Local anaesthetics (LA) are basic drugs that bind to alpha1-acid glycoprotein and cross the placenta by simple diffusion. At physiologic pH they are lipid soluble and exist mainly in the unionised form, enhancing placental transfer. The amount transferred depends on the concentration of unionised (free) drug on the maternal and fetal sides of the placenta, which is turn is dependent on:
1. Maternal concentration:
Total dose of drug administered,
Route of administration,
Rate of absorption,
Metabolism, and
Excretion.

2. Characteristics of the drug:
pKb,
Protein binding (maternal, fetal).

3. Uteroplacental blood flow.

Maternal plasma concentration is largely influenced by the anaesthetic technique including the use of adjuvants such as epinephrine to delay absorption.

Spinal anaesthesia requires a lower total dose of LA than does epidural anaesthesia, resulting in less drug in the maternal circulation. Perineal infiltration and paracervical block (Figure 46.2) often result in higher placental transfer due to rapid uptake of the LA from these highly vascular tissues (1).

Bupivacaine is 96% protein bound, so less free drug is available for transfer than with lidocaine (67% bound). The mean F/M ratio for bupivacaine is approximately 0.3 and for lidocaine 0.5, confirming lidocaine's greater placental transfer. 2-Chloroprocaine is rapidly metabolised by plasma cholinesterase and it was thought that placental transfer was limited. However, transfer does occur (F/M = 0.92) but the levels of unchanged 2-Chloroprocaine are low in the normal infant making it clinically insignificant (2). Maternal and fetal pH and pKb of the LA (3) are of prime importance in placental transfer as only the unionised (free) portion can cross the lipid membrane. With fetal hypoxia and acidosis there is increased transfer as a greater amount of LA is ionized in the fetus. (4) The local anaesthetic is thus "trapped" in the fetus and cannot diffuse back to the maternal circulation. This may lead to LA toxicity in the newborn (5).

Pharmacokinetic data relating to these local anaesthetics is shown in Table 77.1.

References:
1. Philipson EH et al. Am J Obstet Gynecol 1984;149:403

2. Kuhnert BR et al. Anesthesiology 1980;53:21

3. Brown WU et al. Anesthesiology 1975;42:698

4. Gaylard DG et al. Anesth Analg 1990;71:42

5. Morishima HO et al. Anesthesiology 1981;54:182

6. Moore DC. Anesth Analg 1981;60:833