N-Acetylcysteine Administration in Acetaminophen Overdose
N-acetylcysteine (NAC) must be diluted in sterile water for injection, 0.45% sodium chloride (half-normal saline), or 5% dextrose in water prior to intravenous administration, with weight-based dosing of 150 mg/kg loading dose over 15 minutes, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours. 1
Fluid Selection for IV NAC Administration
The FDA-approved formulation requires dilution because undiluted NAC is hyperosmolar (2600 mOsmol/L) and cannot be given directly intravenously. 1 You have three acceptable diluent options:
- Sterile water for injection - Creates solutions ranging from 91-312 mOsmol/L depending on NAC concentration 1
- 0.45% sodium chloride (half-normal saline) - Creates solutions ranging from 245-466 mOsmol/L 1
- 5% dextrose in water (D5W) - Creates solutions ranging from 343-564 mOsmol/L 1
Special Consideration for Pediatric Patients
In pediatric patients, adjust osmolarity to a physiologically safe level (generally not less than 150 mOsmol/L), which makes 0.45% saline plus 5% dextrose particularly advantageous. 1, 2 A case series of 40 children (mean age 9.5 years) demonstrated safe sodium levels when NAC was infused in 0.45% NaCl with 5% dextrose, avoiding the symptomatic hyponatremia that can occur with standard 5% dextrose alone. 2
Standard IV Dosing Regimen (3-Bag Method)
The total recommended dose is 300 mg/kg given as three sequential doses over 21 hours: 1
- Loading dose: 150 mg/kg IV over 15 minutes 3, 1
- Second dose: 50 mg/kg IV over 4 hours 3, 1
- Third dose: 100 mg/kg IV over 16 hours 3, 1
This FDA-approved regimen should be initiated immediately when acetaminophen levels plot in the possible or probable risk zones on the Rumack-Matthew nomogram, ideally within 8-10 hours of ingestion. 4, 3
Alternative Oral Dosing Regimen
For oral administration, give 140 mg/kg loading dose followed by 70 mg/kg every 4 hours for 17 doses (total 72-hour regimen). 4, 5 The oral route demonstrated efficacy in a large multicenter study of 2,540 patients, with hepatotoxicity developing in only 6.1% of at-risk patients when treatment started within 10 hours. 5
Critical Timing Considerations
Treatment efficacy is time-dependent, with optimal outcomes when NAC is started within 8 hours of ingestion. 5, 6 The evidence shows:
- 0-8 hours: Only 2.9% severe hepatotoxicity 3
- 8-10 hours: 6.1% severe hepatotoxicity 5
- 10-24 hours: 26.4% severe hepatotoxicity 5
- 16-24 hours: 41% hepatotoxicity (still better than historical controls) 5
However, NAC remains beneficial even when started up to 24 hours post-ingestion and should not be withheld. 4, 6
Preparation and Storage
The diluted NAC solution can be stored for 24 hours at room temperature after preparation. 1 Visually inspect for particulate matter before administration; the color may range from colorless to slight pink or purple, which does not affect product quality. 1 Research demonstrates that NAC 60 mg/mL diluted in any of the three approved solutions and stored in PVC bags at 25°C maintains at least 98.7% of initial concentration for 72 hours. 7
Common Pitfalls to Avoid
- Never administer undiluted NAC intravenously - the hyperosmolar solution (2600 mOsmol/L) requires dilution 1
- Do not delay NAC while awaiting acetaminophen levels if there is strong suspicion of significant overdose 3
- Monitor for hypersensitivity reactions (rash, hypotension, wheezing) which typically occur 30-60 minutes after initiating infusion 1
- Use extreme caution in asthmatic patients - one patient with asthma died from bronchospasm after IV NAC administration 1
- In pediatric patients, avoid using only 5% dextrose as this can cause symptomatic hyponatremia; prefer 0.45% saline with dextrose 2
Extended Treatment Scenarios
For massive overdose, co-ingestions, or pre-existing liver disease, continue NAC beyond 21 hours if acetaminophen levels remain detectable or if ALT/AST continue rising. 1 Contact a regional poison center (1-800-222-1222) for dosing guidance in these complex cases. 1