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 microg x ml-1 (N2O) or 1.5 microg x ml-1 (Air). Subsequently, the target effect-site concentration was increased by 0.25 (N2O) or 0.5 microg x 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 microg x ml-1 (P = 0.78) during the N2O and 0.00 +/- 0.25 microg x 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.
Doufas
A G
AG
OUTCOMES RESEARCH Institute and Department of Anesthesiology and Pharmacology, University of Louisville, Louisville, KY 40202, USA. agdoufas@louisville.edu
Bakhshandeh
M
M
Bjorksten
A R
AR
Greif
R
R
Sessler
D I
DI
D000328:Adult; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008297:Male; D015742:Propofol / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology
D006993:Hypnotics and Sedatives; D015742:Propofol