Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: A placebo-controlled clinical trial

Autor: Girish Subbarao, Edward Doo, Vicky L. Ng, Robert H. Squires, Dominic Dell Olio, Elizabeth B. Rand, Nanda Kerkar, Steven H. Belle, Anil Dhawan, Kathleen B. Schwarz, Benjamin L. Shneider, Saul J. Karpen, Scott A. Elisofon, Michael R. Narkewicz, Norberto Rodriguez-Baez, Simon Horslen, Rene Romero, Estella M. Alonso, Sharon Lawlor, Patricia R. Robuck, Philip J. Rosenthal, M. James Lopez, Steven J. Lobritto, John C. Bucuvalas, David A. Rudnick
Rok vydání: 2013
Předmět:
Male
medicine.medical_treatment
Autoimmune hepatitis
Medical Biochemistry and Metabolomics
Liver transplantation
Severity of Illness Index
Gastroenterology
Oral and gastrointestinal
law.invention
Randomized controlled trial
law
Medicine
Infusions
Intravenous
Child
Hepatic encephalopathy
Pediatric
Liver Disease
digestive
oral
and skin physiology
Free Radical Scavengers
Pediatric Acute Liver Failure Study Group
Survival Rate
Treatment Outcome
Child
Preschool
6.1 Pharmaceuticals
Female
Intravenous
medicine.drug
Infusions
medicine.medical_specialty
Adolescent
Clinical Trials and Supportive Activities
Clinical Sciences
Immunology
Acute
Placebo
Double-Blind Method
Clinical Research
Internal medicine
Humans
Preschool
Gastroenterology & Hepatology
Hepatology
business.industry
Infant
Newborn
Oxygen transport
Infant
Evaluation of treatments and therapeutic interventions
Liver Failure
Acute
Newborn
medicine.disease
Acetylcysteine
Liver Transplantation
Acetaminophen
Surgery
Clinical trial
Hepatic Encephalopathy
Digestive Diseases
business
Liver Failure
Zdroj: Hepatology (Baltimore, Md.), vol 57, iss 4
ISSN: 0270-9139
Popis: Pediatric acute liver failure (PALF) is a rare and devastating syndrome in which previously healthy children rapidly lose hepatic function due to a variety of causes and become critically ill within days.(1–2) Management is largely supportive unless conditions that are amenable to directed therapy, such as acute acetaminophen toxicity, herpes virus, and potentially treatable causes such as Wilson disease and autoimmune hepatitis are identified and treated.(3–4) Early referral to a liver transplantation (LTx) center, improvements in medical management and LTx are associated with improved survival in PALF.(5) Long term outcomes following LTx for PALF are poor compared to other indications for LTx(6-7), hence the need to identify treatments that improve survival. N-acetylcysteine (NAC), used for treating acute acetaminophen (APAP) toxicity, has been used to treat non-APAP PALF but has not been rigorously tested in a multi-center placebo-controlled clinical trial in children.(8–9) NAC replenishes mitochondrial and cytosolic glutathione stores and is the treatment of choice for acute APAP toxicity.(10–11) Intravenous NAC became incorporated into the general management of acute liver failure in a number of sites in Europe and North America following a small uncontrolled study suggesting improved cardiovascular hemodynamics and oxygen transport in both APAP and non-APAP liver failure in adults.(12) A retrospective single-site review in children affirmed the view that NAC may provide benefit in PALF.(8) In a randomized trial of intravenous NAC versus placebo in adults with non-APAP liver failure, NAC did not improve survival at 21 days.(13) However, an analysis of the secondary outcomes revealed improved LTx-free survival at 3 weeks for those with grade 1–2 hepatic encephalopathy (HE). The primary objective of this study was to determine if a continuous intravenous infusion of NAC for up to seven days would improve overall survival compared to placebo one year following treatment allocation in non-APAP PALF.
Databáze: OpenAIRE
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