Common choice for intentional overdose – mostly young women but males and older adults tend to take bigger amounts…

Acetylcysteine almost universally effective when administered within 8-10 hours – but occasional acute liver failure, with high mortality and still one of the most common reasons for hyperacute liver transplant.

Usually no symptoms in first 24 hours after ingestion – by which time the stress that triggered the ingestion has usually passed… Then just nausea, vomiting- not at all clear that acute liver injury is progressing. Abdominal pain then develops (jaundice unusual).

With very large overdoses, can present early with altered mental status or metabolic acidosis.

With overdoses taken in staggered doses (over more than 1-2 hours) risk higher and nomogram unreliable. Paracetamol level x ALT predictive?

Acute kidney injury is seen with acute liver injury (hepatorenal syndrome) but sometimes is main issue (acute tubular necrosis caused by local CYP450 activation).

CYP450 enzymes produce toxic metabolites. Glutathione is natural antidote but once it is used up cell death starts to occur.

Scottish & Newcastle antiemetic protocol (SNAP) – higher initial acetylcysteine dosing (first bag over 2 hours, second bag over 10 hours – cf prev 21 hour regimen), less anaphylactoid reactions. Current HiSNAP trial looking at even higher doses.

Haemodialysis can be considered in severe metabolic acidosis and high paracetamol levels (>900mg/L) but also removes acetylcysteine so dose needs to be doubled.

Co-ingestion of opiates or anticholinergics may delay absorption, so repeat level?

Low body weight tend to get fluid overloaded. Use saline rather than dextrose

Nomograms vary internationally – UK more conservative than US/Australia.

Activated charcoal useful in acute ingestion (<4 hours) or massive overdose.

Anaphylactoid reactions caused by non-immune histamine release – urticaria, flushing, bronchospasm, but not upper airway compromise, angioedema or hypotension. Not a contraindication to repeat treatment.

INR >3 or ALT >1000 are high risk for liver failure, even before encephalopathy develops.