title: Ketofol dosing simulations for procedural sedation.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the *Emergency Department, Auckland City Hospital; and †Department of Anaesthesiology, University of Auckland, Auckland, New Zealand.
authors.forename: Finn L S
authors.initials: FL
authors.lastname: Coulter
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Hannam
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000777:Anesthetics / Q000008:administration & dosage*; D000932:Antiemetics / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D016292:Procedural Sedation / Q000379:methods; D004338:Drug Combinations; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007649:Ketamine / Q000008:administration & dosage*; D015742:Propofol / Q000008:administration & dosage*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000777:Anesthetics; D000932:Antiemetics; D004338:Drug Combinations; D007649:Ketamine; D015742:Propofol