Fatal overdose of Taxus baccata plant matter treated in a rural district general hospital
- 1 Department of Anaesthesia, Queen Elizabeth Hospital King's Lynn NHS Foundation Trust, King's Lynn, UK
- 2 Department of Anaesthesia, Addenbrooke's Hospital, Cambridge, UK
- Correspondence to Dr Emma Vallis-Booth; evb93@doctors.org.uk
Abstract
A 25-year-old woman presented with cardiogenic shock following intentional overdose of Common Yew (Taxus baccata). The pharmacological mechanisms underlying yew toxicity resulted in failure of multiple treatment modalities including inotropes, vasopressors and attempted pacing. Resuscitation was ultimately unsuccessful. The limited literature available on this kind of overdose suggests that early extracorporeal membrane oxygenation (ECMO) is the mainstay of treatment in severe cases presenting with hypotension and arrhythmias. However, there may be a role for digoxin antibody fragments in maintaining patients presenting to remote sites, to allow transfer to a specialist centre.
Background
Common yew, also known as English yew, is a conifer that is native to Europe. Yew plant overdose is an uncommon presentation and usually occurs secondary to accidental ingestion in a paediatric population. Rarely, it may be the result of an intentional overdose. Toxicity is mediated by taxine alkaloids contained within all parts of the plant except the flesh of the berries.1 Taxine B is thought to be responsible for the majority of cardiotoxic effects seen after ingestion, mediated through sodium and calcium channel blockade. The lethal dose of common yew is not known in humans but is considered to be as low as 50 g of chopped leaves.2
Onset of symptoms is usually within 3–4 hours of ingestion. Patients typically present with bradycardia, broad complex arrhythmias and cardiogenic shock.1 3 There is no known antidote to yew poisoning and treatment aims are mainly supportive, with venoarterial (VA) ECMO being a mainstay of treatment in previous case reports. The National Poisons Information Service (NPIS) has limited information available on managing toxicity due to the rarity. This case and the subsequent literature review highlights the importance of early transfer to a centre capable of providing VA-ECMO, and the potential use of digoxin antibody fragments to stabilise the patient for transfer.
Case presentation
The ambulance service was called to a 25-year-old woman with no psychiatric history: the history was given as ‘collected yew berries and leaves … drank them as a smoothie’. Initially, she was alert and normotensive but en route to hospital she became haemodynamically unstable with a blood pressure of 47/30 mm Hg. She had two self-terminating episodes of ventricular tachycardia (VT) prior to arrival in the emergency department.
On our arrival the patient was maintaining her airway with saturations 99% on 15 L oxygen, respiratory rate 18 breaths per minute, blood pressure 93/56 mm Hg, heart rate 62 beats per minute and Glasgow Coma Score 10/15. An electrocardiogram (figure 1) showed a wide QRS complex rhythm with corrected QT of 660 ms. An initial arterial blood gas was entirely normal.
ECG on arrival of patient to the emergency department. Ventricular rate 72 beats per minute. QRS duration 153 milliseconds. Corrected QT 668 ms.
The rhythm then changed to a pulsed VT with loss of consciousness. A 150J synchronised DC shock was administered; which terminated the VT revealing an underlying wide complex bradycardia. This was initially treated with 600 µg boluses of atropine up to a total of 3 mg while further advice was sought.
Treatment
The NPIS was contacted for urgent advice. Unfortunately, they were unable to recommend any specific treatments except supportive management and early transfer to a centre capable of ECMO. We, therefore, liaised early with our local ECMO centre while continuing to support the patient’s physiology.
We administered 100 mL 8.4% sodium bicarbonate, 30 mg/kg intralipid, 10 mL 10% calcium gluconate and 1 mg epinephrine given as 100 µg boluses within the first 10 min of resuscitation. These measures did not improve the picture of cardiogenic shock with broad complex bradycardia interspersed with accompanying episodes of pulsed VT. A total of 3 DC shocks were given at 150J during episodes of VT.
Due to the worsening clinical picture the anaesthetic consultant performed a rapid sequence induction using propofol and rocuronium and the trachea was successfully intubated. Central venous access was obtained and invasive blood pressure monitoring initiated. Dobutamine was titrated to 40 µg/kg/min and norepinephrine titrated to 0.6 µg/kg/min (submaximal dose to try to minimise reflex bradycardia), in discussion with a cardiology consultant. Activated charcoal was given via a nasogastric tube.
We attempted transcutaneous pacing up to 135 mA without successful electrical capture. At this point the patient had deteriorated significantly, with a blood pressure 63/49 mm Hg and heart rate 15 beats per minute. Cardiac compressions were delivered by the LUCAS mechanical chest compression device. Arterial blood gas showed a metabolic acidosis (pH 7.23, lactate 7.7 mmol/L, base excess −9.5). An isoprenaline infusion, 2 g intravenous magnesium, 2 mg intramuscular glucagon and a second bolus of 30 mg/kg intralipid improved the clinical picture to the point where compressions were halted.
The patient was too unstable for transfer to our local ECMO centre, and VA-ECMO is not locally available on a portable basis. We, therefore, transferred the patient to theatre to make an attempt at transvenous pacing. A pulmonary artery catheter introducer sheath was inserted into the right femoral vein, but prior to pacing wire insertion the patient went into pulseless VT and resuscitation following the Advanced Life Support algorithm was commenced. Arterial blood gas showed a severe metabolic acidosis (pH 7.185) despite a reduction in lactate to 4.6 mmol/L. Six cycles of cardiopulmonary resuscitation demonstrated pulseless VT, following this the rhythm deteriorated to pulseless electrical activity and then asystole over the following 4 min. The decision was taken to stop resuscitation was taken 45 min after cardiac arrest in theatre.
Discussion
Taxine alkaloids A and B cause sodium channel antagonism within myocardial cells, leading to QRS widening and arrhythmias (most commonly VT). They also inhibit L-type calcium channels which are present in cardiac and smooth muscle leading to reduced cardiac contractility and vasodilatation causing profound hypotension.1 3
Onset of symptoms is usually within 3–4 hours of ingestion. Patients typically present with bradycardia, broad complex arrhythmias and cardiogenic shock.1 3 There is no known antidote to Yew poisoning and treatment aims are mainly supportive. The main aims of treatment include:
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Prevention of absorption of plant matter from the gastrointestinal tract.
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Reduction of fraction of free drug.
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Stabilisation of the myocardium to prevent arrhythmias.
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Treatment of arrhythmias and hypotension.
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Correction of acid–base balance and electrolyte disturbance.
Intralipid is becoming increasingly well recognised as a treatment for significant drug toxicity. Its mechanism of action is thought to be by the formation of a ‘lipid sink’ into which lipid soluble drugs dissolve, preventing their action at target sites within the body.4 It is also thought to improve myocardial contractility in cases of drug induced myocardial depression, via the provision of fatty acid substrates. Taxines are lipid soluble,1 and therefore, have the potential to dissolve in intralipid, reducing the fraction of free drug available to cause toxic effects.
In addition to its well-characterised role offsetting metabolic acidosis, 8.4% sodium bicarbonate also contains a significant sodium load (1000 mmol/L). It is, therefore, useful in sodium channel blockade to overcome competitive inhibition at the ion channel, which has the effect of stabilising cardiac myocytes. Glucagon, calcium gluconate and magnesium also have precedent in stabilisation of the myocardium.
The use of atropine in treating bradycardia caused by sodium and calcium channel blockade is likely to be less effective as its action is mediated via parasympathetic blockade which is above the level of the ion channel block. Beta 1 receptor agonists may have an increased role as they can help to overcome competitive inhibition of calcium channels by increasing intracellular calcium levels, though we did not note an improvement in this case. Calcium channel blockade also prevents cardiac muscle contraction even in the presence of electrical stimulation, and prevents propagation of a stimulated action potential. We were unable to achieve pickup during transcutaneous pacing and other cases in the literature5 6 show that limited success has been achieved in these cases with transvenous pacing. The physiological picture of widespread sodium and calcium channel blockade at the level of the cardiac myocyte explains the poor response of our patient to chemical and electrical management of bradycardia.
A review of case reports of substantial overdose of Taxus baccata demonstrated that five of ten cases which survived were treated with VA-ECMO. This was also recommended by NPIS but represents a challenge to district general hospitals without immediate access to ECMO facilities. However, it was noted that four patients were also successfully treated with digoxin-specific Fab antibody fragments.
Digoxin specific Fab is immunoglobulin fragments from sheep that have been immunised with a digoxin derivative. It has a higher affinity for digoxin than the sodium-potassium ATPase pump receptor site hence creates a concentration gradient that extracts digoxin from the intracellular space. Due to taxine B being a glycoside with similar structure to digoxin it is proposed that digoxin specific Fab or an equivalent may be effective in clearing taxine B from receptors. This was demonstrated in one case report7 which showed that serum concentration of taxine (including the fraction bound to Fab fragments) was shown to increase following the administration of digoxin specific Fab. This is suggestive of preferential binding of taxines to the Fab fragments compared with the sodium and calcium channel receptors.
Administration of digoxin specific Fab was not recommended to the treating team by NPIS at the time of the patient’s presentation, but may be a useful addition to the supportive treatment algorithm in cases where VA-ECMO is not immediately available. Digoxin specific Fab is often obtainable locally and may buy time for transfer to a specialist centre to allow ECMO to be commenced.8
Clearance of taxines from the systemic circulation obeys zero order kinetics and is not achieved by haemofiltration.9 Renal failure often complicates resuscitation in cases where the initial efforts are successful, due to the profound hypotension accompanying the initial presentation. This can prolong or prevent recovery in patients even following the resolution of arrhythmia. Fab-digoxin complexes are renally cleared via first order kinetics,10 and a similar mechanism is hypothesised for Fab-taxine fragments. Though haemofiltration does not improve clearance of Fab-taxine fragments, analysis of dialysate does show that it can be filtered, unlike taxines. Treatment with digoxin-specific Fab could, therefore, offer a way to reduce serum taxine concentrations in cases of renal failure following overdose.
Learning points
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Yew tree overdose is rare but the consequences are life-threatening.
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Venoarterial (VA)-ECMO is a mainstay of supportive treatment to allow time for excretion of taxines.
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In remote centres where VA-ECMO is not available intralipid and digoxin antibody fragments represent important temporising measures which are normally locally available to stabilise a patient for transfer.
Ethics statements
Patient consent for publication
Acknowledgments
With thanks to Dr S Greenhill, who supervised the clinical management of the patient. The authors would also like to thanks Victoria Howell and Stuart Greenhill, consultant anaesthetists at the Queen Elizabeth Hospital King's Lynn.
Footnotes
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Contributors EVB has contributed to the design of the work, the data interpretation and the wider clinical review; in addition to approving the final version to be published. SM contributed to the design of the work, the clinical review and the data interpretation.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
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