APAP

APAP is short for acetaminophen, the active ingredient in Tylenol and Feveral. APAP is used to treat fever and pain. It is found as a single drug and in combination with other medications in cold and flu treatments. I touched on APAP in a prior post titled OD. A recent patient and a memory from the past led to today's blog.

APAP toxicity is primary from injury and death of hepatocytes, liver cells. NAPQI is a metabolite, an altered form of APAP as is metabolized by the liver. NAPQI depletes the liver's store of glutathione, an antioxidant. Once the supply of glutathione is exhausted, the hepatocytes are unable to repair the damage caused by NAPQI. Alcohol and medications that use the same pathway for liver metabolism, will exacerbate the toxic effects of APAP. Isoniazid, which is used to treat tuberculosis, and phenobarbital and carbamazipine, both anticonvulsants, are in this group of medications.

In an acute overdose of APAP, either as a suicide attempt or inadvertent excessive dose given by a parent, well established toxic levels are predictable. 200 mg per Kg of body weight is enough to cause liver damage. The level of APAP at 4 hours after a single ingestion can be plotted on the Rumack-Matthew nomogram to help the ER doc decide if the patient requires treatment. Many times we see patients who have been taking excessive amounts of APAP over days. The nomogram is not helpful in these patients.

The early signs of hepatic injury from APAP are not very specific. The patient may have some right upper abdominal discomfort and complain of nausea and vomiting. As the liver is crucial for the maintenance of glucose levels, low blood sugar may be found. Easy bruising is also a sign of liver injury, as the liver manufactures proteins involved in the clotting of blood. As the levels of nitrogen containing toxins, such as ammonia, build up in the blood, the patient may show signs of hepatic encephalopathy. Confusion, problems walking, and lethargy are all signs of effects of these toxins on the brain. A healthy liver normally clears these products of protein metabolism and absorbed toxins from the gastrointestinal track.

Lab tests will reveal elevated liver enzymes, transaminases. Bilirubin may be above normal and later in the course of the disease, abnormal kidney function will be noted. The prothrombin time, a measure of the clotting cascade will begin to rise. The key to a successful outcome is to initiate treatment as soon as possible, preferably before the patient is in significant liver failure.

N-acetylcysteine or NAC is the antidote for APAP damage to the liver. There is an intravenous form of NAC that is sold as Acetadote in the US. Prior to its introduction, NAC had to be given orally. This was a problem because the patients often had vomiting from liver injury and the oral form of NAC smells like rotten eggs. If liver failure has progressed too far, only a liver transplant will save the patient.

Early in my long career, I examined a toddler who looked gravely ill. The child was jaundiced, dehydrated, unresponsive and bled excessively from attempts to establish an IV and draw blood. The lab tests showed all the signs of liver failure. I began NAC by a nasogastric tube as the IV form was not available at that time. The child was transferred to a major pediatric hospital but died from liver failure. The child had been treated for a viral infection with APAP by the parents. The pediatrician had told the parents to give one teaspoon of children's APAP, which contains 160 mg of the drug, every four hours as needed for fever. The problem arose because the parents mistakenly gave one teaspoon of infant APAP, which contains 500 mg, every four hours.

More recently a patient was seen in the ER who was taking more than the maximally recommended dose of APAP for chronic pain. The doses taken were 25-33% above the maximal dose but over many days the liver began to be effected. This patient was started on Acetadote and made a full recovery.

Update:

My mother-in-law is, in the words of the hospice nurse, actively dying. She is unresponsive and hasn't had any oral intake in several days. We are amazed that she is still alive. My wife and I are with mother as I write this post.

The next phase of my career will begin in July. I will be leaving the ER I have called home for the past 28 years. My departure was forced by the hospital administration's displeasure with my relationship with the nursing staff. The outpouring of support from current and former ER nurses, my colleagues in the ER and on the medical staff, EMS personnel, local police officers and firefighters, and my patients has been heartening.

I have decided to remain a B.O.N.E.R. doc. I will stay on nights but in a much less busy ER. The privilege of providing care to those most in need, is my motivation. Stay tuned.