Download pCRRT 2008 - Pediatric Continuous Renal Replacement Therapy

Nutrition
In Pediatric CRRT
Michael Zappitelli, MD, MSc
Nutrition in AKI AND CRRT
McGill University Health Center
Montreal, Quebec, Canada
Objectives
Discuss the impact of nutrition in acute
kidney injury... and vice versa
Discuss clearance of nutrition and nutrition
adjustment in pediatric CRRT.
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
-Acute: increase
-Later: decrease
↑ 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 + APR’s
Impaired nutrient transport
Inefficient/inadequate supply
Impaired A.a. conversion
↓lipid oxidation
Acute Kidney Injury
Critical Illness and Nutrition
Adequate nutrition needed for recovery +
normal functioning of growing child.
Tissue synthesis and immune function.
Desire to avoid over- and under-feeding.
Underfeeding: increase morbidity, mortality,
infection, wound healing, length of ventilation.
Critical Illness and Nutrition
Children: high risk of malnutrition.
High basal metabolic rates.
Limited energy reserves.
High (15-30%) baseline poor nutrition.
Malnutrition AND AKI
Same difficulties/pathophysiology +
Increased difficulty in nutrition provision.
Higher rate of baseline malnutrition/ comorbidities
Metabolic changes of AKI.
Children with AKI – increased risk of malnutrition at PICU
discharge.
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
Metabolic needs vary according to the injury.
RDA versus predictive equations vs direct
measurement (indirect calorimetry).
No single predictive equation shown to
accurately estimate REE.
Limitations to indirect calorimetry in critically ill
patients.
AKI and energy needs
Controversial – AKI per se may not affect
energy expenditure.
Affected more by coexisting conditions.
Almost no data on pediatric AKI and
energy needs.
Indirect calorimetry AND CRRT
IC: measure resting energy expenditure.
Based on: Expired CO2 and O2 (O2 consumption +
CO2 production).
Potential problem with CRRT
HCO3/CO2 fluxes
May affect IC
measurements.
IC may not be
reliable?
Hemofilter
Effluent
Dialysis fluid
Critical Illness – Energy needs
Controversy: ? RDA ? 25-30% above REE.
Mean REE in literature: 35 to 60 kcal/kg/day
(0.15-0.27 MJ/kg/day)
Adults: 25-35 kcal/kg/day – probably need more
in children.
Almost no studies in AKI.
Carbohydrates
Patients become hyperglycemic.
Insulin resistance, ↑hepatic
gluconeogenesis.




Stress hormones
Inflammatory mediators and cytokines
Metabolic acidosis
Pre-existing hyperparathyroidism
Critical Illness - protein
Protein synthesis AND breakdown are
increased: breakdown more increased.
Manifestation: net negative nitrogen
balance, skeletal muscle wasting.
Nitrogen balance = Nin – Nout.
Critical Illness & AKI - protein
Protein metabolism abnormal:
- Reduced renal synthesis of amino acids
- Altered amino acid uptake
- Factors related to critical illness (elevated stress
hormones, increased hepatic gluconeogenesis,
relative insulin resistance).
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.
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
Amino Acid serum levels measured on Days 1, 2 and 5
Amino Acid2
CVVHD initiation % low/normal/high3 Day 2
Tau
Asp
Thr
Ser
Asn
Glu
Gln
Pro
Gly
Ala
Cit
Val
Cys
Met
Ile
Leu
Tyr
Phe
Orn
Lys
His
Arg
43±96, 16
4±3, 3
100±81, 66
53±26, 51
37±21, 30
57±89, 23
315±146, 295
124±66, 111
200±135, 167
195±133, 157
12±7, 10
148±58, 151
27±25, 21
32±52, 16
31±19, 24
78±34, 70
57±38, 42
92±59, 71
47±37, 38
152±65, 136
76±32, 71
43±26, 39
0/ 93.3/6.7
0/ 100.0/ 0
20.0/60.0/20.0
60.0/ 40.0/ 0
0/ 100.0/ 0
0/ 86.7/ 13.3
46.7/ 53.3/ 0
6.7/ 93.3/ 0
26.7/ 66.7/ 6.7
13.3/ 80.0/ 6.7
13.3/ 86.7/ 0
20.0/ 80.0/ 0
20.0/ 60.0/ 20.0
6.7/ 80.0/ 13.3
13.3/ 86.7/ 0
0/ 93.3/ 6.7
6.7/ 73.3/ 20.0
0/ 73.3/ 26.7
0/ 86.7/ 13.3
0/ 86.7/ 13.3
6.7/ 80.0/ 13.3
20.0/ 80.0/ 0
% low/high/normal Day 5
40±102, 14
6.7/ 86.7/ 6.7
5±5, 3
6.7/ 93.3/ 0
99±54, 109
13.3/ 80.0/ 6.7
65±30, 56
53.3/ 46.7/ 0
42±23, 43
0/ 93.3/ 6.7
55±55, 37
0/ 80.0/ 20.0
372±167, 364 0/ 33.3/ 66.7
142±69, 127
0/ 100.0/ 0
186±89, 177
20.0/ 66.7/ 13.3
259±149, 210 13.3/ 80.0/ 6.7
12±8, 11
20.0/ 80.0/ 0
144±43, 142 6.7/ 93.3/ 0
17±24, 10
33.3/ 60.0/ 6.7
37±39, 25
6.7/ 53.3/ 40.0
43±22, 42
6.7/ 93.3/ 0
97±28, 95
0/ 100.0/ 0
51±27, 45
6.7/ 86.7/ 6.7
98±63, 79
0/ 46.7/ 53.3
56±41, 51
0/ 86.7/ 13.3
173±84, 153
0/ 66.7/ 33.3
75±38, 65
6.7/ 80.0/ 13.3
74±56, 55
0/ 93.3/ 6.7
18±14, 13
13±16, 8
105±67, 95
66±34, 58
42±27, 41
119±146, 82
382±261, 336
182±113, 132
190±100, 165
283±192, 236
12±7, 12
140±57, 148
24±35, 12
25±16, 26
45±23, 41
101±41, 100
46±27, 45
83±45, 87
67±84, 52
153±90, 127
65±36, 57
56±31, 50
% low/normal/high
11.1/ 88.9/ 0
11.1/ 66.7/ 22.2
0/ 88.9/ 11.1
44.4/ 55.6/ 0
11.1/ 77.8/ 11.1
11.1/ 44.4/ 44.4
33.3/ 55.6/ 11.1
0/ 88.9/ 11.1
11.1/ 77.8/ 11.1
11.1/ 77.8/ 11.1
22.2/ 77.8/ 0
11.1/ 88.9/ 0
33.3/ 55.6/ 11.1
0/ 88.9/ 11.1
0/ 88.9/ 11.1
11.1/ 77.8/ 11.1
22.2/ 77.8/ 0
0/ 44.4/ 55.6
11.1/ 77.8/ 11.1
11.1/ 66.7/ 22.2
11.1/ 77.8/ 11.1
11.1/ 88.9/ 0
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!
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, submitted.
Age (years)
8.8 ± 6.8 (8.1, 12.8)
CRRT duration (days)
10.2±10.7 (7.0, 11.0) days
Diagnostic category
Sepsis/Infection
Renal
Respiratory
Cardiac
Hematology Oncology
Gastrointestinal/Hepatic
Other
N (%)
74 (38.1)
29 (15.0)
12 (6.2)
21 (10.8)
35 (18.0)
15 (7.7)
9 (4.6)
CRRT indication
Electrolyte imbalance
Fluid overload only
Fluid overload and electrolytes
31 (15.9)
66 (33.9)
98 (50.3)
CRRT modality
CVVHD
CVVH
CVVHDF
94 (48.2)
52 (26.7)
49 (25.1)
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)
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%
Critical Illness & AKI - Lipids
h LDL and VLDL
iCholesterol and HDL-Cholesterol
Impaired Lipolysis
Lipase Activity ~50%
i Lipoprotein Lipase
i Hepatic Triglyceride Lipase
Critical Illness - Vitamins
Water Soluble
Vit B1 Def
Altered Energy Metabolism,
h Lactic Acid, Tubular damage
Vit B6 Def
Altered Amino acid and lipid
metabolism
Folate Def
Anemia
Vit C Def
Limit 200 mg/d as precursor to
Oxalic acid
Potential for losses during CRRT.
Critical Illness - Vitamins
Fat Soluble
Vit D Def
Vit A Excess
Vit E Def
Hypocalcemia
i renal catabolism of
retinol binding protein
i >50% plasma and RBC
CRRT-Vitamins
Amino acid, trace metal and folate clearance by continuous renal replacement
therapy in critically ill children. Zappitelli et al, submitted
16
14
12
10
Serum folate
8
level (ng/ml)
6
4
2
0
*
*
Pre CRRT
Day 2
Day of CRRT
Day 5
Critical Illness – trace metals
-
Deficiencies linked to:
Lymphocyte dysfunction
Cardiovascular dysfunction
Platelet activity
Antioxidant function
Wound healing
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 L3
2±1, 2
66±44, 53 L
9±16, 4 H3
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
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.
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)
Synthesis
Nutritional parameter
Nutrition modality
- Early enteral feeding, will often require parenteral nutrition
Energy
- Approximately 25% above basal metabolic needs as measured by
metabolic cart or estimated with equations.
-20 to 25% as carbohydrates (insulin as needed)
30 to 40% lipid formulations (20% lipid emulsions)
40 to 50% protein
- 2 to 3 g/kg/day with AKI
- Increase intake if on CRRT (by 20%)
Protein
Vitamins
- Daily recommended intake
- Monitor serum folate, water soluble vitamin levels ± replacement
Trace elements
- Daily recommended intake
Monitoring
-Resting energy expenditure, nitrogen balance, electrolytes, vitamins,
trace elements
Consider
- Glutamine
Acknolwedgements
Timothy E. Bunchman
Norma J. Maxvold
Stuart L. Goldstein