///2019 Abstract Details
2019 Abstract Details2019-07-13T07:45:15-05:00

Evaluation of Maternal-Fetal Placental Transfer of Sugammadex Using the Dual-Perfused, Single, Isolated, Human Placental Cotyledon

Abstract Number: BP-05
Abstract Type: Original Research

Michael G. Richardson MD1 ; Raymond F. Johnson B.S.2; Mallika S. Thampy M.D.3; Curtis L. Baysingner M.D.4

AIM: Safe use of sugammadex (SG) in pregnancy has not been established.[1] Extent of placental transfer, predicted to be minimal owing to its molar weight (2,178 g/mol) and high degree of polarity, is unknown. We used the single cotyledon dual-perfusion human placental model, a well-established method of determining placental drug transfer,[2] to measure maternal (M) to fetal (F) transfer of SG.

METHODS: IRB approval was obtained. Healthy women with an uncomplicated term pregnancy undergoing Cesarean delivery gave informed consent. Immediately after delivery, a single cotyledon was cannulated and perfused as previously described,[2] and SG transfer was studied using the closed model (M and F circuits were continuously recirculated).[2] After a 30-min equilibration period, SG (120 mcg/ml) and antipyrine (AP) (200 mcg/ml) were added to the M reservoir and allowed to equilibrate for 3 hours. AP, a freely diffusible flow-limited control marker, was used to control for interplacental variability in lobule size and intralobule experimental perfusion variability. 1 mL samples were taken from M and F circuits at 30-min intervals to measure SG and AP. Five closed experiments were performed. Perfusate sample SG and AP concentrations were measured by LC-Mass Spectrometry (institution’s Mass Spectrometry Core). Moles of drug in M and F circuits were calculated (molar concentration x volume) to derive SG and AP % transfer (amount of drug in F circuit divided by total drug in both reservoirs), as were transfer indices (SG % transfer/AP % transfer).

RESULTS: Five experiments were conducted. Analysis of AP controls confirmed normal control marker transfer. Analysis of SG molecules demonstrated negligible M to F transfer (Fig 1). Fetal SG concentrations were within the detection limit of mass spectroscopy. SG and AP transfer are shown (Fig 2). Mean SG/AT transfer index was 0.09 (SD 0.06) and ranged from 0.03 to 0.18.

CONCLUSIONS: M-F placental transfer of SG was minimal in this model, despite prolonged (3 hrs) exposure of a maternal perfusate concentration exceeding that expected from high-dose (16 mg/kg) SG administration.[3,4] Our results suggest that fetal exposure from maternal administration of clinically relevant doses would be negligible in healthy term pregnant patients.

REF:

1) Varela & Lobato. J Clin Anesth 2015;27:183

2) Johnson RF et al. Anesthesiology 1995;82:459

3) Kleijn et al. Br J Clin Pharmacol 2011;72:415

4) Staals LM et al. Br J Anaesth 2010;104:31



SOAP 2019