Did you know that overdosing on Tylenol (Acetaminophen) can actually be a life or death scenario? It actually claims the lives of about 500 people per year. Rapid detection and early treatment are key to preventing deadly liver damage or securing an organ transplant if the patient’s liver is too far gone.
But, would you believe that using math principles can potentially save the life of the individual that overdosed? Based on a group of mathematicians out of the University of Utah, they have put their special set of skills to use and developed a way to determine when the patient overdosed and how much damage there potentially is, using results from standard blood tests.
The findings provide further evidence that math has relevance in clinical settings with the potential to improve medicine and save lives, according to Fred Adler, U. math professor and co-author of a forthcoming study.
Adler, math doctoral student Chris Remien and their colleagues showed that using only four common medical lab tests – known as AST, ALT, INR and creatinine – the equations can quickly and accurately predict which Tylenol overdose patients will survive with medical treatment and which will die unless they receive a liver transplant.
“Math helps you see the invisible,” Adler said. “You can’t observe liver damage, which matters the most, but you can observe biomarkers and use math to connect backward, in this case to determine how much [acetaminophen] they took and when they took it.”
“I absolutely love this paper. It’s a whole new way of looking at this,” said former U. hepatologist Norman Sussman, who initiated the study. “There are other areas where it could apply, where you have an acute injury, but nothing as common as Tylenol poisoning.”
According to Adler’s paper, acetaminophen is the most common cause of acute liver failure, sending 56,000 Americans to the emergency room every year and resulting in 26,000 hospital admissions. Physicians currently use a statistical model to determine how to treat overdose patients. The new method could be a big improvement because it’s based on well-established knowledge of how the body metabolizes the drug and how the toxicity plays out, according to lead author Chris Remien.
Tylenol itself is not poisonous, but the liver produces a toxin while clearing it from the blood stream. Four grams, or eight tablets, a day is about the maximum the body’s clearing mechanism can safely handle.
“Five times the recommended dose can kill you. I don’t know of any other drug like this,” Adler said. But patients can be effectively treated with an antidote within 24 hours. The trouble is symptoms take a day to appear.
“If I wait another day until I list them for transplant, the chance of getting a liver is that much lower,” Sussman, now a professor at Texas’ Baylor College of Medicine. “If you’re going to get someone transplanted, you have to do it fast or you miss the boat. The patient may pass the window when transplants can be done.”
The method takes measurements of standard biomarkers in the blood. AST (aspartate aminotransferase) and ALT (alanine aminotransferase) are enzymes that are released by dying liver cells, so higher levels indicate liver damage. INR (prothrombin time/international normalized ratio) measures how fast blood clots. Liver cells make clotting factors, so if the liver malfunctions, clotting is slower. Creatinine is a measure of kidney dysfunction, in this case secondary to liver damage.
The team applied the method retrospectively to 53 cases treated at University Hospital, and correctly predicted eight cases that ended in death and 39 where the patient survived. The four cases they got wrong were survivors they predicted would die.
Sussman plans to test the method on future cases arising at the U. and three Texas hospitals.
The U. study appears in Hepatology, a journal devoted to liver function and disease.