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Propafenone ingestion
CASE REPORT pr0pafenone, accidental ingestion
Propafenone Ingestion Propafenone is a type lc antiarrhythmic drug that recently has become available for clinical trials within the United States. We present the case of a 2-year-old child who accidentally ingested 1,800 mg (133 mg/kg) of propafenone. The patient subsequently developed cardiac conduction abnormalities and generalized seizures. Following the administration of IV phenytoin, cardiopulmonary collapse occurred. The patient had a successful outcome with aggressive cardiopulmonary life support. [McHugh TP, Perina DG: Propafenone ingestion. Ann Emerg Med April 1987;16:437-440.] INTRODUCTION First synthesized in 1970, propafenone is an investigational class lc antiarrhythmic drug. 1 It has been used commercially in Europe since 1977 under the trade name Rytmonorm ® and has only recently become available for clinical trials in the United States.I, z We report the case of a child who accidentally ingested a small number of tablets and subsequently developed cardiac conduction disturbances and seizure activity followed by cardiopulmouary collapse. This is the first case of a toxic ingestion of propafenone to be reported in the United States.
Terrance P McHugh, MD, FACEP Debra G Perina, MD Columbia, South Carolina From the Department of Emergency Medicine, Richland Memorial Hospital, Columbia, South Carolina. Received for publication May 16, 1986. Revision received November 4, 1986. Accepted for publication December 2, 1986. Address for reprints: 7errance McHugh, MD, Department of Emergency Medicine, Richland Memorial Hospital, 5 Richland Medical Park Road, Columbia, South Carolina 29203.
CASE REPORT A 2-year-old boy presented with a history of having ingested 12 150-mg tablets of propafenone. A total of 1,800 mg (133 mg/kg) had been swallowed approximately ten minutes prior to his arrival. The child had been well prior to this ingestion and had no significant medical history. On arrival, the child was alert, moving all extremities, and exhibiting good muscular strength. Initial vital signs were as follows: temperature, 36.1 C orally; pulse, 100; and respirations, 24. An initial blood pressure was not obtained. The child weighed 13.5 kg. Auscultation of the chest revealed the presence of normal heart and breath sounds; no heart murmurs or gallops were heard. The remainder of the physical examination was unremarkable. The patient was placed on a cardiac monitor, given 15 mL syrup of ipecac and vomited about 100 mL of gastric contents approximately 30 minutes post ingestion. No pill fragments were seen. After an additional 20 minutes, the child had a generalized seizure that lasted approximately 60 seconds. Concurrent with this seizure, the QRS complex had become much wider (Figure 1). A blood pressure of 60/40 m m Hg was measured, and an IV line using 2.5% dextrose/0.45 normal saline at 20 mL/hr was started. No medication was given to the child during or immediately following the seizure. An ECG showed the presence of a persistent right bundle branch block associated with a first-degree atrioventricular (AV) block and prolongation of the QT interval (Figure 2). While receiving supplemental oxygen by face mask, arterial blood gases revealed a pH of 7.34, pO 2 of 144 m m Hg, and pCO2 of 33 m m Hg. A complete blood count showed a hemoglobin of 10.5 gm/dL and a white cell count of 11,400 (21 polys, 71 lymphs, five monos, one eosinophil, and two basophils). Other laboratory results were as follows: glucose, 92 mg/dL; BUN, 9 mg/dL; sodium, 141 mEq/L; potassium, 4.4 mEq/ L; chloride, 104 mEq/L; serum bicarbonate, 27 mEq/L; creatinine, 0.6 mg/dL; magnesium, 2.4 mEq/L; and calcium, 10.5 mEq/L. A serum and urine drug screen was drawn. Gastric lavage was performed, followed by the administra16:4April 1987
Annals of Emergency Medicine
437/99
PROPAFENONE INGESTION McHugh & Perina
FIGURE 1. ECG monitor tracings ob-
tained during the patient's treatment. Strip A is the initial ECG tracing obt a i n e d on arrival, strip B was obtained i m m e d i a t e l y after the initial seizure, and strip C was obtained just prior to resuscitation efforts. tion of 30 g of charcoal and 4 oz of magnesium citrate• Arrangements were made to transport the child to the pediatric intensive care unit (PICU). At this point he responded to his name but was becoming increasingly lethargic. Repeat vital signs included a blood pressure of 80/60 m m Hg and a heart rate of 70. Following a second generalized seizure, the patient received 200 mg phenobarbital IV and was then, two hours following ingestion, transported to the PICU. The patient received 135 mg of phenytoin IV over several minutes. About 30 minutes later, cardiac monitoring revealed an irregular bradycardia with progressive widening of the QRS and QT interval (Figure 1). Shortly thereafter (2.5 hours following ingestion), no pulse could be palpated and the p a t i e n t s t o p p e d all s p o n t a n e o u s breathing efforts• The patient was intubated and advanced cardiac life support measures were begun using atropine, s o d i u m b i c a r b o n a t e , and dopamine. During the period of cardiopulmonary collapse, the patient remained in electromechanical dissociation. C o n t i n u o u s ECG t r a c i n g s showed periods of bradycardia, down to 35 beats/rain and associated with wide QRS complexes, alternating with periods of tachycardia, up to 120 beats/min and associated with varying QRS morphology• When a palpable blood pressure finally was detected, a junctional r h y t h m of 80 beats/min with a wide QRS predominated• This entire episode occurred over about 60 minutes• The ECG gradually returned to normal over several hours and the patient made an uneventful recovery. He was discharged from the hospital in three days with no residual sequelae. DISCUSSION
Propafenone is a class lc antiarrhythmic agent exhibiting both local anesthetic actions and membrane stabilizing effects on myocardial conduction cells. 3 It blocks the fast inward sodium current, and this action is largely responsible for the decreased 100/438
A,
.....
:,~z,
! B. % : ~ %~ :::6
L%ZL
L;;: ¸
rate of depolarization it produces, z Propafenone slows sinus node automatically and decreases conduction time through both the AV node and the ventricular conduction system.I, 4 This depression of conduction velocity is thought to be the major mechanism by which propafenone terminates atrial and v e n t r i c u l a r arrhythmiasJ In Europe propafenone is used for the suppression of chronic supraventricular tachycardia, the reentrant tachycardia associated with Wolff-Parkinson-White syndrome, ventricular ectopy, and ventricular tachycardia. 3-6 It has been used with success in both pediatric and adult patients. 7 Annals of Emergency Medicine
In addition to quinidine-like activity, propafenone possesses some beta-blocking activity, approximately 5% of the beta-blocking potency of propranolol, as well as minor calcium channel blocking activity, approximately 1% of the activity of ,verapamil.4 Neither effect is well understood but it is thought that the betablocking effects probably are clinically significant.4,5,8 Propafenone may be given by either the IV or oral route of administration. 3 More than 95% of the drug is absorbed after an oral dose and it reaches peak levels approximately two to three hours following ingestion. 8 Absorption occurs by a saturable pro16:4 Aprir 1987
FIGURE 2. A 12-lead E C G o b t a i n e d in t h e e m e r g e n c y d e p a r t m e n t d e m o n strating a right bundle branch block associated with a first-degree heart b l o c k a n d a p r o l o n g e d Q T interval. pafenone and may become so elevated that failure to capture frequently will result, s Levy states that it may not be possible to successfully pace patients unless smaller dosages had been given initially or enough time has passed to allow for sufficient elimination of the drug. ~4
SUMMARY
cess involving presystemic clearance; Connolly noted that a three-fold increase in dosage from 300 mg to 900 rag/day resulted in a ten-fold increase in plasma c o n c e n t r a t i o n s (this increase may be particularly significant in overdose situations as occurred in our case).8,9 Propafenone is more than 97% protein bound and serum digoxin levels will rise if the two drugs are administered c o n c u r r e n t l yJ, 8 The plasma half-life is approximately five to eight hours in most patients, but it is highly individualized and ranges from two hours to 32 hours.g, 8 Propafenone is actively metabolized and less than 1% of an oral dose is excreted u n changed in the urine. 8 M e t a b o l i t e s may contribute to the effectiveness of the drug and at least one metabolite, 5-hydroxy-propafenone, has a n t i a r rhythmic effects of its own. 4 Propafenone causes m a n y ECG changes, most notably prolongation of the PR interval), 2 Other k n o w n ECG changes include the development of right or left bundle branch blocks, i,2 elongation of both the QRS and corrected QT interval, I,3 and slowing of the heart. 6 Hodges et al 1 reported that propafenone prolongs the electrocardiographic PR and QRS intervals by 16% and 18%, respectively. Keller et a110found a direct correlation between serum levels of propafenone and the prolongation of the AV c o n d u c t i o n time. Clinically, p r o p a f e n o n e m a y worsen congestive heart failure or aggrevate an e x i s t i n g a r r h y t h m i a . 2 , 4 Spontaneous v e n t r i c u l a r f i b r i l l a t i o n has been reported following the erroneous oral a d m i n i s t r a t i o n of 1,800 16:4April 1987
mg over one day. n Other reported adverse effects include gastrointestinal complaints such as nausea, constipation, an abnormal metallic taste, and cholestatic jaundice; neurological complaints including headache, dizziness, paresthesias, visual blurring, tremors, and syncope; and a variety of other complaints including general malaise, flushing, sweating, an acneiform rash, and anaphylaxis. 2-6 In addition, one case of m a n i a has b e e n described a n d att r i b u t e d to the s i m u l a r i t y b e t w e e n p r o p a f e n o n e a n d b u p r o p i n . 12 Both drugs b e l o n g to t h e p r o p i o p h e r o n e group. 12 There are no other case reports of seizure activity following propafenone ingestion. It r e m a i n s u n c l e a r if the two generalized seizures e v i d e n t i n our case were a toxic effect of propafenone or were secondary to cerebral hypoperfusion caused by conduction d i s t u r b a n c e s and a r r h y t h m i a s . Phenytoin, w h i c h has class lb antia r r h y t h m i c properties, should be administered with great caution in the presence of preexisting conduction defects. 13 Because some of phenytoin's cardiovascular actions are shared b y propafenone, a potential for exacerbation exists and its administration, as o c c u r r e d i n this case, is c e r t a i n l y questionable. Although it was not attempted in our case, i n s e r t i o n of a p a c e m a k e r may prove ineffective in patients bec o m i n g s y m p t o m a t i c s e c o n d a r y to b r a d y d y s r h y t h m i a s . C o u m e l et al found that stimulation thresholds rise with increasing serum levels of proAnnals of Emergency Medicine
We report the case of a near-fatal propafenone ingestion in a 2-year-old child. W h e n propafenone is released from clinical trials, accidental or suicidal overdoses can be expected to occur. Because of the time delay associated with the use of ipecac, immediate gastric lavage followed by the adm i n i s t r a t i o n of a c t i v a t e d c h a r c o a l m i g h t p r e v e n t t h e rapid o n s e t of s y m p t o m s and should be used. Our case suggests that acute cardiac dysfunction is a major concern in toxic ingestions and that the use of phenytoin to control associated seizure activity is unwise. Prolonged cardiac life support measures were successful i n the resuscitation of this patient.
REFERENCES
1. Hodges M, Salerno D, Granrud G: Doubleblind placebo-controlled evaluation of propafenone in suppressingventricular ectopic activity. Am J Cardiol 1984;54:45D-50D. 2. de Soyza N, Terry L, Murphy ML, et al: Effect of propafenonein patients with stable ventricular arrhythmias. Am Heart J i984;108: 285-289. 3. Schamoth L, Myburgh DP, Schamoth CL, et al: Oral propafenone in the suppression of chronic stable ventricular arrhythmias. Chest 1985;87:448-45i. 4. Brodsky MA, Allon BJ: Propafenone. Chest 1985;88:164-165, 5. Coumel P, Leclercq JF, Assayag P: European experience with the antiarrhythmic efficacy of propafenone for supraventricular and ventricular arrhythmias. Am J Cardiol 1984;54: 60D-66D. 6. Breithardt G, Borggrefe M, WiebringhausE, et ah Effect of propafenonein the Wolff-Parkinson-White Syndrome:Electrophysiologicfindings and long-term follow-up. Am J Cardiol 1984;54:29D-39D. 7. Weber H, Elgoten G, WesselhoeftA: Experience with propafenone in the treatment of arrhythmias in pediatric patients, in Schleppen M, Olsson B (eds): Cardiac Arrhythmias - - Diagnosis, Prognosis, Therapy. Heidelberg, Springler-Verag, 1983, p 183. 8. Siddoway LA, Roden DM, Woosley RI: 439/101
PROPAFENONE INGESTION McHugh & Perina
Clinical pharmacology of propafenone: Pharmacokinetics, metabolism and concentrationresponse relations. A m J Cardiol 1984;54: 9D-12D.
macologic effect on atrioventricular conduction time of the antiarrhythmic drug propafenone. Eur J Clin PharmacoI 1978;13:17-22.
9. Connolly SJ, Kates RE, Lebsach CS, et ah Clinical pharmacology of propafenone. Circulation 1983;68:589-596.
ll. Buss J, Neuss H, Bilgin Y, et al: Malignant ventricular tachyarrhythmias in association with propafenone treatment. Eur Heart J 1985; 6:424-428.
10. Keller K, Meyer-Estorf G, Beck OA: Correlations between serum concentration and phar-
12. Jack RA: A case of mania secondary to propafenone. J Clin Psych 1985;46:104-105.
102/440
Annals of Emergency Medicine
13. Hoffman JR: Pharmacology of cardiovascular drags, in Tintinalli ]E, Rothstein RJ, Krome RL (eds): Emergency Medicine, A Comprehensive Study Guide. New York, McGraw-Hin Book Co, 1985, p 103. 14. Prystowsky EN, Heger JJ, Chilson DA, et ah Antiarrhythmic and electrophysiologic effects of oral propafenone {Discussion II). Am J Cardiol 1984;54:51D-52D.
16:4 April 1987
Propafenone Ingestion Propafenone is a type lc antiarrhythmic drug that recently has become available for clinical trials within the United States. We present the case of a 2-year-old child who accidentally ingested 1,800 mg (133 mg/kg) of propafenone. The patient subsequently developed cardiac conduction abnormalities and generalized seizures. Following the administration of IV phenytoin, cardiopulmonary collapse occurred. The patient had a successful outcome with aggressive cardiopulmonary life support. [McHugh TP, Perina DG: Propafenone ingestion. Ann Emerg Med April 1987;16:437-440.] INTRODUCTION First synthesized in 1970, propafenone is an investigational class lc antiarrhythmic drug. 1 It has been used commercially in Europe since 1977 under the trade name Rytmonorm ® and has only recently become available for clinical trials in the United States.I, z We report the case of a child who accidentally ingested a small number of tablets and subsequently developed cardiac conduction disturbances and seizure activity followed by cardiopulmouary collapse. This is the first case of a toxic ingestion of propafenone to be reported in the United States.
Terrance P McHugh, MD, FACEP Debra G Perina, MD Columbia, South Carolina From the Department of Emergency Medicine, Richland Memorial Hospital, Columbia, South Carolina. Received for publication May 16, 1986. Revision received November 4, 1986. Accepted for publication December 2, 1986. Address for reprints: 7errance McHugh, MD, Department of Emergency Medicine, Richland Memorial Hospital, 5 Richland Medical Park Road, Columbia, South Carolina 29203.
CASE REPORT A 2-year-old boy presented with a history of having ingested 12 150-mg tablets of propafenone. A total of 1,800 mg (133 mg/kg) had been swallowed approximately ten minutes prior to his arrival. The child had been well prior to this ingestion and had no significant medical history. On arrival, the child was alert, moving all extremities, and exhibiting good muscular strength. Initial vital signs were as follows: temperature, 36.1 C orally; pulse, 100; and respirations, 24. An initial blood pressure was not obtained. The child weighed 13.5 kg. Auscultation of the chest revealed the presence of normal heart and breath sounds; no heart murmurs or gallops were heard. The remainder of the physical examination was unremarkable. The patient was placed on a cardiac monitor, given 15 mL syrup of ipecac and vomited about 100 mL of gastric contents approximately 30 minutes post ingestion. No pill fragments were seen. After an additional 20 minutes, the child had a generalized seizure that lasted approximately 60 seconds. Concurrent with this seizure, the QRS complex had become much wider (Figure 1). A blood pressure of 60/40 m m Hg was measured, and an IV line using 2.5% dextrose/0.45 normal saline at 20 mL/hr was started. No medication was given to the child during or immediately following the seizure. An ECG showed the presence of a persistent right bundle branch block associated with a first-degree atrioventricular (AV) block and prolongation of the QT interval (Figure 2). While receiving supplemental oxygen by face mask, arterial blood gases revealed a pH of 7.34, pO 2 of 144 m m Hg, and pCO2 of 33 m m Hg. A complete blood count showed a hemoglobin of 10.5 gm/dL and a white cell count of 11,400 (21 polys, 71 lymphs, five monos, one eosinophil, and two basophils). Other laboratory results were as follows: glucose, 92 mg/dL; BUN, 9 mg/dL; sodium, 141 mEq/L; potassium, 4.4 mEq/ L; chloride, 104 mEq/L; serum bicarbonate, 27 mEq/L; creatinine, 0.6 mg/dL; magnesium, 2.4 mEq/L; and calcium, 10.5 mEq/L. A serum and urine drug screen was drawn. Gastric lavage was performed, followed by the administra16:4April 1987
Annals of Emergency Medicine
437/99
PROPAFENONE INGESTION McHugh & Perina
FIGURE 1. ECG monitor tracings ob-
tained during the patient's treatment. Strip A is the initial ECG tracing obt a i n e d on arrival, strip B was obtained i m m e d i a t e l y after the initial seizure, and strip C was obtained just prior to resuscitation efforts. tion of 30 g of charcoal and 4 oz of magnesium citrate• Arrangements were made to transport the child to the pediatric intensive care unit (PICU). At this point he responded to his name but was becoming increasingly lethargic. Repeat vital signs included a blood pressure of 80/60 m m Hg and a heart rate of 70. Following a second generalized seizure, the patient received 200 mg phenobarbital IV and was then, two hours following ingestion, transported to the PICU. The patient received 135 mg of phenytoin IV over several minutes. About 30 minutes later, cardiac monitoring revealed an irregular bradycardia with progressive widening of the QRS and QT interval (Figure 1). Shortly thereafter (2.5 hours following ingestion), no pulse could be palpated and the p a t i e n t s t o p p e d all s p o n t a n e o u s breathing efforts• The patient was intubated and advanced cardiac life support measures were begun using atropine, s o d i u m b i c a r b o n a t e , and dopamine. During the period of cardiopulmonary collapse, the patient remained in electromechanical dissociation. C o n t i n u o u s ECG t r a c i n g s showed periods of bradycardia, down to 35 beats/rain and associated with wide QRS complexes, alternating with periods of tachycardia, up to 120 beats/min and associated with varying QRS morphology• When a palpable blood pressure finally was detected, a junctional r h y t h m of 80 beats/min with a wide QRS predominated• This entire episode occurred over about 60 minutes• The ECG gradually returned to normal over several hours and the patient made an uneventful recovery. He was discharged from the hospital in three days with no residual sequelae. DISCUSSION
Propafenone is a class lc antiarrhythmic agent exhibiting both local anesthetic actions and membrane stabilizing effects on myocardial conduction cells. 3 It blocks the fast inward sodium current, and this action is largely responsible for the decreased 100/438
A,
.....
:,~z,
! B. % : ~ %~ :::6
L%ZL
L;;: ¸
rate of depolarization it produces, z Propafenone slows sinus node automatically and decreases conduction time through both the AV node and the ventricular conduction system.I, 4 This depression of conduction velocity is thought to be the major mechanism by which propafenone terminates atrial and v e n t r i c u l a r arrhythmiasJ In Europe propafenone is used for the suppression of chronic supraventricular tachycardia, the reentrant tachycardia associated with Wolff-Parkinson-White syndrome, ventricular ectopy, and ventricular tachycardia. 3-6 It has been used with success in both pediatric and adult patients. 7 Annals of Emergency Medicine
In addition to quinidine-like activity, propafenone possesses some beta-blocking activity, approximately 5% of the beta-blocking potency of propranolol, as well as minor calcium channel blocking activity, approximately 1% of the activity of ,verapamil.4 Neither effect is well understood but it is thought that the betablocking effects probably are clinically significant.4,5,8 Propafenone may be given by either the IV or oral route of administration. 3 More than 95% of the drug is absorbed after an oral dose and it reaches peak levels approximately two to three hours following ingestion. 8 Absorption occurs by a saturable pro16:4 Aprir 1987
FIGURE 2. A 12-lead E C G o b t a i n e d in t h e e m e r g e n c y d e p a r t m e n t d e m o n strating a right bundle branch block associated with a first-degree heart b l o c k a n d a p r o l o n g e d Q T interval. pafenone and may become so elevated that failure to capture frequently will result, s Levy states that it may not be possible to successfully pace patients unless smaller dosages had been given initially or enough time has passed to allow for sufficient elimination of the drug. ~4
SUMMARY
cess involving presystemic clearance; Connolly noted that a three-fold increase in dosage from 300 mg to 900 rag/day resulted in a ten-fold increase in plasma c o n c e n t r a t i o n s (this increase may be particularly significant in overdose situations as occurred in our case).8,9 Propafenone is more than 97% protein bound and serum digoxin levels will rise if the two drugs are administered c o n c u r r e n t l yJ, 8 The plasma half-life is approximately five to eight hours in most patients, but it is highly individualized and ranges from two hours to 32 hours.g, 8 Propafenone is actively metabolized and less than 1% of an oral dose is excreted u n changed in the urine. 8 M e t a b o l i t e s may contribute to the effectiveness of the drug and at least one metabolite, 5-hydroxy-propafenone, has a n t i a r rhythmic effects of its own. 4 Propafenone causes m a n y ECG changes, most notably prolongation of the PR interval), 2 Other k n o w n ECG changes include the development of right or left bundle branch blocks, i,2 elongation of both the QRS and corrected QT interval, I,3 and slowing of the heart. 6 Hodges et al 1 reported that propafenone prolongs the electrocardiographic PR and QRS intervals by 16% and 18%, respectively. Keller et a110found a direct correlation between serum levels of propafenone and the prolongation of the AV c o n d u c t i o n time. Clinically, p r o p a f e n o n e m a y worsen congestive heart failure or aggrevate an e x i s t i n g a r r h y t h m i a . 2 , 4 Spontaneous v e n t r i c u l a r f i b r i l l a t i o n has been reported following the erroneous oral a d m i n i s t r a t i o n of 1,800 16:4April 1987
mg over one day. n Other reported adverse effects include gastrointestinal complaints such as nausea, constipation, an abnormal metallic taste, and cholestatic jaundice; neurological complaints including headache, dizziness, paresthesias, visual blurring, tremors, and syncope; and a variety of other complaints including general malaise, flushing, sweating, an acneiform rash, and anaphylaxis. 2-6 In addition, one case of m a n i a has b e e n described a n d att r i b u t e d to the s i m u l a r i t y b e t w e e n p r o p a f e n o n e a n d b u p r o p i n . 12 Both drugs b e l o n g to t h e p r o p i o p h e r o n e group. 12 There are no other case reports of seizure activity following propafenone ingestion. It r e m a i n s u n c l e a r if the two generalized seizures e v i d e n t i n our case were a toxic effect of propafenone or were secondary to cerebral hypoperfusion caused by conduction d i s t u r b a n c e s and a r r h y t h m i a s . Phenytoin, w h i c h has class lb antia r r h y t h m i c properties, should be administered with great caution in the presence of preexisting conduction defects. 13 Because some of phenytoin's cardiovascular actions are shared b y propafenone, a potential for exacerbation exists and its administration, as o c c u r r e d i n this case, is c e r t a i n l y questionable. Although it was not attempted in our case, i n s e r t i o n of a p a c e m a k e r may prove ineffective in patients bec o m i n g s y m p t o m a t i c s e c o n d a r y to b r a d y d y s r h y t h m i a s . C o u m e l et al found that stimulation thresholds rise with increasing serum levels of proAnnals of Emergency Medicine
We report the case of a near-fatal propafenone ingestion in a 2-year-old child. W h e n propafenone is released from clinical trials, accidental or suicidal overdoses can be expected to occur. Because of the time delay associated with the use of ipecac, immediate gastric lavage followed by the adm i n i s t r a t i o n of a c t i v a t e d c h a r c o a l m i g h t p r e v e n t t h e rapid o n s e t of s y m p t o m s and should be used. Our case suggests that acute cardiac dysfunction is a major concern in toxic ingestions and that the use of phenytoin to control associated seizure activity is unwise. Prolonged cardiac life support measures were successful i n the resuscitation of this patient.
REFERENCES
1. Hodges M, Salerno D, Granrud G: Doubleblind placebo-controlled evaluation of propafenone in suppressingventricular ectopic activity. Am J Cardiol 1984;54:45D-50D. 2. de Soyza N, Terry L, Murphy ML, et al: Effect of propafenonein patients with stable ventricular arrhythmias. Am Heart J i984;108: 285-289. 3. Schamoth L, Myburgh DP, Schamoth CL, et al: Oral propafenone in the suppression of chronic stable ventricular arrhythmias. Chest 1985;87:448-45i. 4. Brodsky MA, Allon BJ: Propafenone. Chest 1985;88:164-165, 5. Coumel P, Leclercq JF, Assayag P: European experience with the antiarrhythmic efficacy of propafenone for supraventricular and ventricular arrhythmias. Am J Cardiol 1984;54: 60D-66D. 6. Breithardt G, Borggrefe M, WiebringhausE, et ah Effect of propafenonein the Wolff-Parkinson-White Syndrome:Electrophysiologicfindings and long-term follow-up. Am J Cardiol 1984;54:29D-39D. 7. Weber H, Elgoten G, WesselhoeftA: Experience with propafenone in the treatment of arrhythmias in pediatric patients, in Schleppen M, Olsson B (eds): Cardiac Arrhythmias - - Diagnosis, Prognosis, Therapy. Heidelberg, Springler-Verag, 1983, p 183. 8. Siddoway LA, Roden DM, Woosley RI: 439/101
PROPAFENONE INGESTION McHugh & Perina
Clinical pharmacology of propafenone: Pharmacokinetics, metabolism and concentrationresponse relations. A m J Cardiol 1984;54: 9D-12D.
macologic effect on atrioventricular conduction time of the antiarrhythmic drug propafenone. Eur J Clin PharmacoI 1978;13:17-22.
9. Connolly SJ, Kates RE, Lebsach CS, et ah Clinical pharmacology of propafenone. Circulation 1983;68:589-596.
ll. Buss J, Neuss H, Bilgin Y, et al: Malignant ventricular tachyarrhythmias in association with propafenone treatment. Eur Heart J 1985; 6:424-428.
10. Keller K, Meyer-Estorf G, Beck OA: Correlations between serum concentration and phar-
12. Jack RA: A case of mania secondary to propafenone. J Clin Psych 1985;46:104-105.
102/440
Annals of Emergency Medicine
13. Hoffman JR: Pharmacology of cardiovascular drags, in Tintinalli ]E, Rothstein RJ, Krome RL (eds): Emergency Medicine, A Comprehensive Study Guide. New York, McGraw-Hin Book Co, 1985, p 103. 14. Prystowsky EN, Heger JJ, Chilson DA, et ah Antiarrhythmic and electrophysiologic effects of oral propafenone {Discussion II). Am J Cardiol 1984;54:51D-52D.
16:4 April 1987