Case Reports Sea Mango Cardiac Intoxication Acta Cardiol Sin 2008;24:56-9

Sea Mango Cardiac Intoxication

Ping-Chang Liu, Min-Hui Liu, Shu-Yi Chen, Wen-Jin Cherng and Chao-Hung Wang

Cerbera manghas (sea mango) is one of the poisonous belonging to the family notorious for its cardiac glycoside cardiotoxicity. The and the of sea mango are easily accessible along the coast of Taiwan. We present a case of a 50-year-old male who attempted suicide by ingesting three seeds of the sea mango. The patient was admitted to the coronary care unit because of complete atrioventricular block, followed by sinus exit block. All conduction abnormalities subsided 3 days later with temporary transcutaneous pacing and supportive treatment. He was discharged with no complications.

Key Words: Sea mango · Cardiac toxicity · manghas

INTRODUCTION ture review and suggestions for management.

The ingestion of with cardiac glycoside car- diotoxicity is not uncommon in countries including Sri CASE PRESENTATION Lanka and India.1,2 In Taiwan, especially along coastal regions, sea mango ()isaverycom- A 50-year-old male presented to the emergency de- mon and readily accessible. The fruit of the sea partment of Keelung Chang-Gung Hospital after at- mango turns bright red at maturity and appear very much tempting suicide by ingesting three sea mango seeds. He like the edible mango (Mangifera spp.) fruit. It is quite developed numbness involving the throat, head, and possible to inadvertently ingest the fruit and become in- neck areas and upper extremities soon after he ate the toxicated. Although there have been reports of intoxica- seeds. Upon arrival at the hospital, the patient had dys- tion by similar species, there is not much in the literature pnea, dizziness, and chest tightness with vomiting and regarding sea mango. Information available is either out watery diarrhea developing a few hours later. He had a of date or without scientific description regarding how clear consciousness level, and a physical examination much needs to be ingested to produce intoxication, the was unremarkable except for bradycardia at 30~40 beats clinical course of intoxication, or how to deal with it. per minute (bpm). The blood pressure (BP) was 142/72 Herein, we report a case with sea mango intoxication, mmHg. A 12-lead electrocardiogram (ECG) showed focus on the clinical course and serial changes in blood complete atrioventricular block, with a sinus rate of 78 digoxin and electrolyte levels, and provide a brief litera- bpm and a ventricular rate of 30 bpm (narrow QRS) (Figure 1A). Stand-by transcutaneous pacing was done at a rate of 60 bpm and an output of 50 mA. Laboratory Received: August 3, 2007 Accepted: December 24, 2007 tests,performed5hafterseamangoseedingestion,re- Division of Cardiology, Department of Internal Medicine, Chang vealed a digoxin level of 1.03 ng/mL and a potassium Gung Memorial Hospital, Keelung; Chang Gung University College of Medicine, Taiwan. level of 5.40 meq/L (Figures 2A, B). Renal function and Address correspondence and reprint requests to: Dr. Chao-Hung other laboratory findings were unremarkable. The cal- Wang, MD, Division of Cardiology, Department of Internal Medi- cium level was 9.5 mg/dL. The patient denied previous cine, Chang Gung Memorial Hospital, No. 222, Mai-Chin Road, Keelung, Taiwan. Tel: 886-2-2431-3131; Fax: 886-2-2433-5342; exposure to digoxin, beta-blockers, or calcium channel E-mail: [email protected] blockers. He was admitted to the cardiac care unit. The

Acta Cardiol Sin 2008;24:56-9 56 Sea Mango Cardiac Intoxication potassium level was checked every 12 h, and the hyper- gradually increased from 30 to 60 bpm with the develop- kalemia was treated with calcium gluconate, an insulin ment of high-grade atrioventricular block. When the infusion, and a potassium-lowering agent (Kalimate). No atrioventricular conduction returned back to a one-to- other specific treatment such as digoxin-chelating agents one conduction, there was a period of intermittent sinus or nasogastric lavage was given. The ventricular rate bradycardia (at a rate of 50 bpm) and sinus exit block,

Figure 1. The 12-lead electrocardiograms (ECG) performed upon arrival (A), 3 days later (B), and 6 days later (C). Upon arrival, the ECG showed complete atrioventricular block, with a sinus rate of 78 beats per minute (bpm) and a ventricular rate of 30 bpm (A). Three days later, second-degree sinus exit block, Wenckebach type, was noted (B). Full recovery of the sinus rhythm with normal atrioventricular conduction was noted 6 days later (C).

57 Acta Cardiol Sin 2008;24:56-9 Ping-Chang Liu et al.

Wenckebach type I (Figure 1B). ECGs were performed specific for sea mango intoxication. The ingestion of every 12 h until the patient was symptom-free with a only three sea mango seeds was sufficient to cause a se- normal sinus rhythm and normal atrioventricular con- vere atrioventricular conduction disturbance. The intoxi- duction. He was transferred to an ordinary ward after 2 cation occurred in the presence of non-toxic levels of days of care in the cardiac care unit. A follow-up 12-lead blood digoxin and potassium, and therefore is seemingly ECG showed a sinus rhythm 4 days later (Figure 1C). not explainable by a digoxin effect. The arrhythmia Serum digoxin and potassium levels were monitored caused by the sea mango seed is suggested to be associ- throughout the entire course (Figure 2). The patient was ated with intoxication by another cardiac glycoside, discharged and was asymptomatic at 1 week of clinical without left ventricular systolic function impairment. follow-up. Follow-up 1 year after the hospitalization Last of all, the intoxication resolved with temporary showed no specific sequel and no record of further sui- transcutaneous pacing and supportive treatment. cide attempts. Sea mango is an evergreen plant quite common along coastal areas in Taiwan. The name is de- rived from Cerberus, the hell dog from Greek mythol- DISCUSSION ogy, hence indicating the toxicity of the seeds. The leaves of the sea mango are shiny dark-green and alter- This case report presents some interesting findings nate, ovoid in shape (Figure 3A). The plant is perennial with white . The fruit of the sea mango bears a resemblance to the edible mango (Mangifera spp.) fruit and can be easily ingested accidentally (Figure 3B).2 Both the meat and, especially, the seeds of sea mango are

Figure 3. Flowers, leaves, and fruit of the sea mango. The leaves of the sea mango are shiny dark-green and alternate, ovoid in shape (A). Figure 2. Serial blood digoxin (A) and potassium (B) levels are The plant is perennial with white flowers. The fruit resembles the edible shown. mango (Mangifera spp.) fruit (B).

Acta Cardiol Sin 2008;24:56-9 58 Sea Mango Cardiac Intoxication toxic. This report demonstrates that this plant can cause hibition of the sodium-potassium ATPase pump and an severe toxicity, including complete atrioventricular block, increase in the refractory period of the atrioventricular second-degree sinus exit block, and a variety of associ- node.6 These mechanisms might provide an explanation ated symptoms such as nausea, vomiting, and dizziness. for the presentation of electrocardiography and hyper- The planting of this class of plants should be restricted by kalemia in this patient. national law, or the toxic effects should be clearly labeled The efficacy of antidigoxin Fab fragments has been on the trees to avoid inadvertent ingestion. tried to treat Thevetia peruviana (yellow oleander)-in- Although some reports have suggested that the toxic duced hyperkalemia and bradycardia. It was demon- effect of this class of plants is caused by digoxin, our strated that antidigoxin Fab fragments can safely and case demonstrated that the toxic effect of sea mango can- rapidly reverse yellow oleander-induced arrhythmia and not be completely explained by digoxin.3,4 Immunologi- hyperkalemia.1,7 However, the role of antidigoxin Fab cal assays based on the affinity of antibodies to bind the fragments in patients intoxicated by other plants has not specific molecular structure of digoxin have been used been investigated.7,8 Although the case presented here and show cross-reactions between digoxin and other recovered without using anti-digoxin Fab and the dig- plant cardiac glycosides.4 Therefore, laboratory tests oxin effect did not correlate well with the overall toxic- could detect digoxin levels in the serum even though this ity of sea mango, anti-digoxin Fab may be an option in patient had not taken digoxin. The serum level of dig- cases where patients develop unstable vital signs under oxin may provide a quantitative screening measurement supportive treatments. of cardiac glycosides as an “apparent digoxin concentra- tion”. However, the result might not precisely represent the level of toxin because high toxin concentrations of REFERENCES other glycosides are necessary before digoxin is measur- able in the blood.3,4 Actually, a variety of new cytotoxic 1. Eddleston M, Rajapakse S, Rajakanthan, Jayalath S, Sjostrom L, cardenolide glycosides have been isolated from the seeds Santharaj W, Thenabadu PN, Sheriff MH, Warrell DA. Anti- digoxin Fab fragments in cardiotoxicity induced by ingestion of of sea mango,5 including 3b-O-(2¢-O-acetyl-a- -theveto- L yellow oleander: a randomised controlled trial. Lancet 2000;355: b b syl)-14 -hydroxy-7-en-5 -card-20(22)-enolide, (7,8- 967-72. dehydrocerberin), 17b-neriifolin, deacetyltanghinin, 2. Gaillard Y, Krishnamoorthy A, Bevalot F. :a tangh-inin, cerberin, and 2¢-O-acetyl-cerleaside A. Among ‘suicide tree’ and cause of death in the state of Kerala, India. J these six cardenolide glycosides, ceberin is the main gly- Ethnopharm 2004;95:123-6. coside that possesses potent cardiotoxicity similar to 3. Radford DJ, Gillies AD, Hinds JA, Duffy P. Naturally occurring digoxin, but it has not been purified and formally identi- cardiac glycosides. Med J Aust 1986;144:540-4. 4. Radford DJ, Cheung K, Urech R, et al. Immunological detection fied.2 Hence, it may be difficult to define a prognosis of cardiac glycosides in plants. Aust Vet J 1994;71:236-8. based simply on a commercial laboratory test of digoxin 5. Cheenpracha S, Karalai C, Rat-A-Pa Y, Ponglimanont C, levels. Our patient had severe cardiac glycoside intoxi- Chantrapromma K. New cytotoxic cardenolide glycoside from cation when the digoxin level was at only 1.03 ng/mL. the seeds of Cerbera manghas. Chem Pharm Bull 2004;52: Although sea mango intoxication with hyperkalemia 1023-5. was reported in 1975 and the blood level of potassium 6. Ma G, Brady WJ, Pollack M, et al. Electrocardiographic manifes- was suggested to have prognostic value,2 the mechanism tations: digitalis toxicity. J Emerg Med 2001;20:145-52. 7. Eddleston M, Persson H. Acute plant poisoning and antitoxin an- is still unknown. In addition, all types of arrhythmia tibodies. J Toxicol - Clin Toxic 2003;41:309-15. shown in this case can be seen with digoxin intoxication. 8. Roberts DM, Buckley NA. Antidotes for acute cardenolide (car- Actually, cardenolide glycosides share similar structures diac glycoside) poisoning. Cochrane Database Syst Rev 2006;(4): with digoxin. Their intoxication is manifested by the in- CD005490.

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