Accuracy of dilution of morphine for intrathecal use

Morphine is administered intrathecally alone or in combination with other drugs to provide spinal analgesia. Dose-finding studies have recommended 100 μg be used intrathecally to optimise analgesia and minimise side-effects for caesarean section and hip replacement surgery. Dilute solutions of morphine are generally not available, mandating preparation from a 10 mg/ml ampoule. We postulated that diluting morphine would be inaccurate and imprecise, contributing to the variability in patient response often reported. Twenty consultant and trainee anaesthetists were recruited and asked to prepare 100 μg of morphine from 10 mg/ml vials and from a hypothetical prediluted 500 μg/ml solution. The resultant samples were analysed using liquid chromatography. Prepared morphine doses ranged from 25 μg to 289 μg. Dilution of morphine was less accurate (P=0.001) and more imprecise (P=0.001) compared with using a prediluted solution. A single-step dilution technique using 0.1 ml of a solution diluted to 1.0 mg/ml was more accurate than when a double-dilution technique was used (P=0.047). Given that dose-finding studies suggest that analgesia and side-effects vary at the dose range found in this study, we advocate the use of prediluted solutions. If dilution is to be performed a single-step dilution technique should be used.