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.