Acetaminophen poisoning

Initial supportive care is essential with immediate assessment of the patient’s airway, breathing, and fluid statu before treatment for suspected acetaminophen overdose is initiated.

Assessing for other potential life-threatening co-ingestions is very important.

Administer activated charcoal (AC) if the patient has a stable mental and clinical status and presents to the emergency department within 1 hour of ingestion.

A serum acetaminophen concentration helps to determine the risk for hepatotoxicity, using the Rumack-Matthew nomogram.

Patients with acetaminophen levels below the line for hepatotoxicity on the Rumack-Matthew nomogram may be discharged home after they are medically cleared.

In cases where ingestion occurred with intent to do self-harm, a psychosocial, psychological and/or psychiatric evaluation is indicated.

Patients with acetaminophen plasma levels above the hepatic toxicity possible line on the Rumack-Matthew nomogram are admitted to the hospital for treatment with N -acetylcysteine (NAC).

Patients with evidence of hepatic failure, metabolic acidosis, coagulopathy, and/or encephalopathy require intensive care unit care.

Treatment with N -acetylcysteine (NAC) is nearly 100% hepatoprotective when it is given within 8 hours after an acute acetaminophen ingestion.

It is recommend that the use of NAC to treat acute acetaminophen overdose in patients with either possible or probable risk for hepatotoxicity, according to the Rumack-Matthew nomogram, within 8-10 hours post ingestion.

Because N -acetylcysteine (NAC) therapy is benign and the risk of adverse effects from acetaminophen toxicity is high, it should be given even if the history is unclear but a potentially toxic acetaminophen ingestion is suspected.

NAC should be administered while awaiting a serum APAP level if the patient presents close to or later than 8 hours after an acute ingestion, or if the patient is pregnant.

A late presentation should not preclude NAC administration, and failure to administer NAC is considered medically and legally inappropriate.

Surgical evaluation for possible liver transplantation is indicated in severe hepatotoxicity and potential to progress to hepatic failure.

Criteria for liver transplantation include the following:
Metabolic acidosis

Renal failure

Coagulopathy

Encephalopathy

Oral activated charcoal avidly adsorbs acetaminophen and may be administered if the patient presents within 1 hour after ingesting a potentially toxic dose.

Oral activated charcoal should not be administered if the patient is mentally compromised and does not have a protected airway.

Oral activated charcoal may be of benefit longer than 1 hour after the ingestion if the ingestion involves an agent that delays gastric emptying.

The oral formulation of NAC sold as Mucomyst is the drug of choice for the treatment of acetaminophen overdose.

Regimen for oral NAC starts with a loading dose of 140 mg/kg, followed by 17 doses, each at 70 mg/kg, given every 4 hours, making the duration of the treatment 72 hours.

Oral NAC is safe and effective for as long as 24 hours after a toxic ingestion.

Oral NAC effectively prevents hepatotoxicity, regardless of the initial serum acetaminophen level, if started within 8 hours of the ingestion.

Intravenous N-Acetylcysteine approved for patients with altered mental status, gastrointestinal bleeding or obstruction, and inability to tolerate oral agent,

Continuous IV infusion is recommended for acute ingestion, as follows:

Loading dose: 150 mg/kg IV; mix in 200 mL of 5% dextrose in water (D5W) and infuse over 1 h, 50 mg/kg IV in 500 mL D5W over 4 h, 100 mg/kg IV in 1000 mL D5W over 16 h.

Intermittent IV infusion may be considered for late-presenting or chronic ingestion.

A loading dose of 140 mg/kg IV (diluted in 500 mL D5W) is infused over 1 h.

Maintenance doses of 70 mg/kg IV are given every 4 hours for at least 12 doses.

In about 15% of patients IV administration of NAC is associated with flushing, pruritus, and rash.

Rarely IV NAC can be associated with bronchospasm and hypotension.

Early administration of NAC is more important than GI decontamination with oral activated charcoal in cases of acetaminophen overdose.

The administration of activated charcoal may decrease the bioavailability of oral NAC, but the decrease is clinically insignificant.

Activated charcoal administration may prevent significant APAP absorption from the GI tract and obviate the need for NAC.

Oral NAC administration may be altered with activated charcoal administration in the rare cases where the patient needs multiple doses of activated charcoal for the treatment of a co-ingestant, but intravenous NAC administration is preferable in this situation.

If a patient presents 8-24 hours or later after an acute ingestion, NAC therapy is started and evaluation for laboratory evidence of hepatotoxicity is done.

NAC administration in cases of hepatic failure decreases incidence of cerebral edema and improves survival, and therapy should be initiated if concern exists for potential toxicity while awaiting confirmatory laboratory studies.

NAC may be beneficial for acetaminophen-induced hepatic failure when patients present more than 24 hours after ingestion.

Toxicologists recommend initiating treatment with NAC in patients who present more than 24 hours after ingestion, if an APAP plasma level is detected and if hepatic injury is evident from liver function studies.

The beneficial effect of NAC in late treatment mechanisms include: an antioxidant effect, decreased neutrophil accumulation, and improved microcirculatory blood flow supporting increased oxygen delivery to hepatic tissue.

Continuation of NAC therapy depends on the patient’s clinical status, serum levels of APAP and liver function tests.

The Rumack-Matthew nomogram is not valid in cases of late presentation.

Following multiple ingestions or chronic ingestion of supratherapeutic doses of acetaminophen over hours or days,: evaluation for the presence of a persistent APAP concentrations and liver function are done and NAC therapy is initiated if the patient has elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and measurable
APAP levels.

Vomiting is associated with acetaminophen toxicity, as are activated charcoal and oral NAC therapy, so antiemetic therapy is often necessary for successful administration of oral NAC.

Persistent vomiting prevents oral NAC administration and the drug should be administered intravenously.

Metoclopramide an antiemetic that works by blocking dopamine receptors in the chemeceptor trigger zone of the central nervous system, enhances gastrointestinal motility and accelerates gastric emptying time is to be considered for the treatment of nausea.

Ondansetron is a selective 5-hydroxytryptamine (5HT3) receptor antagonist that blocks serotonin by acting on the vagus nerve peripherally and at the chemoreceptor trigger zone of the central nervous system (CNS), and is more effective than metoclopramide.

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