Metabolic response to stress. Pierre Singer, MD Institute for Nutrition Research Critical Care Medicine Rabin Medical Center Tel Aviv University

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1 Metabolic response to stress Pierre Singer, MD Institute for Nutrition Research Critical Care Medicine Rabin Medical Center Tel Aviv University

2 Disclosures Speaker fees from Abbott, GE, Cosmed, B Braun, Baxter and Fresenius-Kabi Grants from Abbott, Baxter, B Braun and Fresenius-Kabi

3 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

4 Adapted from JC Preiser Stress: Trauma Infection - Surgery Epinephrine Norepinephrine Sympathic drive Uncontrolled catabolism Cytokines Inflammatory mediators Adipokines Anabolic resistance GIT hormones? CHANGES IN: ENERGY EXPENDITURE BODY COMPOSITION

7 High ATP is associated with better outcome 7

8 Adapted from JC Preiser Stress: Trauma Infection - Surgery Epinephrine Norepinephrine Sympathic drive Uncontrolled catabolism Cytokines Imflammatory mediators Adipokines Anabolic resistance GIT hormones? CHANGES IN: ENERGY EXPENDITURE BODY COMPOSITION

9 Phases of the response to injury: REE (Resting Energy Expenditure) is increased after the injury phase EBB Phase FLOW Phase. Energy, heat, O 2 consumption 0 Trauma Injury Phase Day Dead Turning point Anabolic Phase Hypermetabolic period Catabolism Weeks months Late Anabolism Energy consumption increase Elective surgery 10 % Trauma 25 % Peritonitis, sepsis 75 % Burn 100 % 9?

10 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. Crit Care Nov 10;20(1):367 Today the REE increase is less marked

11 Changes in the hypermetabolic period Hemodynamic Hormonal Protein Carbohydrate Fat CO Cortisol Catabolism Gluconeogenesis Lypolysis SVR Glucagon Protein degradation Lactate Lipogenesis AV O 2 Insuline Liver acute phase protein syntesis Insulin resistance Ketone bodies Adrenaline Urea FFA usage of myocard

12 Stress response - Carbohydrate metabolism: Substrate endogenous production. m/min/sq.m Splancnic glucose production Takala J.Baillieres Clin Endocrinol Metab 1997;11:617-27

13 Lipolysis during feeding is increased in injury or sepsis Elwyn DH: Clin Nutr 1993

14 Muscle catabolism mechanisms

15 The graded nature of the response to the surgical trauma 0 Burns Injury Cyst ectomy Sepsis Hip repl. Malnourished Normal Normal fasted 0 grams N per 70 kg Nitrogen balance mg N per kg (Surgical) trauma is accompanied by a negative nitrogen balance Nitrogen balance is more negative than during pure fasting -35 Elwyn et al Crit Care Clin 1987; 3:57 15

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

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

19 The effects of bed rest... Intensive Care Department Decrease in muscle mass

20 Crit Care Med 2015 County

21 Autophagy cleans cell debris, but releases nutrients and is inhibited by feeding

22 Substrate utilization Weissman C, Crit Care Clinics 1999

23 CCM 2015 Qualitative US can evaluate muscle wasting

24 JPEN 2014; 38:880 CT Scan can evalute fat mass and lean body mass of ICU patients

25 Phase angle obtained by bio- impedance is assessing malnutrition

26 Phase angle is predictive of survival and malnutrition

27 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.

Metabolic Abnormalities in the Burn Patient Part 1

Metabolic Abnormalities in the Burn Patient Part 1 Objectives To understand normal body composition and importance of lean body mass To understand the metabolic changes which occur in the burn patient