PCRRT for Metabolic Disease Timothy E Bunchman Professor

PCRRT for Metabolic Disease Timothy E. Bunchman Professor Pediatrics

Signs and Symptoms of Hyperammonemia z. Initially healthy appearing neonate with decompensation after several days z. Often seen after institution of protein feedings z. Lethargy z. Poor feeding z. Vomiting z. Hypotonia bunchman

Signs and Symptoms of Hyperammonemia z. Respiratory distress, tachypnea, apnea z. Irritability z. Seizure activity z. Neurologic deterioration leading to coma z. Death bunchman

Long Term Effects of Neonatal Ammonemia z. Demonstrated correlation between prolonged neonatal hyperammonemic coma and brain damage with impaired intellectual functioning z. Did not demonstrate correlation between peak ammonia level and level of intellectual impairment z[Msall et al. NEJM, 1984] bunchman

Major Causes of Hyperammonemia z. Urea cycle defects z. Organic acidemias z. Transient hyperammonemia of the newborn z. Severe asphyxia - increased protein breakdown during hypoxic stress plus liver damage due to ischemia z. Liver failure - due to multiple causes bunchman particularly infection

Flow Diagram to Evaluate Hyperammonemia acidosis Increased ammonia Lactate/pyruvate No acidosis bunchman Urine for organic acids Plasma amino acids

Flow Diagram to Evaluate Hyperammonemia Sig incr Plasma amino acids citrullinemia Nl. Or sl. increased low urine Orotic acid bunchman THN ASA Incr. Low or absent Incr. ASA CPS OTC

Treatment of Ammonemia Prior to Further Diagnosis z. Prevent further catabolism by providing adequate calories, fluids and electrolytes z. Minimize protein intake z. Provide alternate pathways for ammonia removal z. May require exchange transfusion, peritoneal dialysis or hemodialysis for ammonia removal bunchman

Alternate Pathways for Removal of Ammonia z. Sodium benzoate SODIUM BENZOATE HIPPURATE + GLYCINE z. Cleared by the kidney at 5 X the GFR z. Each mole of benzoate removes one mole of ammonia as glycine bunchman

Alternate Pathways for Removal of Ammonia z. Sodium phenylacetate PHENYL- + GLUTAMINE ACETATE PHENYl. AC ETYLGLUTAMIN E z. Easily excreted in the urine z. One mole of phenylacetate removes 2 moles of ammonia as glutamine bunchman

Alternate Pathways for Removal of Ammonia z. Arginine supplementation provides the urea cycle with ornithine and nacetylglutamate z. Abbreviated version of the urea cycle continues znot recommended for use in arginase deficiency or organic acidemias bunchman

But what do I do when the drugs don’t work? bunchman

You call your friendly dialysis folks bunchman

Mode of RRT z. PD ynope z. Hemodialysis ylooks like a good place to start z. Hemofiltration ya great way to go home at night bunchman

HD Rx of ammonemia (Gregory et al, Vol. 5, abst. 55 P, 1994: ) NH 4 micromoles/l NH 4 rebound with reinstitution of HD Time (Hrs)

micromoles/L NH 4 HD to CRRT (prevention of the rebound) Transition from HD to CVVHD Time (Hrs)

Local experience (Mc. Bryde et al, JASN 2000) z 18 children underwent 20 therapies of RRT due to in-born error of metabolism zmean age 56 + 7. 9 mos zmean weight 15 + 3. 7 kg (smallest 1. 2 kg) zmean duration of therapy 6. 1 + 1. 3 days bunchman

Local experience (Mc. Bryde et al, JASN 2000) z. Modalities used y. HD only-9 xtime on HD 2. 2 + 0. 9 days y. HF only-3 xtime on HF 6. 3 + 2. 9 days y. HD followed by HF-8 xtime on HD + HF 10. 25 + 1. 8 days bunchman

Local experience (Mc. Bryde et al, JASN 2000) z. Outcome y 12/18 patients survived y 2/12 continued to be medication and RRT dependent bunchman

But what do I do when the drugs and RRT doesn’t work? bunchman

You call your friendly liver transplant folks bunchman

Successful Liver Transplantation micromoles/L NH 4 CVVHD for NH 4 Bridge to Hepatic Transplantation Time (days)

Considerations of PCRRT for metabolic disease z. Dialysis Bath z“metabolic cocktail” clearance znutritional needs with the balance of restricted protein intake and amino acid loss via HF bunchman

Hemodialysis Bath Considerations bunchman

Metabolic Cocktail drug clearance z. Drug clearance related ysmall molecular weight yminimal protein binding yvolume of distribution z. Phenylacetate, Benzoate, Arginine all will be cleared y? Re bolus? bunchman

Comparison of Total Amino Acid losses: CVVH vs CVVHD Amino Acid Losses (g/day/1. 73 m 2) (Maxvold et al, Crit Care Med April 2000)

Conclusion z. Hyperammonemia is a medical emergency z. When medical management does not work consider RRT early z. HD should be used initially with HF in tandem z. Liver transplant should be considered if medical and RRT management is not successful bunchman