Acetaminophen Toxicity Calculator — Rumack-Matthew Nomogram & NAC

How to Use This Calculator

1. Enter hours since ingestion (must be ≥ 4 hours for nomogram to apply).
2. Enter the serum acetaminophen level in mcg/mL (μg/mL).
3. Select treatment line (150 mcg/mL UK or 200 mcg/mL US).
4. NAC indication appears instantly based on Rumack-Matthew nomogram.
5. Use the NAC Dosing tab for IV or oral NAC protocol with weight-based doses.
6. Use the Kings College tab for liver transplant criteria assessment.

Formula

Example

Frequently Asked Questions

• What is the Rumack-Matthew nomogram? ▼
  The Rumack-Matthew nomogram is a semi-logarithmic graph published by Barry Rumack and Harvey Matthew in Pediatrics in 1975 (volume 55, pages 871–876) that plots serum acetaminophen concentration (μg/mL) on a logarithmic Y-axis against time since ingestion (hours) on a linear X-axis to determine the risk of hepatotoxicity and the need for N-acetylcysteine (NAC) treatment. The original nomogram used a treatment line starting at 200 mcg/mL at 4 hours post-ingestion and declining with a half-life of approximately 4 hours (the "possible hepatotoxicity" line). Patients with acetaminophen levels above this line have a significant risk of developing hepatotoxicity (defined as ALT or AST > 1000 IU/L) without treatment. A 25% lower "probable hepatotoxicity" line at 150 mcg/mL at 4 hours was described in the original paper and is now the treatment threshold used in UK NHS guidelines (since 2012) and many international recommendations, as it provides a greater safety margin with minimal additional unnecessary treatment. The nomogram applies only to acute single ingestions when the time of ingestion is known accurately, and only to samples drawn at least 4 hours post-ingestion.
• When is N-acetylcysteine (NAC) indicated for acetaminophen overdose? ▼
  NAC is indicated when the serum acetaminophen level plotted on the Rumack-Matthew nomogram at the appropriate time post-ingestion falls at or above the treatment line (150 mcg/mL at 4 hours in UK/conservative practice, 200 mcg/mL at 4 hours in US practice). Beyond nomogram guidance, NAC should also be given when: the time of ingestion is unknown and the acetaminophen level is detectable; staggered or repeated supratherapeutic ingestion is suspected (nomogram does not apply — treat empirically); acute liver failure is present with no clear aetiology; or there is any acetaminophen detected in a patient with pre-existing liver disease, alcoholism, malnutrition, or who is on enzyme-inducing drugs (these factors increase risk at any given level). NAC works by replenishing glutathione, the hepatic reducing agent that conjugates the toxic NAPQI (N-acetyl-p-benzoquinone imine) metabolite. It is most effective when given within 8 hours of ingestion but retains benefit up to 24 hours and even in established liver failure, where it improves oxygen delivery and reduces multi-organ dysfunction independent of its glutathione effect.
• Why does the nomogram only apply starting at 4 hours post-ingestion? ▼
  The Rumack-Matthew nomogram requires serum levels drawn at a minimum of 4 hours after ingestion because acetaminophen is still being absorbed from the gastrointestinal tract during the first 4 hours. Peak serum concentration after an acute oral ingestion typically occurs 30–120 minutes post-dose under normal conditions, but is delayed in overdose due to saturation of first-pass metabolism, pyloric spasm, co-ingestion of anticholinergic drugs, and slowed gastric emptying. A serum level drawn at 1 or 2 hours may significantly underestimate the true peak, leading to false reassurance and a failure to treat a patient who will subsequently have hepatotoxic levels at 4 hours. If a level is drawn before 4 hours and is above the 4-hour threshold, treatment can be initiated immediately without waiting — the concern is only with false negatives from early sampling. Modified-release (extended-release) formulations such as Tylenol Extended Release may delay peak concentrations beyond 4 hours, so a repeat level at 8 hours is recommended for these products even if the 4-hour level is below the treatment line.
• What is the difference between the US 200 mcg/mL and UK 150 mcg/mL treatment thresholds? ▼
  The original Rumack-Matthew nomogram described two lines: a "possible hepatotoxicity" line at 200 mcg/mL at 4 hours (based on the concentration at which the risk of ALT elevation > 1000 IU/L was estimated), and a 25% lower "probable hepatotoxicity" line at 150 mcg/mL at 4 hours. The United States traditionally adopted the 200 mcg/mL line as the treatment threshold, accepting that some patients in the zone between 150 and 200 mcg/mL were at lower absolute risk and avoiding unnecessary NAC treatment. The United Kingdom NHS, in updated guidance from MHRA and NICE in 2012, moved to the 150 mcg/mL line as the sole treatment threshold, eliminating the previous high-risk and low-risk distinction based on staggered ingestion or alcohol use history (which was found to be unreliable in practice). The UK decision was based on the principle that the marginal cost and risk of NAC treatment (primarily anaphylactoid reactions in approximately 14% of cases, rarely severe) is outweighed by the benefit of capturing additional at-risk patients. Most international guidelines now favour the more conservative 150 mcg/mL threshold.
• When is liver transplant considered for acetaminophen toxicity? ▼
  Liver transplant evaluation is triggered when a patient with acetaminophen-induced acute liver failure meets the King's College Criteria (KCC), developed at King's College Hospital London and published by O'Grady et al. in 1989. For acetaminophen-specific liver failure, the KCC are: (1) arterial pH < 7.30 after resuscitation, regardless of other factors — this is the single most predictive criterion with approximately 95% specificity for non-survival without transplant; OR (2) all three of: prothrombin time > 100 seconds (INR > 6.5), serum creatinine > 300 μmol/L (> 3.4 mg/dL), and hepatic encephalopathy grade III or IV — this triples criterion has approximately 67% sensitivity and 95% specificity. Additional features favouring transplant listing include: serum lactate > 3 mmol/L after fluid resuscitation, rate of deterioration, and evidence of multi-organ failure. The decision is a subspecialty determination by hepatology and transplant medicine — KCC guides, not replaces, clinical judgment. Patients meeting KCC should be referred immediately to a liver transplant centre. NAC should continue throughout as it may improve outcomes even in established liver failure.

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