Transcript HD Rx of Hyperammonemia (Gregory et al, Vol. 5,abst. 55P

PCRRT for Metabolic
Disease
Timothy E. Bunchman
Professor Pediatrics
Signs and Symptoms of
Hyperammonemia
Initially healthy appearing neonate with
decompensation after several days
Often seen after institution of protein
feedings
Lethargy
Poor feeding
Vomiting
Hypotonia
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Signs and Symptoms of
Hyperammonemia
Respiratory distress, tachypnea, apnea
Irritability
Seizure activity
Neurologic deterioration leading to coma
Death
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Long Term Effects of
Neonatal Ammonemia
Demonstrated correlation between
prolonged neonatal hyperammonemic
coma and brain damage with impaired
intellectual functioning
Did not demonstrate correlation between
peak ammonia level and level of
intellectual impairment
[Msall et al. NEJM, 1984]
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Major Causes of
Hyperammonemia
Urea cycle defects
Organic acidemias
Transient hyperammonemia of the
newborn
Severe asphyxia - increased protein
breakdown during hypoxic stress plus liver
damage due to ischemia
Liver failure - due to multiple causes
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particularly infection
Flow Diagram to Evaluate
Hyperammonemia
acidosis
Increased
ammonia
Lactate/pyruvate
No
acidosis
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Urine for
organic acids
Plasma amino
acids
Flow Diagram to Evaluate
Hyperammonemia
Sig
incr
Plasma amino
acids
citrulline
citrullinemia
Nl.
Nl. Or sl.
increased
ASA
Incr.
low
urine
Orotic acid
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THN
Low or
absent
Incr.
ASA
CPS
OTC
Treatment of Ammonemia
Prior to Further Diagnosis
Prevent further catabolism by providing
adequate calories, fluids and electrolytes
Minimize protein intake
Provide alternate pathways for ammonia
removal
May require exchange transfusion,
peritoneal dialysis or hemodialysis for
ammonia removal
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Alternate Pathways for
Removal of Ammonia
Sodium benzoate
SODIUM BENZOATE
HIPPURATE
+ GLYCINE
Cleared by the kidney at 5X the GFR
Each mole of benzoate removes one
mole of ammonia as glycine
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Alternate Pathways for
Removal of Ammonia
Sodium phenylacetate
PHENYL- + GLUTAMINE
ACETATE
PHENYlAC
ETYLGLUTAMIN
E
Easily excreted in the urine
One mole of phenylacetate removes 2
moles of ammonia as glutamine
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Alternate Pathways for
Removal of Ammonia
Arginine supplementation provides the
urea cycle with ornithine and nacetylglutamate
Abbreviated version of the urea cycle
continues
not recommended for use in arginase
deficiency or organic acidemias
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But what do I do when the
drugs don’t work?
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You call your friendly
dialysis folks
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Mode of RRT
PD
nope
Hemodialysis
looks like a good place to start
Hemofiltration
a great way to go home at night
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micromoles/l
NH4
HD Rx of ammonemia
(Gregory et al, Vol. 5,abst. 55P,1994: )
2000
1800
1600
1400
1200
1000
800
600
400
200
0
NH4 rebound with reinstitution of HD
0
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1
2
3
4
5
6 10 11 12 13 17 18 19 20
Time
(Hrs)
HD to CRRT
(prevention of the rebound)
1200
micromoles/L
NH4
1000
800
Transition from HD to CVVHD
600
400
200
0
0
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1
2
3
4
5
Time
(Hrs)
10
11
17
Local experience
(McBryde et al, JASN 2000)
18 children underwent 20 therapies of
RRT due to in-born error of metabolism
mean age 56 + 7.9 mos
mean weight 15 + 3.7 kg (smallest 1.2
kg)
mean duration of therapy 6.1 + 1.3 days
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Local experience
(McBryde et al, JASN 2000)
Modalities used
HD only-9
time on HD 2.2 + 0.9 days
HF only-3
time on HF 6.3 + 2.9 days
HD followed by HF-8
time on HD + HF 10.25 + 1.8 days
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Local experience
(McBryde et al, JASN 2000)
Outcome
12/18 patients survived
2/12 continued to be medication and RRT
dependent
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But what do I do when the
drugs and RRT doesn’t
work?
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You call your friendly liver
transplant folks
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CVVHD for NH4 Bridge to
Hepatic Transplantation
800
700
micromoles/L
NH4
600
Successful Liver
Transplantation
500
400
300
200
100
0
1
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2
4
6
8
Time
(days)
10
12
14
16
Considerations of PCRRT
for metabolic disease
Dialysis Bath
“metabolic cocktail” clearance
nutritional needs with the balance of
restricted protein intake and amino acid
loss via HF
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Hemodialysis Bath
Considerations
Electrolyte
Na (meq/l)
Cl (meq/l)
Glucose (mg/dl)
Ca (mg/dl)
MG (meq/l)
HCO3 (meq/l)
K (meq/l)
Phos (mg/dl)
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ARF
140
96
200
3.5
1
40
0-3
0
Metabolic
140
96
200
3.5
1
40
4-5
4-5 (add to B jug)
Metabolic Cocktail drug
clearance
Drug clearance related
small molecular weight
minimal protein binding
volume of distribution
Phenylacetate, Benzoate, Arginine all will
be cleared
? Re bolus?
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Comparison of Total Amino
Acid losses: CVVH vs
CVVHD
(Maxvold et al, Crit Care Med April 2000)
Amino Acid Losses
(g/day/1.73 m2)
16
14
12
10
8
6
4
2
0
CVVH
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CVVHD
Conclusion
Hyperammonemia is a medical emergency
When medical management does not
work consider RRT early
HD should be used initially with HF in
tandem
Liver transplant should be considered if
medical and RRT management is not
successful
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