Symptoms and Management of Acetaminophen (Paracetamol) Toxicity

Introduction

Acetaminophen toxicity is one of the most common causes of liver failure worldwide. It is caused by the excessive use of Paracetamol and other Acetaminophen-containing medications used for relieving pain and fever. These medications are easily available at a low cost in the market, and most of the population considers them safe compared to other drugs. Acute Acetaminophen toxicity will cause immediate symptoms and later on cause multiple organ failures, especially in the liver. Hepatotoxicity (liver toxicity) is the most important side effect of Acetaminophen toxicity and is the most important reason for liver transplantation in the world.

What Is Acetaminophen?

Acetaminophen (otherwise known as Paracetamol) is a drug used for the treatment of fever and pain (mild to moderate). It is the most commonly used oral antipyretic (reduce fever) and analgesic (pain killer) drug. Acetaminophen belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs). They act by inhibiting cyclooxygenase (COX) present in the brain and prevent the production of prostaglandins, which are responsible for fever and pain. It also acts directly on the hypothalamus and produces its antipyretic effects (reducing fever).

What Are the Uses of Acetaminophen?

Acetaminophen is used for the following purposes.

• Relieve fever.

• Sore throats and cold.

• Muscle aches.

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• Headaches.

• Lower back pain.

• Menstrual period pain.

• Toothache.

• Osteoarthritis.

• Mild to moderate pain.

What Is Acetaminophen Toxicity?

Acetaminophen toxicity is caused by the enormous use of Paracetamol and N-acetyl-P-aminophenol (APAP), the most commonly used medications for relieving fever and pain. It can occur due to accidental ingestion of large doses of Acetaminophen or purposeful consumption as a part of suicidal attempts. The maximum recommended daily dosage of Acetaminophen in adults is four grams per day, and in children, it is 90 milligrams per kilogram per day. An excessive dose of Acetaminophen in the human body causes immediate side effects within 24 hours and later progresses to liver damage. Hepatotoxicity is the most important effect of Acetaminophen overdose. It occurs due to the toxic metabolites released from Acetaminophen in the body. N-acetyl-P-benzoquinone imine (NAPQI) is a toxic intermediate produced from Acetaminophen. N-acetyl-P-benzoquinone imine (NAPQI) causes damage to liver cells and reduces the levels of antioxidants present in the liver (glutathione). People with a history of chronic alcohol use, malnutrition, and underlying liver diseases are at increased risk of developing hepatotoxicity and liver damage.

What Are the Symptoms of Acetaminophen Toxicity?

Acetaminophen toxicity will result in an immediate body response within a few hours. These symptoms can be divided into three based on the severity and time of onset.

It includes the following:

• First Phase - It occurs within a few hours after the overdose. Initial symptoms include vomiting, sweating, nausea, and a pale appearance. Some patients develop only mild symptoms within 24 hours of poisoning.

• Second Phase - These symptoms will develop within 24 to 72 hours after Acetaminophen toxicity. During this phase, Acetaminophen is converted to toxic metabolites, which causes liver cell damage. Individuals may experience pain in the right upper portion of the abdomen. During this phase, there will be a rapid increase in the levels of biochemical markers for liver function, including alanine transaminase (ALT), aspartate transaminase (AST), and international normalized ratio (INR). Acetaminophen toxicity may also cause acute kidney failure due to multiple organ dysfunction syndromes and hepatorenal syndrome (kidney failure in individuals with liver damage).

• Third Phase - It occurs three to five days after Acetaminophen toxicity. It consists of multiple organ damage and associated complications. This final stage includes liver necrosis (cell death), low blood sugar, blood coagulation defects, brain swelling, hepatic encephalopathy, septicemia, multiple organ damage, and death.

How Can We Manage Acetaminophen Toxicity?

1. Gastric Decontamination - It can be used as a treatment option only when the patient is admitted within two hours of Acetaminophen overdose. Gastrointestinal absorption of Acetaminophen occurs within two hours. Gastric decontamination is performed within two hours to prevent the gastric absorption of Acetaminophen and reduce toxicity. It can be done in two ways. It includes:

• Gastric Irrigation or Lavage (Stomach Pumping) - It is performed within one hour after ingestion. Gastric lavage involves cleaning the contents present in the stomach to eliminate toxic substances.

• Activated Charcoal - It can be used to reduce the gastrointestinal absorption of Paracetamol. Activated charcoal helps in gastrointestinal decontamination by adsorbing Paracetamol and reducing toxicity. It is given within 30 minutes to two hours for better gastric decontamination.

2. N-acetylcysteine (NAC) -Toxic metabolites produced from Acetaminophen will cause liver damage by inhibiting glutathione (antioxidant). Acetylcysteine reduces Acetaminophen toxicity by restoring glutathione. It is most effective when given within eight hours of overdose and poisoning. Acetylcysteine can be administered orally or intravenously, but the intravenous route of administration shows greater effectiveness. Certain patients will develop allergic reactions after administration (anaphylactic reaction). Proper allergic history and test dose must be taken before administration.

3. Liver Transplantation - Acute liver failure after Acetaminophen toxicity is treated with liver transplantation to avoid death. The diseased liver is replaced with another healthy liver from a donor. The criteria for liver transplant include the following:

• Arterial blood pH lower than 7.3, even after fluid replacement.

• Grade III or grade IV hepatic encephalopathy.

• Prothrombin time more than 100 seconds.

• Serum creatinine levels of more than 300 mmol/L in 24 hours.

Conclusion

Acetaminophen (Paracetamol) toxicity happens due to excessive levels of Acetaminophen in our body. Acetaminophen is commonly used for relieving pain and reducing fever. In low doses, it is safe for consumption and relieves pain, and reduces fever. Accidental ingestion of larger doses or suicidal attempts by consuming Paracetamol tablets will cause toxicity and adverse health effects. Hepatotoxicity is the most important and dangerous effect produced by Acetaminophen toxicity. Early medical management and proper medications can reduce the progression of adverse health effects and prevent multiple organ failures causing death.