What is Acetaminophen Toxicity (Acetaminophen Poisoning)?
Acetaminophen, also known as N-acetyl-para-aminophenol, paracetamol, or APAP, is a common over-the-counter medicine that many people think is very safe because of its wide availability. In fact, over 60 million Americans use acetaminophen every week. It’s found in many combination medicines, often paired with opioids and diphenhydramine, an antihistamine used to relieve allergy symptoms. However, many people don’t realize that these combination medications contain acetaminophen.
Acetaminophen is a type of pain reliever and fever reducer that works differently than Nonsteroidal anti-inflammatory drugs (NSAIDs). The exact way it works isn’t completely known, but it seems to block a specific enzyme called ‘cyclooxygenase’ (COX) in the brain. This helps to ease pain and reduce fever. Acetaminophen may also block the production of certain chemicals called ‘prostaglandins’ in the central nervous system (CNS), which includes the brain and spinal cord. One of the primary effects of acetaminophen is to work on the hypothalamus, a part of the brain that plays a key role in regulating body temperature, thus producing a fever-reducing effect.
What Causes Acetaminophen Toxicity (Acetaminophen Poisoning)?
Acetaminophen, a common over-the-counter medicine used for pain relief and reducing fever, is generally safe to use when taken as directed. However, consuming too much can lead to significant damage to the liver.
For adults, it’s advised not to take more than 650 mg to 1000 mg every 4 to 6 hours, and the total amount taken in a day should not exceed 4 grams. For children, the recommended calculation is a bit different – it’s based on their weight. They should take 15 mg for every kilogram of their weight every 6 hours, but the total they take in a day should not surpass 60 mg for every kilogram of their weight.
If more than 7.5 grams to 10 grams a day, or 140 mg for every kilogram of weight, is consumed, it can result in toxic effects. This highlights the importance of staying within the recommended dose to ensure safety when using the medication.
Risk Factors and Frequency for Acetaminophen Toxicity (Acetaminophen Poisoning)
Acetaminophen toxicity, which refers to an excess of this drug in the body, is a leading cause of liver transplantation around the globe, and the main cause in the U.S. Each year in the United States, it results in:
- 56,000 visits to the emergency department
- 2,600 hospitalizations
- 500 deaths
Half of these cases are unintentional overdoses. While it’s more common in children, adults who get it often experience more severe and life-threatening symptoms.
Signs and Symptoms of Acetaminophen Toxicity (Acetaminophen Poisoning)
Acetaminophen toxicity can develop over time and is broken down into four stages. Each stage has different symptoms and effects on the body.
- The first stage occurs from 30 minutes to 24 hours. During this stage, a person might not show any symptoms, or they might experience vomiting.
- The second stage lasts from 18 hours to 72 hours. In addition to vomiting, symptoms now include pain in the upper right part of the stomach and a decrease in blood pressure.
- The third stage extends from 72 hours to 96 hours. At this point, the liver isn’t functioning properly, which could cause kidney failure, blood clotting disorders, a build-up of acid in the body, and changes in mental state. There might be a return of stomach symptoms, too. This stage is most often when death occurs.
- The fourth and final stage lasts from 4 days to 3 weeks, and it’s marked by a recovery period.
Testing for Acetaminophen Toxicity (Acetaminophen Poisoning)
If your doctor thinks you may have taken too much acetaminophen (commonly known as Tylenol), they will base their diagnosis on the amount of the drug in your blood, even if you don’t have any symptoms. To do this, they may run some tests including liver function tests, and blood clotting tests, which are often referred to as PT/INR. If you’ve had a particularly severe dose, your liver function tests may show abnormalities within 8 to 12 hours of taking the drug. Usually, these liver tests remain abnormal for about 18 to 72 hours.
Your doctor may also find it helpful to check for other drugs in your system, perform an EKG to check your heart, and order a metabolic panel which gives them a broad look at your body’s chemical balance and metabolism. They will specifically look at a measurement called the “Rumack-Matthew Nomogram.” This is a tool doctors use to see if the amount of acetaminophen in your blood is in the danger zone. If your levels are above 150 mcg/mL four hours after ingestion, this is considered toxic and treatment would be started.
However, it’s important to note that this measurement has to be taken between 4 to 24 hours after you took the acetaminophen. This tool also only applies to a single instance of taking too much acetaminophen, not ongoing, repeated situations.
For those who’ve chronically ingested too much acetaminophen, the guidelines are different. In such cases, the amount of acetaminophen in your blood may not match the seriousness of the overdose. Here, the doctor must rely on other risk factors, test results, and their clinical judgment. Overdose is suspected and treated if your acetaminophen level is above 20 mcg/mL, or if your liver function tests are abnormal. In such cases, there is generally less toxicity as the liver has a chance to rebuild its natural defenses.
Treatment Options for Acetaminophen Toxicity (Acetaminophen Poisoning)
If someone accidentally takes too much acetaminophen (the active ingredient in Tylenol), the response depends on when the drug was taken. If the person seeks medical help within one hour of consumption, doctors can start a procedure called GI decontamination to help get rid of the drug from their body. For this, a substance called activated charcoal can be used. However, other techniques such as washing out the stomach or the entire intestine are not effective in this case.
Patients with high levels of acetaminophen in their body must be given immediate medical attention because it can be toxic to the liver. The medication often used for this is called N-acetyl-cysteine (NAC). If given within 8 hours of ingesting the acetaminophen, NAC can effectively safeguard the liver by preventing the formation of harmful substances, replenishing a naturally occurring antioxidant in the body, and aiding in the removal of the drug. NAC is recommended if acetaminophen levels in the blood are toxic, if a large dose was taken more than 8 hours ago, or if there are indications of liver damage.
NAC can be given either intravenously (through a vein) or orally (by mouth). The intravenous method has been found to reduce the overall hospital stay as it is more easily accepted by the patient due to the oral form’s unpleasant smell and taste. The oral method requires 18 doses over 72 hours, while the intravenous method needs only 20 hours of treatment. The intravenous form is often preferred for pregnant women or patients experiencing severe liver failure.
If a patient’s condition worsens, such as developing kidney failure, acid buildup in the body, neurological issues, or problems with blood clotting, they may need evaluation for a liver transplant. Even if a patient seeks help 24 hours after taking acetaminophen, providing NAC might still improve the chances of survival. NAC can help protect liver cells, reduce immune cells that cause inflammation, improve blood flow in the small blood vessels and increase oxygen supply. Dialysis, a procedure to filter waste and excess fluid from the blood, can also be beneficial, especially if kidney failure occurs with acetaminophen poisoning.
There’s no need to change the dose of NAC for those with alcoholism or chronic illness, and it’s considered safe during pregnancy. Also, once the treatment has begun, there is typically no need to continue checking acetaminophen levels. However, if the patient is experiencing full-blown liver failure, NAC treatment should be continued until they receive a liver transplant, recover, or, unfortunately, if the patient passes away.
What else can Acetaminophen Toxicity (Acetaminophen Poisoning) be?
When dealing with a case of acetaminophen toxicity, it’s necessary to rule out other illnesses that might present with similar symptoms. These could include:
- Hepatorenal syndrome (liver and kidney malfunction)
- Viral hepatitis (liver inflammation caused by a virus)
- Wilson’s disease (a rare inherited disorder causing copper to accumulate in the liver, brain, and other vital organs)
- Pancreatitis (inflammation of the pancreas)
- Emergent management of pancreatitis
- Acute tubular necrosis (a serious kidney disorder)
- Amatoxin toxicity (poisoning from certain types of mushrooms)
- Cytomegalovirus infection (a viral infection)
- Gastroenteritis (inflammation of the stomach and intestines, usually due to an infection)
- Peptic ulcer disease (open sores that develop on the inside lining of the stomach)
- Viral hepatitis
- Wilson’s disease
What to expect with Acetaminophen Toxicity (Acetaminophen Poisoning)
If you are diagnosed and treated quickly, the death rate due to acetaminophen (commonly known as Paracetamol) overdose is usually less than 2%. However, if treatment is delayed and severe liver damage has occurred, the chance of death significantly increases. As a last resort, around 1% to 3% of patients with severe liver damage might need to undergo a liver transplant to save their life.
In general, children less than 6 years of age tend to have a better outcome than adults. This is primarily because their bodies are better at neutralising the harmful effects of an overdose of acetaminophen.
The overall outcome for patients can depend on various factors, including:
* Creatinine levels higher than 3.4 mg/dL (Creatinine is a waste product that your kidneys remove from your blood; higher levels indicate your kidneys are not working well).
* Arterial pH less than 7.3 even with adequate fluid hydration (A low pH means your blood is more acidic than it should be, which can harm your body).
* Prothrombin time more than 1.8 times control or an INR of more than 6.5 (these are blood tests that measure how well your blood clots; abnormal results can indicate liver problems).
* Development of grade 3 or 4 encephalopathy (this is severe brain disease which can result from liver damage).
Possible Complications When Diagnosed with Acetaminophen Toxicity (Acetaminophen Poisoning)
Acetaminophen, a common over-the-counter pain medication, can cause harmful skin reactions. Severe reactions include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). These conditions are incredibly painful and can result in blindness or even death. Furthermore, Acetaminophen can induce acute liver failure, a severe condition that often requires an immediate liver transplant.
Dangerous side effects of Acetaminophen:
- Severe skin reactions, such as Stevens-Johnson syndrome (SJS)
- Toxic epidermal necrolysis (TEN)
- Acute generalized exanthematous pustulosis (AGEP)
- Possibility of blindness and death
- Acute liver failure, which may require an immediate liver transplant
Preventing Acetaminophen Toxicity (Acetaminophen Poisoning)
It’s important for everyone to know about the right dosage and possible harmful effects of acetaminophen, a common pain reliever. Both nurses and pharmacists have a big part in teaching families about these risks. To avoid accidental ingestion, it’s always smart to keep acetaminophen stored somewhere kids can’t reach it.