Roberts D M, Buckley N A
Medical School, Australian National University, South Asian Clinical Toxicology Research Collaboration, Canberra, Australian Capital Territory, Australia.
Cochrane Database Syst Rev. 2006 Oct 18;2006(4):CD005490. doi: 10.1002/14651858.CD005490.pub2.
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.
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.
AUTHORS' CONCLUSIONS: 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.
强心苷是天然存在的植物毒素，主要作用于心脏。虽然全球都有关于洋地黄强心苷（地高辛和洋地黄毒苷）中毒的报道，但其他强心苷如黄花夹竹桃引起的心脏毒性也是一个主要问题，在南亚每年有数万例中毒病例。由于这些植物中的强心苷结构相似，急性中毒的治疗方法也类似。这些治疗方法的益处备受关注，特别是考虑到成本因素，因为大多数中毒事件发生在资源非常有限的发展中国家。
确定解毒剂治疗急性强心苷中毒的疗效，特别是阿托品、异丙肾上腺素、多剂量活性炭（MDAC）、1,6-二磷酸果糖、碳酸氢钠、镁、苯妥英和抗地高辛Fab抗体片段。
我们检索了MEDLINE、EMBASE、Cochrane协作网对照试验注册库、临床毒理学当前动态、Info Trac、www.google.com.au以及通过先前检索确定的研究的科学引文索引。我们手动检索了已识别文章的参考文献，并亲自联系了该领域的专家。
确定了将解毒剂给予急性症状性强心苷中毒患者的随机对照试验。
我们独立提取了关于研究设计的数据，包括随机化方法、参与者特征、干预类型和每项研究的结果。我们独立评估了纳入研究的方法学质量。不适合进行汇总分析。
确定了两项随机对照试验，均在黄花夹竹桃中毒患者中进行。一项试验研究了MDAC对死亡率的影响，相对危险度（RR）为0.31（95%置信区间（CI）0.12至0.83），表明有有益效果。第二项研究发现抗地高辛Fab抗体片段在给药后两小时对心律失常的存在有有益效果；RR为0.60（95%CI 0.44至0.81）。两项研究中还注意到了其他益处，且严重不良反应极少。未找到评估解毒剂对其他强心苷影响的研究。还确定了一项正在进行的研究，该研究调查活性炭对急性黄花夹竹桃自我中毒的作用。
有一些证据表明MDAC和抗地高辛Fab抗体片段可能是治疗黄花夹竹桃中毒的有效方法。然而，由于缺乏高质量的对照临床试验，这些干预措施治疗急性洋地黄中毒的疗效和适应证尚不确定。鉴于个体强心苷之间的药代动力学差异，给予黄花夹竹桃中毒患者的解毒剂的效果不能轻易推广到其他强心苷。不幸的是，成本限制了抗地高辛Fab抗体片段等解毒剂在强心苷中毒频繁发生的发展中国家的使用。需要使用可能同样有效的相对便宜的解毒剂进行更多研究。
