Sufentanil transfer in the human placenta during in vitro perfusion

Propose: Sufentanil, a lipophilic opioid, is used to provide analgesia for labour and Caesarean section, but may cause neonatal depression, Factors affecting placental transfer of sufentanil were investigated using human placentas. Study design: Transfer and uptake of sufentanil by the human placenta were studied using a single pass (open) in vitro perfusion model. The effects or change in sufentanil concentration (1-100 ng.ml(-1)) and change in fetal pH (range 7.4-6.8) on placental transfer were studied. Placental metabolism of sufentanil and the effects maternal protein content (fresh human plasma, albumin 4%, Media 199) on placental transfer were also investigated utilizing a closed (recirculated) in vitro perfusion system. Results: Sufentanil transfer was 2% at five minutes and plateaued at 12% by 45 min. The clearance index (Cl=sufentanil clearance/antipyrine clearance) was 0.56 +/- 0.2 for maternal to fetal (MTF) and 0.44 +/- 0.2 in the fetal to maternal (FTM) directions (P=NS), The Cl was 0.5 +/- 0.2 for 1 ng.ml(-1) and 0.61 +/- 0.3 for 100 ng.ml(-1) sufentanil concentration (P=N.S.). The placenta contained 7.1 +/- 2 and 9.8 +/- 3 ng.g(-1) sufentanil following MTF and FTM perfusions for 90 min at 1 ng.ml(-1). The placenta did not metabolize sufentanil. After one hour MTF washout, placental sufentanil content was 2.3 +/- 5 ng.g(-1) with 0.08 ng.ml(-1) sufentanil in the umbilical vein. Maternal plasma decreased MTF Cl from 0.41 +/- 0.1 for albumin and 0.4 +/- 0.1 for Media 199 to 0.17 +/- .06 for plasmia (P < 0.05). Decreasing fetal pH increased MTF Cl from 0.57 +/- .13 at pH 7.4 to 1.6 +/- .4 at pH 6.8 (P = 0.05). Conclusion: Sufentanil crossed the placenta by passive diffusion and accumulated in placental tissue, which acted as a drug depot, slowing the initial transfer. Placental transfer was decreased by maternal plasma proteins, but not by albumin. Fetal acidosis increased placental transfer. Due to its low initial umbilical vein concentration, sufentanil may be the opioid of choice when delivery is imminent (<45 min).