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.

April Fool's Day

As I write this posting, I am looking out at several inches of heavy snow. April Fools indeed. The ER is a place where pranks occur almost daily. The odd, unexpected, quirky and bizarre arrive by foot, wheelchair and ambulance stretcher. The intentional April Fool's day prank are rare and amateurish. Painted on rashes and fake aliens erupting from the body are not going to fool the world's oldest ER doc.

It is the unintentional gag that makes the job fun. Many years ago I was confronted with a mother dragging her 6 year old into the ER screaming that he couldn't breath and was turning blue. A quick glance revealed a smurf like coloration of the hands and face but the child was breathing calmly. I pulled an alcohol wipe from my coat pocket and removed the blue dye that had bled from the child's new sweatshirt. The mother's mouth gaped and she left the ER without saying another word. The rare and unexpected finding keeps me on my toes. When I have completed a history and physical exam and reviewed any records in the hospital's EMR, I form my differential diagnosis. The labs, x-rays, CT's, EKG, and ultrasound should yield findings that I hope I have anticipated. The patient with crushing chest pain and difficulty breathing, who is diaphoretic and whose lungs are congested is probably having an myocardial infarction. The EKG should reveal changes that are consistent with an injury to the heart. The chest x-ray should show evidence of congestive heart failure. The labs tests are likely to show elevation on the CPK I and troponin, markers for myocardial damage. Recently I examined a pleasant octogenarian. She was in obvious distress. She described her abdominal pain and vomiting. Her distended abdomen was very quiet to auscultation. She had diffuse but only mild tenderness. She had an intestinal obstruction by clinical criteria. The possible causes of any presenting complaint are prioritized by likelihood of death or disability. Vascular causes are usually first on the differential diagnosis list. Does this woman have a leaking aneurysm, or a blocked mesenteric artery? The patient was given medications for pain and nausea and labs where sent off. I also ordered a CT of her abdomen without IV or oral contrast. My radiology colleagues would not be happy but I felt that her kidneys would be damaged by the IV dye and she would not be able to tolerate drinking a liter of oral contrast with a bowel obstruction. Her lab tests where abnormal but not specific. As I looked at the CT images, I was stunned. There are diseases that all doctors learn about but rarely encounter. Gall stone ileus is one of those conditions. The gall bladder is a storage tank for bile. When one eats a meal containing fat, the stomach releases a hormone, cholecystokinin. This messenger travels through the veins of the abdomen and stimulates the muscles in the wall of the gall bladder to contract and send bile down the bile duct to the small intestine. The bile will aid in the digestion and absorption of the fat content of a meal. Bile can become like sludge. Stones of bile salts, cholesterol and calcium salts may form in the gall bladder. Long term irritation of the gall bladder wall by gall stones may lead to a connection (fistula) between the gall bladder and the duodenum, the first section of the small intestine. In this patient, that is what had developed. A 2.8 cm gall stone had passed from the gall bladder directly into the small intestine. It meandered down the intestine until it became stuck. The blockage of the intestine by a gall stone is a gall stone ileus. The CT images were identical to ones I had seen in a radiology textbook many years ago. The patient was transferred to a major academic hospital. I am sure that the young doctors will provide excellent care and have a story to tell when they reminisce about their fascinating cases. Unfortunately the unexpected findings may be bad news for the patient. When I was an attending in a teaching hospital, a resident presented a case of a young woman he had evaluated and was ready to send home. The complaint was of vaginal redness and discharge. The evidence of a yeast infection was obvious on physical exam and KOH prep. I introduced myself to the patient and was shocked by her pallor. She denied any sexual experience, or antibiotic use. I told the patient that we were going to do some blood tests. The resident had made the correct diagnosis of the presenting complaint but had ignored the obvious anemic condition of this unfortunate woman. A CBC came back with severe anemia, and a markedly elevated white blood cell count with evidence of leukemic cells. The oncology service was consulted and the patient was admitted. Her impaired immune system from the leukemia had led to the yeast infection. All ER docs have had the experience of treating a child brought in for a "stomach bug". The persistent vomiting and impending dehydration led the parents to seek help. The child shows clear signs of dehydration but the respiratory rate of 40 fills me with dread. A check of the chemistries reveals a diagnosis of diabetes; treatable but a life altering diagnosis. The practice of emergency medicine is controlled chaos. Being rather compulsive and definitely controlling, I may have been better served in another field of medicine. I considered becoming a pathologist when I was a medical student. My advisor told me: internists knew much and do little; surgeons knew little but did much; pathologists knew all, but too late. His opinion of emergency medicine (this was in the mid 1970's), was that it was not a valid career choice. 34 years later I am still an ER doc.