Successful Organ Donation After Yew Intoxication

Dear Editors, we would like to report on a case of a successful organ donation under ongoing extracorporeal life support following a yew intoxication. The European yew (Taxus baccata) is as an ornamental conifer widespread throughout Europe. The poisonousness of yews has been known since ancient times and can lead to life threatening intoxications. All parts of the plant, with exception of the red aril, are poisonous. Measured by its cardiotoxic effect, Taxin B is the most important of the alkaloids contained in yews called taxanes. An ingestion of about 3 to 6.5 mg/kg bodyweight Taxine B is described as potentially lethal for humans (1). In central Germany there is approximately one severe intoxication per year; most intoxications occur with suicidal intent in young adults (2,3). In Germany, brain death (BD) is a necessary condition for organ donation. The second frequent cause of BD is the hypoxic-ischemic encephalopathy (HIE) following cardiac arrest (4). Life threatening yew intoxications are rare (2), but can lead to cardiac arrest and so to HIE. A few years ago, we treated a middle-aged patient with a lethal yew intoxication. For ethical reasons, age and gender can not be specified. The medical history included paranoid schizophrenia, recurrent depressive episodes, and several suicide attempts. The patient ingested around 50 crushed yew needles with suicidal intent. Later, regretting the ingestion, the patient sought medical assistance. Emergency services were called to the location and found a hemodynamically stable patient, already showing a broad complex tachycardia on the ECG. Arriving at a primary care hospital, the patient showed a hemodynamic relevant ventricular tachycardia, which deteriorated into an asystole following electrical cardioversion. After a brief, successful cardiopulmonary resuscitation (CPR), an esophagogastroduodenoscopy (EGD) with application of activated charcoal was performed, and the patient was transferred to a higher-level care facility. As the broad complex tachycardia persisted and a cardiogenic shock developed, a multi-faceted therapy with administration of high dose catecholamines, application of lidocaine, sodium bicarbonate, and digitalis antidote was established. Additionally, a continuous hemodialysis with hemadsorption was applied. Under this therapy the ECG rhythm stabilized temporally before suddenly another cardiac arrest with an asystole occurred. A pacemaker could not be implanted. This time, CPR was prolonged and, as a return of spontaneous circulation (ROSC) did not occur, an extracorporeal life support system (ECLS) was established successfully one hour after the start of CPR. The treatment, after ROSC, addressed a post-cardiac arrest syndrome, with persistent hemodynamic instability, renal failure, and a prolonged metabolic acidosis. During therapy, a lack of wake-up reaction and a loss of brainstem reflexes were observed. As a CT scan of the head showed a pronounced cerebral edema indicating severe HIE, an isoelectric EEG was derived. All criteria of BD were fulfilled. In accordance with the patient's wishes, as expressed by the relatives, the patient was evaluated as an organ donor. We continued intensive care therapy for three days, fully aware of the yew intoxication, to ensure that no toxins remained in the blood. Blood levels of 3,5-dimethoxyphenole and other taxanes, including Taxin B, measured by liquid chromatography-mass spectrometry (Triple Quad 5500+, Sciex, Framingham, USA) were taken on days 1, 2 and 3. It was only on day 3 that no toxins were detected, and therefore BD diagnostics were initiated. Organ-protective intensive care, including ECLS, was maintained until the irreversible confirmed. Subsequently, the liver and both kidneys were 52 successfully donated. The organ quality was as good. Histologic 53 examination of showed a microvesicular fibrosis and this organ was rejected 54 for transplantation. The kidneys were successfully transplanted and showed a good 55 one-year-organ function ( with the toxicological measurements in the presented case. There is some evidence of 74 ineffectiveness of sodium bicarbonate, Lidocaine should be avoided due to its similar 75 effect to Taxine B. The use of pacemakers or an electrical cardioversion is uncertain, 76 because of the underlying myocardial channelopathy. A reported cross-reactivity of 77 yew alkaloids with digitalis antidote was the rationale of its use (9). Best data exists for 78 ECLS (9), despite the fact that it is a procedure prone to complications.The rationale for the use of digoxin immune fab is the potential cross-reactivity of the 80 taxane constituents in the yew plant with the digoxin-specific antibody fragments 81 82Taxin B has a cardioselective effect (6), so that organ damage in severe yew 83 intoxications does not primary result from the toxin but secondarily by the induced 84 cardiogenic shock and cardiac arrest. The observed microvesicular steatosis of the 85 liver is caused by an impaired mitochondrial beta-oxidation. There is no described 86 effect of taxanes on mitochondrial functions and thus considered as the impact of 87 hepatic hypoxia due to a prolonged cardiogenic shock and CPR time. At the time of 88 the declaration of BD, taxanes could not be detected. Postmortem histological analysis 89 of the myocardium showed no signs of inflammation or other pathologies. No long-term 90 effects of taxanes are known, and none were observed in the transplanted organs. 91 92In conclusion, an organ donation after a lethal yew poisoning is possible and leads to 93 good transplantation outcomes. Therefore, ECLS is not only the option with most 94 evidence in therapy of yew intoxications, it also provides an option to optimize organ 95 protective intensive care therapy towards organ donation.