Pharmacological treatment of cardiac glycoside poisoning.

Cardiac glycosides are an important cause of poisoning, reflecting their widespread clinical usage and presence in natural sources. Poisoning can manifest as varying degrees of toxicity. Predominant clinical features include gastrointestinal signs, bradycardia and heart block. Death occurs from ventricular fibrillation or tachycardia. A wide range of treatments have been used, the more common including activated charcoal, atropine, ß-adrenoceptor agonists, temporary pacing, anti-digoxin Fab and magnesium, and more novel agents include fructose-1,6-diphosphate (clinical trial in progress) and anticalin. However, even in the case of those treatments that have been in use for decades, there is debate regarding their efficacy, the indications and dosage that optimizes outcomes. This contributes to variability in use across the world. Another factor influencing usage is access. Barriers to access include the requirement for transfer to a specialized centre (for example, to receive temporary pacing) or financial resources (for example, anti-digoxin Fab in resource poor countries). Recent data suggest that existing methods for calculating the dose of anti-digoxin Fab in digoxin poisoning overstate the dose required, and that its efficacy may be minimal in patients with chronic digoxin poisoning. Cheaper and effective medicines are required, in particular for the treatment of yellow oleander poisoning which is problematic in resource poor countries.

[Repeated unexplained cardiac glycoside poisoning].

One of the major tasks of psychiatry, suicide risk assessment, is supposed to reduce morbidity and mortality. However, assessing suicide risk can be quite challenging because it depends almost entirely upon subjective clinical judgment. The patient is often ambivalent towards committing suicide and may conceal his or her real intentions. Therefore, identification of suicidal intention may be daunting even after thorough, repeated psychiatric evaluations. Hence, clinicians must always maintain a high level of doubt, and act accordingly. In the following report we describe the case of a young man who acted out several concealed and very severe suicide attempts that put his Life at risk. Lacking any apparent risk factors, and due to prolonged efforts to cover up his actions, true evaluation and exposure of suicidal risk was extremely difficult. This case study is reported with the goal of emphasizing the complexity of suicide assessment and the need to frequently re-examine one's findings.

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.

Evaluation of activated charcoal as treatment for Yellow tulp (Moraea pallida) poisoning in cattle.

The efficacy of activated charcoal as a treatment for cattle (n = 57) poisoned by Yellow tulp (Moraea pallida) was investigated. Treatment with activated charcoal resulted in full recovery, irrespective of the degree of posterior paresis, provided that this clinical sign did not develop within the first 12 hours after initial exposure to Yellow tulp-infested grazing. For instance, despite treatment, 1 of 7 cattle succumbed after manifesting mild posterior paresis 6 to 8 h after initial exposure and 3 of 3 treated cattle died after developing severe posterior paresis within 6 to 12 h.

A potential krimpsiekte vaccine.

Krimpsiekte, a chronic form of cardiac glycoside poisoning, is an important plant-induced intoxication of small stock in South Africa. It is caused by cumulative, neurotoxic bufadienolides, such as cotyledoside. A cotyledoside-bovine serum albumin conjugate was synthesized to immunize animals. The efficacy of the cotyledoside-conjugate in inducing an immunological response was ascertained in rabbits (n = 4) and sheep (n = 4) by determining cotyledoside antibody titres with an ELISA using cotyledoside-hen ovalbumin as antigen. The formation of anticotyledoside antibodies was induced in both rabbits and sheep following immunization with the cotyledoside-protein conjugate. Protection provided by the vaccine was demonstrated by challenging sheep (n = 4) with repeated, daily doses of cotyledoside (0.015 mg/kg) administered intravenously, commencing 45 days after the initial vaccination. One control animal died on Day 3 of the challenge period and the other was severely affected after administration of the third cotyledoside dose. The immunized ewes (n = 2) remained clinically unaffected and the challenge was suspended following six daily injections. Vaccination as a means of preventing krimpsiekte seems to be quite feasible and deserves further investigation.

Fatal cardiac glycoside poisoning due to mistaking foxglove for comfrey.

CONTEXT: Accidental ingestion of foxglove (Digitalis purpurea) can cause significant cardiac toxicity. We report a patient who ingested foxglove mistaking it for comfrey and developed refractory ventricular arrhythmias. The patient died despite treatment with digoxin-specific antibody fragments (DSFab) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). CASE DETAILS: A 55-year-old woman presented to the emergency department with nausea, vomiting and generalized weakness eight hours after drinking "comfrey" tea. She had bradycardia (54 beats/min) and hyperkalemia (7.6 mEq/L). Electrocardiogram revealed a first-degree atrioventricular conduction block with premature atrial contractions, followed by polymorphic ventricular tachycardia three hours after arrival. A serum digoxin level was 151.2 ng/mL. The patient developed ventricular fibrillation while waiting for Digibind infusion. Resuscitation was performed and an emergent VA-ECMO was set up. A total of eight vials of Digibind were given over the next 16 hours. She temporarily regained consciousness, but remained hemodynamically unstable and subsequently developed lower limb ischemia and multiple organ failure, and she expired on hospital day seven. A botanist confirmed that the plant was foxglove. CONCLUSIONS: The diagnosis of cardiac glycoside plant poisoning can be difficult in the absence of an accurate exposure history. In facilities where DSFab is unavailable or insufficient, early VA-ECMO might be considered in severely cardiotoxic patients unresponsive to conventional therapy.

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.

The role of fluorescence polarization immuno-assay in the diagnosis of plant-induced cardiac glycoside poisoning livestock in South Africa.

Poisoning with cardiac glycoside-containing plants is collectively the most important plant-associated poisoning of livestock in southern Africa. As a diagnosis of this significant poisoning is currently based on circumstantial evidence, a practical chemical procedure indicating the presence of cardiac glycosides in plants and animal specimens would be of considerable benefit. The fluorescence polarization immunoassay (FPIA) method, used to determine digoxin plasma levels in humans and dogs, was adapted to estimate cardiac glycoside levels in known cardiac-glycoside-containing plants as well as in the rumen and organs of dosed sheep. Positive FPIA values were obtained with bufadienolide-containing plants, while negative results were obtained with plants not known to contain cardiac glycosides. The FPIA has aided in the diagnosis of cardiac glycoside poisoning in livestock and game in 30 outbreaks examined at the Division of Toxicology, Onderstepoort Veterinary Institute. Each outbreak is briefly described. As a result of this assay, a better understanding of cardiac glycoside poisoning has been reached.

[Cardiotoxic plants]. / Rosliny kardiotoksyczne.

In statistics from Poison Information Center in Kraków plant poisonings comprise 2% of the total registered poisonings. In toxicology cardiac glycosides poisonings existing in common foxglove plant, lilies of the valley, oleander are essential. Species of cardiotoxic plants which may cause a danger in Poland are presented in the research. The toxic mechanisms of cardiac glycosides are specified.

Poisoning by antidysrhythmic drugs.

This article discusses the management of antidysrhythmic drug overdoses in children and adolescents.

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.

Cardiac glycoside poisoning in sheep caused by Urginea physodes (Jacq.) Bak. and the isolated physodine A.

Urginea physodes (Jacq.) Bak., a species closely related to or possibly synonymous with U. pusilla, is described and its distribution given. Four bufadienolides were isolated from U. physodes and the approximated LD50 and cumulative effect of some of them determined in guinea pigs. The most toxic one proved to be mildly cumulative. Typical signs of acute cardiac glycoside poisoning, involving the locomotory, gastro-intestinal, respiratory and cardiac system, were seen in the field cases and/or were experimentally induced by the plant. Similar signs could also be induced by injecting the isolated bufadienolide, physodine A, to a sheep.

Krimpsiekte, associated with thalamic lesions, induced by the neurotoxic cardiac glycoside, cotyledoside, isolated from Tylecodon wallichii (Harv.) Toelken subsp. wallichii.

The specific neurotoxic principle of Tylecodon wallichii (Harv.) Toelken subsp. wallichii, the cause of krimpsiekte in small stock, was isolated and identified as the previously described cumulative bufadienolide, cotyledoside. Krimpsiekte was experimentally induced in two sheep by the repeated intravenous administration of cotyledoside at the rate of 0.01-0.015 mg/kg body mass. On day 9, both animals developed clinical signs typical of krimpsiekte, which is characterized by tremors, paresis and recumbency. Both sheep had difficulty in controlling their hindquarters when attempting to lie down. No significant electrocardiograph abnormalities were detected during the experiment which confirms that cotyledoside at low doses does not overtly affect the electrical activity of the heart. No gross lesions were observed in the sheep. The most significant microscopic lesions comprised mild brain oedema and pronounced vacuolation of the white matter of thalamic nuclei. These lesions might explain some of the motor function deficiencies clinically observed in this syndrome. The previously held contention that these neurotoxic cardiac glycosides are indeed the cause of krimpsiekte is, therefore, confirmed.

Krimpsiekte in a sheep following a single dose of Tylecodon ventricosus (Burm. f.) Toelken and the isolation of tyledoside D from this plant species.

Tylecodon ventricosus induced severe respiratory distress in two penned sheep without any electrocardiographic abnormalities being recorded. Based on the results it appears as if T. ventricosus predominantly induces the neuromuscular syndrome referred to as krimpsiekte. A single, relatively large intraruminal dose of 10.0 g/kg induced krimpsiekte in one sheep. Treatment with 5.0 g/kg activated charcoal on two consecutive days did not prevent the development of krimpsiekte. A bufadienolide, tyledoside D, was isolated from semi-dried plant material.

Suspected cardiac glycoside intoxication in sheep and goats in Namibia due to Ornithogalum nanodes (Leighton).

The main clinical and necropsy features of field and experimental cases of suspected cardiac glycoside intoxication following ingestion and dosing of the plant Ornithogalum nanodes, are described. The distribution of intoxication in the area as well as a description of the plant are given. Plant samples tested for cardiac glycosides by fluorescence polarization immuno-assay (FPIA) gave a strong positive reaction. This is a new finding, as other toxic Ornithogalum species in southern Africa are devoid of cardiac glycoside activity and poisoning with them result only in a severe, often fatal diarrhoea, without obvious cardiac involvement. It is also the first record of toxicity of this particular plant.

Cardiovascular glycoside-like intoxication following ingestion of Thevetia nereifolia/peruviana seeds: a case report.

Some plants contain glycoside compounds which determine cardiovascular symptoms similar to those observed after acute toxic digoxin administration. The present case report involves a patient who showed important cardiovascular symptoms following the ingestion of Thevetia nereifolia/peruviana seeds. About 30 min after ingestion, a 65-year-old man presented with dizziness, giddiness, numbness and a burning sensation, diarrhea, sweating, vomiting and ECG changes. At the time of admission he presented with tremors; his body temperature was 37 degrees C, and blood analysis gave the following results: K 5.6 mEq/l, myoglobin 176 IU, troponin T 0.10 ng/ml, PO2 69 mmHg, PCO2 37.4 mmHg, pH 7.33, HCO3- 19.9 mEq/l, hemoglobin 14.8 g/dl, saturation 92.5%. Echocardiography showed a left ventricle with normal global and segmentary contractility. The following days, the patient showed a reduction, until total resolution, of the atrioventricular block and of the alterations of the ST segment. The ectopic beats also resolved; K value before discharge was 4.4 mEq/l. On the third day, the serum levels of digoxin were 0.15 ng/ml. This case report is important because it describes all the cardiovascular and non-cardiovascular signs of glycoside toxicity in an adult patient who accidentally swallowed only two seeds (non-fatal dose) of Thevetia.