have we evolved the disclosures metabolic reserve to · 2012. 7. 19. · lbm complications...

Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?

7/19/2012

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Have We Evolved The Metabolic Reserve To Survive Critical Injury and Illness?

Paul Wischmeyer M.D.

Associate Chair, Clinical and Translational

Research

Director, Nutrition Therapy Service, UCH

Director, Translational Pharmacology and

PharmacoNutrition Laboratory

Professor of Anesthesiology

University of Colorado SOM

© 2012 Abbott Laboratories

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NIH FundingNIDDK- GLND TrialNIGMS- RO1GM078312 NHLBI- TOP-UP Trial

CIHR FundingREDOXS Trial, RE-ENERGIZE Trial

Dept. of Defense/ABA FundingRE-ENERGIZE Trial

Industry Financial Relationships:Occasional Consultant and Speaker:

Abbott, Baxter, Fresenius

DisclosuresDisclosures

2 2

Goals for LectureGoals for LectureUnderstand and describe the

hypermetabolic response to critical illness

Describe how hypermetabolic

3

Describe how hypermetabolic response effects substrate utilization

•How to utilize our understanding of the stress response to plan nutrition therapy (both EN and PN)

4

“Survival For A Lifetime”

5 5

Optimizing Metabolic

Response For Our P ti t ?

6

Patients?


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MetabolismMetabolismin Acute in Acute IllnessIllness

77

XXX

X

1. Increased resting energy expenditure

2. Stress hormones limit lipolysis; stimulate lean body mass catabolism

Pathophysiologic Changes in Hypermetabolic Stress

8

XX

3. Fuel produced via hepatic gluconeogenesis

Wolfe RR. Circ Shock 1981;8:105-115.

9

Energy Expenditure of Organs

Organ% of Resting Metabolic

Rate

Liver 29 (Lipid)

Brain 19 (Glucose)

10

Skeletal muscle 18 (Lipid)

Heart 10 (Lipid)

Kidney 7 (Glucose)

Remainder (ie. bone, fat)

17

Chp 9, Energy balance, body composition… In Insel P et al (eds), Nutrition, 4th ed, Jones and Bartlett Publishers, Boston, 2011, Pg 342

10

Lipid is Preferred Fuel for MOST

Organs!

11

Organs!

Chp 7, Metabolism. In Insel P et al (eds), Nutrition, Jones & Bartlett Publishing, Boston, 2011, pg 298

11

HypermetabolismHypermetabolism

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Most calories from fat (Insulin Resistant!)Most calories from fat (Insulin Resistant!)

Minimal carbohydrate needed for CNS, blood, Minimal carbohydrate needed for CNS, blood, wound, kidneywound, kidney

Metabolism In Critical IllnessMetabolism In Critical Illness

13Wiener M et al, Critical Care Clinics 1987; 3: 25Wiener M et al, Critical Care Clinics 1987; 3: 25

Limited capacity to oxidize Limited capacity to oxidize glucose!glucose!

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Carbohydrate/Lipid Oxidation in Sepsis

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In septic patients and patients post-injury:

Fat!(rather than carbohydrate) is main substrate

Stoner HB: The effect of sepsis on the oxidation of carbohydrate and fat. Br J Surg 1983; 70: 32

Body Challenged To Use Glucose in

Critical Illness!

15

XXX

X

1. Increased resting energy expenditure

2. Stress hormones limit lipolysis; stimulate lean body mass catabolism

Pathophysiologic Changes in Hypermetabolic Stress

16

XX

3. Fuel produced via hepatic gluconeogenesis

4. Lean body mass is not preserved

Wolfe RR. Circ Shock 1981;8:105-115.

Hypermetabolic Stress Is Associated withLoss of Lean Body Mass

28

24

20

16on

(g

/day

) Severe Burn

Injury

Acute Sepsis

17Long CL, et al. JPEN J Parenter Enteral Nutr 1979;3:452-456.

16

12

8

4

0Nit

rog

en E

xcre

ti

p

Infection

Elective Surgery

Days0 10 20 30 40

Critically Ill Patients Can Lose As Much As 1 kg of Lean Body Mass Daily!

18

Loss of lean body mass accelerates in critical illness

Demling RH. Eplasty 2009;9:e9.


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Metabolic Responses to Fasting and Hypermetabolic Stress

FastingHypermetabolic

Stress

Metabolic rate

19

Popp MB, Brennan MF. In: Fischer JF, ed. Surgical Nutrition.Boston, Little, Brown and Company, 1983:423-478.

Body fuels Conserved Wasted

Body protein Conserved Wasted

Urinary nitrogen

How do we Explain Hypermetabolism in How do we Explain Hypermetabolism in History of Mankind ??History of Mankind ??

20

21

How Do We Explain Nutrients Role in Illness and Injury?

Nutrients levels and lean body mass Nutrients levels and lean body mass is lost rapidlyis lost rapidly

Predicts ICU mortalityPredicts ICU mortality

Sh t t t f it l tSh t t t f it l t

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•• Short term stores of vital stress Short term stores of vital stress substrates and nutrientssubstrates and nutrients

• ER and ICU are recent developments

23 23 24


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No ambulance coming...No ambulance coming...

Get well fastGet well fast or die......

How Do We Explain Nutrients Role in Illness and Injury?

25

Get well fast Get well fast or die......

•• Thus…stores/balance of Thus…stores/balance of stress nutrients not stress nutrients not necessarynecessary

Now ambulance does rescue Now ambulance does rescue you..you..

I ICU k li fI ICU k li f

How Do We Explain Nutrients How Do We Explain Nutrients Role in Illness and Injury?Role in Illness and Injury?

26

In ICU we keep you alive for In ICU we keep you alive for months..months..

Now when underfed, you Now when underfed, you accumulate caloric debt and accumulate caloric debt and lose LBMlose LBM

Is that a problem? Is that a problem? 26

Must provide adequate Must provide adequate protein and calories toprotein and calories to

How Do We Explain Nutrients Role in Illness?

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protein and calories to protein and calories to prevent loss of lean prevent loss of lean

body mass!body mass!

27

Loss of Lean Body Mass is Devastating

% Loss of Total LBM Complications

Associated Mortality (%)

10 Decreased immunity, increased infections

10

20 Decreased healing 30

28

20 Decreased healing, weakness, infection 30

30 Too weak to sit, pressure ulcers, pneumonia, no

healing

50

40 Death, usually from pneumonia 100

1970s - 1990s

Adjunctive care

2000 - today

Proactive therapeutic strategy

Evolution of Nutrition Therapy in Critical Care

Nutrition Support Nutrition Therapy

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• Preserve lean body mass

• Maintain immune function

• Avert metabolic complications

• Reduce disease severity

• Diminish complications

• Decrease intensive care unit length of stay

• Improve patient outcomes

McClave SA, et al. JPEN J Parenter Enteral Nutr 2009; 33:277-316.

Who Are Candidates for Nutrition Therapy?

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Prevalence of Malnutrition in Hospitalized Adults

30 50%

Hospital Malnutrition

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30-50%Declines further with hospital stay

Green CJ. Clin Nutr 1999;18(s):3-28 31

Hospital Malnutrition

Weighted

32Clinical Nutrition 2008; 27: 5

Mean41.7%

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Is malnutrition Is malnutrition related torelated to

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related to related to outcome?outcome?

Cumulative MortalityCumulative Mortalityrt

ality

rtal

ity

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Months After HospitalizationMonths After HospitalizationAmerican Journal of Medicine (Cederholm T, Jägrén C, Hellström K. 1995;98:67-74). American Journal of Medicine (Cederholm T, Jägrén C, Hellström K. 1995;98:67-74).

% M

or%

Mor

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We Must Do Better!We Must Do Better!

35

But How??3636


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ICU Nutrition GuidelinesICU Nutrition GuidelinesEarly EN (started at 24–48 h)

NG tube, EN feeding

EN before PN

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Tolerate GRV 350-500

Promotility drugs if EN not tolerated

Small bowel feeding if NG feeding not tolerated

www.criticalcarenutrition.com 37

Right?...

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So.. everyone is So.. everyone is getting early and getting early and

successful enteral successful enteral feeding …feeding …

Right??Right??

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Right??Right??

NO !NO !

New York Hospital Association Survey

43%

40

of patients were

NPO on survey day

International Critical Care Nutrition Survey

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Deliver ~50% of prescribed Kcals/day

f ICU t !

We All Underfeed!

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for ICU stay!

Takes > 60 h to start feeding in ICU!

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Why Do We Why Do We Underfeed?Underfeed?

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Where Do Most Where Do Most Physicians Get Physicians Get

All Their All Their

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Nutrition Nutrition Education?Education?

45 4646

Critically Ill Patients Can Lose As Much As 1 kg of Lean Body Mass Daily!

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Loss of lean body mass accelerates in critical illness

Demling RH. Eplasty 2009;9:e9.

But...Pts who leave “my ICU” get better

and live healthy lives...

48

RIGHT?!?!


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What is the outcome of our ICU patients...

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After they Leave the ICU?

Continued Effect of Sepsis on Survival

50Quartin et al. JAMA 1997; 277:1058-1063

Survival after severe sepsis

51Weycker, et al. CCM 2003

> 40%of Mortality at 6/12

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Month Follow-up Occurs

Post-ICU Discharge

Shiell AM, Griffiths RD et al Clinical Intensive Care 1990;1 (6): 256-262

Surviving patients recover pre-

illness function

53

eventually....Right??

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3 mon

6 mon

6 Minute Walking Distance (Median) Predicted Value

Exercise Ability Following ICU DischargeExercise Ability Following ICU Discharge

49% Predicted!

64% Predicted!

55

0 200 400 600 800

6 mon

12 mon 66% Predicted!

Meters Walked in 6 MinutesMeters Walked in 6 Minutes 55

Physical Role Score (SF-36) Following ICU Discharge

Physical Role Score (SF-36) Following ICU Discharge

60

80

100

Physical Role Score (Med) Normal Value

56

0 0 250

20

40

60

3 months 6 months 12 months

56

But... this must improve after 12

months

57

months....Right??

NO!Exercise Limitation

and Reduced Physical Fxn

58

PERSISTS

5-YEARS

post-ICU

Why ?Why ?

59

Weight change from pre-ICU status

60Herridge et al. NEJM 2003;348:683-693

Not Lean Mass Gain!.. Mostly Fat!


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Loss of Lean Body Mass is Devastating

% Loss of Total LBM Complications

Associated Mortality (%)

10 Decreased immunity, increased infections

10

61

20 Decreased healing, weakness, infection 30

30 Too weak to sit, pressure ulcers, pneumonia, no

healing

50

40 Death, usually from pneumonia 100

6262

How Do We Assess Nutritional Status in the ICU?

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Nutritional AssessmentNutritional AssessmentBiochemical analysisBiochemical analysis

There is NO gold standard marker!

64

standard marker!

All Serum Markers (Albumin, Pre-Albumin, Transferrin)

have poor reliability64

Levels are decreased in critically ill patients

Visceral Proteins Indicate Metabolic Status Rather Than Nutritional Status

Alb i

Acute phase proteins

( C ti

65

Transcapillary protein lossesHepatic synthesis reprioritized

AlbuminPrealbuminTransferrin

(eg, C-reactive protein)

Jensen GL. JPEN J Parenter Enteral Nutr 2006;30:453-463.


If CRP < 5 the Pre-Albumin is better marker

66

better marker

If CRP > 5 patient will not be anabolic and Pre-ALB is pretty

useless!

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If CRP > 5 we have to

67

If CRP > 5 we have to figure out why...

And fix it!!!

What Happens When Adequate Nutrition Is Not

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Given?

What About PN?

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Patients need different goals…Patients need different goals…

How do we decide?How do we decide?

Caloric Intake in Critical IllnessCaloric Intake in Critical Illness

70

BMI??BMI??

70

International Critical Care Nutrition Survey

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HypothesisHypothesis

Relationship of energy/protein to Relationship of energy/protein to clinical outcome clinical outcome (mortality!)(mortality!)

Relationship influenced by Relationship influenced by

72

nutritional risknutritional risk

BMI defines chronic nutritional riskBMI defines chronic nutritional risk

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40 0000

50.0000

60.0000

70.0000

All Patients < 20 20-25 25-30 30-35 35-40 > 40

Relationship of Caloric Intake, 60 day Mortality and BMI

0.0000

10.0000

20.0000

30.0000

40.0000

0 500 1000 1500 2000

Alberda,C, Heyland D et alIntensive Care Med.35:1728-37. 2009 74

Extra-Protein Reduces Mortality as well..

74

Every additional 30 grams/d protein given...

Mortality decreased!

Effect of Increasing Protein on Infection

Multicenter observational study- 207 pts >72 h in ICU

75

For increase of 30 g/d:OR of infection at 28 dHeyland Clinical Nutrition 2011

(REDOXS Study)First 364 pts w/ SF-36 Score at 3 m and/or 6 m

Model *Estimate (CI) P values

(B) Increased protein intake

PHYSICAL FUNCTIONING (PF) at 3 months 2.9 (-0.7, 6.6) P=0.11

Increased Protein Intake Improves Physical Function Post-ICU

76

for increase of 30 gram/day, OR of infection at 28 days

Heyland Unpublished Data

S C UNC ON NG ( ) at 3 o t s .9 ( 0.7, 6.6) 0.

ROLE PHYSICAL (RP) at 3 months 4.4 (0.7, 8.1) P=0.02

STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 3 months

1.9 (0.5, 3.2) P=0.007

PHYSICAL FUNCTIONING (PF) at 6 months 0.2 (-3.9, 4.3) P=0.92

ROLE PHYSICAL (RP) at 6 months 1.7 (-2.5, 5.9) P=0.43

STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 6 months

0.7 (-0.9, 2.2) P=0.39

Has this already been shown in a

multi-center RCT?

77 7878


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0

7979 8080

Why?Why?

81 8282

Did 5 x protein Did 5 x protein save lives?save lives?

83

EDEN Trial Increased Energy Delivery Improves Discharge Home vs. Rehab Center

*

84

Full-Energy

* - p < 0.04 vs Trophic Feeding Rice et al. Crit Care Med 39, 201184


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Optimal Protein and Energy Nutrition Decreases Mortality in Mechanically Ventilated, Critically Ill Patients: A Prospective

Observation Cohort StudyWeijs PJM et al. JPEN, 2012;36(1):60-68

886 MV ICU pts predicted to need artificial nutrition for > 7-10 days

Calories via metabolic cart: min. protein goal- 1.2 gr/kg/d

• Energy/Protein Intake Recorded for MV Period

85

Groups:

- No Target reached:

Neither protein or energy targets achieved during MV period- 412 pts

- Protein + Energy Target reached - 245 pts

- Energy Target reached- 205 pts

No differences in:

Apache, Age, Diagnosis Type by Group 85

Results: Protein Delivery Mean

Optimal Protein and Energy Nutrition Decreases Mortality in Mechanically Ventilated, Critically Ill Patients: A Prospective

Observation Cohort StudyWeijs PJM et al. JPEN, 2012;36(1):60-68

- No Target Achieved: 0.83 g/kg/d

- Energy Target Only: 1.06 g/kg/d

- Protein/Energy Target: 1.31 g/kg/d

86

Achieving Protein/Energy Goals Reduces Risk of Death in High Mortality Risk ICU Patients

PET- Reached Protein/Energy TargetsET- Reached Energy Targets Only

UnadjustedAdjusted for sex, age, BMI, diag.,

hyperglycemic index, and APACHE II

Adjusted for PN Use and Time to Goal Nutrition

87Weijs PJM et al. JPEN, 2012;36(1):60-68

When EN is When EN is not Enough...not Enough...

…Should I Start …Should I Start PN??PN??

88

PN??PN??

88

If EN not feasible in first 7 d in ICU no specialized nutrition therapy should be initiated (C)

SCCM / ASPEN Guidelines 2009SCCM / ASPEN Guidelines 2009PN Guidelines PN Guidelines

89

Patients previously healthy 7 d (E)

Patients with evidence of malnutrition start ASAP (C)

89

ESPEN Guidelines 2009ESPEN Guidelines 2009PN Guidelines PN Guidelines

ALL PATIENTS not expected to be on normal nutrition within 3 d should receive PN w/in 24 to 48 h if no EN contraindicated or not

90

if no EN contraindicated or not tolerated (C)

• ALL PATIENTS receiving less than target EN after 2 d should be considered for supplementary PN. (C)


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They Sound Different

91

Different...

But..

Both advocate Early PN

for

92

for malnourished

patients..

Aren’t There Aren’t There Some New Trials Some New Trials

in PN?in PN?

93

Comparison of Recent and Comparison of Recent and Planned SPN TrialsPlanned SPN Trials

94

Study-1.1-1.2 g/kg/d

What Else Can We Learn From The Differences in These Trials?

95

These Trials?

96

Study-1.1-1.2 g/kg/d


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Keys Factors to Make PN

97

Decisions!

98

99Mortality Risk 99 100

Protein Delivery(1.2-2.0 g/kg/day)

101101

When to consider PNWhen to consider PNPN only after EN and motility agent

Must Deliver 1.2-2.0 g/kg/d Protein

In High Mortality Risk Patients!

102

ote

Well nourished (BMI 25-35)

After no EN for 7

Malnourished (BMI <25, >35)

If EN not at goal in 48-72 h


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In Summary...In Summary...

103

Key ConceptsKey ConceptsFuel use is effected by

hypermetabolic stress

All critically ill pts are candidates for nutrition therapy (with EN and/or PN)

104

Key to provide adequate protein delivery to optimize LBM preservation

Nutrition delivery may be vital to optimizing long term ICU outcome

Have We Evolved The Metabolic Reserve To Survive Critical Injury and Illness?

105

Not Without Help From You!

106

We Can Help Our Patients Evolved

Survival

107

Survival Mechanisms Via

Nutrition!

Just Do It...

108 108


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Alberda C, Gramlich L, Jones N, Jeejeebhoy K, Day AG, Dhaliwal R, Heyland DK. The relationship between nutritional intake and clinical outcomes in critically ill patients: results of an international multicenter observational study. Intensive Care Med. 2009; 35(10):1728-37.

Cederholm T, Jägrén C, Hellström K. Outcome of protein-energy malnutrition in elderly medical patients. Am J Med. 1995;98(1):67-74.

Demling RH. Nutrition, anabolism, and the wound healing process: an overview. Eplasty. 2009;9:e9.

Green CJ. Existence causes and consequences of disease related malnutrition in the hospital and the community, and the clinical and financial benefits of nutritional intervention. Clin Nutr 1999;19(Suppl 2):3S-38S.

Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS; Canadian Critical Care Trials Group. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003;348(8):683-93.

References

109

Heyland DK, Stephens KE, Day AG, McClave SA. The success of enteral nutrition and ICU-acquired infections: a multicenter observational study. Clin Nutr. 2011;30(2):148-55.

Jensen GL. Inflammation as the key interface of the medical and nutrition universes: a provocative examination of the future of clinical nutrition and medicine. JPEN J Parenter Enteral Nutr. 2006;30(5):453-63.

Long CL, Schaffel N, Geiger JW, Schiller WR, Blakemore WS. Metabolic response to injury and illness: estimation of energy andprotein needs from indirect calorimetry and nitrogen balance. JPEN J Parenter Enteral Nutr. 1979;3(6):452-6.

McClave SA, Martindale RG, Vanek VW, McCarthy M, Roberts P, Taylor B, Ochoa JB, Napolitano L, Cresci G; A.S.P.E.N. Board of Directors; American College of Critical Care Medicine; Society of Critical Care Medicine. Guidelines for the Provision andAssessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2009;33(3):277-316.

109

Norman K, Pichard C, Lochs H, Pirlich M. Prognostic impact of disease-related malnutrition. Clin Nutr. 2008;27(1):5-15.

Quartin AA, Schein RM, Kett DH, Peduzzi PN. Magnitude and duration of the effect of sepsis on survival. Department of Veterans Affairs Systemic Sepsis Cooperative Studies Group. JAMA. 1997;277(13):1058-63.

Rice TW, Mogan S, Hays MA, Bernard GR, Jensen GL, Wheeler AP. Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med. 2011;39(5):967-74.

Shiell AM, Griffiths RD, Short AI, Spiby J. An evaluation of the costs and outcome of adult intensive care in two units in the UK. Clin Intensive Care. 1990;1(6):256-62.

Stoner HB, Little RA, Frayn KN, Elebute AE, Tresadern J, Gross E. The effect of sepsis on the oxidation of carbohydrate and fat.Br J Surg. 1983;70(1):32-5.

Weijs PJ, Stapel SN, de Groot SD, Driessen RH, de Jong E, Girbes AR, Strack van Schijndel RJ, Beishuizen A. Optimal protein and energy nutrition decreases mortality in mechanically ventilated, critically ill patients: a prospective observational cohort

References

110

study.JPEN J Parenter Enteral Nutr. 2012;36(1):60-8.

Weycker D, Akhras KS, Edelsberg J, Angus DC, Oster G. Long-term mortality and medical care charges in patients with severe sepsis. Crit Care Med. 2003;31(9):2316-23.

Wiener M, Rothkopf MM, Rothkopf G, Askanazi J. Fat metabolism in injury and stress. Crit Care Clin. 1987;3(1):25-56.

Wolfe RR. Review: acute versus chronic response to burn injury. Circ Shock. 1981;8(1):105-15.

have we evolved the disclosures metabolic reserve to · 2012. 7. 19. · lbm complications...

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