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Conduction abnormalities complicating carbamazepine therapy
LETTERS TO THE EDITOR CONDUCTION ABNORMALITIES CARBAMAZEPINE THERAPY
COMPLICATING
To the Editor: An 87-year-old patient was admitted to the hospital for evaluation of recent-onset seizure activity for which she had been treated with phenytoin, 300 mg orally per day. On admission, the patient was an elderly thin woman in no distress who was oriented to person and place but not to time. Physical examination was otherwise unremarkable. Electrocardiography showed sinus rhythm at 78 with P-R interval of 0.20 and nonspecific ST-T wave abnormalities, which were without change from six months before admission. Laboratory values included normal calcium, magnesium, sodium, and a therapeutic phenytoin level. Carbamazepine was added to the patient’s drug regimen at 100 mg twice daily orally and then increased to 200 mg twice daily orally to attain therapeutic levels of both drugs. The patient was noted to have a heart rate of 30 beats/minute on the fourth hospital day. Electrocardiography showed complete atrioventricular block with an atrial rate of 100 and a ventricular escape of 30. The patient had development of hypotension, decreased mentation, congestive heart failure, and poor peripheral perfusion, which required placement of a temporary transvenous pacemaker. Both anticonvulsants were withheld. Within 24 hours, electrocardiography showed sinus rhythm at a rate of 70 with firstdegree atrioventricular block and right bundle branch block. The latter persisted until three days later, at which time the patient’s electrocardiographic findings were unchanged from admission. Creatine phosphokinase isoenzyme values were normal throughout this four-day period. Phenytoin was reinstituted without change in the patient’s cardiac status. Cardiac effects of carbamazepine, rare but established complications, include congestive heart failure [I], bradycardia [2], and atrioventricular block [3]. The effect of the drug has been studied in dogs by Beerman and Edhag [4], who demonstrated slowing of the idioventricular rate with experimentally induced heart block within one hour if oral administration without effect on intra-atrial or intraventricular conduction. In humans, it has been shown experimentally to increase the degree of atrioventricular block and to decrease ventricular automaticity [5]. There is no clear relation to dose. The effect has been noted after massive overdose and at subtherapeutic levels. It has been noted upon initiation of therapy and has been noted to arise after long-term treatment. One investigator has noted a doseresponse effect. Carbamazepine is a widely used medication for seizure disorders, trigeminal neuralgia, and affective disorders. Clinical recognition of potential toxicity can be difficult in an elderly patient whose complaint of dizziness or unsteadiness may be attributed to a handful of disorders including arrhythmias, metabolic disorders, and poor cerebral perfusion. Beerman et al [6] have advised that the drug be withheld from patients with conduction abnormalities as
February
these may predispose to this toxicity or alter the drug’s effect. In addition to withdrawal of the drug with temporary transvenous pacing as a lifesaving measure, cardiac complications have also been successfully treated by hemoperfusion. CHRISTINE
M. GASPERETTI,
M.D.
Department of Medicine Boston City Hospital Boston, Massachusetts 02118 1. 2. 3.
4. 5.
Terrence CF, Fromm G: Congestive heart failure during carbamazepine therapy. Ann Neurol 1980; 8: 200-201. Herzberg L: Carbamazepine and bradycardia. Lancet 1978; I: 1097-1098. Ladefoged SD, Mogelvang JC: Total atrioventricular block with syncopes complicating carbamazepine therapy. Acta Med Stand 1982; 212: 185-186. Beermann B, Edhag 0: Depressive effects of carbamazepine on idioventricular rhythm in man. Br Med J 1978; 2: 171-172. Beermann 8, Edhag 0, Vallin H: Advanced heart block aggravated by carbamazepine. Br Heart J 1975; 37: 668-671. Submitted
August
14, 1986,
SEVERE SALICYLATE SEPTIC SHOCK
and accepted
INTOXICATION
October
16, 1986
MIMICKING
To the Editor: Salicylate intoxication is an important cause of drug overdose. In adults, delay in diagnosis occurs in up to 30 percent of cases and is associated with major morbidity and mot’tality [I]. We describe a patient with severe salicylate intoxication whose presenting findings were “classic” of septic shock if it were not for the already known diagnosis. A previously healthy 62-year-old man was admitted to the hospital for assessment of acute confusion. Physical examination on admission showed that he was normotensive, confused, and disoriented without any focal neurologic deficit. Over the next six to eight hours, a low-grade fever developed, and he became tachypneic, hypotensive, and oliguric. He was transferred to the intensive care unit and was found to have noncardiogenic pulmonary edema, “high-out put” shock, mixed respiratory alkalosis and anion-gap metabolic acidosis, hyperprothrombinemia, and biochemical changes of rhabdomyolysis. Drug screen showed that he had pure salicylate intoxication with a blood level on admission of 7.7 mM (toxic, more than 1.65 mM). He was initially treated with intravenous dopamine and isotonic sodium bicarbonate under close hemodynamic monitoring with a Swan-Ganz catheter. Forced alkaline diuresis was initiated and maintained with intravenous sodium bicarbonate solution and one dose of furosemide (40 mg) with both blood and urine pH maintained above 7.4 during the treatment period. His course in the hospital is
1987
The American
Journal
of Medicine
Volume
82
381
COMPLICATING
To the Editor: An 87-year-old patient was admitted to the hospital for evaluation of recent-onset seizure activity for which she had been treated with phenytoin, 300 mg orally per day. On admission, the patient was an elderly thin woman in no distress who was oriented to person and place but not to time. Physical examination was otherwise unremarkable. Electrocardiography showed sinus rhythm at 78 with P-R interval of 0.20 and nonspecific ST-T wave abnormalities, which were without change from six months before admission. Laboratory values included normal calcium, magnesium, sodium, and a therapeutic phenytoin level. Carbamazepine was added to the patient’s drug regimen at 100 mg twice daily orally and then increased to 200 mg twice daily orally to attain therapeutic levels of both drugs. The patient was noted to have a heart rate of 30 beats/minute on the fourth hospital day. Electrocardiography showed complete atrioventricular block with an atrial rate of 100 and a ventricular escape of 30. The patient had development of hypotension, decreased mentation, congestive heart failure, and poor peripheral perfusion, which required placement of a temporary transvenous pacemaker. Both anticonvulsants were withheld. Within 24 hours, electrocardiography showed sinus rhythm at a rate of 70 with firstdegree atrioventricular block and right bundle branch block. The latter persisted until three days later, at which time the patient’s electrocardiographic findings were unchanged from admission. Creatine phosphokinase isoenzyme values were normal throughout this four-day period. Phenytoin was reinstituted without change in the patient’s cardiac status. Cardiac effects of carbamazepine, rare but established complications, include congestive heart failure [I], bradycardia [2], and atrioventricular block [3]. The effect of the drug has been studied in dogs by Beerman and Edhag [4], who demonstrated slowing of the idioventricular rate with experimentally induced heart block within one hour if oral administration without effect on intra-atrial or intraventricular conduction. In humans, it has been shown experimentally to increase the degree of atrioventricular block and to decrease ventricular automaticity [5]. There is no clear relation to dose. The effect has been noted after massive overdose and at subtherapeutic levels. It has been noted upon initiation of therapy and has been noted to arise after long-term treatment. One investigator has noted a doseresponse effect. Carbamazepine is a widely used medication for seizure disorders, trigeminal neuralgia, and affective disorders. Clinical recognition of potential toxicity can be difficult in an elderly patient whose complaint of dizziness or unsteadiness may be attributed to a handful of disorders including arrhythmias, metabolic disorders, and poor cerebral perfusion. Beerman et al [6] have advised that the drug be withheld from patients with conduction abnormalities as
February
these may predispose to this toxicity or alter the drug’s effect. In addition to withdrawal of the drug with temporary transvenous pacing as a lifesaving measure, cardiac complications have also been successfully treated by hemoperfusion. CHRISTINE
M. GASPERETTI,
M.D.
Department of Medicine Boston City Hospital Boston, Massachusetts 02118 1. 2. 3.
4. 5.
Terrence CF, Fromm G: Congestive heart failure during carbamazepine therapy. Ann Neurol 1980; 8: 200-201. Herzberg L: Carbamazepine and bradycardia. Lancet 1978; I: 1097-1098. Ladefoged SD, Mogelvang JC: Total atrioventricular block with syncopes complicating carbamazepine therapy. Acta Med Stand 1982; 212: 185-186. Beermann B, Edhag 0: Depressive effects of carbamazepine on idioventricular rhythm in man. Br Med J 1978; 2: 171-172. Beermann 8, Edhag 0, Vallin H: Advanced heart block aggravated by carbamazepine. Br Heart J 1975; 37: 668-671. Submitted
August
14, 1986,
SEVERE SALICYLATE SEPTIC SHOCK
and accepted
INTOXICATION
October
16, 1986
MIMICKING
To the Editor: Salicylate intoxication is an important cause of drug overdose. In adults, delay in diagnosis occurs in up to 30 percent of cases and is associated with major morbidity and mot’tality [I]. We describe a patient with severe salicylate intoxication whose presenting findings were “classic” of septic shock if it were not for the already known diagnosis. A previously healthy 62-year-old man was admitted to the hospital for assessment of acute confusion. Physical examination on admission showed that he was normotensive, confused, and disoriented without any focal neurologic deficit. Over the next six to eight hours, a low-grade fever developed, and he became tachypneic, hypotensive, and oliguric. He was transferred to the intensive care unit and was found to have noncardiogenic pulmonary edema, “high-out put” shock, mixed respiratory alkalosis and anion-gap metabolic acidosis, hyperprothrombinemia, and biochemical changes of rhabdomyolysis. Drug screen showed that he had pure salicylate intoxication with a blood level on admission of 7.7 mM (toxic, more than 1.65 mM). He was initially treated with intravenous dopamine and isotonic sodium bicarbonate under close hemodynamic monitoring with a Swan-Ganz catheter. Forced alkaline diuresis was initiated and maintained with intravenous sodium bicarbonate solution and one dose of furosemide (40 mg) with both blood and urine pH maintained above 7.4 during the treatment period. His course in the hospital is
1987
The American
Journal
of Medicine
Volume
82
381