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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
!"#$%& '(#$%&!"#$%&'#($)*$+,-.#(-$)#$/0,12334 5426
Caractéristiques de la population Caractéristiques de la population admise aux SI (2018)
n 2258Charlson 2.3 ± 2.2Modified frailty index 1.4 ± 1.5SAPS 3 47 ± 21
Quelques termes…
English Français
Sarcopenia Sarcopénie
Constat # 2! Perte massive de masse musculaire après
toute agression
Metabolic response in ICU patients
Jeevanandam M. J Parent Ent Nutr1992,16 : 511-20
WOUND has priority
Protein storesmobilized(catabolic)
WOUND & BODY
have priority
1 7 14 days
cum
ulat
ive
nitr
ogen
defi
cit
(g)
BOD Yhas priority
Protein stores replenished(anabolic)
!"#$%#"&'()*+$&',"-+.&'/"0#.#1#23
CatabolismeCatabolisme protéiqueprotéique: la : la libérationCatabolismed’AACatabolismeCatabolismed’AAd’AA estCatabolismeCatabolisme
estest un protéiqueprotéiqueprotéique: la CatabolismeCatabolisme protéique
un un un phémomènelibérationlibération: la : la : la libération
phémomènephémomènephémomènephémomène adaptatif
)*+,$-.%/
0*$%.%/
0+,1/�
231-3%/&
45,36.%/&
00#73+189/**:#.--+%.,$.1/&.%;*$--$,.3%#<#9.9$,1.&$,.3%
713,: 7=$&/#$.>+?%@3>*+93>@%A&/
B+,=+9=/$15#C#/,#$*:#D#B=5&.3*#EFGFH(II8J!JGKJ!JI
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$-&
!"#$
!"$$
!#$
$
#$
$ % & ' ( "$ "% "& "'
)*+,-,./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
BreakdownSynthesis
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7843
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4%%5.'#6'+27'89:';<<=>=?=@4=AB4%%5.'#6'+27'4C"':'DC"E';<<B>;A<7;<AFGH3#"'#6'+27':!4I';<<?>=J@;BA4%%5.'#6'+27'KK9';<<L>=?@<=
BNS 4ST
K Q%91/$&/ -+&9*/#713,/.%&5%,=/&.&K U$&.*5 $V&31V/MK QW#.%;+&.3%#&$;/
K Q%91/$&/& +1/$>/%/&.& $%M#3X.M$,.3% 3;#00K T3#/;;/9, 3%#-+&9*/#713,/.% V1/$6M3Y%K Z+/*#$+,3K9$%%.V$*.&-K )*+9$>3%#1/*/$&/
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.
9/,:%#$;*($45<$5426782=
>*-?*@?#,/'$#-$,A<$;!B!$542CDC2412632E2F44
9/,:%#$;*($45<$5426782=
>*-?*@?#,/'$#-$,A<$;!B!$542CDC2412632E2F44
Muscle Biopsy Specimens From a Representative Patient on Day 1 and Day 7Healthy muscle is seen on day 1 (A, C) with necrosis and a cellular infiltrate on day 7 (B, D).This infiltrate was CD68 positive on immunostaining, indicating macrophage origin (red). A, B arehematoxylin and eosin stain, and C, D was immunostaining, with CD68 for red, laminin (myofiberoutline) for green, and 4',6-diamidion-2-pheylidole (a nuclear marker) for blue.
Acute Skeletal Muscle Acute Skeletal Muscle Wasting in Critical IllnessWasting in Critical Illness
PuthuchearyWasting in Critical IllnessWasting in Critical Illness
Puthucheary et al JAMA 2013;310:1591
Histological features of CI myopathySchefold J Cachex Sarcopenia Muscle. 2010; 1: 147–157.
[+1P.P$*#N$,/&]#!KO.%+,/#^$*6#_.&,$%9/]#$%M#`+$*.,5#3;#a.;/#;31#(#b/$1&#$;,/1#_.&9=$1>/#;13-#,=/#Q%,/%&.P/#4$1/#R%.,:
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+,-.#(-$3 +,-.#(-$24 +,-.#(-$22 +,-.#(-$25
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Expérience locale
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Expérience locale
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+,-.#(-$22 +,-.#(-$25 +,-.#(-$2C +,-.#(-$2= B#,(
Expérience locale
Constat # 4! Les apports protéo-caloriques sont plus
importants et utiles en phase tardive « post-aigüe »
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AfterAfter the the firefire….0#=+>/#,$&6#3;#1/KV+.*M.%>
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WhatWhat do do wewe needneed ?O$%73Y/1#L#V+**M3e/1#f#/%/1>5
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Hypocaloric / permissive underfeeding
Trickle / trophic feeding
Normocaloric / full feeding244
64
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Q.%#
Normocaloric / full feeding244
64
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How much protein should How much protein should we prescribe
How much protein should How much protein should we prescribewe prescribe?we prescribe
ESPEN guidelines we prescribewe prescribe
ESPEN guidelines ESPEN guidelines Clinwe prescribewe prescribewe prescribe
Clin Nutrwe prescribe
Nutr 2019;38:49
! 1.3 g protein /kg per day should be delivered progressively during the critical illness.
! Grade of Recommendation: O. Consensus (91% agreement)
Statement 3! Physical activity may improve the beneficial
effects of nutritional therapy. ! Consensus (86 % agreement)
Constat # 5! Activité physique et nutrition vont de pair
Early physical and occupational therapy in
mechanically ventilated, critically ill patients.mechanically ventilated, critically ill patients.Schweickert WD Lancet 2009;373:1874
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
MOBILISATION TUBE ET ou TRACHEO
MOBILISATION et LVAD
N/.-$N,/#$B#)$5443D$CG15=33
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
O&.*5<"D.-05'1"+=R$11.E'"D+C.2.1$5.+-P %<%2.->"6GJ"*,D?G(84$<
Effects of exercise on muscle protein Effects of exercise on muscle protein catabolism
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Effects of exercise on muscle protein Effects of exercise on muscle protein catabolism
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Effects of exercise on muscle protein Effects of exercise on muscle protein catabolism
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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
rbitr
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..