Transcript Continuous Veno-venous Hemodiafiltration Therapy for Acute

Continuous Veno-venous
Hemodiafiltration Therapy
for Acute Decompensation
with Cerebral Edema in
Maple Syrup Urine Disease
Joshua J. Zaritsky M.D., Julian A. Martinez M.D., Ora
Yadin M.D.
David Geffen School of Medicine, Mattel Children’s
Hospital at UCLA, Los Angeles, United States
Maple Syrup Urine Disease
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Autosomal recessive disorder characterized by
psychomotor retardation, feeding problems and maple
syrup odor of the urine
Caused by deficiency of branched-chained alphaketoacid dehydrogenase complex
Results in increased plasma concentrations of the
branched-chained amino acids: leucine, isoleucine and
valine
Five phenotypes have been described based on both
clinical and biochemical findings
Management of MSUD
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Dietary therapy to promote normal growth
and development
Prompt recognition and treatment of acute
metabolic decompensation usually triggered by
an intercurrent illness
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Characterized by acute rises in the BCAA with
leucine accumulation leading to neurotoxicty
Cerebral Edema during Episodes of
Metabolic Decompenstation
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Cerebral edema is the leading cause of death during
periods of acute decompensation
Remains unclear why MSUD patients are prone to
cerebral edema (Morton et.al. 2002)
 Intracellular entrapment of osmotically active amino
acids caused by high intracellular leucine levels
 Impairment of normal regulatory volume defensedisrupution of intracellular protein synthesis
 Pathological or iatrogenic decreases in serum sodium
and osmolarity with rapid water flux into cells
Treatment of Acute Decompensation
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Native urinary clearance is low so strategies for
removal of BCAA include
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Nutritional support:
 Inhibition of protein catabolism
 Enhancement of protein synthesis with amino
acid supplementation aimed at promoting
leucine incorporation
Extracorporeal Removal
 Exchange transfusions
 Dialysis; PD, HD and CRRT
Choice of Dialysis Modality
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Literature is largely case based
Guoyon et. al. (1994) compared BCAA clearance
between PD, CAVH and CAVHD in a rabbit
model of MSUD
PD was less efficient than CRRT
 Using CRRT; BCAA clearance paralleled that of
urea
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No comparisons of HD vs. CRRT in cases
complicated by cerebral edema
Case Presentation
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7 yo male with neonatal diagnosis of MSUD presented
to outside hospital with a 2 week history of URI
symptoms and difficulty walking
Diagnosed with pneumonia with a superimposed
asthma exacerbation
Over the period of one week he became progressively
encephalopathic with new onset spastic diplegia despite
dietary modifications
CT upon arrival at UCLA revealed diffuse cerebral
edema with no visible sulcation
Initial leucine level of 285 µmoles/L at outside
hospital. At time of transfer had reached a peak of
1581 µmoles/L
Therapeutic CVVHDF
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Based on his cerebral edema decision made to initiate
CVVHDF
Gambro circuit with M60 filter; Qb of 100ml/min,
Qd of 1500ml/hr and Qr of 750ml/hr , no net
ultrafiltration
Predicted small molecule clearance of
57ml/min/1.73m2
Given an estimated Vd of leucine of 17L (Based on a
weight of 27kg; see Jouvet et.al. 2001) acceptable steady state levels
of leucine were predicted to be reached in 16 hours
Plasma Amino Acid Levels
1800
Plasma levels (μmoles/L)
1600
CVVHDF
1400
leucine
1200
isoleucine
1000
valine
800
600
400
200
0
4
8
12
16
Time (hours)
36
Amino Acid Clearances
Clearance
(ml/min)
Clearance
(ml/min/1.73m2)
Leucine
30.4
52.6
Isoleucine
30.9
53.4
Valine
30.7
53.2
Creatinine
32.2
55.8
Summary
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CRRT clearances of BCAA are similar to those
of other small molecules
CVVHDF is effective in acutely lowering serum
leucine levels during acute decompensation in
MSUD
CVVHDF is a safe therapy for decompensation
in MSUD when complicated by cerebral edema