The Effect of Fentanyl Administration on Plasma Agmatine Concentration In Critically Ill Patients

Abstract

Background: Agmatine, a product of L-arginine metabolism, has been shown to influence opioid tolerance, dependence and withdrawal in animal studies. The purpose of this study was to characterize the plasma agmatine concentration of critically ill, mechanically ventilated patients receiving continuous fentanyl infusion as part of their sedation/analgesia regimen. We hypothesized that these patients would demonstrate lower plasma agmatine levels.Methods: All admissions to our pediatric intensive care unit (PICU) who received mechanical ventilation and fentanyl infusions as part of their sedation/analgesia regimen were eligible. Plasma agmatine concentrations were correlated with patient demographics and medication administration data.Results: Twenty two mechanically ventilated children were enrolled and showed a negative correlation between Δ plasma agmatine concentration and the COMFORT score (r=-0.42, p<0.01), Δ cumulative fentanyl dose (r=-0.48, p<0.01), Δ fentanyl infusion rate (r=-46, p<0.01), and fentanyl infusion duration (r=-37, p<0.01).Conclusions: Mechanically ventilated, critically ill patients receiving prolonged opioid infusions and meeting the definition of tolerance demonstrated lower plasma agmatine concentrations relative to baseline.