体外灌注期间人体胎盘中的舒芬太尼转运

Sufentanil transfer in the human placenta during in vitro perfusion.

作者信息

Krishna B R, Zakowski M I, Grant G J

机构信息

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

出版信息

Can J Anaesth. 1997 Sep;44(9):996-1001. doi: 10.1007/BF03011972.

DOI:10.1007/BF03011972

PMID:9305564

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).

摘要

目的

舒芬太尼是一种亲脂性阿片类药物，用于分娩和剖宫产的镇痛，但可能导致新生儿呼吸抑制。本研究利用人胎盘探讨影响舒芬太尼胎盘转运的因素。

研究设计

采用单程（开放）体外灌注模型研究人胎盘对舒芬太尼的转运和摄取。研究了舒芬太尼浓度变化（1 - 100 ng·ml⁻¹）和胎儿pH值变化（范围7.4 - 6.8）对胎盘转运的影响。还利用封闭（循环）体外灌注系统研究了舒芬太尼的胎盘代谢以及母体蛋白含量（新鲜人血浆、4%白蛋白、199培养基）对胎盘转运的影响。

结果

5分钟时舒芬太尼转运率为2%，45分钟时稳定在12%。母体到胎儿（MTF）方向的清除指数（CI = 舒芬太尼清除率/安替比林清除率）为0.56 ± 0.2，胎儿到母体（FTM）方向为0.44 ± 0.2（P = 无显著性差异）。舒芬太尼浓度为1 ng·ml⁻¹时CI为0.5 ± 0.2，100 ng·ml⁻¹时为0.61 ± 0.3（P = 无显著性差异）。在1 ng·ml⁻¹浓度下进行90分钟的MTF和FTM灌注后，胎盘含舒芬太尼量分别为7.1 ± 2和9.8 ± 3 ng·g⁻¹。胎盘不代谢舒芬太尼。MTF洗脱1小时后，胎盘舒芬太尼含量为2.3 ± 0.5 ng·g⁻¹，脐静脉中舒芬太尼浓度为0.08 ng·ml⁻¹。母体血浆使MTF CI从白蛋白组的0.41 ± 0.1和199培养基组的0.4 ± 0.1降至血浆组的0.17 ± 0.06（P < 0.05）。胎儿pH值降低使MTF CI从pH 7.4时的0.57 ± 0.13增至pH 6.8时的1.6 ± 0.4（P < 0.05）。