Cardiotoxicity in yew berry poisoning.

Yew plants (Taxus species) represent a genus of plants known to be highly toxic, though lethal intoxication is rare. The majority of deaths in yew berry poisonings occur due to its cardiotoxic effect, mediated through generation of a number of fatal tachy- and brady-arrhythmias. However, there are no guidelines on the most effective management in these cases, and interventions vary greatly between published reports. Here we report a case of a 20-year-old female who presented with refractory lethal arrythmia and shock refractory to conventional therapy. She presented to the emergency department and promptly required airway management and hemodynamic support necessitating intensive care unit management. She received many antiarrhythmics, digoxin immune Fab, lipid emulsification, and eventually transvenous pacemaker insertion for overdrive pacing. Despite our interventions, our patient ultimately died after a decision to withdraw care. We also reviewed 43 reports of yew poisoning cases described in the literature. We discuss the most common strategies used to treat such patients including gastric decontamination, antiarrhythmics, electrical pacing, extracorporeal life support and other therapies. We need better understanding of this condition, to identify which therapies offer maximal benefit and to optimize outcomes for this rare but often devastating toxidrome.

Yew poisoning - pathophysiology, clinical picture, management and perspective of fat emulsion utilization.

The article presents pathophysiology, clinical picture and management of yew poisoning. Authors present also their own experiences with treating yew poisoning with fat emulsion. Plants of the yew genus, of which in Europe predominates Taxus baccata, are well known for their toxic properties. Particularly high concentrations of poisonous alkaloids are present in the needles of this evergreen and highly popular decorative plant. The danger associated with accidental or intentional ingestion of yew is primarily related to the cardiotoxic effects of the alkaloids (taxine A and B). Taxine B shows a much stronger toxic effect on the heart than taxine A. It affects atrio-ventricular conduction, what may result in a widening of the QRS complexes, atrio-ventricular blocks (A-V) of II/III degree and even in asystole. Yew poisoning is relative rare and evidence-based treatment guidelines on management of such poisoning is hard to prepare. The first-line treatement should base on suportive therapy. In some cases extracorporeal life support therapies such veno-arterial ECMO should be consider. There are also premise based on case reports and mechanism of action that the use of fat emulsion may be effective rescue treatment.

"Chaotic Arrhythmia" During Successful Resuscitation After Ingestion of Yew (Taxus baccata) Needles.

OBJECTIVE: The study aims to describe the management of a case of life-threatening yew (Taxus baccata) intoxication. BACKGROUND: The needles of the yew tree contain highly cardiotoxic taxines. Intoxication with taxines, typically as part of suicide attempts, may lead to potentially lethal arrhythmias which often require prolonged cardiopulmonary resuscitation and other supportive measures. No specific therapy has been described. In some cases, extracorporeal life support has been used. CASE: After an attempted suicide with yew needles and out-of-hospital cardiac arrest, a female adolescent was resuscitated for 6 hours according to Advanced Cardiovascular Life Support guidelines. Complex ventricular tachycardias were treated by repeated direct current shocks and broad complex bradycardia managed with transvenous cardiac pacing. Antiarrhythmic drugs (amiodarone, lidocaine), magnesium sulfate, and supportive measures (intravenous lipids, sodium bicarbonate) were provided. The arrhythmias finally resolved, and the patient did not show any significant neurological or cardiac short-term sequelae after 24 hours. RESULTS: The authors describe the successful management of a case of severe taxine intoxication by prolonged conventional advanced cardiac life support lasting for more than 6 hours. CONCLUSIONS: In life-threatening yew intoxication, prolonged cardiopulmonary resuscitation is absolutely essential owing to the long duration of the cardiotoxic action of taxines and can lead to an outcome without cardiac or neurological sequelae.

Fatal poisoning by ingestion of Taxus Baccata leaves.

In this report we describe a first suicide case in Serbia related to ingestion of Taxus baccata leaves. A 30-year old woman was found dead, and the green plant material in a plastic bag was found near her bed. Autopsy revealed dark green needle-like leaves in the stomach, similar to that contained in the plastic bag, and both were botanically identified as Taxus baccata, also known as yew. Using gas chromatography-mass spectrometry (GC-MS), 3,5-dimethoxyphenol (3,5-DMP) as toxicological evidence for the ingestion of yew leaves, was detected in biological samples. As the autopsy showed unspecific findings, and also the routine toxicological examination, based upon 3,5-DMP identification, the cause of death was determined to be suicide, caused by yew poisoning.

Clinical Toxicology of Yew Poisoning.

OBJECTIVES: Yew plant materials contain highly toxic taxine alkaloids. Serious ingestions can result in life-threatening toxicity. The purpose of this article is to summarize the literature on the treatment of acute yew poisoning. DATA SOURCES: PubMed (January 1946 to November 2017) was searched using the search terms "taxus/po". EMBASE (1980 to November 2017) was searched using the search terms "taxus/to" and "yew.mp." Web of Science (1945 to November 2017) was searched using the text words taxus, taxine, and yew. STUDY SELECTION AND DATA EXTRACTION: Available English language articles involving case reports, epidemiology, treatment, and outcomes were included. DATA SYNTHESIS: Although not uncommon, unintentional yew poisoning rarely results in significant morbidity or mortality. A total of 26 case reports of yew poisoning were evaluated along with 4 case series articles (totaling 22 additional cases). Only 4 of the 48 total cases (8%) were accidental poisonings, the rest being deliberate ingestions. In 20 patients (42%), it resulted in fatalities. Severe, acute yew poisoning results in symptomatology largely resistant to pharmacotherapy intervention. CONCLUSIONS: Most nonintentional ingestions of yew plant constituents are asymptomatic and require little intervention. Severe poisoning can result in life-threatening cardiac toxicity and require aggressive supportive care. Therapeutic interventions, such as sodium bicarbonate, digoxin immune fab, and hemodialysis that have been utilized in case studies and case series in the literature have little proven benefit. Extracorporeal life support should be considered in severe yew poisoning.

Extracorporeal life support and digoxin-specific Fab fragments for successful management of Taxus baccata intoxication with low output and ventricular arrhythmia.

INTRODUCTION: Yew plants are evergreen shrubs which are widely spread throughout the northern hemisphere. Taxane alkaloid derivatives, mainly taxine B, represent the main toxins of Taxus baccata and are highly cardiotoxic. Due to the lack of randomized clinical trials, case reports on accidental or suicidal yew intoxications build the only source of knowledge of clinical treatment options. CASE REPORT: We report the case of a suicidal yew ingestion admitted to our hospital under prolonged cardiopulmonary resuscitation due to pulseless electrical activity. Extra-corporeal life support (ECLS) was established to maintain adequate organ perfusion. Repeated administration of digoxin-specific Fab antibody fragments, which cross-react with taxine, was associated with an immediate conversion from asystole to broad-complex bradycardia and a gradual normalization of the electrocardiogram (ECG). This was paralleled by a recovery of the cardiac function and weaning from the ECLS. The taxine metabolite 3,5-dimethoxyphenol could be detected by mass spectrometry before but not after the first Fab-fragment treatment. In contrast, the total amount of taxine (including the neutralized, Fab fragment-bound fraction) was increased after each Fab fragment administration, suggesting an accumulation of neutralized, since antibody-bound taxine in the blood by anti-digoxin Fab fragments. DISCUSSION: In conclusion, the successful clinical course of this case suggests a benefit of an early anti-digoxin Fab-fragment administration for the treatment of yew intoxication.

Post-mortem findings in 22 fatal Taxus baccata intoxications and a possible solution to its detection.

BACKGROUND: The yew (Taxus baccata) is a common evergreen tree containing the toxin taxine B. Between 42 and 91 g of yew leaf is lethal to a 70-kg adult. The objective of this article is to present an overview of findings in fatal yew intoxications. METHODS: A search using MeSH terms was performed in PubMed for yew intoxications in the period between January 1960 and August of 2016. RESULTS: We describe a total of 22 cases. Fatal intoxications can be divided into intoxications by leaves, by pulp, by bark and by yew tea. Recognizing yew tea intoxication is difficult since tea no longer contains any botanically recognisable parts. In autopsy and external examination no characteristic findings are reported, regarding the presence of parts of plants. CONCLUSIONS: Indications for yew tree intoxications at a post-mortem examination and autopsy are limited to finding parts of yew tree. The absence of recognisable parts can result in yew intoxications being overlooked. Therefore toxicological screening is recommended in unexplained deaths.

Suicide attempt with self-made Taxus baccata leaf capsules: survival following the application of extracorporeal membrane oxygenation for ventricular arrythmia and refractory cardiogenic shock.

CONTEXT: Yew intoxication has been known for many years; high dose ingestion of Taxus baccata leads to cardiac toxicity mediated by calcium and sodium channel blocking properties. We present a case report of a patient who attempted suicide after T. baccata ingestion, causing refractory cardiogenic shock requiring temporary circulatory assistance by veno-arterial extra corporeal membrane oxygenation (VA ECMO). CASE DETAILS: A 28-year-old man was admitted to the critical care unit of a university hospital for arrhythmia after ingestion of self-made T. baccata leaf capsules. He rapidly developed cardiovascular collapse requiring mechanical ventilation, high dose intravenous catecholamines and electrical cardioversion. A femoro-femoral VA ECMO was implanted due to severe biventricular dysfunction and ventricular arrhythmia, associated with continuous renal replacement therapy. Taxol A, taxol B and baccatin III were detected and measured in both blood and urine samples by high-performance liquid chromatography tandem mass spectrometry, and kinetics suggested urinary excretion. Two days after hospital admission, VA ECMO and continuous renal replacement therapy were removed with full recovery of cardiac function. DISCUSSION: Our experience suggests that circulatory assistance by VA ECMO and continuous renal replacement therapy seem to be effective safe second-line therapeutic options in critically ill cases of severe yew intoxication with refractory cardiogenic shock due to arrhythmia.

Fatal Taxus baccata ingestion with perimortem serum taxine B quantification.

INTRODUCTION: Common yew (Taxus baccata) is a common decorative evergreen shrub with potentially fatal toxicity hallmarked by seizure, arrhythmia and cardiovascular collapse if ingested. Taxine B has been identified as one of the most cardiotoxic taxine alkaloids in Taxus spp, and another alkaloid, 3,5-dimethoxyphenol (3,5-DMP), is used as a marker of ingestion. We present a fatal case of ingestion of yew with perimortem serum and gastric taxine B, and 3,5-DMP concentrations. CASE PRESENTATION: A 22-year-old woman was brought to the emergency department (ED) from a nearby botanical garden after she was found apneic and pulseless after a witnessed generalized tonic clonic seizure. The patient was found to have a wide complex rhythm with persistent cardiovascular collapse and expired despite maximal supportive care in the ED. A baggie of plant material was found on the patient, identified as Taxus baccata. Perimortem serum and gastric samples were analyzed to quantify serum and gastric taxine B and 3,5-DMP concentrations. RESULTS: Perimortem serum showed a 3,5-DMP concentration of 86.9 ng/mL, and taxine B of 80.9 ug/mL. CONCLUSION: We report a perimortem serum and gastric taxine B and 3,5-DMP concentrations in a fatal case of T. baccata toxicity.

Combination of veno-arterial extracorporeal membrane oxygenation and hypothermia for out-of-hospital cardiac arrest due to Taxus intoxication.

A young woman presented with cardiac arrest following ingestion of yew tree leaves of the Taxus baccata species. The toxin in yew tree leaves has negative inotropic and dromotropic effects. The patient had a cardiac rhythm that alternated between pulseless electrical activity with a prolonged QRS interval and ventricular fibrillation. When standard resuscitation therapy including digoxin immune Fab was ineffective, a combination of extracorporeal membrane oxygenation (ECMO) and hypothermia was initiated. The total duration of low flow/no flow was 82 minutes prior to the initiation of ECMO. After 36 hours of ECMO (including 12 hours of electrical asystole), the patient's electrocardiogram had normalized and the left ventricular ejection fraction was 50%. At this time, dobutamine and the ECMO were stopped. The patient had a full neurologic recovery and was discharged from the intensive care unit after 5 days and from the hospital 1 week later.

Yew poisoning of olive baboons (Papio anubis) in captivity: laboratory diagnosis.

OBJECTIVES: Toxic effects of the yew have been known since ancient times. Yew toxicity is due to the content of cyanogenic glycosides and a mixture of alkaloids known as taxines. Taxine B is probably responsible for the most part of adverse effects in poisoned organisms. This particular taxoid is common in body fluids of the yew-poisoned. The present study is engaged with laboratory examination to confirm substances that lead to fatality of a pair of olive baboons (Papio anubis) following ingestion of yew seeds. When both cage mates (male and female) died suddenly, poisoning was suspected because many berries had fallen into the cage from a nearby fruiting yew tree (Taxus baccata) during the windy night before. METHODS: The analysis was performed using electrospray ionization quadrupole time-of-flight mass spectrometry. A flow injection analysis/mass spectrometry setting was prepared for this purpose. RESULTS: The above mentioned mass spectrometry analysis of taxoids confirmed poisoning by taxanes. The presence of taxin B/isotaxin B was confirmed in all investigated samples. Apparently in urine and bile there were concentrations ranging 150-220 ng.mL-1 and in blood serum concentrations 25-30 ng.mL-1. CONCLUSION: It follows from the results obtained that we confirmed that baboons were deadly intoxicated by yew fruits.

Myocardial fibrosis associated with previous ingestion of yew (Taxus sp.) in a Holstein heifer: evidence for chronic yew toxicity in cattle.

Twenty-six 5-month-old Holstein calves were accidentally exposed to discarded branches of yew bushes (Taxus sp.). Several calves were found dead approximately 24 hr after exposure; however, a few calves died several days after exposure. One calf died 18 days after the initial exposure to Taxus sp. and was examined on the farm via necropsy. Gross lesions included ascites, and dilated and flaccid myocardial ventricles. Sections of formalin-fixed heart were submitted to the Indiana Animal Disease Diagnostic Laboratory for histopathologic examination; fresh rumen contents were submitted for toxicologic testing. Histologically, large areas of myocardium were replaced by fibrous connective tissue, suggesting previous myocardial necrosis. Taxus alkaloids were identified in the rumen contents using gas chromatography-mass spectrometry. Based on the clinical history, the gross and histologic lesions, the identification of Taxus alkaloids in the rumen contents, and lack of exposure to other known cardiotoxic agents, yew toxicity was considered the cause of death in this calf. Ingestion of taxines is known to cause acute and subacute toxicity in human beings and animals; however, a chronic clinical course and severe histologic lesions have not been previously associated with yew toxicity. Although only 1 calf was examined, this case suggests that yew toxicity can result in a prolonged clinical course in cattle and can cause histologic myocardial lesions.

Eight cases of fatal and non-fatal poisoning with Taxus baccata.

This paper describes two fatalities, three non-fatal intentional and three accidental oral ingestions of yew (Taxus baccata) leaves. In all cases the post-mortem external examinations showed no signs of violence. Internal examinations revealed small green, needle-like particles on the tongue, in the esophagus and in the stomach. Yew leaves were also identified in the stomach contents, whereas Taxus leaves were cut into small pieces and then ingested in one case. The analytical method used was based on a liquid-liquid-extraction under alkaline conditions followed by LC-MS/MS analysis (QTRAP 5500). Chromatographic separation was achieved by HPLC on a Kinetex C18 2.6u (100×3) mm. The analytical method allows the simultaneous identification and quantification of the commercially available yew alkaloids taxoids (m/z): paclitaxel (854.2→105.0/286.1), 10-deacetyltaxol (10-DAT: 812.2→105.0/286.1), baccatin III (BAC III: 604.0→105.0/327.0), 10-deacetylbaccatin III (10-DAB III: 562.1→105.0/327.0), cephalomannine [taxol B] (562.1→105.0/327.0) and of 3,5-dimethoxyphenol (3,5-DMP: 155.0→111.9/122.9) also encompassing the qualitative analysis of the alkaloidal diterpenoids (Q1→194.0/107.0); reference mass spectra obtained from a yew leaves extract: monoacetyltaxine (MAT: 568.4), taxine B (584.2), monohydroxydiacetyltaxine (MHDAT: 626.4), triacetyltaxine (TAT: 652.4), monohydroxytriacetyltaxine (MHTAT: 668.4). In both fatalities, paclitaxel, 10-DAT and cephalomannine were not identified in urine, cardiac and femoral blood but all taxoids and 3,5-DMP were present in stomach content and excreted into the bile. In urine, highest 3,5-DMP concentration was 7500 µg/L and 23,000 µg/L after enzymatic hydrolysis, respectively. In intentional and accidental poisonings, when electrocardiogram (ECG) examinations revealed ventricular tachycardia and/or prolonged QRS intervals, taxines were identified in plasma/serum, even after the ingestion of a few number of yew leaves, when 3,5-dimethoxyphenol was not even found. According to the data from one near-fatal intentional poisoning, elimination half-life of MAT, TAXIN B, MHDAT and MHTAT in serum was calculated with 11-13 h and taxines were detected up to t=+122 h post-ingestion of approximately two handfuls of yew leaves.

Fatal poisoning with Taxus baccata: quantification of paclitaxel (taxol A), 10-deacetyltaxol, baccatin III, 10-deacetylbaccatin III, cephalomannine (taxol B), and 3,5-dimethoxyphenol in body fluids by liquid chromatography-tandem mass spectrometry.

This method development was to confirm the fatal ingestion of toxic yew plant material in postmortem samples (stomach content, urine, femoral blood, cardiac blood, bile, and brain tissue) collected from a 22-year-old man who committed suicide by ingesting yew leaves. The analytical method was based on a liquid-liquid extraction under alkaline conditions followed by LC-MS-MS analysis. Chromatographic separation was achieved by HPLC on a Kinetex C18 2.6u (100 × 3 mm) coupled to a QTRAP 5500 system. The method allows the simultaneous identification and quantification of the yew alkaloids taxoids paclitaxel (taxol A), 10-deacetyltaxol, baccatin III, 10-deacetylbaccatin III, cephalomannine (taxol B), and 3,5-dimethoxyphenol; the alkaloidal diterpenoids monoacetyltaxine, taxine B, monohydroxydiacetyltaxine, triacetyltaxine, and monohydroxytriacetyltaxine were also identified. The initial hypothesis of yew tree (Taxus baccata) poisoning was confirmed. The quantitative evaluation revealed taxoid concentrations ranging from 4.5 to 132 µg/L (stomach content), 1 to 200 µg/L (urine), <0.5 to 12 µg/L (cardiac blood), <0.5 to 7.3 µg/L (femoral blood), and 4.9 to 290 µg/L (bile). In brain tissue, none of these taxoids could be detected (<0.5 µg/L). In urine, after enzymatic hydrolysis, the concentration of 3,5-dimethoxyphenol (3,5-DMP) was 23,000 µg/L. The alkaloidal diterpenoids were found in all postmortem samples. The newly developed LC-MS-MS method enables the identification of alkaloidal and non-alkaloidal diterpenoids and 3,5-dimethoxyphenol in human body fluids and tissues for the confirmation of accidental or intentional poisonings with yew plant material.

Application of direct PCR in a forensic case of yew poisoning.

Intoxications with yew (Taxus spp.) pose a challenge to forensic toxicology because a variety of Taxus ingredients have been associated with its toxic effects. To provide preliminary evidence in cases where plant material is available, we introduce a novel direct PCR assay for the detection of DNA traces from Taxus spp. This assay has been successfully applied to a forensic case of suicidal poisoning via ingestion of Taxus leaves. PCR primers were designed to target a sequence located in the internal transcribed spacer 1 (ITS1) of nuclear ribosomal DNA, which is well conserved among species of the genus Taxus and can, therefore, be exploited to discriminate between Taxus and other conifers. Because ITS1 exists as a multicopy sequence within the plant genome, the assay provides enough sensitivity to work with trace amounts that are below the DNA content of a single cell. Specificity of the assay was tested with DNA extracts from Taxaceae and selected representatives from other related plant families (Cephalotaxaceae, Cupressaceae and Pinaceae). When combined with the commercial Phire® Plant Direct PCR Kit (Finnzymes), the primers allowed application of a two-step cycling protocol (without the annealing step), and because direct PCR requires only little sample pre-treatment, results from PCR could be obtained within 1.5 h after analysis had begun. Direct PCR was performed with diluted gastric content from the forensic case. Amplification products of the expected size were purified and sequenced. Sequence data were subjected to Basic Local Alignment Search Tool analysis and affiliated with ITS1 from Taxus spp.

[Taxus baccata poisoning]. / Smrtelná otrava tisem cerveným.

Common yew poisoning occurs by per oral application of needles or extracts of needles usually. The determination of the cause of death is more difficult in the latter case. In our article, we advise of circumstances which could be helpful in diagnostic. In addition, we describe the substances contained in yew, their effect, importance and toxicological detection.