Volume of 5% Dextrose for NAC Loading Dose in Acetaminophen Overdose
For a 70 kg adult, dilute the 150 mg/kg loading dose (10,500 mg total) in 200 mL of 5% dextrose and infuse over 15-60 minutes. 1
Standard IV NAC Loading Dose Protocol
The American Association for the Study of Liver Diseases recommends an intravenous loading dose of 150 mg/kg over 15 minutes as the first step of the three-bag protocol. 1 For a 70 kg patient, this equals:
- Total NAC dose: 10,500 mg (150 mg/kg × 70 kg)
- Dilution volume: 200 mL of 5% dextrose 1
- Infusion time: 15 minutes (though some protocols extend this to 60 minutes to reduce anaphylactoid reactions) 2, 3
Complete Three-Bag Dosing Regimen
After the loading dose, continue with the standard protocol: 1
- Second bag: 50 mg/kg (3,500 mg for 70 kg) in 500 mL of 5% dextrose over 4 hours 1
- Third bag: 100 mg/kg (7,000 mg for 70 kg) in 1000 mL of 5% dextrose over 16 hours 1
Alternative Simplified Protocol
A validated alternative uses a single-bag approach: 30 g NAC in 1 L of 5% dextrose, with 150 mg/kg loading dose over 1 hour followed by 14 mg/kg/h for 20 hours. 2 This protocol demonstrated effective resolution of hepatotoxicity with fewer medication errors in clinical practice. 2
Critical Timing Considerations
Start NAC immediately—ideally within 8 hours of ingestion—as this reduces severe hepatotoxicity to only 2.9%, compared to 26.4% when started after 10 hours. 1, 4 Do not delay NAC administration while awaiting confirmatory acetaminophen levels if there is strong suspicion of significant overdose. 1
Important Caveats
Anaphylactoid reactions occur most commonly during the rapid loading dose when plasma concentrations peak at approximately 554 mg/L. 5 Consider extending the loading dose infusion to 60 minutes in patients with asthma or atopy. 2
Pediatric considerations: In children, use 0.45% saline plus 5% dextrose instead of pure 5% dextrose to prevent symptomatic hyponatremia. 6
Massive overdoses (acetaminophen levels above the "300-line" on the Rumack-Matthew nomogram) may require increased NAC dosing beyond the standard protocol, with step-wise increases at the 300-, 450-, and 600-lines. 4, 7
Hepatic failure cases require NAC regardless of time since ingestion, with demonstrated mortality reduction from 80% to 52%. 1, 4