Study of the time course of the clinical effect of propofol compared with the time course of the predicted effect-site concentration: Performance of three pharmacokinetic-dynamic models.
BACKGROUND
In the ideal pharmacokinetic-dynamic (PK-PD) model for calculating the predicted effect-site concentration of propofol (Ce(PROP)), for any Ce(PROP), the corresponding hypnotic effect should be constant. We compared three PK-PD models (Marsh PK with Shüttler PD, Schnider PK with fixed ke0, and Schnider PK with Minto PD) in their ability to maintain a constant bispectral index (BIS), while using the respective effect-site-controlled target-controlled infusion (TCI) algorithms.


METHODS
We randomized 60 patients to Group M (Marsh's model with k(e0)=0.26 min(-1)), Group S1 or Group S2 (Schnider's model with a fixed k(e0)=0.456 min(-1) or a k(e0) adapted to a fixed time-to-peak effect=1.6 min, respectively). All patients received propofol at a constant rate until loss of consciousness. The corresponding Ce(PROP), as calculated by the respective models, was set as a target for effect-site-controlled TCI. We observed BIS for 20 min. We hypothesized that BIS remains constant, if Ce(PROP) remains constant over time.


RESULTS
All patients in Group M woke up, one in Group S1 and none in Group S2. In Groups S1 and S2, BIS remained constant after 11 min of constant Ce(PROP), at a more pronounced level of hypnotic drug effect than intended.


CONCLUSIONS
Targeting Ce(PROP) at which patients lose consciousness with effect-site-controlled TCI does not translate into an immediate constant effect.
Coppens
M
M
Department of Anesthesia, Ghent University Hospital, Belgium.
Van Limmen
J G M
JG
Schnider
T
T
Wyler
B
B
Bonte
S
S
Dewaele
F
F
Struys
M M R F
MM
Vereecke
H E M
HE
D000328:Adult; D000465:Algorithms; D000556:Ambulatory Surgical Procedures; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D016343:Monitoring, Intraoperative / Q000379:methods; D015742:Propofol / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D055815:Young Adult
D018686:Anesthetics, Intravenous; D015742:Propofol