[Multidisciplinary management of voluntary pink oleander poisoning: How to estimate the quantities ingested?] / Prise en charge multidisciplinaire d'une intoxication volontaire au laurier rose : comment estimer les quantités ingérées ?

This is a case of voluntary ingestion of Nerium oleander leaves in an adolescent requiring the use of atropine and emergency chartering of antidigoxin antibodies (Digifab®) due to the difficulty of assessing oleandrin level and associated toxicity. Upon hospital admission, a digoxinemia was performed (0.44µg/mL) and the presence of oleandrine was detected. Oleandrin levels at toxic levels may be suspected by a measure of blood digoxin and explain the patient's clinical signs, which could adapt the therapeutic management.

Unexpected double lethal oleander poisoning.

Nerium oleander is a very popular urban ornamental plant in Europe, but it is also extremely dangerous because it contains several types of glycosides, accidental ingestion of which can cause cardiac arrhythmias and even deaths. The rarity of such cases makes it difficult to think of oleander poisoning without evidences that suggest this possibility as the cause of the unexpected death. This report concerns the discovery of the bodies of 2 young people, a man and a woman, in a forest in conditions of extreme malnutrition. Medicolegal investigations showed neither pathologic nor traumatic causes of death, but the presence of vegetal remains in the stomach was noticed. A common toxicological analysis resulted negative, but the implementation of more detailed investigations showed the presence of digoxin in the blood of both cadavers, excluding the possibility of a pharmaceutical provenience of digoxin, this laboratory result was interpreted as evidence of ingestion of oleander, which contains oleandrine, the cross reaction of which with digoxin is widely described in the literature. Identification of the 2 subjects, which occurred after 4 years, strengthened the hypothesis of accidental poisoning by oleander because it was ascertained that the 2 young people were vegans--extreme vegetarians who reject the ingestion of foods of animal origin and live by eating only what they find in nature.

A Probable Fatal Case of Oleander (Nerium oleander) Poisoning on a Cattle Farm: A New Method of Detection and Quantification of the Oleandrin Toxin in Rumen.

Oleander (Nerium oleander) is an ornamental plant common in tropical and sub-tropical regions that is becoming increasingly widespread, even in temperate regions. Oleander poisoning may occur in animals and humans. The main active components contained in the plant are cardiac glycosides belonging to the class of cardenolides that are toxic to many species, from human to insects. This work describes a case of oleander poisoning that occurred on a small cattle farm and resulted in the fatality of all six resident animals. Furthermore, the investigation of the poisonous agent is described, with particular focus on the characterization of the oleandrin toxin that was recovered from the forage and rumen contents. The innovation of this study is the first description of the detection and quantification of the oleandrin toxin by liquid chromatography-high resolution mass spectrometry (LC-HRMS) in rumen.

Fatal injury in eastern Sri Lanka, with special reference to cardenolide self-poisoning with Cerbera manghas fruits.

OBJECTIVE: Self-poisoning with plant seeds or fruits is a common method of self-harm in South Asia. While most deaths follow ingestion of Thevetia peruviana (yellow oleander) seeds, other plants are locally common. During review of fatal injuries seen in a teaching hospital in eastern Sri Lanka, we noted cases of fatal self-poisoning with Cerbera manghas (sea mango, pink eyed cerbera, odollam tree) fruits. METHODS: We reviewed the post-mortem records of the Batticaloa Teaching Hospital and extracted data on all cases of fatal injury. RESULTS: During 2001 and 2002, 315 post mortems for injury were performed in Batticaloa Teaching Hospital. Intentional self-harm was responsible for 48.6% of cases. While T. peruviana was responsible for 33 deaths, C. manghas self-poisoning caused seven deaths. C. manghas cases had typical features of cardenolide poisoning with cardiac dysrhythmias and hyperkalemia. In the absence of pacing facilities and anti-digoxin Fab, management involved administration of atropine and of insulin and dextrose to lower serum potassium concentrations. CONCLUSIONS: C. manghas self-poisoning has only previously been reported from Kerala and Tamil Nadu in south India. While uncommon in other parts of Sri Lanka, it has become a common method of self-harm in one east coast district, accounting for 20% of fatal self-harm with plants in one hospital. Management was inadequate with the available resources, emphasising the need for an affordable antitoxin for plant cardenolide poisoning.

Antidotes for acute cardenolide (cardiac glycoside) poisoning.

BACKGROUND: 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. OBJECTIVES: 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. SEARCH STRATEGY: 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. SELECTION CRITERIA: 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. MAIN RESULTS: 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.

Efficacy of digoxin specific Fab fragments (Digibind) in the treatment of toad venom poisoning.

Chan Su, a traditional Chinese medication, and Love Stone, a topical aphrodisiac, are both made from dried venom of the toad bufo bufo gargarizans and contain bufalin, cinobufotalin, cinobufagin, and other cardioactive steroids of the bufadienolide class. Deaths have occurred following ingestion of these products and the clinical course resembles digoxin toxicity. The purpose of this study was to determine the efficacy of digoxin specific Fab fragments in treating Chan Su poisoning. An ethanolic extract was prepared from Chan Su. Digoxin specific Fab fragments were reconstituted in normal saline to a concentration of 80 mg/ml. An approximate LD90 dose was determined in preliminary experiments. Mice were then randomly divided into a treatment group of 15 mice and a control group of 30 mice. The treatment group was pretreated with 20 ml/kg of digoxin specific Fab fragment solution by intraperitoneal injection at t = 0, followed by 10 ml/kg of digoxin specific Fab fragments intraperitoneal at t = 30 min. The control group was pretreated with equal volumes of intraperitoneal normal saline at the same times. Immediately following the 30 min injection, both groups were given the estimated LD90 dose of Chan Su extract by subcutaneous injection. An endpoint of survival at 6 h was chosen after preliminary results showed that all deaths occurred in the first 4 h. All 30 of the control mice had seizures followed by death compared to 11 seizures and 7deaths in the 15 treatment mice. These results were statistically significant by Fisher's exact test (p = 0.00003 for mortality and p = 0.009 for seizures). Digoxin specific Fab fragments are effective in the treatment of Chan Su poisoning in mice and may be effective for poisoning by other cardioactive steroids of the bufadienolide class.

Oleandrin distribution in a fatality from rectal and oral Nerium oleander extract administration.

In a fatal (cardiotoxic) case of oleander extract poisoning of a young female, ethanol extracts of blood and tissue homogenates were purified by lead acetate. After removal of excess lead by ammonium sulfate, oleandrin was extracted into chloroform. Oleandrin in the extract concentrates was detected by thin-layer chromatography, with location by fluorescence and chromogenically by means of p-anisaldehyde. Quantitation was performed on dried extracts reconstituted in water/methanol, reacted with hydrogen peroxide, ascorbic acid, and hydrochloric acid, and analyzed by fluorescence spectrophotometry. Excitation was at 355 nm, and fluorescence scanning from 340 to 580 nm. The fluorescence peak at 460 nm was used for the quantitative measurement. The concentrations of oleandrin measured in blood, stomach wall, colon tissue, liver, heart, lung, brain, spleen, and kidney ranged from 10 to 39 micrograms/g, with 200 micrograms/mL in the total gastric content residue submitted for analysis.

Rapid quantitative analysis of oleandrin in human blood by high-performance liquid chromatography.

A simple and rapid method for quantitation of oleandrin in human blood has been developed using an Extrelut column and high-performance liquid chromatography (HPLC). Blood samples spiked with oleandrin were mixed with distilled water and applied to an Extrelut column for elution with ethyl acetate before HPLC. The HPLC separation of the compound from endogeneous impurities was generally satisfactory with the use of a reversed-phase column. Oleandrin showed excellent linearity in the range of 0.05-10 micrograms/g and the limit of detection was 0.02 microgram/g for human blood. The recovery of the compound, which had been spiked to human blood, was more than 90%. The present method is simple and more rapid than those so far reported, and seems useful for analysis of oleandrin in the cases of oleander poisoning.

[A case of oleander poisoning in a cat]. / Een geval van oleanderintoxicatie bij de kat.

This case history describes clinical symptoms and pathological changes in a cat that are consistent with those of oleander intoxication. The clinical symptoms were characterized by vomiting, diarrhoea, and ventricular extrasystoles. On post-mortem examination focal degeneration and necrosis of the myocardium was seen, as well as haemorrhage of myocardium and wall of the gastrointestinal tract. An overview is given of the literature on the diagnosis, pathogenesis, and treatment of oleander intoxication in different animals and in humans.

[Determination of zimarin in urine]. / Opredelenie tsimarina v moche.

Private technique of extraction isolation and purification, chromatographic detection and photometric determination of zimarin in urine is suggested. Detection limit is 0.01 mg, determination limit is 0.1 mg of glycoside in 100 ml of urine. Method makes it possible to detect 66-80% of zimarin added to 100 ml of urine in quantities 0.5-0.1 mg.

First successful curative use of digoxin-specific Fab antibody fragments in a life-threatening coconut crab (Birgus latro L.) poisoning.

We wish to report the first curative use of digoxin-specific Fab antibody fragments in a coconut crab Birgus latro L. poisoning in New Caledonia. The female patient, aged sixty-three with a previous history of cardiovascular and metabolic dysfunctions, showed marked first-degree atrio-ventricular block and several atrial pauses, and was given 760 mg of digoxin-specific Fab antibody fragments. Shortly after the perfusion her electrocardiogram returned to close to normal with only slight first-degree atrio-ventricular block and no more atrial pauses. Neriifolin LC-MS/MS tests performed on the patient's serum and urine samples confirmed cardenolide poisoning. Another, younger patient, with high neriifolin levels in her serum and urine samples only experienced gastro-intestinal symptoms and was discharged without specific treatment. The consumption of coconut crab in New Caledonia should be avoided even though the first of the two cases reported suggests that digoxin-specific Fab antibody fragments can be effective in the treatment of life-threatening poisoning caused by the ingestion of this crustacean.

Double lethal coconut crab (Birgus latro L.) poisoning.

We report a double lethal coconut crab Birgus latro L. poisoning in New Caledonia. Both patients died after showing gastro-intestinal symptoms, major bradycardia with marked low blood pressure, and finally asystolia. Both had significative hyperkaliemia, suggesting a digitaline-like substance intoxication. Traditional knowledge in the Loyalty Islands relates coconut crab toxicity to the consumption of the Cerbera manghas fruit by the crustacean. Elsewhere previous descriptions of human poisoning with the kernel of fruits of trees belonging to the genus Cerbera, known to contain cardiotoxic cardenolides, appear to be very similar to our cases. Cardenolides assays were performed on patient's serum samples, fruit kernel and on the crustacean guts, which lead us to suppose these two fatal cases were the result of a neriifolin intoxication, this toxin having been transmitted through the coconut crab.

In vitro study of the effectiveness of three commercial adsorbents for binding oleander toxins.

INTRODUCTION: Oleander (Nerium oleander) poisoning is a common problem found in many parts of the world. The oleander toxicity is due to oleandrin and its aglycone metabolite oleandrigenin. Activated charcoal is a useful gastrointestinal decontamination agent that limits the absorption of ingested toxins. A relatively new clay product, Bio-Sponge, containing di-tri-octahedral smectite as the active ingredient, is also recommended for adsorbing bacterial toxins in the gastrointestinal tract. Bio-Sponge has been used to prevent gastrointestinal absorption of oleander toxins in livestock but the efficacy of activated charcoal and Bio-Sponge for adsorbing oleandrin and oleandrigenin has not yet been studied. METHODS: An in vitro experiment to compare the efficacy of three commercially available adsorbents was performed. The adsorbents include Bio-Sponge, ToxiBan granules, and a generic grade activated charcoal. RESULTS: ToxiBan granules have the highest adsorptive capacity, followed by the generic grade activated charcoal, and finally, Bio-Sponge. DISCUSSION: Bio-Sponge did not adsorb oleandrin and oleandrigenin at concentrations that are expected to be present in the gastrointestinal tract of poisoned animals. CONCLUSIONS: On the basis of this in vitro study, products containing activated charcoal are more effective for binding oleander toxins and providing gastrointestinal decontamination than products containing di-tri-octahedral smectite. However, the ability of these adsorbents to alter the clinical outcome in oleander-poisoned animals or humans is yet to be evaluated.