What is Acetaminophen Toxicity (Tylenol Overdose)?
Acetaminophen, also known as paracetamol or APAP, is a common drug used for fever and pain relief. One reason for its widespread use is that it’s easily available and considered safe by many. Over 60 million Americans use acetaminophen every week. It is often combined with other medications, including opioids and diphenhydramine, in various products. However, many people may not realize that these combination drugs contain acetaminophen.
Though acetaminophen works differently from common painkillers called NSAIDs, the exact way it operates is not well understood yet. It’s believed to work mainly in the brain, blocking an enzyme known as cyclooxygenase (COX). This blockage helps to reduce fever and pain. Acetaminophen could also suppress the creation of chemicals called prostaglandins in the brain and spinal cord. Furthermore, it seems to have a direct effect on a part of the brain known as the hypothalamus, which helps it lower body temperature.
What Causes Acetaminophen Toxicity (Tylenol Overdose)?
Acetaminophen, which many people use for pain relief, is safe at the right levels. However, if you take too much of it, it can seriously damage your liver. For adults, the safe dosage is 650 mg to 1000 mg every 4 to 6 hours, and you should not take more than 4 grams in a day. For children, they should take 15 mg/kg every 6 hours and not more than 60 mg/kg in a day. It becomes toxic and harmful when taken at levels of 7.5 g/day to 10 g/day, or 140 mg/kg.
Risk Factors and Frequency for Acetaminophen Toxicity (Tylenol Overdose)
Acetaminophen toxicity, or damage to the liver from overuse of acetaminophen, is a major problem worldwide and the leading cause for liver transplantation in the U.S. Every year in the United States, there are 56,000 emergency room visits, 2,600 people are admitted to the hospital, and 500 people die because of acetaminophen toxicity. Surprisingly, half of these cases are due to accidental overdoses.
While children more commonly experience acetaminophen poisoning, adults tend to have more severe and sometimes fatal outcomes.
Signs and Symptoms of Acetaminophen Toxicity (Tylenol Overdose)
Acetaminophen toxicity is a medical condition that typically undergoes four stages. Each stage is marked by different symptoms and levels of downturn or recovery.
- The first stage (30 minutes to 24 hours): At this stage, the patient might not show any symptoms or might experience vomiting.
- The second stage (18 hours to 72 hours): During this period, the patient may have vomiting, pain in the top right area of the abdomen, and low blood pressure.
- The third stage (72 hours to 96 hours): This is a critical period where liver malfunction is prominent, accompanied by kidney failure, blood clotting disorders, metabolic acidosis (a high level of acid in the body), and mental confusion. Digestive system symptoms may return and this is the stage where death is most likely to occur.
- The fourth stage (4 days to 3 weeks): This is the recovery period.
Testing for Acetaminophen Toxicity (Tylenol Overdose)
Acetaminophen (the active ingredient in Tylenol) poisoning is diagnosed based on the amount of the drug found in the patient’s blood. This can be the case even if the patient doesn’t feel sick. Other tests that doctors order include checks of liver function and blood clotting ability. If a large amount of acetaminophen has been taken, the liver function tests can show abnormal results within 8 to 12 hours. Typically, these levels stay high for 18 to 72 hours.
If other drugs were also taken, it can be helpful to test urine for drugs, perform an EKG to check the heart’s electrical activity, and do a metabolic panel to evaluate overall health. If blood tests show a high level of acetaminophen according to a chart known as the Rumack-Matthew Nomogram, treatment should be started. A level higher than 150 mcg/mL four hours after taking the drug is considered toxic. This chart can only be used properly if blood is tested between 4 to 24 hours after the medicine was taken. It does not apply to repeat or chronic poisoning.
For chronic acetaminophen poisoning (i.e., when someone takes too much over a longer period), the chart is not useful. The amount of the drug in the blood doesn’t necessarily match with how severe the overdose is. In these situations, the doctor uses risk factors, lab values, and clinical judgment to figure out if significant poisoning has occurred. Poisoning should be suspected and treated if either the level of the drug is more than 20 mcg/mL or if the liver function tests show abnormal results. Chronic cases can sometimes be less severe as the liver has a chance to regenerate its stores of a substance called glutathione.
Treatment Options for Acetaminophen Toxicity (Tylenol Overdose)
If someone has taken a harmful dose of acetaminophen (commonly known as paracetamol), their treatment will depend on the timing of the drug’s ingestion. If they reach hospital within one hour of taking the drug, professionals may try to cleanse the drug out of their stomach. They would use techniques like feeding the patient activated charcoal, which can absorb the drug to prevent it from entering the bloodstream.
However, patients with high levels of acetaminophen in their body must be admitted to the hospital for a specific treatment involving a medication called N-acetyl-cysteine (NAC). If given within the first 8 hours after taking an overdose, NAC can completely protect the liver from damage. It works by blocking the harmful effects of the overdose, replenishing the body’s natural defenses, and converting the dangerous drugs back into harmless ones.
There are several signs that a patient needs NAC treatment. These include dangerously high levels of acetaminophen in the blood, a high dose of the drug taken more than 8 hours ago, abnormal lab results with drug intake more than 24 hours ago, or signs of liver injury.
NAC can be given both through a vein (intravenously) or swallowed (orally). The intravenous method is usually preferred, as it shortens the hospital stay and doesn’t have the unpleasant smell and taste associated with the oral one. It also requires less frequent dosing- a total treatment time of 20 hours as compared to 72 hours with oral doses.
Patients who continue to worsen, showing signs like kidney failure, altered mental state, blood clotting problems, and severe blood acidity, may be referred to a transplant specialist. And even if treatment begins 24 hours after overdose, NAC may still improve survival by acting as an antioxidant and supporting liver recovery. Hemodialysis, a blood-cleaning procedure, can also be an effective treatment, especially if the kidneys are failing.
Regardless of whether the patient is affected by alcoholism or chronic illness, or if they are pregnant, the NAC dose does not need adjusting. Also, once treatment with NAC has started, there is no need to keep checking acetaminophen levels in the blood. And in critical cases involving severe liver failure, NAC should be continued even beyond 72 hours until the patient either recovers, receives a liver transplant, or unfortunately, passes away.
What else can Acetaminophen Toxicity (Tylenol Overdose) be?
When addressing concerns about potential acetaminophen toxicity, doctors need to consider other health conditions that can present with similar symptoms. These include:
- Hepatorenal syndrome (a condition that impacts the kidneys and liver)
- Viral hepatitis (a liver infection)
- Wilson’s disease (a rare genetic disorder causing copper to build up in the body)
- Pancreatitis (inflammation of the pancreas)
- Sudden onset of pancreatitis that needs immediate treatment
- Acute tubular necrosis (a kidney disorder that results in the death of kidney cells)
- Amatoxin toxicity (poisoning, usually from mushroom consumption)
- Cytomegalovirus infection (a common virus that can impact the whole body)
- Gastroenteritis (also known as stomach flu)
- Peptic ulcer disease (sores in the lining of stomach or duodenum)
- Viral hepatitis (a liver infection)
- Wilson’s disease (a rare genetic disorder causing copper to build up in the body)
Considering these possible conditions, doctors can then proceed with the appropriate tests and treatments for the patient.
What to expect with Acetaminophen Toxicity (Tylenol Overdose)
If a patient is diagnosed and treated quickly, the chance of dying from acetaminophen (commonly known as paracetamol) toxicity is less than 2%. However, if treatment is delayed and severe liver damage has occurred, the chance of dying is much higher. Approximately 1% to 3% of these patients with critical liver damage may need a life-saving liver transplant. Overall, children under the age of 6 tend to have a better chance of recovery than adults. This is mainly because their bodies can eliminate harmful substances, like paracetamol, more efficiently.
Overall, a patient’s chance of recovery depends on the following factors:
* Kidney health, indicated by creatinine levels above 3.4 mg/dL
* Acidic level of the blood, with an arterial pH below 7.3 even after receiving enough fluids
* Ability of the blood to clot, indicated by a prothrombin time more than 1.8 times the normal range or an ‘international normalized ratio’ (INR) of over 6.5
* The presence of severe neurological symptoms, known as grade 3 or 4 encephalopathy.
Possible Complications When Diagnosed with Acetaminophen Toxicity (Tylenol Overdose)
Acetaminophen, a common over-the-counter medicine, can sometimes lead to serious side effects. These include severe skin reactions, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), all of which can cause a lot of pain and potentially lead to blindness or even death. Acetaminophen can also cause acute liver failure, a dangerous condition that could require an emergency liver transplant.
Key Side Effects to Watch For:
- Severe skin reactions which can cause pain or blindness
- Potential fatal conditions like Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP)
- Acute liver failure that may need an urgent liver transplant
Preventing Acetaminophen Toxicity (Tylenol Overdose)
It’s really important for everyone to know more about how to properly use acetaminophen, and understand its potential to be toxic if not used correctly. Nurses and pharmacists have a key role in helping to educate families on the dangers of acetaminophen misuse. It is also very important to keep acetaminophen where children can’t reach it to avoid any accidents.
