Analysis of fentanyl pharmacokinetics, and its sedative effects and tolerance in critically ill children
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Published on: October 16, 2013
Sin Yin Lim1, Jamie L Miller1, Emilie Henry2
1Department of Pharmacy, Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy, Oklahoma City, OK, USA.
Insights
This study found that fentanyl dosing may need adjustment for pediatric patients based on age and weight to achieve therapeutic sedation. Sedation scores can guide fentanyl titration, with tolerance developing quickly in some children.
Area of Science:
- Pediatric Intensive Care
- Pharmacokinetics and Pharmacodynamics
- Anesthesiology
Background:
- Limited pharmacokinetic (PK) and pharmacodynamic data exist for fentanyl in mechanically ventilated children.
- Fentanyl is commonly used for sedation and analgesia in pediatric intensive care units (PICUs).
Purpose of the Study:
- To assess fentanyl pharmacokinetics (PK) in mechanically ventilated children.
- To evaluate sedation outcomes using the State Behavioral Scale (SBS).
- To describe the development of tolerance to fentanyl in this population.
Main Methods:
- Population PK analysis using nonlinear mixed-effects modeling in 17 children (0.1-12 years).
- Assessment of the relationship between initial sedation outcome (SBS) and fentanyl exposure.
- Description of tolerance development based on clinical observations.
Main Results:
- Fentanyl PK was described by a weight-based allometry model; age was a factor for clearance in infants (<6.6 months).
- Seven of twelve nonparalyzed patients achieved goal sedation (SBS ≤0) within the first day at median plasma concentrations of 1.29 ng/ml.
- Eight of nine tolerant patients developed tolerance within one day of achieving goal sedation.
Conclusions:
- Weight-based fentanyl dosing may require age-specific adjustments in pediatric patients to achieve target plasma concentrations.
- State Behavioral Scale (SBS) scores can guide fentanyl titration to maintain therapeutic concentrations (1-3 ng/ml).
- Tolerance to fentanyl can develop rapidly in pediatric patients, typically within a day after goal sedation is reached.
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.
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