Paracetamol overdose in Hong Kong: is the 150-treatment line good enough to cover patients with paracetamol-induced liver injury?

Chan, Simon T B; Chan, Chung-hong; Tse, ML

doi:10.12809/hkmj144481

Cited by 5 publications

(8 citation statements)

References 10 publications

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“…The incidence of 150-treatment line failures in the US has been reported as 1% to 3% and thought to be predominantly due to inaccurate ingestion history. 5 Looking closely at the four cases presented in Chan et al's study, 4 two of them presented late, and in most cases there was an apparent discrepancy between the dose taken and the achieved paracetamol level. Similar to the US experience, an inaccurate ingestion history might explain treatment-line failure for some of these cases.…”

mentioning

confidence: 85%

“…This model of care improves patient outcome and shortens the length of stay for medical treatment. 6,7 Such improvements might explain the observed good outcome for Chan et al's cohort 4 of patients with paracetamol overdose.…”

mentioning

confidence: 94%

“…Thus in 2012 the health department in the UK decided to abandon the two-level approach and apply one treatment line of 100 mg/L for all patients. 3 In the article written by Chan et al, 4 the 150-treatment line has been evaluated and identified a failure rate of 0.45%. All four index patients developed chemical hepatitis that responded to supportive treatment.…”

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confidence: 99%

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Management of acute paracetamol poisoning

Tsui

2015

Hong Kong Med J

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Since 2010, paracetamol has been the most common agent used in Hong Kong for deliberate self-harm by overdose and poisoning.1 It is readily available over-the-counter and is commonly prescribed by doctors. There are more than 900 registered pharmaceuticals that contain paracetamol in Hong Kong. Paracetamol overdose can result in delayed, sometimes life-threatening, liver injury and dosedependent damage. N-acetylcysteine (NAC) is well known to be an effective antidote that can prevent liver injury if administered in time. The decision to give NAC can be facilitated by plotting the serum paracetamol concentration against time since ingestion on the Rumack-Matthew nomogram. In the article written by Chan et al, 4 the 150-treatment line has been evaluated and identified a failure rate of 0.45%. All four index patients developed chemical hepatitis that responded to supportive treatment. The incidence of 150-treatment line failures in the US has been reported as 1% to 3% and thought to be predominantly due to inaccurate ingestion history.5 Looking closely at the four cases presented in Chan et al's study, 4 two of them presented late, and in most cases there was an apparent discrepancy between the dose taken and the achieved paracetamol level. Similar to the US experience, an inaccurate ingestion history might explain treatment-line failure for some of these cases. Further evidence from more robust studies is needed before a recommendation can be made to lower the treatment threshold to the UK standard. Obtaining an accurate history from patients who deliberately self-harm is known to be difficult. Patients may be unwilling or unable to provide accurate information to the clinician. According to the author's own experience in managing such patients, history taking must be done tactfully and sometimes repeatedly from different sources of information. An astute physician should make the decision to give NAC after analysing all the available evidence including the best-gathered history, the clinical presentation, and the remaining treatmenttime window, together with the serum paracetamol level. Laboratory tests may help but can never replace clinical skill, clinical judgement, and experience in patient management.Previously, the responsibility for managing such time-critical overdosed patients was often borne by interns and junior residents. The quality of care provided may not have been optimal. Over the past 10 years emergency physicians and trainees have received intensive training in the management of toxicology cases based on updated evidence and standards. In addition, groups of interested emergency physicians have formed toxicology teams to oversee and support the management of poisoning patients in individual hospitals. This model of care improves patient outcome and shortens the length of stay for medical treatment.6,7 Such improvements might explain the observed good outcome for Chan et al's cohort 4 of patients with paracetamol overdose.

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confidence: 85%

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confidence: 94%

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Management of acute paracetamol poisoning

Tsui

2015

Hong Kong Med J

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“…This “150 line” on the Rumack-Matthews nomogram is a level imposed by FDA to ensure as many patients as possible are treated without increasing the risk of overtreatment and the attendant costs of therapy. [68, 70] In other nations, such as the U.K., the threshold plasma concentration was lowered to 100 mg/L in 2012 [71] This change in national guidelines resulted in an increased proportion of patients being admitted and treated with NAC, most of whom presented with concentrations between 100 and 149mg/L. However, the change was not associated with any increase in adverse reactions to NAC.…”

Section: Specific Antidotes To Treat Dilimentioning

confidence: 99%

“…However, the change was not associated with any increase in adverse reactions to NAC. [71] In Hong Kong, Chan et al[70] reported that only 21% of 893 patients presented with an overdose concentration above the 150 treatment line threshold, with 12.5% having serum levels between 100 and 150ug, and 66.5% were below the 100ug treatment line. They cautioned that while lowering the treatment line to 100ug would cut the NAC failure rate from 0.45% to 0.22%, it needs to be balanced against a higher incidence of anaphylactoid reactions and increased costs.…”

Section: Specific Antidotes To Treat Dilimentioning

confidence: 99%

Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review

Stine¹,

Lewis²

2015

Expert Review of Gastroenterology & Hepatology

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While the pace of discovery of new agents, mechanisms and risk factors involved in drug-induced liver injury (DILI) remains brisk, advances in the treatment of acute DILI seems slow by comparison. In general, the key to treating suspected DILI is to stop using the drug prior to developing irreversible liver failure. However, predicting when to stop is an inexact science, and commonly used ALT monitoring is an ineffective strategy outside of clinical trials. The only specific antidote for acute DILI remains N-acetylcysteine (NAC) for acetaminophen poisoning, although NAC is proving to be beneficial in some cases of non-acetaminophen DILI in adults. Corticosteroids can be effective for DILI associated with autoimmune or systemic hypersensitivity features. Ursodeoxycholic acid, silymarin and glycyrrhizin have been used to treat DILI for decades, but success remains anecdotal. Bile acid washout regimens using cholestyramine appear to be more evidenced based, in particular for lefluonomide toxicity. For drug-induced acute liver failure, the use of liver support systems is still investigational in the United States and emergency liver transplant remains limited by its availability. Primary prevention appears to be the key to avoiding DILI and the need for acute treatment. Pharmacogenomics, including HLA genotyping and the discovery of specific DILI biomarkers offers significant promise for the future. This article describes and summarizes the numerous and diverse treatment and prevention modalities that are currently available to manage DILI.

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Drug-Induced Liver Injury: Highlights from a Review of the 2015 Literature

2016

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Numerous publications contributed to the expanding knowledge base about drug-induced liver injury (DILI) in 2015. New findings from the US Drug Induced Liver Injury Network (DILIN) in their most recently updated registry include a 1- to 3-week delay in the appearance of acute DILI from short-course antibiotics such as cefazolin. They corroborated the finding that acute DILI in patients with underlying liver disease was far more severe and potentially fatal than in patients without liver disease. The only drug that seemed to have an increased risk of hepatotoxicity in these patients was azithromycin. While nearly one in six patients with acute DILI had persistently elevated liver tests at 6 months, and results for 75 % of these patients continued to be abnormal at 12 months, most of these "chronic" injury cases were relatively minor and the result of cholestatic hepatotoxins. Newly described DILI agents include tolvaptan, as well as some new direct-acting antiviral protease inhibitors for chronic hepatitis C. The latter have been associated with serious acute hepatitis, hyperbilirubinemia, and decompensation. Herbal hepatotoxicity continues to be increasingly reported, although applying causality assessment to these cases can, in fact, be more challenging than with prescription drugs. As important as cases with DILI, the class of PCSK9 inhibitors used to lower low-density lipoprotein (LDL) cholesterol have not been associated with significant liver injury, in contrast with other lipid-lowering agents. With respect to pharmacologic DILI risk factors, new data show that drugs metabolized by cytochrome P450 enzymes had a nearly four times higher likelihood of causing DILI. Interestingly, high lipophilicity, which was previously felt to be a risk factor for DILI, was not found to be associated, although more study is needed to confirm this observation. While human leukocyte antigen (HLA) genotypes have been linked to several specific agents, the role of such testing in the general population remains undefined due to the currently low positive and negative predictive values of the available tests. New DILI biomarkers, specifically microRNA-122 and keratin-18, among others, appear to have the necessary predictive value to determine the prognosis and outcome of patients with paracetamol (acetaminophen [AAP])-induced acute liver failure (ALF), and may be of great benefit in deciding who requires N-acetylcysteine (NAC), and for what duration. Treatment options for other forms of DILI remain limited; no firm conclusions can currently be drawn for the use of NAC in non-AAP ALF.

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Paracetamol overdose in Hong Kong: is the 150-treatment line good enough to cover patients with paracetamol-induced liver injury?

Cited by 5 publications

References 10 publications

Management of acute paracetamol poisoning

Management of acute paracetamol poisoning

Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review

Drug-Induced Liver Injury: Highlights from a Review of the 2015 Literature

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