title: Relation between bispectral index measurements of anesthetic depth and postoperative mortality: a meta-analysis of observational studies.
abstract: BACKGROUND
  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.
  
  
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Phipps 455, Baltimore, MD, USA. andres.zorrilla@correounivalle.edu.co.|Faculty of Health, Universidad del Valle School of Medicine, Cali, Colombia. andres.zorrilla@correounivalle.edu.co.
authors.forename: Andres
authors.identifier: http://orcid.org/0000-0001-8140-8486
authors.initials: A
authors.lastname: Zorrilla-Vaca
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Phipps 455, Baltimore, MD, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Healy
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Phipps 455, Baltimore, MD, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Phipps 455, Baltimore, MD, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Grant
mesh_terms: D000758:Anesthesia / Q000009:adverse effects / Q000379:methods*; D000777:Anesthetics / Q000008:administration & dosage / Q000009:adverse effects; D056805:Consciousness Monitors; D006801:Humans; D064887:Observational Studies as Topic; D011183:Postoperative Complications / Q000453:epidemiology / Q000401:mortality*; D011184:Postoperative Period
chemical_list: D000777:Anesthetics