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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 2  |  Page : 667-671

The effect of omega-3 as diet-enhanced immunity on sepsis outcome in critically ill patients


Department of Anesthesia and Intensive Care, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt

Date of Submission28-Nov-2021
Date of Decision11-Jan-2022
Date of Acceptance16-Jan-2022
Date of Web Publication27-Jul-2022

Correspondence Address:
Marwa M Taha
Department of Anaesthesia and Intensive Care, Ministry of Health and Population, Tanta, El Gherbia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_272_21

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  Abstract 


Background
Nutritional supplementation of omega-3 fatty acids has been proposed to modulate the balance of proinflammatory and anti-inflammatory mediators in sepsis and acute lung injury.
Objectives
To evaluate the effect of omega-3 fatty acids as diet-enhanced immunity on sepsis outcome in critically ill patients.
Patients and methods
Sixty patients with early sepsis were divided equally into two groups: group A who received high-dose omega-3 fatty acids for consecutive 7 days besides conventional sepsis treatment, group B: control group who received only conventional sepsis treatment. Both groups were followed up by inflammatory markers, sequential organ failure assessment score monitoring, need for organ-supportive measures, length of ICU stay, mortality rate, final outcome, and complications.
Results
Compared with the control group, the high-dose omega-3 fatty acids exhibited lower levels of white blood cells, C-reactive protein, and procalcitonin at day 5 (P = 0.001, 0.012, and 0.001, respectively) and at day 7 (P = 0.014, 0.008, and 0.29, respectively). As regards serum lactate, there was an insignificant difference between D1–D5 and D1–D7 (P = 0.087 at day 5 and P = 0.80 at day 7). Group A showed a significant decrease in the length of ICU stay (P = 0.035), with the insignificant difference in sequential organ failure assessment score, the need for vasopressor, days free from mechanical ventilation, and mortality rate (P = 0.293, 0.796, 0.201, and 0.781, respectively).
Conclusion
The use of omega-3 therapy is safe and associated with promising effects on inflammatory cascade and may play a role in these patients.

Keywords: critical care, inflammation, nutrition, omega-3 fatty acids, sepsis


How to cite this article:
Attallah HA, El Rhaman A A, Salutan WE, Taha MM. The effect of omega-3 as diet-enhanced immunity on sepsis outcome in critically ill patients. Menoufia Med J 2022;35:667-71

How to cite this URL:
Attallah HA, El Rhaman A A, Salutan WE, Taha MM. The effect of omega-3 as diet-enhanced immunity on sepsis outcome in critically ill patients. Menoufia Med J [serial online] 2022 [cited 2024 Mar 28];35:667-71. Available from: http://www.mmj.eg.net/text.asp?2022/35/2/667/352188




  Introduction Top


Sepsis is the most frequent cause of admission to an ICU and has been recent as the final common pathway of death[1].

Sepsis is the body's overwhelming and life-threatening response to infection that can lead to tissue damage, organ failure, and death. In other words, it is our body's overactive and toxic response to an infection[2].

The progressive increase in the number of sepsis and septic-shock survivors emphasizes the long-term consequences of sepsis such as cognitive dysfunction and functional disabilities and psychiatric morbidity. Moreover, it decreases the health-related quality of life, unplanned hospital readmission, and late mortality[3].

The immune dysfunction in sepsis is complicated by simultaneous participation of the inflammatory and anti-inflammatory responses[4].

Nutrition support is critical in maintaining homeostasis in the ICU patient to provide nutrients for the lean body mass as well as repair and maintenance of organ function[5].

Omega-3 Fas can decrease the production of inflammatory cytokines and eicosanoids and thus may offer benefits to patients with a critical illness[6].

Resolution of inflammation was considered as a passive process at the end characterized by decreased levels of cytokines, prostaglandins, and reactive oxygen species. Conversely, during the last few years, the resolution from inflammation has been more clearly identified as an active process where lipid mediators specifically participate in the resolution process by switching their phenotype. So omega-3 Fa may play a role[7].

The aim of the study was to evaluate the role of omega-3 as diet-enhanced immunity on sepsis outcome in critically ill patients.


  Patients and methods Top


A cohort study was conducted on all patients with early sepsis, admitted to the Critical Care Department, Menoufia University Hospital from September 2018 to September 2020. Patients with sepsis were included in the study after having informed written consent from the patients and approved by the Ethics Committee in Menoufia University.

Exclusion criteria

Severe sepsis, burned patients, HIV patients, significant immunological suppression [white blood cell (WBCs) <5000 cells/mm30], imminence of receiving parenteral nutrition, presence of uncontrolled diarrhea, recent gastrointestinal bleeding, end-stage hepatic or renal disease, life expectancy less than 24 h, and pregnancy.

Inclusion criteria

Patients 18 years, with mild sepsis according to acute physiology and chronic health evaluation score less than 15 and classified according to sequential organ failure assessment score as SOFA.

Study protocol: studied patients were randomized into two groups. Group A received high-dose omega-3 (9 g of supplementation in the form of docosahexaenoic acid and eicosapentaenoic acid DHA and EPA (omega-3 plus)) in three divided doses daily for seven consecutive days, either orally or via nasogastric tube plus conventional sepsis treatment. Group B received only conventional treatment, which consists of treating or eliminating the source of infection, timely and appropriate usage of antimicrobial agents, hemodynamic optimization, and other physiologic organ-supportive measures.

The studied-population diet was enriched with DHA and EPA, although it remained isocaloric and isonitrogenous to the control diet. Patients received enteral nutrition within 6 h of meeting the inclusion criteria. Enteral feeding was delivered at a constant rate to achieve a minimum of 50% basal energy expenditure (BEE, determined using Harris–Benedict equation)×1.3 within the first 24 h. If well tolerated, enteral nutrition was advanced to achieve a minimum of 75% of BBE × 1.3 within 72 h.

The enteral diets were composed of proteins (82 g/day about 16% of total calories), carbohydrates (265 g/day about 54% of total calories), and lipids (63 g/day about 30% of total calories).

Evaluation of patients was done by routine laboratory investigation for monitoring the clinical state of the patient on admission in the intensive care and during nutrition course: daily investigation (CBC), random blood glucose (mg/dl), blood urea nitrogen, serum Na+, serum K+, and creatinine. Twice-weekly investigation: liver functions SGOT and SGPT. Weekly investigation: serum Mg++, serum Ca++, and PO4. On need investigation: blood culture and ABG. Microbiological studies, including pan cultures (sputum, blood, urine, or biological fluid according to clinical suspicion) prior to antibiotic administration. Imaging studies are required to identify the source of sepsis (e.g. chest radiograph).

The two groups were compared for improvement in sepsis outcome by SOFA score – WBC count, serum C-reactive protein (CRP) and serum procalcitonin (PCT), and D1, D5, and D7. Days free from mechanical ventilation. Need a vasopressor. Length of stay in the intensive care. Mortality rate.

CRP was measured in the serum sample by CRP reagent kit that was based on the principle of the latex-agglutination assay described by Singer Plotz, based on an immunological reaction between CRP and antisea bounded to biologically inert latex particles and the CRP test specimen. When serum contains greater than 0.8 mg/dl, CRP is mixed with latex reagent; visible agglutination occurs.

PCT was evaluated by using human PCT, ELISA kit (EIAab Science Co. Ltd., Wuhan, Hubei, CN). PCT was measured in duplication by a specific Immunoassay ELIZA kit requiring 20 μl of serum and 2 h to complete.

The detection range of this immunoassay is 15.6–1000 pg/ml. Immunoassay is measured automatically on a Bio Tek ELx 800 apparatus.

Any unexpected risk that appeared during the course of research was cleared to patients' relatives and to medical ethics committee on time.

All data obtained during the study were confidential. Every patient had a private secret code and the research results were used for scientific purposes.

Statistical analysis

Statistical analysis was done using SPSS 19 (SPSS Inc., an IBM Company, Chicago, Illinois, USA). Values were expressed as mean + SD. Comparisons between groups were performed using the Mann–Whitney U test. Categorical variables were compared with the χ2 test and t test. Wilcoxon's signed rank was calculated by the formula D5–D1 and D7–D1. This was used to calculate the difference between levels of PCT, CRP, and SOFA score in D5–D1 and D7–D1, and the variations of these values were categorized as increasing or decreasing. The significance of these variations by P value (P < 0.05 is considered significant).


  Results Top


Group A had omega-3 in their enteral diet with conventional sepsis treatment and group B had omega-3-free enteral diet with conventional sepsis treatment.

There was no statistically significant difference between group A and group B regarding demographic data and source of infection.

On day 1, the mean value of the WBCs, CRP, and PCT was nearly the same in both groups; there was a statistically significant reduction in group-A patients than in controls as regards the mean levels WBCs [Table 1], CRP, and PCT [Figure 1] at day 5 (P = 0.028, 0.012, and 0.046, respectively) and at day 7 (P = 0.014, 008, and 0.029, respectively).
Figure 1: Procalcitonin at day 1, day 5, and day 7.

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Table 1: White blood cells at day 1, day 5, and day 7

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As regards the length of stay in the ICU, we found that group A exhibited a significantly lower level of the mean value (10.40 ± 6.37 vs. 14.0 ± 6.51, P = 0.035) [Table 2].
Table 2: Length of stay in the ICU

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  Discussion Top


Sepsis is a worldwide problem that can cause devastating patient consequences and drive significant healthcare costs.

The present study examined the anti-inflammatory effect of omega-3 fatty acids as guided by measuring the level of WBCs, serum lactate, CRP, and PCT at the study days 1, 5, and 7, which reflects the effect of high-dose omega-3 fatty acids on drivers of sepsis (primary outcome).

The secondary outcome of omega-3 on reducing the degree of severe sepsis was done by comparing SOFA score, the need of the vasopressors, length of stay in the ICU, days free from mechanical ventilation, and mortality rate.

The mean level of WBCs, CRP, serum lactate, and PCT at day 1 was nearly the same in both group A and group B, which was elevated above the normal range, possibly due to sepsis. The mean level of WBCs, CRP, and PCT at days 5 and 7 was significantly reduced in group A.

Kalogeropoulos et al.[8] similarly found that total plasma omega-3 was inversely associated with CRP, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α). Hosny et al.[9] found that the use of short-term high-dose omega-3 fatty acids plus antioxidant therapy in patients with early sepsis is associated with a reduced mean level of CRP, IL-6, and PCT.

Gultekin et al.[10] studied the impact of omega-3-enriched TPN solution containing omega-9 on blood chemistry and inflammatory markers in septic patients. There was a significant decrease in LTB4 and CRP levels, while decreases in IL-6, TNF-α, and leukocyte levels were not significant.

Ibrahim[11] had investigated the effect of an omega-3-enriched diet on a group of septic critically ill patients. The patients who received omega-3 had lower sepsis indices such as CRP and leukocyte count.

Contrary to these data, Tayyebi-Khoshah et al.[12] had demonstrated that patients with end-stage renal disease undergoing dialysis, supplied with omega-3 (3 g/day for 2 months) had significantly decreased the serum levels of TNF-α.

In the current study, there were insignificant differences in reducing the degree of severe sepsis and days free from mechanical ventilation.

Pontes Arruda et al.[13] and Gultekin et al.[10] also proved that enteral nutrition with EPA/GLA and elevated antioxidants, when used in the early stages of sepsis in patients, can slow the progression of the disease to severe sepsis and septic shock. In Hosny's study, the use of the elevated antioxidants may be responsible for the difference in the findings.

There was no difference in days free from mechanical ventilation. In accordance with the study, Stapleton et al.[14] did a study to show the effect of enteral omega-3 on mechanically ventilated patients with acute lung injury. The authors found that omega-3 did not improve patients' outcomes.

Shirai et al.[15] also supported the study findings, Shirai studied the effect of an enteral diet enriched with omega-3 and antioxidants in patients with sepsis induced acute respiratory-distress syndrome and found that the duration of mechanical ventilation was not shortened, nor improved in the SOFA score or nosocomial infections.

Regarding the length of stay in the ICU, group A exhibited a significant reduction in the length of stay in the ICU.

Kyermanteng et al.[16] studied the cost analysis of omega-3 supplementation in critically ill patients with sepsis. Septic patients supplemented with omega-3 had both lower mean ICU costs and overall hospital costs and a significantly shorter length of stay in the ICU and hospital.

On the other hand, Tayyebi-Khoshah[12] had found that patients who received an omega-3-enriched diet had lower ICU SOFA scores with better organ functions than the patients who received omega-3-free diet. The number of patients requiring mechanical ventilation and the number of mechanical ventilation-free days were comparable in both groups.

Regarding mortality rate, there was a statistically nonsignificant reduction in 28-day mortality. In accordance with the study, a meta-analysis by Wang et al.[17] suggested otherwise. They explain the beneficial effects of omega-3 on sepsis. Presumably, critical illness may well disturb the intestinal environment, thereby upsetting the balance among intestinal flora and further leading to immunosuppression and other undesired consequences in patients with sepsis. In addition, Watson et al.[18] demonstrated that omega-3 supplementation could induce a reversible increase in the counts of bacteria that produce short-chain fatty acids, such as Bifidobacterium, Lactobacillus, and Roseburia. Thus, omega-3 might act as positive modulators in patients with sepsis by altering the gut microbiome and increasing the production of anti-inflammatory mediators, such as short-chain fatty acids.


  Conclusion Top


The use of short-term high-dose omega-3 in patients with early sepsis without the associated organ dysfunction seems to be safe and the associated positive effect on inflammatory cascade and length of ICU stay, meanwhile, it did not affect SOFA score, days free from mechanical ventilation, need for vasopressors, and even mortality rate.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Novosad SA, Sapiano MR, Grigg C, Lake J, Robyn M, Dumyati G, et al. Vital signs: epidemiology of sepsis: prevalence of health care factors and opportunities for prevention. Morb Mort Weekly Rep 2016; 65:864–869.  Back to cited text no. 1
    
2.
Fleischmann C, Scherag A, Adhikari NK. Assessment of global incidence and mortality of hospital treated sepsis. Am J Respir Crit Care Med 2016; 193:259–272.  Back to cited text no. 2
    
3.
Iwashyna TJ, Cooke CR, Wunsch H, Kahn JM. Population burden of long-term survivorship after severe sepsis in older Americans. J Am Geriatr Soc 2012; 60:1070–1077.  Back to cited text no. 3
    
4.
Mostel Z, Perl A, Marck M, Mehdi SF, Lowell B, Bathija S, et al. Post-sepsis syndrome – an evolving entity that afflicts survivors of sepsis. Mol Med 2020; 26:1–4.  Back to cited text no. 4
    
5.
Gleeson M. Immunological aspect of nutrition. Immunol Cell Biol 2016; 94:117–123.  Back to cited text no. 5
    
6.
Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature 2014; 510:92–101.  Back to cited text no. 6
    
7.
Calder PC. Functional roles of fatty acids and their effect on human health. J Parent Enteral Nutr 2015; 39:185–325.  Back to cited text no. 7
    
8.
Kalogeropoulos N, Panagiotakos DB, Chrysochou C, Pitsavos C. Unsaturated fatty acids are inversely associated and omega-3 and omega6 ratios are positively related to inflammation and coagulation markers in plasma of apparently health adults. Clin China Acta 2010; 411:584–591.  Back to cited text no. 8
    
9.
Hosny M, Nahas R, Ali S, Abd Elshafei S, Khaled H. Impact of oral omega-3 fatty acids supplementation in early sepsis on clinical outcome and immunomodulation. Egypt J Crit Care Med 2013; 1:119–126.  Back to cited text no. 9
    
10.
Gultekin G, Sahin H, Inanc N, Uyanik F, Ok E. Impact of omega-3 and omega-9 fatty acids enriched total parenteral nutrition on blood chemistry and inflammatory markers in septic patients. Pak J Med Sci 2014; 30:299–304.  Back to cited text no. 10
    
11.
Ibrahim ES. Enteral nutrition with omega3 fatty acids in critically bill patients: a randomized double blind study. Saudi J Anaesth 2018; 12:529–534.  Back to cited text no. 11
    
12.
Tayyebi-Khoshah H, Houshary J, Dehgan H, Alikhah H, Vatankhah AM, Safaeian AR, et al. Effect of treatment with omega 3 fatty acids on CRP and tumor necrosis factor in hemodialysis patients. Saudi J Kidney Dis Transpl 2012; 23:500–506.  Back to cited text no. 12
    
13.
Pontes Arruda A, Araga AM, Albuquerque JD. Effects of enteral feeding eicosapentaenoic acid, gamma –linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit Care Med 2006; 15:R144.  Back to cited text no. 13
    
14.
Stapleton RD, Martin TR, Weiss NS, Crowley JJ, Gundel SJ, Nathens AB, et al. A phase ii randomized placebo-controlled trials of omega-3 fatty acids for the treatment of acute lung injury. Crit Care Med 2011; 39:1655–1662.  Back to cited text no. 14
    
15.
Shirai K, Yoshida S, Matsumaru N. Effect of enteral diet enriched with eicosapentaenoic acids, gamma linolenic acid, and antioxidants in patients with sepsis induced respiratory distress syndrome. J Intensive Care 2015; 3:24.  Back to cited text no. 15
    
16.
Kyermanteng K, Shen J, Thavorn K. Cost effectiveness of omega-3 fatty acids and length of stay in the ICU and hospital. Clin Nutr ESPEN 2018; 25:63–67.  Back to cited text no. 16
    
17.
Wang C, Han D, Feng X. Omega-3 fatty acids supplementation is associated with favorable outcomes in patients with sepsis: an updated meta-analysis. J Int Med Res 2020; 48:0300060520953684.  Back to cited text no. 17
    
18.
Watson H, Mitra S, Croden FC. A randomized trial of the effect of omega-3 polyunsaturated fatty acid supplement on the human intestinal microbiota. Gut 2018; 67:1974.  Back to cited text no. 18
    


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    Tables

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