The placental transfer of local anaesthetic agents is largely perfusion-limited. Being lipophilic drugs, local anaesthetics can easily cross the placenta by passive diffusion (1, 2, 3). This ensures rapid equilibration between umbilical venous and maternal blood, even though the rate of transfer may be affected by placental uptake and large maternal/fetal protein binding or pH differences. Clinical studies also indicate that umbilical venous concentrations approach those in maternal blood rapidly (4). In addition, local anaesthetic concentrations in umbilical arterial blood have been shown to approach those in umbilical venous blood in approximately 30 minutes, indicating rapid tissue/blood equilibration in the fetus (4, 5).

Total umbilical venous/maternal venous (UV/MV) concentration ratios may differ considerably from unity, even after equilibrium has been achieved. For example, UV/MV ratios of bupivacaine and etidocaine at delivery are usually in the range of 0.2 - 0.4, whereas UV/MV ratios of lidocaine and mepivacaine are generally in the range 0.5 - 0.7. The low UV/MV ratios reflect a considerably smaller degree of plasma protein binding in the fetus compared to the mother and are related to the lower fetal concentrations of alpha1-acid glycoprotein. At equilibrium, free (unbound) blood concentrations on either side of the placenta are likely to be similar, or possibly somewhat higher, on the fetal side, due to ion trapping when the fetus is acidaemic.

A lower UV/MV ratio does not necessarily imply a greater margin of safety for the fetus, since toxicity is likely to be more closely related to free than to total blood concentrations. The important factor in this respect is the ratio of the free drug concentration that is associated with toxicity to the free drug concentration that is achieved in the fetus after maternal dosing. This ratio is in all likelihood greater for bupivacaine and etidocaine than for lidocaine and mepivacaine, indicating the greater safety margin of the former agents (6).

Placental transfer of local anaesthetic agents after epidural administration may yield depressed neurobehavioural scores in the newborn, especially when hypotension occurs. However, in the absence of hypotension or other complicating factors, neurobehavioural scores in infants born with epidural anaesthesia are mostly better when compared with general anaesthesia (7). There is now general agreement that properly conducted epidural anaesthesia does not cause neurobehavioural changes in the newborn.

References:
1. Hamshaw-Thomas A, Rogerson N, Reynolds F. Transfer of bupivacaine, lignocaine and pethidine across the rabbit placenta: Influence of maternal protein binding and fetal flow. Placenta 1984; 5: 61-70.

2. Hamshaw-Thomas A, Reynolds F. Placental transfer of bupivacaine, pethidine and lignocaine in the rabbit: Effect of umbilical flow rate and protein. Br J Obstet Gynaecol 1985; 92: 706-713.

3. Johnson EF, Herman N, Arney TL, Gonzalez H, Johnson V, Downing JW. Bupivacaine transfer across the human term placenta: A study using the dual perfused human placental model. Anesthesiology, 1995; 82: 459-468.

4. Reynolds F, Laishley R, Morgan B, Lee A. Effect of time and adrenaline on the feto-maternal distribution of bupivacaine. Br J Anaesth 1989; 62: 509-514.

5. Tucker GT, Boyes RN, Bridenbaugh PO, Moore DC. Binding of anilide-type local anesthetics in human plasma: Implications in vivo, with special reference to transplacental distribution. Anesthesiology 1970; 33: 304-314.

6. Tucker GT. Pharmacokinetics of local anaesthetics. Br J Anaesth 1986; 58: 717-731.

7. Abboud TK, Nagappala S, Murakawa K et al. Comparison of the effects of general and regional anesthesia for cesarean section on neonatal neurologic and adaptive capacity scores. Anesth Analg 1985; 64: 996-1000.