ESPEN Congress Madrid 2018

Transcription

1 ESPEN Congress Madrid 2018 Lipid Emulsions In Parenteral Nutrition Lipid Emulsions And Outcome In Critical Care Patients K. Demirag (TR)

2 Lipid emulsions and outcome in critical care patients Dr. Kubilay DEMIRAĞ Ege University Hospital Dept of Anesthesiology and Intensive Care Izmir, TURKEY

3 None Conflict of interest

4 Outline Importance of lipids in PN Lipid requirements in ICU Indications, contra-indications and monitoring of lipid provision The effects of different type of lipids in different clinical situations

5 Important source of ENERGY Take part in structure of cell membranes Lipids Supply essential fatty acids (n-3, n-6) Carriers of Vit A,D,E,K

6 Essential fatty acids Essential f.a.

7 Mundi MS, et al. Nutrition in Clinical Practice 2016; 31: 629

8 Lipids in PN acting as precursors of bioactive lipid metabolites such as prostaglandins regulating cell responses including gene expression precursors for the synthesis of modulators of immune function

9 Lipid requirements Min 10 %..to meet the daily essential f.a. and to ensure an adequate absorption of fat-soluble vitamins < %..not to prevent min CH intake 30%, which should maintain a respiratory quotient in the range of

10 Lipid requirements Daily lipid requirement = 1 g/kg/day ( g/kg/day) ESPEN recommends (for ICU patients); 9 12 g/day of linoleic acid (n-6) 1 3 g/day of α-linolenic acid (n-3) ESPEN Guidelines on Parenteral Nutrition: Intensive care, 2009

11 Complications PN - associated liver disease Hypertriglyceridemia Essential fatty acid deficiency

12 Phytosterols Raman M, et al. Nutrients 2017;9:388

13 Complications PN - associated liver disease Hypertriglyceridemia Essential fatty acid deficiency

14 TG hydrolysis and fat oxidation is decreased in ICU patients Endotoxin / TNF-α - TG hydrolysis and fat oxidation by LP lipase Decreased O 2 delivery - Excess amount of lipids Fast infusion rate Hypertriglyceridemia

15 4 days of PN n = 187 (112 LCT/MCT; 75 LCT) 41 % presented H.TG emia

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17 Complications PN - associated liver disease Hypertriglyceridemia Essential fatty acid deficiency

18 Essential fatty acid deficiency 10 % linoleic acid in adipose tissue Might be important in underweight and malnourished patients Minimal parenteral requirements of linoleic acid (n-6) to prevent deficiency = at least 1% of calories (optimal levels being 3% 4%) Linolenic acid (n-3) requirements = 0.2% 0.5% of total calories

19 Monitoring Cutaneous rash, chills, fever (allergy to lipid emulsions) During early phase (3-5 days) daily monitoring of biochemical parameters (including liver enzymes, GGT, alkaline phosphatase, bilirubin, TG) Then 2-3 x /week Liver U/S when necessary

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21 Contraindications Hypersensitivity to lipid emulsion components Severe disorders of lipid metabolism Hypertriglyceridemia associated acute pancreatitis Olive oil-based IVLE s in patients requiring anticoagulation therapy (limited amount of vit K)

22 Why different lipid emulsions have different effects in ICU?

23 Lipid emulsions have different fatty acid composition Calder PC, et al., Clin Nutr 2018;37:1

24 Lipooxygenase Cyclooxygenase Resolvins D and E series Less pro-inflamatory Resolution of inflammation Protectins / Maresins Leukotrienes 5-series LTB5, LTC5, LTD5 EPA + DHA Omega 3 f.a. Prostanoids 3-series PGE3, PGI3, TXA3 Leukotrienes 4-series LTB4, LTC4, LTD4 AA Omega 6 f.a. Prostanoids 2-series PGE2, PGI2, TXA2 Pro-inflamatory Lipoxins Pro-inflamatory

25 The fatty acid composition of lipid emulsions is

26 Soybean oil based lipid emulsions Promotion of inflammation Suppression of immune function Tendency for peroxidation Exacerbation of inflammation after major surgery Immunosuppression in polytrauma patients Hyperbilirubinemia / PN associated liver disease Calder PC, et al., Clin Nutr 2018;37:1

27 SCCM/ASPEN Guidelines SO-based LEs should be withhold during the first week following initiation of PN in the critically ill patient or limiting this to a maximum of 100 g/wk (often divided into 2 doses/wk) if there is concern about essential fatty acid deficiency McClave SA. SCCM/ASPEN Guidelines. JPEN 2016;40:159

28 Olive oil based lipid emulsions Neutral in terms of inflammation Kalish BT. J Parenter Enteral Nutr. 2012;36: Singer P, et al. Clin Nutr 2009;28:387 In surgical patients; Better fatty acid status Increased blood vit E concentration Decreased lipid peroxidation Decreased inflammatory variables Puiggros C, et al. J Parenter Enteral Nutr 2009;33:501 Demirer S, et al. Ann Surg Treat Res 2016;91:309

29 Soybean oil vs Olive oil 100 ICU patients (medical / surgical = 11 / 89) APACHE II = 15 Days on PN = 13 days No difference in; Infectious and noninfectious complications Incidence of ARF Mortality Umpierrez GE, et al. CCM 2012;40:1792

30 Fish oil containing lipid emulsions Effects on inflammatory markers Effects on clinical parameters

31 Fish oil / surgical / inflammation Decrease in IL-6 (n=14, cardiac surgery, perioperative 3x infusion) Berger M, et al. Am J Clin Nutr 2013;97:246 Decrease in IL-6 and TNF-α (n=12, perioperative, 5 days) Weiss G, et al. Br J Nutr 2002;87:89 Decrease in IL-6 and IL-10, leukocyte oxidative burst, increase neutrophil CD-32 expression (n=32, gastrointestinal ca, preoperative 3 days) De Miranda Torrinhas RSM, et al. Clin Nutr 2013;32:503

32 Fish oil / surgical / clinical outcome Decrease in infectious complications 1,3,4,5 Decrease in hospital LOS 1,2,3,4,6,7,8,10 Decrease in ICU-LOS 9 Improved mortality Jiang ZM. Br J Surg 2010;97: Weiss G. Br J Nutr 2002;87:89 3. Zhu M. Chin Med J 2012;125: Klek S. Acta Chir Belg 2005;105: Badía-Tahull MB. Br J Nutr 2010;104: Wichmann MW. Crit Care Med 2007;35: Grimm H. Eur J Nutr 2006;45:55 8. Zhu XH. World J Gastroenterol 2012;18: Heidt MC. Thorac Cardiovasc Surg 2009;57: Tsekos E. Clin Nutr 2004;23:325

33 Fish oil enriched parenteral nutrition in postoperative patients undergoing major abdominal surgery: Metaanalysis 7 RCT s; n=627 5 RCT s; n=387 Fish oil enriched lipid emulsions were associated with a significant reduction in hospital and ICU length of stay Favors FO Hospital LOS Favors FO ICU-LOS Chen B, et al. JPEN 2010;34:387

34 Fish oil enriched parenteral nutrition in postoperative patients undergoing major abdominal surgery: Metaanalysis 7 RCT s; n=539 Fish oil enriched lipid emulsions were associated with a significant reduction in postoperative infection rate Postoperative infections Favors FO Favors control Chen B, et al. JPEN 2010;34:387

35 n-3 fatty acid enriched parenteral nutrition in elective surgical and ICU patients: Metaanalysis 13 ICU, n=762; 10 surgical; n=740 ICU n-3 enriched lipid emulsions were associated with a significant reduction in infections in surgical patients Surgical Infection rate Favors n-3 Favors control Pradelli L, et al. Critical Care 2012;16:184

36 n-3 fatty acid enriched parenteral nutrition in elective surgical and ICU patients: Metaanalysis 8 RCT s; n=615 n-3 enriched lipid emulsions were associated with a significant reduction in hospital and ICU length of stay ICU Surgical Favors n-3 Favors control Favors n-3 Favors control Hospital LOS ICU-LOS Pradelli L, et al. Critical Care 2012;16:184

37 ESPEN Guidelines / Surgery If PN is required post-operatively in the ICU, 2 nd or 3 rd generation lipid emulsions may be administered, and in the case of surgical complications, FO-containing PN is recommended. Weimann A, et al. Clin Nutr 2017;36:623

38 Fish oil / mixed ICU Shorter duration of mechanical ventilation 1 Better oxygenation index 2,4 Increase in gas exchange 5 Fewer days of CRRT 2 Reduction in organ dysfunction in sepsis 3 Decrease in hospital LOS 4,6 Decrease in ICU-LOS 1 Improved mortality 3 1. Edmunds C. Crit Care Med 2014;42: Wang X. J Parenter Enteral Nutr 2008;32: Hall TC. J Parenter Enteral Nutr 2015;39: Barbosa VM. Crit Care 2010;14:R5 5. Barros KV. Clin Nutr 2013;32: Zhu XH. World J Gastroenterol 2012;18:6141

39 n-3 fatty acid enriched lipid emulsions in critically ill patients: ICU Lipids Study 16% decrease n = 159 Medical and surgical APACHE II = 13 PN 5 days 0,1 g FO/kg No difference in; Length of MV ICU / hospital LOS Mortality Grau-Carmona T, et al. Crit Care Med 2015; 43:31 39

40 n-3 fatty acid supplemented parenteral nutrition in adult ICU: Metaanalysis Mortality Favors n-3 Favors n-3 n = RCT s Mixed ICU patients FO vs SO or SO+MCT 0,1-0,2 g FO/kg No difference in terms of mortality and infections New infections Palmer AJ, et al. Crit Care Med 2013; 41:

41 n-3 fatty acid supplemented parenteral nutrition in adult ICU: Metaanalysis ICU-LOS Favors n-3 n = RCT s Mixed ICU patients FO vs SO or SO+MCT 0,1-0,2 g FO/kg Favors n-3 Reduction in hospital LOS by 10 days Hospital LOS Palmer AJ, et al. Crit Care Med 2013; 41:

42 Intravenous fish oil lipid emulsions in critically ill: Metaanalysis Infections Significant reduction in infections n = RCT s Favors fish oil Favors LCT or LCT/MCT Manzanares W, et al. Critical Care 2015;19:167

43 Intravenous fish oil lipid emulsions in critically ill: Metaanalysis Mortality Days on MV No difference in mortality and days on mechanical ventilation Favors fish oil Favors nonfish oil Favors fish oil Favors nonfish oil Manzanares W, et al. Critical Care 2015;19:167

44 Intravenous fish oil lipid emulsions in critically ill: Metaanalysis Hospital LOS ICU-LOS No difference in hospital and ICU length of stay Favors fish oil Favors nonfish oil Favors fish oil Favors non-fish oil Manzanares W, et al. Critical Care 2015;19:167

45 Cumulative Likelihood of Being Discharged from ICU Which alternative lipid emulsion to use? 5 4 n = 451 >72 h ICU stay MV support PN 5 days Fish oil (n=19) 3 Olive oil (n=74) Lipid free (n=70) 2 MCT (n=65) 1 Soybean oil (n=223) 0 Total (n=451) Days from Admission to ICU Edmunds CE, et al. Crit Care Med. 2014;42:1168

46 Canadian Guidelines 2009 Recommendation There are insufficient data to make a recommendation on the type of lipids to be used in critically ill patients receiving parenteral nutrition Recommendation IV lipids that reduce the load of omega-6 fatty acids/soybean oil emulsions should be considered. There are insufficient data on type of soybean reducing lipids Recommendation No change

47 Effect of n-3 fatty acids on mortality in sepsis and sepsis induced ARDS: Metaanalysis 25 RCT s (9 EN, 16 PN) n=2417 No difference in mortality in sepsis No difference in mortality in sepsis induced ARDS Chen HS, et al. Nutrition Journal 2018;17:57

48 Fish oil-enriched enteral and parenteral nutrition appears to be well tolerated and confers additional clinical benefits, particularly in surgical ICU patients, due to its anti-inflammatory and immune-modulating effects. Whilst the evidence base is not conclusive, there appears to be a potential for fish oil-enriched nutrition, particularly administered perioperatively, to reduce the rate of complications and ICU and hospital stay in surgical ICU patients.

49 The ESPEN Expert Group supports the use of olive oil and fish oil in nutrition support in surgical and non-surgical ICU patients but considers that further research is required to provide a more robust evidence base.

50 Timing and dosage are important Administration prior to commencement of inflammation is likely optimal The most favorable effects on survival, infection rates and length of hospital stay occurred when parenteral FO was administered between 0.1 and 0.2 g/kg/d Calder PC, et al. Lipids in the intensive care unit: Recommendations from the ESPEN Expert Group. Clin Nutr 2018;37:1

51 Clin Nutr 2018;37:1075

52 Summary Lipids are integral components of parenteral nutrition support Safe with appropriate dose and monitorization SO based LE s are detrimental in terms of inflammation FO based LE s are promising especially in surgical ICU population Timing and dosage of alternative LE supplementation according to state of inflammation might be important

53 Further reading Calder PC, et al. Lipids in the intensive care unit: Recommendations from the ESPEN Expert Group. Clinical Nutrition 2018;37:1-18 Boisrame-Helms J, et al. Lipid emulsions for parenteral nutrition in critical illness. Progress in Lipid Research 2015;60:1 16 Mundi MS, et al. Emergence of Mixed-Oil Fat Emulsions for Use in Parenteral Nutrition. Journal of Parenteral and Enteral Nutrition 2017;41:3S-13S Klek S. Omega-3 Fatty Acids in Modern Parenteral Nutrition: A Review of the Current Evidence. J. Clin. Med. 2016:5:34 Kreymann KG, et al. Intravenous fish oil in critically ill and surgical patients - Historical remarks and critical appraisal. Clin Nutr. 2018;37: Anez-Bustillos L, et al. Redefining essential fatty acids in the era of novel intravenous lipid emulsions. Clin Nutr. 2018;37:

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