Should NAC Be Given with Normal Saline in Paracetamol Overdose?
Yes, intravenous NAC must be diluted in either normal saline (0.9% NaCl), half-normal saline (0.45% NaCl), 5% dextrose in water (D5W), or sterile water for injection prior to administration—normal saline is an appropriate and commonly used diluent. 1
FDA-Approved Diluent Options
The FDA label explicitly states that NAC is hyperosmolar (2600 mOsmol/L) and must be diluted before intravenous administration in one of three solutions 1:
- Sterile water for injection
- 0.45% sodium chloride injection (half-normal saline)
- 5% dextrose in water
Normal saline (0.9% NaCl) is not listed in the FDA label as a standard diluent option, though half-normal saline (0.45% NaCl) is explicitly approved 1.
Practical Considerations for Diluent Selection
Osmolarity Concerns
The choice of diluent affects the final osmolarity of the NAC solution 1:
- D5W produces the highest osmolarity (343-564 mOsmol/L depending on NAC concentration) 1
- Half-normal saline produces intermediate osmolarity (245-466 mOsmol/L) 1
- Sterile water produces the lowest osmolarity (91-312 mOsmol/L), which may require adjustment to physiologically safe levels, particularly in pediatric patients (generally not less than 150 mOsmol/L) 1
Pediatric Population Evidence
A retrospective case series of 40 pediatric patients (mean age 9.5 years) demonstrated safe use of 0.45% NaCl plus 5% dextrose for NAC infusion, with no cases of symptomatic hyponatremia 2. Mean serum sodium remained stable at 140 mmol/L (range 133-152 mmol/L) throughout treatment 2. This approach was developed specifically to avoid hyponatremia that had been observed with standard dosing in children 2.
Standard NAC Dosing Protocol
The FDA-approved intravenous regimen consists of 1:
- Loading dose: 150 mg/kg over 15 minutes
- Second dose: 50 mg/kg over 4 hours
- Third dose: 100 mg/kg over 16 hours (total 21-hour protocol)
The American Association for the Study of Liver Diseases confirms this same dosing schedule 3.
Critical Pitfalls and Caveats
Do Not Confuse NAC Diluent with Hydration Fluid
The question of NAC diluent is entirely separate from the question of intravenous hydration for contrast-induced nephropathy prevention. For contrast procedures, NAC was studied with concurrent 0.9% normal saline hydration (1 mL/kg/h from 6-12 hours pre-procedure to 6-12 hours post-procedure), but this large trial showed no benefit of NAC for preventing contrast-induced AKI 3. The Canadian Society of Nephrology explicitly recommends against using NAC for contrast-induced AKI prevention based on this high-quality evidence 3.
Preparation Requirements
- Visually inspect the diluted NAC solution for particulate matter and discoloration before administration 1
- The color may range from colorless to slight pink or purple after the stopper is punctured—this does not affect product quality 1
- Diluted solution can be stored for 24 hours at room temperature 1
- Never use a previously opened vial for intravenous administration 1
When to Extend Treatment Beyond 21 Hours
Continue NAC beyond the standard 21-hour protocol if 1:
- Acetaminophen levels remain detectable after the final maintenance dose
- ALT/AST continue rising
- INR remains elevated
- Suspected massive overdose
- Concomitant ingestion of other substances
- Pre-existing liver disease
In these situations, contact a regional poison center (1-800-222-1222) or the special health professional assistance line for acetaminophen overdose (1-800-525-6115) for dosing guidance 1.