Chan Betty S, Isbister Geoffrey K, O'Leary Margaret, Chiew Angela, Buckley Nicholas A
a Clinical Toxicology Unit and Emergency Department , Prince of Wales Hospital , Sydney , New South Wales , Australia ;
b New South Wales Poisons Information Centre , Sydney Children's Hospital at Westmead , Sydney , New South Wales , Australia ;
Clin Toxicol (Phila). 2016 Jul;54(6):488-94. doi: 10.1080/15563650.2016.1175620. Epub 2016 Apr 27.
We hypothesized that in chronic digoxin toxicity, anti-digoxin antibodies (Fab) would be efficacious in binding digoxin, but this may not translate into improved clinical outcomes.
This study aims to investigate changes in free digoxin concentrations and clinical effects on heart rate and potassium concentrations in chronic digoxin poisoning when anti-digoxin Fab are given.
This is a prospective observational study. Patients were recruited if they have been treated with anti-digoxin Fab for chronic digoxin poisoning. Data was entered into a standardised prospective form, supplemented with medical records. Their serum or plasma was collected, analysed for free and bound digoxin and free anti-digoxin Fab concentrations.
From September 2013 to February 2015, 36 patients (median age, 78 years; 22 females) were recruited from 18 hospitals. Median heart rate (HR) was 49 beats/min. Initial median digoxin and potassium concentrations were 4.7 nmol/L (3.6 μg/L) (range: 2.3-11.2 nmol/L) and 5.3 mmol/L (range: 2.9-9.2 mmol/L) respectively. Beta-blockers (n = 18), calcium antagonists (n = 6), spironolactone and/or angiotensin blocking agents (n = 24) were also used concomitantly. Renal impairment and gastrointestinal symptoms were present in 31 (86%) and 22 (63%) patients respectively. Five patients died from conditions unrelated to digoxin toxicity. Median change in HR was 8 beats/min post-Fab with no effect on blood pressure; they were 4, 10 and 17 beats/min for the 1, 2 and ≥3 vials of anti-digoxin Fab groups respectively. Concomitant treatments with potassium lowering agents (12/36) and inotropic drugs (7/36) were used. Gastrointestinal effects resolved in all 22 patients. The median decrease for potassium was 0.3 mmol/L. Digoxin concentration reduced from 3.8 to 0 nmol/L post-Fab. There was a rebound observed in the free digoxin concentration in 25 patients but none had associated clinical deterioration.
One to two vials of anti-digoxin Fab initially bound all free digoxin confirming Fab efficacy. However, this was associated with only a moderate improvement in HR and potassium, suggesting bradyarrhythmia and hyperkalaemia may be from other co-morbidities.
我们推测，在慢性地高辛中毒中，抗地高辛抗体（Fab）能有效结合地高辛，但这可能不会转化为改善的临床结局。
本研究旨在调查给予抗地高辛Fab治疗慢性地高辛中毒时，游离地高辛浓度的变化以及对心率和血钾浓度的临床影响。
这是一项前瞻性观察研究。招募接受抗地高辛Fab治疗慢性地高辛中毒的患者。数据录入标准化前瞻性表格，并辅以病历。收集他们的血清或血浆，分析游离和结合地高辛以及游离抗地高辛Fab浓度。
2013年9月至2015年2月，从18家医院招募了36例患者（中位年龄78岁；22例女性）。中位心率（HR）为49次/分钟。初始地高辛和血钾浓度中位数分别为4.7 nmol/L（3.6μg/L）（范围：2.3 - 11.2 nmol/L）和5.3 mmol/L（范围：2.9 - 9.2 mmol/L）。同时还使用了β受体阻滞剂（n = 18）、钙拮抗剂（n = 6）、螺内酯和/或血管紧张素阻断剂（n = 24）。31例（86%）患者存在肾功能损害，22例（63%）患者有胃肠道症状。5例患者死于与地高辛中毒无关的疾病。使用Fab后HR的中位变化为8次/分钟，对血压无影响；抗地高辛Fab 1瓶、2瓶和≥3瓶组的变化分别为4次/分钟、10次/分钟和17次/分钟。同时使用了降钾药物（12/36）和正性肌力药物（7/36）。所有22例有胃肠道症状的患者症状均缓解。血钾中位数下降0.3 mmol/L。使用Fab后地高辛浓度从3.8降至0 nmol/L。25例患者游离地高辛浓度出现反弹，但均无相关临床恶化。
最初1至2瓶抗地高辛Fab能结合所有游离地高辛，证实了Fab的疗效。然而，这仅使心率和血钾有适度改善，提示缓慢性心律失常和高钾血症可能源于其他合并症。
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