Paracetamol Overdose Flashcards
A 24-year-old woman is receiving an intravenous infusion of acetylcysteine for paracetamol poisoning. Thirty minutes into the infusion, she develops a rash. On examination, her heart rate is 95 beats/min and her blood pressure is 117/78 mmHg. She has a widespread urticarial rash.
What is the most appropriate immediate management?
- Continue acetylcysteine and give adrenaline
- Temporarily stop acetylcysteine and give adrenaline
- Continue acetylcysteine and give adrenaline and hydrocortisone
- Temporarily stop acetylcysteine and give hydocortisone
- Temporarily stop acetylcysteine and give chlorphenamine
Temporarily stop acetylcysteine and give chlorphenamine
A 21-year-old man presents to the Emergency Department following a deliberate paracetamol overdose four hours ago. He is unsure how many tablets he took but thinks ‘it was about 20’. A blood sample is immediately taken - the results are shown below:
- Na+142 mmol/l
- K+4.0 mmol/l
- Urea3.7 mmol/l
- Creatinine77 µmol/l
- Bilirubin 21 µmol/l
- ALP 52 u/l
- ALT 22 u/l
- γGT 41 u/l
- Albumin 38 g/l
- Prothrombin time12 secs
- Plasma paracetamol concentration: 85 mg/litre
As this man took the overdose 4 hours ago we can check his paracetamol levels straight away. Looking at the paracetamol treatment graph he is clearly under the normal treatment line so no treatment is needed.
Paracetamol overdose: management
The following is based on 2012 Commission on Human Medicines (CHM) review of paracetamol overdose management. The big change in these guidelines was the removal of the ‘high-risk’ treatment line on the normogram. All patients are therefore treated the same regardless of risk factors for hepatotoxicity. The National Poisons Information Service/TOXBASE should always be consulted for situations outside of the normal parameters.
The minority of patients who present within 1 hour may benefit from activated charcoal to reduce absorption of the drug.
Acetylcysteine should be given if:
- there is a staggered overdose* or there is doubt over the time of paracetamol ingestion, regardless of the plasma paracetamol concentration; or
- the plasma paracetamol concentration is on or above a single treatment line joining points of 100 mg/L at 4 hours and 15 mg/L at 15 hours, regardless of risk factors of hepatotoxicity
Acetylcysteine is now infused over 1 hour (rather than the previous 15 minutes) to reduce the number of adverse effects. Acetylcysteine commonly causes an anaphylactoid reaction (non-IgE mediated mast cell release). Anaphylactoid reactions to IV acetylcysteine are generally treated by stopping the infusion, then restarting at a slower rate.
*an overdose is considered staggered if all the tablets were not taken within 1 hour
King’s College Hospital criteria for liver transplantation (paracetamol liver failure)
- Arterial pH < 7.3, 24 hours after ingestion
- or all of the following:
- prothrombin time > 100 seconds
- creatinine > 300 µmol/l
- grade III or IV encephalopathy
A 30-year-old man is brought to the ED by his wife. Six hours ago he took 24 paracetamol tablets as a deliberate overdose. Looking at his old notes you can see he has been admitted two times previously with drug overdoses and also that he has grand mal epilepsy. He seizures are currently well controlled with carbamazepine monotherapy. Bloods are taken immediately. His U&Es, LFTs and INR are normal. The paracetamol level is shown below:
Plasma paracetamol concentration92 mg/litre
What is the most appropriate next step in management?
- Check carbamazepine levels
- Organise a CT head
- Start intravenous acetylcysteine
- Repeat the paracetamol level in 4 hours
- Explain that no treatment is indicated
This man is ‘high-risk’ as he takes carbamazepine - an inducer of the P450 enzyme system. His 6 hour level of 92 mg/litre puts him above the high-risk treatment line and hence acetylcysteine should be started.
A 19-year-old woman presents to the Emergency Department with a friend. Ten hours ago she took 20 tablets of paracetamol. There is no past medical history of note. She weighs 60 kg. A nurse has already taken blood for paracetamol levels, U&Es, LFTs and prothrombin time. What is the most appropriate next step in management?
- Check her urine for recreational drugs
- Refer her for counselling
- Wait for the paracetamol levels
- Give activated charcoal
- Start acetylcysteine immediately
Start acetylcysteine immediately
This patient has taken a potentially toxic dose of.10,000 mg (20 * 500 mg). As she weighs 60 kg any dose > 9,000 mg (150 mg/kg * 60 kg) should be considered potentially toxic and acetylcysteine should be started before the blood results are available.
A 20-year-old female is seen in the emergency department after an intentional overdose. She took all the paracetamol in her house which she estimates to be between 10-20 tablets.
On questioning regarding the timing of ingesting the paracetamol, the patient reported taking the tablets with alcohol, whilst removing them from their blister packets. She knows it took 30 minutes to take the tablets as it was after this period when she was found by her parents. She reports taking the last tablet 3 hours prior to arriving in the department.
On arrival in the emergency department, a serum paracetamol level was taken, which came back at 90mg/L.
What is the most appropriate management plan?
- No medical treatment required
- Start activated charcoal treatment followed by N-acetylcysteine treatment
- Start and complete full N-acetylcysteine treatment
- Do not start treatment yet and repeat serum paracetamol level at 4 hours post ingestion
- Start N-acetylcysteine treatment and repeat serum paracetamol level at 4 hours post ingestion
Do not start treatment yet and repeat serum paracetamol level at 4 hours post ingestion.
This patient has potentially taken a significant paracetamol overdose and has presented to the emergency department 3 hours after ingestion. This is not a staggered overdose, as the patient reports taking the tablets over 30 minutes, and a staggered overdose is defined as taking paracetamol over more than a 1 hour period. For this reason, treatment does not need to be started immediately and can be held until a 4-hour post-ingestion paracetamol level result is back. At this point, if the level is confirmed to be above 100 mg/L (on or above the nomogram line) then N-acetylcysteine treatment can be started. Paracetamol levels prior to 4 hours post-ingestion are inaccurate and therefore should not be used to assess the need for treatment.
Medical treatment is potentially needed as the patient may have taken a significant paracetamol overdose. A serum paracetamol level should be taken at 4 hours post-ingestion. If the serum paracetamol level is below the nomogram line no medical treatment will be required.
Activated charcoal can be used to reduce paracetamol absorption in the few patients who present within 1 hour of taking an overdose. As this patient has presented over 1-hour post-ingestion activated charcoal has no role in her management.
The use of N-acetylcysteine may be required however this must first be confirmed via a 4-hour post-ingestion level. As it is unclear as to whether or not the patient’s overdose is significant, treatment should be held until confirmed via 4-hour levels.
If a patient presents following a potentially significant paracetamol overdose and levels will not be available within 8 hours of ingestion, then N-acetylcysteine should be started immediately. Levels can then be taken, and if they are found to be below the nomogram line treatment can be stopped.
DiscussImprove
A 18-year-old male is admitted after deliberately ingesting 40 grams of paracetamol. Twenty-four hours after admission he is reassessed with a view to liver transplantation. Of the following, which one would most strongly indicate the need for a liver transplant?
- CRP 306
- Arterial pH 7.25
- Creatinine 267 µmol/l
- Grade IV encephalopathy
- INR 5.7
Liver transplantation criteria in paracetamol overdose: pH < 7.3 more than 24 hours after ingestion.
The arterial pH is the single most important factor. The creatinine, encephalopathy grade and INR must all be grossly abnormal otherwise.
King’s College Hospital criteria for liver transplantation (paracetamol liver failure)
- Arterial pH < 7.3, 24 hours after ingestion
or all of the following:
- prothrombin time > 100 seconds
- creatinine > 300 µmol/l
- grade III or IV encephalopathy
A 17-year-old female has presented to the emergency department having taken a paracetamol overdose. Her paracetamol levels were recorded on admission and the decision to treat with IV acetylcysteine was made. On admission, her physical observations were all within normal ranges.
You are dealing with another patient when you are called urgently to re-assess this young female. She is now complaining of severe shortness of breath and describes herself as feeling ‘funny’. The IV acetylcysteine was commenced 10 minutes ago. The nurse has kindly carried out a set of observations for you below.
- Respiratory rate - 32 breaths per minute
- Oxygen saturations - 87%
- Blood pressure - 114/71mmHg
- Heart rate - 106bpm
- Temperature - 37.1ºC
What is the most appropriate response to this?
- Continue the infusion
- Continue the infusion and give nebulised salbutamol
- Immediately stop the IV acetylcysteine infusion, give nebulised salbutamol and bleep the on-call hepatobiliary consultant to discuss surgical interventions
- Immediately stop the IV acetylcysteine infusion, give nebulised salbutamol, then re-commence the IV infusion at a slower rate
- Immediately stop the IV acetylcysteine infusion, give nebulised salbutamol, then re-commence the IV infusion at the same rate
Immediately stop the IV acetylcysteine infusion, give nebulised salbutamol, then re-commence the IV infusion at a slower rate
Anaphylactoid reactions to IV N-Acetylcysteine are generally treated by stopping the infusion, then restarting at a slower rate
- The change in this patient’s presentation has occurred after the administration of the IV acetylcysteine. She has described being short of breath, her oxygen saturations have dropped and her respiratory effort has increased. All of this points to bronchospasm, a common anaphylactoid reaction to the acetylcysteine.
- In the case of an anaphylactoid reaction, it is most appropriate to stop the current infusion which is responsible for the change in presentation. Continuing the infusion, regardless of the nebulised salbutamol, would be the incorrect response.
- Following this, adequate symptom control is necessary to treat the bronchospasm, then you would aim to re-start the IV infusion at a slower rate, usually at 50mg/kg over four hours.
- Restarting the IV infusion at the same rate would likely lead to the same outcome.
- Bleeping the on-call hepatobiliary consultant to discuss surgical interventions would be inappropriate here. This is a common anaphylactoid reaction and is not related to the degree of paracetamol overdose.
A 32-year-old man was admitted to the emergency department at 15:00, having taken an overdose of paracetamol. He states that he has attempted suicide due to feeling overwhelmed with his postgraduate degree and that he has felt particularly lonely since he moved to university. When asked how many tablets he has taken, he reluctantly admits to taking 30 paracetamol tablets over the course of the day since waking around 06:00. He has not consumed any other tablets with this overdose. He also cannot remember exactly when he last took some of the tablets, but he knows this was before 13:00.
What is the most appropriate next step?
- Immediately administer IV naloxone
- Immediately administer IV acetylcysteine
- Immediately administer activated charcoal
- Measure plasma paracetamol concentration before administering IV acetylcysteine
- Measure plasma paracetamol concentration before administering activated charcoal
Patients who take a staggered paracetamol overdose should receive treatment with acetylcysteine
Important for meLess important
The correct approach to this patient is to immediately administer IV acetylcysteine. This is because the question stem shows that there has been a staggered paracetamol overdose (30 tablets over approximately 7 hours), and therefore you should give IV acetylcysteine regardless of the possible plasma paracetamol concentration. This is based on the guidance of the 2012 Commission on Human Medicines (CHM) review of paracetamol overdose management (see notes below).
Activated charcoal is not appropriate, as this should only be given when the tablets have been consumed less than 1 hour ago. In this case, ingestion took place at least 2 hours prior, and thus the activated charcoal would have no benefit.
IV naloxone is not suitable in this patient as there is no evidence of an opioid overdose. The question states that he ‘has not consumed any other tablets with this overdose’.
Discuss (4)Improve
Of the following, which one is the most useful prognostic marker in paracetamol overdose?
- ALT
- Prothrombin time
- Paracetamol levels at presentation
- Paracetamol levels at 12 hours
- Paracetamol levels at 24 hours
Prothrombin time
An elevated prothrombin time signifies liver failure in paracetamol overdose and is a marker of poor prognosis. However, arterial pH, creatinine and encephalopathy are also markers of a need for liver transplantation
A young woman with emotionally unstable personality disorder attempts suicide following a breakup with her boyfriend. She had taken a staggered overdose of paracetamol which she soon regrets and she presents to the emergency department seeking treatment. She is commenced on N-acetylcysteine but quickly develops a reaction to the drug transfusion.
What is the most likely underlying cause of her reaction?
- IgA deficiency
- IgE mediated mast cell release
- IgG immune complex formation
- IgM immune complex formation
- Non-IgE mediated mast cell release
Non-IgE mediated mast cell release
N-Acetylcysteine commonly causes an anaphylactoid reaction (non-IgE mediated mast cell release)
Anaphylactoid reactions are defined as reactions that produce the same clinical picture with anaphylaxis but are not IgE mediated. Symptoms, therefore, include airway involvement and sometimes may be severe, leading to cardiovascular collapse and death. Anaphylactoid reactions are derived from the activation of the complement and/or bradykinin cascade and the direct activation of mast cells and/or basophils.
IgE mediated mast cell release describes anaphylaxis which is less common than an anaphylactoid reaction.
IgA deficiency makes individuals more prone to anaphylaxis but alone should not cause a drug reaction.
IgM and IgG immune complex formation describe type III hypersensitivity disorders and not acute drug reactions.
A 27-year-old woman with a history of depression presents to the Emergency Department. She reports taking 50 paracetamol tablets yesterday. Bloods are taken on admission. Which one of the following would most strongly indicate the need for a liver transplant?
- Blood glucose 2.2 mmol/l
- ALT 2364 iu/l
- INR 4.1
- Creatinine 230 µmol/l
- Arterial pH 7.27
Arterial pH 7.27
Liver transplantation criteria in paracetamol overdose: pH < 7.3 more than 24 hours after ingestion
Important for meLess important
The arterial pH is the single most important factor according to the King’s College Hospital criteria for liver transplantation.
A 23-year-old female with severe learning difficulties is brought into the emergency department by her parents following an accidental paracetamol overdose. She was found 30 minutes ago to have mistakenly ingested 16 grams of paracetamol after having been briefly unsupervised.
What is the best initial management of this patient?
- Start N-acetylcysteine immediately
- Start N-acetylcysteine if indicated by paracetamol levels
- Give activated charcoal and then N-acetylcysteine if indicated by paracetamol levels
- Gastric lavage followed by N-acetylcysteine if indicated by paracetamol levels
- Gastric lavage only
Activated charcoal can be used within 1 hour of a paracetamol overdose
Important for meLess important
This patient presented within 1 hour of paracetamol ingestion and based on the clear collateral history this was not a staggered overdose. This means that activated charcoal should be used in this patient in order to prevent further paracetamol being absorbed into the circulation.
There is no indication for immediate N-acetylcysteine (NAC) in this scenario. NAC is used immediately if a paracetamol overdose is staggered or if there is doubt about the chronology of the overdose. However, this scenario has a very clear collateral history from concerned parents regarding the chronology of the overdose.
Although NAC may be required later, activated charcoal should be given immediately as there is a small window of opportunity to prevent further paracetamol absorption.
Gastric lavage and activated charcoal are mutually exclusive interventions and many studies have shown activated charcoal to be superior to gastric lavage. Therefore there is no role of gastric lavage in paracetamol overdose where activated charcoal is available.
A 19-year-old is brought into the emergency department with a paracetamol overdose. The overdose consisted of 60 tablets with half a bottle of rum. They broke up with their partner earlier today and took the overdose impulsively.
Their past medical history is significant for epilepsy treated with carbamazepine, and depression treated with citalopram. In terms of social history, they regularly smoke 10 cigarettes a day and normally drink 4 units a week.
Which part of their medical history puts them at the highest risk for hepatotoxicity?
- Alcohol intake
- Depression treatment
- Epilepsy treatment
- History of smoking
- Impulsive nature
Epilepsy treatment
Paracetamol overdose: acute alcohol intake is not associated with an increased risk of developing hepatotoxicity and may actually be protective.
The main medical concern with a paracetamol overdose is hepatotoxicity. This is influenced by a wide variety of factors, including normal liver functioning, medication use, and nutritional status.
Carbamazepine is a liver enzyme-inducing drug that is classically quoted as placing individuals at high risk of hepatotoxicity following an overdose. This may be due to the drug accentuating the toxicity of paracetamol, or due to long-term treatment with the drug reducing the liver’s store of protective substances. Therefore, this is the correct answer.
Acute alcohol intake is, contrary to popular belief, not associated with an increased risk of hepatotoxicity. This may be due to alcohol inhibiting pathways that break down paracetamol into more toxic substances. Chronic alcohol use is a risk factor, but this is because chronic use weakens the liver over time.
Treatment with citalopram has no influence on the hepatotoxicity of paracetamol following overdose. Whilst citalopram is metabolised and excreted by the liver, it does not cause any liver changes and would therefore not be expected to increased hepatotoxicity.
A history of smoking will not affect the liver to any extent which damages it long term. Therefore, this is not the correct answer.
The impulsive nature of the overdose is more of a concern from a psychiatric point of view, rather than medically being related to hepatotoxicity.
A 29-year-old woman presents to the emergency department after being found at home having taken an overdose. She tells you that she took two packets of paracetamol 500mg tablets (32 tablets in total) around six hours ago. She is admitted to the observation unit for IV n-acetylcysteine.
In this scenario, which of the following factors is not associated with an increased risk of developing hepatotoxicity?
- Acute alcohol intake
- Carbamazepine
- Chronic alcohol excess
- Malnutrition
- St John’s Wort
Acute alcohol intake
Paracetamol overdose: acute alcohol intake is not associated with an increased risk of developing hepatotoxicity and may actually be protective
Important for meLess important
The following groups of patients are at an increased risk of developing hepatotoxicity following a paracetamol overdose:
Patients taking liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine, St John’s Wort)
Patients with a history of chronic alcohol excess
Malnourished patients (e.g. anorexia nervosa) or patients who have not eaten for a few days, due to depletion of glutathione.
Acute alcohol intake is not associated with an increased risk of developing hepatotoxicity and may actually be protective.
