Bailey George P, Wood David M, Archer John R H, Rab Edmund, Flanagan Robert J, Dargan Paul I
Clinical Toxicology, Guy's and St. Thomas' NHS Foundation Trust and King's Health Partners, London, UK.
Emergency Department, St. Mary's Hospital, Imperial College NHS Trust, London, UK.
Br J Clin Pharmacol. 2017 Feb;83(2):393-399. doi: 10.1111/bcp.13099. Epub 2016 Sep 29.
Intravenous 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.
A 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.
Ninety 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 -3.6 mg ml (-6.7 to -2.3) for the first infusion, +0.2 mg ml (-0.9 to +0.4) for the second infusion and -0.3 mg ml (-0.6 to +0.2) for third and fourth infusions.
There 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.
静脉注射乙酰半胱氨酸是对乙酰氨基酚中毒的首选治疗方法。英国2001年的一项先前研究发现,所测的乙酰半胱氨酸输注浓度中有39%与预期浓度相差超过20%。2012年,英国人类用药委员会对乙酰氨基酚过量的处理提出了建议,包括提供基于体重的乙酰半胱氨酸给药表。本研究的目的是评估引入该指南后所给药的输注液中乙酰半胱氨酸浓度的差异。
在一家英国教学医院进行了一项为期6个月的单中心前瞻性研究。配制好后,从首次、第二次以及第三次/任何后续的乙酰半胱氨酸输注液中采集5毫升样本。通过高效液相色谱法在稀释(1:50)的样本中测量乙酰半胱氨酸。对每次输注,根据规定的基于体重的剂量和体积比较所测浓度与预期浓度。
共采集了90个样本。45次(50%)输注的所测浓度与预期浓度的差异≤10%,27次(30%)输注的差异为10% - 20%,14次(16%)输注的差异为20.1% - 50%,4次(4%)输注的差异>50%。首次输注所测浓度与预期浓度的差异中位数(四分位间距)为-3.6毫克/毫升(-6.7至-2.3),第二次输注为+0.2毫克/毫升(-0.9至+0.4),第三次和第四次输注为-0.3毫克/毫升(-0.6至+0.2)。
输注的乙酰半胱氨酸剂量差异有了适度改善。需要进一步开展工作以了解持续存在的差异,并且应考虑简化乙酰半胱氨酸给药方案以降低给药错误风险。