The effects of uterine and umbilical blood flows on the transfer of propofol across the human placenta during in vitro perfusion.
The safety of using propofol in parturients is controversial, and little information is available on the factors that influence the placental transfer of propofol. In this study, we investigated the effects of uterine and umbilical blood flows on the placental transfer of propofol by using the dually perfused human placental cotyledon. Placental transfer was evaluated on the basis of the placental clearances at various uterine and umbilical flow rates. The placental transfer of propofol was significantly facilitated by the increased uterine flow rates over the range from 7.5 to 25 mL/min. The placental clearances of propofol were also dependent on the umbilical flow rates over the range from 0.5 to 4.0 mL/min. In contrast, the placental transfer of antipyrine was flow dependent when the umbilical flow rate was <2.0 mL/min and became permeability limited when it was >2.0 mL/min. No differences in either maternal or fetal venous concentrations of propofol were observed as umbilical flow rates varied from 0.5 to 4.0 mL/min, suggesting that an equilibration across the placenta occurs at low flow rates. These results indicate that fetal uptake of propofol can be profoundly altered by the changes in both uterine and umbilical blood flows observed in various pathophysiologic conditions and that lipid solubility greatly influences placental transfer of drugs.


CONCLUSIONS
Uterine and umbilical blood flows are determinant features in controlling the placental transfer of propofol, and, therefore, changes in these variables would significantly affect the extent of fetal exposure to propofol.
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Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. yhe@partners.org
Seno
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Tsujimoto
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Tashiro
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D000328:Adult; D000465:Algorithms; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D000983:Antipyrine / Q000008:administration & dosage / Q000493:pharmacokinetics; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007773:Lactates / Q000097:blood; D010477:Perfusion; D011247:Pregnancy; D015742:Propofol / Q000493:pharmacokinetics*; D012039:Regional Blood Flow / Q000502:physiology; D014469:Umbilical Arteries / Q000502:physiology*; D014599:Uterus / Q000098:blood supply*
D018686:Anesthetics, Intravenous; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D007773:Lactates; D000983:Antipyrine; D015742:Propofol