ESPE Abstracts (2016) 86 P-P1-10

Current Dilution Methods Cause Large Variations and Inaccuracies when Making up 1 μg Synacthen Dose

Alexandra S Crossa, Pooja Sachdevc, Neil P Wrightb, Imran Jabbard & Charlotte J Eldera,b


aUniversity of Sheffield, Sheffield, UK; bSheffield Children’s Foundation NHS Trust, Sheffield, UK; cNottingham University Hospitals NHS Trust, Nottingham, UK; dSheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK


Background: The low-dose short Synacthen test is a popular diagnostic test of adrenal insufficiency in children. It is employed by 82% of UK paediatric endocrinologists. Although various dosing strategies exist, 1 μg is most commonly employed, however none of the low-dose forms are commercially available. A BSPED survey revealed 14 different methods for diluting 250 μg/ml ampoules.

Objective and hypotheses: Do various dilution strategies result in differences in the resultant Synacthen dose administered?

Method: The ten most popular dilution methods were tested, encompassing different diluents (0.9% saline n=9, 5% dextrose n=1), single (n=6) and double (n=4) dilution strategies and varying initial quantities of Synacthen (0.1–1 ml). Each method was made up five times under simulated ward conditions and three samples taken from different parts of the bag of resultant solution. Samples were frozen then batch-analysed on an hACTH RIA validated for Synacthen. All samples were diluted to 250 pg/ml (most sensitive part of the assay measuring range) and the coefficient variation (CV) calculated.

Results: There was marked variation in Synacthen detected from the three samples taken from the same solution (CV 13.4–194.6%) suggesting inadequate mixing, the five preparations of the same method, suggesting batch to batch variation, and between the 10 different preparation methods (CV range 24.2–163.7%) suggesting inequity between methods. Estimates of the likely Synacthen dose, if administered to patients, ranged from less than 0.04 μg to more than 2 μg.

Conclusion: Considerable variation was observed both within and between dilution methods. Variables, which may affect the actual dose of Synacthen administered, include: poor dilution technique, inappropriate dilution strategies, pharmaceutical manufacturer variation, use of inaccurate ward equipment, volume inconsistencies, lack of adequate mixing and lack of a controlled environment. We recommend low-dose Synacthen be made up under laboratory conditions and call for a commercial preparation of 1 μg Synacthen.

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