A new system to target the effect-site during propofol sedation

Background: We evaluated a new, integrated, covariate‐adjusted, target‐controlled infusion system during sedation with propofol combined with 50% nitrous oxide (N2O) and with propofol only (Air). Methods: The protocol consisted of sequential 15‐minute cycles in 20 volunteers. After a 15‐minute control period, propofol was infused to an initial target effect‐site concentration of 0.25 µg ml−1 (N2O) or 1.5 µg ml−1 (Air). Subsequently, the target effect‐site concentration was increased by 0.25 (N2O) or 0.5 µg ml−1 (Air) for 15 min This sequence was continued until the volunteers lost consciousness as defined by an Observer's Assessment Alertness/Sedation (OAA/S) score = 2. Results: Venous plasma propofol concentrations at the beginning(9 elapsed minutes) and end(15 elapsed minutes) of the pseudo‐steady state period differed by only 0.00 ± 0.16 µg ml−1 (P = 0.78) during the N2O and 0.00 ± 0.25 µg ml−1 (P = 0.91) during the Air trial. OAA/S scores and bispectral index values, as surrogate measures of pharmacodynamic effect, were not different during this time in either trial. The median(25th, 75th percentiles) of the median performance error (%) was −13 (−24, −1) during the N2O and −18 (−26, −9) during the Air trial. The median absolute performance error (%) was 17 (10, 24) in the N2O and 22 (12, 28) in Air trial. The divergence (%/h) was −10 (−26, 4) in the N2O and 14 (−21, 26) in Air trial. The wobble was 7 (5, 10) in the N2O and 6 (4, 8) in the Air trial. Conclusions: When tested with venous blood samples, our TCI system for propofol, using a covariate‐adjusted, integrated pharmacokinetic model to target effect‐site concentrations, demonstrated a clinically acceptable accuracy and stability during mild to moderate sedation.