Acetaminophen (paracetamol) overdose case study
The case
Patient: A 28‑year‑old woman, G2P1, presents to the emergency department (ED) 6 hours after ingesting a large quantity of over‑the‑counter analgesic tablets.
Presenting complaint: Nausea, vague abdominal discomfort and a feeling of “being unwell” for the past 2 hours.
History of present illness:
- Approximately 6 hours ago she took 30 tablets of 500 mg acetaminophen (total dose = 15 g) in a “suicidal attempt” after a heated argument with her partner.
- She vomited once, 30 minutes after ingestion, but did not seek medical help until the vomiting subsided.
- No other substances (alcohol, opioids, antihistamines) were taken.
- No known drug allergies.
Past medical history:
- Unremarkable; no chronic liver disease, no hepatitis B/C, no alcohol misuse.
Family history: Mother with type 2 diabetes; father died of myocardial infarction at 55 y.
Social history: Works as a graphic designer, occasional social alcohol (1–2 drinks/week), non‑smoker.
Examination:
- General: Awake, alert, oriented ×3, mildly anxious.
- Vital signs: BP 120/78 mm Hg, HR 96 bpm, RR 16 /min, Temp 37.2 °C, SpO₂ 98 % on room air.
- Abdomen: Soft, mild epigastric tenderness, no guarding or rebound.
- No jaundice, no peripheral edema, no stigmata of chronic liver disease.
Initial investigations (drawn on arrival):
| Test | Result | Units | Reference |
|---|---|---|---|
| Serum acetaminophen (paracetamol) level | 210 | µg/mL | <30 µg/mL (therapeutic) |
| ALT (alanine aminotransferase) | 45 | U/L | 7–56 |
| AST (aspartate aminotransferase) | 38 | U/L | 10–40 |
| Bilirubin (total) | 0.8 | mg/dL | 0.2–1.2 |
| INR | 1.0 | – | 0.8–1.2 |
| Serum creatinine | 0.9 | mg/dL | 0.6–1.2 |
| Serum electrolytes (Na⁺/K⁺/Cl⁻) | 138/4.2/102 | mmol/L | 135‑145/3.5‑5.0/98‑106 |
| Blood glucose | 92 | mg/dL | 70‑110 |
| Urine toxicology screen | Negative for other drugs | – | – |
The patient is placed on a peripheral IV line and a repeat acetaminophen level is ordered for 4 hours later as per the Rumack‑Matthew nomogram protocol.
Questions
- What is the most likely diagnosis?
- Which clinical and laboratory findings support this diagnosis, and why is the timing of the acetaminophen level important?
- According to current guidelines (2023), what is the recommended antidotal therapy, including dose, route, and duration?
- Outline the monitoring plan (clinical and laboratory) for the first 48 hours after presentation.
- Discuss two major complications of acetaminophen toxicity and their typical time course.
Answers
1. Diagnosis
The patient has acetaminophen (paracetamol) overdose with impending hepatotoxicity. The ingestion of 15 g (≈ 21.4 mg/kg for a 70‑kg adult) exceeds the toxic threshold (> 7.5 g or > 150 mg/kg) and the serum level of 210 µg/mL at 6 hours places her well above the treatment line on the Rumack‑Matthew nomogram.
2. Findings that point to the diagnosis
| Finding | Reason it supports acetaminophen toxicity |
|---|---|
| Dose ingested (15 g) | Exceeds the single‑dose toxic limit (≥ 7.5 g or ≥ 150 mg/kg). |
| Time since ingestion (6 h) | Within the 4‑ to 24‑hour window where serum levels correlate with risk. |
| Serum acetaminophen level 210 µg/mL | On the nomogram, a level > 150 µg/mL at 6 h is above the “treatment line” (≥ 150 µg/mL × (time/4 h)⁰·⁵). |
| Mild epigastric tenderness | Early sign of hepatic injury; nausea/vomiting are common prodromal symptoms. |
| Normal baseline LFTs | Early stage; transaminases typically rise 24‑48 h after ingestion, so normal values do not exclude toxicity. |
| Absence of other drugs | Rules out alternative causes of hepatic injury. |
Why timing matters: The Rumack‑Matthew nomogram is valid only for a single, acute ingestion and for levels drawn 4–24 hours post‑dose. Levels taken earlier may underestimate risk because absorption may be incomplete; levels after 24 h are less useful because hepatic injury may already be underway. Hence the 6‑hour level is appropriate for decision‑making.
3. Antidotal therapy (2023 American Association for the Study of Liver Diseases – AASLD guideline)
N‑acetylcysteine (NAC) is the antidote of choice.
| Parameter | Recommendation |
|---|---|
| Indication | Serum acetaminophen level above the treatment line on the Rumack‑Matthew nomogram, or any ingestion ≥ 150 mg/kg (even if level unavailable). |
| Route | Intravenous (IV) preferred in the ED because of rapid achievement of therapeutic plasma concentrations and reliable dosing. |
| Loading dose | 150 mg/kg diluted in 200 mL 5 % dextrose, infused over 30 minutes. |
| First maintenance | 50 mg/kg diluted in 500 mL 5 % dextrose, infused over 4 hours. |
| Second maintenance | 100 mg/kg diluted in 1000 mL 5 % dextrose, infused over 16 hours. |
| Total duration | 20‑hour IV protocol (total dose ≈ 300 mg/kg). Oral NAC (140 mg/kg loading, then 70 mg/kg every 4 h for 17 doses) is an alternative if IV unavailable. |
| Adjuncts | Alkalinisation of urine is not required; activated charcoal is contra‑indicated after vomiting and > 1 hour post‑ingestion. |
The IV regimen is weight‑based; for a 70‑kg woman the total NAC dose is ≈ 21 g (150 mg/kg = 10.5 g loading, 50 mg/kg = 3.5 g first maintenance, 100 mg/kg = 7 g second maintenance).
4. Monitoring plan (first 48 h)
| Parameter | Frequency | Rationale |
|---|---|---|
| Clinical assessment (mental status, vitals, abdominal exam) | Every 2 h for the first 12 h, then q4 h | Detect early signs of hepatic failure (encephalopathy, hypotension). |
| Serum acetaminophen level | Repeat at 12 h after the first sample (i.e., 18 h post‑ingestion) | Ensure level is falling; if still > 100 µg/mL, consider extended NAC. |
| Liver function tests (ALT, AST, bilirubin, INR) | q6 h for the first 24 h, then q12 h | ALT/AST typically rise 24‑48 h; INR is a sensitive marker of synthetic dysfunction. |
| Renal function (creatinine, electrolytes, urine output) | q12 h | NAC can cause mild renal vasodilation; severe overdose may cause acute tubular necrosis. |
| Serum lactate | q12 h if patient becomes hypotensive or encephalopathic | Elevated lactate may indicate mitochondrial dysfunction in severe toxicity. |
| Coagulation profile (PT/INR) | q12 h (same as LFTs) | Rising INR > 1.5 signals impending hepatic failure. |
| NAC infusion monitoring | Continuous infusion pump; watch for anaphylactoid reactions (rash, bronchospasm) especially during the loading dose. | Stop infusion, give antihistamine, and restart at slower rate if reaction occurs. |
| Imaging (abdominal US/CT) | Only if clinical deterioration (e.g., ascites, hepatic encephalopathy) | To assess for hepatic necrosis or other intra‑abdominal pathology. |
If ALT > 1000 U/L, INR > 1.5, or encephalopathy develops, transfer to a liver transplant centre is indicated.
5. Major complications
Acute hepatic failure (AHF)
- Pathophysiology: N‑acetyl‑p‑benzoquinone imine (NAPQI) depletes glutathione, binds cellular proteins, leading to centrilobular necrosis.
- Time course: Transaminases typically peak 48‑72 h; INR rises concurrently. Clinical signs (jaundice, coagulopathy, encephalopathy) appear 72‑96 h after ingestion.
- Management: NAC continuation, intensive supportive care, evaluation for liver transplantation (King’s College criteria).
Acute kidney injury (AKI)
- Pathophysiology: Direct tubular toxicity from NAPQI and renal vasoconstriction; may be exacerbated by hypotension.
- Time course: Serum creatinine may rise 2‑5 days post‑overdose; oliguria may be present earlier.
- Management: Maintain euvolemia, avoid nephrotoxic drugs, consider renal replacement therapy if refractory uremia or fluid overload.
Other less common complications (e.g., metabolic acidosis, hypoglycemia) can occur but are usually secondary to severe hepatic failure.
Key learning points
- Toxic dose: ≥ 7.5 g (single dose) or ≥ 150 mg/kg in adults; lower thresholds in children.
- Rumack‑Matthew nomogram is the cornerstone for deciding NAC therapy; it is valid only for a single acute ingestion and for levels drawn 4‑24 h post‑dose.
- N‑acetylcysteine restores hepatic glutathione, detoxifies NAPQI, and improves microcirculation; the IV 20‑hour protocol is the current standard (AASLD 2023).
- Early signs (nausea, vomiting, epigastric pain) are nonspecific; normal LFTs at presentation do not exclude impending hepatotoxicity.
- Monitoring includes serial acetaminophen levels, LFTs, INR, and clinical assessment for at least 48 h; delayed transaminase rise is typical.
- Complications: Acute hepatic failure (peak 48‑72 h) and acute kidney injury (2‑5 days) are the two most serious outcomes. Prompt NAC can prevent or mitigate both.
- Contra‑indications to activated charcoal after vomiting or > 1 h post‑ingestion; NAC remains the definitive antidote.
- Psychosocial aspect: All overdose patients should receive a mental‑health evaluation before discharge.
Practice MCQs
1. A 35‑year‑old man presents 5 hours after ingesting 12 g of acetaminophen. His serum level is 180 µg/mL. According to the Rumack‑Matthew nomogram, the appropriate next step is:
A. Observe and repeat level in 12 h
B. Start oral N‑acetylcysteine (NAC) only if level rises above 200 µg/mL
C. Initiate IV NAC using the 20‑hour protocol
D. Give activated charcoal and discharge
Answer: C — The level is above the treatment line at 5 h, indicating a high risk of hepatotoxicity; IV NAC should be started immediately.
2. Which of the following laboratory trends is most predictive of impending acute hepatic failure in acetaminophen overdose?
A. Serum creatinine rising from 0.9 to 1.2 mg/dL within 24 h
B. ALT increasing from 45 U/L to 1200 U/L between 24‑48 h
C. Serum sodium falling from 138 to 132 mmol/L in 12 h
D. Bilirubin rising from 0.8 to 1.0 mg/dL in 48 h
Answer: B — A sharp rise in transaminases (> 1000 U/L) is the hallmark of severe hepatic necrosis and predicts failure.
3. During IV NAC infusion, a patient develops a sudden rash, pruritus, and mild bronchospasm. The best immediate management is:
A. Stop NAC, give epinephrine 0.01 mg/kg IM, and restart NAC at half rate after 30 min
B. Continue infusion at the same rate and add antihistamine
C. Stop NAC, administer antihistamine (e.g., diphenhydramine), and resume NAC at a slower rate once symptoms resolve
D. Switch to oral NAC without any further intervention
Answer: C — Anaphylactoid reactions to IV NAC are managed by stopping the infusion, treating with antihistamine, and then restarting at a slower rate once the reaction subsides. Epinephrine is reserved for true anaphylaxis.
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