Median Effective Concentration of Bupivacaine, Levobupivacaine and Ropivacaine After Intrathecal and Extradural Injection for Pain Relief in the First Stage of Labour

Despite 40 years of epidural analgesia, a consensus still does not exist regarding the best local anesthetic or the best technique for the provision of pain relief in early labour. Two new local anesthetics, levobupivacaine and ropivacaine, have recently been introduced into clinical practice because they have shown reductions in cardiovascular and cerebrovascular toxicity in several small animal, large animal and human volunteer studies. Evidence of improved safety from these studies suggest that the new local anesthetics should be used for surgical anesthesia, such as cesarean section, and limb block, where large volume, high concentrations of local anesthetics are required, and the risk of toxicity is high.

In contrast, the use of levobupivacaine and ropivacaine in small doses for analgesia in labour remains controversial, and bupivacaine remains the intrathecal and extradural local anesthetic of choice in many obstetric units. A change from bupivacaine to one of the newer drugs for analgesia in labour would require evidence documenting a distinct advantage of one the new local anesthetics in providing equivalent pain relief, but with less side effects.

Until now, intrathecal and epidural studies investigating the efficacy of bupivacaine, levobupivacaine and ropivacaine in obstetric anesthesia have focused on a comparison of % weight/volume solutions. However, close scrutiny of the chemical composition of local anaesthetics with the same % weight/volume shows marked differences in molar concentration.

The reason for differences in molar concentration are two-fold. Levobupivacaine is presented commercially as a base and not as a hydrochloride and therefore has 12.7% more molecules than the equivalent concentration of bupivacaine. In addition, ropivacaine has a smaller molecular weight than either drug and thus has 4.5% more molecules than bupivacaine and 8.4% less molecules than levobupivacaine. Although molar differences between drugs are relatively slight, a small reduction in molar concentration may provide similar pain relief, but result in a large reduction in side effects due to the shape and position of the efficacy and side effect dose response curves.

Comparative studies of all three drugs have been inconclusive. Intrathecal studies have shown a potency hierarchy of bupivacaine > levobupivacaine > ropivacaine, but equivalent potency between levobupivacaine and ropivacaine when injected with the opioid, sufentanil.