What medications are incompatible with normal saline?

Medications Incompatible with Normal Saline

Ceftriaxone should never be reconstituted or diluted with calcium-containing solutions including normal saline in neonates, as particulate formation can result, but normal saline is compatible for ceftriaxone administration in older patients. 1

Critical Incompatibilities

Ceftriaxone

• Do not use diluents containing calcium (Ringer's solution, Hartmann's solution) to reconstitute or further dilute ceftriaxone for IV administration due to risk of particulate formation 1
• Normal saline (0.9% sodium chloride) is actually compatible with ceftriaxone at concentrations of 10-40 mg/mL and remains stable for 2 days at room temperature and 10 days refrigerated 1
• When ceftriaxone is mixed with metronidazole, use only 0.9% sodium chloride or 5% dextrose in water; the admixture is stable for 24 hours at room temperature only 1

Sequential Administration Required

• Vancomycin, amsacrine, aminoglycosides, and fluconazole are incompatible with ceftriaxone in admixtures 1
• These drugs must be given sequentially with thorough flushing of IV lines using compatible fluids between administrations 1

Medications Requiring Dilution Before Normal Saline Use

Sodium Bicarbonate in Pediatrics

• If only sodium bicarbonate 8.4% is available, dilute 1:1 with normal saline before administration in children <2 years of age 2
• This dilution prevents hyperosmolar complications in young children 2

Compatible Medications with Normal Saline

Insulin

• Humulin R U-100 is compatible with 0.9% sodium chloride for intravenous infusion at concentrations from 0.1 unit/mL to 1 unit/mL using polyvinyl chloride infusion bags 3
• Admixture bags prepared with insulin in normal saline are stable when refrigerated for 48 hours, then may be used at room temperature for an additional 48 hours 3

Amphotericin B

• Normal saline pre-infusion is recommended to reduce nephrotoxicity risk in patients receiving amphotericin B deoxycholate 4
• Higher ratios of normal saline to amphotericin B dose (NSS/AmBd) are associated with better AKI-free survival 4

Common Pitfalls and Cautions

Physical Mixing Errors

• Never physically mix or piggyback ceftriaxone solutions with other antimicrobial drugs or into diluent solutions other than those specifically listed as compatible 1
• This is a high-risk practice that can lead to precipitation and loss of drug efficacy 1

Large Volume Considerations

• Large volumes of normal saline may cause hyperchloremic metabolic acidosis 5
• Balanced crystalloid solutions (Ringer's lactate, Plasma-Lyte) may be preferable for large-volume resuscitation 5
• Normal saline causes substantially more in vitro hemolysis than Plasma-Lyte A during short-term storage after washing or intraoperative salvage 6

Specific Clinical Scenarios

• Flushing with 0.9% normal saline is recommended for central venous catheter maintenance to prevent thrombosis 2
• In crush syndrome, avoid potassium-containing balanced salt solutions; normal saline is preferred 7