Metabolic response to stress

Pierre Singer, MD Institute for Nutrition Research

Critical Care Medicine Rabin Medical Center

Tel Aviv University

Disclosures

• Speaker fees from Abbott, GE, Cosmed,

B Braun, Baxter and Fresenius-Kabi

• Grants from Abbott, Baxter, B Braun and

Fresenius-Kabi

Main messages

• Acute phase modifies energy expenditure and

substrate utilization

• Anabolic resistance and protein breakdown

are leading to significant muscle loss

• Persistent Inflammation-Immunosuppression

Catabolism Syndrome (PICS) is secondary to

significant nutritional changes

Stress:

Trauma –

Infection -

Surgery

Epinephrine Norepinephrine Sympathic drive

Cytokines Inflammatory mediators

Adipokines

GIT hormones?

Anabolic

resistance Uncontrolled

catabolism

CHANGES IN: ENERGY EXPENDITURE BODY COMPOSITION

Adapted from JC Preiser

7

High ATP is associated with better

outcome

Stress:

Trauma –

Infection -

Surgery

Epinephrine Norepinephrine Sympathic drive

Cytokines Imflammatory mediators

Adipokines

GIT hormones?

Anabolic

resistance Uncontrolled

catabolism

CHANGES IN: ENERGY EXPENDITURE BODY COMPOSITION

Adapted from JC Preiser

Dead Trauma

Day Weeks ------ months

Anabolic Phase

0

EBB Phase FLOW Phase

En

erg

y, h

ea

t, O

2 c

on

sum

pti

on

Late

Anabolism

Turning

point

Injury

Phase

Phases of the response to injury: REE

(Resting Energy Expenditure) is increased after the injury

phase

.

Catabolism

Hypermetabolic period

Energy consumption increase

Elective surgery 10 %

Trauma 25 %

Peritonitis, sepsis 75 %

Burn 100 %

9

?

Resting energy expenditure, calorie and protein consumption in

critically ill patients: a retrospective cohort study. Zusman O, Theilla M, Cohen J, Kagan I, Bendavid I, Singer P.

Today the REE increase is less marked

Crit Care. 2016 Nov 10;20(1):367

Changes in the hypermetabolic period

Hemodynamic Hormonal Protein Carbohydrate Fat

CO Cortisol Catabolism Gluconeogenesis Lypolysis

SVR Glucagon Protein

degradation Lactate Lipogenesis

AV O2 Insuline

Liver acute

phase protein

syntesis Insulin resistance Ketone

bodies

Adrenaline Urea FFA usage of

myocard

.

Stress response - Carbohydrate metabolism: Substrate endogenous production

Splancnic glucose production

m/min/sq.m

Takala J.Baillieres Clin Endocrinol Metab 1997;11:617-27

Lipolysis during feeding is

increased in injury or sepsis Elwyn DH: Clin Nutr 1993

Muscle catabolism mechanisms

Nitrogen balance

-35

-30

-25

-20

-15

-10

-5

0

Burns Injury

Cyst

ectomy Sepsis

Hip

repl.

Malnour-

ished Normal

Normal

fasted

gra

ms

N

p

er 7

0 k

g

0

-100

-300

-400

-200

mg

N p

er k

g

(Surgical) trauma is accompanied by a negative nitrogen balance

Nitrogen balance is more negative than during pure fasting

The graded nature of the response

to the surgical trauma

15

Elwyn et al Crit Care Clin 1987; 3:57

From admission: loss of muscle mass in biopsy and Protein/DNA

Breakdown> Synthesis

TRACERS SHOW AN INCREASE IN SYNTHESIS AND A HIGHER INCREASE IN BREAKDOWN, LEADING TO NEGATIVE NITROGEN BALANCE

Intensive Care Department

The effects

of bed

rest... Decrease in muscle mass

Crit Care Med 2015

County

Autophagy cleans cell debris, but

releases nutrients and is inhibited by

feeding

Substrate utilization Weissman C, Crit Care Clinics 1999

CCM 2015

Qualitative US can evaluate muscle wasting

CT Scan can evalute fat mass and lean body mass of ICU patients

JPEN 2014; 38:880

Phase angle obtained by bio-

impedance is assessing

malnutrition

Phase angle is

predictive of

survival and

malnutrition

Conclusions

• In the acute phase:

– Energy expenditure is increased in a moderate way

– mobilization of substrates to provide glucose,

– obligatory lipolysis,

– Obligatory proteolysis.

• In the stabilized phase, body composition should

be preserved and nutritional support can be

adapted to the patie t’s eeds to preve t fro PICS.