Paracetamol Overdose

Question 1

High risk patients?

Answer 1

Patients taking liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine), chronic alcohol excess, St John’s Wort)

Malnourished patients (e.g. anorexia or bulimia, cystic fibrosis, hepatitis C, alcoholism, HIV) - low gluthathione stores

Patients who have not eaten for a few days

Question 2

Pathophysiology?

Answer 2

Paracetamol inactivated in liver by conjugation producing metabolites glucuronide or sulphate – these are excreted renally.

In OD – liver overwhelmed so paracetamol metabolised by an alternate pathway

Toxic metabolite – N-actely-p-benzoquinone imine (NAPQI) produced by cytochrome p450 – inactivated by glutathione  preventing harm.

When glutathione stores depleted <30% (after ~10 hours)  NAPQI reacts with nucleus of cell - necrosis in liver & kidney tubules.

Question 3

Signs/Symptoms?

> 24 hrs?

Late?

Answer 3

None initially
Vomiting +/- RUQ pain

Jaundice
Encephalopathy from liver failure +/- renal failure (oliguria)

Lactic acidosis

Question 4

Response (Airway)?

Answer 4

Maintain & clear airway

Question 5

Response (Breathing)?

Answer 5

ABG

Question 6

Response (Circulation)?

Answer 6

IV access
Bloods: FBC, U&E’s, LFT’s specifically AST/ALT), glucose, clotting screen, INR, PT
ECG

Question 7

What is the first and second step that need to be recognised after an acute OD?

Answer 7

Establish time since ingestion

Establish if patient is high risk or not

Question 8

Mx if <1 hrs since ingestion and >150mg/kg taken?

Answer 8

Consider activated charcoal

Question 9

Mx if <4 hrs since ingestion?

Answer 9

Check paracetamol level at 4 hrs
Plot level on paracetamol treatment graph
Start N-acetylecysteine (NAC) IV in 5% Dextrose if on or above treatment line (at 4hrs: 100mg/L and 200 mg/L (high risk))

Question 10

Mx if 4-8 hrs since ingestion?

Answer 10

Check paracetamol levels immediately
Plot level on paracetamol treatment graph
Start N-acetylecysteine (NAC) IV in 5% Dextrose if on or above treatment line

Question 11

Mx if 8-24 hrs since ingestion?

Answer 11

Start NAC immediately
Check paracetamol levels
If paracetamol level on or above treatment line continue NAC
If level below treatment line - STOP NAC

Question 12

Mx if >24 hrs since ingestion or unable to to establish?

Answer 12

Start NAC
Check paracetamol level and AST/ALT
If paracetamol level > 66 micro mol/L or >10 mcg/mL or AST/ALT increased or any evidence of renal dysfunction continue NAC.

Question 13

How often should bloods be repeated if treatment is started?

Answer 13

On admission
At 12 hrs
Every 24 hrs subsequently

Question 14

What else can be given IV if needed?

Answer 14

Vitamin K