ESPEN Congress Madrid 2018

Lipid Emulsions In Parenteral Nutrition

Lipid Emulsions And Outcome In Critical Care PatientsK. Demirag (TR)

Lipid emulsions and outcome

in

critical care patients

Dr. Kubilay DEMIRAĞ

Ege University Hospital

Dept of Anesthesiology and Intensive Care

Izmir, TURKEY

kubilay.demirag@ege.edu.tr

Conflict of interest

• None

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

Lipids

Importantsource of ENERGY

Supplyessential fatty

acids

(n-3, n-6)

Carriers of VitA,D,E,K

Take part in structure of cell

membranes

Essential fatty acids

Essential f.a.

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

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

Lipid requirements

• Min 10 % …..to meet the daily essential f.a.

and to ensure an adequate absorption of

fat-soluble vitamins

• < 65-70 %…..not to prevent min CH intake

• 30%, which should maintain a respiratory

quotient in the range of 0.85-0.90

Lipid requirements

• Daily lipid requirement = 1 g/kg/day

(0.7-1.5 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

Complications

• PN - associated liver disease

• Hypertriglyceridemia

• Essential fatty acid deficiency

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

Phytosterols

Complications

• PN - associated liver disease

• Hypertriglyceridemia

• Essential fatty acid deficiency

TG hydrolysis and fat oxidation is

decreased in ICU patients

TG hydrolysis and fat oxidation by LP lipase

Endotoxin / TNF-α

-Decreased O2 delivery

-

Hypertriglyceridemia

Excess amount of lipids

Fast infusion rate

• ≥4 days of PN

• n = 187 (112 LCT/MCT; 75 LCT)

• 41 % presented H.TG’emia

Complications

• PN - associated liver disease

• Hypertriglyceridemia

• 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

Essential fatty acid deficiency

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

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)

Why different lipid emulsions have

different effects in ICU?

Calder PC, et al., Clin Nutr 2018;37:1

Lipid emulsions have different fattyacid composition

Pro-inflamatory

EPA + DHA

Omega – 3 f.a.

AA

Omega – 6 f.a.

Cyclo

ox

yg

en

ase

Lip

oo

xyg

en

ase

Prostanoids

3-series

PGE3, PGI3, TXA3

Leukotrienes

5-series

LTB5, LTC5, LTD5

Prostanoids

2-series

PGE2, PGI2, TXA2

Leukotrienes

4-series

LTB4, LTC4, LTD4

Protectins / Maresins

Pro-inflamatory

Resolvins

D and E series

Lipoxins

Resolution of inflammation

Less pro-inflamatory

The fatty acid composition of lipid

emulsions is

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

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

Olive oil based lipid emulsions

• Neutral in terms of inflammationKalish BT. J Parenter Enteral Nutr. 2012;36:380-388

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 variablesPuiggros C, et al. J Parenter Enteral Nutr 2009;33:501

Demirer S, et al. Ann Surg Treat Res 2016;91:309

Soybean oil vs Olive oil

• 100 ICU patients (medical / surgical = 11 / 89)

• APACHE II = 15

• Days on PN = 13 days

Umpierrez GE, et al. CCM 2012;40:1792

No difference in;

• Infectious and non-

infectious

complications

• Incidence of ARF

• Mortality

• Effects on inflammatory markers

• Effects on clinical parameters

Fish oil containing lipid emulsions

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, leukocyteoxidative burst, increase neutrophil CD-32 expression (n=32, gastrointestinal ca, preoperative 3 days)

De Miranda Torrinhas RSM, et al. Clin Nutr 2013;32:503

• 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 10

1. Jiang ZM. Br J Surg 2010;97:804.

2. Weiss G. Br J Nutr 2002;87:89

3. Zhu M. Chin Med J 2012;125:178

4. Klek S. Acta Chir Belg 2005;105:175

5. Badía-Tahull MB. Br J Nutr 2010;104:737

6. Wichmann MW. Crit Care Med 2007;35:700

7. Grimm H. Eur J Nutr 2006;45:55

8. Zhu XH. World J Gastroenterol 2012;18:6141

9. Heidt MC. Thorac Cardiovasc Surg 2009;57:276

10. Tsekos E. Clin Nutr 2004;23:325

Fish oil / surgical / clinical outcome

7 RCT’s; n=627 5 RCT’s; n=387

Favors FO Favors FO

Fish oil enriched lipid emulsions were

associated with a significant reduction in

hospital and ICU length of stay

Fish oil enriched parenteral nutrition in

postoperative patients undergoing major

abdominal surgery: Metaanalysis

Hospital LOS ICU-LOS

Chen B, et al. JPEN 2010;34:387

7 RCT’s; n=539

Favors FO Favors control

Fish oil enriched lipid emulsions

were associated with a significant

reduction in postoperative infection

rate

Postoperative

infections

Chen B, et al. JPEN 2010;34:387

Fish oil enriched parenteral nutrition in

postoperative patients undergoing major

abdominal surgery: Metaanalysis

Favors n-3 Favors control

ICU

Surgical

13 ICU, n=762; 10 surgical; n=740

n-3 enriched lipid emulsions were

associated with a significant reduction

in infections in surgical patients

n-3 fatty acid enriched parenteral nutrition in elective

surgical and ICU patients: Metaanalysis

Pradelli L, et al. Critical Care 2012;16:184

Infection rate

Favors

n-3

Favors

control

ICU

Surgical

Favors

n-3

Favors

control

n-3 enriched lipid emulsions were

associated with a significant reduction

in hospital and ICU length of stay

8 RCT’s; n=615

n-3 fatty acid enriched parenteral nutrition in elective

surgical and ICU patients: Metaanalysis

Pradelli L, et al. Critical Care 2012;16:184

Hospital LOS ICU-LOS

ESPEN Guidelines / Surgery

• If PN is required post-operatively in the

ICU, 2nd or 3rd 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

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;42:1168

2. Wang X. J Parenter Enteral Nutr 2008;32:236

3. Hall TC. J Parenter Enteral Nutr 2015;39:301

4. Barbosa VM. Crit Care 2010;14:R5

5. Barros KV. Clin Nutr 2013;32:599

6. Zhu XH. World J Gastroenterol 2012;18:6141

Grau-Carmona T, et al. Crit Care Med 2015; 43:31–39

• 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

n-3 fatty acid enriched lipid emulsions in

critically ill patients: ICU Lipids Study

16% decrease

• n = 391

• 8 RCT’s

• Mixed ICU

patients

• FO vs SO or

SO+MCT

• 0,1-0,2 g FO/kg

Palmer AJ, et al. Crit Care Med 2013; 41:307–316

Favors n-3

Favors n-3

New infections

Mortality

n-3 fatty acid supplemented parenteral

nutrition in adult ICU: Metaanalysis

No difference in terms

of mortality and

infections

Favors n-3

Favors n-3

• n = 391

• 8 RCT’s

• Mixed ICU

patients

• FO vs SO or

SO+MCT

• 0,1-0,2 g FO/kg

Reduction in hospital

LOS by 10 days

Palmer AJ, et al. Crit Care Med 2013; 41:307–316

Hospital LOS

ICU-LOS

n-3 fatty acid supplemented parenteral

nutrition in adult ICU: Metaanalysis

• n = 733

• 10 RCT’s

Significant

reduction in

infections

Intravenous fish oil lipid emulsions

in critically ill: Metaanalysis

Manzanares W, et al. Critical Care 2015;19:167

Infections

Favors fish

oil

Favors

LCT or

LCT/MCT

No difference in

mortality and days on

mechanical ventilation

Intravenous fish oil lipid emulsions

in critically ill: Metaanalysis

Mortality

Manzanares W, et al. Critical Care 2015;19:167

Days on MV

Favors fish

oilFavors non-

fish oil

Favors fish

oilFavors non-

fish oil

No difference in hospital

and ICU length of stay

Manzanares W, et al. Critical Care 2015;19:167

Intravenous fish oil lipid emulsions

in critically ill: Metaanalysis

Hospital LOS ICU-LOS

Favors fish

oilFavors non-

fish oil

Favors fish

oil

Favors

non-fish oil

Which alternative lipid emulsion to use?

Days from Admission to ICU

0.0 10.0 20.0 30.0 40.0 50.0 60.0

0

1

2

3

4

5

Cu

mu

lative

Lik

elih

oo

d o

f B

ein

g

Dis

ch

arg

ed

fro

m IC

U

Edmunds CE, et al. Crit Care Med. 2014;42:1168

Lipid free (n=70)

Soybean oil (n=223)

MCT (n=65)

Olive oil (n=74)

Fish oil (n=19)

Total (n=451)

• n = 451

• >72 h ICU stay

• MV support

• PN ≥ 5 days

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.

2013 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.

2015 Recommendation

No change

25 RCT’s (9 EN, 16 PN)

n=2417

No difference in

mortality in sepsis

No difference in

mortality in sepsis

induced ARDS

Effect of n-3 fatty acids on mortality

in sepsis and sepsis induced ARDS:

Metaanalysis

Chen HS, et al. Nutrition Journal 2018;17:57

• 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.

• 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.

• 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

Timing and dosage are important

Calder PC, et al. Lipids in the intensive care unit:

Recommendations from the ESPEN

Expert Group. Clin Nutr 2018;37:1

Clin Nutr 2018;37:1075

Summary

• Lipids are integral components of parenteralnutrition 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

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 Nutrition2017;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;37:1075-1081

• Anez-Bustillos L, et al. Redefining essential fatty acids in the era of novel intravenous lipid emulsions. Clin Nutr. 2018;37:784–789

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