SUMMARY

Horace Well's demonstration of nitrous oxide at Massachusetts General Hospital in 1846 was declared a "humbug" because an inadequate nitrous oxide dose failed to fully blunt the patient's perception of pain from a dental extraction. Ever since, anesthesiologists have struggled with varying definitions of this triad—stimulus, response, and anesthetic drug—in an effort to find a common definition of anesthetic depth. The definition of "depth of anesthesia" has constantly changed over the past 160 years as the drugs used to administer anesthesia evolved and the fundamental knowledge of anesthetic drug effects increased.

In this edition of Anesthesia we have defined anesthetic depth as the probability of nonresponse to stimulation, calibrated against the strength of the stimulus, the difficulty of suppressing the response, and the drug-induced probability of nonresponsiveness at defined drug effect-site concentrations. This definition requires that multiple different stimuli and responses be measured at well-defined drug concentrations. No specific individual stimulus and response measurement will capture depth of anesthesia in a clinically or scientifically meaningful manner. Thus, the anesthesiologist must understand a complex matrix of stimuli, responses, and anesthetic drugs, including their pharmacodynamic (and generally synergistic) interactions. This definition captures the nature of current routine clinical care whereby anesthesiologists observe a series of stimuli from talking to the patient preoperatively to skin incision to intubation. They also observe a range of responses ranging from verbal response to movement to tachycardia and hypertension, and they calibrate these observations of stimuli and responses against the anesthetic drugs used to reduce the probability of response by constantly adjusting the administered dose to achieve the desired anesthetic depth.

In our definition of "depth of anesthesia" we define the need for two components to induce the anesthetic state: hypnosis created with drugs such as propofol or the inhaled anesthetics and analgesia created with the opioids or nitrous oxide. We demonstrate the scientific evidence

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The BIS index is presently the most extensively validated measure of "depth of anesthesia." This monitor correlates well with the effects of hypnotics (particularly propofol, thiopental, and inhaled anesthetic gases) on memory, sedation, and consciousness. The BIS index does not measure the intrinsic brain state. It measures hypnotic drug effect. Nevertheless, titration guided by the BIS index appears to decrease the incidence of intraoperative awareness, currently estimated at 0.2% in healthy patients undergoing general anesthesia. An electrophysiologic measure of analgesia parallel to the BIS index and hypnotic assessment is not currently available.

There is considerable room for the development of additional technology and pharmacologic insight into measures of the depth of anesthesia. The opioid/hypnotic concentration-versus-response surface relationship has not been characterized for many stimulus-response pairs. There are many additional drug interactions that might be profitably characterized (e.g., opioids versus α₂ -adrenergic agonists), as well as higher-dimensional drug interactions (e.g., three-drug interaction surfaces^[28] ). There are cells in the stimulus-response matrix for which only poor EEG predictors (e.g., movement with opioid/nitrous oxide anesthesia, ketamine) are available. Certain important responses are poorly understood (e.g., inflammatory, humeral, neurophysiologic, and psychological responses). Our definition of anesthetic depth and measurement of anesthetic depth will expand as the matrix of stimuli, responses, and the drugs that influence the probability of nonresponse expands with new research and new knowledge.