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Predictive performance of eleven pharmacokinetic models for propofol infusion in children for long-duration
M Hara1, K Masui2, D J Eleveld3
1Department of Anaesthesia, Chiba Children's Hospital, Heta-cho 579-1, Midori-ku, Chiba, Chiba, 266-0007, Japan.
Insights
The Short model demonstrated the best predictive performance for long-duration propofol infusions in children, making it a preferred choice for pediatric anesthesia. This pharmacokinetic model accurately predicted drug concentrations during extended procedures.
Area of Science:
- Anesthesiology
- Pharmacokinetics
- Pediatric Medicine
Background:
- Propofol is a widely used anesthetic agent in pediatric surgery.
- Accurate pharmacokinetic models are crucial for safe and effective propofol administration, especially during long procedures.
- Evaluating existing models in pediatric populations is essential for optimizing anesthetic care.
Purpose of the Study:
- To assess the predictive performance of eleven published propofol pharmacokinetic models.
- To identify the most suitable model for long-duration propofol infusions in children.
- To compare model accuracy using various prediction error metrics.
Main Methods:
- Twenty-one pediatric patients (3-11 years) undergoing anesthesia were included.
- Propofol was administered via continuous infusion (4-14 mg/kg/h) after an initial bolus.
- Blood samples were collected over several hours to analyze propofol concentrations.
- Model performance was evaluated using prediction error (PE), median PE (MDPE), and median absolute PE (MDAPE).
Main Results:
- The Short model and Schüttler model showed acceptable performance within defined error margins.
- The Short model exhibited the highest predictive performance among all evaluated models.
- Two bolus-dose models (Shangguan, Saint-Maurice) and the Paedfusor model showed significant negative divergence PE.
Conclusions:
- The Short model demonstrated robust performance for propofol infusions lasting up to 545 minutes in children.
- This model is recommended for target-controlled infusion in long-duration pediatric anesthesia.
- Accurate pharmacokinetic modeling is vital for optimizing propofol dosing in pediatric patients.
Background:
Predictive performance of eleven published propofol pharmacokinetic models was evaluated for long-duration propofol infusion in children.
Methods:
Twenty-one aged three-11 yr ASA I-II patients were included. Anaesthesia was induced with propofol or sevoflurane, and maintained with propofol, remifentanil, and fentanyl. Propofol was continuously infused at rates of 4-14 mg kg - 1 h - 1 after an initial bolus of 1.5-2.0 mg kg - 1 . Venous blood samples were obtained every 30-60 min for five h and then every 60-120 min after five h from the start of propofol administration, and immediately after the end of propofol administration. Model performance was assessed with prediction error (PE) derivatives including divergence PE, median PE (MDPE), and median absolute PE (MDAPE) as time-related PE shift, measures for bias, and inaccuracy, respectively.
Results:
We collected 85 samples over 270 (130) (88-545), mean (SD) (range), min. The Short model for children, and the Schüttler general-purpose model had acceptable performance (-20%≤MDPE ≤ 20%, MDAPE ≤ 30%, -4% h - 1 ≤ divergence PE ≤ 4% h - 1 ). The Short model showed the best performance with the maximum predictive performance metric. Two models developed only using bolus dosing (Shangguan and Saint-Maurice models) and the Paedfusor of the remaining nine models had significant negative divergence PE (≤-6.1% h - 1 ).
Conclusions:
The Short model performed well during continuous infusion up to 545 min. This model might be preferable for target-controlled infusion for long-duration anaesthesia in children.
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