Acetaminophen overdose

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Paracetamol overdose

Paracetamol overdose is common and may occur accidentally or in the context of self-harm and suicide. Significant overdose can result in liver failure if not promptly treated with the antidote.

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What happens when you overdose on paracetamol?

Paracetamol is usually taken by mouth and is available in tablet, caplet, soluble and liquid forms. The paracetamol passes via the stomach and intestine into the body and leads to pain relief and lowering of a high temperature (fever).

After this, paracetamol is inactivated before being removed from the body. About 20% of the medicine is processed in the intestinal wall and the remainder in the liver. During this process, a small amount of a toxic compound (n-acetyl-p-benzoquinone imine, or NAPQI) is formed in the liver but this is quickly detoxified by a substance called glutathione.

In overdose, the stores of glutathione can be reduced so much that there isn’t enough of it left to remove the increased amounts of NAPQI. The NAPQI then builds up and can damage the liver.

Paracetamol is the most common medicine that is taken as an overdose. It can lead to liver failure in just a few days, even if medication is given to protect the liver. Liver failure can be fatal.

In 2021, there were 227 deaths recorded in England and Wales due to paracetamol overdose. There were 261 deaths in 2022 from paracetamol overdose in England and Wales. There has been a general decrease in deaths from paracetamol overdoses since 1997 when there were 653 deaths in England and Wales.

Why would someone take an overdose?

There are many reasons why someone might take an overdose. This could be due to wish to end one’s life or to cause serious self-harm. An overdose can also be taken accidentally – for example, toddlers may like the taste of liquid paracetamol and people with poor eyesight may take the wrong tablet by mistake.

In some, the act of taking an overdose is a spur-of-the-moment thing, whilst in others it can be pre-planned. Those who have pre-planned may have stockpiled medication, sorted out their affairs (such as writing a will) and also written a suicide note.

Some people take higher than the recommended daily dose of paracetamol for pain over several days. They may not intend to kill themselves, and occasionally may not even realise they are harming themselves until they begin to feel unwell. This might also occur if they are taking two different preparations which both contain paracetamol.

The maximum number of paracetamol that should be taken within 24 hours is eight 500mg tablets. This includes any medication which contains paracetamol such as co-codamol or some cold and flu remedies.

Some people are at increased risk of liver damage from paracetamol. This includes:

• Those on certain medications, such as rifampicin, phenobarbital, phenytoin, carbamazepine and alcohol.
• Those who are malnourished – for example, through chronic illness or eating disorders.
• Those with alcohol-related liver disease.

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Why paracetamol?

Paracetamol is widely available from shops and is present in most homes. The government has limited how much can be bought in one go which may help reduce the number of overdoses. It is reasonably easy to take and so the government has also ruled that it should only be available in blister packs which can mean the tablets are more difficult to get out in large numbers.

What are the symptoms of paracetamol overdose?

There may be no symptoms for the first day. A feeling of sickness (nausea) and being sick (vomiting) may occur a few hours after taking the overdose. After 24 hours there may be pain under the ribs on the right side (where the liver is) and there may be yellowing of the whites of the eyes and the skin (jaundice). Other features include:

• The brain can also be affected with confusion and disorientation (called encephalopathy).
• The kidneys can also be affected with a reduction in urine, and kidney failure can occur.
• Low blood sugar (hypoglycaemia) may occur.
• There may be a build-up of acid in the blood, which can cause faster breathing.
• There may also be features of depression but not always.

Sometimes carers or family members discover that someone has taken an overdose. They may find empty packets or a suicide note. It is important to bring the empty packets and notes to the hospital.

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How is paracetamol overdose assessed in hospital?

The healthcare professional will make a full assessment and will also ask about:

• The number of tablets taken.
• What time the overdose was taken.
• Whether the medicine was in tablet, caplet, liquid or soluble form.
• Whether any other tablets were taken at the same time.
• Whether any alcohol was taken at the same time.
• Any suicide plans, such as whether a note was written.

They will also undertake a full examination which, early on, may not find any abnormalities. Once liver damage sets in there may be jaundice, a tender liver and presence of brain involvement (called encephalopathy). Unfortunately, it is often too late to treat the liver at this point, other than by a liver transplant.

What investigations are needed?

This mainly consists of blood tests and includes:

Paracetamol levels

• If the tablets were all taken in one go: the paracetamol level needs to be checked four hours after the time of the overdose. If the time is unknown or more than four hours have passed then a sample will be taken immediately.
• If the tablets have been taken over several hours or days: this is called a ‘staggered overdose’ and a paracetamol level will be taken immediately and treatment started before the level is back.

Liver function tests

These are a group of blood tests that reveal how the liver is functioning. Early on, they may be normal. They may increase later on, showing that there has been damage to the liver and that liver failure is possible. A blood clotting test (called prothrombin time) is an earlier and better indicator of liver damage.

Prothrombin time

As part of the blood clotting tests that will be requested, this gives an idea of how ‘thin’ the blood is. The liver makes important factors for blood clotting. When the liver becomes damaged, the prothrombin time rises. The higher the level, the more severe the liver involvement. It will be checked several times.

Renal function tests

These are blood tests looking at the function of the kidney. They will show if there is any kidney damage or kidney failure.

Blood sugar levels

Low levels (called hypoglycaemia) can occur when the liver is failing. A fingertip test will often be done hourly.

Arterial blood gas

This involves an arterial blood sample being taken (usually at the wrist where the pulse is taken) and reveals levels of acid in the blood. Acid levels are very tightly controlled by the body and in paracetamol overdose acid levels can rise early. People with higher acid levels are usually sicker.

Other tests that are requested will depend on each individual case and the patient’s course. For example, if other medications were taken, then their levels may need to be checked.

How can paracetamol overdose be treated?

Immediate management will require resuscitation and stabilisation in A&E. If the patient is unstable – such as having low blood pressure – or there is overwhelming liver failure, they will need to be treated on an intensive care unit.

The paracetamol levels will be sent off and once the result is back this is compared with a standard graph – patients who are above a certain line will need treatment. Those below the line may not require treatment.

Treatment is with intravenous N-acetylcysteine (NAC) and is given to all who have high paracetamol levels. If there is any doubt about the time of the overdose or there has been a ‘staggered overdose’, intravenous NAC is started without delay.

All patients will need to be seen by the psychiatric team before discharge. If there is concern about the risk of ongoing severe harm to the patient then they may be admitted to hospital, either with their agreement, or without their agreement under the Mental Health Act (colloquially known as ‘being sectioned’).

N-acetylcysteine (NAC) treatment

NAC protects the liver, partly by restoring glutathione levels and partly by helping the liver to combat toxicity. A full treatment course consists of three consecutive bags of the medicine, mixed with intravenous fluid and given over approximately 24 hours.

During that period several blood tests may be taken to monitor the liver and kidneys. It is most effective when given within eight hours of taking the paracetamol overdose.

If, however, there is ongoing damage from the paracetamol overdose then the NAC treatment may need to be prolonged. NAC is used in children and also in pregnant women. In pregnant women, a paracetamol overdose can affect the liver of the fetus as well and NAC can help prevent this.

The main complication following a paracetamol overdose is liver failure. The patient may need to be referred to the specialist liver unit if the bloods confirm liver failure.

Other features which will help the healthcare professionals to decide if the patient needs to go to a specialist unit include:

• Involvement of the brain.
• Abnormal clotting.
• Kidney impairment.
• Low blood pressure (hypotension).
• Low blood sugar (hypoglycaemia) and high blood acid levels.

Urgent liver transplantation is the only treatment when overwhelming, irreversible liver failure occurs.

Acetaminophen overdose

Acetaminophen (most common brand name Tylenol) is a pain medicine. Acetaminophen overdose occurs when someone takes more than the recommended amount of this medicine. Acetaminophen overdose is one of the most common poisonings. People often think that this medicine is very safe. However, it can be deadly if taken in large doses. This article is for information only. DO NOT use it to treat or manage an actual overdose. If you or someone you are with overdoses, call the local emergency number (such as 911), or the local poison control center can be reached directly by calling the national toll-free Poison Help hotline (1-800-222-1222) from anywhere in the United States.

Where Found

• Anacin-3
• Liquiprin
• Panadol
• Percocet
• Tempra
• Various cold and flu medicines

Note: This list is not all inclusive.

Common dosage forms and strengths:

• Suppository: 120 mg, 125 mg, 325 mg, 650 mg
• Chewable tablets: 80 mg
• Junior tablets: 160 mg
• Regular strength: 325 mg
• Extra strength: 500 mg
• Liquid: 160 mg/teaspoon (5 milliliters)
• Drops: 100 mg/mL, 120 mg/2.5 mL

Adults should not take more than 3,000 mg of single-ingredient acetaminophen a day. You should take less if you are 65 or more years old. Taking more, especially 7,000 mg or more, can lead to a severe overdose problems. If you have liver or kidney disease, you should discuss the use of this drug with your health care provider.

Symptoms

Symptoms may include:

• Abdominal pain, upset stomach
• Appetite loss
• Coma
• Seizures
• Diarrhea
• Irritability
• Jaundice (yellow skin and whites of the eyes)
• Nausea, vomiting
• Sweating

Note: Symptoms may not occur until 12 or more hours after the acetaminophen was swallowed.

Home Care

There is no home treatment. Seek medical help right away.

Before Calling Emergency

The following information is helpful for emergency assistance:

• Person’s age, weight, and condition
• Name of the product (ingredients and strength, if known)
• Time it was swallowed
• Amount swallowed

However, DO NOT delay calling for help if this information is not immediately available.

Poison Control

Your local poison control center can be reached directly by calling the national toll-free Poison Help hotline (1-800-222-1222) from anywhere in the United States. This national hotline will let you talk to experts in poisoning. They will give you further instructions.

This is a free and confidential service. All local poison control centers in the United States use this national number. You should call if you have any questions about poisoning or poison prevention. It does NOT need to be an emergency. You can call for any reason, 24 hours a day, 7 days a week.

What to Expect at the Emergency Room

The provider will measure and monitor the person’s vital signs, including temperature, pulse, breathing rate, and blood pressure. Blood tests will be done to check how much acetaminophen is in the blood. The person may receive:

• Activated charcoal
• Airway support, including oxygen, breathing tube through the mouth (intubation), and ventilator (breathing machine)
• Blood and urine tests
• Chest x-ray
• CT (computerized axial tomography) scan
• ECG (electrocardiogram, or heart tracing)
• Fluids through the vein (intravenous or IV)
• Laxative
• Medicines to treat symptoms, including an antidote, n-acetylcysteine (NAC), to counteract the effects of the drug

People with liver disease are more likely to develop serious complications of acetaminophen overdose. Overdose may be either acute (sudden or short-term) or chronic (long-term), depending on the doses taken, and symptoms may therefore vary.

Outlook (Prognosis)

If treatment is received within 8 hours of the overdose, there is a very good chance of recovery.

However, without rapid treatment, a very large overdose of acetaminophen can lead to liver failure and death in a few days.

References

Aronson JK. Paracetamol (acetaminophen) and combinations. In: Aronson JK, ed. Meyler’s Side Effects of Drugs. 16th ed. Waltham, MA: Elsevier; 2016:474-493.

Ganetsky M. Acetaminophen. In: Walls RM, ed. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 10th ed. Philadelphia, PA: Elsevier; 2023:chap 138.

Version Info

Last reviewed on: 1/2/2023

Reviewed by: Jesse Borke, MD, CPE, FAAEM, FACEP, Attending Physician at Kaiser Permanente, Orange County, CA. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.