Yellow oleander (Thevetia peruviana) is a common shrub found in tropics. It belongs to Apocyanaceae family. It is used as an agent for deliberate self harm especially in rural areas of South India and Srilanka.[1,2,3] All parts of the plant are toxic and contains variety of cardiac glycoside. These include Thevetin A, ThevetinB, Oleandrin, Neriifolin and other unidentified toxins.[4] Ingestion of yellow oleander causes symptoms like nausea, vomiting, abdominal pain, bradycardia, diarrhea, arrhythmias etc. These symptoms are similar to digitalis toxicity.[5,6] Hyperkalemia is the commonest electrolyte abnormality observed. Cardiac toxicity is the commonest life threatenening toxicity. Cardiac glycosides in yellow oleander poisoning will alter the properties of cardiac muscles such as automaticity, rhythmicity, conductivity and contractility. Slowing of automacity can lead to sinus bradycardia, alteration in rhythmicity can lead to sinus bradycardia with junctional escape rhythm, AV Dissociation, Escape rhythm without sinus activity. Bradycardia, atrioventricular blocks, atrial tachy cardia, ventricular tachycardia including bidirectional tachycardia, ventricular fibrillation are the cardiac arrhythmias that can develop in these persons. Direct myocardial depression with hypotension can also be a manifestation. The arryhthmogenic effects of the cardiac glycoside is due to direct effect of toxin on the myocardium and the conducting system of heart and also due to increase in neurally mediated autonomic activity. Cardiacglycosides exert their cardiotoxicity through mediators like histamine, leukotriene, nitricoxide, endothelin, angiotensin and superoxide radicals. The clinical management of yellow oleander poisoning involves stomach wash, supportive care, correction of electrolyte disturbance and temporary pacemaker support in case of severe bradycardia. This study is conducted to provide the clinical profile and treatment outcome of patients admitted with yellow oleander poisoning in a teritiary care centre in South India.

Patients and settings Adult patients with a diagnosis of yellow oleander poisoning, between January 2022 and December 2023 requiring admission to a medical ward, the Medical ICU, or high dependency unit (HDU) of a teaching hospital of GMC Palakkad are included in the study. The patients were identified from the data extracted from inpatient medical records. A diagnosis of yellow oleander poisoning was made when a patient presented with an alleged history of consumption of yellow oleander seeds and exhibited clinical symptoms of yellow oleander toxicity. A detailed history of the number of seeds consumed, time of consumption, time of presentation to hospital, and any form of treatment given prior to presenting to the hospital were documented. Physical examination findings including vital signs like pulse, blood pressure and oxygen saturation were noted from the case records. The results of routine blood tests were noted including complete blood count, liver function tests, renal function tests, and electrolytes. Heart rate, ST-T changes, and rhythm abnormalities from the baseline electrocardiogram (ECG) and serial ECGs subsequently taken were also noted. Treatment outcomes were noted as cured , died, referred. Patient Management and outcome parameters All patients were managed with supportive therapy. This included fluid resuscitation, correction of dyselectrolytemia, hemodynamic support as and when needed, management of cardiac rhythm abnormalities etc. The outcomes of interest were duration of hospital stay, electrolyte abnormalities, ECG changes and mortality. Ethical approval and funding This retrospective observational study protocol was approved by the Institutional Ethics Review Board, Government Medical College, Palakkad. The data for the study was collected from inpatients medical records and collected information was anonymized. Statistical analysis Descriptive statistics were employed for all the variables in the study. All continuous data were expressed as mean with standard deviation. Statistical analysis was done using Statistical Package for Social Sciences for windows.(SPSS Inc version 16)

Baseline Characteristics The study comprised of 64 patients. 46(71.8%) patients were males and 18(28.1%) patients were females. Male to female ratio was 2.55:1. The mean age in years of the patients was 32.66 ±8.31 (mean ±SD).The average time between consumption of yellow oleander and presentation to the hospital was 5.41± 2.16 hrs. Out of 64 patients included in the study 49 (76.56%) patients got admitted to the study centre within 6 hours of consumption of poison,12 (18.75%) patients presented to the study centre within 6-12 hours and 3 (4.68%) presented beyond 12hrs. The number of seeds consumed ranged from 2 to 12 seeds with a median of 4 seeds. 43 patients received treatment in a primary or secondary care centre before presenting to the study centre. All these 43(100%) patients received gastric lavage at the centre where they initially presented for treatment. 6(9.37%) patients received atropine and 14(21.87) patients received IV fluids. On presentation at the study centre 64 (100%) patients received gastric lavage. The commonest symptom at presentation was vomiting in 51 (79.6%) patients, nausea in 10(15.6%), giddiness in 18 (28%) patients. The laboratory parameters at presentation included serum sodium levels were 137.82± 2.59and potassium levels 4.61±0.63(mean±SD)mmol/L. Random blood sugar was 108.84±48.64.The creatinine levels were 0.86±0.29(mean±SD).The demographic charecteristics,laboratory parameters and symptoms at presentation are given in Table 1 Table 1. Demographic,symptoms and laboratory parameters of patients with oleander poisoning ( n-64) Characteristics Number (n) Value Demographic Age,mean (SD) years 64 32.66(8.33) Gender ratio (Male: Female) 64 46:18 Number of seeds consumed Median(IQR) 61 4(3-5) Symptoms Vomiting 64 51 (79.6%) Nausea 64 10(15.6%) Giddiness 64 18 (28%) Laboratory Parameters Sodium,mean(SD) mmol/L 64 137.82(2.59) Potassium,mean(SD)mmol/L 64 4.61(0.63) Random blood sugar mg/dl 64 108.84(48.64) Creatinine mg/dl 64 0.86(0.29) ECG Parameters Normal ECG was found in 36 patients (56.25%) .Of the 28(43.75%) patients with abnormal ECG the commonest abnormality was sinus bradycardia in 12 (18.75%) patients, followed by first degree AV block in 6 (9.3%) patients, 4(6.25%) developed complete heart block and 1(1.56%) had RBBB. T wave abnormality was seen in 5(7.81%) patients. Table 2 ECG changes in patients with yellow oleander poisoning (n=64) Normal ECG 36(56.25) Sinus Bradycardia 12(18.75) First Degree AV block 6 (9.3) Third Degree Av block 4(6.25) RBBB 1 (1.56) T wave abnormality 5 (7.81) Outcomes. 6 patients who developed first degree heart block were treated in Intensive Care Units with atropine injection and isoprenaline infusion with continuous monitoring of heart rhythm. All of them recovered with medical management. 12 patients with sinus bradycardia were treated with orciprenaline tablet and atropine injections (used when HR˂50). 4 patients with complete heart block were referred to higher centre where they received temporary pacemaker support and recovered. The mean±SD duration of hospital stay in patients was 5.27±1.62 days. The overall hospital mortality in our study was zero.

Yellow oleander poisoning is a common form of plant poisoning in South Asia. The plant is widely prevalent in the South Asian tropical region. Easy availability of the plant makes it one of the preferred choice for deliberate self harm by patients. All parts of plant are toxic and leaves and seeds are most commonly consumed by the patients. Gastrointestinal symptoms like nausea and vomiting were the commonest presenting symptom. Hyperkalemia was the most common electrolyte abnormality found in our study. The commonest abnormal ECG finding was sinus bradycardia. Some other studies have shown Mobitz type II block as the commonest ECG abnormality. This is similar to Digoxin toxicity,[7] in which inhibition of Na+/K+ ATPase pump occurs, leading to increased intra cellular concentration of Ca2+ and Na+.[9] Management of yellow oleander poisoning is by supportive measures like maintenance of fluid and electrolyte balance,including prompt correction of dyselectrolytemia[10,11] and temporary pacemaker insertion as and when needed. Use of activated charcoal and digoxin specific antibody fragments are also used as specific therapy. Activated charcoal prevents the absorption of toxin from the gut and interrupts the entero hepatic circulation of cardiac toxin facilitating gastric elimination.[10,12] In a clinical trial by De silva et al use of activated charcoal at a dose of 50gm every 6hrs for 72 hrs caused significant decrease in mortality and occurrence of fatal arrhythmias[13]. But in a major trial by Eddleston et al use of multidose activated charcoal did not show mortality benefit. Clinical trials have failed to demonstrate consistent benefits in using acitivated charcoal regarding mortality benefit[14]. In the institution where the study was conducted activated charcoal was not used in the management as it was not available. Digoxin specific antibody fragments are specific for neutralizing the cardiac glycoside toxins.[10,11] These are found to be effective in successfully reversing the occurrence of cardiac arrhythmias, resulting in decrease in mortality[15,16,17]. A single dose of 1200mg is used in such patients[16,17]. High cost and non availability are the two factors which prevents its regular use in developing countries. Patients with bradycardia are initially managed with atropine or isoprenaline infusion with continuous ECG monitoring. Theoretically such treatments can increase the risk of tachyarrhythmias especially with co existing electrolyte imbalance. Tachyarrhythmias are difficult to treat and can lead to poor prognosis. Temporary pacemaker is the treatment of choice in patients with significant bradycardia ie heart rate less than 40 beats per minute, with heart block or sick sinus syndrome. Currently no guidelines are available for the insertion of temporary pacemaker in yellow oleander poisoning. Temporary pacemaker is lifesaving in yellow oleander poisoning with life threatenening bradyarrhythmias. In developing countries such a facility is usually available in tertiary care teaching institutions, needing referral of such patients to those centres from other healthcare facilities. Hemodialysis and hemoperfusion has no role in the treatment of acute yellow oleander poisoning.[19] The proportion of our patients requiring Temporary Pacemaker Insertion was 4 (6.25%) is similar to earlier studies(6%)[20]. Patients with abnormal ECG findings and bradycardia are more likely to receive TPI. No mortalities were described in our cohort. The usual reported mortality is around 6% in other studies.[5,21,22] In developing countries where treatment with Digoxin antibody fragments are non available or unaffordable, early identification, gut decontamination, correction of fluid and electrolyte imbalance, use of positive chronotropic agents like atropine and isoprenaline under careful monitoring and TPI in patients with severe bradycardia (HR≤40)or complete heart block can improve outcomes in patients with yellow oleander poisoning. In one study TPI did not have added mortality benefits and prolonged duration of hospital stay. Yellow oleander poisoning does not seem to have any long-term sequelae and patients do well after complete recovery. All our patients were provided with psychiatric support after recovery from poisoning before discharge from the centre.

Acute yellow oleander poisoning is common in rural areas of South India.ECG changes and dyselectrolytemia were common in these patients. Early identification of poisoning, gut decontamination, maintenance of fluid and electrolyte balance and TPI in patients with severe bradycardia or varying degrees of heart block can improve the outcome.

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