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Association of serum fentanyl concentration and oxygen desaturation with oversedation in neonates

Research Authors
Kazuhiro Yamamoto, Risa Joji, Mari Hashimoto, Walaa Yousef Bassyouni Mahdy, Ruka Nakasone, Kazumichi Fujioka, Tomohiro Omura, Ikuko Yano
Research Member
Research Abstract

Fentanyl is an intravenously administered sedative during tracheal intubation in neonates with respiratory distress. Overdose of fentanyl leads to oversedation, as there is a direct concentration-effect relationship between the fentanyl serum concentration and respiratory depression in adults [1]. However, the relationship between serum fentanyl concentration and oxygen desaturation with oversedation in neonates still unclear. Our aim is to evaluate the association between  serum fentanyl concentrations and oxygen desaturation with oversedation in neonates receiving artificial ventilation. Patients Our retrospective study included neonate patients given fentanyl for sedation during tracheal intubation. The patients were considered eligible if we could obtain the serum sample during the fentanyl therapeutic period. Measurement of serum fentanyl concentrations Blood samples were collected from the neonates as a routine care. Serum fentanyl concentrations were measured by liquid chromatography-tandem mass spectrometry. Oxygen desaturation Oxygen desaturation (ODS) was defined as percutaneous oxygen saturation less than 90%. During the fentanyl therapeutic period, All serum samples were collected during this period (the points with the highest concentrations were adopted) The occurrence of ODS (%SpO2<90%) was observed. Bayesian estimation Bayesian estimations were performed using the MwPharm++ software. The population pharmacokinetic parameters for fentanyl were established based on a previous report [2]. Volume of distribution (Vd)= 5.26 L/Kg Clearance (CL)= 3.6  L/h. There were no significant differences in patient characteristics between patients with and without ODS. The median fentanyl initial dose tended to be lower in patients with ODS compared to non-ODS patients.  There was no significant difference in fentanyl concentration between patients with and without ODS. The fentanyl concentration per dose (C/D) in patients with ODS was significantly higher than in those with non-ODS. Time to incidence of ODS had a trend to be shorter than the entire fentanyl therapeutic period in the patients with non-ODS. Exposure time may not contribute to the incidence of ODS.