[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 long-term sedation (> or = 72 h) can be achieved in critically ill patients with an EEG median frequency controlled closed-loop system 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 formulations and their lipid load.


METHODS
After institutional approval and written consent, 16 ASA II-IV patients were included in this study. Main inclusion criterion was the necessity for prolonged sedation/analgesia for at least 72 h. Sedation was induced and maintained using continuous infusion of propofol 1% (n = 7) or 2% (n = 9). Analgesia was maintained with continuous infusion of alfentanil. The EEG was recorded from four leads (Fp1,2 and C3,4) 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 depending on the depth of sedation which was assessed clinically using a modified Ramsay score. Alfentanil was applied as TCI. Arterial plasma concentrations 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 EEG 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 remaining sedation period. At the same time, propofol plasma concentrations increased from 0.7 +/- 0.3 microgram/ml to 1.8 +/- 1.3 micrograms/ml. The patients required an average of 2.5 mg/kg/h propofol and 0.030 mg/kg/h alfentanil. Pharmacokinetics of propofol 2% showed an increased volume of distribution when compared to propofol 1%. Alfentanil clearance was found to be reduced with four patients 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 of propofol even for long-term sedation in critically ill patients. EEG median frequencies were similarly low as in deeply anaesthetised patients. No differences in quality of sedation were seen between the two propofol formulations, but propofol 2% seems to be advantageous due to lower lipid load and triglyceride values. Increasing concentrations of propofol at unchanged sedation scores and EEG median frequencies may indicate development of tolerance.
Albrecht
S
S
Klinik für Anästhesiologie, Universität Erlangen. albrecht@anaesthesiologie.med.uni-erlangen.de
Ihmsen
H
H
Suchodolski
K
K
Frenkel
C
C
Schüttler
J
J
D000328:Adult; D000368:Aged; D015760:Alfentanil / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003422:Critical Care; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects; D011175:Positive-Pressure Respiration; D015742:Propofol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors
D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D008055:Lipids; D015760:Alfentanil; D015742:Propofol