Invited Review The Evolving Rationale for Early Enteral Nutrition Based on Paradigms of Multiple Organ Failure Frederick A. Moore, MD ; and Ernest E. Moore,

Invited Review

The Evolving Rationale for Early Enteral Nutrition Based on Paradigms of Multiple Organ Failure

Frederick A. Moore, MD ; and Ernest E. Moore, MDNCP 2009

Frederick A. Moore MD

November 9 , 2012

Evolving Paradigms in Surgical Nutrition

Invited Review

The Evolving Rationale for Early Enteral Nutrition Based on Paradigms of Multiple Organ Failure

Frederick A. Moore, MD ; and Ernest E. Moore, MDNCP 2009

Stress Metabolism & Stress Formula TPN

SIRS/CARS Paradigm & Immune Enhancing Diets

Emergence of PICS & Anabolic Nutrition

Evolving Paradigms in Surgical Nutrition

Denver General HospitalSurg Gyn Obstet 1977

INFECTION

A New Syndrome

ICU Technology Allows Patients

To Survive Single Organ Failure

Ben EisemanBen Eiseman

Chief of Surgery

Ben Eiseman

Denver General HospitalSurg Gyn Obstet 1977

Pick a Topic

INFECTION

Ben Eiseman

MULTIPLE ORGAN FAILURE

UNCONTROLLED SEPSIS

Ben Eiseman

E

John DalyUniversity of Texas - Houston

Ann Surg 1978

Septic AutocannibalismA Failure of Exogenous Nutritional Support

FRANK B. CERRA, M.D., JOHN H.SIEGEL, M.D., BILL COLEMAN, JOHN R. BORDER,M.D.,RAPIER R. McMENAMY,PhD.

Ann Surg 1980Septic AutocannibolismA Failure of Exogenous Nutritional Support

FRANK B. CERRA, M.D., JOHN H.SIEGEL, M.D., BILL COLEMAN, JOHN R. BORDER,M.D.,RAPIER R. McMENAMY,PhD.

Frank Cerra

Buffalo General Hospital

Ann Surg 1980

INJURY STRESS RESPONSEAutocannibolism

EpinephrineGlucagonCortisol +Cytokines (TNF, IL1, IL6)

Wes Alexander

University of Cincinnati

J.WESLEY ALEXANDER MD, BRUCE G. MACMILLAN MD, J. DWIGHT STINNETT PhD, CORA K. OGLE PhD,RICHARD C. BOZIAN MD, JOSEF E. FISHER MD, JANE B. OAKES RD, ROMAINE KRUMMEL BSN

Ann Surg 1980

Beneficial Effects of Aggressive Protein Feeding In Severely Burned Children

ACUTE PROTEIN MALNUTRITION

Muscle Mass

Visceral Protein

Organ Function

Immune Response

INFECTIONS

MULTIPLE ORGAN FAILURE

HYPOTHESIS

Aggressive Nutritional Support

High protein content

Branched chain amino acids

Lower Nonprotien Calorie / Gram of Nitrogen Ratio

Decrease from traditional 150/1 to 100/1

Increased Percentage of Fat

Do not stress glucose metabolism

Designed based on better understanding of stress metabolism

High protein content & special amino acids Lower nonprotein calorie / gram of nitrogen ratio to 100/1

Increased percentage of fat Goal : early positive caloric and nitrogen balance

STRESS TPN FORMULATIONS OF 1980sGREAT EXPECTATIONS

High branched chained amino acids

Perioperative TPN

Early enteral nutrition (EN) vs TPN

Early combined TPN and EN in ICU patientsnutrition

CLINICAL TRIALSTPN FAILED TO MEET EXPECTATIONS

Early PN is Harmful in ICU patients Herndon Study 1 ( 39 Burn patients, TBSA >50% )

Immune suppression with PN (Tcell ratios) (days 7-14) Supplemental PN mortality ( p<0.05 ) 63% v 26% EN alone

Bauer study 2 (RCT 120 ICU patients)EN/PN v EN alone no Δ in ICU LOS or Mortality

Heyland Meta-Analysis 3 : Trend toward greater mortality, increase $No significant Δ in infection, hospital LOS, ventilator days

Sena Study 4: prospectively collected data, retrospectively evaluatedEarly supplemental PN increased risk of infection p <.05

Elke study5 prospective study observational cross sectional, 1 day p prevalence 415 patients sepsis (454 ICU, 310 hospitals)PN associated with higher mortality, EN lowest mortality

1. Herndon J Burn Care Rehab 19891. Herndon J Burn Care Rehab 1989, , 2. Bauer Int Care Med 20002. Bauer Int Care Med 2000

3.Heyland JPEN 20033.Heyland JPEN 2003, 4.Sena JACS 2008, 4.Sena JACS 2008, , 5.Elke CCM 20085.Elke CCM 2008

Early TPN in ICU patients is harmful

NEJM July 1 2011

4640 Patients with Nutrition Risk Score > 2 from 7 Belguim ICUs

2328Early EN (day 2)Late TPN (day 8)

2312Early EN (day 2)Early TPN (day 3)

USA Approach European Approach

Late TPN Early TPN

Predefined Subgroup AnalysisEarly EN not Feasible due to Surgery

517 Patients ( APACHE II = 27 )

Late TPN Early TPN

% Infections 30% 40%

Late TPN had 20% increase likihood of early discharge alive (hazard ratio = 1.2, 95 % CI 1.00 to 1.44, p=0.05)

*

*p=0.01

Nutrition 1990

Ann Surg 1992

J. WESLEY ALEXANDER

Frank B. Cerra

John M. Daly

JPEN 1990

IMMUNE ENHANCING DIETS - 1990s

Nutrition 1990

Ann Surg 1992

JPEN 1990


Nutrition 1990

Ann Surg 1992

JPEN 1990

Different strategy

Early enteral nutrition ( 24 - 48 hr of admission )

Modest dosing ( 14 - 18 kcal/kg/d )

Dosing limit ( 7 - 10 days )


Nutrition 1990

Ann Surg 1992

JPEN 1990

Different goals

Maintain vital gut functions with enteral feeding

Blood flow

Motilty

Barrier function

Local immunity


Nutrition 1990

Ann Surg 1992

JPEN 1990

Different goals

Maintain vital gut functions

Supplementation to modulate inflammation Arginine Glutamine

Omega - 3 fatty acids

Nucleotides


BIMODEL MOF

Denver MOF Database

J Trauma 1996

Early MOF

Late MOF

Shock

Traumatic

Septic

Moderate SIRS

Severe SIRS

Infections Late MOF

Early MOF

SevereImmunosupression

Moderate Immunosupression

MOF OCCURS AS A RESULT OF A

DYSFUNCTIONAL INFLAMMATORY RESPONSE

Innate Immunity Neutrophils

Trauma Moderate SIRS

Severe SIRS

Infections Late MOF

Early MOF

SevereCARS

Moderate

CARS

Risk Factors Host factors Shock Tissue injury

Immunologic Dissonance: A Continuing Evolution in Our Understanding of the Systemic Inflammatory Response Syndrome (SIRS) and the Multiple Organ Dysfunction Syndrome (MODS)

Roger C. Bone, MD Ann Intern Med 1996

Adaptive Immune Response

Roger Bone

CARS

COMPENSATORY ANTI-INFLAMMATORY RESPONSE SYNDROME

Adaptive Immune Response Lymphocytes

Increased Tregs Monneret, G, Debard, AL, Venet, F, et al., Marked elevation of human circulating CD4+CD25+ regulatory T cells in sepsis-induced immunoparalysis. Crit Care Med, 2003. 31(7): p. 2068-71.

T cell anergy Bone, RC. Sir Isaac Newton, sepsis, SIRS, and Cars. Crit Care Med, 1996 24(7): p.1125-8.

Shift from THI to TH2 phenotype Delano, MJ, Scumpia, PO, Weinstein, JS, et al., MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J Exp Med, 2007. 204(6): p. 1463-74.

Macrophage Paralysis -decreased cytokine production-decreased bacterial clearance- decreased antigen presentation

Munoz, C, Carlet, J, Fitting, C, et al., Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest, 1991. 88(5): p. 1747-54

Ayala, A and Chaudry, IH, Immune dysfunction in murine polymicrobial sepsis: mediators, macrophages, lymphocytes and apoptosis. Shock, 1996. 6 Suppl 1: p. S27-38

Lymphocyte Apoptosis Hotchkiss, R. S., Swanson, P. E., Cobb, J. P. et al. Apoptosis in lymphoid and parenchymal cells during sepsis: findings in normal and T- and B-cell-deficient mice. Crit Care Med, 1997 25(8): p. 1298-1307.

Suppressed T cell proliferation De Waal Malefyt R, Haanen J, Spits H, et al: Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 1991; 174:915-924

Adaptive Immunity Changes that Characterize CARS

Shock Moderate SIRS

Severe SIRS

Infections Late MOF

Early MOF



SevereCARS

Moderate CARS

ImmunologicTrajectory of a Complicated ICU Course

Shock Moderate SIRS

Severe SIRS

Infections Late MOF

Early MOF



SevereCARS

Moderate CARS

ImmunologicTrajectory of a Complicated ICU Course

Immune Enhancing Diets

2nd Peak in MOF Disappeared (Why ?)

A 12-Year Prospective Study of Postinjury Multiple Organ FailureHas Anything Changed?

David J. Ciesla, MD; Ernest E. Moore, MD; Jeffrey L. Johnson, MD; Jon M. Burch, MD; Clay C. Cothren, MD; Angela Sauaia, MD

The Changing Pattern and Implications of Multiple Organ Failure after Blunt Injury With Hemorrhagic Shock

Joseph P.Minei, MD; Joseph Cuschieri, MD; Jason Sperry, MD; Ernest E. Moore, MD; Michael A. West, MD, PhD; Brian G. Harbrecht, MD; Grant E. O’Keefe, MD; Mitchell J. Cohen, MD; Lyle L. Moldawer, PhD; Ronald Tompkins, MD, ScD; Ronald V. Maier, MD; the Inflammation and the Host Response to Injury Collaborative Research Program

Arch Surg 2005Denver MOF Database

Glue Grant Database Crit Care Med 2012

Fundamental Changes in Pre - ICU Care of Patients Arriving with Severe Bleeding

Resuscitation – Permissive Hypotension Limit Crystalloids Massive Transfusion Protocols More Focus on Hemorrhage Control

Whole Body CT Scanning Looking for Blushes

Pelvic Fracture Protocols with Pelvic Packing

the ACSepidemic

To address

Recognition That Traditional ICU Care is Harmful

High Tidal Volume Mechanical Ventilation

Liberal Blood Transfusions

Supranormal Oxygen Delivery

Intermittent Dialysis

Early TPN

Late MOF/Deaths are Iatrogenic

More Consistent Implementation of Evidence Based CareDramatically Reduces Mortality

NIH funded study - $ 50 million

8 US Trauma Centers that had other NIH funding.

Study the genomic response to trauma and its impact on patient outcomes.

Need SOPs to control confounding effectsof variable care on patient outcomes.

Glue Grant Experience

2009

2005

Joseph Cuschieri, MD; Jeffery L.Johnson, MD;Jason Sperry, MD; Michael A. West, M, PhD; Ernest E. Moore, MD; Joseph P.Minei, MD; et.al and the Inflammation and Host Response to Injury Large Scale Collaborative Research Program.

Ann Surg 2012

Benchmarking Outcomes in Critically Injured Trauma Patients

Decreasing Mortality with Increasing Compliance to SOPs

Study Year

Driven By Quarterly Audits & Feedback

I'm

Prolonged ICU stays

Manageable Organ Dysfunctions

Recurrent Infections (i.e. Hits) with Milder SIRS

Persistent Acute Phase Response & # Lymphocytes

Decreased Lean Body Mass – a Wasting Disease

Poor Wound Healing & Decubitus Ulcers

Transfer to LTACs for Indolent Deaths



New Phenotype of Chronic Critical Illness has Replaced MOF

& no Overt Late MOF

I'm

Prolonged ICU stays









& no Overt Late MOF


I'm

Prolonged ICU stays







& no Overt Late MOF


CARS is not Late & not Compensatory Basic Lab Observations

Circulating Cytokine/Inhibitor Profiles Reshape the Understanding of the SIRS/CARS Continuum in Sepsis and Predict Mortality

Marcin F. Osuchowski, Kathy Welch, Javed Siddiqui, Daniel G. Remick

J Immunology 2006Simultaneous Pro- & Anti-inflammation

Block Pro-inflammation & Improve Mortality

But has no Effect on Anti-inflammation & CARS

J Immunology 2006

Circulating Cytokine/Inhibitor Profiles Reshape the Understanding of the SIRS/CARS Continuum in Sepsis and Predict Mortality

Marcin F. Osuchowski, Kathy Welch, Javed Siddiqui, Daniel G. Remick

J Immunology 2006Simultaneous Pro- & Anti-inflammation

Block Pro-inflammation & Improve Mortality

But has no Effect on Anti-inflammation & CARS

J Immunology 2006

CARS is not Late & not Compensatory Basic Lab Observations

Glue Grant Hypothesis (Tested in Humans)

SIRS - Excessive Innate Immune Response

CARS – Suppression Adaptive Immune Response

Looking at the Genomic Response After Severe Blunt Trauma

A Genomic Storm – 75% of Genes Up or Down Regulated

A. Gene expression After Severe Trauma B. Up-regulated Innate Immunity

C. Down-regulated Adaptive Immunity

Heat Map of ~ 2500 Genes

ctrl – control

12hrs,1,4,7,14, 21 & 28 daysfor individual patients

Blue – down regulated

Red- up regulated

A Genomic Storm – 75% of Genes Up or Down Regulated

A. Gene expression After Severe Trauma B. Up-regulated Innate Immunity

C. Down-regulated Adaptive Immunity

Significant Findings

The SIRS/CARS phenomenon cannot be confirmed.

There is no evidence of a 2nd hit

Exaggerated and prolonged expression of genes involved in both innate and adaptive immunity discriminates complicated outcome

Simultaneous pro- & anti- inflammation

Failure to achieve homeostasis

Hypothesis

Deregulated Innate Immunity

Deregulated Adaptive Immunity

Complicated Outcome

SIRS - Excessive Innate Immune Response

CARS – Suppression Adaptive Immune Response

Uncomplicated Outcome

Pro-Inflammation

Anti-Inflammation

SIRS

CARS

Early MOF

Fulminant death

Persistent Inflammation Recovery

Protein Catabolism/Cachexia

PICS

Early innate immunity Chronic Low Grade Inflammation

Indolent Death

A. Clinical Response

B. Individual Cell

Response

Macrophage Activation

Macrophage Paralysis

TRegsMDSCs

Dendritic Cells

T Effector Cell Number and Function

Insult

Persistent Inflammatory/immunosuppressionCatabolism Syndrome (PICS)

J Trauma 2112

Wrote a Review Article & Proposed a New Paradigm

Pro-Inflammation

Anti-Inflammation

SIRS

CARS

Early MOF

Fulminant death

Persistent Inflammation Recovery


PICS


Indolent Death


B. Individual Cell

Response



TRegsMDSCs

Dendritic Cells


Insult

Persistent Inflammation/immunosuppressionCatabolism Syndrome (PICS)

J Trauma 2112

10% Impaired immune function

20% Impaired wound healing & rehabilitation

30% Pneumonia & decubitus ulcers

40 % Indolent Death

% Lost

LOSS OF LEAN BODY MASSCLINICAL CONSEQUENCES

Potential PICS Patients – Persistent Inflammatory Hits

Burns ( > 30 % BSA )

Necrotizing pancreatitis

David Herndon

Burned Children Remain Catobolic > 1 yr

Anabolic Agents in Burned Children

Insulin

Propranolol

Oxandrolone

Exercise

Ann Surg 2008

UTMB - Galveston



Major surgery complicated by severe sepsis

UF Shands 2000 – 2010 , 51,577 major surgery patients

2,404 (3.8%) develop severe sepsis

9%

82%

9%Azra Bihorac


9%

82%

9%

Dead at 2 yrs.

14%

62%



9%

82%

9%

Dead at 2 yrs.

14%

62%

Pathway to PICS


Rationale for sepsis screening




Prolonged mechanical ventilation

Ann Intern Med 2010

1 year prospective cohort study from 5 adult ICUs at Duke 126 patients requiring prolonged ventilation

99 ( 79%) discharged alive

457 transitions in location of care (median 4)

150 hospital readmission ( ½ due to sepsis)

457 Transitions in Care

150 Hospital readmissions ( ½ due to sepsis)

Health Outcomes

90 (71%) Survive 3 months

Good

Fair

Poor

9

34

47

3 Months 12 Months

Health Outcomes


Good

Fair

Poor

9

34

47

11 (9%) Good

3 Months 12 Months

Health Outcomes


Good

Fair

Poor

9

34

47

11 (9%) Good

3 Months 12 Months

30 (25%) Fair

27 (21%) Poor

Health Outcomes


Good

Fair

Poor

9

34

47

11 (9%) Good

3 Months 12 Months

30 (25%) Fair

27 (21%) Poor

19 (16%) Dead

45% 1 Year Mortality





Sepsis

Long-term Cognitive Impairment and Functional Disability Among Survivors of Severe SepsisTheodore J. Iwashyna, MD, PhDE. Wesley Ely, MD, MPHDylan M. Smith, PhDKenneth M. Langa, MD, PhD JAMA, October 27, 2010

The Health and Retirement Study from 1996 to 2004

Americans > 50 years old were interviewed every 2 years

Assessed cognitive and physical functional status

Medicare claims - Identified who developed severe sepsis

Compared two interviews before and after severe sepsis

Long-term Cognitive Impairment and Functional Disability Among Survivors of Severe SepsisTheodore J. Iwashyna, MD, PhDE. Wesley Ely, MD, MPHDylan M. Smith, PhDKenneth M. Langa, MD, PhD JAMA, October 27, 2010

The Health and Retirement Study from 1996 to 2004

Americans > 50 years old were interviewed every 2 years

Assessed cognitive and physical functional status

Medicare claims - Identified who developed severe sepsis

Compared two interviews before and two after severe sepsis

Cognitive Impairment of Survivors

Time to sepsis - 3.1 yrs. - 1.1 yrs. 0.9 yr 2.8 yrs

Before Sepsis After Sepsis

Cognitive impairment Mild

Moderate/severe

Second Survey Before Sepsis

Last Survey Before Sepsis

Second Survey After Sepsis

First Survey After Sepsis

6%

17% 17%

Pa

tie

nts

wit

h C

og

nit

ive

Imp

air

me

nt

%25%

20%

15%

10%

5%

0%

Changes in Activities of Daily Living

(n=269) (n=169)

Before Sepsis

No Limitation Mild to Moderate Limitations

Before sepsis

After sepsis

Walk

Dress

Bathe

Eat

Get into bed

Toilet

Prepare meal

Grocery shop

Use telephone

Take meds

Walk

Dress

Bathe

Eat

Get into bed

Toilet

Prepare meal

Grocery shop

Use telephone

Take meds

Manage money

Fraction of Patients with Difficulty Fraction of Patients with Difficulty

0 0.2 0.4 0.6 0.8 1.0 0 0.2 0.4 0.6 0.8 1.0

Manage money

40%





Sepsis

Trauma

Long-term Survival of Adult Trauma PatientsGiana H. Davidson, MD, MPHChristian A. Hamlat, MD, MPHFrederick P. Rivara, MD, MPHThomas D. Koepsell, MD, MPHGregory J. Jurkovich, MDSaman Arbabi, MD, MPH

JAMA, March 9, 2011

25% discharged to SNFs and > 1/3rd died within one year.

Washington State Trauma Database 124,421 patients over 13 years

In hospital mortality

1995 1997 1999 2001 2003 2005 2007

16%

14%

12%

10%

8%

6%

4%

Fa

talit

y R

ate

Case Mortality Rate for Inpatients & 1 Year Postdischarge


JAMA, March 9, 2011




1995 1997 1999 2001 2003 2005 2007

16%

14%

12%

10%

8%

6%

4%


Unchanged Combined 1 year mortality

Postdischarge 1 year mortalityF

ata

lity

Ra

te


JAMA, March 9, 2011




1995 1997 1999 2001 2003 2005 2007

16%

14%

12%

10%

8%

6%

4%

Postdischarge 1 year mortality

25% discharged to SNFs and > 1/3rd dead within one year.

Fa

talit

y R

ate Unchanged Combined

1 year mortality


The Changing Pattern and Implications of Multiple Organ Failure after Blunt Injury With Hemorrhagic Shock

Joseph P.Minei, MD; Joseph Cuschieri, MD; Jason Sperry, MD; Ernest E. Moore, MD; Michael A. West, MD, PhD; Brian G. Harbrecht, MD; Grant E. O’Keefe, MD; Mitchell J. Cohen, MD; Lyle L. Moldawer, PhD; Ronald Tompkins, MD, ScD; Ronald V. Maier, MD; the Inflammation and the Host Response to Injury Collaborative Research Program

Crit Care Med 2012

1002 Severe Blunt Trauma 86 Died within 2 days

916 survive > 2 days

269 (29%) developed MOF No 2nd Peak in MOF Infection

MOF

Death

Glue Grant Database

Patients Ordered Top to Bottom by Time to Recovery (TTR)

No OrganDysfunction

Organ Dysfunction

Dead

Day 14

37%

MOF Recovery

Survival

Days after injury

0 7 days 14 days 21 days 28 days

Pro

po

rtio

n o

f p

atie

nts

Pat

ien

ts o

rder

ed b

y T

TR

B

A

Persistent

Inflammation

Immunosuppression

Catabolism

Inflammation

Immunosuppression

Persistent

Inflammation

Immunosuppression

Catabolism

Inflammation

Immunosuppression

A Paradoxical Role for Myeloid-Derived Suppressor CellsIn Sepsis and Trauma

Alex G Cuenca, Matthew J Delano, Kindra M. Scumpia, Claudia Moreno, Phillip O Scumpia, Drake M LaFace, Philip A Efron and Lyle L Moldawer Mol Med 2011 Crit Care Clin 2010

Linc Moldawer PhD

University of Florida

Dr NIH Inflammation



Induction of myeloid - derived suppressor cells (MDSC)

Released from bone marrow after inflammatory insults

Immature innate immune cells

Poor antigen presentation but cause inflammation

Suppress T-cell responses through different mechanisms



Induction of myeloid - derived suppressor cells (MDSC)

Released from bone marrow after inflammatory insults

Immature innate immune cells

Poor antigen presentation but cause inflammation

Suppress T-cell responses through different mechanisms

A Novel Regulatory Cell Population

Myeloid Derived Suppressor Cells (MDSCs)

Historically referred to as “natural suppressor cells”Bennette, Proc Natl Acad Sci U S A.10:5142-4, 1978

Arise with chronic inflammation and immunologic stress Bronte, Nat Rev Immunol 5:641-654, 2005

Highly conserved response to various inflammatory insults

Bronte, Nat Rev Immunol 5:641-654, 2005

Macrophage

Dendritic Cell

Granulocytes

Common Myeloid Progenitor

Myeloid derived suppressor cells

Factors that promote MDSC expansionG/M/GM-CSF

SCFIL-1IL-6

IL-10IL-12IL-13IL-17

S100A8/9Prostaglandins

VEGFSAACCL2

Common Lymphoid Progenitor

XX

Hemopoeitic Stem Cells

Released from Bone Marrow& Populate Other Hemopoeitic Organs

Pro-Inflammation

Anti-Inflammation

SIRS

CARS

Early MOF

Fulminant death

Persistent Inflammation

Recovery


PICS

Defects in Adaptive Immunity


Indolent Death


B. Individual Cell

Response



TRegsMDSCs

Dendritic Cells


Insult

Pro-Inflammation

Anti-Inflammation

SIRS

CARS

Early MOF

Fulminant death

Persistent Inflammation

Recovery


PICS

Defects in Adaptive Immunity


Indolent Death


B. Individual Cell

Response



TRegsMDSCs

Dendritic Cells


Insult

Conclusions

1) Early TPN to blunt stress matabolism sounds good , BUT!

Consistent signal from numerous studies over 30 years

Early TPN increases infectious complications

Conclusions

2. SIRS/CARS paradigm arose in the mid 1990s to explain the bimodal presentation of MOF

Immune enhancing diets were designed to blunt CARS

Conclusions

3. With advances in ICU care the 2nd peak in late MOF disappeared in early 2000s

4. Ongoing research ? SIRS/CARS paradigm

5. However, the SIRS/CARS paradigm allowed us to define our current clinical challenge : PICS

:

I'm

Prolonged ICU stays







& no Overt Late MOF

Persistent Inflammation/immunosuppression Catabolism Syndrome (PICS)

Conclusions

6. Myeloid derived suppressor cells drive persistent inflammation & catabolism that characterizes PICS

Need to better understand these cells How do we halt their expansion

Counteract their effects

Get them to mature

Develop Strategies for Anabolic Nutrition

Invited Review The Evolving Rationale for Early Enteral Nutrition Based on Paradigms of Multiple Organ Failure Frederick A. Moore, MD ; and Ernest E. Moore,

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