Medical Health Care Advices

Diagnosis

In the initial treatment is crucial to try to determine the dose ingested and the time of evolution. When ingestion is to commit suicide, you should look for the presence of other toxic substances concurrently.

After an overdose, blood levels should be measured between 4 and 24 hours of ingestion. Levels drawn before 4 hours is not reliable for decision making. The value obtained should be assessed according to the Rumack-Matthew nomogram.

The diagnosis of chronic toxicity of paracetamol use is much more difficult because the symptoms are more insidious presentation and the fact of drug intake is not always obtained in the initial evaluation. Hepatotoxicity should be suspected when a patient with paracetamol risk factors (alcohol, fasting, use of inducers of cytochrome P450) has taken more than 4 g in a period of 24 h.

The differential diagnosis should include ischemic hepatitis, viral hepatitis, drug toxicity or other toxins and Reye syndrome.

Treatment

The treatment of acetaminophen poisoning is based on two concepts: gastrointestinal decontamination with activated charcoal and the use of N-acetylcysteine ??(NAC).

Decontamination: The use of activated charcoal is indicated in all patients presenting within 4 hours of ingestion and then if there is use of extended-release preparations or simultaneous intake of drugs that delay gastric emptying. Activated carbon adsorbs paracetamol, reducing its absorption by 90%. Should be administered in a single dose of 1 g/kg. Activated charcoal can join NAC when administered together, but its absorption is greater than that required to reverse the toxicity of paracetamol, so do not recommend increasing the dose of NAC.

N-acetylcysteine ??(NAC) is a glutathione precursor that prevents paracetamol toxicity by limiting the accumulation of NAPQI. It can also bind directly to NAPQI as a glutathione substitute and increases in the non-toxic paracetamol sulphation. In later stages of poisoning, NAC is beneficial through mechanisms anti-inflammatory and antioxidant, in addition to inotropic and vasodilatory properties.
The maximum effectiveness of the NAC is produced when used within the first 10 hours of intake, reducing the hepatotoxicity of 50 to 5% and overall mortality of 8 to 0%. However, the later use has also proven beneficial in these patients.

The indications for treatment with NAC are:

- Patients with plasma concentrations over the possible toxicity line on the Rumack-Matthew nomogram.
- Intake only increased to 7.5 g in an adult (or 150 mg/kg in children) if there is availability of having levels within 8 hours.
- Patients with unknown time of ingestion and plasma levels of 10 mg / mL.
- Patients with a history of excessive consumption of paracetamol and evidence of liver toxicity in laboratory tests.
- The recommended dose is an initial load of 140 mg / kg followed by 17 doses of 70 mg / kg every 4 hours orally. The intravenous formulation, used in Europe, not available in Chile. In our country the only presentation available is the “Mucolytic” in bottles of 15 mL with a concentration of 1 g per 10 mL (70 kg adult would require a loading dose of about 6 bottles). The NAC has an unpleasant odor and may cause nausea or vomiting, decreased when mixed with fruit juice or drink, add ice and/or administering anti-emetics.
- Other measures: The use of cimetidine to inhibit cytochrome P450 has not had the desired effect. Hemodialysis and hemoperfusion are management alternatives that have shown no clear benefit. The use of liver dialysis systems (eg. MARS) might be useful in cases presenting with more than 10 hours after onset.

Indication for liver transplantation

When liver failure is established, the NAC should be administered continuously until improvement in prothrombin time (INR <2). The indication criteria for liver transplantation in patients with fulminant liver failure acetaminophen classically given by the King’s College Hospital include factors other than those used for other etiologies (table) (8). More recently it has been proposed as a criterion for transplant prothrombin time in seconds exceeds the time of overdose within hours or any of the following criteria: INR> 5 at any time, metabolic acidosis, hypoglycemia, or renal failure.

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