Analgo-sedation in intensive care: a quantitative, EEG-based trial with propofol 1% and 2%

Objective: The primary aim of this study was to find out whether adequate l ong-term sedation (greater than or equal to 72 h) can be achieved in critic ally ill patients with an EEG median frequency controlled closed-loop syste m for the application of propofol 1% and 2%. Moreover, we investigated the pharmacokinetics and pharmacodynamics of propofol with respect to possible tolerance and compared the quality of sedation of both propofol formulation s and their lipid load. Patients and methods: After institutional approval and written consent, 16 ASA II-IV patients were included in this study. Main inclusion criterion wa s the necessity for prolonged sedation/analgesia for at least 72 h. Sedatio n was induced and maintained using continuous infusion of propofol 1% (n=7) or 2% (n=9). Analgesia was maintained with continuous infusion of alfentan il. The EEG was recorded from four leads (Fp(1,2) and C-3,C-4) and the EEG median frequency was obtained from the power spectrum (0.5-32 Hz). Propofol was administered computer-controlled with a median frequency setpoint depe nding on the depth of sedation which was assessed clinically using a modifi ed Ramsay score. Alfentanil was applied as TCI. Arterial plasma concentrati ons were measured by HPLC (propofol) and RIA (alfentanil). Pharmacokinetics of propofol and alfentanil were derived using a three compartment model. Results: All patients were successfully sedated for 77+/-9 h. The median EE G frequency during sedation was stable at 1.5+/-0.2 Hz. The sedation score increased from 1 in the first 12 h to values between 2 and 3 for the remain ing sedation period. At the same time, propofol plasma concentrations incre ased from 0.7+/-0.3 mu g/ml to 1.8+/-1.3 mu g/ml. The patients required an average of 2.5 mg/kg/h propofol and 0.030 mg/kg/h alfentanil. Pharmacokinet ics of propofol 2% showed an increased volume of distribution when compared to propofol 1%. Alfentanil clearance was found to be reduced with four pat ients having extremely small clearance values (33+/-3 ml/min). Triglyceride values increased up to 4.5+/-1.2 mmol/l for patients receiving propofol 1% and remained within normal range for propofol 2%. Conclusions: The EEG median frequency can be used for closed-loop control o f propofol even for long-term sedation in critically ill patients. EEG medi an frequencies were similarly low as in deeply anaesthetised patients. No d ifferences in quality of sedation were seen between the two propofol formul ations, but propofol 2% seems to be advantageous due to lower lipid load an d triglyceride values. Increasing concentrations of propofol at unchanged s edation scores and EEG median frequencies may indicate development of toler ance.