Accidental

Digitoxin Poisoning

John J. Iacuone, MD

\s=b\ A healthy 14\m=1/2\-month-old child ingested 1.5 mg of digitoxin by accident. Digitoxin was wrongly identified as digoxin, the initial electrocardiogram was misinterpreted, and the vomiting was underestimated as an important symptom of toxicity. Symptoms persisted and the patient was hospitalized. Serial digitoxin

levels were obtained and correlated with ECG and clinical course. It appears that serial digitoxin levels can be a useful adjunct in diagnosis, assessment of severity, and indication of recovery from digitoxin poisoning. In each patient, it is imperative that ECG, pharmacologic, and clinical indicators of digitalis toxicity be accurately identified for proper assessment of severity and appropriate management. (Am J Dis Child 130:425-427, 1976)

Accidental digitoxin poisoning in il children still occurs despite the widespread use of digoxin in the pedi¬ atrie population. This can occur by ingestion of cardiac glycoside-con-

taining plants,1 pharmacy dispensing

errors,2 and accidental ingestion of

for a relative.3 The last method was the case in our patient. The purpose of this report is to (1) reiterate the continued threat of

digitoxin prescribed

Received for publication Oct 8, 1974; accepted 1975. From the Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University Medical Center, Indianapolis. Dr Iacuone is now a Fellow in Hematology-Oncology, Children's Hospital Research Foundation, Cincinnati. Reprints not available.

April 24,

digitoxin poisoning in children; (2) note some important pharmacologie and toxicologie differences from digoxin; (3) emphasize the need for accurate clinical evaluation in deter¬

mining the severity of the poisoning; (4) illustrate the positive relationship between serial electrocardiograms, di¬ gitoxin levels, and the patient's course; and (5) discuss briefly the possible uses of plasma digitoxin levels in the management of digitoxin poisoning. REPORT OF A CASE A 1414-month-old girl ingested 10 to 15 "digitalis" tablets that belonged to her mother. The mother had been taking one tablet daily for two years for prevention of paroxysmal atrial tachycardia. The pa¬ tient's mother induced vomiting about 45 minutes after the ingestion, then contacted her physician who told her to observe the child and that she might continue to vomit that day. However, persistent vomiting prompted the mother to bring her child to our emergency room about 36 hours after the ingestion. The history obtained by the physician on call in our emergency room indicated that the patient had taken digoxin, 0.1-mg tablets. An ECG at that time was misinter¬ preted as normal. The blood urea nitrogen (BUN) level was 25 mg/100 ml and the serum electrolyte values were normal. The patient was released to the care of her private physician. The vomiting continued and the patient returned to the hospital the following evening for réévaluation. This time the medicine was obtained and correctly identified as digitoxin, 0.1-mg tablets. Reexamination of the previous ECG showed a junctional rhythm. A repeat

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tracing showed first-degree heart (PR interval, wave

0.24 seconds with

no

block ST-T

changes).

The physical examination showed an alert and well-hydrated child. The heart rate was 110 beats per minute. The remainder of the examination including the neurologic examination was completely normal. The patient was admitted to the hospital and placed on continuous ECG monitoring and a clear liquid diet as toler¬ ated. Serial ECGs, digitoxin levels, and serum potassium levels were followed up in the management of this patient. Laboratory data showed the following values: serum sodium, 139 mEq/liter;

potassium, 5.1 mEq/liter; serum chlorides, 100 mEq/liter; CO, combining power, 28 mEq/liter; BUN, 15 mg/100 ml; hemoglobin, 13.1 gm/100 ml; hematocrit, 38%; white blood cells, 9,300/cu mm; and platelets, adequate. Clinical course, ECGs, serum

and digitoxin levels Table.

are

outlined in the

COMMENT

Digoxin is almost completely me¬ tabolized or excreted unchanged in the urine in five days; its peak effect is seen at one to three hours after administration and the serum halflife is 24 hours.4 On the other hand, digitoxin is almost completely ex¬ creted in 18 days; the serum half-life is seven days,5 and the peak effect is seen at eight to ten hours and may last as long as 72 hours.6 Digitoxin is almost completely absorbed from the gastrointestinal tract, in contrast to 50% to 90% of digoxin. Absorption is complete by two hours after inges¬ tion.1 Our patient did not vomit until 45 minutes after taking digitoxin.

SERUM DIGITOXIN

(ng/ml)

40

—j— — - — - — —r 10

12

14

16

20

18

DAYS

Digitoxin Levels ECG Abnormal Clinical Toxicity

Fig 1 .—Serial lead II tracings taken on days to four after ingestion of digitoxin.

one

Thus, a considerable amount, if not all, of the digitoxin was probably ab¬ sorbed. More than 80% of digoxin and digitoxin are excreted in the urine, but only 10% of digitoxin is un¬ changed.1 " The prolonged toxic ef¬ fects in our patient reflect in part the greater role of the liver in the detoxi¬ fication of digitoxin vs digoxin. At the time our patient was first seen, she was thought to be beyond the peak effect of digoxin, since the ECG was misread as normal at 36 hours after ingestion. However, the time interval was well within the duration of toxicity for digitoxin. In fact, this child had ECG and clinical evidence of toxicity on examination in the emergency room. The ECG showed a junctional rhythm; there was persistent vomiting and a history of ingesting up to 1.5 mg of digitoxin, which is one half the estimated lethal dose for adults.6·7 Digitoxin toxicity can be deter¬ mined in three ways: (1) ECG abnor¬ malities, (2) clinical symptoms, and (3) direct measurement of digitalis blood levels. Any of these factors may indi¬ cate

digitalis toxicity

at any

point

in

Fig 2.—Duration of clinical and electrocardiographic levels after ingestion of digitoxin.

toxicity

correlated with

Electrocardiogram Results, Symptoms, and Digitoxin Time Post-

ingestion 36 hr 60 hr

Day 3 Day 4 Day 12 Day 19

ECG Findings Junctional rhythm, no ST-T wave changes First-degree block (PR, 0.24 sec) First-degree block & atrial premature beats Normal (PR, 0.16 sec) Normal Normal

Symptoms Severe vomiting

digitoxin

Levels

Digitoxin Levels,1 ng/ml

Severe vomiting

67.3

Nausea only

72.06

None None None

47.8 14.4 4.0

Digitoxin levels were determined by radioimmunoassay8; therapeutic dose is 20 ml, while a toxic dose would be >30 ng/ml (at our medical center). *

time. The patient was thought to be beyond the peak effect of digoxin; that, together with a supposedly normal ECG, led to the assumption that the patient did not have digitalis toxicity. Both the statistical estima¬ tion of duration of digitalis effect, as based on pharmacokinetic data from the literature, and the interpretation of the ECG later proved to be in error. Our patient exemplifies the impor¬ tance of correct identification of the substance ingested, complete under¬ standing of its toxic manifestations, and reliance on clinical judgment in

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:

2

ng/

the

diagnosis and treatment of any poisoning. Serum digitoxin levels correlated well with ECGs and the patient's clin¬ ical course (Table). The ECG taken at 36 hours after ingestion showed a junctional tachycardia; 60 hours after ingestion there was a marked firstdegree block (PR interval, 0.24 sec¬ onds) (Fig 1). Subsequent tracings show lessening of the first-degree block and a return to normal at five days after ingestion (Fig 1). Conduc¬ tion disturbances are more common expressions of digitalis toxicity in

children with normal hearts.1' It is interesting to note that clinical and ECG evidence of toxicity ceased four days after ingestion, while the digi¬ toxin level remained elevated (Fig 2). Therapeutic levels were present for at least a week after ingestion; the halflife in our patient was calculated to be five days, and the drug could still be detected for at least 19 days (Fig 2). Cessation of toxic effects in the face of therapeutic levels of digitoxin could represent better tolerance of cardiac glycosides in children and less effect of digitalis on a normal heart. Unfor¬ tunately, a digitoxin level was not obtained at the initial visit when ECG abnormalities and clinical symptoms were the most severe. However, it appears that observing serial digi¬ toxin levels may be a useful index in digitoxin poisoning. In cases where the history is not clear and the nature of the medicine is unknown, measure¬ ment of both digoxin and digitoxin levels is indicated as an aid in diag-

nosis. Also, in acute poisoning, digi¬ toxin levels may reflect the severity of the condition when the amount of tablets ingested is unknown. There are several good reviews of digitalis poisoning that contain thera¬ peutic recommendations.61011 Most therapy is concerned with removing any residual digitalis from the stom¬ ach, following up serum potassium levels, and ECG monitoring with therapy dictated by the type of arrhythmia that occurs. It is desirable to maintain serum potassium levels in the high-normal range since fatal arrhythmias are more frequent as the serum potassium level decreases. Pro¬ pranolol hydrochloride has been used with success in supraventricular ar¬ rhythmias, while phenytoin, lidocaine, and intravenously administered po¬ tassium chloride have been used with success in ventricular arrhythmias. When atrioventricular block is severe enough to cause circulatory insuffi¬ ciency, atropine sulfate and ventric-

ular

pacing have been used success¬ fully. Unfortunately, in severe cases of digitalis poisoning, therapy is generally unrewarding. Central ner¬ vous system (CNS) abnormalities are not usually severe in children. Vomit¬ ing, visual disturbances, and lethargy or irritability are the most common CNS manifestations of digitalis toxic¬ ity. Digitalis poisoning remains a threat to the pediatrie patient. In such cases, it is essential to accurately identify the type of digitalis taken because of differences in pharmokinetics and in their toxic manifestations. It seems that measurement of digitoxin levels can be a useful adjunct in digitoxin poisoning as an aid in diagnosis, a guide to the severity, and as an indi¬ cator of recovery.

Dr Watanabe determined serum digitoxin levels. The Indiana University Medical Center, Indianapolis, and Glenna Downton provided technical assistance.

References 1. Goodman L, Gilman A: The Pharmacological Basis of Therapeutics: Textbook of Pharmacology, Toxicology, and Therapeutics for Physicians and Medical Students. New York, MacMillan Co, 1955. 2. Joos HS, Johnson JL: Digitalis intoxication in infancy and childhood. Pediatrics 20:866-876, 1957. 3. Drevets CC: Accidental digitoxin poisoning in children: Report of a case and review of literature. J Pediatr 52:577-583, 1958.

4. Mason DT, Zeles R, Lei G, et al: Current concepts and treatment of digitalis toxicity. Am J Cardiol 27:546-557, 1971.

5. Okita GS: Studies with radioisotope digitalis. J Amer Geriatr Soc 5:163-174, 1957. 6. Gleason M, Gosselin R, Hodge H, et al: Clinical Toxicology of Commercial Products, ed 3. Baltimore, Williams & Wilkins Co, 1969. 7. AMA Drug Evaluations, ed 1. Chicago, American Medical Association, 1971, p 2. 8. Smith TW: Radioimmunoassay for serum

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digitoxin concentrations: Methodology and clinical experience. J Pharmacol Exp Ther 175:352\x=req-\ 360, 1970.

9. Lampe KF: Systemic plant poisoning in children. Pediatrics 54:347-351, 1974. 10. Fowler RS, Rathin L, Keith JD: Accidental digitalis intoxication in children. J Pediatr 64:188-200, 1964. 11. McNamara DG, Brewer EJ, Ferry GC: Accidental poisoning of children with digitalis. N Engl J Med 271:1106-1108, 1964.