Fish Oil Supplementation Does Not Affect Cognitive Outcomes in Cardiac Surgery Patients in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Trial

Abstract

Background: Cognitive decline has been reported following cardiac surgery, leading to great interest in interventions to minimize its occurrence. Long-chain n-3 (ω-3) polyunsaturated fatty acids (PUFAs) have been associated with less cognitive decline in observational studies, yet no trials have tested the effects of n-3 PUFAs on cognitive decline after surgery.

Objective: We sought to determine whether perioperative n-3 PUFA supplementation reduces postoperative cognitive decline in patients postcardiac surgery.

Methods: The study comprised a randomized, double-blind, placebo-controlled, multicenter, clinical trial conducted on cardiac surgery recipients at 9 tertiary care medical centers across the United States. Patients were randomly assigned to receive fish oil (1-g capsules containing ≥840 mg n-3 PUFAs as ethyl esters) or placebo, with preoperative loading of 8-10 g over 2-5 d followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first. Global cognition was assessed using in-person testing over 30 d with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (primary outcome), Mini-Mental State Exam (secondary outcome), and Trails A and B (secondary outcome) tests. All end points were prespecified. Statistical methods were employed, including descriptive statistics, logistic regression, and various sensitivity analyses.

Results: A total of 320 US patients were enrolled in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Cognitive Trial (OCT), a substudy of OPERA. The median age was 62 y (IQR 53, 70 y). No differences in global cognition were observed between placebo and fish oil groups at day 30 (P = 0.32) for the primary outcome, a composite neuropsychological RBANS score. The population demonstrated resolution of initial 4-d cognitive decline back to baseline function by 30 d on the RBANS.

Conclusion: Perioperative supplementation with n-3 PUFAs in cardiac surgical patients did not influence cognition ≤30 d after discharge. Modern anesthetic, surgical, and postoperative care may be mitigating previously observed long-term declines in cognitive function following cardiac surgery. This trial was registered at clinicaltrials.gov as NCT00970489.

Figures

FIGURE 1

CONSORT diagram showing screening, randomization, and follow-up for OCT, a substudy of OPERA. CONSORT, Consolidated Standards of Reporting Trials; OCT, Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation Cognitive Trial; OPERA, Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status.

FIGURE 2

These data represent the results of the RBANS (A), with a population age-adjusted mean (±SD) of 100 ± 15 and lower scores indicating worse global cognition; MMSE (B); Trails A scores (C); and Trails B scores (D). The total number of observations for each of these cognitive tests at each time point is listed at the bottom of each graph. In each graph a similar pattern appears for both the intervention (n–3 PUFA) and placebo groups, namely an initial decline in cognitive performance followed by a recovery to baseline function by postoperative day 30. There were no clinically meaningful or statistically significant differences between groups. DID, difference-in-difference; MMSE, Mini-Mental Status Examination; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; Trails A and B, Trailmaking Tests A and B.