地高辛测定：螺内酯、坎利酮及其他甾体类药物频繁、显著且可能具有危险性的干扰作用。

Digoxin assays: frequent, substantial, and potentially dangerous interference by spironolactone, canrenone, and other steroids.

作者信息

Steimer Werner, Müller Christine, Eber Barbara

机构信息

Institute for Clinical Chemistry and Pathobiochemistry, Munich University of Technology, Klinikum rechts der Isar, D-81675 Munich, Germany.

出版信息

Clin Chem. 2002 Mar;48(3):507-16.

PMID:11861441

Abstract

BACKGROUND

A case of digoxin toxicity resulted from falsely low values with the MEIA II assay for digoxin (AxSYM; Abbott). The low results were caused by negative interference from canrenone and spironolactone, the latter of which has recently been advocated for the treatment of severe heart failure. Analytical interference from spironolactone has been reported, but little information is available for this effect with newer digoxin assays.

METHODS

We examined nine assays (AxSYM, IMx, TDx, Emit, Dimension, aca, TinaQuant, Elecsys, and Vitros for interference by spironolactone, canrenone, and three metabolites. Additionally, all routine digoxin measurements (AxSYM) over a period of 16.5 months (n = 3089) were monitored for interference.

RESULTS

Suppression of the expected values by canrenone (3125 microg/L) was observed for the AxSYM (42% of expected value), IMx (51%), and Dimension (78%) assays. A positive bias was observed for the aca (0.7 microg/L), the TDx (0.62 microg/L), and the Elecsys (>0.58 microg/L). Twenty-five of 669 routinely monitored patients had falsely low results. Nineteen of these had potentially toxic concentrations of digoxin (Emit; >2.0 microg/L), although the AxSYM assay indicated therapeutic or less severe toxic concentrations (Delta(max) = 7.1 microg/L). Except for two unresolved cases, this was attributable to spironolactone, canrenone, hydrocortisone, or prednisolone. Standard doses of spironolactone (up to 50 mg/day) in patients with heart failure displayed inhibition <11%.

CONCLUSIONS

The frequency and magnitude of the false-negative results particularly compromise the use of both microparticle enzyme immunoassays. Not only may toxic concentrations remain unidentified, but intoxication could occur should dosage be increased because of falsely low results. With 11 million digoxin tests/year ordered in the US, conceivably many patients could be adversely affected.

摘要

背景

采用地高辛MEIA II检测法（AxSYM；雅培公司）时，因检测值错误地偏低而导致了一例地高辛中毒病例。检测结果偏低是由坎利酮和螺内酯的负干扰所致，其中螺内酯最近被推荐用于治疗重度心力衰竭。虽然已有关于螺内酯分析干扰的报道，但关于其对新型地高辛检测法影响的信息却很少。

方法

我们检测了九种检测法（AxSYM、IMx、TDx、Emit、Dimension、aca、TinaQuant、Elecsys和Vitros）对螺内酯、坎利酮及三种代谢产物的干扰情况。此外，还对16.5个月期间（n = 3089）所有常规地高辛检测（AxSYM）进行了干扰监测。

结果

对于AxSYM检测法（为预期值的42%）、IMx检测法（51%）和Dimension检测法（78%），观察到坎利酮（3125微克/升）对预期值有抑制作用。对于aca检测法（0.7微克/升）、TDx检测法（0.62微克/升）和Elecsys检测法（>0.58微克/升），观察到有正偏差。在669例接受常规监测的患者中，有25例检测结果错误地偏低。其中19例患者的地高辛浓度可能具有毒性（Emit检测法；>2.0微克/升），尽管AxSYM检测法显示为治疗浓度或毒性较轻的浓度（最大差值 = 7.1微克/升）。除两例未解决的病例外，这可归因于螺内酯、坎利酮、氢化可的松或泼尼松龙。心力衰竭患者使用标准剂量的螺内酯（最高50毫克/天）时，抑制率低于11%。