Acetaminophen overdose: A 48-hour intravenous N-acetylcysteine treatment protocol

Smilkstein, Martin J.; Bronstein, Alvin C.; Linden, Christopher H.; Augenstein, W Lynn; Kulig, Kenneth; Rumack, Barry H.

doi:10.1016/s0196-0644(05)81352-6

Cited by 246 publications

(135 citation statements)

References 17 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…1,3,21,27 This includes immediate transfer to a unit experienced in the management of this condition and with facilities of LT because it is the only absolute treatment for many causes of this devastating condition. 28,29 As shown in early studies in adults' with acetaminophen-induced ALF 18,[30][31][32][33][34][35] NAC is a safe drug with minor side effects, most of them self-limited or resolved with either the use of antihistamine drugs or by lowering the infusion rate. In the current study adverse effects were mentioned only in 11% of children and NAC was discontinued in 1.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Safety and efficacy of N-acetylcysteine in children with non-acetaminophen-induced acute liver failure

et al. 2007

View full text Add to dashboard Cite

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 nonacetaminopheninduced ALF between 1989 and 2004 was undertaken. ALF was defined as either international normalized ratio of prothrombin time (INR) Ͼ 2 and abnormal liver function or INR Ͼ1.5 with encephalopathy and abnormal liver function. Children were divided into the following groups: Group 1 (1989)(1990)(1991)(1992)(1993)(1994), standard care (n ϭ 59; 34 [58%] male; median age 2.03 yr, range 0.003-15.8 yr); and Group 2 (1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004), standard care and NAC administration (n ϭ 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 Ͻ 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 ϭ 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 ϭ ns and length of hospital stay was 25 (range, 1-264) days vs. 19 (range, 1-201) days, P ϭ 0.05. The 10-yr actuarial survival was 50% in Group 1 compared to 75% in Group 2, P ϭ 0.009. Survival with native liver occurred in 13 (22%) in Group 1 vs. 48 (43%) in Group 2, P ϭ 0.005; 15 (25%) in Group 1 died without transplant vs. 21 (19%) in Group 2, P ϭ ns; and LT was performed in 32 (54%) vs. 42 (38%), P ϭ ns. Death after transplantation occurred in 15 (39%) in Group 1 vs. 8 (16%) in Group 2, P ϭ 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. Liver Transpl 14: [25][26][27][28][29][30] 2008 See Editorial on Page 7Acute liver failure (ALF) in children is a rare but often fatal condition without liver transplantation (LT). [1][2][3] Multiorgan dysfunction in ALF is believed to derive from oxidative stress due to reactive oxygen species and reactive nitrogen species 4 and from immunological injury mediated by cytokines. 5-8 N-acetylcysteine (NAC) is a thiol-containing agent that scavenges free oxygen radicals and replenishes cellular mitochon...

show abstract

Section: Discussionmentioning

confidence: 99%

“…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. Liver Transpl 14: [25][26][27][28][29][30] 2008 …”

mentioning

confidence: 99%

Safety and efficacy of N-acetylcysteine in children with non-acetaminophen-induced acute liver failure

et al. 2007

View full text Add to dashboard Cite

show abstract

“…To conform to past studies, severe liver injury was defined as an AST > 1,000 IU/L. 5,6 For epidemiologic and descriptive purposes, patients were grouped by type of presentation. Single acute ingestion (self-poisoning) was defined as a single supratherapeutic acetaminophen ingestion.…”

Section: Methodsmentioning

confidence: 99%

“…2 Effective protocols have been developed and tested to stratify risk and treat patients who present soon after a single large dose of acetaminophen. [3][4][5][6] Unfortunately, many patients do not present this way. Some present after a delay long enough to metabolize all of the acetaminophen, or after two or more ingestions over several hours, and some present after several days of excessive self-medication for pain or fever.…”

mentioning

confidence: 99%

Population‐based Incidence and Outcome of Acetaminophen Poisoning by Type of Ingestion

Bond

Hite

1999

Academic Emergency Medicine

View full text Add to dashboard Cite

Abstract. Objectives: 1) To determine, in a population-based sample, the observed frequency of acetaminophen overdose-related ED evaluation and hospitalization. 2) To examine the relative frequency of hospitalization by pattern of ingestion, the outcome of each group, and the presence or absence of postulated risk factors. Methods: This study was a 46-month, retrospective chart review of all acetaminophen-related visits, by patients at least 10 years of age, to either of the two hospitals that serve a fourcounty region of central Virginia. Results: Of 636 charts identified for review, only 137 involved acute or chronic acetaminophen overdose. One hundred twenty-six patients presented after an acute ingestion; 122 of these patients gave a history of a single, supratherapeutic ingestion of acetaminophen. Twenty-five patients were hospitalized for treatment. Eighteen of these were treated with N-acetylcysteine (NAC) based on the Rumack-Matthew nomogram; one suffered significant hepatic injury. The other seven presented at least 18 hours after ingestion, with no measurable serum acetaminophen. Two of these suffered significant hepatic injury. Four additional patients presented after multiple ingestions within 24 hours. Three were hospitalized, but none experienced significant injury. Only 11 patients were evaluated for chronic acetaminophen overmedication for pain (more than 6 g/day over a period of more than 24 hours). Four were admitted for treatment; three suffered significant hepatic injury. Thus, the observed incidence of acute acetaminophen ingestion in this region was 21.4/100,000/yr (95% CI = 17.7 to 25.2). The observed incidence of hospitalization for acute acetaminophen toxicity was 4.8/100,000/yr (95% CI = 3.0 to 6.5). The observed incidence of hospitalization for all acetaminophen poisoning was 5.5/100,000/yr (95% CI = 4.1 to 7.0). High ethanol consumption was present more frequently in those who suffered hepatic injury. Conclusions: Most patients evaluated for acetaminophen ingestion present early following acute single overdose. Relatively few of these patients require hospitalization and, for those hospitalized, the outcome is good. More significantly, acetaminophen overdose patients whose risk cannot be estimated using the Rumack-Matthew nomogram represented 44% of those hospitalized and 83% of those who suffered significant hepatic injury. Emergency physicians need to determine how they can impact the outcome of these patients. Efforts should be directed at further characterizing historical, physical, and biochemical markers of risk and at determining in which circumstances hospitalization for NAC or other therapies is justified.

show abstract

“…The administration of an additional NAC bolus or extending the duration of the 6.25 mg/kg/h infusion may be appropriate in certain clinical scenarios [13][14][15][16]. Treatment beyond 21 h is indicated when patients have evidence of hepatotoxicity evidenced by elevations in aminotransferases, abnormalities in predictors of poor prognosis, or persistent APAP detected by laboratory testing.…”

Section: Disclaimermentioning

confidence: 99%

ACMT Position Statement: Duration of Intravenous Acetylcysteine Therapy Following Acetaminophen Overdose

2016

J. Med. Toxicol.

View full text Add to dashboard Cite

Acetaminophen overdose: A 48-hour intravenous N-acetylcysteine treatment protocol

Cited by 246 publications

References 17 publications

Safety and efficacy of N-acetylcysteine in children with non-acetaminophen-induced acute liver failure

Safety and efficacy of N-acetylcysteine in children with non-acetaminophen-induced acute liver failure

Population‐based Incidence and Outcome of Acetaminophen Poisoning by Type of Ingestion

ACMT Position Statement: Duration of Intravenous Acetylcysteine Therapy Following Acetaminophen Overdose

Contact Info

Product

Resources

About