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Fetal, Preterm, and Term Neonate Exposure to Remifentanil: A Systematic Review of Efficacy and Safety

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Abstract

Background

Owing to its pharmacodynamic properties, especially the rapid onset and short duration of its action, the use of remifentanil in obstetric anesthesia, as well as in neonatology, might be increasingly used.

Objective

We conducted a systematic review to assess the efficacy and safety of remifentanil in preterm and term neonates. Outcomes of interest were neonatal adaptation after fetal exposure; neonatal pain, distress, and discomfort control during invasive procedures; and the occurrence of hemodynamic effects or respiratory depression induced by remifentanil infusion.

Methods

Given the different contexts of use, we have organized this work into three parts: (A) use of remifentanil for labor or cesarean section, with exposure of the fetus before birth, (B) brief use for neonatal procedural analgesia, and (C) prolonged use for sedation/analgesia of neonates. The bibliographic search was conducted based on keywords using electronic medical databases (DATABASE, Cochrane Library, PubMed, and EMBASE) from 1 January 2000 until 31 December 2022.

Results

Twenty-two articles were included (10 in part A, 5 in part B and 7 in part C). Prospective, controlled, randomized, blinded, and intention-to-treat trials were retained. Neonates were well adapted after exposure to remifentanil in the fetal period. Pain, stress, and discomfort were controlled during a brief or prolonged invasive procedure when remifentanil was used for sedation/analgesia. The physiological parameters were stable and the procedures were straightforward. Chest wall rigidity appeared to be a common side effect, but this can be managed by slow and continuous infusion and by using the minimum effective dose.

Conclusions

Remifentanil appears to be effective and safe in the short term in preterm and full-term neonates. However, its safety is compromised by the risk of chest wall rigidity. It should be used in appropriate neonatal units and in the presence of physicians able to monitor its side effects. Long-term outcomes have not been evaluated, to our knowledge.

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Authors and Affiliations

  1. Pediatric Intensive Care Unit, Robert Debré University Hospital, APHP, 75019, Paris, France

    Arielle Maroni

  2. Department of Neonatal Medicine, Cochin-Port Royal Hospital, APHP, 75014, Paris, France

    Marie-Stéphanie Aubelle

  3. Department of Neonatal Paediatrics, Trousseau Hospital, APHP, Sorbonne Université, 26 Av. du Dr Arnold Netter, 75012, Paris, France

    Clément Chollat

  4. Université Paris Cité, Inserm, NeuroDiderot, 75019, Paris, France

    Clément Chollat

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  1. Arielle Maroni
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Correspondence to Clément Chollat.

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A.M., C.C., and M.S.A. have no conflicts of interest to declare.

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A.M. drafted the protocol and manuscript; acquired, analyzed, and interpreted the data; and provided final approval for publication. C.C. helped analyze and interpret the data, revised the manuscript for important intellectual content, provided final approval for publication, and agreed to be accountable for all aspects of the work. M.S.A. contributed to the conception and design of the work, revised the manuscript for important intellectual content, helped analyze and interpret the data, and provided final approval for publication.

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Maroni, A., Aubelle, MS. & Chollat, C. Fetal, Preterm, and Term Neonate Exposure to Remifentanil: A Systematic Review of Efficacy and Safety. Pediatr Drugs 25, 537–555 (2023). https://doi.org/10.1007/s40272-023-00583-w

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