PCRRT for Metabolic Disease

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PCRRT for Metabolic Disease

• Timothy E. Bunchman
• Professor Pediatrics

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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
  particularly infection

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Flow Diagram to Evaluate Hyperammonemia
Urine for organic acids
acidosis
Increased ammonia
Lactate/pyruvate
No acidosis
Plasma amino acids
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Flow Diagram to Evaluate Hyperammonemia
citrullinemia
Sig incr
THN
Nl.
Plasma amino acids
Nl. Or sl. increased
citrulline
ASA
Incr.
ASA
low
Low or absent
CPS
urine
Orotic acid
OTC
Incr.
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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
• Cleared by the kidney at 5X the GFR
• Each mole of benzoate removes one mole of ammonia
  as glycine

SODIUM BENZOATE
HIPPURATE
GLYCINE
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Alternate Pathways for Removal of Ammonia

• Sodium phenylacetate
• Easily excreted in the urine
• One mole of phenylacetate removes 2 moles of
  ammonia as glutamine

PHENYlACETYLGLUTAMINE
PHENYL-ACETATE

GLUTAMINE
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Alternate Pathways for Removal of Ammonia

• Arginine supplementation provides the urea cycle
  with ornithine and n-acetylglutamate
• 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 dont 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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HD Rx of ammonemia(Gregory et al, Vol. 5,abst.
55P,1994 )
NH4 rebound with reinstitution of HD
NH4 micromoles/l
Time (Hrs)
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HD to CRRT(prevention of the rebound)
Transition from HD to CVVHD
NH4 micromoles/L
Time (Hrs)
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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 doesnt
work?
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You call your friendly liver transplant folks
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CVVHD for NH4 Bridge to Hepatic Transplantation
Successful Liver Transplantation
NH4 micromoles/L
Time (days)
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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
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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)
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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