Sufentanil transfer in the human placenta during in vitro perfusion.
OBJECTIVE
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.


METHODS
Transfer and uptake of sufentanil by the human placenta were studied using a single pass (open) in vitro perfusion model. The effects of 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 of 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 (CI = 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 CI 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 CI from 0.41 +/- 0.1 for albumin and 0.4 +/- 0.1 for Media 199 to 0.17 +/- .06 for plasma (P < 0.05). Decreasing fetal pH increased MTF CI from 0.57 +/- .13 at pH 7.4 to 1.6 +/- .4 at pH 6.8 (P < 0.05).


CONCLUSIONS
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).
Krishna
B R
BR
Department of Anesthesiology, New York University Medical Center, NY 10016, USA.
Zakowski
M I
MI
Grant
G J
GJ
D000138:Acidosis / Q000378:metabolism; D016362:Analgesia, Obstetrical; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D002585:Cesarean Section; D036861:Delivery, Obstetric; D004058:Diffusion; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005315:Fetal Diseases / Q000378:metabolism; D005333:Fetus / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007231:Infant, Newborn; D007743:Labor, Obstetric; D008431:Maternal-Fetal Exchange; D008657:Metabolic Clearance Rate; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy / Q000097:blood; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D017409:Sufentanil / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors; D014471:Umbilical Veins
D000701:Analgesics, Opioid; D001798:Blood Proteins; D012709:Serum Albumin; D017409:Sufentanil