Chan Su or Senso is a traditional Chinese medicine and it is prepared from the dried white secretion of the auricular glands and the skin glands of Toad.1) The extracts of toad stimulate myocardial contraction and they have anesthetic and antibiotic actions, so they were used for the treatment of dyspnea, edema, palpitation, tonsillitis, sore throat, toothache and sinusitis.1)2)

The cardiotonic components in toad venom consisted of bufogenins, bufadiennolides or bufotoxins, and these components serve as cardioactive steroids; their structure are similar to those of the conventional cardiac glycosides such as digoxin.3) Bufotoxins have the ability to inhibit the activity of the membrane enzyme sodium-potassium adenosine triphosphatase(Na+/K+-ATPase).4) The patients who overdose with toad medical preparations experience symptoms that are similar to the effects of digoxin intoxication, such as nausea, vomiting, general malaise, tachybradyarrhythmia and cardiopulmonary arrest.1-3)5)

We report here on a case of the toad venom poisoning that showed various degrees of atrioventricular(AV) block and nonsustained ventricular tachycardia(VT).

A 54-year-old man was referred to our hospital due to nausea and vomiting. He had prepared toad soup with two toads for lunch and he ate the soup with makgeolri, raw rice wine. After about 30 minutes after ingestion, he began to suffer from nausea, vomiting, dizziness and numbness over the oral mucosa and both extremities. He visited a local hospital and was referred to our hospital without any preliminary management.

He arrived at our emergency department 2 hours after he ate the toad soup. Physical examination revealed an alert mental status, the blood pressure was 80/40 mmHg, the heart rate was irregular at 36 beats per minute and the body temperature was 36.6℃. The electrocardiogram (ECG) showed varying degrees of AV block, and there was PR prolongation and a tent-shaped T wave(Fig. 1A). The laboratory data revealed a white blood cell count of 12,960/mm³ with 72.5% neutrophils, the hemoglobin was 14.9 gm/dL, the sodium was 132 mmol/L, the potassium 6.09 mmol/L and the creatinine 1.25 mg/dL. His serum digoxin level was 1.62 ng/mL(the therapeutic range of digoxin is from 0.8 ng/dL to 2.0 ng/mL) and he had no previous medication history. He underwent gastric lavage with actvivated charcoal and an invtravenous infusion of the insulin and 20% dextrose for the management of hyperkalemia and to induce temporary pacing. After a bolus injection of atropine, the ECG showed the 1 : 1, prolonged AV conduction(Fig. 2). During his medical management, the electrocardiogram showed nonsustained monomorphic VT(Fig. 3) 4 hours after he ate the toad soup.

The second day of the admission, the potassium level was 5.14 mmol/L and the digoxin level was 0.21 ng/mL. The ECG showed Wenchebach and first degree AV block(Fig. 1B, C). On the third day after admission, the potassium level was 3.71 mmol/L and the digoxin level was below 0.17 ng/mL. The ECG showed a normal PR interval and no abnormal findings(Fig. 1D). He was discharged on the fifth day of admission and he had no symptoms, abnormal laboratory tests and ECG results at discharge.

Toads have a pair of well-defined skin glands behind the eyes, and these glands secrete venom. This venom is found in the skin and plasma.1)2) Previous studies have confirmed that toad venom contains several types of toxic substances.1)2)4-6) These toxic substances can be divided into three groups. The first group is the bufotoxins, which have effects similar to the cardiac glycosides, and their exact mechanism of cardiotrophic activity has not been well defined. Yet their clinical activity may be related to their digitalis-like structure. Bufotoxins (bufadienolides) have a six member lactone ring and the cardenolides, which are cardiac glycosides derived from a plant, they have a five member lactone ring(Fig. 4). The cardioactive compounds in the second group are the catecholamines, and there are several catecholamines in toad venom. Epinephrine has been found at as high as a 5% concentration in the venom. The third group is the indoleakylamines, which include bufothionine, serotonin, bufotenine, cinobufotenine and dehydobufotenine. The toxicity of toad venom cannot be abolished or reduced by heating. The signs and symptoms of toad intoxication include fever, blurred vision, a numb sensation over the oral mucosa, seizure, hallucination, dysryhthmias, nausea, vomiting, diarrhea, dizziness, mental confusion, hypotension, sinus arrest with AV block and sudden death.1)2)7) These symptoms are similar to those of digitalis intoxication.

Cardiac glycoside has a positive inotropic action and it alters the electrophysiology of the heart muscle via binding to and inhibition of the enzyme Na+/K+-ATPase on the surface membrane of myocardial cells.8) When Na+/K+-ATPase is inhibited, then the sodium-calcium exchanger removes accumulated intracellular sodium in exchange for calcium. This exchange increases sarcoplasmic calcium and it is the mechanism responsible for the positive inotropic effect of digitalis. Inhibition of the Na+/K+-ATPase pump also results in an increase in extracellular potassium. Since the skeletal muscle, with its sheer mass, contains the major pool of Na+/K+-ATPase in the body, the severity of hyperkalemia is determined by the K+ released from the skeletal muscles.8) Cardiac glycoside also has complex electrophysiological effects that are a combination of indirect, parasympathectic and direct effects on specialized pacemakers and conduction tissues.9)10) Digoxin usually decreases the automaticity and it increases the maximal diastolic resting membrane potential in the atrial and AV nodal cells as a result of augmented vagal tone and decreased sympathetic nervous system activity. These effects are accompanied by prolongation of the effective refractory period and decreased AV nodal conduction velocity. At toxic doses, these effects result in various degrees of bradydysrhythmia and slowing of the conduction tissue, along with a decreased refractory period of the myocardium and increased automaticity. Intracellular calcium overload creates transient depolarizations, giving rise to triggered dysrhythmias. Chi et al6) reported that the level of serum potassium has prognostic implications for toad intoxication and if hyperkalemia develops, then the treatment of toad intoxication must be more aggressive to prevent mortality. Besides acute hyperkalemia, the characteristic ECG features may also provide important clues for the diagnosis of cardiac glycoside toxicity. The typical ECG changes include flattened or inverted T waves, shortened QT intervals, depressed ST segments and rhythmic changes. These cardiac glycoside changes may complicate or mask the typical ECG features of hyperkalemia.11) In our case, the ECG showed a varying degree of AV block that resembled the ECG features of digitialis intoxication, and there were narrow and tent-shaped T waves that resembled the ECG features of hyperkalimia(Fig. 1A). Hyperkalemia(6.09 mmol/L) was present in our case and we treated the patient with insulin and dextrose infusion. Digoxin toxicity can be reversed by antidigoxin immunotherapy.12)13) Purified Fab fragments from digoxin-specific antisera are now commercially available. Brubacher et al3) reported that digoxin specific Fab fragments are effective in the treatment of Chan Su poisoning and they may be effective for poisoning by other cardioacitve steroids of the bufadienolide class.

Digoxin-like immunoreactive substance was detected in our patient's serum, and elevation of the serum digoxin concentration was noted when this was assayed by an immunological method.12)13) This is possibly due to the similarity in chemical structures between toad venom and digoxin, resulting in crossreactivity of toad venom with the digioxin immunoassay antibody. The method to detect the digoxin level in our hospital is also immunological assay; digoxin was detected in the serum of our patient and he was without previous digoxin medication.

We report here on a 54-year-old man who ate toad soup and the result of the clinical symptoms and laboratory tests showed digoxin intoxication-like effects. The laboratory result showed an elevated digoxin level (1.62 ng/mL) and potassium level(6.09 mmol/L), and the electrocardiogram of the patient showed high-degree, Wenchebach and first degree atrioventricular block and nonsustained ventricular tachycardia. The patient was discharged on the 5^th day without any complication after conservative management.