Follow Clinical End Points, Not Clock, for Acetaminophen Overdose

SAN DIEGO – The clock has run out on 20-hour and 72-hour protocols for treating acetaminophen overdose. Clinical end points such as acetaminophen concentration and AST or ALT levels now determine when to end therapy.

In the mid-2000s, a 20-hour protocol for treatment with intravenous acetylcysteine generally replaced the traditional 72-hour protocol for treatment with oral acetylcysteine, but the 20-hour protocol has proved insufficient in rare cases of overdose on very, very large amounts of acetaminophen, Dr. Kennon J. Heard said.

In some of these patients, so much acetaminophen gets stored in the GI tract that the patient continues to absorb acetaminophen during the 20 hours of treatment. If treatment stops at 20 hours, "they’re going to have another overdose. They’re going to go on and get sick," he said at the annual meeting of the Society of Hospital Medicine.

Most toxicologists now prefer to end treatment based on clinical end points instead of time-based protocols. The new approach gets nearly all patients with acetaminophen overdose out of the hospital before 72 hours, and most patients still get treated for only 20 hours, said Dr. Heard, an emergency medicine physician at the University of Colorado and director of the Medical Toxicology Fellowship at the Rocky Mountain Poison and Drug Center, Denver.

Follow serum acetaminophen levels until all of the drug has been metabolized, indicated by serum levels below 10 mg/L or, ideally, undetectable levels. Make sure that markers of liver injury –ALT, (alanine aminotransferase), AST (aspartate aminotransferase) International Normalized Ratio, and creatinine – are improving or at least stable before ending therapy, he advised.

"If their AST or ALT starts out normal and stays normal, you can stop at 20 hours. If the AST or ALT is going up, we like to see it clearly start to go down or at least stabilizing at 20 hours, or sometimes even sooner," he said. "As long as the patient is clinically well, the ALT and AST are improving and they don’t have any acetaminophen on board, you can stop treatment."

In cases of massive overdose, in which the patient presents with a serum acetaminophen level greater than 500 mg/L or has a level greater than 75 mg/L after 20 hours of treatment, consult with your local poison center experts, Dr. Heard added.

Prolonged treatment may be needed, and some experts have suggested giving higher doses of acetylcysteine because the very high levels of acetaminophen may exceed the ability of acetylcysteine to detoxify the patient, he said.

"These cases are rare. We usually have one or two of them a year," Dr. Heard said.

Historically, the 72-hour protocol for treatment with oral acetylcysteine was developed before acetaminophen assays were routinely available in the United States. Patients were hospitalized for 3 days, "drinking stuff that smelled terrible, and generally, it was probably a waste of a lot of resources" because studies have subsequently shown that most patients don’t need 72 hours of treatment, he said.

With oral therapy, it seemed that as long as patients started treatment within 10-20 hours of overdose, they would recover. After development of intravenous acetylcysteine and shortening of the protocol to 20 hours, however, these rare cases of treatment failure began showing up.

Dr. Heard has been a consultant or received research grants from Cadence Pharmaceuticals, McNeil Consumer Healthcare, and Cumberland Pharmaceuticals.

SAN DIEGO – The clock has run out on 20-hour and 72-hour protocols for treating acetaminophen overdose. Clinical end points such as acetaminophen concentration and AST or ALT levels now determine when to end therapy.

In the mid-2000s, a 20-hour protocol for treatment with intravenous acetylcysteine generally replaced the traditional 72-hour protocol for treatment with oral acetylcysteine, but the 20-hour protocol has proved insufficient in rare cases of overdose on very, very large amounts of acetaminophen, Dr. Kennon J. Heard said.

In some of these patients, so much acetaminophen gets stored in the GI tract that the patient continues to absorb acetaminophen during the 20 hours of treatment. If treatment stops at 20 hours, "they’re going to have another overdose. They’re going to go on and get sick," he said at the annual meeting of the Society of Hospital Medicine.

Most toxicologists now prefer to end treatment based on clinical end points instead of time-based protocols. The new approach gets nearly all patients with acetaminophen overdose out of the hospital before 72 hours, and most patients still get treated for only 20 hours, said Dr. Heard, an emergency medicine physician at the University of Colorado and director of the Medical Toxicology Fellowship at the Rocky Mountain Poison and Drug Center, Denver.

Follow serum acetaminophen levels until all of the drug has been metabolized, indicated by serum levels below 10 mg/L or, ideally, undetectable levels. Make sure that markers of liver injury –ALT, (alanine aminotransferase), AST (aspartate aminotransferase) International Normalized Ratio, and creatinine – are improving or at least stable before ending therapy, he advised.

"If their AST or ALT starts out normal and stays normal, you can stop at 20 hours. If the AST or ALT is going up, we like to see it clearly start to go down or at least stabilizing at 20 hours, or sometimes even sooner," he said. "As long as the patient is clinically well, the ALT and AST are improving and they don’t have any acetaminophen on board, you can stop treatment."

In cases of massive overdose, in which the patient presents with a serum acetaminophen level greater than 500 mg/L or has a level greater than 75 mg/L after 20 hours of treatment, consult with your local poison center experts, Dr. Heard added.

Prolonged treatment may be needed, and some experts have suggested giving higher doses of acetylcysteine because the very high levels of acetaminophen may exceed the ability of acetylcysteine to detoxify the patient, he said.

"These cases are rare. We usually have one or two of them a year," Dr. Heard said.

Historically, the 72-hour protocol for treatment with oral acetylcysteine was developed before acetaminophen assays were routinely available in the United States. Patients were hospitalized for 3 days, "drinking stuff that smelled terrible, and generally, it was probably a waste of a lot of resources" because studies have subsequently shown that most patients don’t need 72 hours of treatment, he said.

With oral therapy, it seemed that as long as patients started treatment within 10-20 hours of overdose, they would recover. After development of intravenous acetylcysteine and shortening of the protocol to 20 hours, however, these rare cases of treatment failure began showing up.

Dr. Heard has been a consultant or received research grants from Cadence Pharmaceuticals, McNeil Consumer Healthcare, and Cumberland Pharmaceuticals.

SAN DIEGO – The clock has run out on 20-hour and 72-hour protocols for treating acetaminophen overdose. Clinical end points such as acetaminophen concentration and AST or ALT levels now determine when to end therapy.

In the mid-2000s, a 20-hour protocol for treatment with intravenous acetylcysteine generally replaced the traditional 72-hour protocol for treatment with oral acetylcysteine, but the 20-hour protocol has proved insufficient in rare cases of overdose on very, very large amounts of acetaminophen, Dr. Kennon J. Heard said.

In some of these patients, so much acetaminophen gets stored in the GI tract that the patient continues to absorb acetaminophen during the 20 hours of treatment. If treatment stops at 20 hours, "they’re going to have another overdose. They’re going to go on and get sick," he said at the annual meeting of the Society of Hospital Medicine.

Most toxicologists now prefer to end treatment based on clinical end points instead of time-based protocols. The new approach gets nearly all patients with acetaminophen overdose out of the hospital before 72 hours, and most patients still get treated for only 20 hours, said Dr. Heard, an emergency medicine physician at the University of Colorado and director of the Medical Toxicology Fellowship at the Rocky Mountain Poison and Drug Center, Denver.

Follow serum acetaminophen levels until all of the drug has been metabolized, indicated by serum levels below 10 mg/L or, ideally, undetectable levels. Make sure that markers of liver injury –ALT, (alanine aminotransferase), AST (aspartate aminotransferase) International Normalized Ratio, and creatinine – are improving or at least stable before ending therapy, he advised.

"If their AST or ALT starts out normal and stays normal, you can stop at 20 hours. If the AST or ALT is going up, we like to see it clearly start to go down or at least stabilizing at 20 hours, or sometimes even sooner," he said. "As long as the patient is clinically well, the ALT and AST are improving and they don’t have any acetaminophen on board, you can stop treatment."

In cases of massive overdose, in which the patient presents with a serum acetaminophen level greater than 500 mg/L or has a level greater than 75 mg/L after 20 hours of treatment, consult with your local poison center experts, Dr. Heard added.

Prolonged treatment may be needed, and some experts have suggested giving higher doses of acetylcysteine because the very high levels of acetaminophen may exceed the ability of acetylcysteine to detoxify the patient, he said.

"These cases are rare. We usually have one or two of them a year," Dr. Heard said.

Historically, the 72-hour protocol for treatment with oral acetylcysteine was developed before acetaminophen assays were routinely available in the United States. Patients were hospitalized for 3 days, "drinking stuff that smelled terrible, and generally, it was probably a waste of a lot of resources" because studies have subsequently shown that most patients don’t need 72 hours of treatment, he said.

With oral therapy, it seemed that as long as patients started treatment within 10-20 hours of overdose, they would recover. After development of intravenous acetylcysteine and shortening of the protocol to 20 hours, however, these rare cases of treatment failure began showing up.

Dr. Heard has been a consultant or received research grants from Cadence Pharmaceuticals, McNeil Consumer Healthcare, and Cumberland Pharmaceuticals.