How is remifentanil reconstituted?

Remifentanil Reconstitution

Remifentanil must be reconstituted by adding 1 mL of diluent per mg of remifentanil powder, shaken well to dissolve, yielding a concentration of approximately 1 mg/mL, and then further diluted to a final concentration of 20,25,50, or 250 mcg/mL before administration—it should never be administered without dilution. 1

Step-by-Step Reconstitution Protocol

Initial Reconstitution

• Add 1 mL of diluent per mg of remifentanil lyophilized powder 1, 2
• Shake the vial well to completely dissolve the powder 1
• This yields a reconstituted solution containing approximately 1 mg/mL of remifentanil 1

Diluent Selection

• Sterile water or 0.9% saline are the recommended diluents for reconstitution 1, 3
• Ultrapure water maintains remifentanil stability at pH < 4 for up to 24 hours 3
• 0.9% saline also maintains stability without significant degradation over 24 hours 3
• Avoid sodium bicarbonate solutions (pH 8.65), which cause significant remifentanil degradation (P < 0.001) 3

Final Dilution Requirements

After initial reconstitution, remifentanil must be further diluted to one of the following final concentrations before administration 1:

• 20 mcg/mL: Add reconstituted remifentanil to achieve 1 mg in 50 mL, 2 mg in 100 mL, or 5 mg in 250 mL 1
• 25 mcg/mL: Add reconstituted remifentanil to achieve 1 mg in 40 mL, 2 mg in 80 mL, or 5 mg in 200 mL 1
• 50 mcg/mL: Add reconstituted remifentanil to achieve 1 mg in 20 mL, 2 mg in 40 mL, or 5 mg in 100 mL 1
• 250 mcg/mL: Add reconstituted remifentanil to achieve 5 mg in 20 mL 1

Concentration Selection by Clinical Context

• Pediatric patients (≥1 year): Use 20 or 25 mcg/mL final concentration 1
• Monitored anesthesia care: Use 25 mcg/mL final concentration 1
• General anesthesia maintenance: Any of the four concentrations may be used based on infusion pump capabilities and patient weight 1

Critical Safety Considerations

Administration Requirements

• Remifentanil must be administered via continuous IV infusion using an infusion device 1
• The drug should never be administered without dilution from the initial 1 mg/mL reconstituted solution 1

Mixing with Other Agents

• Do NOT mix remifentanil with propofol in the same syringe 4
• When remifentanil solution and propofol emulsion are combined, they separate and layer, with remifentanil rising to the top and propofol settling to the bottom 4
• This separation results in unpredictable and unreliable drug concentrations delivered to patients 4
• Mixing remifentanil with propofol also substantially increases pH (to approximately 6.50), causing significant remifentanil degradation 3

pH and Stability Concerns

• Isolated remifentanil remains stable at pH < 4 for 24 hours 3
• Remifentanil degrades significantly when pH increases above 6.5, which occurs when mixed with propofol or alkaline solutions 3
• The amount of degradation product detected is proportional to the degree of remifentanil degradation observed 3

Tubing Management

• Upon discontinuation, the IV tubing must be cleared to prevent inadvertent administration of remifentanil at a later time 1
• This is critical given remifentanil's potent opioid effects and the risk of respiratory depression 1