Cardenolides are naturally occurring plant toxins which act primarily on the heart. While poisoning with the digitalis cardenolides (digoxin and digitoxin) are reported worldwide, cardiotoxicity from other cardenolides such as the yellow oleander are also a major problem, with tens of thousands of cases of poisoning each year in South Asia. Because cardenolides from these plants are structurally similar, acute poisonings are managed using similar treatments. The benefit of these treatments is of interest, particularly in the context of cost since most poisonings occur in developing countries where resources are very limited.
To determine the efficacy of antidotes for the treatment of acute cardenolide poisoning, in particular atropine, isoprenaline (isoproterenol), multiple-dose activated charcoal (MDAC), fructose-1,6-diphosphate, sodium bicarbonate, magnesium, phenytoin and anti-digoxin Fab antitoxin.
We searched MEDLINE, EMBASE, the Controlled Trials Register of the Cochrane Collaboration, Current Awareness in Clinical Toxicology, Info Trac, www.google.com.au, and Science Citation Index of studies identified by the previous searches. We manually searched the bibliographies of identified articles and personally contacted experts in the field.
Randomised controlled trials where antidotes were administered to patients with acute symptomatic cardenolide poisoning were identified.
Data collection and analysis
We independently extracted data on study design, including the method of randomisation, participant characteristics, type of intervention and outcomes from each study. We independently assessed methodological quality of the included studies. A pooled analysis was not appropriate.
Two randomised controlled trials were identified, both were conducted in patients with yellow oleander poisoning. One trial investigated the effect of MDAC on mortality, the relative risk (RR) was 0.31 (95% confidence interval (CI) 0.12 to 0.83) indicating a beneficial effect. The second study found a beneficial effect of anti-digoxin Fab antitoxin on the presence of cardiac dysrhythmias at two hours post-administration; the RR was 0.60 (95% CI 0.44 to 0.81). Other benefits were also noted in both studies and serious adverse effects were minimal. Studies assessing the effect of antidotes on other cardenolides were not identified. One ongoing study investigating the activated charcoal for acute yellow oleander self-poisoning was also identified.
There is some evidence to suggest that MDAC and anti-digoxin Fab antitoxin may be effective treatments for yellow oleander poisoning. However, the efficacy and indications of these interventions for the treatment of acute digitalis poisoning is uncertain due to the lack of good quality controlled clinical trials. Given pharmacokinetic differences between individual cardenolides, the effect of antidotes administered to patients with yellow oleander poisoning cannot be readily translated to those of other cardenolides. Unfortunately cost limits the use of antidotes such as anti-digoxin Fab antitoxin in developing countries where cardenolide poisonings are frequent. More research is required using relatively cheap antidotes which may also be effective.
用於急性cardenolide (cardiac glycoside)中毒之解毒劑
Cardenolides是天然的植物毒素，其主要作用於心臟。雖然全世界有digitalis cardenolides (digoxin與digitoxin)中毒的報告，但來自其他cardenolides如黃夾竹桃的心臟毒素也是一個重要的問題，每年在南亞有成千上萬的中毒個案。因為來自這些植物的cardenolides的結構相似，因此中毒時也採用類似的治療方式。這些治療的好處備受關注，尤其是成本方面，因為大部分的中毒事件發生在資源有限的發展中國家。
確定解毒劑對於治療急性cardenolide中毒的效用，尤其是atropine，isoprenaline (isoproterenol)，multipledose activated charcoal (MDAC)，fructose1,6diphosphate，sodium bicarbonate，magnesium，phenytoin與antidigoxin Fab抗毒素。
我們檢索MEDLINE，EMBASE，the Controlled Trials Register of the Cochrane Collaboration，Current Awareness in Clinical Toxicology，Info Trac，www.google.com.au，與之前檢索確定的科學文獻索引研究。我們人工檢索已確定文章的參考書目並親自連絡該領域的專家。
確定兩篇隨機對照試驗，兩篇皆在黃夾竹桃中毒的病患進行。一篇試驗調查MDAC對於死亡率的效果，其relative risk (RR)為0.31 (95% confidence interval (CI)為0.12至0.83)，也就是說MDAC具有有利的效果。第二篇研究發現在給予antidigoxin Fab抗毒素兩個小時後對於心律不整具有有利的效果；RR為0.60 (95% CI為0.44至0.81)。另外兩篇研究也發現其他的效果且副作用的嚴重性不大。沒有評估解毒劑對於其他cardenolides效果的研究被確認。發現有一篇調查活性炭用於急性黃夾竹桃自我中毒的研究正在進行中。
一些證據認為MDAC與antidigoxin Fab抗毒素也許對於黃夾竹桃中毒是有效果的治療。然而，由於缺少品質良好的對照臨床試驗，因此這些用於治療急性digitalis中毒的介入措施之效用與指引並不確定。由於個別cardenolides之間其藥物動力學的差異，因此解毒劑用於黃夾竹桃中毒病患的效果無法容易被轉換給那些其他的cardenolides。不幸地，在cardenolide經常中毒的發展中國家，成本限制了解毒劑如antidigoxin Fab抗毒素的使用。需要更多使用相對便宜且也許是有效的解毒劑的研究。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。