Paracetamol Overdose

Question 1

Paracetamol Dose and Liver Damage

Answer 1

• Less than 150mg/kg: unlikely
• More than 250mg/kg: likely
• More than 12g total - potentially fatal

Question 2

Paracetamol Overdose Pathophysiology

Answer 2

Paracetamol is well absorbed, blood plasma concentration peaks after one hour.
Inactivated by liver producing glucorinide or sulphate, renaly excreted
-In overdose pathway becomes saturated, leading to metabolism in alternative pathway
-Results in N-acetyl-p-benzoquinone imine (NAPQI) which is inactivated by glutathione
-When glutathione depleted below 30%, NAPQI reacts with cell and causes necrosis in liver and kidney tubules

Question 3

Paracetamol Overdose Presentation

Answer 3

• Asymptomatic for first 24hrs/ nonspecific abdominal symptoms
• Hepatic necrosis after 24hrs (elevated transaminases RUQ pain, jaundice) can progress to ALF
• Encephalopathy, oliguria, hypoglycaemia, renal failure (day 3), lactic acidosis
• Usually very little to find on examination until ALF (jaundice, hepatic flap, encephalopathy and tender hepatomegaly)

Question 4

Paracetamol Overdose and Alcohol?

Answer 4

Alcohol inhibits liver enzymes, reduces production of NAPQI, chronic alcoholism may increase production

Question 5

Paracetamol Overdose Ix

Answer 5

• Paracetamol level
• U/Es, LFTs, glucose, clotting screen, ABG (acidosis can occur in 10% of ALF)
• FBCs and salicylate not needed

Question 6

Paracetamol Overdose Mangement

Answer 6

• If level plotted on or above nomogram line, give acetylcysteine regardless of RFs
• If any doubt over timing of ingestion (e.g. staggered overdose) give acetylcysteine without delay
• If overdose linked to modified release, IV, or massive overdose then discuss with toxicology
• ICU if fulminant liver failure
• Psychiatric referral
• Same management in pregnancy

Question 7

N-acetylcysteine

Answer 7

• Precursor to glutathione
• No contra-indications, even if previously reported reaction benefits outweigh risk
• Full course is three consecutive doses

Question 8

Paracetamol Overdose Late Presentation

Answer 8

If presentation >24hrs after ingestion

• Measure INR, creatinine, ALT and venous blood acid/base or bicarbonate
• If any are abnormal discuss with National Poisons Information Centre

Question 9

Paracetamol Overdose Criteria for Referral

Answer 9

-Encephalopathy, INR >2.0, renal impairment, pH <7.3, SBP <80, hypoglycaemia, metabolic acidosis

Question 10

Paracetamol Overdose Criteria for Liver Transplant

Answer 10

Arterial ph <7.3 or if all of the following occur

-Creatinine over 300, PT >100, grade III/IV encephalopathy