title: Nomogram line crossing after acetaminophen combination product overdose.
abstract: BACKGROUND
  The Rumack-Matthew nomogram predicts the risk of hepatotoxicity following acute acetaminophen overdose based on a serum concentration obtained ≥ 4-hour post-ingestion. Some patients with low-risk concentrations at 4 hours may have subsequent values indicating increased risk (above the nomogram treatment line), especially if coingestants that slow gastrointestinal motility are involved. The treatment line currently used to identify low risk patients in the United States, Canada, and Australia begins at 150 mcg/mL (993 μmol/L) and intersects at 18.75 mcg/mL (124.1 μmol/L) 16 hours post-ingestion.
  
  
  OBJECTIVE
  To determine the incidence of nomogram line crossing after acute overdose of acetaminophen combination products containing an opioid or antihistamine.
  
  
  METHODS
  This was a prospective cohort study of hospitalized patients reported to a regional poison center (RPC) after acute overdose of a combination product containing an opioid or antihistamine. If a 4-hour acetaminophen concentration was detectable but below the nomogram treatment line, the RPC recommended repeat concentrations. Patients were entered into the study if at least one subsequent concentration was available. During follow-up calls hospital providers were queried regarding clinical features, treatment, and indicators of liver injury.
  
  
  RESULTS
  Over a 4-year period 76 patients met entry criteria. 5/76 (6.6%) had measureable acetaminophen concentrations below the treatment line at or close to 4-hour post-ingestion followed by values above the line obtained at 6.5-12.5 hours. Four of the five were treated with acetylcysteine and none developed hepatotoxicity. Four of the five had clinical features reported to the RPC suggesting toxicity from the opioid or antihistamine component.
  
  
  CONCLUSIONS
  After acute overdose of acetaminophen combination products, patients with detectable but non-toxic 4-hour acetaminophen concentrations should have repeat concentrations obtained in a time frame that would allow providers to initiate acetylcysteine treatment, if needed, without undue delay.
authors.affiliation: a Nebraska Regional Poison Center , Omaha , NE , USA ;
authors.forename: Ronald I
authors.initials: RI
authors.lastname: Kirschner
authors.affiliation: b School of Pharmacy, University of Wyoming , Laramie , WY , USA ;
authors.forename: Christina M
authors.initials: CM
authors.lastname: Rozier
authors.affiliation: c College of Public Health, University of Nebraska Medical Center , Omaha , NE , USA.
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Smith
authors.affiliation: a Nebraska Regional Poison Center , Omaha , NE , USA ;
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Jacobitz
mesh_terms: D000082:Acetaminophen / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D000111:Acetylcysteine / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D000701:Analgesics, Opioid / Q000506:poisoning; D000931:Antidotes / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control; D002648:Child; D003661:Decision Support Techniques; D004338:Drug Combinations; D062787:Drug Overdose / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D005260:Female; D006633:Histamine Antagonists / Q000506:poisoning; D006801:Humans; D008297:Male; D008875:Middle Aged; D049451:Nomograms; D011039:Poison Control Centers; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000931:Antidotes; D004338:Drug Combinations; D006633:Histamine Antagonists; D000082:Acetaminophen; D000111:Acetylcysteine
keywords: Paracetamol; combination products; nomogram