Dr Ahmad Shaltut Othman Anaesthesiologist & Intensivist Hosp Sultanah Bahiyah Alor Setar

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1 FEEDING WITH FISH OIL Dr Ahmad Shaltut Othman Anaesthesiologist & Intensivist Hosp Sultanah Bahiyah Alor Setar

2 New horizons in clinical nutrition from Support to Therapy

3 Landmarks in Parenteral Nutrition Therapy

4 ω= methyl end Essential Fatty Acids

5 FO - rich sources of -3 fatty acids (FAs) - eicosapentaenoic acid (EPA; C20:5) - docosahexaenoic acid (DHA;C22:6) Omega-3 fatty acids (fish oils) metabolized to prostaglandins of 3 series and leukotrienes of the 5 series (anti-inflammatory properties).

6 HUMAN FATTY ACID PATHWAYS

7 n-3 lipids offer a possible counterbalance to the negative effects of n-6 fatty acids (minimize the synthesis of proinflammatory eicosanoids)

8 N-3 PUFA & Immunity

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10 Resolution of Acute Inflammation

11 n-6 lipids n-3 lipids Infusion of n-6 based LE may aggravate the hyperinflammatory response in SIRS Addition of FO - n-3 lipids, leads to a more balanced immune response avoiding hyperinflammation and subsequent immune paralysis

12 EPA and DHA in fish oil exert beneficial anti-inflammatory effects Effects of fish oil based ω-3 fatty acids on immune response Pro-inflammatory cytokines Effective response Anti-inflammatory cytokines SIRS... without ω-3 fatty acids (ω- 3 FA) from fish oil with ω-3 fatty acids (ω- 3 FA) from fish oil SIRS: Systemic Inflammatory Response Syndrome CARS: Compensatory Anti-inflammatory Response Syndrome TNFα IL-1 IL-6 IL-8 ω-3 FA IL-10 Postulated time course CARS TGF-β IL-13 ω-3 FA IL-4 Graph modified according to Mayer K et al Fish oil containing lipid emulsions may protect against excessive inflammatory response More balanced immune response Result in a faster resolution of inflammation and patient s recovery Mayer K et al. Curr Opin Clin Nutr Metab Care 2006, 9(2):

13 Fish Oil Main source is oily fish Typical intake around 0.25 g/day Parenteral administration better than enteral due to bioavailability Significant and rapid increase in EPA and DHA concentrations in plasma within hours after parenteral administration

14 RESEARCH

15 A randomized, controlled, clinical trial, N=25 50:50 mixture of MCT, LCT or 50:40:10 mixture of MCT, LCT and fish oil.

16 At Day 6the ratio PO2/FiO2 was significantly high in the fish oil group (P = 0.047) Barbosa et al. Critical Care 2010

17 Proportion of patients with po2/fio2 < 200 and < 300 at D6 were significantly lower in FO group The fish oil group received an average of 6.4 g/d of FO

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19 Conclusion Inclusion of fish oil in PN provided to septic ICU patients increases plasma EPA status associated with more marked changes in some cytokines in plasma, improved gas exchange trend towards reduced length of hospital stay

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21 Omega 3 fatty acids lowers magnitude of inflammatory response, modulate immune response. suppressive effect on TNF-ἀ and ACTH was significantly more pronounced in the two low-dose groups (0.2 g/kg) compared with the single or double 0.5-g/kg doses of the previous trial

22 6 RCTs (n=390 patients) evaluated FO containing emulsions, either parenteral nutrition (PN) or enteral nutrition (EN) fed patients Parenteral FO dose between 0.1 and 0.2 g/kg/d Conclusion - FO containing LE may be able to decrease mortality and ventilation days in the critically ill.

23 Effects of fish oil lipid emulsion strategies on mortality Fish oil containing lipid emulsions were associated with a trend towards a reduction in mortality (risk ratio [RR]= 0.71, 95 % confidence intervals [CI] , P= 0.08;

24 Effects of parenteral fish oil lipid emulsions on infections fish oil containing emulsion strategies had no effect in reducing infectious complications (RR= 0.76, 95% CI , P= 0.35, heterogeneity I2 = 0%)

25 Effects of parenteral fish oil lipid emulsions on ventilation days Fish oil containing emulsions showed a trend towards reduction in the duration of mechanical ventilation days (WMD 1.41, 95% CI 3.43, 0.61, P=0.17

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27 Fish Oil

28 4 databases, 21 RCTs N=21 FO-enriched lipid emulsions SO lipid emulsions MCT lipid emulsion

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30 Mortality Infectious complications

31 Total cost Length of hospital stay Conclusion FO is likely to reduced the LOH stay, occurrence of infectious events and may not increase overall medical costs, FO may be a safe and preferable choice for patient post-surgery.

32 Stanislaw Klek J. Clin. Med. 2016, 5, 34; doi: /jcm improve clinical outcomes in pediatric, surgical, cancer, and critically ill patients - proven safety and tolerability profile and cost-effective Critical Care Nutrition ASMIC 2016

33 23 studies (n = 1502 patients: n = 762 admitted to the ICU) RCT comparing n-3 PUFA-enriched LE with standard LE (i.e. soybean oil, MCT/LCT or olive/soybean oil emulsions) in surgical and ICU patients receiving PN. FO - no clear data from RCTs on optimum doses but must exceed 0.1 to 0.15 g/kg/d. Conclusion - n-3 PUFAs-enriched PN regimens are safe and effective in reducing the infection rate and hospital/icu stay in surgical and ICU patients.

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35 FO regimens are associated reduction in the infection rate FO regimens are associated reduction in ICU & Hospital LOS

36 The effects of different IV fat emulsions on clinical outcomes in critically ill patients. Edmunds CE1, Brody RA, Parrott JS, Stankorb SM, Heyland DK. Cumulative hazard curve of the likelihood of patients being discharged from ICU alive (p<0.001) 451 pts lipid-free group, soybean oil group, MCT group, olive oil group, fish oil group FO OO LF MCT SO Critical Care Medicine Dec

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39 Curr Opin Clin Nutr Metab Care 2014, 17:

40 Must be given as part of a complete nutrition formula or as a supplement to complete nutrition (protein & calorie) delivery When FO is disassociated from complete enteral nutrition delivery, the beneficial effects are no longer observed Curr Opin Clin Nutr Metab Care 2014, 17:

41 Critical Care Nutrition ASMIC 2016

42 Critical Care Nutrition ASMIC 2016

43 Critical Care Nutrition ASMIC 2016

44 Key Messages Lipid emulsions are not only a source for calories but clearly have an impact on immunologic properties FO as part of a complete nutrition formula or as a supplement to complete nutrition to show clinical benefit The parenteral route may be a more reliable strategy to provide FO than the enteral route due to better bioavailability Critical Care Nutrition ASMIC 2016

45 Key Messages A daily dose of 0.1 and 0.2 g/kg/d (? pharmacologic amount) would be able to produce balanced pro- /anti-inflammatory effects influencing physiological endpoints More research is needed to optimize the proper patient, dose, and timing of administration of FO containing emulsions in the critically ill population Critical Care Nutrition ASMIC 2016

46 THANK YOU FOR YOUR ATTENTION Critical Care Nutrition ASMIC 2016