Safety and efficacy of N-acetylcysteine in children with non-acetaminophen-induced acute liver failure.
Acute liver failure (ALF) carries a high mortality in children. N-acetylcysteine (NAC), an antioxidant agent that replenishes mitochondrial and cytosolic glutathione stores, has been used in the treatment of late acetaminophen-induced ALF and non-acetaminophen-induced ALF. In our unit, NAC was introduced as additional treatment for non-acetaminophen-induced ALF in 1995. The aim of this study was to evaluate the safety and efficacy of NAC in children with ALF not caused by acetaminophen poisoning. A retrospective review of medical records of 170 children presenting with nonacetaminophen-induced ALF between 1989 and 2004 was undertaken. ALF was defined as either international normalized ratio of prothrombin time (INR) > 2 and abnormal liver function or INR >1.5 with encephalopathy and abnormal liver function. Children were divided into the following groups: Group 1 (1989-1994), standard care (n = 59; 34 [58%] male; median age 2.03 yr, range 0.003-15.8 yr); and Group 2 (1995-2004), standard care and NAC administration (n = 111; 57 [51%] male; median age 3.51 yr, range 0.005-17.4 yr). NAC was administered as a continuous infusion (100 mg/kg/24 hours) until INR < 1.4, death, or liver transplantation (LT). The median duration of NAC administration in Group 2 was 5 (range, 1-77) days. Complications were noted in 8 (10.8%) children: rash in 3, arrhythmia in 3, and dizziness and peripheral edema in 1. One child had an allergic reaction (bronchospasm) and NAC was stopped. A total of 41 (71%) children in Group 1 vs. 85 (77%) in Group 2 required admission to intensive care, P = not significant (ns). The length of intensive care stay was 6 (range, 1-58) days in Group 1 vs. 5 (range, 1-68) days in Group 2, P = ns and length of hospital stay was 25 (range, 1-264) days vs. 19 (range, 1-201) days, P = 0.05. The 10-yr actuarial survival was 50% in Group 1 compared to 75% in Group 2, P = 0.009. Survival with native liver occurred in 13 (22%) in Group 1 vs. 48 (43%) in Group 2, P = 0.005; 15 (25%) in Group 1 died without transplant vs. 21 (19%) in Group 2, P = ns; and LT was performed in 32 (54%) vs. 42 (38%), P = ns. Death after transplantation occurred in 15 (39%) in Group 1 vs. 8 (16%) in Group 2, P = 0.02. In conclusion, NAC is safe in non-acetaminophen-induced ALF. In this retrospective study NAC was associated with a shorter length of hospital stay, higher incidence of native liver recovery without transplantation, and better survival after transplantation.
Kortsalioudaki
Christine
C
Paediatric Liver Centre, King's College London School of Medicine at King's College Hospital, London, UK.
Taylor
Rachel M
RM
Cheeseman
Paul
P
Bansal
Sanjay
S
Mieli-Vergani
Giorgina
G
Dhawan
Anil
A
D000082:Acetaminophen; D000111:Acetylcysteine / Q000008:administration & dosage*; D000293:Adolescent; D018712:Analgesics, Non-Narcotic; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D017114:Liver Failure, Acute / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008297:Male; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
D018712:Analgesics, Non-Narcotic; D016166:Free Radical Scavengers; D000082:Acetaminophen; D000111:Acetylcysteine