Can D5 (Dextrose 5%) Replace Normal Saline as a Drug Diluent?
Yes, D5W can be used as a diluent for many injection drugs and may actually be preferable to normal saline in certain clinical contexts, particularly to avoid iatrogenic hypernatremia and hyperchloremia in critically ill patients.
Evidence-Based Rationale
D5W Is Explicitly Recommended in Guidelines
Multiple high-quality guidelines specifically recommend D5W as a diluent for various medications:
- Ranitidine for anaphylaxis: Should be diluted in 5% dextrose to 20 mL total volume and injected IV over 5 minutes 1
- Dopamine for refractory hypotension: 400 mg in 500 mL D5W administered at 2-20 mcg/kg/min 1
- Vasopressin: Can be diluted in either 5% dextrose water OR normal saline (25 U/250 mL) at 0.01-0.04 U/min 1
- Sodium bicarbonate for tricyclic antidepressant toxicity: 150 mEq NaHCO3 per liter of D5W 1
- Epinephrine infusions: Can be prepared in D5W at 1 mg in 250 mL yielding 4 mcg/mL 1
Clinical Advantages of D5W Over Normal Saline
Prevention of hypernatremia and hyperchloremia is a major advantage:
- A retrospective cohort study of 844 ICU patients found that changing the default diluent from D5W to normal saline significantly increased hypernatremia (27.3% vs 14.6%, p<0.001) and hyperchloremia (36.9% vs 20.4%, p<0.001) 2
- Drug diluents accounted for 21.4% of total infusion volume in critically ill patients 2
- Another study identified normal saline used to dissolve drugs and keep catheters open as a major modifiable risk factor for ICU-acquired hypernatremia 3
- The authors explicitly recommend dissolving drugs in D5W to prevent potentially harmful sodium overloading and hypernatremia 3
Drug-Specific Compatibility Considerations
Not all drugs are compatible with D5W, and compatibility must be verified:
- Diazepam: Compatible with D5W at dilutions of 1:40 (5 mg in 40 mL) for 6-8 hours, and 1:50 or greater for 24 hours 4
- Intrathecal chemotherapy: Methotrexate, cytarabine, and thiotepa can be prepared in normal saline, SWFI, or lactated Ringer's, with most centers using normal saline 5
- Peripheral nerve hydrodissection: Both D5W and normal saline are effective, with D5W showing consistently favorable outcomes 6
Clinical Algorithm for Diluent Selection
When to Prefer D5W:
- Critically ill ICU patients at risk for hypernatremia 2, 3
- Patients receiving large volumes of drug diluents 2
- When guidelines explicitly recommend it (ranitidine, dopamine, vasopressin) 1
- Peripheral nerve entrapment treatment 6
When to Prefer Normal Saline:
- Fluid resuscitation for hypotension/anaphylaxis: 1-2 L boluses at 5-10 mL/kg in first 5 minutes 1
- Volume expansion for shock states 1
- When drug compatibility with D5W is unknown or poor
- Intrathecal chemotherapy (conventional practice) 5
Critical Caveats:
- Always verify drug-specific compatibility before using D5W as a diluent 4
- Monitor blood glucose levels when using D5W, especially in diabetic patients 7
- In patients with cardiac or renal compromise, monitor for fluid overload regardless of diluent choice 7
- D5W provides no sodium replacement and should not be used when sodium repletion is needed 2
Bottom Line
The conventional practice of defaulting to normal saline for all drug dilutions is outdated and potentially harmful in critically ill patients. D5W is a safe and often superior alternative that reduces the risk of iatrogenic electrolyte abnormalities without compromising drug efficacy, provided drug-specific compatibility is confirmed 2, 3.