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AER 2019
25ème AER : 19 & 20 novembre 2020
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QUELLE NUTRITION A LA PHASE INITIALE ?
Jean-Charles Preiser, MD, PhDErasme University Hospital, Brussels
Actualités en réanimationLyon, 21 novembre 2019
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« Ou :Ce qui était considéré comme Vrai hier n’est plus forcément La Vérité aujourd’hui »
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Am J Respir Crit Care Med. 2017 Jun 8. doi: 10.1164/rccm.201705-0919ED
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Jeevanandam M. J Parent Ent Nutr1992,16 : 511-20
WOUND has priority
Protein storesmobilized(catabolic)
WOUND & BODY
have priority
1 7 14 days
cum
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ive
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The 3 post-injury phases
Preiser, Ichai, Orban, Groeneveld
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Phase aïgue / précoceQuelques heures à 3-7 jours..•Anorexie•Dépense énergétique limitée•Utilisation préférentielle du glucose comme substrat énergétique
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muscle
glucose
brain
Fatty acids
erythrocytes
LymphocytesWBC
liver
Injuredtissues
lactate
METABOLIC ADAPTATION TO STRESS
Insulino-dependencr
alanine
adipocytes
glycerol
Insulino-dependencer
Insulinoindependence
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Rate of basal glucose production and endogenous production during glucose infusion in various
conditions
Wolfe RR, Eur J Clin Nutr 1999
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Critically ill patients are able to match their REE
Tappy L et al Crit Care Med 1998; 26: 860
• Resting metabolic rate 1824 kcal/ day
• Glycemia 7.3 mmol/L
• Endogenous glucose production 360 g/ day (1360 kcal/d)
• Net protein balance -117 g/ day
3 day starvation
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Figure 1. The relative change ((M-value after surgery/M-value after surgery) × 100) in insulin sensitivity after different surgical procedures and surgical approaches (open vs laparsocopic
cholecystectomy).
Ljungqvist O JPEN J Parenter Enteral Nutr 2012;36:389-398
Copyright © by The American Society for Parenteral and Enteral Nutrition
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Determination of insulin sensitivityBrain
Othercells
Insulin losses (liver, kidneys)
Glucose
Insulin
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Liver
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Insulin sensitivity
Effective insulin
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Dextrose Absorption
• Model-based approach:• Clinically validated in many trials
(real-time BG control, retrospectiveclinical, and simulated trials)
• Correlates well with euglycaemic-clamp ISI (r = 0.99)
• Provides a means to quantify SI and IR in critically ill patients
• SI identified hourly for everypatient
• BG system model
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Individual time couse of insulin sensitivity
N = 81 patients, all staying 3 days or longer form Uyttendaele et al, Critical Care 2017
Time (hours)
SI (L/mU/min)Type 2 DM
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PENDANT LA PHASE AIGUE
LES BESOINS CALORIQUES SONT
INFERIEURS A LA DEPENSE ENERGETIQUE.
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N = 1,171
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0.0
0.5
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Hiesmayr et al NutritionDay 2007-2013, n= 9870
D1-D7 >D7
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The pyramid of evidence-based medicine
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Casaer MP, Van den Berghe G. N Engl J Med 2014;370:1227-1236.
Recent large nutrition RCT’s
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Am J Clin Nutr 2011
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Caloric intake in the EPaNIC trial
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Outcomes – EPaNIC trialCasaer et al NEJM 2011
0
10
20
30
40
50
HospLOS
ICU LOS New inf MV >2d RRT CRP
*
*
*
*
**
Primaryoutcome
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Late PN Early PN
Casaer MP & Langouche L et all, CCM, 2013
Hermans G. et al. Lancet Resp. Med. ; 2013
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Supplementary Appendix.• In post hoc subgroup analyses, we compared late initiation of
parenteral nutrition with early initiation in patients for whom early enteral nutrition was surgically contraindicated (517 patients who had undergone complicated pulmonary, esophageal, abdominal, or pelvic surgery and who had a mean APACHE II score of 27±11).
• Together, these high-risk subgroups predictably received a median of 0 kcal (interquartile range, 0 to 163) per day of enteral nutrition by day 7. Among these patients, the rate of infection was lower in the late-initiation group (29.9%) than in the early initiation group (40.2%, P = 0.01).
• In the late-initiation group, there was a relative increase of 20% in the likelihood of earlier discharge alive from the ICU (hazard ratio, 1.20; 95% CI, 1.00 to 1.44; P = 0.05; P = 0.11 for interaction)
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0
2
4
6
8
10
12
14
16
18
20
New infection LOS Mortality Duration MV
EarlyLate
Outcomes – PEPaNIC trialFivez et al NEJM 2016
*
**
Primaryoutcomes
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The pyramid of evidence-based medicine
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Infectious complications
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WHY COULD HIGH CALORIC INTAKE BE DETRIMENTAL DURING THE
ACUTE / EARLY PHASE?
WE NEED TOOPEN THE ENGINE!!
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• Overfeeding• Autophagy• Refeeding
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• Overfeeding• Autophagy• Refeeding
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Ziegler et al N Engl J Med. 2009;361:1088
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Rate of basal glucose production and endogenous production during glucose infusion in various
conditions
Wolfe RR, Eur J Clin Nutr 1999
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Energy estimation and measurement in critically ill patients.Fraipont V, Preiser JC.JPEN J Parenter Enteral Nutr. 2013 Nov-Dec;37(6):705-13
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• Overfeeding• Autophagy• Refeeding
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Damage removal : Autophagy
isolation membrane
Atg factors (Atg1)Beclin1PI3K class III
M.P.C., K.U.Leuven
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isolation membrane
Elongation
autophagosome
Atg factors (Atg1)Beclin1PI3K class III
Atg12Atg5 Atg12-5/16Atg16Atg8 Atg8-PE(LC3-I) (LC3-II)
p62
Ubiquitin
Substrate
Damage removal : Autophagy
M.P.C., K.U.Leuven
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isolation membrane
autolysosome
Elongation
autophagosome
lysosome
Atg factors (Atg1)Beclin1PI3K class III
Atg12Atg5 Atg12-5/16Atg16Atg8 Atg8-PE(LC3-I) (LC3-II)
p62
Ubiquitin
Substrate
Damage removal : Autophagy
M.P.C., K.U.Leuven
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isolation membrane
autolysosome
Elongation
autophagosome
lysosome
Atg factors (Atg1)Beclin1PI3K class III
Atg12Atg5 Atg12-5/16Atg16Atg8 Atg8-PE(LC3-I) (LC3-II)
p62
Ubiquitin
Substrate
Masiero E et al. Cell Metab 2009
LC3-II / LC3-I
Damage removal : Autophagy
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Activators of autophagy ?
Fasting
Cellular stress
Hypoxia
+isolation
membraneautolysosome
Elongation
autophagosome
lysosome
M.P.C., K.U.Leuven
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Suppressors of autophagy ?
Nutrients
Growth Factors
Insulin
-isolation
membraneautolysosome
Elongation
autophagosome
lysosome
M.P.C., K.U.Leuven
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• Overfeeding• Autophagy• Refeeding
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Refeedingsyndrome
Refeedinghypophosphatemia
Refeeding : tout un spectre!
Le plus Fréquenten SI
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Jeûne prolongé
Glucagon insuline
Glycogénolyse puis gluconéogenèse
Maintien de l’homéostasie glucidique
Fonte des stocks de lipides et protéines: énergie et substrats
gluconéogénétiques
Re-nutrition
Consommation /shift co-facteursde la glycolyse : PO4, thiamine,
K, Mg
Sécretion insuline +++
Utilisation glucides (énergie)
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In clinical practice, in case of refeedingsyndrome….• Hypophosphatemia• Hypokaliemia• Hypomagnesemia• Thiamin deficiency
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• Standard care • Intervention
- Reduce support to 20 kcal/h- Replace phosphate (protocol)- Thiamine (at least 100 mg IV/d)- other B-group vitamins- monitoring of K, Mg
- Gradual return to normal intake protocol (40 – 60 kcal/h, 80 – 100%) unless P drop < 0.71 mmol/l
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WHAT ABOUT PROTEIN INTAKES?
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A reappraisal of nitrogen requirements for patients with critical illness and trauma
80
Dickerson et al. 2012
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IV aminoacid therapy for kidney functionDoig Intensive Care Med 2015;41:1197
• Objective:• To determine whether IV AA therapy preserves kidney
function in patients at risk of AKI• Intervention:
• Random allocation to receive a daily supplement up to 100g AA or standard
• Main outcome:• Duration of renal dysfunction
• Results :• 474 patients (235 standard, 239 AA) – no difference in
duration of renal dysfunction / transient improvement in GFR
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Critical Illness is Associated With Anabolic Resistance
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Table 2. Nutrition characteristics in ICU after randomisation a
Variable Early 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)
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‘High protein intake during the early phase of critical illness: yes or no?’JC Preiser, Crit Care 2018 .
PRO CON
- Increase muscle proteinsynthesis- Easily absorbed- IV infusion safe
- Increases ureagenesis and oxidation of AA- No effect on muscle protein breakdown- Fuel auto-cannibalism- Glucagon release
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Am J Respir Crit Care Med. 2017 Jun 8. doi: 10.1164/rccm.201705-0919ED
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Hypocaloric / permissive underfeeding
Trickle / trophic feeding
Normocaloric / full feeding100
50
0
Percentage ofenergy expenditure
Time
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Hypocaloric / permissive underfeeding
Trickle / trophic feeding
100
50
0
Percentage ofenergy expenditure
Time
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Permissive underfeeding is no longer abusive nor insulting!
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Ability to match > 50% REE within 3 days ?
YES NO
Contra-indication to EN ?
WaitStart EN
Gradual increase of infusion rate (target 25 kcal/kg.d)
and optimise delivery (pro-motility agents, post-pyloric tube)
YES NO
Day 5-7 < 80 % of prescription delivered by enteral route
Consider complementary PN (to match caloric debt)
EN still contra-indicated
Parenteral nutrition
Not a problem
Vincent JL & Preiser JCThe Lancet (2013)
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Hippocrate (470-377 av. JC) « Que ta nourriture soit ton médicament! »
Primum non nocere… avec une nutrition inadéquate: apports excessifs à la phase aïgue, insuffisants en phase tardive
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June 2-3, 2020