Relation between bispectral index measurements of anesthetic depth and postoperative mortality: a meta-analysis of observational studies

  • Andres Zorrilla-Vaca
  • Ryan J. Healy
  • Christopher L. Wu
  • Michael C. Grant
Reports of Original Investigations



The association between anesthesia depth and mortality is still controversial. There are a number of narrative reviews on this topic that affirm this association, but their conclusions were based only on qualitative analyses. The aim of this meta-analysis of observational studies was to examine the potential association between depth of anesthesia as a low bispectral index (BIS) and mortality using appropriate quantitative methods.


The literature was systematically reviewed in three main electronic databases (MEDLINE, EMBASE, Google Scholar) to identify all articles from inception through December 2015 regarding the association between depth of anesthesia and mortality. Inclusion criteria were restricted to observational studies that used multivariable Cox proportional regression methodology and reported adjusted hazard ratios (aHR). Pooled effect size was measured using a random effects model. Subgroup analysis was performed post hoc based on follow-up duration (30 days and ≥ one year).


Eight observational studies that included 40,317 patients were evaluated in this meta-analysis. The results showed a statistically significant association between the depth of anesthesia as measured by low BIS (< 40-45), and mortality (pooled aHR, 1.21; 95% CI, 1.07 to 1.38; P = 0.003). Subgroup analysis showed that the association between depth of anesthesia (measured by low BIS) and mortality was significant for studies with a follow-up duration of ≥ one year (n = 23,347; pooled aHR, 1.10; 95% CI, 1.00 to 1.21; P = 0.04) but was not significant for studies with a follow-up duration of 30 days (n = 16,970; pooled aHR, 1.38; 95% CI = 0.81 to 2.36; P = 0.24).


Existing observational studies support a significant association between depth of anesthesia (as measured by BIS) and long-term mortality (≥ one year), although it was without statistical significance at 30 days. Larger prospective, randomized trials are necessary to establish a definitive conclusion about whether this association represents true causality or is an epiphenomenon.


Postoperative Mortality Adjusted Hazard Ratio Minimal Alveolar Concentration Bispectral Index Anesthetic Depth 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Relation entre les mesures de l’indice bispectral de profondeur de l’anesthésie et la mortalité postopératoire: méta-analyse des études observationnelles



L’association entre profondeur de l’anesthésie et mortalité reste controversée. Un certain nombre d’études narratives sur ce sujet affirment que l’association existe, mais leurs conclusions étaient uniquement basées sur des analyses qualitatives. L’objectif de cette méta-analyse d’études observationnelles était d’examiner une association potentielle entre la profondeur de l’anesthésie sous forme d’indice bispectral (BIS) bas et la mortalité au moyen de méthodes quantitatives adaptées.


Les publications sur trois principales bases de données électroniques (MEDLINE, EMBASE, Google Scholar) ont fait l’objet d’une recherche systématique pour identifier tous les articles concernant l’association entre profondeur de l’anesthésie et mortalité, depuis leur création jusqu’en décembre 2015. Les critères d’inclusion étaient limités aux études observationnelles ayant utilisé la méthodologie de régression multifactorielle proportionnelle de Cox et les rapports de risques rapportés ajustés (aHR). La taille de l’effet combiné a été mesurée au moyen du modèle à effets aléatoires. Une analyse post hoc de sous-groupe a été effectuée en fonction de la durée du suivi (30 jours et ≥ un an).


Huit études observationnelles ayant inclus 40 317 patients ont été évaluées dans cette méta-analyse. Les résultats ont montré une association statistiquement significative entre la profondeur de l’anesthésie mesurée par un BIS bas (< 40 à 45) et la mortalité (aHR combiné, 1,21; IC à 95 %, 1,07 à 1,38; P = 0,003). L’analyse de sous-groupe a montré que l’association entre la profondeur de l’anesthésie (mesurée par un BIS bas) et la mortalité était significative pour les études dont la durée de suivi était ≥ un an (n = 23 347; aHR combiné, 1,10; IC à 95 %, 1,00 à 1,21; P = 0,04), mais elle n’était pas significative pour les études dont la durée de suivi était de 30 jours (n = 16 970; aHR combiné, 1,38; IC à 95 % = 0,81 à 2,36; P = 0,24).


Les études observationnelles existantes sont en faveur d’une association significative entre la profondeur de l’anesthésie (mesurée par le BIS) et la mortalité à long terme (≥ 1 an), même s’il n’y a pas eu de signification statistique à 30 jours. De plus grandes études randomisées prospectives sont nécessaires pour parvenir à une conclusion et déterminer si cette association présente un véritable lien de causalité ou n’est qu’un épiphénomène.



We thank the staff at the William H. Welch Medical Library, with whom we consulted when conducting the literature review for this analysis. We also thank the staff at the Biostatistics Department at the Johns Hopkins Bloomberg School of Public Health, with whom we consulted regarding the statistical analyses.

Conflicts of interest

None declared.

Editorial responsibility

This submission was handled by Dr. Hilary P. Grocott, Editor-in-Chief, Canadian Journal of Anesthesia.

Author contributions

Andres Zorrilla-Vaca and Michael C. Grant contributed substantially to all aspects of this manuscript, including conception and design; acquisition, analysis, and interpretation of data; and drafting the article. Christopher L. Wu contributed substantially to the conception and design of the manuscript. Ryan J. Healy contributed substantially to the acquisition of data.

Supplementary material

12630_2017_872_MOESM1_ESM.pdf (189 kb)
Supplementary material 1 (PDF 189 kb)


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Copyright information

© Canadian Anesthesiologists' Society 2017

Authors and Affiliations

  1. 1.Department of Anesthesiology and Critical Care MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Faculty of HealthUniversidad del Valle School of MedicineCaliColombia

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