Introduction: Hyperammonemia is a life-threatening condition. However, clearance of ammonia via extracorporeal treatment has not been systematically evaluated. Methods: We searched EMBASE and MEDLINE databases. We included all publications reporting ammonia clearance by extracorporeal treatment in adult and pediatric patients with clearance estimated by direct dialysate ammonia measurement or calculated by formula. Two reviewers screened and extracted data independently. Results: We found 1,770 articles with 312 appropriate for assessment and 28 studies meeting eligibility criteria. Most of the studies were case reports. Hyperammonemia was typically secondary to inborn errors of metabolisms in children and to liver failure in adult patients. Ammonia clearance was most commonly reported during continuous renal replacement therapy (CRRT) and appeared to vary markedly from <5 mL/min/m2 to >250 mL/min/m2. When measured during intermittent hemodialysis (IHD), clearance was highest and correlated with blood flow rate (R2 = 0.853; p < 0.001). When measured during CRRT, ammonia clearance could be substantial and correlated with effluent flow rate (EFR; R2 = 0.584; p < 0.001). Neither correlated with ammonia reduction. Peritoneal dialysis (PD) achieved minimal clearance, and other extracorporeal techniques were rarely studied. Conclusions: Extracorporeal ammonia clearance varies widely with sometimes implausible values. Treatment modality, blood flow, and EFR, however, appear to affect such clearance with IHD achieving the highest values, PD achieving minimal values, and CRRT achieving substantial values especially at high EFRs. The role of other techniques remains unclear. These findings can help inform practice and future studies.

1.
Gupta
S
,
Fenves
AZ
,
Hootkins
R
.
The role of RRT in hyperammonemic patients
.
Clin J Am Soc Nephrol
.
2016
;
11
(
10
):
1872
8
. .
2.
Warrillow
SJ
,
Bellomo
R
.
Preventing cerebral oedema in acute liver failure: the case for quadruple-H therapy
.
Anaesth Intensive Care
.
2014
;
42
(
1
):
78
88
. .
3.
Redant
S
,
Beretta-Piccoli
X
,
Mugisha
A
,
Attou
R
,
Kaefer
K
,
De Bels
D
, et al.
Hyperammonemia, the last indication of high-volume hemodiafiltration in adult and children: a structured review
.
Blood Purif
.
2019
;
48
(
4
):
330
5
. .
4.
Raina
R
,
Bedoyan
JK
,
Lichter-Konecki
U
,
Jouvet
P
,
Picca
S
,
Mew
NA
, et al.
Consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy
.
Nat Rev Nephrol
.
2020
;
16
(
8
):
471
82
.
5.
El-Hattab
AW
.
Inborn errors of metabolism
.
Clin Perinatol
.
2015
;
42
(
2
):
413
39
. .
6.
Cordoba
J
,
Blei
AT
,
Mujais
S
.
Determinants of ammonia clearance by hemodialysis
.
Artif Organs
.
1996
;
20
(
7
):
800
3
. .
7.
Schaefer
F
,
Straube
E
,
Oh
J
,
Mehls
O
,
Mayatepek
E
.
Dialysis in neonates with inborn errors of metabolism
.
Nephrol Dial Transplant
.
1999
;
14
(
4
):
910
8
. .
8.
Rajpoot
DK
,
Gargus
JJ
.
Acute hemodialysis for hyperammonemia in small neonates
.
Pediatr Nephrol
.
2004
;
19
(
4
):
390
5
. .
9.
Westrope
C
,
Morris
K
,
Burford
D
,
Morrison
G
.
Continuous hemofiltration in the control of neonatal hyperammonemia: a 10-year experience
.
Pediatr Nephrol
.
2010
;
25
(
9
):
1725
30
. .
10.
Slack
AJ
,
Auzinger
G
,
Willars
C
,
Dew
T
,
Musto
R
,
Corsilli
D
, et al.
Ammonia clearance with haemofiltration in adults with liver disease
.
Liver Int
.
2014
;
34
(
1
):
42
8
. .
11.
Liu
J
,
Lkhagva
E
,
Chung
H-J
,
Kim
H-J
,
Hong
S-T
.
The pharmabiotic approach to treat hyperammonemia
.
Nutrients
.
2018
;
10
(
2
):
140
. .
12.
Wiegand
C
,
Thompson
T
,
Bock
GH
,
Mathis
RK
,
Kjellstrand
CM
,
Mauer
SM
.
The management of life-threatening hyperammonemia: a comparison of several therapeutic modalities
.
J Pediatr
.
1980
;
96
(
1
):
142
4
. .
13.
Ring
E
,
Zobel
G
,
Stöckler
S
.
Clearance of toxic metabolites during therapy for inborn errors of metabolism
.
J Pediatr
.
1990
;
117
(
2 Pt 1
):
349
50
. .
14.
Sperl
W
,
Geiger
R
,
Maurer
H
,
Guggenbichler
JP
.
Continuous arteriovenous haemofiltration in hyperammonaemia of newborn babies
.
Lancet
.
1990
;
336
(
8724
):
1192
3
. .
15.
Heringlake
S
,
Böker
K
,
Manns
M
.
Fatal clinical course of ornithine transcarbamylase deficiency in an adult heterozygous female patient
.
Digestion
.
1997
;
58
(
1
):
83
6
. .
16.
Braun
MC
,
Welch
TR
.
Continuous venovenous hemodiafiltration in the treatment of acute hyperammonemia
.
Am J Nephrol
.
1998
;
18
(
6
):
531
3
. .
17.
Wong
KY
,
Wong
SN
,
Lam
SY
,
Tam
S
,
Tsoi
NS
.
Ammonia clearance by peritoneal dialysis and continuous arteriovenous hemodiafiltration
.
Pediatr Nephrol
.
1998
;
12
(
7
):
589
91
. .
18.
Chen
CY
,
Chen
YC
,
Fang
JT
,
Huang
CC
.
Continuous arteriovenous hemodiafiltration in the acute treatment of hyperammonaemia due to ornithine transcarbamylase deficiency
.
Ren Fail
.
2000
;
22
(
6
):
823
36
. .
19.
Picca
S
,
Dionisi-Vici
C
,
Abeni
D
,
Pastore
A
,
Rizzo
C
,
Orzalesi
M
, et al.
Extracorporeal dialysis in neonatal hyperammonemia: modalities and prognostic indicators
.
Pediatr Nephrol
.
2001
;
16
(
11
):
862
7
. .
20.
Chan
WK
,
But
WM
,
Law
CW
.
Ammonia detoxification by continuous venovenous haemofiltration in an infant with urea cycle defect
.
Hong Kong Med J
.
2002
;
8
(
3
):
207
10
.
21.
Lai
YC
,
Huang
HP
,
Tsai
IJ
,
Tsau
YK
.
High-volume continuous venovenous hemofiltration as an effective therapy for acute management of inborn errors of metabolism in young children
.
Blood Purif
.
2007
;
25
(
4
):
303
8
. .
22.
Arbeiter
AK
,
Kranz
B
,
Wingen
AM
,
Bonzel
KE
,
Dohna-Schwake
C
,
Hanssler
L
, et al.
Continuous venovenous haemodialysis (CVVHD) and continuous peritoneal dialysis (CPD) in the acute management of 21 children with inborn errors of metabolism
.
Nephrol Dial Transplant
.
2010
;
25
(
4
):
1257
65
. .
23.
Falk
MC
,
Knight
JF
,
Roy
LP
,
Wilcken
B
,
Schell
DN
,
O’Connell
AJ
, et al.
Continuous venovenous haemofiltration in the acute treatment of inborn errors of metabolism
.
Pediatr Nephrol
.
1994
;
8
(
3
):
330
3
. .
24.
Bunchman
TE
,
Barletta
GM
,
Winters
JW
,
Gardner
JJ
,
Crumb
TL
,
McBryde
KD
.
Phenylacetate and benzoate clearance in a hyperammonemic infant on sequential hemodialysis and hemofiltration
.
Pediatr Nephrol
.
2007
;
22
(
7
):
1062
5
. .
25.
Kiley
JE
,
Pender
JC
,
Welch
HF
,
Welch
CS
.
Ammonia intoxication treated by hemodialysis
.
N Engl J Med
.
1958
;
259
(
24
):
1156
61
. .
26.
Kaneda
H
,
Haruyama
T
,
Chiba
S
,
Sugai
Y
,
Hirasawa
T
,
Takeuchi
M
, et al.
A patient with recurrent hepatic encephalopathy and chronic renal failure treated successfully with long-term hemodialysis
.
Tohoku J Exp Med
.
1977
;
123
(
3
):
227
34
. .
27.
Watson
AJ
,
Chambers
T
,
Karp
JE
,
Risch
VR
,
Walker
WG
,
Brusilow
SW
.
Transient idiopathic hyperammonaemia in adults
.
Lancet
.
1985
;
2
(
8467
):
1271
4
. .
28.
Rutledge
SL
,
Havens
PL
,
Haymond
MW
,
McLean
RH
,
Kan
JS
,
Brusilow
SW
.
Neonatal hemodialysis: effective therapy for the encephalopathy of inborn errors of metabolism
.
J Pediatr
.
1990
;
116
(
1
):
125
8
. .
29.
Tuchman
M
,
Mauer
SM
,
Holzknecht
RA
,
Summar
ML
,
Vnencak-Jones
CL
.
Prospective versus clinical diagnosis and therapy of acute neonatal hyperammonaemia in two sisters with carbamyl phosphate synthetase deficiency
.
J Inherit Metab Dis
.
1992
;
15
(
2
):
269
77
. .
30.
Pimentel
JL
 Jr
,
Brusilow
SW
,
Mitch
WE
.
Unexpected encephalopathy in chronic renal failure: hyperammonemia complicating acute peritonitis
.
J Am Soc Nephrol
.
1994
;
5
(
4
):
1066
73
.
31.
Elshihabi
I
,
Brzowski
A
,
Kaye
C
,
Kearon
P
.
Efficiency of hemodialysis therapy for a urea cycle defect in a neonate
.
Clin Nephrol
.
1995
;
43
(
3
):
208
9
.
32.
Summar
M
,
Pietsch
J
,
Deshpande
J
,
Schulman
G
.
Effective hemodialysis and hemofiltration driven by an extracorporeal membrane oxygenation pump in infants with hyperammonemia
.
J Pediatr
.
1996
;
128
(
3
):
379
82
. .
33.
Vats
A
,
Kashtan
CE
,
Tuchman
M
,
Mauer
M
.
Hemodialysis catheter placement and recirculation in treatment of hyperammonemia
.
Pediatr Nephrol
.
1998
;
12
(
7
):
592
5
. .
34.
Levesque
R
,
Leblanc
M
,
Cardinal
J
,
Teitlebaum
J
,
Skrobik
Y
,
Lebrun
M
.
Haemodialysis for severe hyperammonaemic coma complicating urinary diversions
.
Nephrol Dial Transplant
.
1999
;
14
:
458
61
.
35.
Lévesque
R
,
Cardinal
J
,
Leblanc
M
.
Haemodialysis for hyperammonaemic encephalopathy
.
Nephrol Dial Transplant
.
2000
;
15
(
7
):
1101
. .
36.
Siegel
NJ
,
Brown
RS
.
Peritoneal clearance of ammonia and creatinine in a neonate
.
J Pediatr
.
1973
;
82
(
6
):
1044
6
. .
37.
Pipili
C
,
Polydorou
A
,
Pantelias
K
,
Korfiatis
P
,
Nikolakopoulos
F
,
Grapsa
E
.
Improvement of hepatic encephalopathy by application of peritoneal dialysis in a patient with non-end-stage renal disease
.
Perit Dial Int
.
2013
;
33
(
2
):
213
6
. .
38.
Krisper
P
,
Haditsch
B
,
Stauber
R
,
Jung
A
,
Stadlbauer
V
,
Trauner
M
, et al.
In vivo quantification of liver dialysis: comparison of albumin dialysis and fractionated plasma separation
.
J Hepatol
.
2005
;
43
(
3
):
451
7
. .
39.
Savy
N
,
Brossier
D
,
Brunel-Guitton
C
,
Ducharme-Crevier
L
,
Du Pont-Thibodeau
G
,
Jouvet
P
.
Acute pediatric hyperammonemia: current diagnosis and management strategies
.
Hepat Med
.
2018
;
10
:
105
15
. .
40.
Kiley
JE
,
Welch
HF
,
Pender
JC
,
Welch
CS
.
Removal of blood ammonia by hemodialysis
.
Proc Soc Exp Biol Med
.
1956
;
91
(
3
):
489
90
. .
41.
Huizenga
JR
,
Tangerman
A
,
Gips
CH
.
Determination of ammonia in biological fluids
.
Ann Clin Biochem
.
1994
;
31
(
Pt 6
):
529
43
. .
42.
Hester
JR
,
Korzun
WJ
,
Mabry
LU
.
Blood ammonia stability revisited
.
Clin Lab Sci
.
2015
;
28
(
3
):
173
7
. .
43.
Hemodialysis Adequacy 2006 Work Group
.
Clinical practice guidelines for hemodialysis adequacy, update 2006
.
Am J Kidney Dis
.
2006
;
48
(
Suppl 1
):
S2
90
.
44.
Uchino
S
,
Fealy
N
,
Baldwin
I
,
Morimatsu
H
,
Bellomo
R
.
Pre-dilution vs. post-dilution during continuous veno-venous hemofiltration: impact on filter life and azotemic control
.
Nephron Clin Pract
.
2003
;
94
(
4
):
c94
8
. .
45.
Clark
WR
,
Henderson
LW
.
Renal versus continuous versus intermittent therapies for removal of uremic toxins
.
Kidney Int Suppl
.
2001
;
78
:
S298
303
. .
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.