Anesthetic drugs

9.1

Introduction

The challenges of general and regional anesthesia in pregnancy are to optimize maternal physiological function, preserve uteroplacental blood flow and oxygen delivery while avoiding unwanted effects of fetal exposure to drugs.

The likelihood of maternal and fetal exposure to anesthetic drugs is not insignificant. Current evidence suggests that between 1% and 2% of pregnant women will undergo a nonobstetric surgical procedure during pregnancy in developed nations [ ]. If absolutely necessary, surgery should be delayed to the second trimester of pregnancy to reduce the risk of both teratogenicity and miscarriage, although there is currently no firm evidence to support this approach. Elective surgery and therefore anesthesia should be avoided in pregnancy if at all possible. Postnatally, surgery should ideally take place only after the first six postpartum weeks to allow resolution of the physiological changes of pregnancy. Emergency surgery must proceed regardless of gestational age in order to preserve the life of the mother with the possible adverse effects to the fetus included in the consent process.

At delivery, intervention rates involving the use of general or local anesthetics vary widely across the world. Overall epidural rates (including operative delivery and labor analgesia) are as high as 95% in some regions in the United States. There is also an increasing overall rate of caesarean delivery worldwide, with the Dominican Republic delivering 58.1% of babies via cesarean section [ ]. The increasing incidence of these procedures means more women are exposed to anesthetic drugs. For cesarean delivery, regional anesthesia is preferred where possible as it minimizes the risks associated with general anesthesia including pulmonary aspiration of gastric contents, failed intubation, inappropriate maternal awareness, maternal gastric ileus postoperatively, and fetal exposure to drugs. No studies have shown a beneficial effect on the outcome of pregnancy after regional anesthesia compared to general anesthesia. Before the initiation of any anesthetic technique, resuscitation facilities should be available for both mother and fetus.

9.2

General anesthesia

General anesthetics may be divided into intravenous (IV) and inhaled volatile anesthetics. Indications for general anesthesia in pregnancy are listed in Table 9.1 and include urgency of delivery due to maternal or fetal indications, or operative delivery where regional anesthesia is not appropriate. As stated in other chapters, pharmacokinetic and pharmacodynamic profiles are altered in pregnancy and drugs for general anesthesia should be titrated as a result.

The uteroplacental circulation is not autoregulated and so fetal perfusion is critically dependent on maternal systolic driving pressure. Hypotension in general anesthesia is common. This is due to the combination of decreased systemic vascular resistance in pregnancy due to progesterone, which is exacerbated by volatile or IV anesthetic agents, and aortocaval compression from the gravid uterus. This is further exacerbated if the patient is in the supine position. Obstetric patients after the first trimester should undergo general anesthesia in the supine position with 15° left lateral tilt to reduce aortocaval compression. Meticulous attention should be paid to the maintenance of maternal systolic blood pressure through the use of IV fluids and vasopressors to ensure adequate placental flow.

9.3

Inhalational anesthetics

The minimum alveolar concentration (MAC) of volatile agents is a term used to describe the potency of anesthetic vapors. It is defined as the concentration that prevents movement in response to skin incision in 50% of unpremedicated subjects studied at sea level (1 atm), in 100% oxygen. Hence, it is inversely related to potency, and the more potent the agent, the lower the MAC value.

Although it is more than 160 years since the first use of modern anesthetics, the mechanism of action of volatile anesthetics still remains elusive [ ]. Inhaled anesthetic agents act in different ways at the level of the central nervous system with pre- and postsynaptic effects found. They may disrupt synaptic transmission by interfering with the release of excitatory or inhibitory neurotransmitters from the presynaptic nerve terminal, by altering the reuptake of neurotransmitters or by changing the binding of neurotransmitters to the postsynaptic receptor sites [ ]. There is a high correlation between lipid solubility and anesthetic potency suggesting inhalational anesthetics have a hydrophobic site of action and direct interaction with the neuronal plasma membrane is likely.

In pregnancy, neural tissues show increased sensitivity to effects of volatile anesthetics. The MAC is reduced by 30% under the influence of progesterone and endogenous endorphins [ , ]. The 25% increased alveolar minute volume from the first trimester [caused by both increases in respiratory rate (by 15%) and tidal volume (by 40%)] leads to a more rapid induction of general anesthesia than in the nonpregnant population if an inhalational induction technique were to be used. In most cases of general anesthesia in the parturient, preoxygenation with 100% oxygen precedes rapid sequence IV induction with cricoid pressure to secure the airway and to reduce the likelihood of pulmonary aspiration. This is followed by maintenance with 0.5–1.0 MAC of volatile anesthetic agents in either an air/oxygen or nitrous oxide/oxygen mix. Nitrous oxide has a rapid alveolar uptake and remains an important adjunct to reduce the risk of awareness during emergency cesarean delivery. Nitrous oxide, if administered in high concentrations for long periods (more than 50% concentration for over 24 h), has been shown to be a weak teratogen in rodents. Studies voicing concerns regarding nitrous oxide teratogenicity are not supported in clinical practice to date [ ]. Insufficient general anesthesia or analgesia may cause awareness and substantial maternal catecholamine release which is generally considered to be more detrimental to the fetus. Awareness during cesarean section is much more likely than during other procedures. The fifth National Audit Project (NAP5) in the United Kingdom found an incidence of awareness of 1:670 during cesarean section compared to 1:20,000 for all procedures combined [ ].

The high lipid solubility and low-molecular weight of all commonly used volatile anesthetics (isoflurane, sevoflurane, and desflurane) facilitate rapid transfer across the uteroplacental unit to the fetus. Prolonged induction to delivery time has been shown to result in lower Apgar scores in the fetus [ ]. Low doses of volatile anesthetics in combination with nitrous oxide may improve uterine blood flow but may also induce uterine relaxation. After the fetus is delivered, increasing concentrations of nitrous oxide, systemic opioids and IV oxytocin may be used to reduce the amount of volatile anesthetic required and to encourage uterine contraction. Nitrous oxide is poorly soluble and may be eliminated from the blood into the alveoli very rapidly. This effectively dilutes alveolar air, and available oxygen, so that when room air is inspired hypoxia may result. This “diffusion hypoxia” may occur in the neonate after delivery and so it would seem prudent to administer supplemental oxygen to any neonate exposed to high concentrations of nitrous oxide immediately before delivery [ ].

9.4

Intravenous anesthetics

Rapid sequence induction (RSI) is the administration of a potent IV anesthetic agent to induce unconsciousness followed by a rapidly acting neuromuscular blocking agent to achieve motor paralysis for tracheal intubation. The choice and dose of IV induction agent is crucial to ensure a balance between excellent intubating conditions with minimal maternal recall, and high maternal blood concentrations with subsequent adverse maternal haemodynamic effects and fetal transfer. The lipophilic characteristics of IV anesthetic agents enhance their transfer across the placenta.