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Propofol: A Review of its Role in Pediatric Anesthesia and Sedation

CNS Drugs volume 29, pages 543–563 (2015)Cite this article

A Correction to this article was published on 13 August 2018

Abstract

Propofol is an intravenous agent used commonly for the induction and maintenance of anesthesia, procedural, and critical care sedation in children. The mechanisms of action on the central nervous system involve interactions at various neurotransmitter receptors, especially the gamma-aminobutyric acid A receptor. Approved for use in the USA by the Food and Drug Administration in 1989, its use for induction of anesthesia in children less than 3 years of age still remains off-label. Despite its wide use in pediatric anesthesia, there is conflicting literature about its safety and serious adverse effects in particular subsets of children. Particularly as children are not “little adults”, in this review, we emphasize the maturational aspects of propofol pharmacokinetics. Despite the myriad of propofol pharmacokinetic-pharmacodynamic studies and the ability to use allometrical scaling to smooth out differences due to size and age, there is no optimal model that can be used in target controlled infusion pumps for providing closed loop total intravenous anesthesia in children. As the commercial formulation of propofol is a nutrient-rich emulsion, the risk for bacterial contamination exists despite the Food and Drug Administration mandating addition of antimicrobial preservative, calling for manufacturers’ directions to discard open vials after 6 h. While propofol has advantages over inhalation anesthesia such as less postoperative nausea and emergence delirium in children, pain on injection remains a problem even with newer formulations. Propofol is known to depress mitochondrial function by its action as an uncoupling agent in oxidative phosphorylation. This has implications for children with mitochondrial diseases and the occurrence of propofol-related infusion syndrome, a rare but seriously life-threatening complication of propofol. At the time of this review, there is no direct evidence in humans for propofol-induced neurotoxicity to the infant brain; however, current concerns of neuroapoptosis in developing brains induced by propofol persist and continue to be a focus of research.

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Authors and Affiliations

  1. Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 2001, Cincinnati, OH, 45229, USA

    Vidya Chidambaran, Andrew Costandi & Ajay D’Mello

  2. Department of Anesthesia and Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA

    Vidya Chidambaran & Andrew Costandi

Authors
  1. Vidya Chidambaran
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  2. Andrew Costandi
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  3. Ajay D’Mello
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Correspondence to Vidya Chidambaran.

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Funding

Preparation of this manuscript was supported by the Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA. No financial support except departmental salary support for the authors VC, AC, and AD. The writing of the review article was also facilitated by protected research time supported by Eunice Kennedy Shriver National Institute Of Child Health and Human Development of the National Institutes of Health under award number K23HD082782 (PI: VC)

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All authors (VC, AC, and AD) listed in this manuscript have no conflicts of interest relevant to this article to disclose.

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Chidambaran, V., Costandi, A. & D’Mello, A. Propofol: A Review of its Role in Pediatric Anesthesia and Sedation. CNS Drugs 29, 543–563 (2015). https://doi.org/10.1007/s40263-015-0259-6

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Keywords

  • Sevoflurane
  • Dexmedetomidine
  • Mitochondrial Disease
  • Emergence Delirium
  • Fospropofol