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Journal of Electrocardiology 44 (2011) 470 – 472 www.jecgonline.com
Electrocardiographic changes during inhalational oleander toxicity☆ Subramanian Senthilkumaran, MD, a,⁎ Ramachandran Meenakshisundaram, MD, b Andrew D. Michaels, MD, MAS, c Ponniah Thirumalaikolundusubramanian, MD b b
a Sri Gokulam Hospitals and Research Institute, Salem, India Chennai Medical College Hospital and Research Center, Irungalur, Trichy, India c St. Joseph Hospital, Humboldt Medical Specialists, Eureka, CA, USA Received 21 October 2010
Inhalational oleander toxicity was considered in a family of 4 by history of exposure to smoke from burning oleander twigs. Electrocardiography revealed first- and second-degree atrioventricular block with digoxin-like ST–T-wave changes, suggestive of oleander toxicity in the absence of exposure to digoxin or other herbal medicines, and without systemic illness. Complete blood count, biometabolic profile, chest x-ray, and echocardiography did not reveal any abnormalities. Electrocardiographies normalized within 4 days when kept away from offending agents. Because oleander plant materials are used for burning, people are exposed to inhalational oleander toxicity. Hence, practitioners shall consider such poisonings in them. © 2011 Elsevier Inc. All rights reserved.
Biomass smoke; Environmental hazard; Inhalational toxicity; Plant toxin; Oleander; Cardiac Glycoside; Conduction defects; ECG changes
Introduction The burning of wood is the oldest source of domestic energy for cooking, heating, and lighting since ancient times. Harmful effects including pulmonary and cardiovascular diseases secondary to exposure to biomass smoke have been documented.1 Here we report 4 members of a family who presented with features of oleander toxicity with positive digoxin assay following inhalation of smoke from the burning of scavenged oleander twigs. Case report A 32-year-old female agriculture worker (index case) from a village near Salem in the state of Tamil Nadu in India presented to the emergency room with a history of generalized weakness and dizziness of 2 days with a syncopal episode. There was no history of fever, chest pain, palpitations, or any known allergic disorders. She was not on any other medications. She was living with her husband and 2 children. Otherwise, her medical history was ☆
None of the authors have a conflict of interest to report. ⁎ Corresponding author. Department of Accident, Emergency and Critical Care Medicine, Sri Gokulam Hospital and Research Institute, Salem, Tamil Nadu 636004, India. E-mail address: [email protected]
0022-0736/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2010.12.002
not significant. On examination, she was conscious and stable. There was no pallor, clubbing, pedal edema, or evidence of hypothyroidism/hyperthyroidism. She had a pulse rate of 36 beats/min (irregular), blood pressure of 70/40 mm Hg, respiratory rate of 14/min, and cannon waves in the neck. She was afebrile, and her room air oxygen saturation was 96%. Auscultation revealed no murmur or gallop. Systemic examination did not reveal any abnormalities. Her resting electrocardiogram (ECG) showed sinus rhythm with low ventricular rate due to second-degree type I (in view of narrow QRS) atrioventricular heart block (Fig. 1). Transcutaneous pacing pads were applied. Laboratory findings showed a normal hemogram, serum biochemistry, and urinalysis. Serum sodium, calcium, magnesium, phosphorus, potassium, troponin T, and thyroid function tests were within normal limits. Her human immunodeficiency virus status was seronegative, and her echocardiogram was within normal limits. She reported that her son (8 years) and daughter (14 years) also had a sense of weakness. Examination among them revealed irregular pulse with a rate of 40 and 42 beats/min, respectively. Electrocardiogram of the boy showed sinus bradycardia with second-degree block (Fig. 2), and the girl had first-degree atrioventricular block (Fig. 3). This had raised a doubt whether there could be a common source, preferably a poison. Husband of the index case (father of the children) was asymptomatic and involved in
S. Senthilkumaran et al. / Journal of Electrocardiology 44 (2011) 470–472
Fig. 1. 12-Lead ECG of the mother.
manual work. He had pulse rate of 48 beats/min with occasional premature atrial complexes. He had a sinus node rate of about 60/min in the ECG with a speed of 25 mm/s. His ECG showed diffuse ST depression in lateral leads with a short QT interval suggestive of cardiac glycoside toxicity. Each family member had normal hematology, blood chemistry, and echocardiography. All 4 were free from any muscular or systemic disorders. The family members were certain that they have not taken any prescription or over-the-counter medications, digoxin, oleander, or any other herbal medicines. Serum radioimmunoassay for digoxin was carried out and revealed digoxin levels in the mother, son, daughter, and father of 8.69, 5.24, 4.65, and 3.98 mmol/dL, respectively. On careful interrogation, she disclosed that she used dry oleander twigs as domestic energy source for the past 3 months. The patients
were started on multidose activated charcoal orally for a day. The final diagnosis was drug-induced atrioventricular block probably due to inhalational oleander toxicity. Our diagnosis was supported by normalization of the rhythm within 4 days. All patients remained symptom free with the absence of offending agents. Discussion All parts of the oleander plant either fresh or dried contain highly toxic cardenolides, including thevetin A, thevetin B, neriifolin, and peruvoside, which are structurally and functionally similar to that of classic digitalis glycosides.1 Their poisonous effect and toxicity following oral2 and cutaneous3 route have been documented. Indeed, reports on primary intoxication due to inhalational
Fig. 2. 12-Lead ECG of the son.
S. Senthilkumaran et al. / Journal of Electrocardiology 44 (2011) 470–472
Fig. 3. 12-Lead ECG of the daughter.
oleander toxicity could not be obtained to the best of our ability. Electrocardiographic changes are the most obvious markers of yellow oleander toxicity. It may produce myriad ECG changes, similar to cardiac glycoside toxicity. There was no history of oleander ingestion with any symptoms or signs consistent with oleander toxicity. The diagnosis4 was further substantiated by the detection of “digoxin” by radioimmunoassay for digoxin. In view of cross-reactivity between the various antibodies used in the radioimmunoassay and the different cardiac glycoside present in oleander, digoxin assays quantitatively confirm the suspected diagnosis of oleander exposure5 but cannot indicate its severity. Multiple lay print media have reported that poisoning may occur by consuming food cooked on Nerium oleander branches either due to accidentally stirring of the food with the oleander stem or smoke settling on cooked foods, although all 4 family members reaffirmed that they never stirred with the oleander twigs and all vessels were covered with a lid during and after cooking. To rule out the likelihood of oral ingestion through food, the cooked food material and drinking water from their house were subjected for toxicologic analysis, which was negative for oleandrin. The smoke generated from burning oleander twigs may have a complex mixture of a large number of gaseous and particulate components along with highly toxic cardenolides, which are not even lost on drying6 or burning. Inhalation of these toxic agents may produce injury in the respiratory tract, extending from the nose to the alveoli. The toxins may have crossed the alveolar capillary membrane or airway cells by transcytosis rather than paracellular movement. The contributory factors are the intensity and duration of the exposure, particle size, water solubility of the agent, and microinjuries in the airway.7 All 4 members of the family were exposed to the effects of smoke as they lived in a poorly ventilated single room for living and cooking. The mother was exposed to smoke averaging 4 to 6 hours every day, which might have contributed to greater toxicity due to intensity and duration.
Variations in the degree of toxicity observed among case series were supported by previous reports. Limitations Limitations include non-demonstration of components of oleander in the blood and biomass smoke. Hence, further experimental studies are suggested to ascertain inhalational oleander toxicity. Conclusion Physicians should be aware of the various ways people are exposed to nonpharmaceutical cardioglycoside while handling a case of conduction disorders. The cardenolides are more abundant in nature, which is highly toxic. Oleander is also known to hold its toxicity even after drying and burning. Rural people should be discouraged in using oleander plant material for burning purposes either at home or at public places. Acknowledgment We thank Dr K. Arthanari, MS, for his logistic support. References 1. Radford D, Gillies A, Hinds J, Duffy P. Naturally occurring cardiac glycosides. Med J Aust 1986;144:540. 2. Langford S, Boor P. Oleander toxicity: an examination of human and animal toxic exposures. Toxicology 1996;109:1. 3. Senthilkumaran S, Saravanakumar S, Thirumalaikolundusubramanian P. Cutaneous absorption of oleander: fact or fiction. J Emerg Trauma Shock 2009;2:43. 4. Dasgupta A, Datta P. Rapid detection of oleander poisoning using digoxin immunoassays: comparison of five assays. Ther Drug Monit 2004;26:658. 5. Osterloh J, Herold S, Pond S. Oleander interference in the digoxin radioimmunoassay in a fatal ingestion. JAMA 1982;247:1596. 6. Ada S, Al-Yahya M, Al-Farhan A. Acute toxicity of various oral doses of dried Nerium oleander leaves in sheep. Am J Chin Med 2001;29:525. 7. Zelikoff J, Chen L, Cohen M, Schlesinger R. The toxicology of inhaled woodsmoke. J Toxicol Environ Health B Crit Rev 2002;5:269.