title: Mortality within 2 years after surgery in relation to low intraoperative bispectral index values and preexisting malignant disease.
abstract: BACKGROUND
  A correlation between deep anesthesia (defined as time with Bispectral Index (BIS) <45; T(BIS <45)) and death within 1 yr after surgery has previously been reported. In order to confirm or refute these findings, we evaluated T(BIS <45) as an independent risk factor for death within 1 and 2 yr after surgery and also the impact of malignancy, the predominant cause of death in the previous report.
  
  
  METHODS
  Mortality within 2 yr after surgery, causes of death and the occurrence of malignant disease at the time of surgery were identified in a cohort of 4087 BIS-monitored patients. Statistically significant univariate predictors of mortality were identified. In order to allow for comparison with previous data, the following multivariate analysis was first done without, and thereafter with, preexisting malignancy status, the predominant cause of death.
  
  
  RESULTS
  One-hundred-seventy-four (4.3%) patients died within 1 yr and another 92 during the second year (totaling 6.5% in 2 yr). T(BIS <45) was a significant predictor of 1- and 2-yr mortality when preexisting malignant disease was not among the co-variates (hazard ratio [HR] 1.13 [1.01-1.27] and 1.18 [1.08-1.29], respectively). Further exploration confined the significant relation between postoperative mortality and T(BIS <45) to patients with preexisting malignant diagnoses associated with extensive surgery and less favorable prognosis. The most powerful predictors of 2-yr mortality in the model, including preexisting malignancy, were ASA physical score class IV (HR 19.3 [7.31-51.1]), age >80 yr (HR 2.93 [1.79-4.79]), and preexisting malignancy associated with less favorable prognosis (HR 9.30 [6.60-13.1]).When the initial multivariate regression was repeated using preexisting malignancy status among the co-variates in the model, the previously significant relation between 1, and 2-yr mortality and T(BIS <45) did not reach statistical significance.
  
  
  CONCLUSIONS
  Using a similar set of co-variates as in previous work, we confirmed the statistical relation between 1-yr mortality and T(BIS <45), and we extended this observation to 2-yr mortality. However, this relation is sensitive to the selection of co-variates in the statistical model, and a randomized study is required to demonstrate that there really is a causal impact from and T(BIS <45) on postoperative mortality and, if it does, the effect is probably very weak in comparison with co-morbidity as assessed by ASA physical score, the preexisting malignancy status at surgery and age.
authors.affiliation: Department of Physiology and Pharmacology, Section for Anesthesia and Intensive Care, Karolinska Institutet, Stockholm, Sweden. majlisl@ltkalmar.se
authors.forename: Maj-Lis
authors.initials: ML
authors.lastname: Lindholm
authors.forename: Stefan
authors.initials: S
authors.lastname: Träff
authors.forename: Fredrik
authors.initials: F
authors.lastname: Granath
authors.forename: Scott D
authors.initials: SD
authors.lastname: Greenwald
authors.forename: Anders
authors.initials: A
authors.lastname: Ekbom
authors.forename: Claes
authors.initials: C
authors.lastname: Lennmarken
authors.forename: Rolf H
authors.initials: RH
authors.lastname: Sandin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D015331:Cohort Studies; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative; D015999:Multivariate Analysis; D009369:Neoplasms / Q000401:mortality / Q000503:physiopathology* / Q000601:surgery*; D016016:Proportional Hazards Models; D012307:Risk Factors; D055815:Young Adult