How to dilute morphine for intravenous (IV) administration?

Morphine IV Dilution Guidelines

For intravenous morphine administration, dilute the concentrated solution (typically 10 mg/mL) with normal saline or sterile water to achieve the desired concentration, with the most accurate technique being a single-step dilution to 1 mg/mL followed by extraction of the required volume using a 1 mL syringe with manual shaking to ensure proper mixing.

Critical Dilution Technique

Recommended Method (Most Accurate)

• Use a single-step dilution technique: dilute morphine 10 mg/mL to 1 mg/mL (1:10 dilution), then extract the desired volume using a 1 mL syringe, and shake the syringe manually to ensure homogeneous mixing 1, 2
• This technique (designated T5 in research) produces the smallest difference between actual and intended morphine concentration compared to all other dilution methods 1
• Single-step dilution is significantly more accurate than double-dilution techniques (P = 0.047) 2

Techniques to AVOID

• Never extract 0.1 mL directly from a 10 mg/mL vial using a 1 mL syringe without subsequent dilution and shaking—this produces morphine concentrations more than double the intended dose (208 μg instead of 100 μg) 1
• Avoid double-dilution techniques, which are less accurate than single-step methods 2
• Do not use diluted solutions without shaking, as inadequate mixing results in concentration variability of 25-289 μg when targeting 100 μg 2

Practical Dilution Protocol

For Standard IV Bolus Administration

• Dilute morphine from 10 mg/mL ampoules to 1 mg/mL by adding 1 mL of morphine to 9 mL of normal saline or sterile water 1, 2
• Shake the syringe vigorously by hand to ensure complete mixing 1
• Extract the required dose volume from this 1 mg/mL solution 1, 2
• For example, to obtain 1.5 mg for IV titration, extract 1.5 mL from the 1 mg/mL solution 3, 4

For IV Titration in Severe Pain

• Prepare morphine 1 mg/mL solution as described above 1, 2
• Administer 1.5 mg IV bolus (1.5 mL of 1 mg/mL solution) every 10 minutes until pain relief or adverse effects occur 3, 4
• This titration method achieves satisfactory pain relief in 84% of patients within 1 hour 3

Common Pitfalls and Safety Considerations

Accuracy Concerns

• Dilution errors are extremely common: prepared morphine doses range from 25 μg to 289 μg when targeting 100 μg, representing up to 3-fold overdosing or 75% underdosing 2
• Without proper dilution technique, there is significant variability in actual morphine concentration, which contributes to unpredictable patient responses 2
• Using prediluted commercial solutions eliminates dilution errors entirely and should be preferred when available 2

Mixing Requirements

• Failure to shake the diluted solution results in significantly higher morphine concentrations (199 μg vs. 119 μg when targeting 100 μg) 1
• Morphine does not mix homogeneously by simple dilution alone—manual agitation is essential 1

Route-Specific Considerations

• The oral to IV morphine potency ratio is 2:1 to 3:1, meaning 20-30 mg oral morphine equals approximately 10 mg IV morphine 3
• When converting from oral to IV morphine, divide the oral dose by 3 3
• IV morphine achieves peak plasma concentrations within 15-30 minutes, with more rapid onset than oral administration 3

Alternative Administration Routes

Subcutaneous Administration

• Subcutaneous morphine is the preferred alternative when oral route is not feasible 3
• The oral to subcutaneous potency ratio is identical to IV (2:1 to 3:1) 3
• Subcutaneous administration is simpler, less painful than intramuscular, and has similar absorption to IV 3

Continuous IV Infusion

• For continuous infusions in children, morphine clearance is 20.5 ± 2.8 mL/kg/min, which is 3-fold higher than after single IV doses 5
• Target serum morphine concentration of 75 μg/L provides adequate analgesia during surgery in children 5
• Continuous infusion is preferred over intermittent boluses for patients requiring ongoing parenteral morphine 3