Acetylcysteine Injection Dilution
For intravenous administration of acetylcysteine, dilute the 20% inhalational solution to a 2.6% concentration by adding 150 mL of 20% N-acetylcysteine to 1 liter of 5% dextrose in water (D5W), filtered through a 22-micron filter. 1
Standard Dilution Protocol
The recommended dilution creates a final concentration of approximately 30 grams of N-acetylcysteine in 1 liter of D5W, which is stable for up to 60 hours at room temperature. 2, 1
Preparation Steps
- Use the 20% inhalational N-acetylcysteine solution (200 mg/mL) as the source product 1
- Add 150 mL of the 20% solution through a 22-micron filter into 1 liter of D5W 1
- This creates a 2.6% solution (approximately 30 g/L) suitable for intravenous administration 2, 1
- The solution remains chemically stable for at least 60 hours at ambient conditions (25°C, 65% relative humidity) 1
Dosing Regimen Using This Dilution
The standard three-bag FDA-approved regimen can be simplified using a single-bag preparation:
- Loading dose: 150 mg/kg administered over 1 hour 2
- Maintenance infusion: 14 mg/kg/hour for 20 hours 2
- Total treatment duration is typically 21 hours, though may be extended based on clinical parameters 2
Alternative FDA-Approved Regimen
For reference, the traditional three-bag FDA regimen uses different dilutions 3:
- Bag 1: Loading dose of 150 mg/kg in 200 mL D5W over 60 minutes
- Bag 2: 50 mg/kg in 500 mL D5W over 4 hours
- Bag 3: 100 mg/kg in 1000 mL D5W over 16 hours
Stability and Safety Considerations
The diluted solution meets USP standards for stability, sterility, and pyrogen-free status when properly prepared:
- Chemical stability is maintained with <10% decomposition for 60 hours at room temperature 1
- At 72 hours, degradation reaches 10-15%, exceeding acceptable limits 1
- Solutions remain free from bacterial growth for at least 72 hours 1
- Endotoxin/pyrogen testing is negative when prepared under sterile technique 1
Critical Preparation Pitfalls to Avoid
- Do not use solutions older than 60 hours - degradation exceeds acceptable limits after this timepoint 1
- Always use a 22-micron filter during preparation to ensure sterility 1
- Maintain sterile technique throughout preparation to prevent contamination 4
- Do not dilute in normal saline - D5W is the appropriate diluent 2, 1
Dosing Adjustments for Massive Overdose
For patients with acetaminophen concentrations above the "300-line" on the Rumack-Matthew nomogram, consider increasing the maintenance infusion rate:
- Standard maintenance: 14 mg/kg/hour 2
- For massive overdoses (>300-line): stepwise increases in dosing may be necessary 5
- Patients above the 300-line develop hepatotoxicity at higher rates and may benefit from dose escalation 5
Monitoring During Administration
Key parameters to monitor include:
- Hepatic transaminases (AST/ALT) - hepatotoxicity defined as AST >1000 units/L 6, 2
- Serum acetaminophen concentrations 6
- Infusion-related adverse reactions occur in approximately 6% of patients but rarely require discontinuation 6
- Mean duration of therapy is 25.6 hours, with mean length of stay 2.99 days 2
Common Administration Errors
The simplified single-bag protocol reduces but does not eliminate medication errors 2:
- Loading dose rate errors are most common (11 rate-related errors per study) 2
- Dose-related errors occur less frequently (8 per study) 2
- Therapy interruptions >60 minutes are rare (occurred in only 3/70 patients) 2
Clinical Efficacy
All patients with hepatotoxicity (AST >1000 units/L) due to acute acetaminophen toxicity had complete resolution and successful discharge when treated with this protocol. 2
- The simplified regimen is effective and well-tolerated 2
- Intravenous administration offers advantages over oral including shorter hospital stay, patient convenience, and avoidance of reduced bioavailability from charcoal or vomiting 6
- Meta-analysis shows similar outcomes between IV and oral routes when treatment is initiated within 24 hours 6