Evaluation of fentanyl disposition and effects in newborn piglets as an experimental model for human neonates

PLoS One. 2014 Mar 4;9(3):e90728. doi: 10.1371/journal.pone.0090728. eCollection 2014.

Abstract

Background: Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates.

Methods: Fentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225-300 min). Also plasma samples for quantification of fentanyl were drawn.

Results: A "reliable degree of sedation" was observed up to T = 210-240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment.

Conclusion: The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Intravenous / administration & dosage
  • Anesthetics, Intravenous / pharmacokinetics*
  • Anesthetics, Intravenous / pharmacology*
  • Animals
  • Female
  • Fentanyl / administration & dosage
  • Fentanyl / pharmacokinetics*
  • Fentanyl / pharmacology*
  • Heart Rate / drug effects
  • Hemodynamics / drug effects
  • Humans
  • Infant, Newborn
  • Male
  • Models, Animal
  • Respiration / drug effects
  • Respiration, Artificial
  • Swine

Substances

  • Anesthetics, Intravenous
  • Fentanyl

Grant support

This study was partially supported by grants from the Spanish Carlos III Health Institute: FIS 10/943 and RD12/0026/0001 (Red SAMID: Maternal, Child Health and Development Research Network, within the framework of the VI Spanish National Plan for R+D+i 2008-2012). It was also supported by a predoctoral grant to one of the authors (EE) from the Research Staff Training Program (Basque Country Government) and by an INNPACTO project of the Spanish Ministry of Science and Innovation — MICINN (ITP-09000-2010-002), which is financed by the European Regional Development Fund (FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.