Study Objectives: To evaluate the transfer properties of methohexital and t
he influence of protein binding using the in vitro human placental perfusio
n model.
Design: Fresh term human placentae from healthy parturients were perfused b
idirectionally via a cannulated fetal chorionic artery and vein and needles
placed into the maternal intervillous space. Maternal-to-fetal (M-->F) and
fetal-to-maternal (F--M) transfer and ultimate distribution of methohexita
l runs investigated using a closed (recirculating) placental perfusion mode
l.
Setting: Obstetric anesthesia laboratories of two university medical center
s.
Patients: No patient participation occurred as placentae were obtained afte
r delivery.
Intervention: M-->F alzd F-->M transfer of methohexital was compared in vit
ro in perfusates with equal protein concentrations (2 g/100 mt in both perf
usates) or albumin-simulated physiologic protein Binding concentrations (ma
ternal 8 g/100 mL; fetal 4 g/100 mL).
Measurements and Main Results: Data obtained consisted of measurements of m
ethohexital and antipyrine concentrations by high-performance liquid chroma
tography. Glucose and lactate concentrations and perfusate loss were measur
ed to assess placental viability. Methohexital protein binding was assessed
at 2, 4, and 8 g/100 mL of albumin by equilibrium. The transfer index of 0
.83 +/- 0.11 for the M-->F perfusions was significantly greater (p less tha
n or equal to 0.05) than in the F-->m direction (0. 61 +/- 0. 04) when albu
min concentration runs equal in both perfusates. This transfer asymmetry di
sappeared when albumin concentrations simulating maternal (8 g/100 mL) vers
us fetal (4 g/100 mL) protein concentrations in the perfusate were used (M-
->F 0.87 +/- 0.12 and F-->M 0.5 +/- 0.11).
Conclusion: Methohexital readily crosses the placenta in both directions. P
rotein binding has significant effects on the degree of transfer of methohe
xital at any time when compared with antipyrine and its ultimate fetal/mate
rnal distribution. (C) 2000 by Elsevier Science Inc.