Published Online
on January 23, 2003

A more recent version of this article appeared on February 1, 2003

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Submitted on August 7, 2002
Accepted on August 19, 2002

Lower Endotoxin Immunity Predicts Increased Cognitive Dysfunction in Elderly Patients After Cardiac Surgery

Joseph P. Mathew MD^*; Hilary P. Grocott MD, FRCPC; Barbara Phillips-Bute PhD; Mark Stafford-Smith MD; Daniel T. Laskowitz MD; Daniel Rossignol PhD; James A. Blumenthal PhD; Mark F. Newman MD; for the Neurologic Outcome Research Group (NORG*) and; and the Cardiothoracic Anesthesiology Research Endeavors (CARE) Investigators of the Duke Heart Center

From the Department of Anesthesiology (J.P.M., H.P.G., B.P.-B., M.S.-S., M.F.N.); the Department of Medicine, Division of Neurology (D.T.L.); and the Department of Psychiatry and Behavioral Sciences (J.A.B.), Duke University Medical Center, Durham, NC, and Eisai, Inc (D.R.), Teaneck, NJ.

^* To whom correspondence should be addressed. E-mail: mathe014{at}mc.duke.edu.

Background and Purpose--Although coronary artery bypass graft surgery (CABG) improves the quality of life and functional capacity for numerous patients, many also exhibit impairment in cognitive function immediately after surgery. Although the etiology of this cognitive decline is multifactorial, the inflammatory response to the primary insult may modulate the extent of dysfunction. Patients with low preoperative levels of anti-endotoxin core antibody (EndoCAb) are more likely to experience adverse outcomes, suggesting that decreased immunity to endotoxin causes a heightened release of inflammatory mediators. We therefore sought to determine the association of decreased EndoCAb and the incidence of postoperative cognitive decline.

Methods--EndoCAb levels were measured before surgery in 460 patients undergoing elective CABG. Cognitive function was measured preoperatively and 6 weeks postoperatively. Multivariable analysis accounted for the effects of age, Parsonnet score, sex, body mass index, baseline cognition, years of education, history of hypertension, bypass time, cross-clamp time, and number of grafts.

Results--At 6-week follow-up, 122 patients (36%) showed cognitive decline. Lower preoperative EndoCAb levels were associated with a greater incidence and severity of postoperative cognitive decline. The elderly with decreased endotoxin immunity are particularly susceptible to this decline (relative risk=1.97 for age >64).

Conclusions--Reduced preoperative endotoxin immunity is a predictor of increased postoperative cognitive dysfunction in patients undergoing CABG, particularly in those >60 years old. Interventions that increase IgM EndoCAb levels might improve cognitive function after cardiac surgery.

Key words: cognitive disorders • coronary artery bypass surgery • endotoxemia

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