From the Guidelines
For acetaminophen toxicity causing liver failure, the recommended N-acetylcysteine (NAC) intravenous regimen is a loading dose of 150 mg/kg administered over 15 minutes, followed by 50 mg/kg over 4 hours, and then 100 mg/kg over 16 hours, as this protocol has been shown to be effective and safe in numerous controlled trials 1.
Key Considerations
- The treatment should be initiated as soon as possible after acetaminophen ingestion, ideally within 8-10 hours for best outcomes, though it may still provide benefit when started later 1.
- NAC should be diluted in 5% dextrose solution rather than normal saline.
- For patients weighing over 100 kg, some clinicians cap the dose calculation at 100 kg to avoid excessive dosing.
- The mechanism of action involves NAC replenishing glutathione stores, which are depleted during acetaminophen metabolism, thereby preventing the toxic metabolite NAPQI from causing hepatocellular damage.
- Treatment duration may be extended beyond 21 hours if liver enzymes remain elevated or the patient shows signs of ongoing liver injury.
- Common side effects include nausea, vomiting, and anaphylactoid reactions, particularly during the loading dose, which may require slowing the infusion rate.
Recent Guidelines
- The American Gastroenterological Association Institute guidelines support the use of NAC in patients with ALF related to acetaminophen, with a strong recommendation 1.
- The management of liver failure in general intensive care units also recommends the initiation of N-acetylcysteine therapy without waiting for, and regardless of, the results of serum acetaminophen determinations, with a strong agreement 1.
Administration
- NAC may be given orally (140 mg/kg by mouth or nasogastric tube diluted to 5% solution, followed by 70 mg/kg by mouth q 4 h 17 doses) or intravenously, with the intravenous route being preferred in patients with ALF due to potential issues with oral administration 1.
- Allergic reactions may be successfully treated with discontinuation, antihistamines, and epinephrine for bronchospasm.
From the Research
Acetylcysteine Drip Dose for Liver Failure due to Acetaminophen Toxicity
- The standard treatment for acetaminophen-induced liver injury is N-acetylcysteine, which is a known scavenger of reactive oxygen species (ROS) 2.
- Acetaminophen overdose has a 66% chance of recovery with early N-acetylcysteine treatment and supportive care 3.
- The American Association for the Study of Liver Diseases (AASLD) 2011 guideline suggested that N-acetylcysteine could improve spontaneous survival when given during early encephalopathy stages for patients with non-paracetamol-related acute liver failure 4.
- However, the available evidence is inconclusive regarding the effect of N-acetylcysteine compared with placebo or no N-acetylcysteine, as an adjunct to usual care, on mortality or transplant rate in non-paracetamol-induced acute liver failure 4.
- N-acetylcysteine remains the standard of care in the setting of acetaminophen toxicity 5.
Dosage and Administration
- The exact drip dose of acetylcysteine for liver failure due to acetaminophen toxicity is not specified in the provided studies.
- However, it is mentioned that N-acetylcysteine is given at a dose of 100 mg/kg in an experimental study on rats 6.
- Further research is needed to determine the optimal dose and duration of N-acetylcysteine treatment for acetaminophen-induced liver injury.
Alternative Treatments
- Leuco-methylene blue (LMB) has been shown to have a protective effect against acetaminophen-induced liver injury in an experimental study on rats 6.
- LMB significantly reduced serum levels of liver enzymes and increased the expression of genes involved in mitochondrial biogenesis and antioxidant defense.
- However, more research is needed to confirm the efficacy and safety of LMB as a treatment for acetaminophen-induced liver injury in humans.