Ketofol dosing simulations for procedural sedation.

Abstract

Propofol mixed with racemic ketamine (or "ketofol") is popular for short procedural sedation and analgesia, yet the optimal combination is unknown. We aimed to determine a ketofol dosing regimen for short procedural sedation and analgesia of 5- to 20-minute duration in healthy patients (2-20 y). Pharmacokinetic-pharmacodynamic parameters were used to simulate drug concentration and effect profiles over time for different ketamine-to-propofol ratios (1:1-1:10). The target effect was a Children's Hospital of Wisconsin Sedation Scale score of less than 2. Combined effects were additive, with a propofol EC50 of 1.54 μg/mL (concentration required to produce hypnosis in 50% of patients), a ketamine EC50 of 0.44 μg/mL, and a slope of 5.3. Emergence threshold concentrations for propofol were 2.0 μg/mL in children and 1.8 μg/mL in adults as well as 0.5 μg/mL for ketamine (children and adults). The EC50 for propofol antiemesis was 0.343 μg/mL. A ketamine-to-propofol ratio of 1:3 was the best combination for intermittent dosing, achieving a rapid onset of a Children's Hospital of Wisconsin Sedation Scale score of less than 2 within 1 minute and a time to emergence of 9 to 19 minutes in all ages after a 10-minute sedation. The optimal ketofol dosing in children (2-11 y) was 0.1 mL/kg initially followed by 0.05 mL/kg at 2 minutes and then 0.025 mL/kg for the subsequent doses. The adults (12-20 y) received 0.05 mL/kg of ketofol initially followed by 0.025 mL/kg for the subsequent doses. These regimens maintain a propofol antiemesis for 30 to 40 minutes after the last dose. We suggest an optimal ratio of racemic ketamine to propofol of 1:3 for boluses during short procedures (5-20 minutes). A short ketofol infusion, ratio 1:4, is a suitable alternative to intermittent boluses. Ratios greater than 1:3 result in delayed recovery after 20 minutes.