Neonatal depression after obstetrical analgesia with pethidine. the role of the injection-delivery time interval and of the plasma concentrations of pethidine and norpethidine

Authors

  • P. Belfrage,

    1. Department of Obstetrics, Karolinska Hospital, Stockholm
    2. Department of Clinical Pharmacology, Karolinska Hospital, Stockholm
    3. Department of Anesthesiology, Karolinska Hospital, Stockholm
    4. Department of Analytical Pharmaceutical Chemistry, Biomedical Center, University of Uppsala, Uppsala, Sweden
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  • L. O. Boréus M.D.,

    Corresponding author
    1. Department of Obstetrics, Karolinska Hospital, Stockholm
    2. Department of Clinical Pharmacology, Karolinska Hospital, Stockholm
    3. Department of Anesthesiology, Karolinska Hospital, Stockholm
    4. Department of Analytical Pharmaceutical Chemistry, Biomedical Center, University of Uppsala, Uppsala, Sweden
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  • P. Hartvig,

    1. Department of Obstetrics, Karolinska Hospital, Stockholm
    2. Department of Clinical Pharmacology, Karolinska Hospital, Stockholm
    3. Department of Anesthesiology, Karolinska Hospital, Stockholm
    4. Department of Analytical Pharmaceutical Chemistry, Biomedical Center, University of Uppsala, Uppsala, Sweden
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  • L. Irestedt,

    1. Department of Obstetrics, Karolinska Hospital, Stockholm
    2. Department of Clinical Pharmacology, Karolinska Hospital, Stockholm
    3. Department of Anesthesiology, Karolinska Hospital, Stockholm
    4. Department of Analytical Pharmaceutical Chemistry, Biomedical Center, University of Uppsala, Uppsala, Sweden
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  • N. Raabe

    1. Department of Obstetrics, Karolinska Hospital, Stockholm
    2. Department of Clinical Pharmacology, Karolinska Hospital, Stockholm
    3. Department of Anesthesiology, Karolinska Hospital, Stockholm
    4. Department of Analytical Pharmaceutical Chemistry, Biomedical Center, University of Uppsala, Uppsala, Sweden
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Department of Clinical Pharmacology, Karolinska Hospital, S- 104 01 Stockholm, Sweden

Abstract

Pethidine (100 mg) was administered i.m. to women in labor at different times before delivery. The interval before respiration in the newborn became sustained was shorter if pethidine was given less than one hour before delivery. The respiratory rate of the newborn increased after naloxone injection in 40 per cent of the cases, mostly when intrauterine exposure to pethidine exceeded one hour. The plasma concentrations of pethidine and norpethidine were measured in mother and newborn. The concentrations in the umbilical vein and artery indicated a continuous net transfer of pethidine from mother to fetus for approximately two hours. This correlates with the clinical finding of maximal neonatal depression 2–3 hours after maternal injection. The concentrations of norpethidine increased with a longer time interval between injection and delivery, but were probably too low to have any effect on the newborn. Neonatal depression seems to be related to the amount of unmetabolized pethidine that has been transferred from mother to fetus but not to norpethidine as had been suspected earlier.

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