Introduction

Patient’s staying in ICUs with critical condition such as sepsis, acute lung injury (ALI), acute respiratory distress syndrome (ARDS) or multiple trauma, excessive inflammation often leads to multiple organ dysfunction syndrome and death (Carcillo et al., 2017). Malnutrition is one of the outcomes of ICU admission which aggravates clinical status including disruption of immune system function, respiratory muscles, ventilation capacity and gastrointestinal tolerance and leads to loss of lean body mass (Lew et al., 2017). As a result of these impairments, complications such as esophagitis, gastroesophageal reflux, pulmonary aspiration and infections can lead to sepsis, multi-organ failure and death (Lew et al., 2017). Supportive nutrition via reducing oxidative stress, modulates inflammatory response, feeding tolerance that could be helpful for critically ill patients (Hegazi and Wischmeyer, 2011). Among the supportive nutrition therapies, fatty acid based formulas which have considerable role in the mechanism of regulating immune system might have a important role in clinical outcomes in ICU patients.
The influence of fat intake on composition of cell membrane could alter immune inflammatory responses like neutrophils and macrophages function consequently (Hegazi and Wischmeyer, 2011). Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the most important long chain fatty acid that serves as precursors of anti-inflammatory mediators (Calder, 2006) and suppress the production of cytokines IL-6 and TNF-α, both in vivo and vitro (Das, 2013) whereas arachidonic acid (AA) as an omega-6 fatty acid is precursor to inflammatory eicosanoids and leukotriene mediators (Calder, 2006). However, γ-Linolenic acid (GLA) is an omega-6 fatty acid and unlike arachidonic acid has shown anti-inflammatory properties. Nutritional supplementation with this fatty acid combined with omega-3 fatty acids boosts the immune system (Calder, 2006).
A meta-analysis of 17 clinical trials suggested routine supplementation with omega-3 fatty acids should be avoided because the overall evidence had very low quality and was insufficient to justify the routine use of omega-3 fatty acids in the management of sepsis (Lu et al., 2017). The effects of supplementation with fatty acids on ICU patients showed contradictory findings. Recently Chen et al (Chen et al., 2017) showed that the beneficial effect of omega-3 fatty acids supplementation for treatment of acute lung injury and acute respiratory distress syndrome contributed to the improvement of PaO2/FiO2 ratio, as well as ventilator-free day and decreased ICU-free days; while in another study, supplementation with omega-3 did not cause any significant changes in oxygenation, ventilator free days, ICU free- days and mortality (Stapleton et al., 2011).
Dietary antioxidants such as vitamin C and E act by reducing oxidative stress and as a scavenger of oxidant products to help immune system (Carr and Maggini, 2017, Lewis et al., 2019).
Several Randomized Controlled Trials (RCTs) on this certain formula have been performed for sepsis (Pontes-Arruda, 2005, Pontes-Arruda et al., 2011, Grau-Carmona et al., 2011), ARDS (Elamin et al., 2005, Shirai et al., 2015, Pacht et al., 2003, Nelson et al., 2003), ALI (Schott and Huang, 2012, Rice et al., 2011, Theilla et al., 2007) and multiple trauma (Kagan et al., 2015) reporting contradictory effects. A meta- analysis of 6 clinical trials in critically ill patients showed that immunomodulatory diet containing omega-3 fatty acid, γ-linolenic acid and antioxidants did not have any significant effect on ventilator free- days, ICU free- days and risk of mortality in ALI and ARDS patients, but in subgroup with high mortality it was found to be useful (Li et al., 2015). A number of RCTs about immunomodulatory diet containing omega-3 fatty acid, γ-linolenic acid and antioxidants showed significant reduction in mortality (Gadek et al., 1999, Pontes-Arruda et al., 2006) and improvement in oxygenation (Gadek et al., 1999, Pontes-Arruda et al., 2006, Singer et al., 2006) and ICU free-days (Gadek et al., 1999) and ventilator-free days (Pontes-Arruda et al., 2006, Singer et al., 2006). On the other hand, few RCTs showed no significant change in mortality (Grau-Carmona et al., 2011, Singer et al., 2006), oxygenation (Grau-Carmona et al., 2011, Rice et al., 2011) and ventilator free-days (Grau-Carmona et al., 2011). A meta-analysis (Li et al., 2015) examining the effects of immunomodulatory formula on clinical outcomes excluded the effects on PaO2/FiO2, duration of mechanical ventilation and duration of hospital stays.
Therefore, we conducted a systematic review and meta-analysis for the first time provide a precise estimate of the overall effects of omega-3 fatty acid, γ-linolenic acid and antioxidant supplementation on clinical outcomes and mortality in critically ill patients.