Consistency of remifentanil concentrations in propofol-Remifentanil infusions. A laboratory-based study

---

Background

This laboratory study assessed whether propofol combined with remifentanil in the same syringe resulted in consistent remifentanil concentration delivery throughout a 57 min administration period.  This is important as many anaesthetists choose to use a single-pump, multi-agent technique when administering a propofol-remifentanil, paediatric, total intravenous anaesthetic (TIVA).

Methods

Drug sampling

• 30mL syringe contained 28.5mL of 1% propofol with 1.5mL of remifentanil (100mcg/mL, reconstituted with 0.9% saline) to yield a 1% propofol and 5microg/mL remifentanil solution.
• The solution was infused by an Alaris PK pump using a Paedfuser TCI model with infusion conditions intended to mimic a typical infusion. (Terumo 30mL syringe with BD leur lock cannula, B Braun 180cm minimum volume extension line, Baxter interlink injection site and a 22G, 25mm IV cannula)
• Drug samples were taken during 5 different experimental runs:

1. 10kg hypothetical patient with the TCI infusion run three times. Samples were taken at time 0, 1 min and 2 min post initial bolus and then every 5 minutes until 57 minutes.
2. 20kg hypothetical patient with the TCI infusion run two times. Samples were taken at time 0, 1 min and 2 min post bolus and then every 5 minutes until 57 minutes.

* 57 minutes was chosen as this was the median duration of paediatric surgery in a previously published large case study.

Sample analysis

Following preparatory steps, the samples were analysed via a mass spectrometer to determine the remifentanil concentrations using a standard curve created from known remifentanil concentrations.

Findings

• Of all the models run, the largest variation in remifentanil concentration was 0.8 microg/mL (range 4.8-5.6 microg/ mL) in the first 10kg model. The average concentration administered in the 57 min was 5.2 microg/mL.
• The remainder of the models had a lower variation in remifentanil concentration (10kg run 2 = 0.4 microg/mL, 10kg run 3 = 0.6 microg/mL, 20kg run 1 = 0.6 microg/mL, 20kg run 2 = 0.6 microg/mL)

Discussion

This pragmatic study demonstrated that the greatest variation in remifentanil concentration was within 12% of the intended concentration for administration. Whether this is clinically significant would depend on the clinical situation. Arguably, the short half-life of remifentanil would preclude this from causing any clinically significant adverse effect.

Previous studies have demonstrated issues with miscibility and de-emulsification when high concentration mixtures of propofol and remifentanil (25-100mcg/mL) were held static and positioned vertically. This study did not assess the effect on propofol in this situation.  However, it did demonstrate that the remifentanil concentration remained reasonably consistent when a concentration of 5 microg/mL is combined with 1% propofol and continuously moved through an infusion within 10 minutes of combination.

Practical points

This study demonstrated relatively consistent remifentanil concentrations under the following conditions:

1. The drugs were combined within 10 minutes of commencing the infusion
2. The infusion ran continuously for 57 minutes
3. The remifentanil concentration was 5microg/mL in a 30mL syringe of 1% Propofol

Unresolved questions:

1. Is propofol susceptible to de-emulsification or does it become unstable in this studied admixture?
2. Using this same experimental model, what is the effect on the concentration administered if a higher remifentanil concentration is used?
3. Does an infusion duration of greater than one hour result in less predictable remifentanil concentration administration?

Reviewed by Dr Anita Flynn