Should Normal Saline (NS) be given to a patient with a paracetamol overdose?

Should Normal Saline Be Given in Paracetamol Overdose?

Normal saline (NS) is NOT a treatment for paracetamol overdose itself—the only proven antidote is N-acetylcysteine (NAC), which must be administered immediately. 1 However, NS serves as the diluent for intravenous NAC administration and provides supportive care for fluid management. 2

The Role of Normal Saline in Paracetamol Overdose Management

NS as NAC Diluent (Primary Use)

NAC must be diluted before intravenous administration because it is hyperosmolar (2600 mOsmol/L), and normal saline (0.45% sodium chloride) is one of three FDA-approved diluents. 2

• The FDA label specifies that NAC can be diluted in sterile water for injection, 0.45% sodium chloride (half-normal saline), or 5% dextrose in water prior to IV administration 2
• Using 0.45% saline plus 5% dextrose has been shown to prevent symptomatic hyponatraemia in children, which can occur with standard 5% dextrose-only dilution 3
• A case series of 40 pediatric patients demonstrated safe sodium levels (mean 140 mmol/L) when NAC was infused in 0.45% NaCl with 5% dextrose 3

Supportive Fluid Management

NS may be used for general supportive care in paracetamol overdose patients, particularly those with:

• Dehydration from vomiting (common in the first 24 hours post-ingestion) 4
• Fulminant hepatic failure requiring ICU-level supportive care for fluid and electrolyte management 1, 4
• Renal dysfunction, which develops in severe cases and requires careful fluid balance 4

Critical Treatment Algorithm: What Actually Matters

Immediate Actions (Do NOT Wait for Labs)

1. Administer activated charcoal (1 g/kg) if patient presents within 4 hours of ingestion, given just prior to starting NAC 1
2. Start NAC immediately if:
   • Ingestion ≥10 grams or 150 mg/kg 1, 5
   • Any suspicion of hepatotoxicity (elevated transaminases) 1
   • Unknown time of ingestion with detectable paracetamol level 1
   • Fulminant hepatic failure with suspected paracetamol cause 1

NAC Dosing Regimen (The Only Proven Antidote)

The FDA-approved three-bag IV regimen is: 2

• Loading dose: 150 mg/kg over 15 minutes (diluted in NS or other approved diluent)
• Second dose: 50 mg/kg over 4 hours
• Third dose: 100 mg/kg over 16 hours (total 21-hour protocol)

Alternative two-bag regimen (from recent Australian/New Zealand guidelines) has similar efficacy with fewer adverse reactions: 6

• 200 mg/kg over 4 hours
• 100 mg/kg over 16 hours

Common Pitfalls Regarding Fluids

Do NOT delay NAC administration to obtain IV access for "fluid resuscitation"—NAC is the priority, and the NAC infusion itself provides fluid. 1 The critical window is 0-8 hours post-ingestion, where NAC provides maximal hepatoprotection with only 2.9% developing severe hepatotoxicity; this increases to 26.4% when treatment begins 10-24 hours post-ingestion. 1

Do NOT use NS as a substitute for NAC—there is no evidence that hydration alone prevents paracetamol hepatotoxicity. 7 The only interventions proven to reduce mortality are NAC (reduces mortality from 80% to 52% in fulminant hepatic failure) and liver transplantation in selected cases. 8, 1

Special Considerations for Fluid Choice

In pediatric patients, strongly consider using 0.45% saline plus 5% dextrose as the NAC diluent rather than 5% dextrose alone to prevent hyponatraemia. 3 Standard IV dosing with 5% dextrose has been shown to cause symptomatic hyponatraemia in children. 3

For massive overdoses (paracetamol concentrations more than double the nomogram line), increased NAC dosing is required, which means more diluent volume—monitor for fluid overload. 6