Calc Function

    • Calcs that help predict probability of a diseaseDiagnosis
    • Subcategory of 'Diagnosis' designed to be very sensitiveRule Out
    • Disease is diagnosed: prognosticate to guide treatmentPrognosis
    • Numerical inputs and outputsFormula
    • Med treatment and moreTreatment
    • Suggested protocolsAlgorithm

    Disease

    Select...

    Specialty

    Select...

    Chief Complaint

    Select...

    Organ System

    Select...

    Patent Pending

    Acetaminophen Overdose and NAC Dosing

    Calculates PO/IV NAC dosing for acetaminophen overdose (and nomogram to determine toxic 4 hour level).
    Favorite
    When to Use
    Pearls/Pitfalls
    Why Use

    When to use the Rumack-Matthew nomogram:

    • Acute, single ingestions (where entire ingestion occurs within an 8-hour period).
    • A known time of ingestion.
    • Immediate release formulation.
    • Absence of formulations or coingestants that alter absorption and bowel motility (e.g., anticholinergics, opioids).
    • An acetaminophen concentration obtained prior to 4 hours post-ingestion cannot be plotted on the Rumack-Matthew nomogram, and only confirms acetaminophen exposure, not toxicity.
    • Get an accurate time of ingestion: the Rumack-Matthew nomogram is entirely dependent on knowing time of ingestion.
    • Start NAC treatment within 8 hours post-ingestion to decrease the risk of hepatotoxicity (AST or ALT > 1000 IU/L).
    • In patients presenting 8-24 hours post-ingestion, start NAC while awaiting the acetaminophen concentration; once this is resulted, NAC can be continued or discontinued depending on the level.
    • The Rumack-Matthew nomogram is the most sensitive risk prediction tool in medical toxicology.
    • It identifies patients at very low risk of developing hepatotoxicity after acetaminophen overdose and who do not require NAC.
    • All patients above the nomogram line should be treated with NAC to decrease the risk of developing hepatotoxicity. (See More Info section)
    lbs
    Rumack-Matthew Nomogram
    About the Creator
    Dr. Barry H. Rumack
    Content Contributors
    • Scott Lucyk, MD

    Result:

    Please fill out required fields.

    Next Steps
    Evidence
    Creator Insights

    Advice

    • Early administration of NAC (< 8 hours post-ingestion) is vital to decreasing the risk of hepatotoxicity; acetaminophen is a leading cause of drug-induced liver injury.
    • Acetaminophen is widely available in prescription and over-the-counter medications, either as single agent or combination products (e.g., dextromethorphan, opioids, diphenhydramine).
    • Maintain a strong index of suspicion for acetaminophen toxicity in all patients with intentional drug overdose and those with therapeutic misadventures (e.g. taking excessive amounts of a single product, or using recommended doses of several different acetaminophen containing products).

    Management

    If known time of ingestion

    • Obtain acetaminophen concentration at 4 hours post-ingestion or as soon as possible thereafter.
    • Plot acetaminophen concentration on Rumack-Matthew nomogram.*
    • If above “treatment line” (line connecting 150 mg/mL (993 mmol/L) at 4 hours and 4.7 mg/mL (31 mmol/L) at 24 hours), NAC is indicated.

    Unknown time of ingestion

    • Determine earliest possible time of ingestion:
      • If < 24 hours post-ingestion, plot on Rumack-Matthew nomogram and initiate NAC if above “treatment line.”*
    • If earliest time of ingestion cannot be estimated:
    • Treatment with NAC is indicated if:
      • Detectable acetaminophen concentration.
      • Abnormal aminotransferases (AST or ALT).

    Extended release formulations/coingestions of opioids, anticholinergics, or other medications that will slow gut motility

    • Obtain initial 4 hour post-ingestion acetaminophen concentration.
      • If above treatment line, NAC is indicated.*
      • If below treatment line, repeat acetaminophen concentration at 6 to 7 hours post-ingestion.
        • If above treatment line, NAC should be initiated within 8 hours post-ingestion.

    Chronic acetaminophen ingestion

    • Patients taking repeated, supratherapeutic (> 4g/day) acetaminophen ingestions.
      • Treatment with NAC indicated if:
        • Detectable acetaminophen concentration.
        • Abnormal aminotransferases (AST or ALT).

    Critical Actions

    Serum acetaminophen concentration should be sent in all patients presenting with intentional overdose or those using excessive amounts of acetaminophen containing products.

    NAC treatment should be initiated within 8 hours post-ingestion to decrease risk of hepatotoxicity.

    Formula

    Actual body-weight dosing, starting with loading dose and then variable rates depending on PO vs. IV, as below.

    PO

    Loading dose is 140mg/kg PO, then 17 more doses every 4 hours of 70mg/kg PO. If patient vomits within 1 hour of dose, it must be repeated.

    IV

    Patients >40 kg:

    • Loading Dose: 150 mg/kg in 200 mL of diluent administered over 60 minutes.
    • Dose 2: 50 mg/kg in 500 mL of diluent administered over 4 hours.
    • Dose 3: 100 mg/kg in 1000 mL of diluent administered over 16 hours.

    Patients >20 - 40kg

    • Loading Dose: 150 mg/kg in 100 mL of diluent administered over 60 minutes.
    • Dose 2: 50 mg/kg in 250 mL of diluent administered over 4 hours.
    • Dose 3: 100 mg/kg in 500 mL of diluent administered over 16 hours.

    Patients

    • Loading Dose: 150 mg/kg in 3 mL/kg of body weight of diluent administered over 60 minutes.
    • Dose 2: 50 mg/kg in 7 mL/kg of body weight of diluent administered over 4 hours.
    • Dose 3: 100 mg/kg in 14 mL/kg of body weight of diluent administered over 16 hours.

    Facts & Figures

    Rumack-Matthew nomogram

    • Best if NAC started within 8-10 hours of ingestion, but may still be effective up to 24 hours after ingestion.
    • May be given PO or IV.
      • Oral formulation (Mucomyst, generic) 140 mg/kg orally loading dose then 70 mg/kg orally every 4 hours for 68 hours (17 doses).
      • IV formulation (Acetadote, or using oral solution) 150 mg/kg over 60 minutes, then 50 mg/kg over 4 hours (12.5 mg/kg/hr), then 100 mg/kg over 16 hours (6.25 mg/kg/hr).

    Evidence Appraisal

    Rumack BH, 1981

    • Nationwide, multiclinic open study started in 1976 at the Rocky Mountain Poison Center, Denver, to assess the effectiveness of oral acetylcysteine in preventing hepatotoxicity in patients with acetaminophen overdose presenting within 24-hours of ingestion.
    • 662 consecutive patients with acetaminophen overdose.
    • Incidence of hepatotoxicity and time to treatment for patients with acetaminophen concentration in probable toxic range (line intersecting 200 mg/mL (1324 mmol/L) at 4 hours and 50 mg/mL (331 mmol/L) at 12 hours) were:
      • 7% when treated within 10 hours of ingestion.
      • 29% when treated within 10 to 16 hours of ingestion.
      • 62% when treated within 16 to 24 hours of ingestion.

    Prescott LF, 1979

    • 100 cases of acetaminophen poisoning treated with intravenous (IV) N-acetylcysteine (NAC).
    • Serum acetaminophen concentration above a line intersecting 200 mg/mL (1323 mmol/L) at 4 hours and 30 mg/mL (199 mmol/L) at 15 hours.
    • Incidence of hepatotoxicity:
      • 0/40 patients treated within 8 hours of ingestion.
      • 1/62 (1.6%) patients treated within 10 hours of ingestion.
      • 20/38 (53%) patients treated within 10 to 24 hours of ingestion.
    • Retrospective analysis of 57 patients treated with supportive care alone (no IV NAC) showed 33/57 (58%) incidence of hepatotoxicity.

    Smilkstein MJ, 1988

    • 11,195 cases of suspected acetaminophen overdose; described outcomes of 2,540 cases treated with 72 hour oral N-acetylcysteine.
    • In patients at probable risk for hepatotoxicity (acetaminophen concentration above a line intersecting 200 mg/mL (1323 mmol/L) at 4 hours and 50 mg/mL (331 mmol/L) at 12 hours and below a line intersecting 300 mg/mL (1985 mmol/L) at 4 hours and 75 mg/mL (496 mmol/L) at 12 hours):
      • 6.1% developed hepatotoxicity when NAC was initiated within 10 hours of ingestion.
      • 26.4% developed hepatotoxicity when NAC was initiated within 10 to 24 hours of ingestion.
    Dr. Barry H. Rumack

    About the Creator

    Barry H. Rumack, MD, is currently director emeritus of the Rocky Mountain Poison and Drug Center and director, Office of Professionalism at UC Denver. He is a retired professor emeritus of pediatrics at the University of Colorado School of Medicine.



    To view Dr. Barry H. Rumack's publications, visit PubMed

    Content Contributors
    • Scott Lucyk, MD