Is it safe to add medications to Dextrose Normal Saline (DNS)?

Avoid Adding Medications to Dextrose Normal Saline (DNS)

Medications should not be added to Dextrose Normal Saline (DNS) unless specific pharmaceutical compatibility and stability data are available from the manufacturer or an accredited laboratory. 1

Primary Recommendation

• Mixing medications with DNS in administration lines must be avoided unless validated by the manufacturer or accredited laboratory 1
• This is a strong recommendation with consensus from multiple international guidelines including ESPGHAN/ESPEN/ESPR/CSPEN and ESPEN 1

Why This Matters: The Science Behind Drug Incompatibility

Chemical Interaction Risks

• DNS admixtures show high potential for drug interactions leading to incompatibilities or stability issues 1
• Interactions occur through three main mechanisms: physiological interactions, altered drug behavior due to patient condition, and direct chemical interaction in the tubing during administration 1
• The pH of DNS (typically pH 5.0-7.0) significantly affects drug ionization—a drug that is unionized at pH 5.0 may be fully dissociated at pH 7.0, causing precipitation 1

Unpredictable Drug Behavior

• Studies on drug compatibility are specific to the particular branded product tested and cannot be extrapolated to other formulations 1
• Medications contain excipients (inactive substances) in addition to active ingredients, which can interact unpredictably with DNS components 1
• Drug pooling can occur in "non-circulating fluid spaces" at sharp corners and hanging loops within tubing, particularly at low flow rates, and may not be cleared by flushing 1

Dosing Accuracy Problems

• Adding medication into infusion sets can force a bolus of equivalent volume of DNS ahead of the medication, causing unpredictable delivery 1
• If the drug dose volume is less than the residual volume of tubing, delivery to circulation may be delayed 1

Safe Alternatives

Use Separate Administration Lines

• Infuse medications through an alternative line rather than mixing with DNS 1
• This eliminates compatibility concerns and ensures predictable drug delivery 1

When Mixing Is Absolutely Necessary

• Only proceed if the manufacturer or accredited laboratory has validated the specific combination 1
• A matrix table detailing permissible limits for additions must be obtained from the supplier 1
• Alternative ingredients should never be substituted without expert advice or repeat validation 1

Critical Pitfalls to Avoid

• Never extrapolate compatibility data from one DNS formulation to another—pH and composition variations make this dangerous 1
• Do not assume that because a drug is compatible with normal saline, it will be compatible with DNS—the dextrose component changes the chemical environment 1
• Avoid relying on literature reports of compatibility without confirming they used the exact same branded products you are using 1

Special Considerations for Specific Medications

Amphotericin B Deoxycholate

• Must be administered in 5% dextrose (not DNS) with slow infusion over 6-8 hours at 0.08 mg/kg/hour 1
• Pre-medication with diphenhydramine or acetaminophen is recommended to avoid drug-related reactions 1
• To avoid nephrotoxicity, 1 L of normal saline can be given before and after the infusion—but separately, not mixed 1

Calcium-Containing Solutions

• Calcium chloride should preferably be administered via central venous catheter due to severe tissue injury risk with infiltration 1
• If no central access is available, use calcium gluconate through a secure peripheral IV instead 1