Effect of n-3 fatty acids on cerebral markers and the inflammatory response in sepsis

Introduction

Patients with sepsis are at high risk of developing sepsis-associated delirium (SAD), which is associated with increased mortality and may be an important risk factor for the development of long-term cognitive dysfunction. Mechanisms leading to SAD are unclear, therapy and prophylaxis unsatisfactory. Inflammation and its effects on the brain may play an important role. We hypothesized that n-3 fatty acids will have a beneficial effect on systemic inflammation and hence cerebral markers in sepsis.

Methods

Randomized single-blind design. Patients >18 years admitted for treatment of sepsis. Exclusion criteria were thrombocytopenia, brain injury or tumors, intracranial infection and history of stroke. Patients received treatment according to the Surviving Sepsis Campaign and were randomly allocated to a group with or without daily supplemental intravenous n-3 fatty acids (Omegaven™; Fresenius Kabi, 2 ml/kg/day). Daily screening for SAD was performed. CRP, IL-6, IL-8, S-100β, and neuron-specific enolase (NSE) were monitored on days 1, 2, 3, and 7. The primary endpoint was the area under the curve of the S-100β time course.

Results

Eighteen patients were included. SAPS II scores and baseline values for CRP, IL-6, IL-8, NSE and S-100β for patients with and without supplemental n-3 fatty acids were 51 ± 14 vs 57 ± 22, 241 ± 65 vs 218 ± 106 mg/l, 2,054 ± 2,822 vs 734 ± 1,467 pg/ml, 312 ± 503 vs 90 ± 96 pg/ml, 25 ± 7 vs 21 ± 8 μg/ml, and 0.57 ± 0.90 vs 0.24 ± 0.24 μg/ml, respectively. In agreement with earlier data, patients with SAD had higher values for S-100β (P = 0.019) [1]. AUC for S-100β was 2.73 ± 2.89 vs 0.95 ± 0.74 (P = 0.14) for patients receiving supplemental n-3 fatty acids and controls, respectively. While none of the differences reached significance, IL-6 and IL-8 declined more rapidly in the n-3 fatty acid-treated group whereas cerebral markers showed an opposite trend. The number of patients with SAD and the duration of SAD were not different in both groups.

Conclusions

Interpretation of the results is hampered by unevenly distributed baseline characteristics and more patients need to be investigated. In this small sample no beneficial effect of n-3 fatty acids on cerebral markers was found.