Powerpoint of presntasi

1. ESPEN LLL Course
Topic 18 - Nutritional Support in Intensive Care Unit Patients
Energy in the ICU
Module 18.1
M. Hiesmayr, MD, MSc

2. Outline: Energy
• Energy production in human
-quantitative physiology
-regulation & storage
-sensing of deprivation
• Effects of critical illness
•ATP
•Mitochondria & respiratory chain:
•Substrates
• Measurement & strategic
•Estimation
•Measurement
•Kcal & RQ
•special conditions: renal replacement, ECMO

3. Energy = ATP
•ATP
- Exclusive form of energy in humans supported by FAD, NAPD & Creatin
Phosphate
- generated from glycolysis & oxydative phosphorylati
- All macronutrients (glucose, lipids, amino acids) are
- possible substrates but also alcohol and some infused substances like lactate,
acetate, malate and citrate
- 1 mol= 507.18 g
•Units
- Jo ul e: 1 Newton. 1 meter
- Kcal= 4.18 kJ
- Watt= 1 J/second
- (climbing a stair 200 W = 172 Kcal ,
- at rest 80 W = 70 Kcal)
-

4. ATP content in ICU patients
• correlates with severity (norepinephrine)
Brealey D et al (M.Singe r} Lancet 2002; 360: 219-2

5. Mitochondria:
stress I nutrients & morphology
Wai T, Langer T Trends in Endocrinology and Metabolism 2016; 27:105

6. CP - ATP in ICU patients
•

7. ATP & ADP in adult human
• ATP very fast recycling!
• Any disturbance of
oxydative
phosphorylation affects
cellular energy
availability
• ATP:ADP ratio in tissue 200:1 ??

8. Exercise increases energy
consumption
Comparison with HBE
Minimal exercise (3/6W) necessitates
more energy than in controls
Extra energy of 30 min exercise: 4.5 I V0 2 or 30 Kcal
Exercise in ICU is often of short duration (fatigue)
Hickmann CE et al lntens Care M ed 2014; 40: 548-55

9. 24 h Fasting & Refeeding
Volume
Glycogen
Lipid
Awad et al Cli n Nutr 2010: 29:538

10. Relative contribution of processes to whole
body energy consumption
• Protein turnover
• Na+/K+ ATPase
• Mitochondrial proton leak
• Triacylglycerol turnover
• Calcium cycling
• Gluconeogenesi s
• Ure agenesis
• Actinomyosin ATPase
• DNA/RNA turnover
• Substrate cycling
20-30%
20-28%
20-25%
<3%
4-10%
5-10%
<3%
<80/o
<20/o
<5%
r
ICU patie nts: Flat batteries = less essential processes reduced
Rolfe OF, Brow n GC. Physiol Rev 1997; 77: 731-58.
Singer M Crit Care 2017; 21 (Suppl 3 ): 309

11. Formula & weight:
a trick to be more precise
Whatever ,,tr ick" is applied > 50% of energy estimates are out of range
Graf S e t a l. Clin Nutr 2017; 36: 224-28

12. - - -
How much energy consumes
an intact organ
Leibel e t al.Met bo lis m 1984; 33:164-170 & Wang et al.
-= Am J Physio l End ocrinol M
etab 2000
; 27 9: E539 - E545
-

13. Body mass balance

14. Mitochondria adapt to stress:
fusion & fission
•Mitochondria division to recover
membrane potential or mitophagy or death
Friedman JR & Nunnari J Nature 2014; 505: 335-34

15. From substrate to energy
• Glucose (180 g/mole)
C6H120 6 + 6 0 2 = 6 CO2 + 6 H20 + 4 kcal/g
2
RQ =6/6 = kcal/0 =120
• Fat (Palmitic acid 256 g/mole)
C16H320 2 + 23 0 2 = 16 CO2 + 16 H20 + 9 kcal/g
RQ =1
6 /23 =0.7 kcal/0 2=100
• Aminoacids (89-204 g/mol Alanin 89 g/mole)
2(C3H70 2N)+ 6 0 2 = 5 CO2 + 5 H20 + CH40 N2 4 kcal/g
PHA
• Citrate
• Alcohol
RQ =5/6 =0.83 kcal/0 2=104
RQ =17/23=0.74 kcal/0 2= 57
RQ = 1.33
RQ = 0.67

16. Metabolic rate in sepsis
Kreyman et a l. Cr1tt Ca re Med 1993; 21: 101 2-19

17. Basal energy use versus age & gender
Speakman & Weste rte rp, Am J Clin Nutr 2010; 92: 826-834

18. Step 3: ICU
adaptive nutrition
With Progressive ,,artificial nutrition” (EN/PN) the feeding from inside
the body program is progressively reduced and body loss is reduced

19. Metabolic rate &
temperature in sepsis
None of the sepsis states was associated with an
increase of REE when temperature increased
2 factors: centralisation I proton leakage
Kreymann et al. Crit Care Med 1993; 21: 1012-19

20. Autophagy at the crossroads of
catabolism and anabolism

21. ICU treatment modifies energy
production/consumption:
level of sedation
Terao Yet al Crit Care Med 2003; 31: 830-3.

22. A complex city as an analogy
Activity (metabolic) can be determined by observing how much fuel is transported
in and what remains on the train on the way out. Alternatively you observe the
waste (smoke). Observing exported products ignores internal activity.

23. USE of a specific device
for metabolic measurement
VE is determined either with a
mixing chamber or with a
flowmeter breath by breath.
The difficulty is the
Synchronisation of the measured
gas concentrations with the
expiratory flow.
Fi0 2 appears to fluctuate in
some ventilators.

24. Ho rton et al. JAP 20 01; 90 :1 5 5- 16 3
3 days no nutrition:
induced insulin resistance

25. Phase 1: in daily life
the body has reserves

26. Creatine Phosphate - ATP:
an dual exercise system
Creatine Phosphate:
A battery for 15 seconds
Lactate in muscle
ATP appears less
efficient after 15
seconds because
another energy
provider (CP) was
used initially
Bangsbo J et al A
m J Physiol Endocrinol Metab 280; E956
Lactate release into blood
• I
ATP Production plateau:
After 15 seconds

27. Indirect calorimetry: the
calculations

28. REE vs substrate provision:
outcome at 60 days
Best outcome at substrate
supply for 70% of measured
REE
means that 30% of
substrates are endogenously
produced in the critically ill and
are not suppressed at this
stage of illness
by artificial nutrition provided at
REE .
Zusman et al. Crit Care 2016; 20: 367

29. 3100 Kcal
on indirect calorimetry
Patient: male 80 kg 185 cm 72 a temp 37.3°C
ruptured AAA repair with large transfusion
- Day 6 in ICU
- Arousable on minimal continuous opiods
- CRP 12 falling
- Pressure support (11mbar) ventilation 9
Liter/'
- Ileus / IAP 15 mbar / GRV 450 ml
- Nearly anuric / CRRT
- Trophic feeding + PN 1500 Kcal/24 hours
• Impossible!

30. ECMO: full double IC
calorimetry for the patient & the
ECMO circuit
90% of gas e xchange via ECMO
Applying the Weir formula on the combined
Data produced a REEcomposite of 1703 kcal/day.
Implementing the manual-derived VO2 and
VCO2 membrane oxygenator characteristics
into the Weir formula retrived a REE of
1729 kcal/day. The Faisy-Fagon and Harris-
Benedict equations yielded REE values of 1373
And 1563 kcal/d. Application of the ESPEN
Guideline estimated REE in our patient at
1675 kcal/d

31. Indirect Calorimetry:
conditions?
- Stability for 30 minutes
- No change in drugs(all ?)
- Vasoactive
- Sedation/pain
- Fluid
• Postprandial/fasted?
• Fi02 < 0.6
• PEEP <14 (PIP???)
• No leak
• No CRRT? 1.5-4°/o underestimation?
• No ECMO?

32. Correct amount Of
macronutrients in disease
states?
Singer P Hiesmayr M et al, clin nutr 2014; 33:246-51

33. ICU: energy factors
• Sedation
• Pain treatment
• Muscle relaxants
• Antiphlogistic
• Antipyretic
• Shock
• Vasoconstriction
• Organ loss
• Organ
dysfunction
• Awakening
• Dyspnea
• Weaning
• Shivering
• Seizures
• Delirium
• Infla mm a tio n
• Fever
• Wounds
• Organ repair
• Physiotherapy_

34. Learning objectives:
• Protein metabolism in the critically ill
• Higher protein intake increases whole protein content in
the body
• What is the best protein intake during the early or late
period of the acute phase and in the post acute phase for
PICS or rehabilitation
• No strong evidence for high protein administration
(more than 1.3 g/kg/d) in ICU patients
• Disease specific protein thera
py for trauma,renal or frail
and elderly patients

35. Conclusion
• Energy = ATP production is depressed in ICU
patients.
• Substrates (CHO/Lipid/Protein(AA) are the fuel
to produce ATP in oxydative phosphorylation
• Many factors modify energy consumption in
ICU: treatments and organ priorities
• Measurement is better than all formula but
does only suggest the amount of fuel needed in
the actual clinical state
• Extreme amount of fuel can impair endogenous
repair mechanism (mitophagylautophagy)

36. Proteolysis for substrate
endogenous production
Singer et al: ESPEN guideline: Nutriton in ICU, Clin Nutr 2019

37. Assessment
• Nitrogen output
• FFM through bioeletrical
impedance
• Ultra sound
• CT
• MRI
• Stable isotopes
• Biopsy

38. EFFECTS Of 2-WEEK BED RESTON
INFLAMMATORY MEDIATORS IN HEALTHY YOUNG
J Clin Endocrlnol Metab 2008

39. NitrogenLoss
Factors:
• Weight
+0.5g/10kg
• Height
+0.4g/ 10c m
• Age - 1.4g 60a
- 1.8g
80a
• Gender (f) - 1.2g
• Death - l .Og
• BMI no effect
• Time in ICU !!!
• Baseline
• 12g / day

40. Clinical consequences of protein and muscle loss

42. Skeletal muscle quality as assessed by
CT-derived skeletal muscle density is
associated with 6-month mortality in
mechanically ventilated critically ill patients

43. Should We Prescribe More
Protein to Critically Ill Patients?
Heyland DK1,2,3, Stapleton R4, Compher C5

44. What to do to improve
outcome and preserve
muscles?
• Give more?
• Give early?

46. What is early?
• The timing: starting during the
first 72 hours, regardless of the
dose?
• The amount: Early and plenty:
up to 1 g/kg/d within 72 hours

47. Increase in
mortality?
Casaer M P, W il m er A, Hermans G, Wouters PJ, M esott en D, Van den
Berghe G. Role o f disease and macronutrient dose in the random ized
co nt ro ll ed EPaNIC t rial. A post hoc analysis. Am J Respir Crit Care
Med 2013; 187: 247- 255.

48. 60 days mortality: 36% in early and 43% in
late protein administration (p<0.001 for
difference) Cox analysis: HR 0.84, 95% Cl 0.72-
0.98, p=0.01

49. Every 1 g of
protein
increases
Survival by
1%
Resting energy expenditure,calorie and
protein consumptionin critically ill
patients: a retrospective cohort study
Crit Ca re 2016
Oren Zusman1* , Miriam Theilla2,3, Jonathan Cohen2,4, Ilya Kagan2 , Itai Bendavid2 and Pierre Singer2,4

50. Nutr Clin Pract. 2017; 32: 121-5 1275
High protein
Intake > 2
g/kg/day
Recommended
Like in cancer,
Burns,
Nutrition Support for Persistent Inflammation,
Immunosuppression, and Catabolism Syndrome
Frederick A. Moore, MD1 ; Stuart Phillips, PhD2 ; Craig McClain,
MD3 ; Jayshil J. Patel, MD4 ; and Robert Martindale, MD, PhD5

52. Organs with a large turnover may be susceptible to decreased free amino-
acids. Some organs are prioritized in acute illness.
Attaix D,Boirie Y Normal protein homeostasis
Daily protein turnover
in individual organs