- Enter the hours since ingestion and the serum APAP level to assess nomogram risk.
- Enter the patient's weight (kg) to calculate the weight-based IV NAC 21-hour protocol doses.
- Results update automatically as you type.
- If ingestion time is unknown or >8 hours ago, consider empirical NAC while awaiting results — do not delay treatment.
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When to Use
Use this tool in any suspected acetaminophen overdose presenting within 24 hours of ingestion, AKI workup where acetaminophen hepatotoxicity and hepatorenal syndrome is suspected, and in CKD patients who have taken potentially toxic doses.
Appropriate population
Adults with acute single ingestion of acetaminophen with a known ingestion time and a serum APAP level drawn at 4–24 hours post-ingestion. Also applicable for empirical NAC decisions before the level returns.
When NOT to rely on this nomogram alone
The Rumack-Matthew nomogram applies only to single acute ingestions with known time. It is not validated for chronic/staggered overdose, extended-release formulations (check level at 4h AND 8h), unknown ingestion time, or pediatric patients. In these cases, treat empirically or consult Poison Control.
CKD & renal considerations
Acetaminophen is generally the preferred analgesic over NSAIDs in CKD — but overdose still occurs. NAC is renally cleared but dose modification is generally NOT required in CKD. NAC has nephroprotective properties and may reduce risk of acute tubular injury in hepatotoxicity-driven hepatorenal syndrome.
Pearls & Pitfalls
Do not wait for symptoms
Acetaminophen hepatotoxicity is clinically silent for the first 24–72 hours. By the time jaundice, encephalopathy, or coagulopathy develop, the therapeutic window for NAC may have closed. Early NAC (within 8 hours of ingestion) is nearly 100% effective at preventing hepatic failure.
Anaphylactoid reactions
IV NAC causes anaphylactoid reactions in approximately 10% of patients — most commonly during the loading dose (flushing, urticaria, bronchospasm). These are not true allergic reactions. Slow the infusion rate, administer IV antihistamines (diphenhydramine or promethazine), and resume at a slower rate. Do not discontinue NAC unless anaphylaxis with cardiovascular compromise.
Pitfalls
- A level below the treatment line does NOT guarantee safety if ingestion timing is uncertain — treat empirically.
- Extended-release (ER) acetaminophen: draw levels at 4h AND 8h; a single 4-hour level can miss delayed absorption.
- Chronic excessive dosing ("therapeutic misadventure"): the nomogram does not apply — check LFTs and treat based on clinical picture.
- Concomitant alcohol use, fasting, or CYP2E1-inducing drugs (isoniazid, rifampin) increase hepatotoxicity risk even at lower APAP levels.
- Do not rely solely on the nomogram in patients with pre-existing liver disease.
Why Use It
Acetaminophen (paracetamol) is the leading cause of acute liver failure in the United States and a common hepatotoxin worldwide, including the Philippines. The Rumack-Matthew nomogram (1975) provides a validated, log-linear decision boundary based on serum APAP level and hours post-ingestion to identify patients who need antidotal therapy. IV N-acetylcysteine replenishes hepatic glutathione stores, detoxifying the reactive NAPQI metabolite responsible for hepatocellular necrosis. When given within 8 hours of ingestion, it is nearly uniformly effective.
From a nephrology perspective, acetaminophen-induced acute liver failure can progress to hepatorenal syndrome (HRS) — a severe form of AKI with a poor prognosis. Early NAC therapy prevents liver injury, thereby preventing HRS. Additionally, NAC itself has been shown to have direct nephroprotective effects in several settings.
Acetaminophen Overdose — Nomogram & NAC Dose Calculator
Enter values below. Both calculators update automatically. Use together: first assess nomogram risk, then calculate NAC doses if indicated.
Part A — Rumack-Matthew Nomogram Risk Assessment
Part B — IV NAC Dose Calculator (21-Hour Standard Protocol)
Next Steps
Use the nomogram result and clinical context to guide immediate management.
- Level ABOVE treatment line: Start IV NAC immediately. Calculate doses using Part B above. Do not wait for symptoms.
- Level BELOW treatment line (reliable timing): Monitor; NAC may not be required, but maintain clinical vigilance. Repeat LFTs at 24 hours.
- Unknown or uncertain ingestion time: Treat as high risk — start empirical NAC while awaiting further history.
- Rising AST/ALT despite NAC: Continue NAC beyond the standard 21 hours; hepatology consultation; assess for acute liver failure criteria (coagulopathy, encephalopathy).
- Signs of hepatorenal syndrome (rising creatinine, oliguria, no volume response): Nephrology + hepatology co-management. Consider terlipressin or norepinephrine + albumin. Liver transplant evaluation if acute liver failure.
- Always contact Poison Control for complex presentations (Philippines: 02-8524-1078 / DOH hotline).
Evidence & References
Rumack-Matthew Nomogram — Treatment Thresholds
| Hours post-ingestion | Treatment line threshold (µg/mL) |
|---|---|
| 4 h | 150 |
| 6 h | 100 |
| 8 h | 75 |
| 10 h | 57 |
| 12 h | 43 |
| 15 h | 28 |
| 20 h | 15 |
| 24 h | 9.5 |
Formula (log-linear interpolation): Threshold µg/mL = 150 × e−0.190 × (hours − 4) for hours 4–24.
IV NAC — Standard 21-Hour Protocol (FDA-Approved)
| Dose | Amount | Diluent | Duration |
|---|---|---|---|
| Loading (Dose 1) | 150 mg/kg | 200 mL D5W | 60 minutes |
| Second dose | 50 mg/kg | 500 mL D5W | 4 hours |
| Third dose | 100 mg/kg | 1000 mL D5W | 16 hours |
Total dose = 300 mg/kg over 21 hours. Acetylcysteine injection 200 mg/mL concentration (Acetadote).
References
- Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. 1975;55(6):871–876.
- Acetadote (acetylcysteine) Prescribing Information. Cumberland Pharmaceuticals. 2004.
- Yarema MC, Johnson DW, Berlin RJ, et al. Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning. Ann Emerg Med. 2009;54(4):606–614.
