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Fetal death after successful conversion of fetal supraventricular tachycardia with digoxin and verapamil
Placental inulin permeability
Volume 158 Number 5
5. 6. 7. 8. 9. 10. 11.
sion permeability of cyanocobalamin in human placenta. Am J Physiol 1986;250:R459-64. Brandes JM, Abramovici H, Peretz A. Passage of inulin from gravida to fetus in normal pregnancy and during cesarean section. Obstet Gynecol 1971;37:877-80. Flexner LB, Pohl HA. Transfer of radioactive sodium across the placenta of the' guinea pig. Am J Physiol 1941; 132:594-606. Friis-Hansen B. Body water compartments in children. Pediatrics 1961 ;28: 169-81. Waugh WH. Photometry of inulin and polyfructosan by use of a cysteine/tryptophan reaction. Clin Chern 1977; 23:639-45. Snedecor GW, Cochran WG. Statistical methods. 7th ed. Ames, Iowa: Iowa State University Press, 1980. Chamberlain PF, Manning FA, Morrison I, Lange IR. Circadian rhythm in bladder volumes in the term human fetus. Obstet Gynecol 1984;64:657-60. Flexner LB, Cowie DB, Hellman LM, Wilde WS, Vos-
12. 13. 14.
15.
burgh GJ. The permeability of the human placenta to sodium in normal and abnormal pregnancies. AM J OBSTET GYNECOL 1948;55:469-80. Longworth LG. Diffusion in liquids. In: Gray DE, ed. American Institute of Physics handbook. 3rd ed. New York: McGraw-Hill, 1972. Lanman RC, Burton JA, Schanker LS. Diffusion coefficients of some 14 C labelled saccharides of biological interest. Life Sci 1971; 10:803-11. Faber JJ. Diffusional exchange between foetus and mother as a function of the physical properties of the diffusing materials. In: Comline KS, Cross KW, Dawes GS, Nathanielsz PW, eds. Foetal and neonatal physiology. Cambridge: Cambridge University Press, 1973. Wilbur JD, Power GG, Longo LD. Reply to "A mathematical model: comment on the placental water exchange model of Wilbur, Power, and Longo." Am J Physiol l979;236:R89-91.
Fetal death after successful conversion of fetal supraventricular tachycardia with digoxin and verapamil John Owen, MD, Edward V. Colvin, MD, and Richard 0. Davis, MD Birmingham, Alabama A case of nonimmune hydrops fetalis associated with a supraventricular tachycardia was successfully treated with digoxin and verapamil. After resolution of the hydropic changes, however, the fetus unexplainedly died. Side effects from the drug therapy may have been responsible for the event. (AM J 0BSTET GYNECOL 1988;158:1169-70.)
Key words: Fetal supraventricular tachycardia, fetal death, in utero treatment with digoxin and verapamil Fetal supraventricular tachycardia is an uncommon event and a treatable cause of nonimmune hydrops fetalis. To date most of what is known about fetal supraventricular tachycardia has come from case reports. Until prospective, randomized studies are performed, the optimal management of fetal supraventricular tachycardia will remain uncertain. Maternal administration of digoxin and verapamil has been previously described.' We report a case of nonimmune hydrops fetalis associated with fetal supraventricular tachycardia that was successfully converted with digoxin and verapamil. Although complete ultrasonographic resolution of the hydropic changes
From the Departments of Obstetrics and Gynecology and Pediatric Cardiology, University of Alabama Hospitals. Received for publication October I, 1986; revised March 16, july 27, and August 17, 1987; accepted September 22, 1987. Reprint requests: John Owen, MD, Department of Obstetrics and Gynecology, University Station, Birmingham, AL 35294.
occurred, the fetus died. We believe this is the first report of a fetal death after successful therapy of a supraventricular tachycardia.
Case report A 28-year-old woman, para 2-0-0-2, at 32 weeks' gestation was transferred to the University of Alabama at Birmingham with a diagnosis of nonimmune hydrops fetalis. Approximately 2 weeks earlier she had noticed rapidly increasing abdominal girth, and an ultrasound examination showed polyhydramnios and a hydropic fetus with a heart rate of 260 bpm. On arrival her vital signs were normal, her cervix was closed, and the remainder of her general physical examination was within normal limits. Routine admission laboratory test results, a fetal cell stain, and a Coombs test were unremarkable. A portable Doppler unit measured the fetal heart rate at 260 bpm. An ultrasound examination showed polyhydramnios and a fetus with marked ascites and small bilateral pleural effusions. A fetal echo1169
1170 Owen, Colvin, and Davis
May 1988
Am J Obstet Gynecol
cardiogram showed two equal-sized ventricles with normal atrioventricular valves and mild bilateral atrial dilatation. The predominant rhythm was tachycardic, with a rate ranging between 260 and 280 bpm. This rhythm would intermittently break into brief periods of a slower rhythm. During the slower rhythm the atrial and ventricular rates were identical, suggesting a sinus rhythm rather than an increase in the degree of atrioventricular block. There were also occasional single premature beats suggesting a reentry mechanism for the supraventricular tachycardia. In the first 24 hours the patient received a total of 1.25 mg of digoxin. Her peak level after this was 2.4 mg/L (therapeutic range 0.5 to 2.2 mg/L). She then received oral digoxin, 0.5 mg twice a day, but the trough levels fell below 1.0 mg/L. The oral digoxin dosage was increased to 0.875 mg twice a day and the trough level rose to 1.2 mg/L. On day 3 the pediatric cardiologist recommended the addition of oral propranolol, 20 mg four times daily. After 48 hours with no response, the propranolol was stopped. Verapamil, 80 mg by mouth three times daily, was begun on day 8, after waiting 48 hours for the propranolol to be eliminated. Digoxin dosing was changed to the intravenous route, which has a higher and more reliable bioavailability. With doses in the range of 0.75 to 1.0 mg/24 hr, trough levels approached 2.0 mg/L. On day 10 short periods of normal fetal heart rate were documented. On day 11 the oral verapamil dosage was increased to 120 mg three times daily. By day 13 the fetal heart rate was consistently in the normal range, and the digoxin dosage was decreased from 0.75 mg to 0.5 mg/24 hr. Two days later the trough digoxin level was 1.4 mg/L, and no further levels were measured. A nonstress test done on day 17 was reactive. The patient was discharged on day 19 to continue oral digoxin (0.625 mg four times daily) and oral verapamil (120 mg three times daily) therapy. She returned to us on day 28 at 36 weeks' gestation, at which time an ultrasound examination showed complete resolution of the hydropic changes and persistent hydramnios. A reactive nonstress test had been documented 2 days earlier. Over the next 2 days she became aware of the complete absence of fetal activity. Her private obstetrician
confirmed the fetal death and induced labor with oxytocin. A 3300 gm male infant with no obvious abnormalities was delivered. An autopsy request was declined. Comment
This report describes a fetal death after successful therapy of nonimmune hydrops fetalis secondary to a fetal supraventricular tachycardia. The possible explanations for this event include a fatal congenital heart defect and side effects from the therapy. There have been reports of cardiac decompensation after the use of intravenous verapamil in infants with supraventricular tachycardia. 2 Presumably, that problem occurred because of a simultaneous fall in systemic vascular resistance and cardiac contractility. It seems unlikely that this occurred here, because the symptoms of congestive heart failure had abated with verapamil therapy. Both digoxin and verapamil are known to decrease conduction in the atrioventricular node and to increase the level of atrioventricular block. It is possible that the combination may have resulted in complete heart block with an inadequate ventricular escape rate. In adults verapamil has been shown to impair the excretion of digoxin. It is possible that, in the 9 days between discharge and the death, the digoxin level rose enough to cause complete heart block. Whether this effect can take place in the fetus is not known, but one might gradually reduce the doses of digoxin and verapamil while monitoring the fetus frequently for persistence of the normal rhythm. One might also ask if more frequent fetal monitoring would have detected the apparent decompensation in time to act, and would the fetus have survived had delivery occurred after resolution of the hydropic changes and attainment of fetal pulmonary maturity?
REFERENCES 1. Kleinman CS, Cope! JA, Weinstein EM, eta!. Treatment of fetal supraventricular tachyarrhythmias. JCU 1985; 13:265-73. 2. Ebstein M, Kiel EA, Victoria BE. Cardiac decompensation following Verapamil therapy in infants with supraventricular tachycardia. Pediatrics 1985;75:737.
Volume 158 Number 5
5. 6. 7. 8. 9. 10. 11.
sion permeability of cyanocobalamin in human placenta. Am J Physiol 1986;250:R459-64. Brandes JM, Abramovici H, Peretz A. Passage of inulin from gravida to fetus in normal pregnancy and during cesarean section. Obstet Gynecol 1971;37:877-80. Flexner LB, Pohl HA. Transfer of radioactive sodium across the placenta of the' guinea pig. Am J Physiol 1941; 132:594-606. Friis-Hansen B. Body water compartments in children. Pediatrics 1961 ;28: 169-81. Waugh WH. Photometry of inulin and polyfructosan by use of a cysteine/tryptophan reaction. Clin Chern 1977; 23:639-45. Snedecor GW, Cochran WG. Statistical methods. 7th ed. Ames, Iowa: Iowa State University Press, 1980. Chamberlain PF, Manning FA, Morrison I, Lange IR. Circadian rhythm in bladder volumes in the term human fetus. Obstet Gynecol 1984;64:657-60. Flexner LB, Cowie DB, Hellman LM, Wilde WS, Vos-
12. 13. 14.
15.
burgh GJ. The permeability of the human placenta to sodium in normal and abnormal pregnancies. AM J OBSTET GYNECOL 1948;55:469-80. Longworth LG. Diffusion in liquids. In: Gray DE, ed. American Institute of Physics handbook. 3rd ed. New York: McGraw-Hill, 1972. Lanman RC, Burton JA, Schanker LS. Diffusion coefficients of some 14 C labelled saccharides of biological interest. Life Sci 1971; 10:803-11. Faber JJ. Diffusional exchange between foetus and mother as a function of the physical properties of the diffusing materials. In: Comline KS, Cross KW, Dawes GS, Nathanielsz PW, eds. Foetal and neonatal physiology. Cambridge: Cambridge University Press, 1973. Wilbur JD, Power GG, Longo LD. Reply to "A mathematical model: comment on the placental water exchange model of Wilbur, Power, and Longo." Am J Physiol l979;236:R89-91.
Fetal death after successful conversion of fetal supraventricular tachycardia with digoxin and verapamil John Owen, MD, Edward V. Colvin, MD, and Richard 0. Davis, MD Birmingham, Alabama A case of nonimmune hydrops fetalis associated with a supraventricular tachycardia was successfully treated with digoxin and verapamil. After resolution of the hydropic changes, however, the fetus unexplainedly died. Side effects from the drug therapy may have been responsible for the event. (AM J 0BSTET GYNECOL 1988;158:1169-70.)
Key words: Fetal supraventricular tachycardia, fetal death, in utero treatment with digoxin and verapamil Fetal supraventricular tachycardia is an uncommon event and a treatable cause of nonimmune hydrops fetalis. To date most of what is known about fetal supraventricular tachycardia has come from case reports. Until prospective, randomized studies are performed, the optimal management of fetal supraventricular tachycardia will remain uncertain. Maternal administration of digoxin and verapamil has been previously described.' We report a case of nonimmune hydrops fetalis associated with fetal supraventricular tachycardia that was successfully converted with digoxin and verapamil. Although complete ultrasonographic resolution of the hydropic changes
From the Departments of Obstetrics and Gynecology and Pediatric Cardiology, University of Alabama Hospitals. Received for publication October I, 1986; revised March 16, july 27, and August 17, 1987; accepted September 22, 1987. Reprint requests: John Owen, MD, Department of Obstetrics and Gynecology, University Station, Birmingham, AL 35294.
occurred, the fetus died. We believe this is the first report of a fetal death after successful therapy of a supraventricular tachycardia.
Case report A 28-year-old woman, para 2-0-0-2, at 32 weeks' gestation was transferred to the University of Alabama at Birmingham with a diagnosis of nonimmune hydrops fetalis. Approximately 2 weeks earlier she had noticed rapidly increasing abdominal girth, and an ultrasound examination showed polyhydramnios and a hydropic fetus with a heart rate of 260 bpm. On arrival her vital signs were normal, her cervix was closed, and the remainder of her general physical examination was within normal limits. Routine admission laboratory test results, a fetal cell stain, and a Coombs test were unremarkable. A portable Doppler unit measured the fetal heart rate at 260 bpm. An ultrasound examination showed polyhydramnios and a fetus with marked ascites and small bilateral pleural effusions. A fetal echo1169
1170 Owen, Colvin, and Davis
May 1988
Am J Obstet Gynecol
cardiogram showed two equal-sized ventricles with normal atrioventricular valves and mild bilateral atrial dilatation. The predominant rhythm was tachycardic, with a rate ranging between 260 and 280 bpm. This rhythm would intermittently break into brief periods of a slower rhythm. During the slower rhythm the atrial and ventricular rates were identical, suggesting a sinus rhythm rather than an increase in the degree of atrioventricular block. There were also occasional single premature beats suggesting a reentry mechanism for the supraventricular tachycardia. In the first 24 hours the patient received a total of 1.25 mg of digoxin. Her peak level after this was 2.4 mg/L (therapeutic range 0.5 to 2.2 mg/L). She then received oral digoxin, 0.5 mg twice a day, but the trough levels fell below 1.0 mg/L. The oral digoxin dosage was increased to 0.875 mg twice a day and the trough level rose to 1.2 mg/L. On day 3 the pediatric cardiologist recommended the addition of oral propranolol, 20 mg four times daily. After 48 hours with no response, the propranolol was stopped. Verapamil, 80 mg by mouth three times daily, was begun on day 8, after waiting 48 hours for the propranolol to be eliminated. Digoxin dosing was changed to the intravenous route, which has a higher and more reliable bioavailability. With doses in the range of 0.75 to 1.0 mg/24 hr, trough levels approached 2.0 mg/L. On day 10 short periods of normal fetal heart rate were documented. On day 11 the oral verapamil dosage was increased to 120 mg three times daily. By day 13 the fetal heart rate was consistently in the normal range, and the digoxin dosage was decreased from 0.75 mg to 0.5 mg/24 hr. Two days later the trough digoxin level was 1.4 mg/L, and no further levels were measured. A nonstress test done on day 17 was reactive. The patient was discharged on day 19 to continue oral digoxin (0.625 mg four times daily) and oral verapamil (120 mg three times daily) therapy. She returned to us on day 28 at 36 weeks' gestation, at which time an ultrasound examination showed complete resolution of the hydropic changes and persistent hydramnios. A reactive nonstress test had been documented 2 days earlier. Over the next 2 days she became aware of the complete absence of fetal activity. Her private obstetrician
confirmed the fetal death and induced labor with oxytocin. A 3300 gm male infant with no obvious abnormalities was delivered. An autopsy request was declined. Comment
This report describes a fetal death after successful therapy of nonimmune hydrops fetalis secondary to a fetal supraventricular tachycardia. The possible explanations for this event include a fatal congenital heart defect and side effects from the therapy. There have been reports of cardiac decompensation after the use of intravenous verapamil in infants with supraventricular tachycardia. 2 Presumably, that problem occurred because of a simultaneous fall in systemic vascular resistance and cardiac contractility. It seems unlikely that this occurred here, because the symptoms of congestive heart failure had abated with verapamil therapy. Both digoxin and verapamil are known to decrease conduction in the atrioventricular node and to increase the level of atrioventricular block. It is possible that the combination may have resulted in complete heart block with an inadequate ventricular escape rate. In adults verapamil has been shown to impair the excretion of digoxin. It is possible that, in the 9 days between discharge and the death, the digoxin level rose enough to cause complete heart block. Whether this effect can take place in the fetus is not known, but one might gradually reduce the doses of digoxin and verapamil while monitoring the fetus frequently for persistence of the normal rhythm. One might also ask if more frequent fetal monitoring would have detected the apparent decompensation in time to act, and would the fetus have survived had delivery occurred after resolution of the hydropic changes and attainment of fetal pulmonary maturity?
REFERENCES 1. Kleinman CS, Cope! JA, Weinstein EM, eta!. Treatment of fetal supraventricular tachyarrhythmias. JCU 1985; 13:265-73. 2. Ebstein M, Kiel EA, Victoria BE. Cardiac decompensation following Verapamil therapy in infants with supraventricular tachycardia. Pediatrics 1985;75:737.