Cardiotoxicity of Yew

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Case report

Cardiotoxicity of yew

a,* b c a

Ondřej Piskač , Jan Stříbrný , Hana Rakovcová , Martin Malý

Kardiologické oddělení Interní kliniky, Ústřední vojenská nemocnice a Vojenská fakultní nemocnice, Praha,

Czech Republic

Vojenský ústav soudního lékařství, Ústřední vojenská nemocnice Vojenská fakultní nemocnice, Praha,

Czech Republic

Klinika pracovního lékařství 1. lékařská fakulta, Univerzita Karlova v Praze a Všeobecná fakultní nemocnice v Praze,

Czech Republic

a r t i c l e i n f o a b s t r a c t

Article history: The Common Yew (Taxus baccata) is an ornamental tree. The taxine alkaloids contained in

Received 2 September 2014 yew berries, needles or bark are poisonous. The lethal dose for an adult is reported to be 50 g

Received in revised form of yew needles. Patients who ingest a lethal dose frequently die due to cardiogenic shock, in

20 November 2014 spite of resuscitation efforts. Although no speciﬁc therapy exists, in some patients the

Accepted 21 November 2014 asystole phase can be overcome by instituting extracorporeal membrane oxygen therapy

Available online 23 December 2014 (ECMO). Therapeutic procedures reported in the literature are only referred to in published

case reports and it is not self-evident whether they have been effective or whether the

Keywords: patient had ingested a non-lethal dose of the toxins. In our case report, we describe lethal

Yew intoxication by common yew needles in a suicide attempt and summarize the treatment

Poisoning options referred to in literature.

ECMO

cases are rather asymptomatic thanks to the small dose eaten.

Introduction

Common yew poisoning following a suicide attempt is rare,

however with severe prognosis (Table 1).

The Common Yew (Taxus baccata) contains poisonous taxine

alkaloids that are contained in yew berries, needles or bark.

Case report

The lethal dose for an adult is reported to be 50 g of yew

needles. According to the statistical evidence of the Toxico-

logical Information Service in the Czech Republic, common The Emergency Medical Service advised the hospital of the

yew poisoning is seen in minority children in the total number imminent arrival of a 25-year-old male patient with a high

of consultations. Consumption by accident is relatively suspicion of common yew poisoning following a suicide

frequent, especially by children up to the age of three. These attempt. The patient's girlfriend called medical assistance at

* Corresponding author. Tel.: +420 608542403.

E-mail address: [email protected] (O. Piskač).

http://dx.doi.org/10.1016/j.crvasa.2014.11.003

c o r e t v a s a 5 7 ( 2 0 1 5 ) e 2 3 4 – e 2 3 8 e235

Table 1 – Statistics of consultations in cases of poisoning, Toxicological Information Service, Rakovcová MD.

Year Consultations Common Common Children Common Severe Suicidal Severe

in total yew yew – up to up to 3 years yew adults course attempts course

number consultations the age of (out of the (older than following following

18 years previous 18 years) accidental suicidal

column) consumption attempts

2014 15,224 147 113 82 34 0 2 0

2013 15,072 117 88 78 29 0 10 0

2012 14,702 82 59 44 23 0 6 1

2011 12,879 162 110 73 52 0 8 2

2010 11,776 76 66 48 10 0 4 0

2009 10,019 85 79 64 6 0 1 1

2008 9741 71 63 43 8 0 3 0

2007 11,423 93 79 61 14 0 8 2

2006 9965 86 64 60 12 0 1 1

2005 9502 86 64 55 12 0 6 0

2:15 p.m. after the patient himself notiﬁed her of the poisoning function tests as well as blood minerals were normal, only a

by telephone shortly after ingesting the poisonous infusion. borderline potassium level of 3.4 mmol/L was found, yet

Upon arrival to the Emergency Department at 3:05 p.m., the accompanied by the abovementioned acidosis. The acid–base

patient was still breathing spontaneously and was haemody- balance was corrected by administering 200 mL of 8.4%

namically stable with arterial blood pressure on admission of NaHCO3. ECG continued to show sinus rhythm, however, with

105/75 mmHg, pulse 100/min and a saturation of 100%. ECG further QRS complex widening to 0.16 ms. At 3:40 p.m. the

recorded by EMS showed sinus tachycardia with a wide QRS patient became unconscious with ventricular ﬁbrillation.

complex of 0.15 ms (Fig. 1). Gastric lavage was performed Repeated deﬁbrillations were performed while a continuous

before arriving at the hospital, and in the Emergency amiodarone infusion was being administered. Due to the

Department lavage was repeated using a nasogastric tube. development of an arrhythmia storm with a cardiogenic

Laboratory tests on admission revealed acidosis with a pH of shock, the patient was sedated and orotracheal intubation

7.1 and lactate level of 2.5 mmol/L. Blood count, renal and liver (OTI) was performed with subsequent artiﬁcial pulmonary

Fig. 1 – ECG shows broad QRS complex tachycardia.

e236 c o r e t v a s a 5 7 ( 2 0 1 5 ) e 2 3 4 – e 2 3 8

ventilation (APV), with the need for repeated cardiopulmonary When yew poisoning is suspected, toxicological screening

resuscitation (CPR). The patient's condition required a gradual relies on thin-layer chromatography and the detection of 3,5-

increase in catecholamine support. Due to severe bradycardia dimethoxyphenol, yet speciﬁcity is not 100%. During intoxica-

with a bizarre wide QRS complex temporary cardiac pacing tion, positive values of 3,5-dimethoxyphenol usually amount

was instituted. However, despite echocardiographic veriﬁca- to over 300 ng/mL [6]. Precise laboratory conﬁrmation requires

tion of correct insertion, this gradually lost effect. Lactate level direct detection of taxines by high-performance liquid

escalated to 9.1 mmol/L and pH could not be increased over chromatography in combination with mass spectrometry.

7.25, despite repeated slow boluses of 200 mL of 8.4% NaHCO3; The biological half-life of taxine metabolites ranges between

potassium level was decreasing below 3.3 mmol/L in spite of 11 and 13 h and after ingestion they may still be detectable

substitution. Haemodynamically the patient became severely even around 120 h following digestion [7].

unstable, receiving resuscitation doses of adrenaline with Due to the presence of the unsaturated lactone group, the

noradrenaline. The hemodialysis treatment administered had chemical structure of taxines is similar to that of digitalis,

no effect; the patient developed electromechanical dissocia- which may lead to false-positive results of digoxin testing.

tion followed by asystole and died at 8:00 p.m. Autopsy showed The time from ingesting a lethal dose to death is usually 2–

congestion of the brain and lungs where alveolar haemorrhage 5 h, with symptoms occurring from 30 min to 1 h following

was present. Except for dilated right heart chambers, no ingestion. Signs of yew poisoning are non-speciﬁc, including

remarkable macroscopic ﬁndings were noted in the heart. Yew nausea, vomiting, impaired colour vision, abdominal pain or

needles were found in the lumen of the small intestine. muscle spasms. Clinical symptoms include dilated pupils,

Common yew intoxication was subsequently conﬁrmed also dyspnoea, tachycardia in the earlier phase followed later by

by toxicological analysis of the stomach contents from the ﬁrst bradycardia, tonic–clonic convulsions, somnolence or even

lavage performed by the Emergency Medical Service. unconsciousness. ECG may show multiple extrasystoles at the

early stage of poisoning, followed by persistent ventricular

tachycardias and ventricular ﬁbrillation; preterminally, a

Discussion

bizarre, signiﬁcantly widened QRS complex with bradycardia

occurs. Terminally, electromechanical dissociation and asys-

The Common Yew (Taxus baccata) also known as the English tole follows. Laboratory tests usually show metabolic acidosis,

Yew or the European Yew, classiﬁed in the Taxaceae family, is both hypo- and hyperkalaemia, and hyponatraemia. Labora-

a medium-sized, evergreen tree growing to 10–15 m. Seven tory signs of renal or liver failure are not described and were

species occur over a large area of the Northern Hemisphere in not recorded in our patient either.

Europe, Asia, in the north of Africa, and 1 species is found in Digestion of yew needles is very slow (frequently found in

Indonesia. Yew is rare in the Czech Republic. Yew bark is the GIT during autopsy); absorption is accelerated by low

reddish-brown and scaly. Yew needles are arranged in two ﬂat gastric pH. Primary and essential therapy is gastric lavage

rows along twigs and live for approximately 8 years before performed as soon as possible before the patient is brought to

falling off. The Common Yew is dioecious, the male cones are hospital. The effect of administering bicarbonate by stomach

globose, and female ﬂowers are bud-like terminal ovules tube to alkalize digestive juices and, theoretically, to decrease

subtended by one or two pairs of bracts. The entire plant, with the absorption of taxines from the GIT into blood, was not

the exception of the red aril is poisonous as it contains taxine shown in an animal study and there is no evidence that its

alkaloids. The lethal dose for an adult is reported to be 50 g of administration would be beneﬁcial in humans. In several

yew needles. Historically, yew extracts were used as an cases, intravenous administration of bicarbonate by bolus

abortifacient and for assassination; yew wood was used for with subsequent continuous administration with dose adjust-

making bows and, when stained black, the timber, also known ment according to the actual level of blood pH was, along with

as German ebony, was used to make furniture. Today, due to the correction of metabolic acidosis, also effective in shorten-

their attractive appearance and rare occurrence, yews are used ing the QRS complex, followed by a good clinical response [8]. If

predominantly, if not only, as ornamental trees [1]. metabolic acidosis progresses and lactate increases despite

Yew alkaloids (taxines) have been known since the mid- maximum pharmacological intervention, a hemoelimination

19th century when Peretti performed chemical analysis of method ought to be initiated. In a Swiss case report, a patient

English Yew needles. It was not until the mid-20th century, with a temporary pacemaker receiving excessive doses of

however, that Graf and Boeddeker discovered that taxine was a catecholamines with progressing metabolic acidosis was

heterogenous mixture. Later on, spectrophotometry, chroma- treated with high-ﬂux hemoﬁltration with gradual catechol-

tography and infrared analysis made it possible to recognize amine support regression while the acid–base status was

two major types of taxine alkaloids – taxine A and taxine B [2]. returning to normal. The monitoring of taxine B concentra-

Gradually, the other isoforms and esters of the major taxines tions in this patient's haemoﬁltrate, serum and urine showed

were identiﬁed in further investigation such as isotaxine B or that taxine B, and thus probably also taxine A, cannot be

taxine I and II [3]. Taxine B is responsible for the greatest removed by dialysis and their elimination is only endogenous,

cardiac toxicity [4]. The mechanism of its effect involves the by zero-order pharmacokinetics. This may mean that the

elevation of cytoplasmic calcium in cardiac myocytes with cardiotoxicity of taxines is caused not only by direct Na/Ca

sodium and calcium channels antagonism. The effect is channel blockade, but also by a deleterious effect on the acid–

similar to that of verapamil. The cardiac speciﬁcity of taxines base balance [9].

is high. The gastrointestinal tract is affected to a far lesser Recurring malignant ventricular arrhythmias usually do

extent and the effect is not speciﬁc [5]. not respond to amiodarone administration; high doses of

c o r e t v a s a 5 7 ( 2 0 1 5 ) e 2 3 4 – e 2 3 8 e237

lidocaine are more effective [8]. If such treatment is not effective

Ethical statement

and the patient's consciousness is depressed due to the

development of cardiogenic shock, complex resuscitation

therapy is continued with OTI, APV with combined catechol- The authors conﬁrm that the work was done according to

amine support and external heart massage. When bradycardia ethical standards.

with hypotension occurs, external or transvenous temporary

pacemaking is fully indicated; however, with the progression of

Informed consent

the negative inotropic effect of taxines and the development of

electromechanical dissociation, this therapy also loses efﬁcacy.

At this point, most patients die, with the exception of patients in The patient cannot sign any informed consent due to his

whom the asystole has been managed using ECMO [10]. It is severe health condition, but he did not mention verbally any

documented that after the elimination of taxines, the myocar- disagreement with health care in the hospital nor did he

dial functions are recovered completely in surviving patients verbally deny permission to spread anonymous information

[11]. Chronic myocardial dysfunction due to necrosis followed about his case. I did not mention his name or information to

by ﬁbrosis was described in literature only after intoxication in avoid recognizing his identity in my work.

cattle [12]. In terms of comprehensive resuscitation care, a case

of effective combination of mild therapeutic hypothermia with

r e f e r e n c e s

mechanical external massage followed by ECMO institution and

continuation of mild therapeutic hypothermia with a resulting

good neurological status as well as cardiovascular functions is

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documented [13]. As regards comprehensive post-resuscitation

346.

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357–358.

condition improved. However, in these case reports, the

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toxicity in swine, Academic Emergency Medicine 9 (2002)

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–

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ﬂ

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None declared.

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Funding body

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