Circuitous diagnosis in concealed self-poisoning with Nerium oleander*

To the Editor:

A 60-year-old male prisoner, with a known history of depression, collapsed while walking in the garden of the prison. At examination, the physician noted that he complained of gastrointestinal discomfort, nausea, abdominal pain and cold sweat. His blood pressure was 90/60 mmHg, heart rate 64 beats per minute and Glasgow Coma Scale score 11. There were no signs of seizure. The first diagnosis suspected by the physician was an acute myocardial infarction. An electrocardiography (ECG) was performed, which excluded this cause. Deliberate self-poisoning was not at first suspected because the patient had consistently refused antidepressant treatment and was not taking any other drug. He was followed by a psychiatrist once a month. The patient was transported under medical supervision to the emergency department. After admission, he continued to vomit without chest pain. Abdominal palpation showed epigastric tenderness without guarding or tenseness. His condition abruptly worsened with mental confusion, weakness and bradycardia with sino-atrial node block and junctional escape rhythm leading to isorhythmic dissociation (Fig. 1). Mechanical ventilation with 8 ml/kg tidal volume under fraction of inspired oxygen (FiO₂) 60% was initiated. Bradycardia was corrected by administration of two boli doses of atropine (1 mg). A contrast-enhanced brain scan excluded a cerebrovascular accident. Toxicological screening revealed no poisons (tricyclic antidepressants, paracetamol, benzodiazepines, carbamates or barbiturates). However, digoxin level was 0.87 μg/l (therapeutic range 0.6–1.2 μg/l), although this drug had not been prescribed to the patient. Blood chemical findings showed hyperkalaemia at 5.8 mmol/l treated with sodium bicarbonate (1.4%, 500 ml) within 30 min. Sodium and magnesium were normal. Urine samples showed no poisons. In view of these laboratory results, the prison physician was requested to conduct an inquiry into the cause. The prison cell was searched for empty drug containers, and the prisoner who shared the cell was interrogated. The patient was given digoxin-specific Fab antibody fragments intravenously to treat digoxin poisoning at a dose of 160 mg in infusion over 20 min. The electrocardiogram, metabolic disturbances and haemodynamic parameters became normal. After 3 days in intensive care, the patient stated that every day for several days before the episode, he had consumed oleander leaves that he had picked in the prison garden, with suicidal intent.

Fig. 1. Sinus node bradycardia with sino-atrial block and junctional rhythm escape. Wide QRS (130 ms) with right block bundle branch block and left anterior hemiblock. Heart rate: 39 beats/min.

Digoxin was assayed on the Dimension® (Siemens, Saint-Denis, France) clinical chemistry system, using an immunoassay technique in which free and digoxin-bound antibody-enzyme species are separated using magnetic particles. The sensitivity of this method, defined as the lowest concentration of digoxin that can be distinguished from zero, is fixed at 0.06 μg/l. The results of toxicological analyses led to the diagnosis of digoxin poisoning. The pathophysiological mechanisms of N. oleander poisoning have been well described in the literature.¹ It is important to remember that the toxicity of the glycosides contained in the plant is similar to that of digitalis glycosides, which inhibit plasma membrane Na ⁺ /K ⁺ -ATPase and result in increased intracellular calcium.² The increase in intracellular Ca^{2 +} ions also raises the resting membrane potential of the cell, leading to increasing rates of spontaneous cellular depolarisation and myocardial automaticity.³ Recently, methods for the identification and quantification of oleandrin in biological matrices have been described. These include immunoassays using chemiluminescence (ACS), radiolabelling (RIA), and fluorescence polarisation (FPIA) as detection systems.^4,5 Oleandrin may be detected in blood by high-performance liquid chromatography and mass spectrometry (HPLC/MS), but this expensive technique was not available in our teaching hospital.⁶ In our case, the positive blood test results for digoxin can be explained by cross-reactivity between digoxin and oleandrin. The first limitation in our management of the patient was the impossibility of quantifying the plant toxin because the measurement technique was not available in our institution. The second limitation was that the physicians did not establish the diagnosis of plant poisoning. Following their reasoning of digoxin poisoning, the treatment initiated was in accordance with expert opinion⁶ and consisted of the administration of equimolar doses of Digibend^® at a dose of 160 mg in intravenous infusion for 20 min. This treatment led to an improvement in the patient's condition.

Anti-digoxin Fab fragments are now considered first-line therapy for severe digoxin poisoning in patients with life-threatening dysrhythmias, cardiogenic shock and hyperkalaemia. Treatment is guided by clinical status and should not be based on measured digoxin blood levels, which are not correlated with the severity of poisoning. In our case, the dose given to treat the supposed digoxin poisoning was lower than the doses recommended in the literature for N. oleander poisoning.^1,7 Higher doses are required with oleandrin poisoning because the antibody has lower binding affinity with natural cardiac glycosides. However, lower doses have been administered with a favourable clinical outcome.^3,8 Such an approach would have to be studied carefully to determine whether small doses of Fab fragments do reduce the number of deaths or simplify further patient management.⁷

Diagnosis of poisoning by N. oleander is difficult because it is very rare in France, particularly in a prison context. In regions where the oleander is a common plant, physicians should be aware of the possibility of oleander poisoning if patients present severe cardiac manifestations and ECG abnormalities similar to digoxin toxicity. Moreover, the medico-legal consequences of such poisoning in a prison context require particular attention.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.