose of a steroid to reduce peritumour oedema appears safe, but accelerates foetal lung maturity. Most anti-emetic drugs
can be given during pregnancy with broad clinical experience supporting use of agents such as metoclopramide and droperidol; serotonin
receptor antagonists may also be administered [9, 10]. Subsequent to use of magnesium in the mother, reduced muscle tone, respiratory
failure, pulmonary oedema, and prolonged muscle relaxant activity may be seen in the newborn.

Timing of neurosurgery in relation to gestational age

The clinical diagnosis of intracranial pathology is frequently delayed in pregnant women because neurological symptoms may be
mistaken for those secondary to pregnancy. Whenever neurosurgery is considered in the pregnant patient, the decision to perform
surgery should be primarily based on neurosurgical rather than obstetric considerations (Figure 2) [5, 11]. The indications for surgery
depend on clinical neurological assessment, and determination of the location and histology of the lesion. For purely elective neurosur-
gery, pregnancy may be allowed to proceed to term. When neurosurgery is considered essential, but the neurological condition is stable,
prolongation of gestation can be permitted with close monitoring of mother and foetus. Once gestation has reached 32 weeks, vaginal

- 7 -
or Caesarean delivery can occur, followed by a craniotomy. This is not because the threshold for foetal viability begins at 32 weeks, but
because the risks of preterm delivery even at this gestation are believed to be proportionately less compared with the risks to the foetus
of therapies directed at the mother such as treatment with hyperosmotic solutions. Where neurosurgery needs to be performed at an
emergency procedure, Caesarean section should be performed if there is a viable, near-term foetus. In an unstable patient at an early
stage of gestation required emergency neurosurgery, this would be undertaken with the foetus in-utero. In this situation the risks to the
foetus should be made very clear.

PREGNANT NEUROSURGICAL PATIENT

ELECTIVE ESSENTIAL EMERGENCY NEUROSURGERY

st nd nd
1 / Early 2 Late 2 / early
rd
trimester 3 trimester
postpartum postpartum

Delay until postpartum

If no or minimal increased
risk to mother, permit
gestational advancement

NEUROANAESTHESIA

If greater than minimal ► Consult obstetrician / neonatologist

increased risk to mother,
proceed with neurosurgery
► With viable near-term foetus:
Offer general anaesthesia,
for Caesarean section, then
► Administer best possible neuro-
anaesthesia for mother,
► With intact pregnancy: Modify by caring
for foetal well-being
► Use foetal monitoring if of clinical utility

Figure 2. Timing of neurosurgery in relation to gestational age and tasks of neuroanaesthesia

(modified from Ng and Kitchen [5] and Rosen [11])

- 8 -
Management of emergency neuroanaesthesia

Once the clinical history and diagnosis has been established a plan for anaesthesia can be tailored to the individual patient that an-
ticipates the requirements for neurosurgical management, in relation to the gestational age, and designed to preserve foetal well-being.

Anaesthesia for cranial neurosurgery during pregnancy

Before induction of anaesthesia, acid aspiration prophylaxis is important for women in whom pregnancy has extended past the first
trimester, especially if there is a history of gastro-oesophageal reflux. Sodium citrate is recommended, supplemented by inhibitors of
gastric acid secretion [9, 10]. In view of the combination of a limited maternal reserve and an exaggerated foetal response to maternal
hypoxia, hypercapnia, and acidosis, maternal hypoxia must be prevented. Because rapid desaturation in pregnant women occurs with
the arterial oxygen tension decreasing at least twice the rate as in non-pregnant women if hypoventilation and apnoea occurs, careful
pre-oxygenation is mandatory. Difficult airway management algorithms such as the modified ASA algorithm [18] may be helpful for man-
aging the airway, but no guidelines specifically address pregnant patients. Despite a 17-fold greater incidence of failed intubation than in
the general surgical population [8], a patent airway needs to be assured even in pregnant patients with airway compromise, respiratory
distress, or impaired consciousness. Tracheal intubation in morbidly obese patients may be very difficult. Optimal preparation to ensure
the sniffling position, a rapid sequence induction with cricoid pressure, a short-handled laryngoscope and a tube with a small diameter
than normal may help to achieve successful intubation. However, if attempts to intubate or rescue airway management with a supraglottic
device fail, there is little scope to delay performing an immediate emergency cricothyrotomy or tracheostomy. That may be the only avail-
able option to save mother and foetus. Ideally, an awake fibreoptic intubation should be used when there is a known or suspected difficult
airway or facial or cervical spine injury [19]. An awake mother may provide the best conditions for preventing haemodynamic instability
and aspiration during intubation. A smooth rapid-sequence intravenous induction is required early in the second trimester. Agents should
be immediately to hand to attenuate the hypertensive response to laryngoscopy and tracheal intubation, and the hypotension associated
with induction. Inhalational, balanced, and total intravenous anaesthetic techniques have all been used successfully for maintenance of
anaesthesia. To detect haemodynamic changes and maintain stability, intra-arterial blood pressure (IABP) monitoring should be estab-
lished before induction. Fluid administration and vasopressors (Table 2) are used to preserve cerebral and uteroplacental perfusion. If
neurosurgically feasible, patients should be placed in the left lateral position to avoid aorto-caval compression during long procedures.
Although ephedrine has historically been the vasopressor of choice, phenylephrine is now often used. It may offer some advantages such
as better maternal cardiovascular stability and improved neonatal acid-base status [20].

The exact target range for blood pressure during intracranial procedures have not been defined yet, but generally, the BP should be
kept within baseline normotensive levels or should be targeted to ~ 140/90 mmHg. If the intracranial pressure (ICP) is increased, reducing
the BP is inadvisable, while a systolic BP < 150 mm Hg has been recommended for normotensive patients with an unsecured cerebral
aneurysm [21]. Ventilatory goals should be determined by end-tidal capnography and arterial blood gas measurements. High arterial
oxygen pressure and, in advanced pregnancy, mild hyperventilation should be instituted within physiological parameters appropriate for
the gestational age. Pregnancy induces a compensatory respiratory alkalosis that eventually results in a maternal paCO2 of 30-32 mmHg
and a pH of 7.4 to 7.45.

Body temperature in the pregnant neurosurgical patient should be kept within normal limits. If hypothermia is deliberately induced
as a neuroprotective strategy, foetal temperature will inevitably change along with maternal temperature. Although not fully investigated,
mild-to-moderate hypothermia does not appear to increase foetal morbidity. If maternal respiratory acidosis is prevented, foetal blood gas
and acid-base status parallel those of the mother. Despite an increase in uterine vascular resistance and a decrease in uterine blood flow
during hypothermia, oxygen transfer is unaffected. Both maternal and foetal heart rate decrease during cooling, followed by an increase
during rewarming. Use of short-term neuroprotective hyperventilation needs to be restricted to the minimum period possible. In pregnant
neurosurgical patients, an increase in maternal alkalosis constricts pH-sensitive umbilical vessels, which decreases blood flow and in-
duces a leftward shift in the oxyhaemoglobin dissociation curve. As a result, an increased affinity of maternal haemoglobin for oxygen
and thus a decreased placental oxygen transfer occurs. Hypocapnia produced by excessive positive pressure ventilation increases mean
intrathoracic pressure, decreases venous return, and reduces cardiac output, resulting in reduced uterine blood flow, foetal hypoxia and
acidosis. Moreover, paCO2 values appreciably > 32 mmHg represent hypercapnia, which is associated with increased cerebral blood
flow and foetal respiratory acidosis. To control the ICP, mannitol administered in the pregnant neurosurgical patient may adversely affect

- 9 -
the foetus by inducing maternal hypotension and uterine hypoperfusion. Hyperosmolar substances may also force free water from the
foetus and amniotic fluid to the mother, which may cause contraction of foetal blood volume, cyanosis, and foetal bradycardia. Because
of concerns about the effects of foetal dehydration, use of hyperosmotic fluids should be restricted. Low doses of mannitol have been
administered without adverse foetal outcomes, but should be used with caution; high doses should be avoided.

Anaesthesia for combined Caesarean section and intracranial neurosurgery

Once the pregnancy has reached the late second or third trimester, delivery by Caesarean section followed by emergency neurosur-
gery is almost always performed under general anaesthesia. The risk of postpartum haemorrhage secondary to uterine atony during sub-
sequent neurosurgery, despite use of oxytocic treatment may require changing the volatile-based anaesthesia used for the Caesarean
section to intravenous anaesthesia for neurosurgery. [22]. Total intravenous anaesthesia with propofol has been associated with a slight
decrease in neonatal neurobehavioral performance scores as compared with balanced anaesthesia using thiopental and maintenance
with volatile agents [23]. Synthetic oxytocin may cause hypotension and result in increases in heart rate and cardiac output, but it has
been used without adverse effects in brain tumour patients. Ergometrine, a potent venoconstrictor, may produce hypertension and rise in
what is possibly already an elevated ICP in the presence of a blood-brain barrier that has lost its integrity, but may also decrease intrac-
ranial blood volume via cerebral venous constriction.

Anaesthesia for Caesarean section after recent cranial neurosurgery

If neurosurgery has been successfully performed in the late second or third trimester and the foetus has remained viable, the preg-
nancy can continue to term [24] with vaginal delivery as the primary goal. If Caesarean section is required, epidural anaesthesia is the
preferred mode if the parturient is alert, co-operative and does not have raised ICP. If the ICP is elevated, obstetric analgesia and an-
aesthesia is more controversial because none of the options is without hazard. Brainstem herniation and intracranial haemorrhage is a
potential risk if accidental dural puncture should occur, and epidural block is contra-indicated in patients with raised ICP [5, 10]. Epidural
injection of local anaesthetic has also caused a significant increase in ICP attributable to dural compression and cephalad displacement
of cerebrospinal fluid when space-occupying lesions or severe intracranial hypertension are present. However, this can be mitigated by a
slow injection of incremental volumes of the loading dose combined with a continuous infusion for maintenance of analgesia [25]. On the
other hand, the possible adverse effects of general anaesthesia on parturients with intracranial hypertension are further increases in ICP
and cerebral oedema during induction and emergence, pulmonary aspiration of gastric contents, failed tracheal intubation and neonatal
depression. The advantages and disadvantages of each anaesthetic technique must be considered in each patient.

Anaesthesia for interventional radiology

Often patients undergo interventional neuroradiology before neurosurgery or instead of an open procedure, when they are treated by
an endovascular technique. Successful vaginal delivery has been reported after coiling of an (un)ruptured intracranial aneurysm during
pregnancy [26, 27]. Neuroradiological interventions usually require general anaesthesia and invasive BP monitoring, whereas diagnostic
procedures can be performed with minimal sedation. Before femoral artery cannulation, uterine displacement for gestations > 20 weeks
should be performed. If foetal compromise is detected during the procedure, it must be halted and an emergency Caesarean section be
performed if the foetus is at viable gestational age. Under such circumstances, intracranial catheters are withdrawn, the femoral artery
sheaths left in-situ, and any the heparin administered to facilitate the neuroradiological procedure reversed.

In the event of an uncontrollable obstetric haemorrhage, endovascular embolisation of the uterine artery may be performed. The po-
tential risks for neuroradiation-induced foetal abnormalities are highly dependent on foetal age at exposure time [8]. Radiological adverse
effects are uncommon below 5 Rad after 17 weeks’ gestation, with 12-20 Rad being recognised as the threshold for teratogenesis (for
comparison an abdominal or pelvic CT scan will expose the foetus to 5-10 Rad). With direct cranial irradiation only, exposure of the ab-
domen and pelvis is limited further with appropriate shielding. Foetal risk also depends on the gestational age with gross malformations
induced by significant radiation exposure during organogenesis (4-8 weeks gestation) and severe mental impairment if exposure occurs
during neurological development (10-17 weeks gestation).

- 10 -
Special scenarios: anaesthesia for traumatic brain or spinal cord injuries

The principles and policies governing neurosurgical interventions for traumatic brain injury (TBI) and spinal cord injury remain unal-
tered in pregnant patients [28, 29]. It is essential that hypoxia and hypotension are avoided throughout management. If it is possible to
delay intubating the pregnant trauma victim until she has arrived at the hospital or before neurosurgery, awake fiberoptic intubation may
be a good choice of airway management [8]. When a combination of head and cervical spine injuries are present, respiratory depression
and the likelihood of aspiration can be reduced in awake patients if systemic analgesics and sedatives can be carefully titrated to maintain
communication. High or uncontrolled ICP is the most common cause of death and neurologic disability after TBI [28]. It has been shown
that brain oedema and intracranial hypertension develop in 40% of patients with severe TBI. To maintain adequate brain perfusion follow-
ing trauma, cerebral perfusion pressure (CPP) should be kept > 60 mmHg. If ICP increases above 20 mmHg, several treatment options
exist. After initiation of basic measures such as haemodynamic optimisation or use of deep sedation and analgesia, use of hyperosmolar
agents, hypothermia or decompressive craniotomy may be indicated. However, as previously mentioned, many of these measures may
affect the foetus adversely: use of vasopressors may compromise uteroplacental perfusion, prolonged exposure to sedatives may have
a negative effect on the foetal brain, and hyperosmolar agents redistribute free water from the foetus to the mother. So far, the effects of
mild therapeutic hypothermia on the foetus are unclear, but may not be detrimental. Decompressive craniotomy may therefore be the only
treatment choice for long-term elevated ICP that allows continuation of pregnancy over a longer period [8].

The management of spinal cord injury depends upon the site, extent, and duration of the spinal cord lesion [29]. Overall, the ap-
proach is no different than that for non-pregnant patients [8]. Complete transection of the spinal cord leads to flaccid paralysis, spinal or
neurogenic shock and cardiovascular instability. If the lesion is above C4, bradycardia may develop. Blockade of sympathetic autonomic
function by the cord injury typically results in decreased cardiac output, warm dry skin with loss of sensation and hypothermia. Because
signs of hypovolaemia may not be clinically apparent, fluid and volume therapy should be guided by invasive haemodynamic monitoring.
Vasopressors such as dobutamine may be necessary to increase cardiac function and systemic perfusion. Dobutamine does not reduce
uterine perfusion and has not been associated with teratogenic effects. The therapeutic value of applying high-dose methylprednisolone
as a ‘neuroprotective’ therapy has been called into question by neurosurgical specialty societies [29]. With the exception of incomplete
spinal cord injuries, no potential benefits appear to result from steroid administration. Autonomic hyper- or dysreflexia occurs in up to
85% of patients with a spinal cord injury above the level of the splanchnic autonomic outflow (T5/6 segment) at 1-3 weeks after injury
[29]. Usually this indicates the resolution of the period of neurogenic shock. A stimulus below the level of spinal injury causes paroxysmal
release of catecholamines with the result of serious consequences such as severe hypertension, tachycardia, flushing, sweating, anxiety,
convulsions or even intracerebral haemorrhage and death. Typically, the precipitating stimulus may be the result of a full bladder, a dis-
tended colon or possibly the onset of labour. To interrupt this autonomic hyperreflexia, regional anaesthesia or inhalational anaesthetics
are used. If not available, symptomatic treatment with labetalol or other antihypertensive agents is an alternative approach. Over aggres-
sive therapy, however, may result in hypotension after spinal cord injury that also needs to be avoided.

Anaesthesia for parturients with spinal cord injuries

In parturients with previous spinal cord injuries and a transection above ~ T6/7, uterine contractions pose a high risk of acute auto-
nomic hyperreflexia. Therefore, patient management is most appropriately conducted in centres with expertise in both obstetric and spinal
cord injuries. [30-33]. Pre-emptive initiation of continuous epidural analgesia in the early stages of labour has been used successfully
to prevent autonomic dysreflexia. Close maternal haemodynamic and foetal monitoring are required to identify stimuli that might induce
instability associated with exacerbations of autonomic hyperreflexia. Rapid initiation of treatment with nifedipine or clonidine titration (off-
label) has been used successfully to prevent symptom manifestation. Glyceryl trinitrate, labetalol, and small doses of diazoxide have
been advocated as effective alternatives to hydralazine for acute hypertension, but may reduce foetal blood flow. If there is a requirement
to expedite delivery and autonomic hyperreflexia has been problematic, a combined spinal-epidural technique may be useful. During
labour, magnesium sulphate can also be used for the management of hyperreflexia. Because of the practicalities in patients with previous
spinal cord injuries, it may not be easy to accomplish insertion of epidural analgesia from a technical point of view. Previous spinal surgery
and resultant scars may increase difficulty when trying to identify the epidural space and result in multiple puncture attempts, subdural
injection, accidental dural puncture or vascular trauma. Sometimes access to the epidural space via the caudal approach may be the
only suitable route to insert an epidural catheter. Determination of the ‘optimal’ epidural drug combination likely to provide satisfactory
analgesia in labour and suppress the likelihood of autonomic hyperreflexia has not been established. Most centres experienced in the
care of such patients combine an opioid and a local anaesthetic at doses similar to those used in other parturients.

- 11 -
Anaesthesia for spinal neurosurgical procedures

In the pregnant patient, acute progressive neurologic deficits or cauda equine syndrome originating from a spinal tumour, haemor-
rhage from tumours, spontaneous haematomas, vertebral vascular malformations or symptomatic disk prolapse can necessitate urgent
spinal surgery [34]. The prone position is often used for spinal surgery in pregnancy which may cause difficulties with foetal monitoring,
with an emergency Caesarean section, and with increased epidural venous bleeding, but may also increase the placental perfusion [5,
10]. It has been reported that some pregnant women have positioned themselves prone for lumbar spinal surgery under epidural an-
aesthesia. In contrast, some practitioners avoid neuroanaesthesia for spinal surgery in the prone position during pregnancy, and await
delivery by Caesarean section.

Foetal monitoring and tocolysis

Although there is no evidence to show that peri-operative uterine or foetal monitoring improves foetal outcome [35], its use may be
advocated in consultation with the obstetricians in the second and third trimesters of pregnancy. An external cardiotocograph can moni-
tor uterine activity when the fundus is above the umbilicus. Doppler monitoring indicates changes in foetal heart rate (FHR) that may
signal alterations in uterine perfusion, maternal ventilation, or foetal well-being. Baseline FHR changes also occur in the healthy foetus,
and anaesthetic drug-induced diminished beat-to-beat FHR variability is common [36]. However, if foetal bradycardia develops intra-
operatively, maternal hypotension or hypoxia must be suspected, and efforts to improve uteroplacental flow and foetal oxygenation must
be undertaken. If signs of foetal compromise persist, an emergency Caesarean section with temporary interruption of the neurosurgical
treatment is required, provided that the foetus is at a viable stage of gestation and that facilities for delivery at prematurity are available.
If labour occurs at pre-viable or very premature age, tocolysis is necessary to preserve the pregnancy. Volatile anaesthetics provide a
degree of uterine relaxation, but prophylactic tocolysis is only used if the risk of foetal loss is high. Tocolytic agents have considerable
maternal side-effects and their efficacy for non-obstetric surgery has not been proven. Cardiotocograph monitoring in the postoperative
period is useful to detect and treat preterm labour as early as possible.

Intensive care after neuroanaesthesia in pregnancy

After major surgery, trauma, or with instability, pregnant patients should be admitted to an intensive care unit for observation and
further management. All common, necessary critical care measures should be performed; even prone positioning for acute respiratory
distress syndrome (ARDS) after blunt chest trauma in late pregnancy may be used successfully as long as any direct pressure to the ab-
domen and gravid uterus is avoided [37]. Appropriate analgesia should be offered for maternal comfort, mobility and reduction of undesir-
able haemodynamic and foetal disturbances. A multi-modal approach combining local anaesthetic techniques, opioids and paracetamol
may be the best analgesic technique. Opioid agents should not be withheld, but close monitoring to prevent maternal and foetal hypoxia
are necessary. Patient-controlled analgesia is another option.

Key learning points

• Throughout the continuum of care, maintenance of uteroplacental perfusion and foetal oxygenation by avoidance of maternal hy-
poxia, hypotension, hypocarbia, and acidosis are of the utmost importance for foetal survival without injury in a pregnant neurosur-
gical patient.
• During or before neurosurgery, Caesarean section is not always warranted, but emergency Caesarean section needs to be consid-
ered if foetal distress develops and persists, or if a viable foetus may better be protected from emergency neurosurgery because
of maternal instability. Cardiotocograph monitoring of viable gestations ( >20 weeks’ gestation) should be initiated and continued
throughout maternal resuscitation, neurosurgery and postoperative management.
• Within the chain of pre-hospital and peri-operative care, anaesthetists contribute significantly to maternal, and thus to foetal, physi-
ological stabilisation by providing neuroanaesthesia based on a prudent choice of management modalities and drugs. However,
exact physiological measurements of the pregnant mother and foetus may often be impossible, so that therapy must be offered to-
gether with individualised assessment of mechanisms and types of diseases or injuries sustained, age of gestation and co-existing
disorders.
• Centres caring for pregnant neurosurgical patients should have protocols and education in place with input from local experts rep-
resenting all the disciplines involved in managing this unique multidisciplinary task.

- 12 -
References

1. Cohen-Gadol AA, Friedman JA, Friedman JD, et al. Neurosurgical management of intracranial lesions in the pregnant patient: a
36-year institutional experience and review of the literature. Journal of Neurosurgery 2009; 111: 1150-7.
2. Gaist D, Pedersen L, Cnattingius S, Sorensen HT. Parity and risk of subarachnoid hemorrhage in women. A nested case-control
study based on national Swedish registries. Stroke 2004; 35: 28-33.
3. Selo-Ojeme DO, Marshman LAG, Ikomi A, et al. Aneurysmal subarachnoid haemorrhage in pregnancy. European Journal of
Obstetrics and Gynaecology 2004; 116: 131-43.
4. Bateman BT, Schumacher HC, Bushnell CD, et al. Intracerebral hemorrhage in pregnancy: frequency, risk factors, and outcome.
Neurology 2006; 67: 424-9.
5. Ng J, Kitchen N. Neurosurgery and pregnancy. Journal of Neurology, Neurosurgery and Psychiatry 2008; 79: 745-52.
6. Kuczkowski KM. Trauma in the pregnant patient. Current Opinions in Anesthesiology 2004; 17: 145-50.
7. Weinberg L, Steele RG, Pugh R, Higgins S, Herbert M, Story D. The pregnant trauma patient. Anaesthesia and Intensive Care
2005; 33: 167-80.
8. Himmelseher S, Kuczkowski KM. Trauma in pregnancy. In: International textbook of obstetric anesthesia and perinatal medicine.
Kuczkowski KM, Drobnik L, eds. Warsaw, Poland: Medmedia, 2010: 17-27.
9. Van de Velde M, de Buck F. Anesthesia for non-obstetric surgery in the pregnant patient. Minerva Anestesiologica 2007; 73: 235-
40.
10. Wang LP, Paech MJ. Neuroanesthesia for the pregnant woman. Anesthesia and Analgesia 2008; 107: 193-200.
11. Rosen MA. Management of anesthesia for the pregnant surgical patient. Anesthesiology 1999; 91: 1159-63.
12. Weiner CP, Eisenach JC. Uteroplacental blood flow. In: Obstetric anesthesia, principles and practice, 3rd ed. Chestnut DH,
ed. Philadelphia, USA: Elsevier Mosby, 2004: 37-48.
13. Neindorff M. [Fetomaternal pharmacology: anaesthesiological approach in surgical interventions during pregnancy]. Anaesthesist
2010; 5: 479-90.
14. Zakowski MI, Herman N. The placenta: Anatomy, physiology, and transfer of drugs. In: Obstetric anesthesia, Principles and
Practice, 3rd ed. Chestnut DH, ed. Philadelphia, USA: Elsevier Mosby, 2004: 49-65.
15. Kuczkowski KM. Nonobstetric surgery during pregnancy: What are the risks of anesthesia? Obstetrical and Gynecological Survey
2003; 59: 52-6.
16. Wang C, Slikker W. Strategies and experimental models for evaluating anesthetics: effects on the developing nervous system.
Anesthesia and Analgesia 2008; 106: 1643-58.
17. Pedersen H, Santos AC, Finster M. Obstetric anesthesia. In: Handbook of clinical anesthesia. Barash PG, Cullen BF, Stoelting
RK, eds. Philadelphia, USA: Lippincott; 1991: 343-55.
18. Wilson WC. Trauma: airway management. (http://www.asahq.org/Newsletters/2005/11-05/wilson11_05.html).
19. Kuczkowski KM, Fouhy SA, Greenberg M, Benumof JL. Trauma in pregnancy. Anaesthetic management of the pregnant trauma
victim with unstable cervical spine. Anaesthesia 2003; 58: 822.
20. Cooper DW, Carpenter M, Mowbray P, et al. Fetal and maternal effects of phenylephrine and ephedrine during spinal anesthesia
for cesarean delivery. Anesthesiology 2002; 97: 1582-90.
21. Hoff RG, van Dijk GW, Mettes S, et al. Hypotension in anaesthetized patients during aneurysm clipping: not as bad as expected?
Acta Anaesthesiologica Scandinavica 2008; 52: 1006-11.
22. Boker A, Ong BY. Anaesthesia for Cesarean section and posterior fossa craniotomy in a patient with von Hippel-Lindau disease.
Canadian Journal of Anaesthesia 2001; 48: 387-90.
23. Van de Velde M, Teunkens A, Kuypers M, Dewinter T, Vandermersch E. General anaesthesia with target controlled infusion of
propofol for planned Caesarean section: maternal and neonatal effects of a remifentanil-based technique. International Journal of
Obstetric Anesthesia 2004; 13: 153-8.
24. Bharti N, Kashyap L, Mohan VK. Anesthetic management of a parturient with cerebellopontine-angle meningioma. International
Journal of Obstetric Anaesthesia 2002; 11: 219-21.
25. Chen SH, Sung YH, Chang PJ, Liu YC, Tsai YC. The management of labour using continuous lumbar epidural analgesia with
0.2% ropivacaine in a parturient with traumatic brain injury. European Journal of Anaesthesiology 2005; 22: 634-43.
26. Kizilkilic O, Albayram S, Adaletti I, et al. Endovascular treatment of ruptured intracranial aneurysms during pregnancy: report of
three cases. Archives of Gynecology and Obstetrics 2003; 268: 325-8.
27. Allen G, Farling P, McAtamney D. Anesthetic management of the pregnant patient for endovascular coiling of an unruptured
intracranial aneurysm. Neurocritical Care 2005; 4: 1-3.
28. Bullock, R, Chestnut RM, Clifton G, et al. Guidelines for the management of severe traumatic brain injury. The Brain Trauma
Foundation and the American Association of Neurological Surgeons, Joint Section of Neurotrauma and Critical Care. Journal of
Neurotrauma 2007; 24(Suppl 1): S1-S104.
29. Consortium for Spinal Cord Medicine. Early acute management in adults with spinal cord injury: a clinical practice guideline for
health-care professionals. Journal of Spinal Cord Medicine 2008; 31: 403-79.

- 13 -
30. Maehama T, Izena H, Kanazawa K. Management of autonomic hyperreflexia with magnesium sulfate during labor in a woman
with spinal cord injury. American Journal of Obstetrics and Gynecology 2000; 183: 492-3.
31. Ribes Pastor MP, Vanarase M. Peripartum anaesthetic management of a parturient with spinal cord injury and autonomic
hyperreflexia. Anaesthesia 2004; 59: 88-99.
32. Skowronski E, Hartmann K. Obstetric management following traumatic tetraplegia: Case series and literature review. Australian
and New Zealand Journal of Obstetrics and Gynaecology 2008; 48: 485-91.
33. Kuczkowski KM. Labor analgesia for the parturient with prior spinal surgery: what does an obstetrician need to know? Archives of
Gynecology and Obstetrics 2006; 274: 373-5.
34. Al-Areibi A, Coveney L. Anaesthetic management for sequential Cesarean delivery and laminectomy. Canadian Journal of
Anaesthesia 2007; 54: 471-4.
35. Balki M, Manninen PH. Craniotomy for suprasellar meningioma in a 28-week pregnant woman without fetal heart rate monitoring.
Canadian Journal of Anaesthesia 2004; 51: 573-6.
36. Tuncali B, Aksun M, Katircioglu K, Akkol I, Savaci S. Intraoperative fetal heart rate monitoring during emergency neurosurgery in
a parturient. Journal of Anesthesia 2006; 20: 40-3.
37. Kenn S, Weber-Carstens S, Weizsaecker K, Bercker S. Prone positioning for ARDS following blunt chest trauma in late
pregnancy. International Journal of Obstetric Anesthesia 2009; 18: 268-71.

- 14 -