Remifentanil: achieving a 'standard concentration': a reply.

Abstract

Thank you for the opportunity to reply to Drs Winter and Moore [1] on variation in the volume of fluid in bags labelled as containing 100 ml of saline. They provide a useful reminder that when drugs are diluted by addition to a bag of fluid, the drug concentration may be somewhat lower and more variable than when the drug is added to a measured volume of the dilution fluid in a 50-ml syringe. The range of concentrations that they calculate is, however, within 10% of the intended concentration. We would agree that, in the case of remifentanil, the resulting variability in drug concentration in the infusion is less than the inter-patient variability in the dose required to produce a given effect, and that the infusion rate is usually titrated to clinical effect. Therefore, we consider this variation in volume is not in itself a reason to avoid diluting remifentanil in a bag of intravenous infusion fluid. Remifentanil is initially reconstituted by adding a small volume of fluid to the glass vial to produce a reconstituted solution with a concentration of approximately 1 mg.ml-1. It is then further diluted to produce the final diluted solution for infusion. There are issues to be considered if remifentanil is to be diluted in a bag of fluid and then subsequently drawn into 50-ml syringes for use in a syringe driver. First, remifentanil from one vial should not be administered to more than one patient [2]. Second, some summaries of product characteristics for remifentanil state that the product should be used immediately after dilution [3]. Furthermore, if diluted remifentanil is left in an intravenous fluid infusion bag with the intention of using it later, the risk exists of it being mistaken for fluid for infusion, or for flushing cannulae, and it being accidentally administered. Variation in the concentration of remifentanil infusion solutions may occur due to differences in the completeness with which the remifentanil is withdrawn from the glass vial following initial reconstitution. More generally, studies of the preparation of syringes of diluted drugs for intravenous infusion in intensive care have found that error or inaccuracy in the preparation of infusion is common. In most cases, the measured drug concentration was more than 10% above or below the intended concentration [4, 5]. The use of syringes prefilled with the diluted drug by a pharmaceutical company or hospital pharmacy was recommended as a solution to this problem. However, in the case of remifentanil, the poor stability of the drug once diluted has been a barrier to the use of prefilled syringes. Our recommendation that “Within an anaesthetic department, it is preferable to stock only one concentration of propofol and to dilute remifentanil to a single, standard concentration” [6] is intended to reduce the risk of accidentally programming a pump with a remifentanil concentration very different from that actually in the syringe (or bag), for example 20 μg.ml-1 rather than 50 μg.ml-1. This would be likely to have significant clinical effects.