Quelles leçons tirer de la Quelles leçons tirer de la réanimation sur

Quelles leçons tirer de la Quelles leçons tirer de la réanimation sur réanimation sur sarcopénie

Quelles leçons tirer de la sarcopéniesarcopénie et réanimation sur réanimation sur sarcopéniesarcopénie

nutrition?

Prof Jean-Charles PreiserService des Soins Intensifs

Hôpital Erasme – Université Libre de Bruxelles

The T2E congress – Paris, 2019

Constat # 1! Evolution de la population de réanimation

Evolution de la population de réanimation

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Caractéristiques de la population Caractéristiques de la population admise aux SI (2018)

n 2258Charlson 2.3 ± 2.2Modified frailty index 1.4 ± 1.5SAPS 3 47 ± 21

Quelques termes…

English Français

Sarcopenia Sarcopénie

Constat # 2! Perte massive de masse musculaire après

toute agression

Metabolic response in ICU patients

Jeevanandam M. J Parent Ent Nutr1992,16 : 511-20

WOUND has priority

Protein storesmobilized(catabolic)

WOUND & BODY

have priority

1 7 14 days

cum

ulat

ive

nitr

ogen

defi

cit

(g)

BOD Yhas priority

Protein stores replenished(anabolic)

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CatabolismeCatabolisme protéiqueprotéique: la : la libérationCatabolismed’AACatabolismeCatabolismed’AAd’AA estCatabolismeCatabolisme

estest un protéiqueprotéiqueprotéique: la CatabolismeCatabolisme protéique

un un un phémomènelibérationlibération: la : la : la libération

phémomènephémomènephémomènephémomène adaptatif

)*+,$-.%/

0*$%.%/

0+,1/&#00

231-3%/&

45,36.%/&

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Cumulative N balance in mechanically ventilated Cumulative N balance in mechanically ventilated Cumulative N balance in mechanically ventilated Cumulative N balance in mechanically ventilated Cumulative N balance in mechanically ventilated Cumulative N balance in mechanically ventilated Cumulative N balance in mechanically ventilated patients receiving full enteral feeding

)1$-&

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!"$$

!#$

$

#$

$ % & ' ( "$ "% "& "'

)*+,-,./0*123

Days

Weight loss Protein lossloss *Weight lossloss(%)

Protein(%)

5 11.2 - 16.8

10 15.2 - 20.8

15 19.2 - 24.8

20 23.0 - 29.0

25 26.8 - 33.2

* in vivo neutron analysis. Hill G.L. J Parent Enteral Nutr 16, 197-218, 1992

! 7 - 14 g nitrogen / d.

! 220 - 440 g lean tissue / d

> 80-200 g/d muscular proteins

Protein losses during critical illness

Constat # 2 bis! Perte massive de masse musculaire après

toute agression! Persistante malgré les apports protéiques

Protein metabolism in trauma patients with Protein metabolism in trauma patients with or without brain injury

Petersen SR et al, J. Trauma 1993; 34: 653

0

1

2

3

4

5

Healthy BMI MI

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Table 2. Nutrition characteristics in ICU after randomisation a

VariableEarly Goal-directed Nutrition

(N=100)Standard of Care

(N=99)Measured b energy requirement, kcal/day

2069 (1816 - 2380) 1887 (1674 - 2244)

Calculated c energy requirement, kcal/day

1950 (1750 - 2125) 1875 (1650 - 2100)

Energy intake, kcal/day 1877 (1567 - 2254) 1061 (745 - 1470)

Energy balance d, kcal/day -66 (-157 - -6) -787 (-1223 - -333)

Measured e protein requirement, g/kg/day

1.63 (1.36 - 2.05) 1.16 ( 0.89 - 1.62)

Protein intake, g/kg/day 1.47 (1.13 - 1.69) 0.50 (0.29 - 0.69)

Protein balance d, g/kg/day -0.28 (-0.76 - 0.11) -0.69 (-1.02 - -0.38)

P-urea, mmol/l 13.5 (8.7 – 21.9) 9.0 (5.6 – 14.4)

24-hour urinary urea, mmol/day 516 (368 – 760) 320 (175 – 482)

Constat # 3! Le syndrome post-soins intensifs…

POSTPOST-POST-POST-POSTINTENSIVE CARE POSTPOSTINTENSIVE CARE INTENSIVE CARE INTENSIVE CARE SYNDROME

Constat # 3 bis! Le syndrome post-soins intensifs

comporte une composante neuro-musculaire « ICU-acquired weakness »

Quelques termes…

English Français

Sarcopenia Sarcopénie

Tetraparesia Tétraparésie / plégie

Polyneuropathy Polyneuropathie

Myopathy Myopathie

Wasting syndrome Cachexie

ICU-acquiredweakness

Faiblesse musculaire acquise en réanimation / soins intensifs

Potential mechanisms of ICUAWSchefold Schefold J Cachex Sarcopenia Muscle. J Cachex Sarcopenia Muscle. 2010; 1: 1472010; 1: 147–2010; 1: 147–157157.

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Muscle Biopsy Specimens From a Representative Patient on Day 1 and Day 7Healthy muscle is seen on day 1 (A, C) with necrosis and a cellular infiltrate on day 7 (B, D).This infiltrate was CD68 positive on immunostaining, indicating macrophage origin (red). A, B arehematoxylin and eosin stain, and C, D was immunostaining, with CD68 for red, laminin (myofiberoutline) for green, and 4',6-diamidion-2-pheylidole (a nuclear marker) for blue.

Acute Skeletal Muscle Acute Skeletal Muscle Wasting in Critical IllnessWasting in Critical Illness

PuthuchearyWasting in Critical IllnessWasting in Critical Illness

Puthucheary et al JAMA 2013;310:1591

Histological features of CI myopathySchefold J Cachex Sarcopenia Muscle. 2010; 1: 147–157.

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Constat # 4! Les apports protéo-caloriques sont plus

importants et utiles en phase tardive « post-aigüe »

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Hypocaloric / permissive underfeeding

Trickle / trophic feeding

Normocaloric / full feeding244

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How much protein should How much protein should we prescribe

How much protein should How much protein should we prescribewe prescribe?we prescribe

ESPEN guidelines we prescribewe prescribe

ESPEN guidelines ESPEN guidelines Clinwe prescribewe prescribewe prescribe

Clin Nutrwe prescribe

Nutr 2019;38:49

! 1.3 g protein /kg per day should be delivered progressively during the critical illness.

! Grade of Recommendation: O. Consensus (91% agreement)

Statement 3! Physical activity may improve the beneficial

effects of nutritional therapy. ! Consensus (86 % agreement)

Constat # 5! Activité physique et nutrition vont de pair

Early physical and occupational therapy in

mechanically ventilated, critically ill patients.mechanically ventilated, critically ill patients.Schweickert WD Lancet 2009;373:1874

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MOBILISATION TUBE ET ou TRACHEO

MOBILISATION et LVAD

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WORKING HYPOTHESES OF THE WORKING HYPOTHESES OF THE STUDIESStudy 1- Is passive physical activity able ! to influence muscle mass (anthropometric/echography)?! to influence muscle function (electrophysiology)?! to decrease the loss in muscle proteins (nitrogen

balance and 3-MH/creatinine ratio)?

Study 2- Which are the effects of an increase in the intensity of physical activity?

Study 3- Which are the effects of increased caloric / protein intakes?

Study 1 : Passive mobilisationStudy 1 : Passive mobilisationPreiser De Prato et al J Novel Physioth 2014

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Effects of exercise on muscle protein Effects of exercise on muscle protein catabolism

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Constat # 6! Il y a des interventions

« pharmaconutritionnelles » prometteuses..

Maximizing muscle protein anabolism: the roleof protein quality (sport medicine).

Tang JE, Phillips SM.Curr Opin Clin Nutr Metab Care. 2009;12:66-71

Increase inMuscle Mass (kg)

Régulation de la synthèse protéique par les acides aminés

La voie mTOR

Anthony 2000, Crozier 2005, Walrand 2008

Muscle squelettique

Regulation of muscular protein synthesis

Selected aminoacidsLeucine

Leucine is able to stimulate MPS

Dardevet 2000

Skeletalmuscle

Régulation de la synthèse protéique

par les acides aminésExemple de la citrulline

05

10152025

AL R NEAA CIT

Uni

tés A

rbitr

aire

s

*

*¤

ANOVA+ test PLSD Fisher. * vs. AL, p < 0,05, ¤ vs. R, p < 0,05

P70S6kinase1 (forme phosphorylée Thr389)

05

101520253035

A.L R NEAA CIT

**

¤

ANOVA+ test PLSD Fisher. * vs. AL, p < 0,05, ¤ vs. R, p < 0,05

S6(forme phosphorylée Ser240/244)

Uni

tés A

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aire

s

Akt

mTOR

4E-BP1

EIF4GEIF4AEIF4E

Initiation de la traduction

Facteurs de croissance

p70S6K1

S6

Citrulline

Moinard, 2007

VitaminVitamin D! Vitamin D deficiency associated with loss of type 2

myocytes! Vitamin D supplementation increases MPS (in non-

critically ill)! VDR expressed on the surface of muscle cells! VDR-KO mice have a low muscle mass and functional

impairment! Vitamin D is involved in the control of the expression

of several genes linked to protein metabolism (MAP kinase (p38, JK, ENK))

DIRECT

Direct effects on the intracellularpathways of regulation

INDIRECT

Inflammation, insulin resistance

Pittas, 2007

Constats! Evolution de la population de réanimation

! Perte massive de masse musculaire après toute agression persistante malgré les apports protéiques

! Le syndrome post-soins intensifs comporte une composante neuro-musculaire « ICU-acquired weakness »

! Les apports protéo-caloriques sont plus importants et utiles en phase tardive « post-aigüe »

! Activité physique et nutrition vont de pair

! Il y a des interventions « pharmaconutritionnelles » prometteuses..