Paracetamol / Poisoning

Question 1

symptoms of paracetamol overdose ?

Answer 1

Common: nausea, vomiting and abdominal pain

After 2-3 days: features of hepatic necrosis with right subcostal pain and tenderness, nausea, vomiting, jaundice, acute kidney injury and hepatic encephalopathy.

Loin pain, haematuria and proteinuria after the first 24 hours may indicate acute kidney injury

Question 2

Investigation for paracetamol overdose ?

Answer 2

fbc , ue , lft , coag , BICARBONATE , GLUCOSE,

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unless staggered overdose

WAIT UNTIL 4 HOURS FROM LAST INGESTION.
plasma paracetamol concentration from all patients.

Plasma concentrations measured less than 4 hours after ingestion cannot be interpreted.

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VBG = severe metabolic acidosis
ABG

Question 3

when should acetylcytiene be given ?

Answer 3

plasma paracetamol concentration is on or above 100mg/L at 4 hours

after 4 hours if the paracetamol levels on the paracetamol nomogram falls on the treatment line

and 15mg/L at 15 hours

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staggered overdose = considered staggered if all the tablets were not taken within 1 hour

OR IF THERE IS DOUBT OVER THE PARACETMOL INGESTION TIME, regardless of the paracetmaol concentration

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Serious toxicity may occur in patients ingesting more than 150 mg/kg in ANY 24 HOUR PERIOD

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patients who present more than 8 hours if they are clearly jaundiced or have hepatic tenderness
ALT is above the upper limit of normal

Question 4

managment of paracetamol overdose ?

Answer 4

if patients presents with 1 hour of ingestion of paracetamol they may benefit from activated charcoal

There is normally no indication to start acetylcysteine without a paracetamol blood concentration provided the result can be obtained and acted upon within 8 hours of ingestion

Question 5

acetylcytiene admnistration ?

Answer 5

12 hour protocol or standard 21 hour using TOXBASE

loading :
1) 200 mL 5% glucose or 0.9% sodium chloride
100 mg/kg acetylcysteine
over 2 hours

2)1000 mL 5% glucose or 0.9% sodium chloride
200 mg/kg acetylcysteine
10 hours

Question 6

Acetylcysteine should be continued if ANY of the following criteria are met in the 12 hour regime

Answer 6

re-check the plasma paracetamol concentration, INR, U&Es, and ALT at, or just before, the end of the 2nd treatment bag

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if any of the follow NAC should be continued

1) ALT is above the upper limit of the normal range

2) The ALT has doubled or more from admission (even within the normal range)

3) The paracetamol concentration is greater than 10 mg/L

Continue at the dose and infusion rate used in the 2nd treatment bag (10-hour). It is not necessary to give a further loading dose unless a second overdose has been taken.

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If the ALT is normal but INR has increased

Both paracetamol and acetylcysteine treatment may cause an increase in INR in the absence of liver injury.

an increase in INR of 0.4 or less can be considered for discharge.

increase in INR of 0.5 or more, stop acetylcysteine and recheck INR and ALT after 4 - 6 hours.

After this 4 - 6 hour if :

INR is unchanged or falling
AND

ALT is less than two times the upper limit of normal

If the criteria above are not met - restart acetylcysteine

Question 7

King’s College Hospital criteria for liver transplantation

Answer 7

Usually used after 48 hours of paracetamol ingestion as this is when liver necrosis becomes severe risk

Arterial pH < 7.3

or all of the following:
prothrombin time > 100 seconds / INR >6.5

creatinine > 300 µmol/l

grade III or IV encephalopathy

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Other predictors of poor prognosis without transplant

Lactate >3.5 mmol/L

Phosphate >3.75 mg/dL

Question 8

graph may mislead when ?

Answer 8

HIV +ve (hepatic glutathione), or if long-acting paraceta- mol has been taken, or if pre-existing liver disease or induction of liver enzymes has occurred.

Paracetamol produces harmful metabolite such as NAPQI
Which decreases the liver glutathione, as it uses it to make it less toxic with conjugating glutathione to it.