Most textbooks still recommend a single dose of thiopental 4–5 mg/kg as induction agent of choice for GA in CS, arguing that this approach should result in an acceptable depth of anaesthesia for the mother with only limited neonatal depression. Propofol, in a dose sufficient for induction and to prevent maternal awareness (2–2.5 mg/kg), depresses the infant more (lower Apgar and NASC) than thiopental and causes a reduction in maternal blood pressure. Neither the use of propofol in general nor a thiopental dose exceeding 250 mg is licenced for the use in pregnancy. Hence, their use is off-label. Because of the limited global availability of thiopental, propofol becomes increasingly popular for induction. Ketamine crosses the placenta rapidly but an induction dose of 1 mg/ kg appeared not to be associated with lower Apgar scores or more need for resuscitation. Based on current literature, all three induction agents can be used safely.

Historically, opioids were administered only after umbilical cord clamping in an attempt to avoid respiratory depression of the neonate. However, in the presence of maternal disease, a judicious use of opioids can provide haemodynamic stability offering protection from an abrupt increase in arterial pressure. Opioids at induction might also increase anaesthetic depth and help to avoid awareness, which is a significant problem in obstetric general anaesthesia. All opioids have a high trans-placental passage resulting in dose-dependent neonatal depression. Due to its rapid onset and offset, the use of remifentanil has gained increasing popularity for obstetric GA in high-risk women. A recent meta-analysis on the maternal and foetal effects of remifentanil for GA in parturients undergoing CS found that remifentanil attenuated the maternal circulatory response to intubation and surgery. Less negative base excess and higher pH in the remifentanil group suggested a beneficial neonatal effect. It was concluded that an adequately powered trial addressing neonatal side effects of remifentanil is warranted. Remifentanil doses differed sharply among the included studies and dose–response effects should be further defined to find the optimal dose for both mother and infant [9, 10]. All doses of remifentanil are associated with a transient respiratory depression of the newborn. It is mandatory to anticipate neonatal resuscitation when remifentanil is used, especially in preterm infants.

Muscle relaxants are used to facilitate endotracheal intubation and to provide optimal surgical conditions. Until recently, 1 mg/kg of succinylcholine was routinely used for RSI because of its rapid onset. Succinylcholine is highly ionized and poorly lipid soluble, and only small amounts undergo trans-placental transfer without clinical relevance for the neonate. Rocuronium was introduced in 1994. Due to its rapid onset in higher doses (1 mg/kg), it soon gained popularity for RSI in the obstetric patient. Rocuronium did not adversely affect neonatal Apgar scores, acid-base measurements, time to sustained respiration or neurobehavioural scores [11].

All volatile anaesthetics cross the placenta and will cause a dose-dependent neurological depression of the neonate. Moreover, high doses of volatile anaesthetic agents have been associated with acute cardiovascular depression of the neonate [12]. Concentrations of volatile anaesthetics higher than 1 minimum alveolar concentration (MAC) should be avoided during caesarean section to avoid inappropriate respiratory adaptation because of neurological depression. Moreover, long-term neurological effects should be considered.

When exposed to anaesthetics drugs, the foetal or neonatal brain can be injured, resulting in long-term neurobehavioral deficits. Preclinical studies noted anaesthetic-induced developmental neurotoxicity (AIDN) with all general anaesthetic agents, even the ones approved for paediatric anaesthesia. The degree of which this AIDN occurs in humans has yet to be confirmed in well-designed clinical trials [13].

Normal perfusion of the foeto-maternal unit is mandatory for foetal wellbeing. Uterine-placental blood flow is mostly dependent upon maternal cardiac output and blood pressure. Vascular re-modelling of the uterine spiral arteries in a normal pregnancy involves a loss of smooth muscle and the elastic lamina from the vessel wall and a 5–10 fold dilation of the vessel mouth. This loss of smooth muscle makes the arteries less responsive to endogenous or exogenous sympathetic input.

Most anaesthetic drugs used for a general anaesthesia reduce maternal cardiac output, resulting in a lower blood pressure. This reduction in maternal cardiac output may lead to a reduction of uteroplacental blood flow. Since spiral arteries are not responsive to vaso-active drugs, the use of these drugs will correct maternal cardiac output and blood pressure and re-establish placental blood flow. In case of pre-eclampsia, spiral arteries do not manage to develop normally and will still respond to vaso-active drugs. Vasoconstriction of the spiral arteries will reduce the already impaired placental blood flow in pre-eclampsia and can acutely jeopardize the foetuses’ life. In pre-eclampsia, the ideal vasopressor is still a field of research.

Due to an inadequate technique of general anaesthesia for caesarean section (light anaesthesia with omission of opioids), a hypertensive response may occur during laryngoscopy and intubation. In healthy parturients, this time-limited rise in blood pressure will probably not cause any harm to the mother but in some patients with co-existing disease (especially pre-eclampsia) a sudden rise in blood pressure can cause intracranial haemorrhage. Though, the increase of catecholamine levels that accompanies the increase in blood pressure can jeopardize the uteroplacental blood flow that is of utmost importance if the foetus is in acute distress (often the case if general anaesthesia for caesarean section is warranted).

Many medications have been used to attenuate this response with varying success. Most of these drugs have been studied in patients with pre-eclampsia. Some authors prefer esmolol (1.5 mg/kg) or NTG (2 μg/kg), in combination with propofol (2 mg/kg) [14] while others will use, for reasons of availability, cost-effectiveness and safety, magnesium for the control of the hypertensive response in pre-eclampsia. The institution of the author of this chapter prefers the use of remifentanil for this purpose. Apart from the fact that remifentanil is a perfect surgical analgesic that in addition to propofol will prevent awareness during caesarean section, it permits to attenuate the maternal response to laryngoscopy with a time-limited neonatal depression [15]. A recent meta-analysis on the maternal and foetal effects of remifentanil for general anaesthesia in parturients undergoing caesarean section found that remifentanil attenuated the maternal circulatory response to intubation and surgery [9]. Less negative base excess and higher pH in the remifentanil group suggested a beneficial neonatal effect. It was concluded that an adequately powered trial addressing neonatal side effects of remifentanil is warranted. Remifentanil doses differed strongly among the included studies and dose–response effects should be further defined to find the optimal dose for both mother and infant [9]. Park et al. demonstrated that a single bolus of remifentanil of 0.5 or 1 mg/kg for induction of anaesthesia in severely pre-eclamptic patients attenuated maternal heart rate and pressor responses, with only minimal and transient neonatal respiratory depression [16]. More recently, Yoo et al. determined the effective dose (ED50/ED95) of remifentanil to prevent the pressor response to intubation in patients with severe pre-eclampsia. Intubation-induced increases of heart rate and blood pressure were attenuated in a dose-dependent manner by remifentanil, with the ED50 and ED95 being 0.59 [95% confidence interval (95% CI) 0.47–0.70] and 1.34 (1.04–2.19) mg/kg, respectively. However, all doses of remifentanil were associated with a transient respiratory depression of the newborn, and higher doses were associated with maternal hypotension (13%) [17]. The anticipation of brief neonatal resuscitation is necessary when remifentanil is used.

Rapid sequence induction with cricoid pressure, no mask ventilation and tracheal intubation remains the gold standard for a caesarean section under general anaesthesia. Reduced oxygen reserve due to a reduced functional residual capacity and an increased oxygen demand result in a shorter time to desaturation during apnoea. Preoxygenation with 100% oxygen is an effective measurement to prologue the time to desaturation, resulting in a longer time between induction and intubation. Keeping in mind that airway management and difficult intubation in pregnant patients are more frequent than in the routine surgical population, a difficult airway should always be anticipated with the right equipment and algorithms. Oxygenation and ventilator goals should be a PaO₂ above 70 mmHg and a PaCO₂ of 28–32 mmHg. Maternal hypoxia results in foetoplacental vasoconstriction, which reduces placental blood flow and foetal oxygen transfer and will compromise the foetus [18]. Maternal hypocarbia and lower bicarbonate are normal adaptations to pregnancy. Further hyperventilation should be avoided to prevent impairment of the uterine blood flow and maternal pH control within normal ranges for pregnancy is essential [18].

During mechanical ventilation, pregnant patients usually need higher peak inspiratory pressures and a positive end-expiratory pressure to overcome the increased chest wall compliance and the higher abdominal pressure due to the pregnant uterus [18]. The increased intrathoracic pressure can result in a reduction of the venous return and cardiac output and thus aggravate the haemodynamic effects of the aortocaval compression.

Nausea and vomiting are common symptoms after anaesthesia (general and loco-regional) for caesarean section with an incidence of 20–60%. Intraoperatively this can be challenging for the obstetrician, and it can be associated with accidental surgical trauma, jeopardizing the mother and the foetus. Moreover, there is a risk for aspiration of gastric content, resulting in bronchospasm, hypoxemia and postoperatively pneumonitis. Maternal hypoxemia can also adversely affect the foetus. Hypotension, reduced cardiac output, surgical stimulation and peri-operatively used drugs (opioids and uterotonics) have all been suggested to contribute to this high incidence. Many agents are efficacious in the prevention of nausea and vomiting, but there are no data on the potential adverse effects on the mother and neonate [24]. Hypotension is probably the most important cause of intraoperative nausea and vomiting (IONV). Hypoperfusion and consequent ischemia of the brainstem may lead to the activation of the vomiting centre. Also, gut hypoperfusion with the release of emetogenic substances has been suggested as possible cause of IONV [25]. Prevention or treatment of hypotension will decrease the incidence of IONV. Phenylephrine may be associated with less IONV compared to ephedrine, and a prophylactic continuous infusion seems more effective than bolus administration [25]. Interestingly, a recent study suggested that prophylactic ondansetron in obstetric patients undergoing spinal anaesthesia not only decreased the incidence of IONV but also improved the degree of hypotension and reduced the required amount of vasopressors [26].

Hypotension remains the most important side effect of spinal anaesthesia for a caesarean section with a reported incidence between 20% and 80%. The sympathetic block will result in a decreased systemic vascular resistance and venous return, impaired cardiac output and eventually decreased uteroplacental perfusion. The risk of foetal acidemia depends on the severity and duration of the hypotensive episode [27]. Active management to prevent spinal-induced hypotension and prompt treatment of spinal-induced haemodynamic changes minimize the adverse effect on foetal outcome.

Several methods have been described to prevent or treat spinal hypotension. Physical methods (e.g. leg wrapping) and the prevention of aortocaval compression (left lateral tilt) have been useful preventive measurements to attenuate the severity of hypotension. Also lowering the dose of spinal anaesthetic drugs can reduce the incidence and the severity of the spinal hypotension. However, the cornerstone of the management of spinal-induced hypotension relies on the use of vasopressors, intravascular fluid therapy or a combination of both. All described preventive interventions have been shown to reduce the incidence but did not eliminate the need for active treatment of hypotension [28].