Analysis of fentanyl pharmacokinetics, and its sedative effects and tolerance in critically ill children

Abstract

Introduction: Fentanyl pharmacokinetic and pharmacodynamic data are limited in mechanically ventilated children. This study aimed to assess the fentanyl pharmacokinetics (PK), the sedation outcome, and the development of tolerance in children receiving fentanyl continuous infusion. Methods:This study included children admitted to the pediatric or cardiovascular intensive care unit between January 1 and October 31, 2016, who were >30 days to <18 years of age, receiving ventilatory support via endotracheal tube or tracheostomy, and receiving a fentanyl infusion. Population PK analysis was performed using a nonlinear mixed-effects model. The relationship between initial sedation outcome using State Behavioral Scale (SBS) and fentanyl exposure was assessed, and the observations consistent with tolerance were described.Results: Seventeen children, with a median age of 0.83 years (range: 0.1-12) and weight of 8.7 kg (range: 3.4-52), were included. The fentanyl PK was adequately described by a weight-based allometry model with the power of 0.75 for clearance (CL=89.8 L/hr/70 kg) and distributional CL, and 1 for volumes of distribution. In infants <6.6 months, age was an additional factor for CL (31.4 L/h/70 kg) to account for age-related maturation. Seven of twelve nonparalyzed patients achieved goal sedation, defined as >80% of SBS scores ≤0 per 24 h, on the first day of fentanyl infusion with a median plasma concentration of 1.29 ng/ml (interquartile range: 0.78-2.05).Eight of the nine tolerant patients developed tolerance within a day of reaching goal sedation. Conclusion:Different weight-based fentanyl dosing rates may be required for infants and children of different ages to achieve similar plasma concentrations. Using SBS scores may guide the dosing titration of fentanyl that resulted in plasma concentrations within the therapeutic range of 1-3 ng/ml. For those who developed tolerance to fentanyl and/or a sedative, it was noted one day after goal sedation was achieved.

Analgesic Efficacy of Oxycodone in Postoperative Dressings after Surgical Treatment of Burn Wounds: A Randomised Controlled Trial

“…Most of the information about the effectiveness and safety of opioids in burn patients comes from studies using opioids to treat surgical pain during dressing. Systematic opioids are standard practice for treating burn injuries and pain in most of the centres in North America and Europe [25,26].…”

“Difficult to Sedate”: Successful Implementation of a Benzodiazepine-Sparing Analgosedation-Protocol in Mechanically Ventilated Children

“…The mg/hour fentanyl dosing does not take into account the weight-based clearance in younger children who may be bigger in size. However, we used SBS scores in our study, which may have helped guide the dosing titration of fentanyl to achieve therapeutic plasma concentrations [ 27 , 28 ].…”

“…However, we used SBS scores in our study, which may have helped guide the dosing titration of fentanyl to achieve therapeutic plasma concentrations [27,28].…”

Síndrome de Abstinência a Sedativos e Analgésicos na UTI Pediátrica.

“…O fentanil é um medicamento da classe dos opioides e também necessita de desmame. Deste modo, é feita a substituição do fentanil intravenoso pela metadona via oral como prevenção contra abstinência de opióides [25][26][27] . A clonidina via oral foi utilizada por 26,92% dos pacientes para desmame da dexmedetomidina intravenosa.…”