T K Kim1, P J Niklewski2, J F Martin3, S Obara4, T D Egan5. 1. Department of Anesthesiology SOM 3C444, University of Utah School of Medicine, 30 North 1900 East, Salt Lake City, UT 18132, USA Department of Anesthesia and Pain Medicine, Pusan National University, Busan, Korea. 2. Ethicon Endo-Surgery, Inc., 4545 Creek Road, Cincinnati, OH, USA Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA. 3. Department of Anesthesia and Pain Medicine, Pusan National University, Busan, Korea. 4. Department of Anesthesiology SOM 3C444, University of Utah School of Medicine, 30 North 1900 East, Salt Lake City, UT 18132, USA Department of Anesthesiology, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima 960-1295, Japan. 5. Department of Anesthesiology SOM 3C444, University of Utah School of Medicine, 30 North 1900 East, Salt Lake City, UT 18132, USA talmage.egan@hsc.utah.edu.
Abstract
BACKGROUND: Although the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) is frequently used in sedation-related drug and device studies, a major shortcoming is that it does not differentiate between lighter and deeper levels of general anaesthesia because the only noxious stimulus of the MOAA/S is a trapezius squeeze. The primary aim of this investigation was to expand the MOAA/S score to include truly noxious stimulation, thereby extending the dynamic range of the assessment to include sedation states consistent with deeper levels of general anaesthesia. METHODS: Twenty healthy volunteers received target controlled infusions of fentanyl (target=0.8 ng ml(-1)) and propofol (starting at 0.5 µg ml(-1) and gradually increasing to 5 µg ml(-1)). At each propofol concentration, a MOAA/S score was obtained before and after tetanic electrical stimulation. The tetanic electrical stimulation current was gradually increased until the subject responded or until 50 mA was delivered without a response. A pharmacodynamic model was constructed to characterize the concentration-effect relationship between propofol and the MOAA/S scores. RESULTS: All subjects required a significantly higher propofol concentration to produce unresponsiveness to tetanic electrical stimulation at 50 mA compared with a standardized trapezius squeeze. The pharmacodynamic model adequately characterized the concentration-effect relationship. CONCLUSIONS: The Extended Observer's Assessment of Alertness and Sedation (or EOAA/S) extends the range of the widely used MOAA/S score to include truly noxious stimulation, thereby enabling the identification of drug-induced central nervous system depression representative of surgical anaesthesia.
BACKGROUND: Although the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) is frequently used in sedation-related drug and device studies, a major shortcoming is that it does not differentiate between lighter and deeper levels of general anaesthesia because the only noxious stimulus of the MOAA/S is a trapezius squeeze. The primary aim of this investigation was to expand the MOAA/S score to include truly noxious stimulation, thereby extending the dynamic range of the assessment to include sedation states consistent with deeper levels of general anaesthesia. METHODS: Twenty healthy volunteers received target controlled infusions of fentanyl (target=0.8 ng ml(-1)) and propofol (starting at 0.5 µg ml(-1) and gradually increasing to 5 µg ml(-1)). At each propofol concentration, a MOAA/S score was obtained before and after tetanic electrical stimulation. The tetanic electrical stimulation current was gradually increased until the subject responded or until 50 mA was delivered without a response. A pharmacodynamic model was constructed to characterize the concentration-effect relationship between propofol and the MOAA/S scores. RESULTS: All subjects required a significantly higher propofol concentration to produce unresponsiveness to tetanic electrical stimulation at 50 mA compared with a standardized trapezius squeeze. The pharmacodynamic model adequately characterized the concentration-effect relationship. CONCLUSIONS: The Extended Observer's Assessment of Alertness and Sedation (or EOAA/S) extends the range of the widely used MOAA/S score to include truly noxious stimulation, thereby enabling the identification of drug-induced central nervous system depression representative of surgical anaesthesia.