The patient, a 24-year-old woman, was in a semi-conscious state when she was admitted to the emergency department. When the patient was found, there was an empty box of paracetamol (acetaminophen) and diazepam, and a drug overdose was initially suspected. In addition, patients also took carbamazepine to treat epilepsy. At the time of admission, the patient’s blood acetaminophen concentration was 100 mg/L (660 μmol/L), and she was estimated to have taken the drug for 4-8 hours.
There are many reports of similar cases. Usually, patients have different levels of consciousness disorder, confusion, nausea and vomiting when they are admitted to the hospital. Ancillary examinations can occasionally see an increase in liver enzymes. However, whether it is clinical or auxiliary examination, it usually lacks specificity. The early identification of acetaminophen poisoning is more dependent on medical history, such as a large history of medication, especially the recent use of a large number of cold medicines.
Highly active metabolites produced by cytochrome P450 enzymes can cause severe hepatotoxicity. The toxic metabolite (N-acetyl-p-benzoquinoneimine; NAPQI) produced at therapeutic dose can be detoxified by glutathione; in the case of excess, once the glutathione reserve is depleted, hepatotoxicity may occur after taking the drug for 8 hours. In the next few days, it causes fulminant hepatic failure.
As shown in the figure below, the horizontal axis is the time of administration and the vertical axis is the blood concentration of acetaminophen.
Treatment should be considered if the concentration is above the standard line (different from the US and UK standard lines). From the above figure, we can also see that the accuracy of whether the plasma concentration of acetaminophen is poisoned is decreasing with time. If the blood drug concentration data cannot be obtained within 8 hours of taking the drug, the clinician will There is no need to wait for the blood concentration test results, you need to pay more attention to the patient’s dose (Australia: ≥ 200 mg / kg or 10 g; UK: > 75 mg / kg or 4 g) or some overdose Evidence of liver toxicity (taking more than 24 hours).
Antidote to acetaminophen poisoning
1. N-acetylcysteine (NAC)
N-acetylcysteine (NAC) and methionine are substrates for glutathione synthesis, and antidote containing NAC components include injections and oral preparations, and NAC injections are the major antidote in many countries.
Randomized controlled trials have shown that the common side effects of intravenous infusion of NAC detoxification are allergic reactions, including rash, itching, vomiting, flushing, shortness of breath, hypotension, etc. The risk of adverse reactions depends to some extent on the infusion rate, slow point loss The risk will be smaller.
Therefore, when using NAC injection, you should control the infusion rate and pay close attention to whether the patient has an allergic reaction. Other serious adverse reactions associated with NAC infusion are mainly due to the use of excessive amounts of medication, such as a 10-fold normal dose, which may result in a fatal allergic reaction. In addition, nausea and vomiting are also common.
Methionine can only be taken orally, used in low-income countries, and is one of the basic drugs of the WHO. There is little data on adverse reactions associated with oral methionine, and vomiting is common.
3. Activated carbon
Other detoxification treatments include early use of activated carbon to reduce the body’s absorption of acetaminophen, and two large randomized controlled trials have shown that the use of activated carbon is very safe.
In addition, hemodialysis can be used to improve the elimination of acetaminophen, but current research on this aspect is limited, and safety and effectiveness have not been well evaluated.
This patient was detoxified by intravenous infusion of NAC (N-acetylcysteine) injection.
Early identification and treatment of acetaminophen poisoning
Because of the potential hepatotoxicity of acetaminophen, the FDA issued a statement in 2014 calling for warning doctors not to give patients more than 325 mg of acetaminophen. High doses not only do not improve analgesic effects, but also cause liver toxicity.
History + clinical manifestations + blood concentration detection
The medical history is mainly considered from three aspects:
1. Excessive intake of acetaminophen;
2. Increased cytochrome P450 enzyme activity (such as the intake of carbamazepine in this patient);
3. Detoxification substances are insufficient for glutathione.
According to the time after taking the drug, the clinical manifestations of poisoning can be divided into four phases:
1. Remove drugs: induce vomiting, gastric lavage, activated carbon, etc.
2. Promote excretion: hemodialysis.
3. Detoxification treatment: specific antidote NAC (oral preparations and injections).
► Oral 72 h program:
The load was 140 mg/kg, the maintenance amount was 70 mg / kg, once every 4 h, and the dose was administered 17 times for 72 h. If vomiting occurs within 1 h after taking the drug, the drug should be administered repeatedly. Note that NAC tablets are difficult to drink with water, can be dissolved by juice or cola, or administered through a gastric tube.
► Venous 20 h program:
150 mg/kg NAC was diluted in 200 ml of 5% glucose solution, and the infusion was completed in 15-60 min; 50 mg/kg NAC was diluted in 500 ml of 5% glucose solution, and was transferred in 4 h; 100 mg/kg NAC was diluted in In 5% glucose solution 1 L, 16 h was lost.
III. Discharge standard
1. End of NAC treatment (oral 72 h regimen or intravenous 20 h regimen);
2. No nausea, vomiting, pain in the right upper quadrant, discomfort in the kidney area, etc.;
3. Liver enzymes are normal; INR is normal or decreasing;
4. Cr is normal, no red blood cells and proteins are found in urine.
Attachment: acetaminophen indications, contraindications and drug interactions
Indications: used to relieve mild to moderate pain, such as headache, joint pain, migraine, toothache, muscle pain, neuralgia and dysmenorrhea. Can also be used for fever, such as cold and fever.
Contraindications: 1. Those who are allergic to this medicine. 2. Patients with severe liver and kidney dysfunction. 3. Alcoholism.
1. In patients with barbiturates (such as phenobarbital) or antispasmodic drugs (such as belladonna), long-term application of this product can cause liver damage.
2. The drug is taken with chloramphenicol to prolong the half-life of the latter and enhance its toxicity (vomiting, hypotension, hypothermia).
3. This medicine can inhibit the metabolism of warfarin or hinder the formation of blood clotage factor, thereby increasing the risk of warfarin causing bleeding.
4. Isoniazid can increase the hepatotoxicity of this drug.
5. The drug is long-term combined with aspirin, other salicylate drugs or other non-steroidal anti-inflammatory drugs (such as the annual cumulative dose of 1000g, applied for more than 3 years), can significantly increase the toxicity of the kidneys (including kidney Nipple necrosis, kidney and bladder tumors, etc.).
6. This medicine can inhibit the metabolism of vinegar coumarin or interfere with the formation of blood clots, thereby increasing the anticoagulant effect of acenocoumarol. The amount of anticoagulant should be adjusted when used together.
7. Phenytoin and sulfinpyrazone are combined with this drug. Carbamazepine is used in large doses and frequently with this drug to increase the metabolism of the drug and increase the toxicity to the liver.
8. Long-term alcohol abuse The use of this drug is more hepatotoxic, which may cause ethanol to induce cytochrome P4502E1 (CYP2E1) metabolism, resulting in more toxic metabolites produced by this drug.
9. Food (especially carbohydrate foods) can slow down the absorption of the drug and reduce the peak plasma concentration.