Why Medications Are Mixed with NSS, D5LR, and 10% Dextrose Water
Primary Rationale for Diluent Selection
The choice of intravenous diluent depends on three critical factors: the medication's chemical compatibility, the patient's metabolic state (particularly glucose and sodium balance), and the clinical goal of preventing osmotic complications while maintaining drug stability. 1
Normal Saline Solution (NSS/0.9% NaCl)
NSS is the preferred diluent for most medications requiring isotonic dilution because it maintains chemical stability without pH-related precipitation and provides approximately 300 mOsm/kg H₂O tonicity that matches plasma osmolality 1, 2
Medications like phenytoin sodium demonstrate superior stability in NSS compared to dextrose solutions, maintaining >95% concentration for 8 hours, whereas dextrose solutions cause rapid concentration decline and crystal formation 2
NSS must be avoided in hypernatremic dehydration or nephrogenic diabetes insipidus because its tonicity (
300 mOsm/kg H₂O) exceeds typical urine osmolality (100 mOsm/kg H₂O) by 3-fold, requiring approximately 3 liters of urine to excrete the osmotic load from 1 liter of fluid, risking serious hypernatremia 3Injectable medications like streptomycin, amikacin, kanamycin, and capreomycin are routinely diluted in NSS for intramuscular or intravenous administration at standard doses 3
Dextrose 5% in Lactated Ringer's (D5LR)
D5LR combines glucose supplementation with balanced electrolyte replacement, making it appropriate for specific scenarios requiring both metabolic support and sodium correction 1
The American Academy of Pediatrics recommends D5 1/2NS (similar composition to D5LR) for continued rehydration in children after initial volume expansion, particularly when serum sodium is normal or elevated, at infusion rates typically 1.5 times the 24-hour maintenance requirements 1
This combination prevents hypoglycemia during prolonged procedures while providing electrolyte balance, though it carries risks of hyperglycemia requiring monitoring 1
10% Dextrose Water (D10W)
D10W is specifically indicated for pediatric resuscitation and diabetic ketoacidosis management when higher glucose concentrations are needed to prevent hypoglycemia while continuing other treatments 3, 1
The American Diabetes Association recommends switching to D5 or D10 with 0.45-0.75% NaCl when serum glucose reaches 250 mg/dL during DKA treatment to prevent hypoglycemia while continuing insulin therapy to clear ketoacidosis 1
For pediatric patients at risk for hypoglycemia who are dependent on IV fluids, D10 normal saline meets glucose requirements of 4-6 mg/kg/min 1
D10W is listed as essential resuscitation medication for pediatric emergency departments alongside D50W for different age-appropriate glucose replacement needs 3
Clinical Decision Algorithm
Step 1: Assess Patient's Metabolic State
If hypernatremic or pure water deficit exists: Use 5% dextrose alone (not NSS) because it delivers essentially no renal osmotic load once dextrose is metabolized, allowing controlled decrease in plasma osmolality 3, 1
If diabetic ketoacidosis after initial resuscitation (glucose <250 mg/dL): Switch to D5 or D10 with 0.45-0.75% saline to prevent hypoglycemia while continuing ketoacidosis treatment 1
If pediatric maintenance with hypoglycemia risk: Use D10 normal saline to meet metabolic glucose demands 1
Step 2: Consider Medication Compatibility
For medications requiring pH stability (like phenytoin): Use NSS or lactated Ringer's, never dextrose solutions which cause rapid degradation and crystallization 2
For injectable antibiotics (aminoglycosides, capreomycin): NSS is standard diluent for intramuscular or intravenous administration 3
For medications requiring stability testing: Ibuprofen and norepinephrine both demonstrate stability in either NS or D5W, though specific storage conditions vary 4, 5
Step 3: Monitor for Complications
The American Heart Association recommends frequent assessment of cardiac, renal, and mental status during fluid resuscitation to minimize risk of fluid overload and pulmonary edema 1
Monitor serum glucose hourly during acute resuscitation, then every 2-4 hours once stable to prevent both hyperglycemia and hypoglycemia 1
The European Society for Clinical Nutrition and Metabolism recommends monitoring serum sodium and osmolality to ensure correction rate does not exceed 8 mEq/day for hyponatremia or 3 mOsm/kg H₂O per hour for hyperosmolar states to prevent cerebral edema 1
Critical Pitfalls to Avoid
Never use salt-containing solutions (especially NaCl 0.9%) in hypernatremic dehydration or nephrogenic diabetes insipidus because the osmotic load will worsen hypernatremia, potentially requiring 3 liters of urine output per liter of fluid administered 3
Avoid dextrose-containing hypotonic solutions in neurosurgical patients or traumatic brain injury because they can contribute to cerebral edema; 0.9% saline is first-line therapy in these populations 1
Do not initiate IV fluid replacement with dextrose-containing solutions in routine elective surgery as even 500 ml of D5NS causes significant hyperglycemia (>10 mmol/L in 72% of patients), and hypoglycemia does not occur with non-dextrose crystalloids despite average fasting times of 13 hours 6
In patients with impaired renal function presenting with normo-osmolar, nonketotic, hyponatremic diabetic syndrome, large quantities of saline are unnecessary and potentially dangerous because compensatory hyponatremia maintains normal osmolality 7
Special Population Considerations
The American Geriatrics Society recommends careful monitoring for fluid overload in geriatric patients receiving D5 1/2NS to minimize risk of pulmonary edema 1
The American Academy of Pediatrics suggests particularly close observation for cerebral edema during osmolality correction in pediatric patients under 20 years to prevent long-term neurological damage 1
For patients unable to self-regulate fluid intake who must fast >4 hours, 5% dextrose in water at usual maintenance rate is reasonable, providing no renal osmotic load and typically decreasing urine volume considerably 1