It is reasonable to assume that every patient undergoing general anesthesia around the world is monitored according to a standard of care promoted by organizations representing the field. Apart from temperature and inhaled anesthetic measurement, routine monitors focus predominantly on aspects of cardiac and respiratory function. Although first formally suggested in 1937,1 the use of electroencephalographic brain monitoring has not been universally embraced in anesthetic practice, despite the fact that the brain is arguably the major target organ for the therapeutic effects of general anesthetics. In this issue of Anesthesia & Analgesia, Ben-Menachem and Zalcberg2 report the attitudes and usage patterns of anesthesiologists towards processed electroencephalogram (pEEG) monitors based on a survey of Australian practitioners. The investigators hypothesized that the interpretation of the evidence regarding the effectiveness of pEEG monitors in preventing intraoperative awareness largely drove the usage of pEEG monitors.
Thirty percent of the anesthesiologists contacted completed the online surveys (estimated to be about 8% of Australian anesthesiologists). Many of the respondents regarded pEEG monitors as superior at preventing intraoperative awareness with postoperative recall (AWR) compared with alternative preventative techniques. Notably, 74% felt that pEEG monitoring should be mandatory for patients undergoing total IV anesthesia (TIVA) with muscle relaxants. From the standpoint of preventing AWR, this perception could be viewed as consistent with published clinical trials and a synthesis of the evidence.3–5 Furthermore, this recommendation seems sensible given that we cannot currently monitor propofol concentration in real time, and there is more interpatient variability in response to propofol than there is to potent volatile agents.6,7 On the other hand, there has been only 1 randomized controlled trial specifically focusing on TIVA,5 and it is unclear whether the control group was managed with computerized target-controlled infusion, the most appropriate comparator. Therefore, pending more compelling evidence, we feel that it is premature to mandate as standard of care the use of pEEG monitoring for patients undergoing TIVA with muscle relaxants, although we share this clinical intuition.
In our opinion, the strongest current evidence is that a protocol based on bispectral index monitoring, one of several currently available pEEG monitors, is not superior to a protocol based on end-tidal anesthetic concentration (ETAC) monitoring coupled with an alarm for low concentration (e.g., 0.5 to 0.7 minimum alveolar concentration [MAC]).8–10 Although there could be a concern for bias in this statement given our roles in the conduct of these investigations, we base this conclusion on the number of patients prospectively studied across the 3 trials (approximately 27,000), the breadth of patient population (high-risk and unselected samples), and the number of hospitals where the data were gathered (6 across 4 institutions in the United States and Canada).8–10 The evidence is also strong that a bispectral index–based protocol is superior to routine anesthesia care, absent a protocol based on low ETAC alerts.4,10 The success of volatile agents in preventing AWR might relate to their “promiscuous” binding; unlike propofol, which binds predominantly to the γ-aminobutyric acid type A receptor, volatile agents act at multiple molecular targets and through several pathways to produce amnesia and general anesthesia.11,12 There is little interpatient variability in responsiveness to volatile anesthetics; over a narrow concentration range (standard deviation approximately 10%), they reliably render patients unresponsive, and the amnesic effects occur at very low concentrations (approximately 0.3 MAC).7,13,14 As such, we were surprised that the responses to the survey did not reflect a decisive majority regarding the probable lack of superiority of pEEG devices in preventing AWR compared with inhalational anesthetic techniques with ETAC alerts and when patients are not pharmacologically paralyzed.
Interestingly, 87% of respondents felt that a pEEG monitor was strongly indicated for patients with a history of awareness. Although there is recent evidence showing an estimated and adjusted 5-fold increased risk of AWR in patients with a history of AWR,15 there is no evidence in this population that a pEEG monitor is superior in preventing awareness to inhalational anesthesia with a low ETAC alert. A comparison of the evidence and the reported attitudes expressed in the survey is summarized in Table 1.
Apart from the prevention of awareness, many practitioners who responded to the survey expressed the view that pEEG monitoring could be used as a titration aid allowing anesthesiologists to safely administer less anesthesia, leading to improved early postoperative recovery and, more controversially, decreased morbidity. The evidence from large clinical trials is conflicting regarding the effectiveness of pEEG monitors in guiding decreased volatile anesthetic administration.4,8–10,16 A likely explanation is that for many patients there is a poor concentration–response relationship between anesthetic concentrations and pEEG indices, with a plateau in this relationship commonly found over a wide and clinically relevant range of volatile anesthetic concentrations.17 This poor concentration versus pEEG index relationship makes it less likely to achieve fine titration using the index. Even if precise titration is difficult, hypothesis-generating evidence has emerged in recent years that cumulative time with low pEEG index values is associated with adverse outcomes, including delirium, cognitive decline, and death.16,18 Perhaps the most compelling data regarding pEEG monitors and postoperative outcomes relate to the potential prevention of delirium, which is a significant adverse outcome with major consequences for patients and the health system. Three randomized, controlled studies and a secondary analysis of a randomized trial with a different primary outcome have all pointed to the possibility that pEEG guidance of anesthesia might be associated with a clinically relevant reduction in postoperative delirium.16,19–21 Our perspective is that mandating pEEG usage for this indication would be premature, especially since the mechanism of this reduced incidence is unclear. In our recent secondary analysis of the BAG-RECALL trial, a lower anesthetic concentration was an independent predictor of delirium, in contrast to the other trials.21 Beyond mechanistic concerns, there is the longstanding observation that findings from early and small randomized trials may not be replicated in later and larger studies.22 There are multiple examples of impressive positive clinical trials, which have been embraced and have led to mandated changes in standard-of-care, with subsequent studies finding contradictory results.23,24 Unfortunately, in some cases, this necessitated confusing policy reversals and de-implementation, a difficult process. Large, independent comparative effectiveness trials, with appropriate control groups, should be conducted to clarify whether or not pEEG guidance truly promotes improved postoperative outcomes.
In contrast to the results obtained from Australian anesthesiologists, we know from the NAP-5 study that 25% of United Kingdom anesthesiologists occasionally use pEEG devices in their practice and fewer than 2% use a pEEG routinely.25 The large discrepancy between reported usage in Australia and the United Kingdom (and probably elsewhere in the world, including the United States) warrants consideration. Methodologically, the nationwide NAP-5 audit may have yielded more representative results. However, factors other than objective evidence are likely to be influencing both attitudes toward and usage patterns of pEEG monitors during general anesthesia. Deficiencies in implementation are common throughout medicine and should be a quality improvement priority for our field. Where compelling evidence has already emerged, systematic efforts at implementation should be employed. For example, standards of care should be reconsidered and revised if pEEG monitors are shown conclusively to decrease awareness in pharmacologically paralyzed patients undergoing TIVA. On the other hand, where evidence is ambiguous, mandatory implementation is definitely not appropriate and could waste resources and promote disaffection among clinicians. An example of an attempt at premature implementation is the guideline from the National Institute of Health and Care Excellence in the United Kingdom, which recommended the use of pEEG devices as standard-of-care for older, more vulnerable surgical patients.26 This advice is counter to the established practice in the United Kingdom and is lacking evidential backing.
Going forward, it is necessary to emphasize that monitoring the brain during general anesthesia is an evolving science, and it is likely that neurobiologically informed monitors will be developed and refined. These future monitors will hopefully have higher fidelity in discriminating brain states, with broader applicability to anesthetic practice. If brain monitoring is demonstrated convincingly to impact patient outcomes other than intraoperative awareness, the next major challenge for the field will be translating that evidence to standardized practice patterns. As the Australian and NAP-5 surveys suggest, we must “mind the gap” between data and decision making in order to understand better how to bridge evidence and changes in practice.
Name: Michael S. Avidan, MBBCh.
Contribution: This author helped write the manuscript.
Attestation: Michael S. Avidan approved the final manuscript.
Name: George A. Mashour, MD, PhD.
Contribution: This author helped write the manuscript.
Attestation: George A. Mashour approved the final manuscript.
This manuscript was handled by: Franklin Dexter, MD, PhD.
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