Paracetamol poisoning

Question 1

How many hospital admissions are due to self-poisoning with paracetamol?

Answer 1

up to 40% of all admission

- most deaths are associated with deliberate poisoning

Question 2

What is the pathophysiology of paracetamol toxicity?

Answer 2

mechanism of NAPQI induced hepatic injury incl:
- glutathione depletion
- direct oxidizing and arylating effects
paracetamol induced renal damage also probably results from formation of NAPQI

Question 3

What are the factors that influence paracetamol hepatoxicity ?

Answer 3

dose of paracetamol ingested/absorbed
plasma paracetamol conc
time to antidote admin
whether the tablets were taken as a single acute event or in a staggered fashion

Question 4

What are the doses of paracetamol and the likelihood of serious liver damage?

Answer 4

<75 mg/kg = extremely unlikely
75-100mg/kg = rare
>150 = possible

Question 5

What is used clinically to determine if a patient is likely to suffer liver damage or not?

Answer 5

Use the paracetamol normogram = Y-axis = plasma conc of paracetamol and x-axis = hours after ingestion

• below the curve = liver damage unlikely
• above the line = predicts significant liver damage - requires anti-dotal meds

Question 6

Why can’t you have a plasma concentration before 4 hours?

Answer 6

because the drug is still being processed

Question 7

What is the antidote for paracetamol poisoning ?

Answer 7

glutathione precursors - supplement dietary glutathione to augment the potential to detoxify NAPQI (NAPQI can’t be detoxified because GSH is saturated)
Most widely used antidote= acetylcysteine (IV with 5% glucose)

Question 8

What are the adverse effects of acetylcysteine therapy?

Answer 8

approx. 10-15% suffer anaphylactoid features
flushing, urticaria, pruritus, bronchospasm
histamine mediated
rarely- angio-odema, wheezing, resp distress, hypotension
Reactions occur immediately following admin of 150mg/kg bag
- occasionally an anti-histamine is necessary

Question 9

What is the 8 hour rule?

Answer 9

provided a patient is treated within 8 hours of overdose they are not at risk of significant liver damage
always worth waiting for plasma conc following a single overdose provided the result will be available within 8 hour time limit

Question 10

When does the time normogram become less reliable?

Answer 10

Beyond 15 hours

Question 11

What is considered a staggered overdose?

Answer 11

any pt thats taken a paracetamol overdose over more than 60 mins - still need to be treated with acetylcysteine

Question 12

What is the 24 hour rule?

Answer 12

Clinically significant hepatotoxicity is extrememly unlikely in any patient who 24 hours most recent paracetamol ingestion is:

• asymptomatic
• no paracetamol detectable in plasma
• normal ALT activity
• normal INR

Question 13

What are the clinical features at presentation on day 1 ?

Answer 13

asymptomatic

nausea, vomiting, abdominal pain, anorexia, pallor

Question 14

What are the clinical features at presentation on day 2 ?

Answer 14

may become asymptomatic
nausea and vomiting
hepatic tenderness +/- generalised abdominal pain
occasionally mild jaundice

Question 15

What are the clinical features at presentation on day 3-5 ?

Answer 15

if severe poisoning - jaundice leads to liver failure and encephalopathy
back pain and renal tenderness can lead to renal failure
DIC +/- liver failure
cardiac arrhythmias = arrest

Question 16

What biochemical and haematological abnormalities can be seen ?

Answer 16

AST/ALT increased
Bilirubin increased
blood sugars decreased
phosphate decreased (renal tubular leak) - early warning sign of renal damage 
metabolic acidosis 
INR increased 
Clotting factors - 2, 5, 7 reduced 
platelets reduced

Question 17

In late presenters what biomarkers provide prognostic information?

Answer 17

PT/INR 
creatinine- the higher the worse prognosis 
pH - most sensitive marker 
presence of encephalopathy 
age - >50 do much worse