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Nutrition
In Pediatric CRRT:
what should we be doing?
Michael Zappitelli, MD, MSc
Montreal Children’s Hospital
McGill University Health Center
Montreal, Quebec, Canada
Objectives
• Nutrition in critical illness and AKI
• Impact of CRRT on nutrition.
• Recommendations.
Critical Illness
X
No real prevention/treatment
Acute Kidney Injury
X
Left with:
1) Modifying the negative effects of AKI
2) Providing adequate nutrition
??? Modify outcome???
Poorer outcome, increased mortality
Critical Illness
hormone changes
-Insulin resist
-Increase stress
↑ cytokines
MALNUTRITION
Uremia
Acidosis
Altered Glucose
metab.
Cytokines
Altered substrate utilization
CH2O: ↑hepatic gluconeogenesis
(shift away from glycolysis)
↑lipogenesis
- Inefficient glucose oxidation
- Insulin resistance
- Shift in use of amino acids:
gluconeogenesis
Impaired nutrient transport
Inefficient/inadequate supply
Impaired A.a. conversion
↓lipid oxidation
Acute Kidney Injury
Malnutrition
• Delayed wound healing
• Muscle wasting
• Impaired organ function
• Infection susceptibility
• ?prolonged hospitalization
Overfeeding
• Hyperglycemia
• Fatty Liver
• Increased CO2 production.
Want to avoid under- and over- feeding
Critical Illness and Nutrition
Admission
•
Children: high risk of
malnutrition.
•
High basal metabolic rates.
PICU discharge
Hulst et al, Clinical Nutrition, 2004
•
Limited energy reserves/reduced “stores”
•
The smaller the child, the higher the relative energy and protein needs
•
Children require nutrition for “maintenance” and for growth.
•
High (15-30%) baseline poor nutrition.
Briassoulis et al, Nutrition, 2001
Malnutrition AND AKI
+
• Increased difficulty in nutrition provision.
• Metabolic changes of AKI.
• Children with AKI – increased risk of malnutrition
(decline in wt SD scores) at PICU discharge.
Hulst et al, J Nutritional Biochemistry, 2006
• RRT – increases nutritional losses.
Nutrition and AKI
•
Problem: No evidence-based guidelines.
•
Difficulty to show effect on hard outcomes.
•
1)
2)
3)
4)
Recommendations based on
Adult studies
Known metabolic alterations with AKI
Nutrition in critically ill children
Measuring nutritional losses by RRT.
Critical Illness – Energy needs
• Negative energy balance = wt loss and
growth compromised
• RDA versus predictive equations vs direct
measurement (indirect calorimetry).
• No single predictive equation shown to
accurately estimate REE.
• - +/- 75% of true REE!
AKI and energy needs
• Controversial – AKI per se probably not
affect energy expenditure.
• Affected more by coexisting conditions.
Indirect Calorimetry
• Indirectly measures REE my measuring inspired O2 and
expired CO2 – relates to “fuel use”.
• Patient should be in “steady state”.
• Not reliable with very high FiO2.
• ETT and chest tubes leaks – not reliable.
Indirect calorimetry AND CRRT
•
•
IC: measure resting energy expenditure.
Potential problem with CRRT
HCO3/CO2 fluxes
May affect IC
measurements.
IC may not be
reliable?
Hemofilter
Effluent
Dialysis fluid
Critical Illness – Energy needs
• Adults: 25-35 kcal/kg/day – probably need
more in children.
• Mean REE in literature: 35 to 60
kcal/kg/day (0.15-0.27 MJ/kg/day)
• Almost no studies in AKI.
Energy needs
Increased REE:
Fever
Sepsis
Post-prandial state
Acute events (procedures, ventilatory changes)
ASA, caffeine
High temperature environment
Decreased REE:
Paralytics, sedatives
Decreased temperature
Avoid over and underfeeding
Carbohydrates
• Patients become hyperglycemic.
• Insulin resistance, ↑hepatic gluconeogenesis.
– Stress hormones
– Inflammatory mediators and cytokines
– Metabolic acidosis
– Pre-existing hyperparathyroidism
Effects of CRRT
Glucose
• There may be glucose loss with glucose “–”
solutions (? as high as 40-80 g/day in adults).
• BUT hyperglycemia is actually usually a problem
– so probably not very significant.
• If use glucose-solutions: use “physiologic” –
avoid unnecessary shifts.
Critical Illness & AKI - Lipids
h LDL and VLDL
• iHDL-Cholesterol
Impaired Lipolysis
• Lipid turnover is increased with critical
illness.
• FFA source of fuel for gluconeogenesis
• So, need to give lipids
Effects of CRRT
• Lipid losses
• Minimal/none
Critical Illness – trace metals
•
-
Deficiencies linked to:
Lymphocyte dysfunction
Cardiovascular dysfunction
Platelet activity
Antioxidant function
Wound healing
Effects of CRRT
Losses
Trace metals:
Protein binding very high, so though MW is very small.
But protein binding is altered, redistribution occurs, maybe more
clearance.
Different trace metals found to be low in critically ill patients, especially
zinc and selenium. These are antioxidants.
Consider replacing with additional supplementation.
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, unpublished
We studied nutrient balance in critically ill children receiving CVVHD to:
(1) determine the dialysis clearance of, and
(2) quantify amino acid, trace metal and folate losses, and
(3) calculate the extent to which CVVHD losses impact daily nutrient balance.
• Prospective study, 5 days.
• Inclusion: 1 mth to 21 years, about to be initiated on CRRT
• Exclusion criteria: ESRD, prior dialysis therapy during admission, s/p Renal Tx,
likely mortality within 24 hours.
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted
Standard CVVHD:
PRSIMA: M60 or M100 AN69 filter
Qb = 2-4 ml/min/1.73msq, Qd = 2L/hour/1.73msq, Normocarb
Citrate regional anticoaggulation + CaCl
Data Collection:
Daily:
• ALL fluids in, ALL fluids out
• Nutrition: EN, PN, blood products, citrate/calcium, etc
• All amino acid, folate, zinc, selenium, copper, chromium, manganese contents
LAB:
BLOOD:
Day 1 (peri CVVHD start), prefilter amino acids, folate, trace metals.
Day 2: prefilter amino acids, folate, trace metals.
Day 5: prefilter amino acids, folate, trace metals.
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted
LAB:
Day 2 and Day 5:
6 to 12 hr effluent collection: amino acids, folate, trace metals + total Nitrogen
6 to 12 hour urine collection: idem
CVVHD and urine clearance calculated
Grams/micrograms amino acid, folate, trace metal losses calculated
Nutrient balances calculated
Trace metal, folate and nitrogen concentrations in dialysis fluid (n=2), citrate (n=2),
packed red cells (n=1) and fresh frozen plasma (n=1).
Dialysis fluid Citrate
Selenium (mcg/ml)
Copper (mcg/ml)
Chromium (mcg/ml)
Zinc (mcg/ml)
Manganese (mcg/ml)
Folate (ng/ml)
Nitrogen (g/ml)
0.0015
0
0.0002
0.01
0.00025
NA
NA
0.0005
0
0.0107
0.03
0.00125
NA
NA
Packed red cells
0.039
0.20
0.0011
0.66
0.0014
3.1
0.004
Frozen plasma
0.097
0.97
0.0013
0.74
0.0004
14.8
0.011
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted
Selenium
Copper
Chromium
Zinc
Manganese
Folate
K1 Day 2
K Day 5
2
(ml/min/1.73m ) (ml/min/1.73m2)
Serum concentrations_____________________
Initiation
Day 2
Day 5
Reference range2
10.1±7.2, 9.5
0.4±0.3, 0.3
24.0±10.6, 25.4
4.2±4.1, 3.2
9.0±12.9, 4.6
29.4±54.9, 16.2
55±19, 49
88±21, 87 L
2±1, 2
66±44, 53 L
9±16, 4 H
16±12, 12
8.6±3.9, 7.2
0.54±0.46, 0.44
24.7±7.1, 26.0
4.0±2.4, 2.9
38.2±121.4, 5.1
15.6±3.2, 16.3
61±24, 59
110±27, 106
2±1, 2
68±28, 61
8±15, 3 H
10±4, 9
64±23, 63
104±27, 103
2±0.4, 2
76±38, 68
8±15, 3 H
8±2, 7
23 to 190 (µg/l)
90 to 190 (µg/dl)
0 to 2.1 (µg/l)
60 to 120 (µg/dl)
0 to 2
(µg/l)
5.4 to 40 (ng/l)
Only selenium balance was negative on Days 2 and 5.
Churchwell et al, NDT, 2007
Critically ill adults receiving CVVHD and CVVHDF
Transmembrane clearances
Much lower clearance of selenium and chromium
Overall, trace metal clearance negligible (0.5 – 5.0 ml/min).
Critical Illness - protein
• Protein synthesis AND breakdown are increased:
breakdown more increased.
• Manifestation: proteolysis, net negative nitrogen
balance, skeletal muscle wasting.
• Nitrogen balance = Nin – Nout.
• Generally goal is + NB = less protein catabolism ?
= better outcome
Critical Illness & AKI - protein
- Reduced renal synthesis of amino acids
- Factors related to critical illness (elevated stress hormones,
increased hepatic gluconeogenesis, relative insulin
resistance).
Ferrando et al, Crit Care Med, 2007
- Redistribution of amino acids to areas of injury, for
inflammation, gluconeogenesis
- Losses
AKI and protein
• Protein synthesis CAN be increased by
providing more amino acids.
Bellomo et al, Int J of Artif Organs, 2002
Scheinkestel et al, Nutrition, 2003
• Still very difficult to achieve positive N
balance.
What amino acids should we give?
• Essential and non-essential amino acids.
• “non-essential” just means that the body produce them
endogenously… but body has to “work” to generate
these.
• If only give large amounts of EAA: protein synthesis
increases, NEAA depletion
Glutamine and arginine
• Supplementation thought to improve immune function
and GI function.
Arginine:
- “immunomodulating”
- Precursor to NO
• Rats with I-R AKI: large amounts of Arg led to increased
GFR ?due to increased NO.
Glutamine:
Neu et al – less sepsis with glutamine supplementation (J
Peds 1997 131:691-699)
Avenell, 2006 – meta-analysis, suggests publication bias.
Effects of CRRT
Losses
Amino acids: mean size = 145 Da
Affected by plasma concentration – glutamine is
one of highest, so often highest losses.
Affected by: Filter size, Qd, Qb, Qr.
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted
CVVHD clearance of amino acids measured on Day 2 and Day 5
N=15
Amino
Acid
Day 2 (n=15)
K1 CVVHD
CVVHD Losses
K Renal (n=2)
2
(ml/min/1.73m )
(mcg/kg/d)
(ml/min/1.73m2)
Mean±SD, Median Mean±SD, Median Mean
Day 5 (n=9)
K CVVHD
CVVHD Losses
K Renal (n=3)
2
(ml/min/1.73m )
(mcg/kg/d)
(ml/min/1.73m2)
Mean±SD, Median Mean±SD, Median
Mean
Tau
Asp
Thr
Ser
Asn
Glu
Gln
Pro
Gly
Ala
Cit
Val
Cys
Met
Ile
Leu
Tyr
Phe
Orn
Lys
His
Arg
104.5±179.0, 32.9
335.8±483.7, 53.6
31.9±25.0, 22.6
29.1±25.6, 17.8
37.2±32.1, 32.3
9.4±10.6, 6.2
19.4±20.1, 13.2
38.3±32.7, 31.2
28.1±25.7, 18.0
26.1±24.6, 15.4
25.6±24.3, 15.9
24.8±22.0, 14.8
27.4±54.5, 8.6
18.0±19.9, 8.2
29.9±29.8, 17.3
22.9±20.9, 13.6
22.2±23.3, 10.7
23.9±20.8, 12.9
8.4±8.7, 12.9
7.7±9.0, 2.8
13.2±15.8, 10.0
15.8±17.1, 8.0
77.8±111.2, 24.2
234.0±349.8, 51.1
38.8±25.1, 29.8
34.6±27.7, 22.3
35.5±19.8, 34.3
6.1±5.0, 3.8
85.4±152.9, 21.2
37.5±21.9, 27.3
35.3±30.2, 19.8
37.9±38.8, 25.2
39.3±50.4, 25.7
39.1±37.3, 25.1
34.7±29.9, 44.3
26.8±31.1, 17.2
38.6±34.7, 22.1
32.2±28.8, 22.7
36.5±41.3, 21.4
34.9±29.7, 26.4
91.0±249.7, 10.6
108.4±299.5, 9.6
33.4±66.3, 15.7
45.8±68.6, 8.6
8.4±11.1, 4.8
3.9±4.1, 3.2
15.7±18.5, 9.9
8.1±8.6, 5.7
7.7±8.1, 4.5
2.7±4.0, 1.8
47.4±63.7, 23.0
24.3±22.2, 17.6
16.0±16.1, 7.5
23.4±21.2, 13.5
2.8±4.5, 1.3
16.8±13.4, 12.7
0.8±1.2, 0.5
5.9±13.5, 12.7
6.0±5.7, 4.3
11.6±9.2, 7.8
9.2±13.5, 4.3
18.4±23.1, 7.8
3.4±5.0, 1.0
10.0±11.1, 4.4
8.0±15.9, 2.8
11.4±23.4, 3.5
1.0
2.6
4.1
3.6
9.8
0.6
2.2
0.2
3.9
5.2
4.1
5.2
0.5
3.6
6.9
3.9
4.4
4.5
0.3
0.3
0.7
1.8
4.5±5.4, 1.8
5.6±4.4, 2.6
11.9±5.9, 12.0
6.0±3.3, 5.0
5.0±3.4, 5.3
1.6±0.7, 1.7
44.2±30.7, 34.5
19.4±11.2, 20.5
12.0±7.1, 14.1
20.0±11.5, 24.1
1.5±1.1, 1.4
14.4±6.9, 13.9
1.3±1.1, 1.1
2.2±1.8, 2.2
5.4±2.7, 4.3
10.3±5.2, 10.9
5.6±2.7, 5.2
11.3±6.2, 10.1
2.5±3.4, 1.4
8.7±8.9, 5.6
4.5±3.8, 5.1
6.0±4.8, 4.1
2.1
12.0
18.9
9.2
28.6
1.0
0.7
0.8
12.9
6.9
5.7
5.5
5.2
5.1
6.6
4.4
10.5
7.0
0.7
0.9
12.1
6.2
Combined results of clearance of essential amino acids by CRRT.
Zappitelli et al (submitted) and Maxvold et al, Critical Care, 2000 (n=6).
60
50
40
K
ml/min/1.73m2
30
20
10
0
Thr Glu Gln Pro Gly Ala Val Met Phe Lys His Arg
Amino Acids
Several studies, adult and child: ~ 10-20% intake “lost” through hemofilter.
Both studies: Highest losses with Glutamine/Glutamic acid
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted
Protein and energy intake and output at CVVHD1 initiation, Day 2 and Day 5.
Protein intake
(g/kg/d)
N balance
(g/kg/d)
Caloric intake
(kcal/kg/d)
Caloric balance
(kcal/kg/day)
CVVHD initiation (N=15)
Mean±SD, Median
Day 2 (N=15)
Mean±SD, Median
1.98±1.24, 1.75
2.04±1.02, 2.09
1.85±0.60, 2.08
NA
-0.88±1.60, -0.22
-0.23±0.19, -0.24
32.6±27.6, 23.8
40.3±22.3, 33.6
43.2±18.4, 42.7
-0.4±25.4, -8.0
+7.7±21.7, +1.5
Day 5 (N=9)
Mean±SD, Median
+10.6±17.7, +10.8
Maxvold et al, Crit Care Med, 2000
Protein intake was 1.5 g/kg/day – Negative nitrogen balance
It’s not easy to achieve a positive nitrogen balance.
Logic: bigger filter, higher Qd or Quf = increased clearance
Does increasing protein intake help?
•
Scheinkestel et al.
1. Nutrition, 2003
In 11 critically ill adults on CRRT, protein intake 2.5
g/kg/day led to a) normal amino acid levels and b)
positive nitrogen balance.
2. Nutrition, 2003
50 critically ill adults on CRRT: 1.5 vs 2.0 vs 2.5
g/kg/day.
NB related to protein intake.
NB related to hospital stay
Protein intake 2.5 g/kg/d: improved survival!
Effects of CRRT
Losses
Water soluble vitamins:
Vit C - Limit 200 mg/d as precursor to Oxalic acid
Vit B1 (thiamine) - Altered Energy Metabolism,
h Lactic Acid, Tubular damage
Folate -
Anemia
These are antioxidants – “good stuff”
Consider replacing.
CRRT-Vitamins
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted
Clearance folate: about 16 ml/min/1.73m2 on Days 2 and 5
16
14
12
10
Serum folate
8
level (ng/ml)
6
4
2
0
*
*
Pre CRRT
Day 2
Day of CRRT
Day 5
What are we doing?
Protein and calorie prescription for children and young adults receiving CRRT:
a report from the Prospective Pediatric Continuous Renal Replacement Therapy
Registry group. Zappitelli et al, CCM, accepted.
We reviewed data from the Prospective Pediatric CRRT (ppCRRT) Registry to
(1) evaluate current protein and caloric prescription practices for critically ill children
and young adults with AKI receiving CRRT and
(2) evaluate the factors associated with over- and under-prescription of protein
and calories.
Retrospective study
ppCRRT centers with >=10 patients
Inclusion: eGFR<75 at CRRT start and required protein and caloric data.
Exclusion: toxin and/or metabolic disorders.
Data
Protein and caloric prescription at every circuit start.
Calculated REE
Protein and calorie prescription for children and young adults receiving CRRT:
a report from the Prospective Pediatric Continuous Renal Replacement Therapy
Registry group. Zappitelli et al, submitted.
2
1
0
Protein intake
(g/kg/day)
3
4
5
Daily change in protein prescription during treatment with CRRT.
1
2
3
4
5
6
excludes outside values
Day of CRRT
7
8
9
10
Protein and calorie prescription for children and young adults receiving CRRT:
a report from the Prospective Pediatric Continuous Renal Replacement Therapy
Registry group. Zappitelli et al, submitted.
75
50
0
25
Caloric Intake
(kcal/kg/day)
100
125
150
Daily change in caloric prescription during treatment with CRRT.
1
2
3
4
5
6
excludes outside values
Day of CRRT
7
8
9
10
Protein and calorie prescription for children and young adults receiving CRRT:
a report from the Prospective Pediatric Continuous Renal Replacement Therapy
Registry group. Zappitelli et al, submitted.
Characteristics (N)
N=195
Gender
Males (111)
Females (84)
p-value1
Age Group
≤ 1 year (35)
1 to ≤13 years (95)
>13 years (65)
p-value
MODS (155)
No MODS (40)
p-value
Survival
Survivors (117)
Non-survivors (78)
p-value
CRRT indication
Electrolytes (31)
Fluid overload (66)
Electrolytes and
fluid overload (98)
p-value
Protein intake (g/kg/day)
Initial
Maximal
1.4, 1.0[1.4]
1.3, 1.0[1.2]
0.7
2.0, 1.6[1.6]
1.9, 1.8[1.5]
0.9
1.5, 1.8[1.5]
1.3, 1.0[1.2]
1.4, 1.0[1.0]
0.09
2.5, 2.4[2.3]
2.0, 1.9[1.5]
1.6, 1.3[1.1]
0.009*
1.3, 1.0[1.2]
1.5, 1.0[0.8]
0.1
1.9, 1.8[1.5]
2.0, 1.3[1.7]
0.2
1.4, 1.0[1.2]
1.3, 1.0[1.3]
0.6
2.0, 1.6[1.5]
1.8, 1.8[1.7]
0.9
1.2, 1.0[0.9]
1.6, 1.2[1.2]
1.2, 1.0[1.3]
1.6, 1.4[1.1]
2.1, 1.8[1.8]
2.0, 1.8[1.6]
0.07
0.2
All groups:
-Maximal protein>initial
Multivariate predictors of
maximal protein intake
- Younger age
- Higher initial protein Rx
- #CRRT days
Protein Rx >2g/kg/day in 40%
AKI and nutrition
• Bellomo’s “cardinal rules” (Bellomo, Blood Purif, 2002):
1) The presence of renal disease should never
lead to restriction in nutritional support.
1) Protein catabolism due to MODS or severe
illness FAR outweighs that due to AKI.
3) Effect of CRRT on catabolism is small.
Synthesis
Nutritional parameter
Nutrition modality
- Early enteral feeding, will often require parenteral nutrition
Energy
- Approximately 25-40% above basal metabolic needs as measured by
metabolic cart or estimated with equations (de Klerk et al, Int Care Med, 2002).
-20 to 25% as carbohydrates (insulin as needed)
30 to 40% lipid formulations (20% lipid emulsions)
40 to 50% protein
Protein
- 2 to 2.5 g/kg/day with AKI (Multiple references)
- Increase intake if on CRRT (by 20%)
Vitamins
- Daily recommended intake
- Monitor serum folate, water soluble vitamin levels ± replacement (? 2X
RDA)
Trace elements
- Daily recommended intake; consider extra zinc and selenium
Monitoring
-Resting energy expenditure, nitrogen balance, electrolytes, vitamins, trace
elements
Consider
- Glutamine
Synthesis
1. Assure that any effects of CRRT on nutrition
are being addressed.
2. Use CRRT initiation to review nutritional
management.
3. Daily reassessment.
4. Multidisciplinary approach.
Acknowledgements
Dialysis Solutions Inc.
Baxter Healthcare
•Stuart Goldstein
•ppCRRT registry authors/collaborators
•Timothy Bunchman
•Norma Maxvold