POISONING AND OVERDOSES Flashcards
Pathophysiology of paracetamol poisoning?
Once ingested, paracetamol reaches peak concentration at 4 hours with an average half life of 2 hours (may be significantly increased if hepatic dysfunction)
Paracetamol is primarily metabolised in the liver via conjugation with the addition of glucuronide to form a water soluble metabolite that can be excreted in the urine. When there is excess paracetamol conjugation becomes saturated and paracetamol is converted into the metabolite NAPQI
NAPQI has a short half-life and is usually conjugated by the addition of glutathione, which is then renally excreted. When glutathione stores are depleted, excess NAPQI binds to hepatocellular proteins and results in oxidative damage, mitochondrial dysfunction and ultimately hepatocellular injury.
What can increase the risk of severe hepatotoxicity in paracetemol OD?
Anything that affects glutathione reserves such as fasting, malnourished, chronic excess alcohol consumption and certain liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine, St John’s wort)
How does acute alcohol consumption affect paracetamol OD?
Evidence says it may have a protective effect against hepatotoxicity by inhibiting microsomal acetaminophen oxidation and thereby reducing NAPQI production
Whats the most common cause of acute liver failure requiring liver transplantation in the UK?
Paracetamol OD
What doses of paracetamol OD are associated with serious or fatal effects?
Unlikely to cause toxicity unless staggered <75mg/kg
Serious adverse effects when >150mg/kg
Potentially fatal when >12g
What is a staggered ingestion of paracetamol?
excessive ingestion of paracetamol over a period longer than one hour, usually in the context of self-harm.
Serious toxicity may occur in patients who have ingested > 150 mg/kg in any 24 hour period.
Rarely, toxicity may occur for ingestions between 75-150 mg/kg.
Doses consistently < 75 mg/kg in any 24 hour period are unlikely to be toxic. However, if paracetamol above the recommended daily dose (4g/24 hours in adults) is ingested for the two preceding days or more, the risk increases.
How should you treat pt if you do not know the time of ingestion of paracetamol in a OD?
Treat as a staggered OD to be on the safe side
Natural history of symptoms after a paracetamol OD?
Asymptomatic in early stages
12-36 hours later they may get abdo pain. Some may have N&V
48-72 hours RUQ pain, n&v, jaundice, AKI, hepatic encephalopathy (indicates hepatic necrosis)
Investigations after a paracetamol OD?
FBC
U&E
LFTs
Bone profile
VBG or ABG - pH, bicarbonate, lactate
BM (can cause hypoglycaemia later when liver is damaged)
Paracetemol levels
Salicylates levels
When can we use a nomogram for a paracetamol OD?
If single paracetamol ingestion where an accurate time is known
Not applicable if co-ingestants or modified release ingestions
Can’t be used before 4 hours or after 16 hours
What is the paracetamol nomogram?
A graph that plots paracetamol concentration against time from ingestion
If the paracetamol concentration lies on or above the treatment line, NAC should be administered. This is used for patients who have ingested paracetamol over one hour or less and presented within 8 hours. As the plasma paracetamol concentration reaches its peak at 4 hours, it is important not to take a paracetamol level within 4 hours of the last ingestion.
How to use a nomogram on obese pt who had a paracetamol OD?
Use a max body weight of 110kg even if they weight over this so that we dont underestimate
MOA of NAC?
Precursor to glutathione so increases glutathione stores that can bind to NAPQI and reduce the toxic efefcts
Management of paracetamol OD if they present within 1 hour?
50g activated charcoal if they have taken >12g or 150mg/kg
Otherwise watch and wait
Management of a single ingestion paracetamol OD if they present <8 hours?
Consider activated charcoal if they present wtihin 1 hour
Measure serum paracetamol and LFTs after 4 hours and plot nomogram -> start NAC if over line
Management of a single ingestion paracetamol OD if they present 8-24 hours?
Start IV NAC if dose >150mg/kg
Then measure paracetamol and LFTs and plot on nomogram. If under treatment line and ALT/AST <50 then stop NAC
Management of a single ingestion paracetamol OD if they present >24 hours?
If clearly jaundiced or hepatic tenderness or ALT high then start IV NAC immediately
Measure serum patacetamol and LFTs. If paracetamol still detectable and ALT raised and INR >1.3 then keep on NAC
Management of a staggered OD of paracetamol?
Start IV NAC
If >4 hours since last ingestion then check serum paracetamol levels and do bloods.
Only stop if paracetamol <10, INR <=1.3, ALT is normal and no symptoms of liver damage
Prognosis if given NAC <8 hours after ingestion in paracetamol OD?
Survival should be 100%
What is the new protocol for giving NAC after a paracetamol OD?
Scottish and Newcastle Acetylcysteine Protocol (SNAP) - a 12 hour protocol to try to reduce the rate of adverse reactions
Complications of paracetamol OD?
Severe hepatocellular necrosis -> acute liver failure and encephalopathy
Renal tubular necrosis
Coma
Death
How do we make the decision to refer a pt to a liver transplant centre after a paracetamol OD/
Using the Kings College Criteria
