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TECHNOLOGY, COMPUTING, AND SIMULATION

Mortality Within 2 Years After Surgery in Relation to Low Intraoperative Bispectral Index Values and Preexisting Malignant Disease

Maj-Lis Lindholm, PhD, RN^*, Stefan Träff, MD, Fredrik Granath, PhD, Scott D. Greenwald, PhD, Anders Ekbom, MD, PhD, Claes Lennmarken, MD, PhD, and Rolf H. Sandin, MD, PhD^*

From the *Department of Physiology and Pharmacology, Section for Anesthesia and Intensive Care, Karolinska Institutet, Stockholm, Sweden; Department of Anesthesia and Intensive Care, University Hospital, Linköping, Sweden; Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden; and Aspect Medical Systems, Norwood, Massachusetts.

Address correspondence and reprint requests to Maj-Lis Lindholm, PhD, RN, Department of Anesthesia and Intensive Care, Länssjukhuset, S-39185 Kalmar, Sweden. Address e-mail to majlisl{at}ltkalmar.se.

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.

CONCLUSION: 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.