Remifentanil and propofol are sometimes used together for anesthesia. However, we must consider whether both drugs remain active when they are given together - are they physically compatible? The propofol package insert discusses only compatibility with certain IV fluids. The remifentanil package insert states that remifentanil and propofol are compatible, but gives no relative concentration data. Neither of the package inserts address whether mixtures of remifentanil and propofol are stable. This study was performed to determine if remifentanil and propofol could be mixed in either polyvinylcloride (PVC) bags or polypropylene syringes, and retain their stability for 36 hours at warm room temperature (22º-24º C). All controls and admixtures were assayed for content of each drug by using high-performance liquid chromatography assays.
Remifentanil was diluted with sterile water and mixed with propofol 10 mg/ml, so that the test solutions contained final remifentanil concentrations of either 50 �g/ml or 5 �g/ml. Controls for each drug concentration studied, propofol alone and remifentanil alone, were also prepared. All samples were prepared in triplicate and stored at 22º-24ºC under ambient light. Samples for remifentanil and propofol assay were removed aseptically at 0, 1, 2, 3, 4, 6, 12, 24 and 36 hours. At each sampling time, the syringes and bags were visually assessed for color and clarity, and a pH meter was used to measure the pH of each solution. Remifentanil and propofol in controls and samples were considered "stable" as long as the drug concentration in each syringe bag remained greater than 90% of the initial concentration.
The mixture of remifentanil at 50 �g/ml and propofol at 10 mg/ml was stable for up to 36 hours, when stored in 20 ml plastic syringes. Color and clarity remained good for all mixtures and controls and the pH remained in the 3.9-4.0 range at all sampling times.
The mixture of 50 µg/ml remifentanil and 10 mg/ml propofol was stable for only up to 3 hours when stored in PVC bags. Individual control solutions of remifentanil were stable for up to 36 hours in identical storage conditions, but the propofol solutions were stable only up to 6 hours. Color and clarity remained very good for all mixtures and controls and the pH remained in 3.95-4.0 range at all sampling times.
The low concentration mixture of 5 µg/ml remifentanil and 10 mg/ml propofol was stable only up to one hour when stored in 20 ml plastic syringes at 22º-24ºC. Individual control solutions of each medication were stable up to 36 hours under identical conditions. Color and clarity remained very good. The instability is apparently caused by the resulting pH of 7.2-7.6 of the medication mixture, at which degradation of the ester functionality of the remifentanil is likely.
A low concentration mixture of 5 µg/ml remifentanil and 10 mg/ml propofol was not stable stored in PVC bags. Individual control solutions of each medication were stable up to at least six hours and color and clarity remained good. The instability of this mixture is again presumed to be caused by the hydrolysis of the ester functionality of the remifentanil at this non-acid pH.
This study demonstrates that remifentanil and propofol can be mixed in polypropylene syringes and used for up to 36 hours, provided that the remifentanil concentration is 50 �g/ml. However, PVC bags containing this same mixture can not be used after more than 3 hours. The 5 �g/ml remifentanil and propofol mixture is stable for only one hour in polypropylene syringes, but is not sufficiently stable in PVC bags to be used for even one hour. In addition, propofol should be stored in PVC bags only up to 6 hours.
The lack of stability of propofol in PVC bags is presumed to be caused by the interaction of propofol with the bag. The instability of 5 µg/ml remifentanil in syringes and PVC bags is probably a result of hydrolysis of the ester group of remifentanil, which occurs readily at the pH 7-7.5 range of the prepared mixtures
| Syringe |
Concentration(s) |
PVC bag |
Polypropylene |
| Propofol |
10 mg/ml |
6 hr |
36 hr |
| Remifentanil |
50 µg/ml |
36 hr |
36 hr |
| Remifentanil |
5 µg/ml |
36 hr |
36 hr |
Propofol/
Remifentanil |
10 mg/ml
50 µg/ml |
3 hr |
36 hr |
Propofol/
Remifentanil |
10 mg/ml
5 µg/ml |
not stable
( < 1 hr) |
36 hr |
