1. 2015;18;349-357Rationale for Prospective Assays of Intrathecal Mixtures Including Morphine, Ropivacaine and Ziconotide: Prevention of Adverse Events and Feasibility in Clinical Practice
   Prospective Study
   Helene Kieffer, PharmD, François Bore, MD, Pierre Yves Dubois, MD, Nathalie Lebrec, MD, Caroline Folliard, PharmD, Catherine Devys, PharmD, Christophe Bazin, PharmD, and Denis Dupoiron, MD.

BACKGROUND: Use of intrathecal admixtures is widespread, but compounding these is sometimes challenging and may result in errors and complications causing super-potency or sub potency adverse events in patients or malfunctions in the pump itself.

OBJECTIVE: The purpose of this study is to evaluate the accuracy of compounding of intrathecal admixtures through a prospective, systematic quantitative analysis of each component of the mixture before delivery to patients.

STUDY DESIGN: Observational follow up prospective study of intrathecal mixtures components concentrations before refills.

SETTINGS: Assays were performed on all intrathecal admixtures produced by the ICO-Paul Papin compounding pharmacy between January 2013 and October 2014 using Ultra High Performance Liquid Chromatography (U.H.P.L.C.). In addition, pH levels of admixtures have been measured since June 2014. When measured concentrations were 15% above or below the required concentrations, the mixture was excluded and compounded again.

RESULTS: 1729 mixtures were analyzed. Mean deviation from theoretical values was -1.17% ± 0.28% for morphine, -0.95% ± 1.07% for ropivacaine, and 4.82% ± 0.6% for ziconotide. Exclusion rates were 8.33% overall, but fell from 11.67% in 2013 to 4.97% in 2014. Most exclusions were caused by inaccuracy in the dose of ziconotide. Average mixture pH of the 603 tested admixtures was 4.83 ± 0.6%.

LIMITATIONS: This study is monocentric and limitations include also its non-randomized nature with no clinical comparison of the rate of adverse events with a refill process without control of each component concentrations.

CONCLUSION: Prospective assays provide benefits in ensuring accuracy of intrathecal mixture compounding and in preventing overdosing or sub dosing, most notably concerning Ziconotide.