Acute poisoning of acetaminophen (paracetamol): diagnosis and treatment of intensive care

2021-07-29 12:06 AM

When an overdose of acetaminophen, the toxic metabolite NAPQI increases, exceeding the neutralizing capacity of glutathione, which is toxic to the liver and kidneys.

Paracetamol is the most widely used analgesic and antipyretic. Currently, on the market, there are many different brands of paracetamol containing paracetamol. This is a generally safe drug, but when overdosed can cause toxicity, mainly causing hepatocellular necrosis and nephrotoxicity.

Mechanism of toxicity: Normally, over 85-90% of acetaminophen is metabolized in the liver by glucoronyl and sulfate pathways under the action of cytochrome P450 enzymes to non-toxic products. 5-15% is metabolized to NAPQI (N-acetyl-p-aminophenol) which has toxic effects but is inactivated by glutathione to mercaptan, non-toxic cysteine. When an overdose of acetaminophen, the toxic metabolite NAPQI increases, exceeding the neutralizing capacity of glutathione, which is toxic to the liver and kidneys.

Definite diagnosis

Question: There are two cases

Taking a toxic dose: patients taking paracetamol with a toxic dose of > 140mg/kg, in alcoholics, malnourished, cirrhosis, taking other drugs that are toxic to the liver, maybe poisoned with lower doses.

Overdose for repeated treatment can also cause poisoning: drink > 2 times, each time > 4g over a period of > 8 hours.

Symptoms: divided into 4 stages over time

Stage 1 (0.5-24 hours): immediately after oral administration: usually asymptomatic:

Nausea, vomiting.

Sweating, discomfort.

May increase AST, ALT.

Clinical examination was normal.

Phase 2: 24-72 hours:

Anorexia, nausea, vomiting.

AST, ALT increased, bilirubin increased, PT time was prolonged, renal function decreased.

Stage 3: (72 - 96 hours):

Liver failure: jaundice, coagulopathy, hepatic encephalopathy, hepatic coma leading to death.

Acute renal failure: may be associated with liver failure.

Multi-organ failure.

Stage 4 (from 4-14 days): if the patient is alive, the liver function recovers completely without leaving fibrosis:

Test:

Toxic:

Rumack-Matthew. Graph

Time from drinking to taking blood for testing (hours)

Qualitative: Paracetamol is positive in gastric juice or urine, indicating that the patient has taken paracetamol.

Quantification of blood paracetamol, determining the risk of poisoning in most cases, deciding the indication or termination of specific treatment: blood collection at about 4-24 hours after oral administration. If the blood is drawn earlier, the results are not significant, and if the blood is taken later, the concentration is already negative. If the results are not clear poisoning should take the second time after 8 hours (in case of slow absorption), then compare with the Rumack - Matthew graph.

Blood and urine tests: urea, sugar, creatinine, electrolytes, AST, ALT, basic coagulation, tests to exclude hepatitis due to other causes. Total urinalysis.

Diagnostic imaging: chest X-ray, abdominal ultrasound.

Other tests: depending on the patient's condition.

Diagnosis of complications

Acute liver failure: encephalopathy due to liver disease (disordered consciousness, coma, cerebral edema), coagulopathy, decreased platelets, increased NH3, increased lactate, hypoglycemia, decreased albumin,...

Bleeding: due to coagulation disorders due to liver failure.

Acute renal failure.

Differential diagnosis

Hepatitis, liver failure, hepatic coma due to viral hepatitis, alcoholism and other causes.

Treatment

Stabilize the patient

Emergency treatment to stabilize the patient's condition:

Apply as a rule, treat severe conditions (such as respiratory failure, hypotension...).

Toxic removal:

Induce vomiting: if the patient has taken paracetamol within 1 hour.

Gastric lavage: when the patient has taken it within 6 hours.

Activated charcoal: after the patient is induced vomiting or gastric lavage. Use a dose of 1g/kg, combined with a sorbitol equivalent dose.

Antidote:

N - acetylcysteine (Mucomyst, Acemuc...).

Point:

+ Patients taking paracetamol dose > 140mg/kg within 72 hours, liver enzymes have not increased, there is no or no blood paracetamol concentration test.

+ Overdose for repeated treatment with paracetamol concentration > 20mcg/ml or elevated liver enzymes.

+ Patients suspected of taking paracetamol overdose but the dose is unknown, within 72 hours, liver enzymes have not increased.

+ Patient has paracetamol concentration above the recommended treatment line of the graph.

+ Patients who take paracetamol overdose (> 4g/24 hours), come late, regardless of paracetamol concentration but have hepatitis or liver failure, paracetamol poisoning cannot be ruled out.

Dosage:

+ Patients without hepatitis symptoms:

+ Oral N-acetylcysteine: initial dose: 140mg/kg, later doses 70mg/kg/time, 4 hours/time (17 doses).

+ N-acetylcysteine ​​intravenous infusion: initial dose 150mg/kg, infused over 60 minutes, next dose 50mg/kg, infused over 4 hours, maintenance dose 100mg/kg, infused over 16 hours.

Usage time:

+ Using blood paracetamol gas is negative and liver enzymes do not increase.

+ In case there is no concentration test: until the above dose is used, liver enzymes do not increase. If liver enzymes increase, continue to use maintenance dose until enzymes are normal.

+ Patients with symptoms of hepatitis, liver failure: use the same as above and last until the hepatitis is gone.

How to use:

+ Mix N-acetylcysteine ​​in oral form into a 5% solution, you can add juice to make it easier to drink. The interval between doses is 4 hours, if the patient vomits after taking the drug, then take the same dose again after 1 hour. If the patient has just started taking activated charcoal, they can still take it normally.

+ Active antiemetic: before taking medicine, the patient should take the antiemetic drug: Primperan 10mg x 1 intravenous tube, if vomiting is still present, give the patient a slow dose or slow drip over nasogastric tube (patient is not conscious), booster injection or aminazin 25mg x 1/2-1 intramuscularly.

If the patient vomits after taking the dose, repeat the dose after 1 hour.

Other treatments:

Rehydration, electrolytes.

Patients with poor appetite due to vomiting: antiemetic, 10-20% glucose infusion to nourish.

Hepatitis: supportive treatment as a rule.

Acute renal failure: treatment according to general principles.

Monitoring:

Liver enzyme tests, kidney function.

Monitor the use of N-acetylcysteine

The patient's vomiting, whether the patient is taking the correct dose or not; Follow-up tests (as above).

Prevention

Advise patients not to abuse paracetamol, be cautious because there are many different preparations containing paracetamol.

Caution should be exercised when giving paracetamol to patients who are alcoholic, have liver disease, are being treated with hepatotoxic drugs, or are malnourished.

For patients who self-destruct, examine and treat according to psychiatric specialties to avoid recurrence of poisoning.