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Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants

Artikel i vetenskaplig tidskrift
Författare E. Norman
Jenny Kindblom
A. Rane
A. C. Berg
U. Schubert
B. Hallberg
V. Fellman
Publicerad i Acta Paediatrica
Volym 108
Nummer/häfte 8
Sidor 1441-1446
ISSN 0803-5253
Publiceringsår 2019
Publicerad vid Institutionen för medicin
Sidor 1441-1446
Språk en
Länkar dx.doi.org/10.1111/apa.14744
Ämnesord Fentanyl, Pain, Pharmacokinetics, Preterm infants, continuous-infusion, initial validation, procedural pain, morphine, analgesia, newborns, intubation, management, outcomes, scale, Pediatrics
Ämneskategorier Pediatrik

Sammanfattning

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 mu g/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 mu g/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 mu g/kg seems not effective for skin-breaking procedures.

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