Cesarean delivery is one of the most common surgical procedures. In the United States, more than 1 million cesarean sections are performed each year, accounting for more than 30% of births. The majority of these procedures are performed using a regional technique; general anesthesia is reserved for patients who have a contraindication to a regional block or for emergencies, when there is not enough time for a regional block. Consequently, general anesthesia for cesarean delivery is relatively rare, and providers may be less comfortable administering it to parturients. Their discomfort is warranted. Although straightforward, general anesthetic for cesarean section is fraught with adverse events, including an increased risk of awareness, aspiration, difficult airway with hypoxia, drug-related uterine atony, and neonatal respiratory depression.
Numerous studies have characterized how physiologic changes of pregnancy alter the distribution, metabolism, and concentration-effect relationship of anesthetic drugs. Unfortunately, for most anesthetics, this body of knowledge has not transferred into dosing recommendations specific to the parturient. Anesthesiologists are left to rely on experience and careful titration to achieve unconsciousness and analgesia while avoiding adverse effects.
The purpose of this chapter is to review how physiologic changes associated with pregnancy influence kinetic and dynamic behavior of anesthetic drugs when used for general anesthesia under emergency conditions and explore through simulation how dosing technique may contribute to worrisome adverse effects.
PHARMACOKINETIC CONSIDERATIONS IN PREGNANCY
A summary of physiologic changes that influence intravenous anesthetic drug kinetics is presented in Table 37–1. Volume of distribution increases for most drugs due to a 40% to 45% increase in blood volume as well as an increase in body fat and total body water during pregnancy.1 Protein binding is reduced secondary to a 25% decline in albumin levels toward the end of pregnancy. Although levels of α-1-acid glycoprotein can decline in pregnancy, as an acute phase protein, levels exhibit a variable pattern. In some studies, third-trimester levels did not differ significantly from those obtained from nonpregnant women of childbearing age.2 Accelerated redistribution of intravenous anesthetics can be expected secondary to a 40% increase in cardiac output.1
Table 37–1Physiologic changes in pregnancy that influence anesthetic drug kinetics. ||Download (.pdf) Table 37–1 Physiologic changes in pregnancy that influence anesthetic drug kinetics.
|Drug distribution || |
| Cardiac output ||⇑ |
| Body fat ||⇑ |
| Blood volume ||⇑ |
| Total body water ||⇑ |
Drug protein binding
To α-1-acid glycoprotein
⇓ ⇑ or no change
|Metabolism || |
| Hepatic blood flow ||No change |
Cytochrome P450 activity
CYP3A4, 2D6, 2C9, UGT
| Pseudocholinesterase ||⇓ |
|Elimination || |
| Biliary ||⇓ ⇑ or no change |
| Renal ||⇑ |
Elimination and metabolism are significantly altered during pregnancy. Hepatic blood flow does not appreciably change; however, some enzymatic activity is decreased (CYP1A2, CYP2C19) and some increased (CYP3A4, CYP2D6, CYP2C9, UGT)....