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

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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.
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Keywords: Effect-site; nitrous oxide; propofol; proportional-integral-derivative (PID); sedation; target-controlled infusion

Document Type: Research Article

Affiliations: 1: OUTCOMES RESEARCH™ Institute and Department of Anesthesiology and Pharmacology, University of Louisville, Louisville, KY, 2: Department of Anesthesiology, University of California San Francisco, San Francisco, CA, USA 3: Department of Anesthesia, Royal Melbourne Hospital, Parkville, Vic., Australia, 4: Department of Anesthesiology and Intensive Care Medicine, Donauspital/SMZO Hospital, Vienna, Austria,

Publication date: 2003-09-01

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