Prolonged local myometrial blockade prevents preterm labor after fetal surgery in a leporine model

Postoperative premature labor remains the foremost limiting factor to the development of fetal surgery. Most attempts at controlling this complication have involved the use of drugs delivered systemically to the mother. This study assessed the effects of prolonged local anesthetic blockade of the myometrium on preterm delivery after open fetal surgery.

Eighteen New Zealand rabbits at 23 days' gestation (term, 31 to 33 days) were divided in three groups. In group I (n = 6), the most proximal fetuses of both uterine horns were submitted to open amputation of a forelimb; in a few animals, one of the uterine horns was empty, hence, only one fetus was manipulated. In groups II (n = 5) and III (n = 7), an identical surgical procedure was performed. In group II, immediately before hysterotomy, the myometrium was injected with 0.5 mL of 0.5% bupivacaine along the incision line. In group III, only saline was injected. In group II, before uterine closure, the incised area of the myometrium was injected with 1.5 mL of a novel suspension of biodegradable polylactic-co-glycolic acid microspheres loaded with 75% w/w bupivacaine and 0.05% w/w dexamethasone. This suspension previously has been shown to provide peripheral nerve blockade for approximately 5 days. In group III, microspheres without any drug were injected.

Abortion rates were significantly different among the groups: 83.3% (five of six) for the does in group I, zero in group II, and 71.4% (five of seven) in group III (P < .05). The absence of abortions observed in group II occurred despite the fact that the fetal mortality rate was significantly higher in this group (87.5%, seven of eight fetuses) than in groups I (0) and III (33.3%, 4 of 12 fetuses, P < .05).

Prolonged local blockade of the myometrium with bupivacaine inhibits preterm labor after fetal surgery in rabbits. The high fetal mortality rate observed in this study may be caused by "transplacental" transfer of the local anesthetic to the fetus. Notably, the abortifacient effect of a dead fetus was completely suppressed by the local blockade. Studies using microspheres with local anesthetics that do not cross the placenta, in animal models with longer gestational periods, are warranted.