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Placental transfer: Anesth drugs

Placental exchange can occur by one of five mechanisms:

  1. Bulk Flow (water)
  2. Active Transport (Amino acids, vitamins, ions, Ca, Fe)
  3. Pinocytosis (large molecules, such as immunoglobulins)
  4. Breaks (direct mixing of blood—responsible for Rh sensitization)
  5. Diffusion (Respiratory gases and most drugs used in anesthesia)

All inhalational agents and most intravenous agents freely cross the placenta; however, inhalational agents cause little fetal depression when they are given in limited doses (< 1 MAC) and delivery occurs within 10 min of the induction of anesthesia.

Intravenous agents readily cross the placenta and can be detected in the fetal circulation. With the exception of benzodiazepines, fetal affects are limited by drug distribution, metabolism, and possibly placental uptake.

Opiates readily cross the placenta, but their effects on neonates at delivery vary considerably. In terms of respiratory depression, morphine produces the most, fentanyl the least. Remifentanil also readily crosses the placenta and has the potential to produce respiratory depression in newborns. Fetal blood concentrations of remifentanil are generally about half those of the mother just prior to delivery. The UA/UV ratio is about 30%, suggesting fairly rapid metabolism of remifentanil in the neonate. Epidural or intrathecal opiates to a lesser extent, generally produce minimal neonatal effects.

Muscle Relaxants are highly ionized which impedes placental transfer, resulting in minimal effects on the fetus.

Local anesthetics are weakly basic drugs that are principally bound to 1-acid glycoprotein. Placental transfer depends on three factors: (1) pKa, (2) maternal and fetal pH, and (3) degree of protein binding. Except for chloroprocaine, fetal acidosis produces higher fetal-to-maternal drug ratios because binding of hydrogen ions to the nonionized form causes trapping of the local anesthetic in the fetal circulation. Highly protein-bound agents diffuse poorly across the placenta; thus, greater protein binding of bupivacaine and ropivacaine, compared with that of lidocaine, likely accounts for their lower fetal blood levels. Chloroprocaine has the least placental transfer because it is rapidly broken down by plasma cholinesterase in the maternal circulation.

Anesthetic adjuncts like maternally administered ephedrine, -adrenergic blockers (such as labetalol and esmolol), vasodilators, phenothiazines, antihistamines (H1 and H2), and metoclopramide are transferred to the fetus. Atropine and scopolamine, but not glycopyrrolate, cross the placenta; the latter’s quaternary ammonium (ionized) structure results in only limited transfer.

Other References

  1. Keys to the Cart: November 1, 2019 Link