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Biologic intoxication due to digitalis-like substance after ingestion of cooked toad soup
CASE REPORT
Biologic Intoxication Dye to Digitalis-Like gu;tance After Ingestron of Cooked Toad Ming-Shyan Chern, MD, Ching-Ying Ray, BS, and Delon Wu, MD ntoxication due to ingestion or mouthing of toadsis well known to Iveterinarians. 1,2Dogs and cats develop severesymptomsthat often result in a lethal outcome. Salivation, cyanosisand vomiting are commonmanifestations in dogs after toad ingestion. Neurologic symptoms may dominate the clinical picture in severe cases.In humans, mortality and convulsive disorders have been previously observed.3Recently we encountered a patient with cardiopulmonary arrest and severe bradyarrhythmia after ingestion of toad soup. A 31-year-old male labor worker was transferred to our hospital 2 hours after a successful cardiopulmonary resuscitation. He had been well until the day of admission, when he consumed a bowl of toad soup (Bufo melanosticus Schneider) that was stewed with rice wine. Thirty minutes later, he experienced nausea, vomiting, dizziness, blurred vision and general weakness, which was followed by perioral numbness and unconsciousness.He was taken to another hospital, where cardiopulmonary arrest was noted and he wassuccessfully resuscitated.On arrival, his systolic blood pressure was 40 mm Hg, heart rate was 46 beats/ min and body temperature was 36°C. The neck veins were not engorged. The lungs were clear. The heart revealed no S3 or Sq or murmur. Liver and spleen were not palpable. There was no leg edema.An electrocardiogram revealedsinus arrest or sinus slowing with emergence of shifting atria1 pacemaker and From the Section of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung Medical College, 199Tung Hwa North Road, Taipei, Taiwan, Republic of China. This study was supportedin part by a grant from the National ScienceCouncil (NSC-790412-B-182-11) of the Republic of China. Manuscript receivedAugust 14, 1990;revised manuscript received and accepted September 28, 1990.
high-grade atrioventricular block; the QRS complex was normal (Figure IA). The white blood cell count was 29,900/mm3with a segmentform of 86% and a bandform of 3%; the hemoglobin was 15.0 gm/dl. Analysis of the arterial blood gas showed a pH of 7.293, a partial carbon dioxide pressure of 47.5 mm Hg, a partial oxygenpressure of 43.4 mm Hg, and a bicarbonate content of 23.0 mEq/liter. Blood chemistry values were 223 mg/dl for glucose, 1.6 mgj dl for creatinine, 129 mEq/liter for sodium, 4.2 mEq/liter for potassium, 51 U/liter for aspartate transaminase, 8.2 mg/dl for calcium and 2.0 mg/dl for phosphate. Serum creatine kinase was 215 U/liter with 100% MM fraction. A serum ‘digoxin” level measuredon admission was 2.1 rig/ml (by fluorescence energy transfer immunoassay). After an intravenous bolus of 1 mg of atropine, heart rate increased to 110 beatslmin and blood pressure to 100/70 mm Hg. The electrocardiogram showeda sinus rhythm at a rate of 107 beatslmin and a Mobitz type I atrioventricular block (Figure IB). A bolus of 1 mgof atropine was given every 6 hours for the subsequent 36 hours. An electrocardio-
gram recorded 19 hours after admission showed sinus rhythm at a rate of 58 beatslmin andfirst-degree atrioventricular block with a PR interval of 0.22 second (Figure 1C). Threedays after admission, the electrocardiogram was normal, with a sinus rate of 52 beatslmin and a PR of 0.16 second (Figure 1D). The symptoms subsided gradually and the patient was asymptomatic 30 hours after ingestion of the toad soup. A repeat blood chemistry 48 hours after admission wascompletely normal. Follow-up serum digoxin levels were 0.7 rig/ml on day 3 and KO.4 rig/ml on day 7. The dried extracts of the toad skin havebeenusedasa cardiotonic agent in China (Wan Su) and in Japan (Senso). Some local people in Taiwan also consider toad soup a blood detoxicating agent and consume it to purify the blood. The toad venom contains many biologically active substancesthat are secretedprimarily in the parotid gland, but are also present in skin and plasma.1T4-6 The toxic effects of toad venom can be attributed to the glycosidic portion of the bufotoxin complex.2 The symptoms in our patient with nausea, vomiting, dizziness, blurred vision, mental confusion, hypotension and sinus arrest with atrioventricular block are similar to symptomsof clinically severe digitalis intoxication. The high serum digoxin level measured by fluorescenceenergy transfer immunoassayis probably due to cross-reaction of the glycoside-like substancewith the assay.There is no
FIGURE 1. serial ekhcard ~ographii tracings on admission (A), after intravenous bohm of 1 mg of atropine (B), 19 hours after admission (C), and 3 days after admissien (D). See text for deWIs.
THE AMERICAN JOURNAL OF CARDIOLOGY FEBRUARY 15, 1991
443
known antidote to bufotoxin. However, propranolol has been shown to be effective in preventing ventricular fibrillation in the canine model of bufo intoxication.2 Propranolol was contraindicated in our patient becauseof sinus arrest and high-grade atrioventricular block. Isoproterenol is not advised because neurologic symptoms and ventricular fibrilla-
444
may be notentiated bv catecholaminesSAtrdpineor pacemakertherapy appears to be a reasonableappreach when symptomsare primarily due to bradycardia. tiOn
1. Bedford PCG. Toad venom toxicity and its clinical occurrence in small animals in the United Kingdom. Vet Ret 1974;94:613-614. 2. Palumba NE, Perri S, Read G. Experimental induction and treatment of toad poisoning in the dog. J
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 67
am vet hhd ASSO~ 1975:167:1ooo-1005, 3. Hitt M, Ettinger DD. Toad toxicity (letter). N Engl J Med 1986; 314~1517~1518. 4. Flier JS. Ouabain-like activity in toad skin and its implications for endogenous regulation of ion transport. Nature 1918; 274285-286. 5. Flier JS, Ma&s-Flier E, Pallotta JA, Mclsaac D. Endogenous digitalis-like activity in the plasma of toad bufo marinus. Nature 1979;279:341-343. 6. Lichtstein D, Kachalsky S, Deutch J. Identification of a ouabain-like compound in toad skin and plasma as a bufodienolide derivative. LifeSci 1986; 38:1261&1270.
Biologic Intoxication Dye to Digitalis-Like gu;tance After Ingestron of Cooked Toad Ming-Shyan Chern, MD, Ching-Ying Ray, BS, and Delon Wu, MD ntoxication due to ingestion or mouthing of toadsis well known to Iveterinarians. 1,2Dogs and cats develop severesymptomsthat often result in a lethal outcome. Salivation, cyanosisand vomiting are commonmanifestations in dogs after toad ingestion. Neurologic symptoms may dominate the clinical picture in severe cases.In humans, mortality and convulsive disorders have been previously observed.3Recently we encountered a patient with cardiopulmonary arrest and severe bradyarrhythmia after ingestion of toad soup. A 31-year-old male labor worker was transferred to our hospital 2 hours after a successful cardiopulmonary resuscitation. He had been well until the day of admission, when he consumed a bowl of toad soup (Bufo melanosticus Schneider) that was stewed with rice wine. Thirty minutes later, he experienced nausea, vomiting, dizziness, blurred vision and general weakness, which was followed by perioral numbness and unconsciousness.He was taken to another hospital, where cardiopulmonary arrest was noted and he wassuccessfully resuscitated.On arrival, his systolic blood pressure was 40 mm Hg, heart rate was 46 beats/ min and body temperature was 36°C. The neck veins were not engorged. The lungs were clear. The heart revealed no S3 or Sq or murmur. Liver and spleen were not palpable. There was no leg edema.An electrocardiogram revealedsinus arrest or sinus slowing with emergence of shifting atria1 pacemaker and From the Section of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung Medical College, 199Tung Hwa North Road, Taipei, Taiwan, Republic of China. This study was supportedin part by a grant from the National ScienceCouncil (NSC-790412-B-182-11) of the Republic of China. Manuscript receivedAugust 14, 1990;revised manuscript received and accepted September 28, 1990.
high-grade atrioventricular block; the QRS complex was normal (Figure IA). The white blood cell count was 29,900/mm3with a segmentform of 86% and a bandform of 3%; the hemoglobin was 15.0 gm/dl. Analysis of the arterial blood gas showed a pH of 7.293, a partial carbon dioxide pressure of 47.5 mm Hg, a partial oxygenpressure of 43.4 mm Hg, and a bicarbonate content of 23.0 mEq/liter. Blood chemistry values were 223 mg/dl for glucose, 1.6 mgj dl for creatinine, 129 mEq/liter for sodium, 4.2 mEq/liter for potassium, 51 U/liter for aspartate transaminase, 8.2 mg/dl for calcium and 2.0 mg/dl for phosphate. Serum creatine kinase was 215 U/liter with 100% MM fraction. A serum ‘digoxin” level measuredon admission was 2.1 rig/ml (by fluorescence energy transfer immunoassay). After an intravenous bolus of 1 mg of atropine, heart rate increased to 110 beatslmin and blood pressure to 100/70 mm Hg. The electrocardiogram showeda sinus rhythm at a rate of 107 beatslmin and a Mobitz type I atrioventricular block (Figure IB). A bolus of 1 mgof atropine was given every 6 hours for the subsequent 36 hours. An electrocardio-
gram recorded 19 hours after admission showed sinus rhythm at a rate of 58 beatslmin andfirst-degree atrioventricular block with a PR interval of 0.22 second (Figure 1C). Threedays after admission, the electrocardiogram was normal, with a sinus rate of 52 beatslmin and a PR of 0.16 second (Figure 1D). The symptoms subsided gradually and the patient was asymptomatic 30 hours after ingestion of the toad soup. A repeat blood chemistry 48 hours after admission wascompletely normal. Follow-up serum digoxin levels were 0.7 rig/ml on day 3 and KO.4 rig/ml on day 7. The dried extracts of the toad skin havebeenusedasa cardiotonic agent in China (Wan Su) and in Japan (Senso). Some local people in Taiwan also consider toad soup a blood detoxicating agent and consume it to purify the blood. The toad venom contains many biologically active substancesthat are secretedprimarily in the parotid gland, but are also present in skin and plasma.1T4-6 The toxic effects of toad venom can be attributed to the glycosidic portion of the bufotoxin complex.2 The symptoms in our patient with nausea, vomiting, dizziness, blurred vision, mental confusion, hypotension and sinus arrest with atrioventricular block are similar to symptomsof clinically severe digitalis intoxication. The high serum digoxin level measured by fluorescenceenergy transfer immunoassayis probably due to cross-reaction of the glycoside-like substancewith the assay.There is no
FIGURE 1. serial ekhcard ~ographii tracings on admission (A), after intravenous bohm of 1 mg of atropine (B), 19 hours after admission (C), and 3 days after admissien (D). See text for deWIs.
THE AMERICAN JOURNAL OF CARDIOLOGY FEBRUARY 15, 1991
443
known antidote to bufotoxin. However, propranolol has been shown to be effective in preventing ventricular fibrillation in the canine model of bufo intoxication.2 Propranolol was contraindicated in our patient becauseof sinus arrest and high-grade atrioventricular block. Isoproterenol is not advised because neurologic symptoms and ventricular fibrilla-
444
may be notentiated bv catecholaminesSAtrdpineor pacemakertherapy appears to be a reasonableappreach when symptomsare primarily due to bradycardia. tiOn
1. Bedford PCG. Toad venom toxicity and its clinical occurrence in small animals in the United Kingdom. Vet Ret 1974;94:613-614. 2. Palumba NE, Perri S, Read G. Experimental induction and treatment of toad poisoning in the dog. J
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 67
am vet hhd ASSO~ 1975:167:1ooo-1005, 3. Hitt M, Ettinger DD. Toad toxicity (letter). N Engl J Med 1986; 314~1517~1518. 4. Flier JS. Ouabain-like activity in toad skin and its implications for endogenous regulation of ion transport. Nature 1918; 274285-286. 5. Flier JS, Ma&s-Flier E, Pallotta JA, Mclsaac D. Endogenous digitalis-like activity in the plasma of toad bufo marinus. Nature 1979;279:341-343. 6. Lichtstein D, Kachalsky S, Deutch J. Identification of a ouabain-like compound in toad skin and plasma as a bufodienolide derivative. LifeSci 1986; 38:1261&1270.