The standard treatment protocol for paracetamol poisoning may be inadequate following overdose with modified release formulation: a pharmacokinetic and clinical analysis of 53 cases

Salmonson, Heléne; Sjöberg, Gunilla; Brogren, Jacob

doi:10.1080/15563650.2017.1339887

Cited by 22 publications

(9 citation statements)

References 22 publications

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“…In the previous guidelines, management was very similar to that for immediate release paracetamol. However, evidence from case series from Australia and Europe has shown that this approach appears inadequate . Patients developed acute liver injury despite standard treatment such as early acetylcysteine and decontamination.…”

Section: Modified Release Paracetamol Ingestionsmentioning

confidence: 99%

Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand

Chiew

Reith

Pomerleau

et al. 2019

Medical Journal of Australia

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Introduction Paracetamol is a common agent taken in deliberate self‐poisoning and in accidental overdose in adults and children. Paracetamol poisoning is the commonest cause of severe acute liver injury. Since the publication of the previous guidelines in 2015, several studies have changed practice. A working group of experts in the area, with representation from all Poisons Information Centres of Australia and New Zealand, were brought together to produce an updated evidence‐based guidance. Main recommendations (unchanged from previous guidelines) The optimal management of most patients with paracetamol overdose is usually straightforward. Patients who present early should be given activated charcoal. Patients at risk of hepatotoxicity should receive intravenous acetylcysteine. The paracetamol nomogram is used to assess the need for treatment in acute immediate release paracetamol ingestions with a known time of ingestion. Cases that require different management include modified release paracetamol overdoses, large or massive overdoses, accidental liquid ingestion in children, and repeated supratherapeutic ingestions. Major changes in management in the guidelines The new guidelines recommend a two‐bag acetylcysteine infusion regimen (200 mg/kg over 4 h, then 100 mg/kg over 16 h). This has similar efficacy but significantly reduced adverse reactions compared with the previous three‐bag regimen. Massive paracetamol overdoses that result in high paracetamol concentrations more than double the nomogram line should be managed with an increased dose of acetylcysteine. All potentially toxic modified release paracetamol ingestions (≥ 10 g or ≥ 200 mg/kg, whichever is less) should receive a full course of acetylcysteine. Patients ingesting ≥ 30 g or ≥ 500 mg/kg should receive increased doses of acetylcysteine.

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Section: Modified Release Paracetamol Ingestionsmentioning

confidence: 99%

Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand

Chiew

Reith

Pomerleau

et al. 2019

Medical Journal of Australia

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“…Although it is safe to use in clinical doses in human medicine, the studies shows that toxicity caused by overdose APAP may cause liver and kidney damage and even deaths may develop [1,2]. Because paracetamol is one of the commonest drugs taken in overdose and involved in deliberate self-poisoning in many countries [3][4][5]. At therapeutic doses, the majority of APAP is metabolized by sulphation (20-30%) and glucuronidation (45-55%), while 5-9% is converted to N-acetyl-para-benzoqinonimine (NAPQI), a highly reactive metabolite by cytochrome p450 (CYP 450) enzymes [6].…”

Section: Introductionmentioning

confidence: 99%

The potential protective role of folic acid against acetaminophen-induced hepatotoxicity and nephrotoxicity in rats

2021

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Folic acid (FA), is a group B vitamin, has high reactive oxygen radicals quenching ability, resulting in protection against oxidative damage in aerobic cell. Acetaminophen (N-acetyl-paminophenol, APAP) is a nonsteroidal anti-inflammatory drug, and can promote oxidative damage in liver and kidney tissues. The aim of this study was to investigate whether folic acid has protective effects on oxidative liver and kidney injury caused by experimental APAP toxication. Forty female Sprague dawley rats were divided into 5 groups; control, APAP, FA, APAP+FA, and APAP+N-acetylcysteine (NAC) groups. APAP toxication was induced by oral gavage (3 g/kg bodyweight). FA (20 mg/kg bodyweight) and NAC (150 mg/kg bodyweight) were given by oral gavage to the specified groups. Oxidant and antioxidant parameter were determined in liver and kidney tissues. In addition, the liver and kidney tissues were histological evaluated. When compared with APAP group, superoxide dismutase (SOD) and catalase activities and glutathione levels were statistically higher, malondialdehyde (MDA) level and myeloperoxidase activity (except liver tissue) were statistically lower in both APAP+FA and APAP+NAC. Liver and kidney MDA level and kidney SOD activity were significantly lower in APAP+NAC group compared with APAP+FA group. Co-administration of NAC with APAP was found to provide protection, but hepatic cords were defective in some places and some glomerular tubules also had dilatation. Necrotic areas was reduced in the liver and the glomerular structure was in good condition in the APAP+FA group. As a result, FA might have a protective effect against APAP-induced hepato-nephrotoxicity and oxidative stress in rat.

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“…Modified-release products use a different method of prolonging acetaminophen absorption. These products have been associated with markedly delayed absorption and unexpected toxicity . These products are marketed in Europe and Australia but not in the US or Canada, to our knowledge.…”

Section: Discussionmentioning

confidence: 99%

Management of Acetaminophen Poisoning in the US and Canada

Dart,

Mullins,

Matoushek

et al. 2023

JAMA Netw Open

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ImportanceThe US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management.ObjectiveTo develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada.Evidence ReviewFour clinical toxicology societies (America’s Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023.FindingsThe search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed.Conclusions and RelevanceThis qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.

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The standard treatment protocol for paracetamol poisoning may be inadequate following overdose with modified release formulation: a pharmacokinetic and clinical analysis of 53 cases

Cited by 22 publications

References 22 publications

Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand

Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand

The potential protective role of folic acid against acetaminophen-induced hepatotoxicity and nephrotoxicity in rats

Management of Acetaminophen Poisoning in the US and Canada

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