Chan Betty S, Isbister Geoffrey K, Chiew Angela, Isoardi Katherine, Buckley Nicholas A
Clinical Toxicology Unit & Emergency Department, Prince of Wales Hospital, Sydney, New South Wales, Australia.
New South Wales Poisons Information Centre, Sydney, Australia.
Clin Toxicol (Phila). 2022 Apr;60(4):433-439. doi: 10.1080/15563650.2021.1968422. Epub 2021 Aug 23.
For acute digoxin poisoning, it has been recommended to give bolus doses of 10-20 vials or potentially larger than needed doses calculated from dose ingested or the measured concentration. However, a recent revision of internal Poisons Information Centre guidelines prompted a change of our recommendations, specifically instead of large boluses, to use titrating repeated low doses of digoxin antibodies(Digoxin-Fab) based on bedside assessment of cardiac toxicity.
This is a prospective observational study of patients with acute digoxin poisoning identified through two Poisons Information Centres and three toxicology units. Patient demographics, signs and symptoms of digoxin toxicity, doses and response to Digoxin-Fab, free and bound serum digoxin concentrations. Outcomes were recorded and analysed.
From September 2013 to September 2020, 23 patients with 25 presentations (median age 56 years, females 56%) were recruited. Median dose ingested was 13 mg(IQR: 9.5-25). Median heart rate (HR) was 41 beats/min before treatment. Initial median digoxin and potassium concentrations were 14.5 nmol/L (IQR: 10.9-20) [11.2 µg/L(IQR: 8.4-15.4)] and 5 mmol/L (IQR: 4.5-5.4 mmol/L), respectively. Gastrointestinal symptoms and acute kidney injury were present in 22 patients (88%) and 5 patients (20%), respectively. Four patients received an initial bolus dose of Digoxin-Fab of 5-20 vials. Twenty-one patients received repeated titrated doses (1-2 vials) of Digoxin-Fab and the median total dose was 4 vials (IQR: 2-7.5). Median maximal change in HR post-Digoxin-Fab was 19 beats/min. The median potassium concentration decrease post-Digoxin-Fab was 0.3 mmol/L. Total dose used in the titration group was 25% and 35% of the predicted doses based on the amount of digoxin ingested or measured serum concentration, respectively. Twelve had free digoxin concentrations measured. Free digoxin concentrations dropped to almost zero after any dose of Digoxin-Fab. Ten patients had a rebound of digoxin >2.6 nmol/L (2 µg/L). There were no deaths from acute digoxin toxicity.
The new practice of using small, titrated doses of Digoxin-Fab led to a considerable reduction in total usage and major savings. The clinical response to titrated doses was safe and acceptable in acute digoxin poisoning.
对于急性地高辛中毒,建议静脉推注10 - 20瓶,或者根据摄入剂量或测量浓度计算出可能超过所需的剂量。然而,最近内部毒物信息中心指南的修订促使我们改变了建议,具体而言,不再使用大剂量推注,而是根据床边心脏毒性评估,使用重复低剂量的地高辛抗体(地高辛免疫Fab片段)进行滴定。
这是一项前瞻性观察性研究,研究对象是通过两个毒物信息中心和三个毒理学单位确定的急性地高辛中毒患者。记录患者的人口统计学信息、地高辛中毒的体征和症状、地高辛免疫Fab片段的剂量和反应、游离和结合的血清地高辛浓度。对结果进行记录和分析。
2013年9月至2020年9月,招募了23例患者,共25次就诊(中位年龄56岁,女性占56%)。摄入的中位剂量为13毫克(四分位间距:9.5 - 25)。治疗前的中位心率为41次/分钟。初始地高辛和钾浓度的中位数分别为14.5纳摩尔/升(四分位间距:10.9 - 20)[11.2微克/升(四分位间距:8.4 - 15.4)]和5毫摩尔/升(四分位间距:4.5 - 5.4毫摩尔/升)。22例患者(88%)出现胃肠道症状,5例患者(20%)出现急性肾损伤。4例患者初始接受了5 - 20瓶的地高辛免疫Fab片段推注剂量。21例患者接受了重复滴定剂量(1 - 2瓶)的地高辛免疫Fab片段,中位总剂量为4瓶(四分位间距:2 - 7.5)。地高辛免疫Fab片段治疗后心率的最大中位变化为19次/分钟。地高辛免疫Fab片段治疗后钾浓度的中位数下降了0.3毫摩尔/升。滴定组使用的总剂量分别是根据摄入地高辛量或测量血清浓度预测剂量的25%和35%。12例患者测量了游离地高辛浓度。任何剂量的地高辛免疫Fab片段后,游离地高辛浓度几乎降至零。10例患者地高辛出现>2.6纳摩尔/升(2微克/升)的反弹。没有患者死于急性地高辛中毒。
使用小剂量滴定的地高辛免疫Fab片段的新方法导致总用量大幅减少并节省了大量费用。在急性地高辛中毒中,滴定剂量的临床反应是安全且可接受的。