title: Rationale for Prospective Assays of Intrathecal Mixtures Including Morphine, Ropivacaine and Ziconotide: Prevention of Adverse Events and Feasibility in Clinical Practice.
abstract: 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.
  
  
  METHODS
  Observational follow up prospective study of intrathecal mixtures components concentrations before refills.
  
  
  METHODS
  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%.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Prospective assays provide benefits in ensuring accuracy of intrathecal mixture compounding and in preventing overdosing or sub dosing, most notably concerning Ziconotide.
authors.forename: Denis
authors.initials: D
authors.lastname: Dupoiron
authors.forename: Catherine
authors.initials: C
authors.lastname: Devys
authors.forename: Christophe
authors.initials: C
authors.lastname: Bazin
authors.forename: Caroline
authors.initials: C
authors.lastname: Folliard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lebrec
authors.forename: François
authors.initials: F
authors.lastname: Boré
authors.forename: Pierre Yves
authors.initials: PY
authors.lastname: Dubois
authors.forename: Hélène
authors.initials: H
authors.lastname: Kieffer
mesh_terms: D000328:Adult; D000368:Aged; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000592:standards*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007278:Injections, Spinal / Q000379:methods; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D010147:Pain Measurement / Q000379:methods; D011446:Prospective Studies; D000077212:Ropivacaine; D020960:omega-Conotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D000577:Amides; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D020960:omega-Conotoxins; D009020:Morphine; C078452:ziconotide; D000077212:Ropivacaine