A Mouthful of Death: Acetaminophen Overdose

Submitted by Theodore J. Powell, RN, MSN, Ph.D.

Tags: abdominal pain acetaminophen death emergency department end of life liver injury overdose suicide

A Mouthful of Death: Acetaminophen Overdose

Share Article:

You have just received the report on an overdose patient who will be coming from the Emergency Department to your floor. Sixteen-year-old Amanda had an argument with her mother and tried to commit suicide by taking a Amouthful of acetaminophen. About two hours after taking the medication Amanda got scared and informed her mother of what she had done.

Upon arrival in the Emergency Department, approximately three hours after her overdose, Amanda was immediately started on treatments to help prevent liver damage that could lead to her death. In this article you will learn about acetaminophen and how it can damage the liver, tests performed when there is an acetaminophen overdose, treatments commonly used in an acetaminophen overdose and the supportive care of an acetaminophen overdose patient.

Also known by its chemical name, N -acetyl-p -aminophenol or APAP, acetaminophen became an over-the-counter medication in the 1950's. An analgesic-antipyretic, acetaminophen is available as a single drug or in combination with other common prescription and over-the-counter medications such as Lortab™, Anacin™ and Midol™. Acetaminophen is available under the brand name Tylenol™ and other trade or generic names. The brand name Tylenol™ is derived from it's chemical name N -acetyl-p -aminophenol. Although acetaminophen is exceptionally safe when taken in therapeutic doses, liver damage can occur by taking more than the recommended dose or when taken with other substances such as alcohol.

In the United States, attempted suicide accounts for more than two thirds of acetaminophen-related liver injuries, whereas accidental overdoses account for only one third of the cases.1

The liver accomplishes many important functions such as storing glycogen, regulating blood glucose, plasma protein synthesis, hormone production, removing waste products from your blood and breaking down (metabolizing) and eliminating toxins. When you eat, the liver absorbs and stores fat, sugars, vitamins and other nutrients that you have consumed. When acetaminophen is taken into the body, the liver metabolizes it into the chemical N -acetyl-benzoquinoneimine (NAPQI). Although acetaminophen itself is nontoxic to the liver, the metabolite NAPQI can destroy liver cells (hepatocytes).

The liver metabolizes approximately 90 percent of the absorbed acetaminophen dose into water soluble sulfate and glucuronide conjugates.2 These conjugates are then removed from the blood
stream by the kidneys and eliminated from the body. Most of the remaining acetaminophen binds to glutathione and is then excreted as nontoxic mercapturate conjugates. Glutathione, which is manufactured inside the cell, is often called the body's master detoxifier. Consuming foods rich in sulphur-containing amino acids, such as asparagus, garlic and avocado, can help increase liver glutathione levels. The drug N-acetylcysteine (NAC) or acetylcysteine, commonly known by the brand name Mucomyst™, is quickly metabolized into glutathione once it enters the body.

In an acetaminophen overdose the stores of glutathione are used up and NAPQI is not detoxified. The NAPQI which is not detoxified can then bond to the lipid bilayer of hepatocytes causing them to become necrotic. In addition to NAPQI using up the stores of glutatione in the body, other factors can affect the amount of glutatione available. Malnutrition, chronic alcoholism, age and diet can lower the body's glutatione stores. Alcohol (ethanol) and other substances or drugs can increase the production of NAPQI thus increasing the possibility of hepatic injury.

Acetaminophen can be purchased in regular strength, extra strength, extended-release form, arthritis formula and in several pediatric strengths. It is available in liquid and chewable forms, and in tablets. Both the extended-release and arthritis formula tablets have an outer layer that dissolves immediately, then the remaining medication dissolves slowly allowing pain relief for up to eight hours. The extended-release form of acetaminophen should be swallowed whole, not chewed.

The recommended dose of regular acetaminophen for adults and children 12 years of age or older is up to 650 milligrams every four to six hours. The recommended dose of extra-strength acetaminophen is up to 1000 milligrams every four to six hours. Extended-release acetaminophen has a recommended dose of 1300 milligrams every eight hours. For children less than 12 years of age and/or less than 50 kilograms in weight the recommended dose of acetaminophen is 10 to 15 milligrams per kilogram of the child's body weight every four to six hours. Acetaminophen extended-release, extra strength and arthritis formulas are not recommended for children less than 12 years of age. Quickly absorbed from the upper gastrointestinal tract, acetaminophen peak plasma levels occur between 30 and 60 minutes when a therapeutic dose is taken. When an overdose is consumed, the peak plasma level usually occurs within four hours. In adults, a single dose of 12 grams (24 extra-strength tablets) and in children less than 12 years of age a single dose of 250 milligrams per kilogram, can cause liver toxicity. A person who takes a fatal dose of acetaminophen may seem well for a day or two before the signs and symptoms of hepatic or kidney failure become apparent.

Although Amanda said that she had taken a A "mouthful" of pills, and her mother brought a half-empty acetaminophen extra-strength bottle, the reported history of how much acetaminophen was ingested is often inaccurate and is not a reliable guide to therapy. Obtaining a blood serum concentration of acetaminophen is the only way to correctly assess the risk of hepatotoxicity.

As stated earlier, peak plasma levels in an overdose occur approximately four hours after ingestion. The emergency department physician may order blood tests upon Amanda's arrival, but will usually wait four hours after the acetaminophen ingestion before ordering a serum acetaminophen concentration. Treatment, however, is started immediately upon
Amanda's arrival to the hospital.

Treatment for an acetaminophen overdose can vary depending on the physician and on hospital policy. The first step would be to empty the patient's stomach by lavage or by inducing emesis with syrup of ipecac. Then activated charcoal may be administered, followed by oral or intravenous doses of acetylcysteine. However, oral acetylcysteine is absorbed by activated charcoal thereby decreasing its effectiveness. If activated charcoal treatment is given, the patient will need to be lavaged prior to the administration of oral acetylcysteine. Although the United States Federal Drug Administration has approved the administration of acetylcysteine intravenously, many doctors in the United States still prefer using the oral preparation. Dialysis has not been found to be an effective treatment for acetaminophen overdoses.

Acetylcysteine should be administered immediately if the acetaminophen ingestion occurred within 24 hours or less, and must be started within 10 hours to protect against severe liver damage. When the result of the acetaminophen plasma concentration is available, the physician can refer to an acetaminophen toxicity nomogram (Rumack-Matthew nomogram)3 to determine if acetaminophen plasma concentrations are in the toxic range and if maintenance doses of acetylcysteine are needed. Acetylcysteine 20% solution is available in 4, 10 or 30-milliliter rubber-stoppered glass vials. The recommended loading dose of acetylcysteine is 140 mg per kg of body weight and the recommended maintenance doses are 70 mg per kg of body weight every four hours for a total of 18 doses (including the loading dose). If the patient vomits the oral loading or maintenance doses within one hour of administration, the dose should be repeated. Before giving oral doses of acetylcysteine you must dilute the 20% solution to a 5% concentration with cola drinks, other soft drinks, or juice. If the patient is unable to retain orally administered acetylcysteine, the doses may be diluted with sterile water and administered by duodenal intubation. Antiemetics such as Reglan™ and Zofran™ may be used if the patient becomes nauseated.

Blood will be drawn for baseline levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, blood sugar, serum urea nitrogen (BUN), serum creatinine, electrolytes and prothrombin time to monitor hepatic and renal function and electrolyte-fluid balance. An initial acetaminophen concentration would be drawn four hours after ingestion to accurately measure potential hepatotoxicity. These tests would then be drawn at least daily to serve as a basis for determining the need for continuing maintenance doses of acetylcysteine and for other treatments.

ALT, AST, bilirubin and the prothrombin time may be abnormal when there is liver damage. ALT is an enzyme produced in hepatocytes. Even though only a liver biopsy accurately indicates the degree of liver damage, an increase in ALT roughly correlates with the degree of damaged hepatocytes.

AST, an enzyme similar to ALT, is produced in the liver and also in muscle tissue. ALT can be elevated in other conditions than liver damage, such as in myocardial infarction. Bilirubin is a product that results when old blood cells are broken down. It is removed from the blood by the liver, conjugated, and then secreted into the bile. Indirect bilirubin is increased in cases of increased production, decreased uptake, or decreased conjugation by the liver. Direct bilirubin is increased when there is decreased secretion by the liver, or a bile duct obstruction. The prothrombin time (PT) is one type of blood clotting test and is prolonged when some of the clotting factors created by the liver are low. Blood sugars are obtained because the liver helps maintain a proper level of glucose in the blood. BUN levels indicate the amount of urea, which is a waste product of protein metabolism, that is being manufactured by the liver. Severe liver failure causes a reduction of urea in the blood.

Creatinine levels are obtained to ascertain how well the kidneys are functioning. Acute renal failure that occurs with liver disease is referred to as Hepatorenal syndrome (HRS). HRS is usually indicative of an end-stage of perfusion to the kidney due to a deteriorating liver.

While taking the report on Amanda, you were informed that, except for her serum acetaminophen concentration, her blood test results were all within normal limits. Four hours after ingestion, Amanda's blood acetaminophen concentration was 100 ug/mL, which is below hepatotoxicity on an acetaminophen toxicity nomogram. Acetaminophen overdose patients can be cared for on a Medical/Surgical floor unless there are obvious signs of liver damage.

Amanda has just arrived on your floor and while assisting her to bed you notice black smudges around her mouth and on her hands. In your report you were informed that Amanda did not receive syrup of ipecac to induce emesis. She had been lavaged, received activated charcoal, lavaged again and was given her initial dose of acetylcysteine.

Nausea, vomiting and other gastrointestinal symptoms may occur in the large doses of acetylcysteine needed to treat an acetaminophen overdose. Your patient may also develop a rash, with or without fever, from taking acetylcysteine.

Observe acetaminophen overdose patients for mental status changes or clinical signs of encephalopathy. Cerebral edema (which would be detected by a CT scan of the head) can occur in the late stages of an acetaminophen overdose.

Your patient's PT can be prolonged with hepatic injury. Continuously assess your patient for signs of coagulopathy such as bleeding gums, skin bruising and GI bleeding. Vitamin K or fresh frozen plasma may be a necessary treatment.

Since the liver helps maintain blood glucose levels, routine finger stick testing of blood sugar may be ordered.

Notify the physician if your patient complains of acute abdominal pain. Abdominal pain may be a sign of pancreatic injury caused by significant hepatotoxicity. Pancreatic injury is assessed by obtaining lipase and amylase levels.

Acetaminophen crosses the placental barrier. A pregnancy test (concentration of human chorionic gonadotropin) should be obtained in all women of childbearing age who are suspected to have ingested a toxic amount of acetaminophen.

Because Amanda's overdose was intentional, a psychiatric consult has been ordered.

And of course, don't forget psychological support. Hospitalization can be scary, especially for a 16-year-old girl, and the treatments given for an acetaminophen overdose can be uncomfortable and humiliating.

When you report to work the following day, you find that Amanda's ALT is slightly elevated and her blood acetaminophen concentration is 4 ug/mL. Her AST, PT and blood glucose level are within normal limits. The physician has therefore written an order for Amanda to be discharged home.

Because the liver can regenerate if not too severely damaged, Amanda will not experience long term complications from her acetaminophen overdose. If her liver had been so severely damaged that it could not regenerate, the physician may have discussed the need for a liver transplant with Amanda and her mother.

When taking care of an accidental or intentional acetaminophen overdose patient, it is essential that the nurse knows how acetaminophen can cause hepatotoxicity. He or she needs to understand how blood tests such as ALT, AST, bilirubin and PT can indicate liver damage.

The nurse administering acetylcysteine, an antidote for acetaminophen overdoses, needs to know how to prepare and administer this drug. The acetaminophen overdose patient must be continuously observed for gastrointestinal distress, rashes, mental status changes, coagulopathy,
hypoglycemia and pancreatitis.

Although not all acetaminophen overdose patients will survive, proper nursing care can help increase the comfort and decrease the mortality rates of these patients.

1. Dennis Lee, MD, Jay W. Marks, MD, ATylenol (Acetaminophen) Liver Damage@, http://www.Medicinet.com (Feb, 2009).

2. A conjugate is formed by the union of two compounds.

3. An acetaminophen nomogram is only used with a one-time ingestion of pediatric, regular strength or extra-strength acetaminophen. It is not accurate when extended-release acetaminophen is taken, or when multiple doses of acetaminophen are taken over a period of