Acetaminophen Overdose Calculator

Understanding Acetaminophen (Paracetamol) Toxicity & The Rumack-Matthew Nomogram

Acetaminophen (paracetamol / APAP) is one of the most common pharmaceutical agents involved in intentional and unintentional poisonings worldwide. In therapeutic doses, acetaminophen is safely metabolized via glucuronidation and sulfation in the liver. In acute overdose, these normal metabolic pathways become saturated, shunting excess drug to cytochrome P450 enzymes (primarily CYP2E1) which produces the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI).

When hepatic glutathione stores deplete below approximately 30%, NAPQI binds covalently to hepatocytes, causing acute hepatic centrilobular necrosis and potentially fulminant liver failure.

The Rumack-Matthew Nomogram Equation

The Rumack-Matthew nomogram plots serum acetaminophen concentration against time elapsed since a single acute ingestion. In North America and many international guidelines, the standard "150-line" (also known as the treatment line) is defined by an exponential decay curve starting at $150\text{ }\mu\text{g/mL}$ ($993\text{ }\mu\text{mol/L}$) at 4 hours post-ingestion with an assumed 4-hour half-life:

$$C_{\text{treatment}}(t) = 150 \times \left(0.5\right)^{\frac{t - 4}{4}} = 150 \times 2^{\frac{4 - t}{4}}$$

Where:

• $t$ is time elapsed in hours ($4 \le t \le 24$).
• $C_{\text{treatment}}(t)$ is the serum threshold in $\mu\text{g/mL}$ ($\text{mg/L}$).
• To convert to SI units ($\mu\text{mol/L}$), multiply $\mu\text{g/mL}$ by $6.614$.

Key Nomogram Reference Values

Role of N-Acetylcysteine (NAC)

N-acetylcysteine (NAC) is the definitive antidote for acetaminophen poisoning. It acts primarily by restoring depleted hepatic glutathione pools and enhancing non-toxic sulfate conjugation. When initiated within 8 hours of acute ingestion, NAC is nearly 100% effective in preventing severe hepatotoxicity and death.

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