Clinical Toxicology (2013), Early Online: 1 Copyright © 2013 Informa Healthcare USA, Inc. ISSN: 1556-3650 print / 1556-9519 online DOI: 10.3109/15563650.2013.857778
LETTER TO THE EDITOR
Letter in response to Predicting the requirement for N-acetylcysteine in paracetamol poisoning from reported dose
NAC is started incrementally earlier than 8 h after ingestion of APAP. Smilkstein et al., in a study examining NAC efficacy in APAP overdose, demonstrated that there was no statistically significant difference in the incidence of hepatotoxicity between patients treated between 0 and 4 h postingestion and those treated 4–8 h post-ingestion.2 Therefore with no defined benefit of early initiation of therapy, the added cost of therapy, and potential adverse effects of NAC, we see no benefit to early empiric therapy if the APAP concentration can be determined within 8 h post-ingestion.
Clinical Toxicology Downloaded from informahealthcare.com by University of Virginia on 11/15/13 For personal use only.
To the Editor: We read with interest the recent paper discussing early treatment with NAC in patients with paracetamol [APAP] poisoning based on reported ingestion dose.1 We agree that the need to treat patients with single acute ingestions above the Rumack–Matthew nomogram in a timely fashion is critical as delays to NAC significantly affect outcome.2 Also, it is worth reinforcing that since adverse events related to IV NAC are inversely related to APAP concentration,3 there is an additional potential benefit to initiate treatment as early as possible. Duffull and Isbister state that the reported paracetamol ingestion dose is a reliable predictor of patients being above the nomogram’s treatment line and that such a metric could be used to empirically initiate antidotal therapy before the APAP concentration is known. The authors conclude that at a reported dose of 50 g, over 90% of patients require NAC treatment and, thus, this value could be used as a “cut-off” to initiate early treatment. We are hesitant to accept these conclusions based on two simple concepts. First, the median reported ingestion was 10 g with an interquartile range of 6–16 g. Thus, with 75% of the data points below the 16 g dose and an unknown distribution between 16 and 100 g, this conclusion is based on very limited data. More importantly, it is fairly universally accepted that NAC should be started if the APAP concentration cannot be determined within 8 h of ingestion.2 Additionally, there are reasonable data to suggest that there is no change in outcome when
Shazia Rahman and Brian Gilberti NYU School of Medicine, New York, NY, USA Adam J. Berman Department of Emergency Medicine, North Shore University Hospital, Manhasset, NY, USA
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Duffull SB, Isbister GK. Predicting the requirement for N-acetylcysteine in paracetamol poisoning from reported dose. Clin Toxicol 2013; 51:772–776. 2. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med 1988; 319:1557–1562. 3. Nasrin P, Waring WS, Sharma S, Ludlam C, Megson I, Bateman DN. Risk factors and mechanisms of anaphylactoid reactions to acetylcysteine in acetaminophen overdose. Clin Toxicol 2008; 46:697–702.
Received 10 October 2013; accepted 16 October 2013. Address correspondence to Dr. Adam J. Berman, MD, Department of Emergency Medicine, North Shore University Hospital, 300 Community Drive, Manhasset, NY 11030, USA. E-mail: [email protected]
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LETTER TO THE EDITOR
Letter in response to Predicting the requirement for N-acetylcysteine in paracetamol poisoning from reported dose
NAC is started incrementally earlier than 8 h after ingestion of APAP. Smilkstein et al., in a study examining NAC efficacy in APAP overdose, demonstrated that there was no statistically significant difference in the incidence of hepatotoxicity between patients treated between 0 and 4 h postingestion and those treated 4–8 h post-ingestion.2 Therefore with no defined benefit of early initiation of therapy, the added cost of therapy, and potential adverse effects of NAC, we see no benefit to early empiric therapy if the APAP concentration can be determined within 8 h post-ingestion.
Clinical Toxicology Downloaded from informahealthcare.com by University of Virginia on 11/15/13 For personal use only.
To the Editor: We read with interest the recent paper discussing early treatment with NAC in patients with paracetamol [APAP] poisoning based on reported ingestion dose.1 We agree that the need to treat patients with single acute ingestions above the Rumack–Matthew nomogram in a timely fashion is critical as delays to NAC significantly affect outcome.2 Also, it is worth reinforcing that since adverse events related to IV NAC are inversely related to APAP concentration,3 there is an additional potential benefit to initiate treatment as early as possible. Duffull and Isbister state that the reported paracetamol ingestion dose is a reliable predictor of patients being above the nomogram’s treatment line and that such a metric could be used to empirically initiate antidotal therapy before the APAP concentration is known. The authors conclude that at a reported dose of 50 g, over 90% of patients require NAC treatment and, thus, this value could be used as a “cut-off” to initiate early treatment. We are hesitant to accept these conclusions based on two simple concepts. First, the median reported ingestion was 10 g with an interquartile range of 6–16 g. Thus, with 75% of the data points below the 16 g dose and an unknown distribution between 16 and 100 g, this conclusion is based on very limited data. More importantly, it is fairly universally accepted that NAC should be started if the APAP concentration cannot be determined within 8 h of ingestion.2 Additionally, there are reasonable data to suggest that there is no change in outcome when
Shazia Rahman and Brian Gilberti NYU School of Medicine, New York, NY, USA Adam J. Berman Department of Emergency Medicine, North Shore University Hospital, Manhasset, NY, USA
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Duffull SB, Isbister GK. Predicting the requirement for N-acetylcysteine in paracetamol poisoning from reported dose. Clin Toxicol 2013; 51:772–776. 2. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med 1988; 319:1557–1562. 3. Nasrin P, Waring WS, Sharma S, Ludlam C, Megson I, Bateman DN. Risk factors and mechanisms of anaphylactoid reactions to acetylcysteine in acetaminophen overdose. Clin Toxicol 2008; 46:697–702.
Received 10 October 2013; accepted 16 October 2013. Address correspondence to Dr. Adam J. Berman, MD, Department of Emergency Medicine, North Shore University Hospital, 300 Community Drive, Manhasset, NY 11030, USA. E-mail: [email protected]
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