Paracetamol overdose

Question 1

What damage results from toxic doses of paracetamol?

Answer 1

severe hepatocellular necrosis and, less frequently, renal tubular necrosis

Question 2

What are the early features of paracetamol poisoning?

Answer 2

nausea and vomiting, settles within 24 hours

Question 3

What does the recurrence of nausea and vomiting 2-3 days after paracetamol poisoning indicate?

What are the other possible features?

Answer 3

development of hepatic necrosis

in addition to nausea and vomiting: right subcostal pain and tenderness

Question 4

How long after paracetamol overdose is liver damage maximal and what may it lead to?

Answer 4

3-4 days

liver failure, encephalopathy, coma, death

Question 5

How should the total dose of paracetamol in mg/kg be calculated for obese patients weighing >110kg?

Answer 5

use body weight of 110kg rather than actual boddy weight

Question 6

What is the drug which prevents or reduced the severity of liver damage in paracetamol overdose?

Answer 6

acetylcysteine (or N-acetylcysteine, NAC)

Question 7

When is NAC most effective for treating paracetamol overdose?

Answer 7

if given within 8 hours of paracetamol ingestion

Question 8

What is the difference between acute paracetamol overdose and staggered paracetamol overdose?

Answer 8

• acute overdose = ingestion of potentially toxic dose in 1 hour or less
• staggered overdose = ingestion of a potentially toxic dose of paracetamol over more than 1 hour

Question 9

What is considered the paracetamol dose likely to be toxic?

Answer 9

>150mg/kg (NICE says <75mg/kg unlikely to cause serious toxicity)

Question 10

What are 5 situations when adults and children 6 years and over should be referred to hospital for medical assessment for paracetamol overdose?

Answer 10

1. Have ingested paracetamol in context of self harm
2. Symptomatic
3. Have ingested 75mg/kg or more of paracetamol in 1hr or less
4. have ingested more than a licensed dose and more than or equal to 75mg/kg in a 24h period, or on more than licensed dose on each of preceding 2 or more days
5. time of ingestion uncertain but dose ingested is >75mg/kg

Question 11

What are the 3 criteria for children under 6 years to be admitted to hospital for medical assessment for paracetamol overdose?

Answer 11

any one of the following:

1. symptomatic
2. have ingested >150mg/kg of paracetamol in 1h or less
3. uncertainty about dose ingested or circumstance of ingestion

Question 12

What additional management for paracetamol overdose should be considered if a patient presents early?

Answer 12

activated charcoal should be administered if patient presents within 1hr of ingesting paracetamol in excess of 150mg/kg

Question 13

What is the point at which paracetamol level should be measured following potential overdose?

Answer 13

must be after 4 hours (less than this and samples cannot be accurately interpreted)

Question 14

What are 4 indications for commencing acetylcysteine treatment in patients with potential paraacetamol overdose?

Answer 14

1. plasma-paracetamol falls on or above treatment line on the paracetamol treatment graph (measured >4h)
2. who present within 8 hours of ingestion of more than 150mg/kg of paracetamol if there is going to be a delay of 8 hours or more in obtaining the paracetamol concentration after the overdose
3. who present 8-24h after ingestion of overdose >150mg/kg even if plasma-paracetamol concentration not yet available
4. who present >24h after ingestion of overdose if jaundice or hepatic tenderness, raised ALT, INR>1.3, concentration detectable

Question 15

What are 5 indications for treatment a patient with NAC if they present >24hours after ingestion of the overdose?

Answer 15

1. Jaundice
2. Hepatic tenderness
3. Raised ALT
4. INR >1.3
5. Paracetamol concentration is detectable

Question 16

When should you consider giving acetylcysteine treatment in patients presenting within 24h of overdose even if plasma paracetamol concentration is below the treatment line?

Answer 16

biocheical tests suggest acute liver injury (specifically ALT and INR)

Question 17

When is treatment with acetylcysteine not indicated/if started, it should be stopped?

Answer 17

paracetamol concentration is below treatment line or undetectable, INR+ALT normal, patient asymptomatic

Question 18

How should you manage a patient if the time of ingestion is unknown?

Answer 18

staggered overdose

Question 19

What is the definition of therapeutic paracetamol excess?

Answer 19

ingestion of a potentially toxic dose of paracetamol with intent to treat pain or fever and without self-harm intent during its clinical use

Question 20

What are 3 criteria for a therapeutic overdose to be referred to hospital?

Answer 20

1. symptomatic
2. ingested > licensed dose and >75mg/kg in any 24h period
3. ingested > licensed dose but <75mg/kg/24h on each of the preceding 2 or more days

Question 21

How should patients with suspected therapeutic overdose with clinical features of hepatic injury (jaundice, hepatic tenderness) be managed?

Answer 21

treated urgently with acetylcysteine

Question 22

How should patients with suspected therapeutic excess of paracetamol be maanged if there is uncertainty about whether the presentation was due to therapeutic excess?

Answer 22

manage as staggered overdose

Question 23

Which patients with staggered overdose should be referred to hospital for medical assessment?

Answer 23

all patients with staggered overdose

Question 24

What is the management of staggered overdose of paracetamol?

Answer 24

all patients should be treated with acetylcysteine without delay (i.e. don’t wait for paracetamol level)

Question 25

What are 5 factors in staggered overdose that suggest clinically significant hepatoxicity is unlikely?

Answer 25

1. if there has been at least 4 hours or more since last paracetamol ingestion
2. patient has no symptoms suggesting liver damage
3. paracetamol concentration <10mg/L
4. ALT within normal range
5. INR <1.3

ALL of the above must be met

Question 26

What are the 2 acetylcysteine regimens for treatment paracetamol overdosage?

Answer 26

1. standard 21-hour regimen
2. modified 12-hour regimen (aka Scottish and Newcastle Acetylcysteine Protocol, SNAP) - unlicensed

Question 27

What is the only time the SNAP 12-hour acetycysteine regimen should be used for paracetamol overdosage?

Answer 27

after discussion with a senior clinician

Question 28

How is the standard 21-hour regimen of acetylcysteine given? Describe each part of the regimen

Answer 28

3 consecutive IV infusions over 21h. Requisite dose of acetylcysteine is added to glucose 5% or sodium chloride 0.9% IV infusion

• 1st infusion: 150mg/kg (see weight-specific charts) of acetycysteine added to 200ml glucose 5% or NaCl 0.9% over 1hr
• 2nd infusion: 50mg/kg added to 500ml glucose 5% or NaCl .9% over 4hrs
• 3rd infusion: 100mg/kg added to 1L glucose 5% or NaCl 0.9% over 16hrs

Question 29

How can the charts available on the BNF/TOXBASE be used to guide the acetylcysteine regimen?

Answer 29

they show the volume (rather than mass in mg) of acetylcysteine needed for an IV infusion for weight specific groupings, based on the 200mg/ml concentration of acetylcysteine ampoules

Question 30

When writing up a prescription for N-acetylcysteine what should be taken into account for the total volume?

Answer 30

add the volume of glucose 5% or NaCl 0.9% and the volume of acetylcysteine added (see chart) to give total

Question 31

How is the paracetamol normogram aka treatment graph interpreted?

Answer 31

patients whose paracetamol concentrations are on or above the treatment line should be treated with acetylcysteine by IV infusion

can only be interpreted at least 4h after infusion

only used for non-staggered (acute) overdose

plasma paracetamol concentration on or above treatment line should be regarded as carrying serious risk of liver damage