Guarding the Threshold: Depth-of-Anesthesia Monitoring and its Impact on the Neuroendocrine-Inflammatory Stress Response: A Systematic Review

Abstract

Background: Intraoperative depth-of-anesthesia (DoA) monitoring using processed-EEG indices (Bispectral Index [BIS], Entropy, Narcotrend) was developed to prevent intraoperative awareness, but a growing body of evidence suggests it may also modulate the neuroendocrine-inflammatory response to surgical stress. This review frames the anesthetic titration strategy itself as the primary exposure and neuroendocrine/inflammatory biomarkers as the outcome, a pairing not addressed by prior reviews in this space.

Methods: MEDLINE/PubMed and general web search (search-engine mediated; institutional access to Embase, Scopus, Web of Science, and Cochrane CENTRAL was not available for this review) were searched for randomized controlled trials and comparative cohort studies evaluating processed-EEG-guided anesthesia against standard or alternative-depth anesthesia, reporting at least one neuroendocrine (cortisol, ACTH, glucose) or inflammatory (IL-6, TNF-α, CRP, IL-1β, IL-10) biomarker. Reference lists of included studies were hand-searched. One identified study was excluded after discovery that it had been formally retracted. Given cross-study heterogeneity, findings were synthesized by vote-counting direction of effect rather than pooled meta-analysis.

Results: Seven studies (plus one retrospective cohort retained for mechanistic context only) met inclusion criteria, spanning cardiac (CABG/OPCAB), thoracic (VATS lobectomy), and abdominal/gastrointestinal surgery in adult and elderly populations. Monitoring modalities included BIS, Spectral/State Entropy, and Narcotrend. Deeper or monitor-titrated anesthesia favored attenuated TNF-α in 3 of 4 studies, lower CRP in 2 of 2 studies, lower IL-1β in 2 of 2 studies, and lower IL-6 in 2 of 3 studies reporting each marker; no study reported a biomarker moving in the direction of harm under monitor-guided titration for these markers.

Conclusions: Across a modest but consistent evidence base, anesthetic depth-titration strategy shows a directionally consistent association with attenuated postoperative inflammatory cytokine release, without evidence of harm. The evidence base remains limited in size and heterogeneous in monitoring modality and biomarker timing; a fully resourced multi-database systematic search with formal meta-analysis is needed before these findings can inform practice guidance.