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Sufentanil transfer in the human placenta during in vitro perfusion.

Abstract

PURPOSE

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 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).

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).

Authors+Show Affiliations

,

Department of Anesthesiology, New York University Medical Center, NY 10016, USA.

,

Source

MeSH

Acidosis
Analgesia, Obstetrical
Analgesics, Opioid
Blood Proteins
Cesarean Section
Delivery, Obstetric
Diffusion
Female
Fetal Blood
Fetal Diseases
Fetus
Humans
Hydrogen-Ion Concentration
Infant, Newborn
Labor, Obstetric
Maternal-Fetal Exchange
Metabolic Clearance Rate
Placenta
Pregnancy
Protein Binding
Serum Albumin
Sufentanil
Time Factors
Umbilical Veins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9305564

Citation

Krishna, B R., et al. "Sufentanil Transfer in the Human Placenta During in Vitro Perfusion." Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie, vol. 44, no. 9, 1997, pp. 996-1001.
Krishna BR, Zakowski MI, Grant GJ. Sufentanil transfer in the human placenta during in vitro perfusion. Can J Anaesth. 1997;44(9):996-1001.
Krishna, B. R., Zakowski, M. I., & Grant, G. J. (1997). Sufentanil transfer in the human placenta during in vitro perfusion. Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie, 44(9), pp. 996-1001.
Krishna BR, Zakowski MI, Grant GJ. Sufentanil Transfer in the Human Placenta During in Vitro Perfusion. Can J Anaesth. 1997;44(9):996-1001. PubMed PMID: 9305564.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sufentanil transfer in the human placenta during in vitro perfusion. AU - Krishna,B R, AU - Zakowski,M I, AU - Grant,G J, PY - 1997/9/26/pubmed PY - 1997/9/26/medline PY - 1997/9/26/entrez SP - 996 EP - 1001 JF - Canadian journal of anaesthesia = Journal canadien d'anesthesie JO - Can J Anaesth VL - 44 IS - 9 N2 - PURPOSE: 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 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). 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). SN - 0832-610X UR - https://www.unboundmedicine.com/medline/citation/9305564/Sufentanil_transfer_in_the_human_placenta_during_in_vitro_perfusion_ DB - PRIME DP - Unbound Medicine ER -