Phase II Randomised Controlled Trial Of The Effects Of Parenteral Fish Oil Emulsion On Pro And Anti Inflammatory Markers And Clinical Outcome In Critically Ill Septic Patients In Intensive Care Unit

Introduction:

Sepsis is a leading cause of mortality in critically ill patients on the intensive care unit (ICU). Death from sepsis in the ICU is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with omega- 3 fish oil has been demonstrated to attenuate the effects of uncontrolled inflammation and may be clinically beneficial in reducing morbidity from organ dysfunction.

Trial design:

A phase 2 randomised controlled trial investigating the effects of parenteral omega-3 on critically ill patients in ICU in a single institution.

Methods:

Participants: Consecutive patients with sepsis were considered for the trial. Sepsis was defined as the presence of a known or suspected infection and two or more SIRS criteria (Systemic inflammatory response syndrome).

Interventions: 60 patients were randomised to receive either parenteral fish oil (FO) and standard medical care or standard medical care only.

Hypothesis: Administration of omega 3 fish oil emulsion will not alter the level of proinflammatory and anti-inflammatory markers in critically ill patients with sepsis on Intensive Care Unit as compared to controls.

Outcome: The primary outcome measure was the effect of omega-3 on various inflammatory markers including cytokine, complement, resolvins and protectins (measured using ELISA, LC-MS). The secondary outcome measure was clinical benefit measured using SOFA score and 28-day mortality. Cytokines and complement were analysed used ELISA. Resolvins & protectins were analysed using LC-MS. Data was analysed using Strata statistical tool.

Results:

Sixty patients were included in the study, 30 in the control group and 30 in the treatment group. The baseline demographics were matched for the two cohorts. A significant increase (p=0.001) was detected in the concentration of pro-inflammatory mediators PGE2, PGF2a, TXB2 in the control group while the anti-inflammatory mediators 4HDHA, 17HDHA were significantly higher in the FO group (p=0.01). Omega-3 significantly reduced IL-17 in FO group (p=0.035). Also, the concentration of other pro-inflammatory cytokines (E-selectin, VCAM, ICAM, TNFR1, TNF-α, IL-17, IL-12, IL-6, IL-1b) were reduced in the FO group. Omega-3 improved outcomes in C3 depleted patients by 50%. Patients treated with parenteral fish oil were associated with a significant reduction in new organ dysfunction (delta-SOFA 2.2±2.2 vs. 1.0±1.5, p=0.005 and maximum-SOFA 10.1±4.2 vs. 8.1±3.2, p=0.041). Patients treated with fish oil demonstrated a reduction in 28-day mortality (26% in control vs 13% in FO, p=0.19).

Conclusion:

This study has demonstrated that omega-3 altered the concentrations of various pro and anti-inflammatory mediators significantly resulting in clinical benefit. It was safe in critically ill septic patients in ICU.