ARTICLES THE LANCET • Vol 355 • March 18, 2000 967 Summary Background Severe cardiac glycoside cardiotoxicity after ingestion of yellow oleander seeds is an important problem in rural areas of Sri Lanka. Currently, patients must be transferred to the capital for temporary cardiac pacing. We did a randomised controlled trial to investigate whether anti- digoxin Fab could reverse serious oleander-induced arrhythmias. Methods After a preliminary dose-finding study, 66 patients who presented to hospital with a serious cardiac arrhythmia were randomised to receive either 1200 mg of anti-digoxin Fab or a saline placebo. A 12-lead electrocardiogram, 3 min rhythm strip, and blood sample for measurement of electrolytes and cardiac glycosides were taken before treatment and at 12 timepoints thereafter. Findings 34 patients received anti-digoxin Fab and 32 received placebo. The presenting arrhythmia had resolved completely after 2 h in 15 antibody-treated patients and two controls (p<0·001); 24 and five patients, respectively, were in sinus rhythm at 8 h (p<0·001). Kaplan-Meier analysis of time to first reversal showed a significant response to anti- digoxin Fab. The heart rate increased in cases, from 49·1 per min at baseline to 66·8 at 2 h, but not in controls (50·6 per min at baseline to 51·5; p<0·001). Mean serum potassium concentrations decreased from 4·9 mmol/L to 4·1 mmol/L at 2 h in cases; no such decrease occurred in controls. Interpretation Anti-digoxin Fab fragments are a safe and effective treatment for serious cardiac arrhythmias induced by yellow oleander. Their use in small rural hospitals in Sri Lanka should minimise costly transfer of patients and reduce the numbers of deaths; however, further study will be required to confirm this reduction. Lancet 2000; 355: 967–72 Introduction Ingestion of sufficient quantities of any part of the common (Nerium oleander) or yellow (Thevetia peruviana) oleander can produce a syndrome similar to digoxin poisoning. 1,2 Accidental oleander poisoning occurs throughout the tropics and subtropics: 303 cases were reported in Texas during 1994 1 and oleander caused 27% of the paediatric plant poisonings in Australia during 1972–78. 3 Fatal poisonings have been reported from across the world. 4–10 Deliberate self-poisoning with yellow oleander is a recent phenomenon in Sri Lanka. The first cases occurred in Jaffna between 1981 and 1983, after publicity surrounding the suicide of two girls who ingested oleander seeds. 11 In some areas, 40% of self-poisoning cases are now linked to oleander seeds, particularly in teenagers, with an annual incidence of more than 150 per 100 000. 12,13 This epidemic imposes a substantial burden on the Sri Lankan health services. The most severely affected patients are transferred to the coronary-care unit (CCU) of the Cardiology Institute in Colombo for cardiac pacing. 12 The transfer is long and hazardous, commonly taking more than 4 h. Patients die before and during transfer to the CCU; some die soon after arrival. Standard therapy in the CCU is to observe patients and then insert a pacemaker in those with marked arrhythmias. There is a pressing need for a treatment that can be used in small peripheral hospitals. Polyclonal anti-digoxin Fab fragments are recommended for the treatment of life- threatening cardiac glycoside poisoning. 14,15 Although this recommendation for digoxin poisoning is based on a large open-label multicentre study, 16 the use of these fragments in poisonings by other glycosides is based solely on case reports, commonly with poor results. 17–22 We assessed the efficacy and safety of anti-digoxin Fab fragments in patients with cardiac arrhythmias induced by yellow oleander. Methods Patients The study was designed in two parts: a dose-finding study to identify an effective dose of anti-digoxin Fab; and a randomised, double-blind, placebo-controlled trial of this dose in the treatment of oleander-induced cardiotoxicity. The trial was reviewed by the ethics review committee of Colombo University’s Faculty of Medicine and done with the approval of the Sri Lankan Health Authorities. Patients admitted to the Cardiology Institute with a history of yellow-oleander ingestion were included in the study if they showed electrocardiographic (ECG) evidence of sinus bradycardia (<40 per min), sinus arrest or block, atrial tachyarrhythmias, or second or third degree atrioventricular block. Patients were excluded if they had hypotension (systolic blood pressure <80 mm Hg), bradycardia, or ventricular tachycardia together with signs of shock. Excluded patients were given anti-digoxin Fab immediately on a compassionate basis. Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomised controlled trial M Eddleston, S Rajapakse, Rajakanthan, S Jayalath, L Sjöström, W Santharaj, P N Thenabadu, M H R Sheriff, D A Warrell Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK (M Eddleston BM, Prof D A Warrell FRCP); Department fo Clinical Medicine, University of Colombo, Sri Lanka (S Rajapakse MD, Rajakanthan MRCP, S Jayalath MB, Prof M H R Sheriff FRCP); Institute of Cardiology, National Hospital of Sri Lanka, Colombo, Sri Lanka (Rajakanthan, W Santharaj MRCP, P N Thenabadu FRCP); and Protherics, London EC1 7HN, London, UK (L Sjöstruøm PhD) Correspondence to: Prof D A Warrell, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK (e-mail: david.warrell@ndm.ox.ac.uk)