Abstract

Backgroud: It is assumed that the atemporal propofol Cp-effect relationship behaves as a bidirectional sigmoid curve, corresponding one effect to one Cp1. Our hypothesis proposes that a real steady state model would show an intrinsic pharmacodynamic hysteresis with different Cp at loss of command (LOC) and the recovery of the response (ROC). Method and Study Subjects: To represent equilibrium Cp-Ce steps, 14 healthy volunteers, after IRB approval and written informed consent form, monitored with ECG, NIBP, CO2et, Sa02, and BIS, received propofol TCI in ef fect mode Schnider PK model in stepped plateaus 0.5 ug / ml of 7 minutes each, except at (LOC) plateau at which lasted 14 minutes. Af ter this we scaled two steps further reaching the maximal EEG depression. Then we proceeded to declines equal in magnitude and duration than the increases until reaching less than Cpcalc of 0.5 ug / ml. Venous samples were taken at the end of each step or every 7 min, to evalu- ate Propofol PK model performance2 by HPLC. We evaluate Explicit Amnesia, dropping a 60ml water syringe, loss of eyelash reflex, loss (LOC) and recov- ery (ROC) of consciousness, BIS during the entire process. The AnestFusorTM software3 was used to control the syringes, to store the EEG data and cal- culate the Cp every one second. Student t test for multiple comparison was used. Results: Basal BIS value was 97 and maximal depression 36 (23-50). The propofol Schnider PK performance was MDPE or bias of 0% and MDAPE or imprecision of 26%. The measured Cp at LOC was 2.06 ug/ml and 1.46 ug/ml at ROC (p< 0.05 ), with similar BIS (N.S). The BIS pre ROC was (49 [74-42]) statistically lower than the BIS value at LOC (64 [76-53]) (p< 0.05), but with similar measured Cp (N.S). Conclusions: Our results did not behave as a sigmoidal unique curve. We observed an intrinsic pharmacodynamic hysteresis between induction and emergency, reflecting probably the bistable characteristic of each neurologic condition. References: 1. BJA 98(6); 701-4, 2007 2. J PharmacokinetBiopharm 199