case study in rrt in in born error of metabolism timothy e. bunchman pediatric nephrology &...
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Case Study in RRT in In Born Error of Metabolism
Timothy E. Bunchman
Pediatric Nephrology & Transplantation
VCU School of Medicine
www.pcrrt.com
In Born Error of Metabolism
• 2.9 kg infant presents at 48 hours of life with lethargy.
• Child is afebrile, BP is 75/40, HR of 130 BPM, RR of 50 BPM
• On exam “floppy” infant with poor neurologic tone
In Born Error of Metabolism
• Normal laboratory data shows of – H/H of 15/45; Cr of 0.9 mg/dl (maternal) , K of
4.3 mq/dl, Ca of 9.5 mg/dl, Phos of 6.0 mg/dl (nl)
• Abnormal laboratory data shows– CO2 of 14 mg/dl and a ammonia of 1533
micromls/l (nl < 40)
OA UCD
Lethargy/coma 100% 100%
Axial hypotonia 100% 100%
Abnormal movements 78% 81%
Feeding difficulties/vomiting 78% 68%
Dyspnea/tachipnea 57% 56%
30 newborns at OBG:OA 14 pts : 8 PA, 4 MMA, 1 HMG, 1 IVA
UCD 16 pts : 3 CPS, 4 OTC, 5 AL, 3 AS,1 HHH
Dionisi-Vici et al. J Inher Met Dis 2003
INCIDENCE• Overall: 1:9160• Organic Acidurias: 1:21422• Urea Cycle Defects: 1:41506• Fatty Acids Oxidation Defects: 1:91599
AGE OF ONSETNeonate: 40%Infant: 30%Child: 20%Adult: 5-10% (?) Dionisi-Vici et al, J Pediatrics, 2002.
“SMALL MOLECULES” DISEASES INDUCING CONGENITAL HYPERAMMONEMIA.
• hyperammonemia is extremely toxic to the brain (per se or through intracellular excess glutamine formation) causing astrocyte swelling, brain edema, coma, death or severe disability,
thus:• emergency treatment has to be started
even before having a precise diagnosis since: • prognosis mainly depends on coma
duration
KEY POINTS FACING TO A HYPERAMMONEMIC NEWBORN
PROGNOSIS OF HYPERAMMONEMIC COMAIS DEPENDENT ON COMA DURATION.
from Msall M et al, N Eng J Med 1984.
TREATMENT of SEVERE NEONATAL HYPERAMMONEMIA
? IMMEDIATE MEDICAL THERAPY
NO RESPONSE RESPONSE
DIALYSIS
MAINTAINANCE MEDICAL THERAPY + REFEEDING
IMMEDIATE DIALYSIS+ MEDICAL THERAPY
MAINTAINANCE MEDICAL THERAPY
+REFEEDING
Pharmacological treatmentbefore having a diagnosis
AIMSprecursors catabolism anabolism
• stop protein • caloric intake 100 kcal/kg• insulin …and
endogenous depuration• arginine 250 mg/Kg/2 hrs + 250 - 500 mg/Kg/day • carnitine 1g i.v. bolus 250 - 500 mg/Kg/day • vitamins (B12 1 mg,biotin 5-15 mg)• benzoate 250 mg/Kg/2 hrs + 250 mg/Kg/day or
peroral phenylbutyrate (only after UCD diagnosis)
Picca et al. Ped Nephrol 2001
time
urea
PD
HD
CRRT
[C]generation rate clearance
ammonium?
RRT intervention
• Child was electively intubated for airway protection
• Foley catheter placed for use for urine collection and accurate I/O
• Na Pheyacetate, Na Benzoate, Arginine Cl, Carnitine were all begun once urine and plasma amino and organic acids obtained.
RRT intervention
• A 7 Fr 10 cm MedComp “softline” duel lumen vascular access placed
• HD begun using a blood prime and a Phoenix (Gambro)– BRF of 70 mls/min (~ 22 mls/kg/min)– DFR of 500 mls/min with a physiologic K and
Phos bath• Ammonia levels collected at 1 hr intervals
Ammonia Clearance
0
200
400
600
800
1000
1200
1400
1600
1800
1 2 3 5 7 11 15 17 19
HD Begins
Time (hours)
Am
mon
ia (
mic
rom
ol/l
)
HD Ends
RRT intervention
• At 2 hours of HD the ammonia was ~ 200 micromls/l and HD was exchanged for CVVHDF (Gambro Prisma M 60 membrane) using the same vascular access
• A blood prime bypass maneuver was performed• Replacement rate of 2 liters per hour and a dialysate
rate of 1 liter per hour• (HD clearance was 30 l/hr now decreased to 3 l/hr)
Ammonia Clearance
0
200
400
600
800
1000
1200
1400
1600
1800
1 2 3 5 7 11 15 17 19
HD Begins
Time (hours)
Am
mon
ia (
mic
rom
ol/l
)
HD Ends HF BeginsHF Ends
RRT intervention
• A few practical comments• Ammonia is non-osmolar so no risk of
dialysate disequilibrium exists • In Born Error of metabolism infants appear
to be polyuric so keeping them intubated and keeping them “wet” is important
TREATMENT of NEONATAL HYPERAMMONEMIA
HOSPITALIZATION
DIAGNOSISPHARMACOLOGICAL
TREATMENT
DIALYSIS
NO RESPONSE RESPONSE
RE-FEEDING
NH
4p (
per
cen
t o
f in
itia
l val
ue)
Time (hours)0 5 10 15 20 25
0
20
40
60
80
100
120
140
160
180 PD patients
0 10 20 30 40 50 60
0
20
40
60
80
100 CAVHD patients
0 10 20 30 40 50 600
20
40
60
80
100 HD patients
TIME (hours)
0 10 20 30 40 50 60
0
20
40
60
80
100 CVVHD patients
NH
4p (
per
cen
t o
f in
itia
l val
ue)
Picca et al. Ped Nephrol 2001
AMMONIUM CLEARANCE AND FILTRATION FRACTION USING DIFFERENT DIALYSIS MODALITIES.
Patient
(n)
Type of
Dialysis
Qb
(ml/min)
Qd
(ml/min)
Ammonium Clearance (ml/min/kg
BW)
Ammonium Filtration Fraction
(%)
3
CAVHD
10-20
8.3 (0.5 l/h)
0.87-0.97
12.5-14.3
3
CVVHD
20-40
33.3-83.3 (2-5 l/h)
2.65-6.80
53.0-58.0
2
HD
10-15
500
3.95-5.37
95.0-96.0
Picca et al., 2001
DIALYSIS IN NEONATAL HYPERAMMONEMIA.Data of the literature
Type of dialysis (No of pts.)
NH4 in vivo clearance (ml/min/kg
BW)
Survivors Pts. with
neurological improvement
Hypotensive pts. (%)
Peritoneal dialysis (n=16)
0.71 0SD
9 (56%)
3 (18%) 0-16%
Hemodialysis (n=17) 6.4 3SD 12 (70%) 10 (62%) 0-63%
Continuous hemofiltration
(n=6) 1.2 0.1SD
4 (67%)
3 (50%)
0-25%
Continuous hemodialysis
(n=16) 4.4 1SD
13 (81%)
10 (62%)
0-19%
From : Siegel 73, Wiegand 80, Ring 92, Rutledge 90, Sperl 90, Thompson 91, Falk 94,
Gregory 94, Sadowsky 96, Picca 97, Schaefer 99, Picca 01, Chan 02, Rajpoot 04, McBryde 04.
Drug clearance
• Where as ammonia is a small molecular wt compound Na Phenylacetate and Na Benzoate are also small, non protein bound
• So will your therapy clear the drug?
Solute Clearance in I E M
0
200
400
600
800
1000
1200
1400
PrefilterHD
Postfilter HD
PrefilterHF
Postfilter HF
AmmoniaNaPhenyNaBenz
Conclusion
• Hyperammonemia of the new born is a medical and dialytic emergency
• Immediate institution of medical therapy is needed and a early decision of RRT institution is needed
Conclusion
• PD has little to offer in this disease• HD is the preferred modality and
prevention of the rebound can occur by transitioning HD to HF
• With RRT monitor K and Phos closely to avoid loss of these electrolytes during the RRT
