From the Guidelines
The recommended N-acetylcysteine (NAC) infusion dose is a loading dose of 150 mg/kg in 5% dextrose over 15 minutes, followed by a maintenance dose of 50 mg/kg over 4 hours, and then 100 mg/kg over 16 hours. This dosing regimen is based on the most recent and highest quality study available, which is the 2005 AASLD position paper on the management of acute liver failure 1.
Key Considerations
- The NAC infusion dose should be administered as early as possible, but may still be of value 48 hours or more after acetaminophen ingestion.
- The treatment protocol consists of three infusions: an initial loading dose, a second infusion over 4 hours, and a third infusion over 16 hours.
- Patients with active gastrointestinal bleeding or worsening mental status may require intravenous administration of NAC.
- Allergic reactions to NAC may be successfully treated with discontinuation, antihistamines, and epinephrine for bronchospasm.
Administration Details
- The loading dose is 150 mg/kg in 5% dextrose over 15 minutes.
- The maintenance dose is 50 mg/kg over 4 hours, followed by 100 mg/kg over 16 hours.
- Oral administration of NAC is also possible, with a dose of 140 mg/kg by mouth or nasogastric tube diluted to 5% solution, followed by 70 mg/kg by mouth every 4 hours for 17 doses.
Monitoring and Duration
- Monitor liver function tests and acetaminophen levels during treatment.
- Continue NAC infusion beyond the initial 21-hour regimen if acetaminophen levels remain detectable or liver enzymes are elevated.
- NAC works by replenishing glutathione stores, which helps detoxify the toxic acetaminophen metabolite NAPQI, and also acts as an antioxidant and improves microcirculatory blood flow in the liver 1.
From the FDA Drug Label
DOSAGE GUIDE AND PREPARATION Doses in relation to body weight are: Loading Dose of Acetylcysteine ** Body Weight Grams of Acetylcysteine mL of 20% Acetylcysteine mL of Diluent Total mL of 5% Solution ... The loading dose is 140 mg per kilogram of body weight. The maintenance dose is 70 mg/kg.
The N-acetylcysteine (NAC) infusion dose is as follows:
- Loading dose: 140 mg/kg of body weight
- Maintenance dose: 70 mg/kg of body weight 2
From the Research
N-acetylcysteine (NAC) Infusion Dose
The NAC infusion dose can vary depending on the specific treatment protocol and the patient's condition.
- A study published in 2011 3 investigated a novel dosing regimen for the immediate administration of NAC on admission at a lower infusion rate, and found that an infusion of 110 mg/kg over the first 5 h (22 mg/kg/h) followed by the last two phases of the conventional regimen, or 200 mg/kg over 9 h (22.6 mg/kg/h) followed by the last phase of the conventional regimen could be used.
- Another study from 2011 4 used a two-stage infusion regimen of 150 mg/kg bolus over 1 h followed by a continuous infusion of 10 mg/kg/h for 20 h in children with paracetamol poisoning.
- A 2019 study 5 described a simplified NAC treatment after paracetamol overdose, with a total dose of 300 mg/kg given over 20 hours and 15 minutes, and suggested a modified regime with two infusions instead of three.
- A 1991 study 6 used a 48-hour IV NAC treatment protocol with a loading dose of 140 mg/kg followed by 12 doses of 70 mg/kg every four hours.
- A 2019 study 7 proposed a strategy for step-wise increases in NAC dosing in response to high acetaminophen concentrations at the 300-, 450-, and 600-lines after acute massive acetaminophen overdoses, but did not specify exact doses.
Key Considerations
- The choice of NAC infusion dose and protocol may depend on the specific clinical scenario and the patient's risk of hepatotoxicity.
- Different studies have used varying doses and protocols, and the most appropriate dose and protocol may depend on the individual patient's needs and circumstances.
- The studies cited above 3, 4, 5, 6, 7 provide evidence for different NAC infusion doses and protocols, but the optimal approach may vary depending on the specific clinical context.