Intravenous N‐acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: A placebo‐controlled clinical trial
dc.contributor.author | Squires, Robert H. | en_US |
dc.contributor.author | Dhawan, Anil | en_US |
dc.contributor.author | Alonso, Estella | en_US |
dc.contributor.author | Narkewicz, Michael R. | en_US |
dc.contributor.author | Shneider, Benjamin L. | en_US |
dc.contributor.author | Rodriguez‐baez, Norberto | en_US |
dc.contributor.author | Olio, Dominic Dell | en_US |
dc.contributor.author | Karpen, Saul | en_US |
dc.contributor.author | Bucuvalas, John | en_US |
dc.contributor.author | Lobritto, Steven | en_US |
dc.contributor.author | Rand, Elizabeth | en_US |
dc.contributor.author | Rosenthal, Philip | en_US |
dc.contributor.author | Horslen, Simon | en_US |
dc.contributor.author | Ng, Vicky | en_US |
dc.contributor.author | Subbarao, Girish | en_US |
dc.contributor.author | Kerkar, Nanda | en_US |
dc.contributor.author | Rudnick, David | en_US |
dc.contributor.author | Lopez, M. James | en_US |
dc.contributor.author | Schwarz, Kathleen | en_US |
dc.contributor.author | Romero, Rene | en_US |
dc.contributor.author | Elisofon, Scott | en_US |
dc.contributor.author | Doo, Edward | en_US |
dc.contributor.author | Robuck, Patricia R. | en_US |
dc.contributor.author | Lawlor, Sharon | en_US |
dc.contributor.author | Belle, Steven H. | en_US |
dc.date.accessioned | 2013-05-02T19:35:10Z | |
dc.date.available | 2014-05-23T15:04:20Z | en_US |
dc.date.issued | 2013-04 | en_US |
dc.identifier.citation | Squires, Robert H.; Dhawan, Anil; Alonso, Estella; Narkewicz, Michael R.; Shneider, Benjamin L.; Rodriguez‐baez, Norberto ; Olio, Dominic Dell; Karpen, Saul; Bucuvalas, John; Lobritto, Steven; Rand, Elizabeth; Rosenthal, Philip; Horslen, Simon; Ng, Vicky; Subbarao, Girish; Kerkar, Nanda; Rudnick, David; Lopez, M. James; Schwarz, Kathleen; Romero, Rene; Elisofon, Scott; Doo, Edward; Robuck, Patricia R.; Lawlor, Sharon; Belle, Steven H. (2013). "Intravenous Nâ acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: A placeboâ controlled clinical trial ." Hepatology 57(4): 1542-1549. <http://hdl.handle.net/2027.42/97484> | en_US |
dc.identifier.issn | 0270-9139 | en_US |
dc.identifier.issn | 1527-3350 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/97484 | |
dc.description.abstract | N‐acetylcysteine (NAC) was found to improve transplantation‐free survival in only those adults with nonacetaminophen (non‐APAP) acute liver failure (ALF) and grade 1‐2 hepatic encephalopathy (HE). Because non‐APAP ALF differs significantly between children and adults, the Pediatric Acute Liver Failure (PALF) Study Group evaluated NAC in non‐APAP PALF. Children from birth through age 17 years with non‐APAP ALF enrolled in the PALF registry were eligible to enter an adaptively allocated, doubly masked, placebo‐controlled trial using a continuous intravenous infusion of NAC (150 mg/kg/day in 5% dextrose in water [D5W]) or placebo (D5W) for up to 7 days. The primary outcome was 1‐year survival. Secondary outcomes included liver transplantation‐free survival, liver transplantation (LTx), length of intensive care unit (ICU) and hospital stays, organ system failure, and maximum HE score. A total of 184 participants were enrolled in the trial with 92 in each arm. The 1‐year survival did not differ significantly ( P = 0.19) between the NAC (73%) and placebo (82%) treatment groups. The 1‐year LTx‐free survival was significantly lower ( P = 0.03) in those who received NAC (35%) than those who received placebo (53%), particularly, but not significantly so, among those less than 2 years old with HE grade 0‐1 (NAC 25%; placebo 60%; P = 0.0493). There were no significant differences between treatment arms for hospital or ICU length of stay, organ systems failing, or highest recorded grade of HE. Conclusion : NAC did not improve 1‐year survival in non‐APAP PALF. One‐year LTx‐free survival was significantly lower with NAC, particularly among those <2 years old. These results do not support broad use of NAC in non‐APAP PALF and emphasizes the importance of conducting controlled pediatric drug trials, regardless of results in adults. (H EPATOLOGY 2013) | en_US |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.title | Intravenous N‐acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: A placebo‐controlled clinical trial | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor, MI | en_US |
dc.contributor.affiliationother | Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA | en_US |
dc.contributor.affiliationother | Kings College, London, UK | en_US |
dc.contributor.affiliationother | Northwestern University, Evanston, IL | en_US |
dc.contributor.affiliationother | University of Colorado SOM and Children's Hospital Colorado, Boulder, CO | en_US |
dc.contributor.affiliationother | University of Texas Southwestern Medical Center, Dallas, TX | en_US |
dc.contributor.affiliationother | Birmingham Children's Hospital, Birmingham, UK | en_US |
dc.contributor.affiliationother | Baylor College of Medicine, Houston, TX | en_US |
dc.contributor.affiliationother | Cincinnati Children's Hospital, Cincinnati, OH | en_US |
dc.contributor.affiliationother | Columbia University, New York, NY | en_US |
dc.contributor.affiliationother | Children's Hospital of Philadelphia, Philadelphia, PA | en_US |
dc.contributor.affiliationother | University of California‐San Francisco, San Francisco, CA | en_US |
dc.contributor.affiliationother | University of Washington, Seattle, WA | en_US |
dc.contributor.affiliationother | Hospital for Sick Children, Toronto, Canada | en_US |
dc.contributor.affiliationother | Indiana University, Indianapolis, IN | en_US |
dc.contributor.affiliationother | Mt. Sinai Medical Center, New York, NY | en_US |
dc.contributor.affiliationother | Washington University, St. Louis, MO | en_US |
dc.contributor.affiliationother | Johns Hopkins University, Baltimore, MD | en_US |
dc.contributor.affiliationother | Emory University, Atlanta, GA | en_US |
dc.contributor.affiliationother | Children's Hospital of Boston, Boston, MA | en_US |
dc.contributor.affiliationother | National Institutes of Health, National Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, MD | en_US |
dc.contributor.affiliationother | Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA | en_US |
dc.contributor.affiliationother | Emory‐Children's Center, 2015 Uppergate Dr. NE, Atlanta, GA 30322‐1015 | en_US |
dc.contributor.affiliationother | Professor of Pediatrics, University of Pittsburgh, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Ave., Pittsburgh, PA 15224 | en_US |
dc.identifier.pmid | 22886633 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/97484/1/26001_ftp.pdf | |
dc.identifier.doi | 10.1002/hep.26001 | en_US |
dc.identifier.source | Hepatology | en_US |
dc.identifier.citedreference | Vodovotz Y. Translational systems biology of inflammation and healing. Wound Repair Regen 2010; 18: 3 ‐ 7. | en_US |
dc.identifier.citedreference | Wood JH, Partrick DA, Johnston RB Jr. The inflammatory response to injury in children. Curr Opin Pediatr 2010; 22: 315 ‐ 320. | en_US |
dc.identifier.citedreference | Masubuchi Y, Nakayama J, Sadakata Y. Protective effects of exogenous glutathione and related thiol compounds against drug‐induced liver injury. Biol Pharm Bull 2011; 34: 366 ‐ 370. | en_US |
dc.identifier.citedreference | Mi Q, Li NY, Ziraldo C, Ghuma A, Mikheev M, Squires R, et al. Translational systems biology of inflammation: potential applications to personalized medicine. Per Med 2010; 7: 549 ‐ 559. | en_US |
dc.identifier.citedreference | Antoniades CG, Berry PA, Wendon JA, Vergani D. The importance of immune dysfunction in determining outcome in acute liver failure. J Hepatol 2008; 49: 845 ‐ 861. | en_US |
dc.identifier.citedreference | Modig J, Sandin R. Haematological, physiological and survival data in a porcine model of adult respiratory distress syndrome induced by endotoxaemia. Effects of treatment with N‐acetylcysteine. Acta Chir Scand 1988; 154: 169 ‐ 177. | en_US |
dc.identifier.citedreference | Peristeris P, Clark BD, Gatti S, Faggioni R, Mantovani A, Mengozzi M, et al. N‐acetylcysteine and glutathione as inhibitors of tumor necrosis factor production. Cell Immunol 1992; 140: 390 ‐ 399. | en_US |
dc.identifier.citedreference | Rank N, Michel C, Haertel C, Lenhart A, Welte M, Meier‐Hellmann A, et al. N‐acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double‐blind study. Crit Care Med 2000; 28: 3799 ‐ 3807. | en_US |
dc.identifier.citedreference | Khandelwal N, James LP, Sanders C, Larson AM, Lee WM. Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure. HEPATOLOGY 2011; 53: 567 ‐ 576. | en_US |
dc.identifier.citedreference | Yazigi N, Tial G, Filipovich A, Bucuvalas JC. Natural killer dysfunction in pediatric acute liver failure. Am J Transplant 2008; 8 ( Supp s2 ): 327A. | en_US |
dc.identifier.citedreference | Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002; 137: 947 ‐ 954. | en_US |
dc.identifier.citedreference | Lee WM. Etiologies of acute liver failure. Semin Liver Dis 2008; 28: 142 ‐ 152. | en_US |
dc.identifier.citedreference | James LP, Alonso EM, Hynan LS, Hinson JA, Davern TJ, Lee WM, et al. Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause. Pediatrics 2006; 118: e676 ‐ 81. | en_US |
dc.identifier.citedreference | Davern TJ, 2nd, James LP, Hinson JA, Polson J, Larson AM, Fontana RJ, et al. Measurement of serum acetaminophen‐protein adducts in patients with acute liver failure. Gastroenterology 2006; 130: 687 ‐ 694. | en_US |
dc.identifier.citedreference | O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics 1979; 35: 549 ‐ 556. | en_US |
dc.identifier.citedreference | Cox DR. Regression models and life tables. J R Stat Soc Ser B 1972; 34: 187 ‐ 220. | en_US |
dc.identifier.citedreference | Walsh TS, Lee A. N‐acetylcysteine administration in the critically ill. Intensive Care Med 1999; 25: 432 ‐ 434. | en_US |
dc.identifier.citedreference | Molnar Z, Shearer E, Lowe D. N‐Acetylcysteine treatment to prevent the progression of multisystem organ failure: a prospective, randomized, placebo‐controlled study. Crit Care Med 1999; 27: 1100 ‐ 1104. | en_US |
dc.identifier.citedreference | Durand P, Debray D, Mandel R, Baujard C, Branchereau S, Gauthier F, et al. Acute liver failure in infancy: a 14‐year experience of a pediatric liver transplantation center. J Pediatr 2001; 139: 871 ‐ 876. | en_US |
dc.identifier.citedreference | Baliga P, Alvarez S, Lindblad A, Zeng L. Posttransplant survival in pediatric fulminant hepatic failure: the SPLIT experience. Liver Transpl 2004; 10: 1364 ‐ 1371. | en_US |
dc.identifier.citedreference | Dhawan A. Etiology and prognosis of acute liver failure in children. Liver Transpl 2008; 14 ( Suppl 2 ): S80 ‐ S84. | en_US |
dc.identifier.citedreference | Squires RH Jr, Shneider BL, Bucuvalas J, Alonso E, Sokol RJ, Narkewicz MR, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr 2006; 148: 652 ‐ 658. | en_US |
dc.identifier.citedreference | Polson J, Lee WM. AASLD position paper: the management of acute liver failure. HEPATOLOGY 2005; 41: 1179 ‐ 1197. | en_US |
dc.identifier.citedreference | Squires RH Jr. Acute liver failure in children. Semin Liver Dis 2008; 28: 153 ‐ 166. | en_US |
dc.identifier.citedreference | Rivera‐Penera T, Moreno J, Skaff C, McDiarmid S, Vargas J, Ament ME. Delayed encephalopathy in fulminant hepatic failure in the pediatric population and the role of liver transplantation. J Pediatr Gastroenterol Nutr 1997; 24: 128 ‐ 134. | en_US |
dc.identifier.citedreference | Baker A, Alonso ME, Aw MM, Ciocca M, Porta G, Rosenthal P. Hepatic failure and liver transplant: Working Group report of the second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2004; 39 ( Suppl 2 ): S632 ‐ S639. | en_US |
dc.identifier.citedreference | Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz RT, Larson AM, et al. Intravenous N‐acetylcysteine improves transplant‐free survival in early stage non‐acetaminophen acute liver failure. Gastroenterology 2009; 137: 856 ‐ 864, 64 e1. | en_US |
dc.identifier.citedreference | Harrison PM, Wendon JA, Gimson AE, Alexander GJ, Williams R. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med 1991; 324: 1852 ‐ 1857. | en_US |
dc.identifier.citedreference | Prescott LF, Illingworth RN, Critchley JA, Stewart MJ, Adam RD, Proudfoot AT. Intravenous N‐acetylcystine: the treatment of choice for paracetamol poisoning. Br Med J 1979; 2: 1097 ‐ 1100. | en_US |
dc.identifier.citedreference | Marzullo L. An update of N‐acetylcysteine treatment for acute acetaminophen toxicity in children. Curr Opin Pediatr 2005; 17: 239 ‐ 245. | en_US |
dc.identifier.citedreference | Sklar GE, Subramaniam M. Acetylcysteine treatment for non‐acetaminophen‐induced acute liver failure. Ann Pharmacother 2004; 38: 498 ‐ 500. | en_US |
dc.identifier.citedreference | Kortsalioudaki C, Taylor RM, Cheeseman P, Bansal S, Mieli‐Vergani G, Dhawan A. Safety and efficacy of N‐acetylcysteine in children with non‐acetaminophen‐induced acute liver failure. Liver Transpl 2008; 14: 25 ‐ 30. | en_US |
dc.identifier.citedreference | Soltys KA, Mazariegos GV, Squires RH, Sindhi RK, Anand R. Late graft loss or death in pediatric liver transplantation: an analysis of the SPLIT database. Am J Transplant 2007; 7: 2165 ‐ 2171. | en_US |
dc.identifier.citedreference | Zhang H, Limphong P, Pieper J, Liu Q, Rodesch CK, Christians E, et al. Glutathione‐dependent reductive stress triggers mitochondrial oxidation and cytotoxicity. FASEB J 2012; 26: 1442 ‐ 1451. | en_US |
dc.identifier.citedreference | Yang R, Miki K, He X, Killeen ME, Fink MP. Prolonged treatment with N‐acetylcystine delays liver recovery from acetaminophen hepatotoxicity. Crit Care 2009; 13: R55. | en_US |
dc.identifier.citedreference | Wuyts WA, Vanaudenaerde BM, Dupont LJ, Demedts MG, Verleden GM. N‐acetylcysteine reduces chemokine release via inhibition of p38 MAPK in human airway smooth muscle cells. Eur Respir J 2003; 22: 43 ‐ 49. | en_US |
dc.identifier.citedreference | Flanagan RJ. The role of acetylcysteine in clinical toxicology. Med Toxicol 1987; 2: 93 ‐ 104. | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.