Paracetamol Overdose

Define therapeutic excess

Excessive paracetamol (>licensed daily dose = >75 mg/kg/24h) taken w intent to treat pain or fever and without intent of self-harm

What are S&S of paracetamol overdose?

- May be asymptomatic
- Nausea
- Vomiting
- Loin pain
- Haematuria
- Proteinuria
- Jaundice
- Abdo pain
- Coma
- Severe metabolic acidosis

What are the main principles of management of paracetamol overdose?

- Depends on timing of ingestion, dose, and clinical condition
- Mainstay: N-acetylcysteine
- Guided by nomogram

What are the management guidelines for ingestion over 24 hours ago?

Start N-acetylcysteine immediately if pt has jaundice, RUQ tenderness, elevated ALT, INR >1.3, or paracetamol concentration is detectable

What factors put patients at increased risk of toxicity following paracetamol overdose?

- Regular alcohol excess
- Pre-existing liver disease
- Glutathione-deplete states
- HIV
- Malnutrition

What is the King's College Criteria that advises urgent transfer for liver transplantation?

- Arterial pH <7.3

OR ALL OF:

- Serum creatinine >300 micromol/L (3.4 mg/dL)

- PTT >100s

- Grade III or IV encephalopathy

What are the actions of acetylcysteine?

- Acts by replenishing glutathione stores
- May help repair oxidative damage

What is the management for an infusion reaction?

1) Stop infusion
2) Administer antihistamine (IV chlorphenamine) and bronchodilator (nebulized salbutamol) if required
3) Once reaction has subsided, restart infusion, often at slower rate

What abnormal result is most likely to be seen on VBG of paracetamol overdose?

Severe metabolic acidosis

What medication is the mainstay of treatment of paracetamol overdose?

N-acetylcysteine

What are the management guidelines for ingestion <1h ago of a dose >150mg/kg?

Administer activated charcoal

What are the management guidelines for ingestion within 8-24h and dose >150mg/kg?

Start N-acetylcysteine immediately

What is the management for a staggered overdose?

Start N-acetylcysteine immediately

How are paracetamol overdoses classified?

- Acute overdose
- Staggered overdose
- Therapeutic excess

Define acute overdose

Excessive amounts in less than 1 hr, usually in context of self-harm

Define staggered overdose

Excessive amounts of paracetamol ingested over more than 1 hour, usually in context of self-harm

What is the pathophysiology of paracetamol overdose?

Buildup of toxic substance called NAPQI (N-acetyl-p-benzoquinone-imine) -> glutathione stores rapidly depleted = unable to inactivate NAPQI -> unmetabolized NAPQI causes liver and kidney damage

What are DDs for paracetamol overdose?

- Acute gastritis/gastroenteritis (nausea and vomiting, sometimes abdo pain)
- Renal colic (loin pain, haematuria, nausea and vomiting)
- Liver diseases e.g. hepatitis or cirrhosis (jaundice, abdo pain, coma)
- Metabolic acidosis (caused by conditions like kidney disease, lactic acidosis, or DKA)

What blood tests may be used to assess paracetamol overdose?

- FBC
- LFTs
- U&Es
- Clotting
- Venous blood gas

What investigation can be used to guide decisions on treatment of paracetamol overdose?

Nomogram (plots paracetamol levels)

What are the management guidelines for ingestion <4h ago?

Wait until 4 hours to take a paracetamol-concentration level and treat w N-acetylcysteine based on level

What are the management guidelines for ingestion within 4-8 hours and a dose >150 mg/kg?

Start N-acetylcysteine immediately if there is going to be a delay of over 8h in obtaining paracetamol level

What is the King's College Criteria?

Used to predict mortality from paracetamol overdose and to identify pts who would potentially benefit from liver transplantation

What results are associated with poor prognosis 24h post-ingestion?

- Prolonged pro-thrombin time (PPTT)
- Raised creatinine
- Low blood pH

When should a plasma-paracetamol concentration be taken post-ingestion?

Btwn 4-15 hours post-ingestion (misleading if earlier, inaccurate after 15h)

When should acetylcysteine be started before the plasma-paracetamol concentration is known?

- >8h since overdose
- Staggered overdose
- Doubt over time of ingestion

Why is acetylcysteine given immediately for treatment of staggered overdose?

Plasma-paracetamol is uninterpretable and treatment graph is unreliable

What complication can arise from IV administration of acetylcysteine?

Infusion reaction -> rash and bronchospasm within first hour of initiating treatment

What are complications associated with paracetamol toxicity?

Liver and renal failure