Depth of anesthesia causality dilemmas: the next generation.

In 2005, the suggestion arose that a relatively ‘‘deeper’’ anesthetic, independent of hypotension, might entail a risk of increased postoperative mortality. At the time, little consideration was given to the possibility that a processed electroencephalogram (EEG) value indicative of a low depth of anesthesia index (DOAI) might represent an adverse condition in the central nervous system (CNS) as the underlying cause of the greater risk of mortality, i.e., that a low DOAI is a marker of the propensity for mortality and not the cause. A decade later and in this issue of the Journal, Leslie and Short review the data that address this ‘‘causality dilemma’’ and conclude that it is unresolved. I see less ambiguity in the quandary than they do. From my viewpoint, there is already compelling evidence that an anesthetic-sensitive CNS, as reflected by a greater than average reduction in DOAI in response to anesthetics, is an independent marker of a propensity for early mortality. My reasoning is as follows: There is compelling evidence from non-surgical situations that cognitive impairment (CI) is associated with early mortality. There is also ample evidence that CI is prevalent preoperatively in some surgical populations. The association of CI with early mortality is unlikely to be erased by the process of undergoing anesthesia and surgery. For a time, the ‘‘missing link’’ in this argument was confirmation that CI results in lower DOAI values in response to standardized doses or concentrations of anesthetic agents. It seems intuitively likely that such should be the case, but remarkably few investigations have addressed that proposition. I can identify only three but all point in the same direction. Laalou et al. observed that patients with CI required less propofol to achieve a target bispectral index (BIS) range than a cognitively normal agematched comparator group. Ni et al. (abstract in English, text in Chinese) exposed CI and cognitively normal patients older than 65 yr to standardized concentrations of sevoflurane and they observed lower BIS values in the CI group. Erdogan et al. identified patients with and without preoperative CI and observed that the CI patients with lower pre-induction BIS values achieved lower BIS scores in response to a standardized induction dose of propofol. In all three investigations, the CNS of the CI patients was more sensitive to anesthetic agents, at least as reflected by the DOAI response. The link appears to exist, i.e., CI patients are anesthetic sensitive by DOAI metrics. Additional data support an association between anesthetic sensitivity and a propensity for mortality. In the B-Unaware trial, patients who suffered early mortality achieved depth of anesthesia targets with lower concentrations of inhaled agents, i.e., the CNS was more sensitive to the depressive effect of anesthetics. The ‘‘triple low’’ data set cited by Leslie and Short— from my perspective, these data have too often been viewed with some lack of objectivity— also contains findings that argue against an adverse effect of low DOAI conditions per se. Time-pressured journal readers who read only abstracts and on some occasions that will include almost all of us might easily export the suggestion from the abstract of the Triple Low paper that, ‘‘OMG, the unnecessarily deep anesthesia that anesthesiologists ‘routinely tolerate’ is killing our patients!’’ While that data set does, in fact, contain a subgroup that affirms the association between the J. C. Drummond, MD Department of Anesthesiology, University of California, San Diego, San Diego, CA, USA