An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose

Abstract

BACKGROUNDIntravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight-based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. METHODSA 6-month single-centre prospective study was undertaken at a UK teaching hospital. After preparation, 5-ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high-performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight-based dose and volume were made for each infusion. RESULTSNinety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10-20% for 27 (30%) infusions, 20.1-50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of À3.6 mg ml À1 (À6.7 to À2.3) for the first infusion, +0.2 mg ml À1 (À0.9 to +0.4) for the second infusion and À0.3 mg ml À1 (À0.6 to +0.2) for third and fourth infusions. CONCLUSIONThere has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors.

An evaluation of the role of mixing techniques in the observed variation in acetylcysteine infusion concentrations

“…Our group and others have previously hypothesized that inadequate mixing of infusions may result in heterogeneous concentrations of acetylcysteine within the infusion fluid . Results from this study, however, indicate that mixing does not play a substantial role in the variation of infusion concentrations.…”

“…Our study did not reproduce findings from previous studies that had shown a large variation in acetylcysteine infusion concentrations . This may be partially due to the fact that our experiments were conducted by a single researcher who was aware that the concentration of the samples would be assessed and the infusions were prepared in a laboratory environment rather than a comparatively chaotic ward or emergency department environment.…”

“…In this and the previous studies from our group and others , acetylcysteine was used as a model to assess accuracy in the delivery of intravenous infusions; however, it is likely that similar errors occur with other intravenous medications, such as antibiotics and anticoagulants, many of which have a narrow therapeutic window. Inaccuracies in dosing may have a considerable clinical impact and thus improving the education of healthcare professionals to improve accuracy is essential to ensure consistent preparation of intravenous medications.…”

“…Bailey et al . reassessed the variation in the concentration of acetylcysteine in infusions following these changes and found a moderate improvement in dosing accuracy, although 20% of the acetylcysteine concentrations still differed by more than 20% of the expected dose, and 4% differed by more than 50% of the expected dose .…”

A comment on ‘An assessment of the variation in the concentrations of acetylcysteine in infusions for the treatment of paracetamol overdose’

“…Bailey et al . found that half of the bags deviated by >10% between measured and expected concentrations . One in five deviated by >20%.…”