{"id":"95af6688-e12b-5699-a1ed-ee65afce6621","stable_key":"7de430a5-1a36-5231-b931-35cc01d8f3bf:apap-the-nomogram-and-the-antidote","predicate":"causes","statement":"Acetaminophen overdose is the leading cause of acute liver failure in Canada and around the world with approximately 4,500 hospitalisations each year in Canada and about 6% of those hospitalised developing liver injury including acute liver failure that may require transplant or lead to death, and on the Rumack-Matthew nomogram derived from patients not treated with antidote a serum concentration above 200 milligrams per litre at 4 hours carries a 60% incidence of severe hepatotoxicity and 5% mortality rising to 90% and 24% at 300 milligrams per litre, with treatment by N-acetylcysteine required above 140 milligrams per litre at 4 hours.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"d1f0cffd-22f9-5b57-a5f1-ae712fe26c38","mechanism_event_label":"Above a concentration that can be read off a chart, the liver fails in most people unless the antidote is given.","subject":{"id":"a901be21-7915-543c-ac67-c39ef72b0d03","slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"},"object":{"id":"872ec0ad-f690-5d02-a1bf-93c38edabb6f","slug":"acute-liver-failure","display_name":"Acute liver failure","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d1f0cffd-22f9-5b57-a5f1-ae712fe26c38","stable_key":"7de430a5-1a36-5231-b931-35cc01d8f3bf:apap-the-nomogram-and-the-antidote-event","event_type":"observed_intervention","label":"Above a concentration that can be read off a chart, the liver fails in most people unless the antidote is given.","description":"Acetaminophen overdose is the leading cause of acute liver failure in Canada and around the world with approximately 4,500 hospitalisations each year in Canada and about 6% of those hospitalised developing liver injury including acute liver failure that may require transplant or lead to death, and on the Rumack-Matthew nomogram derived from patients not treated with antidote a serum concentration above 200 milligrams per litre at 4 hours carries a 60% incidence of severe hepatotoxicity and 5% mortality rising to 90% and 24% at 300 milligrams per litre, with treatment by N-acetylcysteine required above 140 milligrams per litre at 4 hours.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4f1a77d8-b410-579e-b2ad-86b94b09f3c2","slug":"rumack-matthew-nomogram","display_name":"The Rumack-Matthew nomogram relating serum concentration and time to hepatotoxicity risk","entity_type_key":"cellular_process"},"role":"decision_tool","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b5fa7a22-e5a7-58d9-9e39-91a611aa431e","slug":"n-acetylcysteine","display_name":"N-Acetyl-L-cysteine","entity_type_key":"small_molecule"},"role":"antidote","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ef21db0e-101c-5e8b-b779-9f2cf798b185","slug":"liver-necrosis","display_name":"Hepatic necrosis","entity_type_key":"cellular_process"},"role":"underlying_injury","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"43887d3e-e850-568f-9585-659c5561b3a7","slug":"napqi","display_name":"N-Acetyl-p-benzoquinone imine / NAPQI","entity_type_key":"small_molecule"},"role":"responsible_metabolite","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"a901be21-7915-543c-ac67-c39ef72b0d03","slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"872ec0ad-f690-5d02-a1bf-93c38edabb6f","slug":"acute-liver-failure","display_name":"Acute liver failure","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; 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The nomogram figures it quotes are derived from patients not treated with antidote, which is stated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Above a concentration that can be read off a chart, the liver fails in most people unless the antidote is given.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[apap-p36191122] Point-of-Care Testing and N-Acetylcysteine for Acute Acetaminophen Overdose (2021). https://pubmed.ncbi.nlm.nih.gov/36191122/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"623e8834-fed0-58ea-8c93-8dd13fceb748","evidence_kind":"source_excerpt","locator":"Lines 428-439","start_line":428,"end_line":439,"excerpt":"### apap-the-nomogram-and-the-antidote\nAcetaminophen overdose is the leading cause of acute liver failure in Canada and around the world with approximately 4,500 hospitalisations each year in Canada and about 6% of those hospitalised developing liver injury including acute liver failure that may require transplant or lead to death, and on the Rumack-Matthew nomogram derived from patients not treated with antidote a serum concentration above 200 milligrams per litre at 4 hours carries a 60% incidence of severe hepatotoxicity and 5% mortality rising to 90% and 24% at 300 milligrams per litre, with treatment by N-acetylcysteine required above 140 milligrams per litre at 4 hours.\nCondition category: biomarker_context\nnutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404.\nplain_language: Above a concentration that can be read off a chart, the liver fails in most people unless the antidote is given.\norganism: Human\ntissue_or_cell_type: Liver\nexperimental_model: Review of point-of-care testing and antidote guidance for acute overdose\nlimitations: A health-technology review rather than primary research. The nomogram figures it quotes are derived from patients not treated with antidote, which is stated.\nexposure: Serum acetaminophen concentration interpreted against the Rumack-Matthew nomogram\nevidence_span: {\"source_cache\": \"artifacts/paracetamol-research/36191122.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"859db1958aeb26b75a34a32e4dd1c4713dc7db413717cefe62a3659856db7568\", \"start_char\": 0, \"end_char\": 3325, \"text_sha256\": \"859db1958aeb26b75a34a32e4dd1c4713dc7db413717cefe62a3659856db7568\"}\n[apap-p36191122] Point-of-Care Testing and N-Acetylcysteine for Acute Acetaminophen Overdose (2021). https://pubmed.ncbi.nlm.nih.gov/36191122/","model_system":"Review of point-of-care testing and antidote guidance for acute overdose","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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