Advertisement

Harmful effects of fentanyl on the fetus and placenta?

      To the Editor: We read with great interest the recent article by Smith et al
      • Smith R.P.
      • Miller S.L.
      • Igsheva N.
      • Peebles D.M.
      • Glover V.
      • Jenkin G.
      • et al.
      Cardiovascular and endocrine responses to cutaneous electrical stimulation after fentanyl in the ovine fetus.
      because their findings corroborate recent data produced during our research involving fetal cardiac surgery in midgestation fetal sheep (100 to 110 days).
      The intensive studies of Fisk and others have documented important fetal stress responses, such as acute cerebral redistribution
      • Teixeira J.M.
      • Glover V.
      • Fisk N.M.
      Acute cerebral redistribution in response to invasive procedures in the human fetus.
      to invasive procedures performed on the fetus. Similarly, others have reported a harmful fetal stress response to fetal cardiac surgery.
      • Reddy V.M.
      • McElhinney D.B.
      Update on prospects for fetal cardiovascular surgery.
      Because of its salutary cardiovascular effects, high dose fentanyl (100-500 μg/kg) has often been the drug of choice for managing newborn stress responses, especially during open-heart surgery. Therefore, we set out to evaluate the potential efficacy of fentanyl in reducing fetal stress responses to fetal cardiac surgery.
      To our surprise, we noted an adverse reaction to high-dose fentanyl, similar to those reported by Smith et al.
      • Smith R.P.
      • Miller S.L.
      • Igsheva N.
      • Peebles D.M.
      • Glover V.
      • Jenkin G.
      • et al.
      Cardiovascular and endocrine responses to cutaneous electrical stimulation after fentanyl in the ovine fetus.
      For example, we noticed that higher doses of fentanyl resulted in paradoxic increase in fetal heart rate (Figure 1). Simultaneously, we saw a decrease in fetal pH and pO2 (Figures 1 and 2), again similar to observations of Smith et al with high-dose fentanyl. Smith et al did not report any significant effect on the pCO2; however, we saw an increase in fetal pCO2 with higher concentrations of fentanyl (Figure 2).
      Indeed, we wonder whether high-dose fentanyl may indeed be harmful to placenta. Investigators have identified placental opiate receptors; their role in placental biology remains unknown. Kopecky et al
      • Kopecky E.A.
      • Ryan M.L.
      • Barrett J.F.
      • Seaward P.G.
      • Ryan G.
      • Koren G.
      • Amankwah K.
      Fetal response to maternally administered morphine.
      and others have previously shown the ability of opiates such as morphine to cause vasoconstriction of the placental and umbilical vasculature. A similar effect could be happening with high-dose fentanyl, resulting in poor placental gas exchange and leading to a rise in pCO2 and pH and a drop in pO2. In response, the fetus may shunt blood to the vital organs (the heart and brain), a “brain sparing” effect, as seen by the Fisk group, with a 30% increase in cerebral blood flow (correlating with the increased heart rate).
      Fentanyl dosing in prenatal obstetric management is usually of small quantity. However, clinicians involved in fetal therapeutics may use higher doses of fentanyl, applying weight-adjusted neonatal dosing standards. Although species differences may exist, we feel caution is warranted in the clinical setting until further studies are conducted. Examination of the umbilical blood flow before and after fentanyl administration may help clarify the mechanisms involved.

      References

        • Smith R.P.
        • Miller S.L.
        • Igsheva N.
        • Peebles D.M.
        • Glover V.
        • Jenkin G.
        • et al.
        Cardiovascular and endocrine responses to cutaneous electrical stimulation after fentanyl in the ovine fetus.
        Am J Obstet Gynecol. 2004; 190: 836-842
        • Teixeira J.M.
        • Glover V.
        • Fisk N.M.
        Acute cerebral redistribution in response to invasive procedures in the human fetus.
        Am J Obstet Gynecol. 1999; 18: 1018-1025
        • Reddy V.M.
        • McElhinney D.B.
        Update on prospects for fetal cardiovascular surgery.
        Curr Opin Pediatr. 1997; 9: 530-535
        • Kopecky E.A.
        • Ryan M.L.
        • Barrett J.F.
        • Seaward P.G.
        • Ryan G.
        • Koren G.
        • Amankwah K.
        Fetal response to maternally administered morphine.
        Am J Obstet Gynecol. 2000; 183: 424-430

      Linked Article

      • Reply
        American Journal of Obstetrics & GynecologyVol. 193Issue 1
        • Preview
          I thank Dr Sedgwick et al for writing with their results, which support our findings, and for agreeing that fentanyl should be used with caution in this setting. Measurement of umbilical blood flow, as suggested, may help clarify the mechanism, although in pilot studies in sheep we found difficulties restraining the ewe made obtaining good quality flow velocity waveforms with ultrasound problematic, while anesthetizing the ewe may affect the underlying mechanisms. Implanting flow probes in or around the umbilical cord is technically challenging.
        • Full-Text
        • PDF