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A Randomized Comparison Between Midazolam and Thiopental for Elective Cesarean Section Anesthesia

III. Placental Transfer and Elimination in Neonates

Department of Anesthesiology, Esbjerg Central Hospital, Esbjerg, Denmark; Department of Clinical Research, Roche, Ltd, Huiberre, Denmark; Departments of Clinical Research and Biological Pharmaceutical Research, F. Hoffman-La Roche & Co., Ltd., Basel, Switzerland; and Division of Clinical Pharmacology, Department of Medicine, University Hospital, Kantonspital, Basel, Switzerland.

Abstract

Forty neonates delivered by cesarean section were studied, half being delivered of mothers in whom anesthesia was induced with midazolam (0.3 mg/kg intravenously) and half of mothers given thiopental (4 mg/kg). At delivery, blood samples from mother and the umbilical vein were drawn for determination of plasma concentrations of thiopental, midazolam, and -hydroxymidazolam. Over the next 60 hours, three blood samples were drawn using a randomized procedure of two blood samples at 30 different times. Placental transfer, expressed as the umbilical/maternal concentration ratio, was 0.96, 0.66, and 0.28, respectively, for thiopental, midazolam, and -hydroxymidazolam. The transfer of thiopental was significantly more rapid than the transfer of midazolam and -hydroxymidazolam. The population average of elimination half-life in neonates was 6.3 hours for midazolam and 14.7 hours for thiopental. Both values are substantially larger than those found in previous studies in adults.

Key Words: ANESTHESIA, OBSTETRIC • ANESTHETICS, INTRAVENOUS—thiopental, midazolam • HYPNOTICS, BENZODIAZEPINES— midazolam • PHARMACOKINETICS, THIOPENTAL, MIDAZOLAM

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