What about using a mixed solution of remifentanil (opioid analgesic) and propofol (hypnotic agent) in one syringe for Total Intravenous Anesthesia (TIVA)?

From the Guidelines

Mixing remifentanil and propofol in a single syringe for Total Intravenous Anesthesia (TIVA) is not recommended due to physicochemical incompatibility and the potential for unpredictable drug delivery. The primary concern is that remifentanil is water-soluble and typically prepared in an aqueous solution, while propofol is a lipid emulsion, which can lead to emulsion instability and potential precipitation when mixed 1.

Key Considerations

• Separate administration of remifentanil and propofol using dedicated infusion pumps allows for independent titration of each medication to achieve optimal anesthetic depth and analgesia based on the patient's individual needs during different phases of surgery.
• The standard approach for TIVA involves two separate target-controlled infusions or weight-based infusions, allowing precise control over the anesthetic state while maintaining safety and predictability.
• Studies have shown that combination regimens, such as propofol with an opioid and benzodiazepine, can be effective and safe for sedation, but these medications are typically administered separately, not mixed in a single syringe 1.

Clinical Implications

• Clinicians should prioritize separate administration of remifentanil and propofol to ensure predictable drug delivery and minimize the risk of adverse events.
• The use of separate infusion pumps enables clinicians to adjust one component without affecting the other, such as reducing propofol while maintaining analgesia during emergence.
• The standard approach for TIVA should be followed to maintain safety and predictability, and to ensure optimal outcomes for patients undergoing surgery.

From the FDA Drug Label

Compatibility with Other Therapeutic Agents Remifentanil hydrochloride for injection has been shown to be compatible with Diprivan® (propofol) Injection when coadministered into a running IV administration set

The FDA drug label does not provide information on the stability or compatibility of a mixed solution of remifentanil and propofol in one syringe. No conclusion can be drawn about the safety or efficacy of using a mixed solution of remifentanil and propofol in one syringe for Total Intravenous Anesthesia (TIVA) based on the provided drug labels 2 2.

From the Research

Mixed Remifentanil and Propofol in One Syringe for Total Intravenous Anesthesia (TIVA)

• The practice of mixing remifentanil and propofol in the same syringe for TIVA has been evaluated in several studies 3, 4, 5, 6.
• A study published in 2016 found that remifentanil and propofol undergo separation and layering when mixed in the same syringe, which can lead to unreliable concentrations of the drugs being delivered to patients 3.
• Another study published in 2020 highlighted the potential risks of mixing propofol and remifentanil, including changes in drug concentration over time, nonuniform mixing, and the risk of bacterial contamination 4.
• However, a randomized controlled study published in 2021 found that using a mixed solution of remifentanil and propofol for TIVA did not result in any statistically significant differences in recovery and clinical outcomes compared to the standard TIVA technique using separate drug infusions 5.
• A prospective study published in 2023 compared the use of a single target-controlled infusion pump-delivered mixed propofol and remifentanil with two target-controlled infusion pumps-delivered propofol and remifentanil in patients undergoing breast cancer surgery, and found that the mixed solution provided adequate hypnotic and analgesic effects with fewer adjustments of the target-controlled infusion pump 6.
• An earlier study published in 2000 compared anesthesia using remifentanil combined with either isoflurane, enflurane, or propofol in patients undergoing short-procedure surgery, and found that all three regimens were effective and well-tolerated 7.

Key Findings

• Mixing remifentanil and propofol in the same syringe can lead to separation and layering of the drugs, resulting in unreliable concentrations being delivered to patients 3.
• The use of a mixed solution of remifentanil and propofol for TIVA may be a practical implementation for busy ambulatory centers performing general anesthesia 5.
• The mixed solution can provide adequate hypnotic and analgesic effects with fewer adjustments of the target-controlled infusion pump 6.