Predictive Performance of PK Models for Propofol Infusion in Children

BJA: British Journal of Anaesthesia · February 10, 2017

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.