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Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants
Author(s) -
Norman Elisabeth,
Kindblom Jenny M.,
Rane Anders,
Berg AnnCathrine,
Schubert Ulf,
Hallberg Boubou,
Fellman Vineta
Publication year - 2019
Publication title -
acta paediatrica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 115
eISSN - 1651-2227
pISSN - 0803-5253
DOI - 10.1111/apa.14744
Subject(s) - medicine , fentanyl , pharmacokinetics , anesthesia , gestational age , pharmacodynamics , volume of distribution , pharmacology , pregnancy , biology , genetics
Aim Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 μg/ mL for procedural pain. Methods Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3–34.1 weeks) and 2 μg/kg (n = 8, 27.4; 25.3–30.7 weeks) fentanyl, respectively, before skin‐breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed. Results The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/ mL at 15–31 minutes, two and four hours and the half‐lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low‐ and high‐dose groups, respectively. A significant correlation was seen between weight at study inclusion and half‐life (Spearman′s r = −0.9, p < 0.001), volume of distribution (r = −0.8, p < 0.01) and clearance (r = −0.9, p < 0.01) in the low‐dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated. Conclusion The inter‐individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 μg/kg seems not effective for skin‐breaking procedures.