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Anesthetic Depth and Complications After Major Surgery
Study Questions:
In patients undergoing major noncardiac surgery, is there a causal relationship between deeper anesthesia and greater risk of adverse postoperative outcomes?
Methods:
Patients ≥60 years old with significant comorbidity (American Society of Anesthesiologists [ASA] III-IV), scheduled for major elective surgery, were randomly assigned to receive deeper versus lighter anesthesia, determined by active titration to bispectral index (BIS) processed electroencephalography (EEG) targets of 50 versus 35 BIS units, goals at a high-end and slightly below low-end of the range typically recommended to afford safe surgical conditions, and an acceptably low risk of intraoperative awareness. In the lighter and deeper arms (“BIS50” and “BIS35”), BIS was to be maintained within ± 5 units of target, and intraoperative mean arterial pressure maintained with vasoactive medication to a clinically acceptable range determined for each patient prior to randomization. Maintenance anesthetic was restricted to volatile agents (isoflurane, sevoflurane, or desflurane). The primary outcome was 1-year all-cause mortality, while secondary outcomes included a variety of nonfatal complications, 1-year disability-free survival, incidence of proven awareness during surgery, and quality of recovery; analysis was by intention-to-treat.
Results:
Among 6,644 patients enrolled at 74 institutions, those receiving deeper anesthesia had no significant increase in 1-year mortality (incidence 7% in the BIS50 vs. 6% in the BIS35 groups; hazard ratio, 0.88; 95% confidence interval, 0.73-1.01), and no difference in secondary outcomes, including quality of recovery, hospital length-of-stay, 1-year disability-free survival, sepsis, or cardiovascular complications, compared to patients receiving light anesthesia. One patient from the BIS50 group had confirmed intraoperative awareness. Anesthetic use was 30% lower in the BIS35 group, but mean arterial pressures differed by only 4 mm Hg between groups. Only 66% of patients successfully remained within 5 BIS-units from targeted value; among those meeting the goal, average BIS separation between randomization groups was only 8.4 units.
Conclusions:
Deeper anesthesia, titrated to BIS value of 35 versus 50, had no significant impact on 1-year mortality or other important clinical outcomes among a large population of high-risk older patients undergoing major surgery, when mean arterial pressure was maintained within clinically acceptable ranges by vasoactive medication.
Perspective:
Although previous observational studies raised concerns about associations between deep anesthesia and adverse outcomes among elderly patients, findings from this randomized trial reject that relationship, demonstrating that the depth of anesthesia itself, when titrated to one of two moderate but distinct BIS targets, did not affect 1-year mortality or any other clinically significant outcome. It is important to remember that this lack of outcome difference was observed in a population receiving a standardized protocol of volatile anesthesia, where “deep anesthesia” had a lower limiting boundary, and appropriate hemodynamic goals were established and maintained. Targeting anesthesia to specified BIS ranges often proved challenging, especially when lighter anesthesia was attempted. Some of that challenge can be explained by the limitations of processed EEG as a sole determinant of appropriate anesthetic depth. Although BIS reflects hypnosis, it will not signal escalating anesthetic requirements from fluctuations in surgical stimulation as rapidly as a broad set of parameters that includes a variety of hemodynamic and neuromuscular responses.
Clinical Topics: Heart Failure and Cardiomyopathies, Prevention
Keywords: Anesthesia, Arterial Pressure, Comorbidity, Electroencephalography, Intraoperative Awareness, Isoflurane, Length of Stay, Methyl Ethers, Risk Assessment, Sepsis, Secondary Prevention, Elective Surgical Procedures, Treatment Outcome
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