Ketamine Diluent Selection
Normal saline (0.9% sodium chloride) is the preferred diluent for ketamine, with D5W as an acceptable alternative; lactated Ringer's solution should be avoided when sodium bicarbonate therapy might be needed concurrently. 1
FDA-Approved Diluent Options
The FDA label for ketamine explicitly permits three diluents for dilution 1:
- Sterile Water for Injection, USP
- 0.9% Sodium Chloride Injection, USP (Normal Saline)
- 5% Dextrose in Water (D5W)
For induction dosing, the 100 mg/mL concentration must be diluted with an equal volume of one of these three agents and used immediately after dilution 1. For maintenance infusions (1 mg/mL concentration), ketamine can be added to 500 mL of either D5W or normal saline 1.
Clinical Considerations for Diluent Selection
Normal Saline as First Choice
Normal saline represents the most versatile option because 1, 2:
- It maintains chemical stability for extended periods (91 days demonstrated in polypropylene syringes at both room temperature and refrigeration) 2
- It avoids potential glucose-related complications in diabetic or critically ill patients
- It remains compatible if sodium bicarbonate therapy becomes necessary (lactated Ringer's contains potassium and should be avoided in this scenario) 3
D5W as Acceptable Alternative
D5W is equally acceptable from a stability standpoint 1:
- The FDA label specifically endorses D5W for both dilution and maintenance infusions 1
- Multiple other anesthetic agents (dopamine, vasopressin, epinephrine) use D5W as standard diluent 4
- Blood glucose monitoring is prudent when using D5W, particularly in diabetic patients 4
Lactated Ringer's: A Critical Contraindication Context
While lactated Ringer's is not mentioned in the FDA label for ketamine, important considerations exist 3:
- Avoid lactated Ringer's if sodium bicarbonate therapy might be required, as the potassium content (4 mEq/L) in lactated Ringer's contradicts the hyperkalemia treatment goal of bicarbonate 3
- In crush syndrome or any hyperkalemic state, potassium-containing solutions like lactated Ringer's are contraindicated 3
- If ketamine is being used in trauma or critical care settings where metabolic acidosis requiring bicarbonate is possible, normal saline is the safer default choice 3
Practical Stability Data
Research demonstrates excellent stability across diluents 2, 5, 6:
- Ketamine-morphine combinations in normal saline remained stable for 91 days at both 23°C and 5°C 2
- Ketamine-hydromorphone mixtures in normal saline maintained >90% concentration for 7 days at 25°C 5
- Concentrated ketamine infusions (250 mg in 50 mL normal saline) can safely run for 72 hours without microbiological contamination 6
- A military anesthesia protocol successfully used ketamine 200 mg mixed with midazolam and vecuronium in 50 mL normal saline 7
Recommended Algorithm for Diluent Selection
Use normal saline (0.9% sodium chloride) as default unless specific contraindications exist 1, 2:
First-line choice: Normal saline - provides maximum flexibility for concurrent therapies and avoids glucose administration 1, 2
Alternative: D5W - appropriate when normal saline is contraindicated (severe hypernatremia, hyperchloremic acidosis) or when glucose administration is desired 1
Avoid lactated Ringer's - not FDA-approved for ketamine dilution, and the potassium content creates potential complications if sodium bicarbonate becomes necessary 3, 1
Common Pitfalls to Avoid
- Never use lactated Ringer's if treating or at risk for hyperkalemia, as the 4 mEq/L potassium content contradicts bicarbonate therapy goals 3
- Do not inject undiluted 100 mg/mL ketamine intravenously - always dilute with equal volume of approved diluent first 1
- Avoid mixing ketamine with alkaline solutions in the same line, as this principle applies broadly to many anesthetic agents 8
- Use diluted solutions immediately after preparation per FDA guidance, though research shows extended stability is possible under controlled conditions 1, 2