Thiopental pharmacodynamics: II. Quantitation of clinical and electroencephalographic depth of anesthesia

This study examined the relationship among pseudo-steady-state (constant) serum thiopental concentrations, clinical anesthetic depth as assessed by several perioperative stimuli, and the electroencephalogram (EEG). Twenty-six ASA physical status 1 or 2 patients participated in the study. Two constant serum thiopental concentrations were maintained in each patient using a computer-controlled infusion pump. The first randomly assigned target serum concentration of 10-30 μg/ml was maintained for 5 min to allow serum:brain equilibration. Then the following stimuli were applied at 1-min intervals: verbal command, tetanic nerve stimulation, trapezius muscle squeeze, and laryngoscopy. A second, higher, randomly assigned target serum concentration of 40-90 μg/ml was then achieved and maintained by the computer-controlled infusion pump. The previously described stimuli were reapplied, after which laryngoscopy and intubation was performed. A positive response was recorded if purposeful extremity movement or coughing was observed. Using the quantal movement or cough response and the measured constant serum thiopental concentration, the probability of no movement to each stimulus was characterized using logistic regression. The serum thiopental concentrations that produced a 50% probability of no movement response for the clinical stimuli were as follows: 15.6 μg/ml for verbal command, 30.3 μg/ml for tetanic nerve stimulation, 39.8 μg/ml for trapezius muscle squeeze, 50.7 μg/ml for laryngoscopy, and 78.8 μg/ml for laryngoscopy followed by intubation. The EEG was analyzed using aperiodic waveform analysis to derive the number of waves per second. A biphasic relationship between constant serum thiopental concentration and the EEG number of waves per second was observed. Loss of responsiveness to verbal stimulation occurred when the EEG was activated at 15-18 waves/s. Marked EEG slowing and isoelectric EEG (1-3 waves/s) associated with high serum thiopental concentrations (> 50 μg/ml) were necessary to prevent movement response to profound noxious stimuli such as laryngoscopy and intubation. The biphasic thiopental concentration-EEG relationship and the isoelectric EEG at the high serum thiopental concentrations needed to prevent purposeful movement responses limit the utility of the EEG as a measure of anesthetic depth when thiopental is used alone. This study demonstrates a conceptual approach to quantitate the serum thiopental concentration versus clinical and EEG depth of anesthesia.