 Welcome to Yamato Avidu series. This is Toxicology 3.3. In this segment, we will discuss presentation and treatment for acetaminophen and aspirin toxicity. Please review the previous two videos before this one. We will focus on acetaminophen and aspirin toxicity. These two remain the most common and the most deadly toxins. First, acetaminophen. This drug targets the liver. It causes hepatocelular damage, necrosis, and liver failure. Let's say you have a patient who has taken, say, a handful of extra-strength Tylenol or acetaminophen. How many tablets do you think will be toxic? 10, 20, 30, 50? The toxic dose for acetaminophen is 150 mg per kilogram. So let's say the patient is 60 kilos. The toxic dose would be how much? That's right. It would be 150 times 60. That will give us 9,000 mg, which is equal to 9 grams. Each pill of extra-strength acetaminophen is 500 mg. And therefore 9 grams of acetaminophen translate to 18 tablets. So again, 9,000 mg divided by each pill, which has 500 mg, that gives us 18 tablets. Which is about a handful of pills. How would patients with acetaminophen toxicity present? Patients generally present with four stages of toxicity. These four stages usually affect the GI tract and the liver. Stage one is very non-specific. It involves nausea and vomiting. Stage two starts to involve the liver directly. As the liver becomes more inflamed, you will get right upper quadrant tenderness. The AST and ALT will start to increase. Stage three is where the patient is the sickest. This is when they develop fulminant, hepatic failure. Patients will have coagulopathy, since the liver is unable to give clotting factors. Lactic acidosis and encephalopathy. Stage four are for those who survive this, gradual recovery. These are the four stages of acetaminophen toxicity. How do we diagnose patients with an acetaminophen toxicity? We'll start first by history. We need to find out when the ingestion took place and how much the patient has ingested. Any level that is higher than toxic dose warrants treatment. Next part of the diagnosis involve Laptis. Since the toxicity involves rise of ALT, AST and coagulopathy, we would check for these specific lab tests. We also use a special nomogram in conjunction to our serum acetaminophen level. This is the RUMAC Matthew nomogram for acetaminophen toxicity. This nomogram uses the serum level of acetaminophen and the time since the ingestion to tell us whether the patient is going to be toxic or not. Let's see how this works. Let's say our patient took the drug six hours ago and the serum level is 400. Now make sure you check the unit because your lab may use a different unit and you have to use a different nomogram. Let's say this is the unit we're using which is micrograms per milliliter. You can see that the patient's level is clearly as the probable hepatic toxicity range. Therefore, we will start treatment with the antidote. We have a specific antidote for acetaminophen. It is endocidal cysteine. If it is given early, it will stop acetaminophen's damage to the liver. This medication can be given either orally or intravenously. In Canada, we often use the intravenous approach. To summarize, acetaminophen is toxic at over 115 milligrams per kilogram. It causes damage to the liver. We want to plot the serum level and the time since ingestion on the nomogram. If the patient is toxic by the nomogram, we want to start endocidal cysteine as a direct antidote. Next, we will discuss aspirin toxicity. For an acute ingestion, the toxic dose of aspirin is about 300 milligrams per kilogram. In a 60 kilogram patient, it translates to about 18,000 milligrams of aspirin. If we're using 325 milligram tablets of aspirin, this translates to about 50 tablets. How do patients present with aspirin toxicity? Three main systems will be targeted. Neurological, GI, and respiratory. For a neurological system, patients can often complain of tinnitus. More non-specifically, patients can often complain of lethargy or confusion. They can also present with seizures. For GI tract, patients often complain of nausea and vomiting. They can often lose quite a bit of volume from the vomiting alone. For the respiratory system, patients complain or show hyperventilation and gradually can go into respiratory distress. In terms of diagnosis, similar to citaminophen, you will want to ask on history when the patients have taken the medication and how much they might have taken. In terms of laboratory workup, you want to do routine blood work to see if the patient is dehydrated or not. We should also draw a serum salicylate level. If you remember, in the last video, we talked about blood gas in toxicology. You might remember that aspirin is one of the medications that causes an anion gap metabolic acidosis. Because of that, getting a blood gas in a patient who potentially have taken aspirin would be very helpful for us. When you get back a blood gas of a patient who might have taken aspirin, you might notice two things. One, an anion gap metabolic acidosis. Normally, in patients who have metabolic acidosis, the body would try to compensate by breathing out extra CO2. In the patients who have also taken an extra aspirin overdose, the aspirin causes the patients to hyperventilate even more. Therefore, instead of just breathing enough CO2 to make the pH normal, the patients will hyperventilate and cause them to blow off more CO2 than they should. Therefore, they overshoot and on the blood gas, you are going to see a respiratory alkalosis. To the point, it has overcompensated and caused the pH to go higher than normal and therefore the patient becomes alkalemic. This is a very important concept in trying to understand how aspirin works in the body and therefore explaining it by the blood gas. This is how we treat patients who are aspirin toxic. First, supportive, who ensure the airway is intact and patent, ensure the patient is oxygenating and ventilating properly. We also give IV fluids to support their circulation. The next part has to do with aspirin's unique mechanism in the body. The body eliminates aspirin through the kidneys. In the kidney, the clearance of aspirin increases with urine pH. The more alkaline the pH of the urine, the less aspirin is being reabsorbed. Therefore, we want the urine pH to be higher. How do we do that? We do that by alkalinizing the blood. We use sodium bicarbonate to alkalinize the serum and therefore the urine. We give sodium bicarb intravenously. Then we test the pH of the urine. We then titrate how much bicarb we are giving through the IV by checking the pH that it has to be more than 7.5. This method is known as urine alkalinization. If after this treatment, the patient is looking sicker, on the blood gas there is a severe acid base imbalance. The patient is getting sicker in terms of more neurological deficits such as seizure, cerebral edema, or the patient has significant respiratory deterioration. We will use hemodialysis to get rid of the aspirin. In summary, aspirin toxicity more than 300 mg per kg acts on the brain, the GI tract, and respiratory system. Treatment is sodium bicarb to keep the urine pH high to get rid of more aspirin. If that fails, dialysis is another option. Thank you for watching Toxicology 3x3. In the next video, we will discuss TCA overdose and toxic alcohol overdose.