Transcript IMPLEMENTATION & USE of CRRT in PEDIATRIC INTOXICATIONS

METABOLIC DERANGEMENTS,
HEPATIC FAILURE & PCRRT
Patrick D. Brophy MD
University of Michigan
Pediatric Nephrology
Objectives
Metabolic Disorders and Amenability to CRRT
Hyperammonemia
– Prescription
– Fine points of care
– Combination therapy
Considerations of CRRT in Hepatic Failure
– Hepatic Insufficiency
– Role of CRRT-bridge to transplant
– Liver support
Metabolic Disorders
Multiple metabolic disorders have been
described that are amenable to various forms of
RRT.
– Maple Syrup Urine Disease (BCAA—Build up lead to
cerebral edema)
Puliyanda et.al. 2002:17:239-242
Jouvet et.al. 2001:27:1798-1806
– Urea Cycle Defects- hyperammonemia
– Organic Acidemias (accumulation of Acyl Co-A esterssecondary inhibition of urea cycle enzymes)
Hyperammonemia- clinical
Most Cases develop in neonatal period
– Feeding refusal/intolerance
– Vomiting
– Abnormal muscle tone
– Lethargy
– Seizures
– Coma
– Death
Hyperammonemia-etiology
Urea Cycle Defects
– Carbamyl Phosphate Synthetase (CPS)
– N-acetylglutamate synthetase
– Ornithine Transcarbamylase (OTC)
– Argininosuccinate synthetase (ASA)
– Argininosuccinate Lyase (AL)
– Arginase
Hyperammonemia-etiology
Organic Acidemias
– Propionic Acidemia
– Methylmalonic Acidemia
– Isovaleric Acidemia
– Ketothiolase Acidemia
– Multiple carboxylase deficiency
– Glutaric Acidemia Type II
– 3-Hydroxy-3-methylglutaric acidemia
Hyperammonemia-etiology
Other
– Lysinuric protein intolerance
– Hyperornithinemia-HyperammonemiaHomocitrullinemia
– Periodic Hyperlysinuria with
Hyperammonemia
– Transient Hyperammonemia of the Newborn
(THN)
Flow Diagram to Evaluate
Hyperammonemia
Sig
incr
Plasma amino citrulline
acids
citrullinemia
Nl.
Nl. Or sl.
increased
ASA
Incr.
low
urine
Orotic acid
THN
Low or
absent
Incr.
ASA
CPS
OTC
Treatment of
HyperAmmonemia
Aim: rapid therapy to prevent permanent brain
damage or death
Prevent further catabolism by providing
adequate calories, fluids and electrolytes
Minimize protein intake
Provide alternate pathways for ammonia
removal
– Sodium benzoate
– Sodium phenylacetate
– Arginine supplementation
Mode of RRT
PD
– Some clearance-but less than optimal
– Too long for optimal removal, may not be able
to keep place with NH4 generation
Hemodialysis
– looks like a good place to start
Hemofiltration
– a great way to go home at night
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
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
1
2
3
4
5
Time
(Hrs)
10
11
17
Hyperammonemia
(McBryde et al, paper in progress)
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
Hyperammonemia
(McBryde et al, paper in progress)
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
Hyperammonemia
(McBryde et al, JASN 2000)
Outcome
– 12/18 patients survived
– 2/12 continued to be medication and RRT
dependent
Neonatal Hyperammonemia
Picca et.al Pediatr Nephrol 2001:16:862867
Reviewed prognostic indicators
– CAVHD N=4
– CVVHD N=4
– HD N=2
Neonatal Hyperammonemia
Findings:
– NH4 levels decreased with all modalities
(1419 to 114 micromoles/L) with CVVHD
giving the highest NH4 clearance & HD giving
best NH4 extraction (hemodynamic instability)
– 5 had good outcome/5 had poor (not specific
to modality) primarily associated with Coma
duration < 33 hrs (CNS delay/Death)
– Early intervention is key!
Hepatic Failure
Definition: Loss of functional liver cell
mass below a critical level results in liver
failure (acute or complicating a chronic
liver disease)
Results in: hepatic encephalopathy &
Coma, Jaundice, cholestasis, ascites,
bleeding, renal failure, death
Hepatic Failure
Production of Endogenous Toxins & Drug
metabolic Failure
Bile Acids, Bilirubin, Prostacyclins, NO, Toxic fatty
acids, Thiols, Indol-phenol metabolites
These toxins cause further necrosis/apoptosis and
a vicious cycle
Detrimental to renal, brain and bone
marrow function; results in poor vascular
tone
Hepatic Failure- Role of CRRT
Objective:
– CRRT support can buy time, help prevent
further deterioration/complication and allow
Potential recovery of functional critical cell mass
Management of precipitating events that lead to
decompensated disease
Bridge to liver transplantation
CVVHD for NH4 Bridge to
Hepatic Transplantation
800
700
micromoles/L
NH4
600
Successful Liver
Transplantation
500
400
300
200
100
0
1
2
4
6
8
Time
(days)
10
12
14
16
Hepatic Failure-Role of CRRT
CRRT may not improve overall outcome of
liver failure- but does provide stability and
prolongs life in the setting of hepatic failure
Primary applications include use in control
of elevated ICP in fulminant hepatic failure
(Davenport Lancet 1991:2:1604)
Management of Cerebral Edema through
middle molecule removal- reversal of
Coma (Matsubara et.al. Crit Care Med1990:8:1331)
Hepatic Failure-Role of CRRT
Improved Cardiac Stability also noted in
patients with Hepatic & Renal Failure
– IHD vs CAVH vs CAVHD compared
– Noted a decrease in Cardiac Index of ~ 15%
in HD treated patients (also increase in ICP ~
45% in HD)
– CAVHD/CVVHD- cardiac index decreased by
~3% and no change noted in ICP
–
Davenport et.al. Crit Care Med 1993: 21:328-338
Hepatic Failure-Role of CRRT
Others:
– Fluid Balance
– Nutritional support
– Uremic Clearance
Future Horizons
Currently Undergoing Clinical Evaluation
– Liver Assist Devices – several companies (ie MARSMolecular Adsorbents Recycling System)
– Both Biological and non- biological systems (ie
porcine hepatocytes/hemodialysis filters/hemofilters
– Engage principles of both convection and diffusion (ie
albumin dialysate) and anionic trapping with charcoal
regeneration chambers for albumin
– Huge potential Impact on critical care &
Transplantation!
(p. brophy)
ACKNOWLEDGEMENTS
– MELISSA GREGORY
– ANDREE GARDNER
– JOHN GARDNER
– THERESA MOTTES
– TIM KUDELKA
– LAURA DORSEY & BETSY ADAMS