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Adenosine use in pregnancy: Lack of effect on fetal heart rate
Adenosine Use in Pregnancy: Lack of Effect on Fetal STEPHEN LEFFLER,
Heart Rate
MD, DAVID R. JOHNSON,
The treatment for supraventricular tachycardia in pregnancy is somewhat controversial. Although a variety of medications have been used to terminate this rhythm during pregnancy, all have actual or theoretical draw backs. Adenosine Is a relatively new medication with an extremely short half-life and is effective in the treatment of supraventricular tachycardia. We report a case in which this medication was used successfully during pregnancy. In addition, we found that adenosine had no effect on fetal heart rate in this case. (Am J Emerg Med 1992;10:548-549. Copyright 0 1992 by W.B. Saunders Company)
Adenosine is a naturally occurring pm-me-based nucleoside with antiarrhythmic properties.’ By transiently depressing sinoatrial node automaticity and slowing atrioventricular conduction time, it is effective in terminating supraventricular tachycardia (SVT).‘.* Adenosine’s effectiveness and safety have been well reported in adults and children.‘” In addition, there has been a recent case report of the successful use of adenosine in pregnancy, although no attempt was made to monitor the fetal response.4 We report a case in which adenosine was successfully used to terminate SVT in a pregnant patient. Fetal heart rate was continuously monitored via Doppler and was unaffected. This case suggests that it may be possible to use adenosine to safely treat SVT in pregnant patients without affecting fetal heart rate. CASE REPORT The 21-year-old patient (gravida 3, para 2) was 41 weeks pregnant by dates. She had a past medical history significant for SVT that had previously been controlled with vagal maneuvers. On the day of presentation the patient was complaining of rapid heart rate. which had been present for more than 1 hour. Vital signs in the emergency department were as follows: pulse rate, 2lO/min; blood pressure, 100/60 mm Hg; respiratory rate, 161 min; and temperature, 36.4”C. Fetal heart tones were measured by Doppler at 16Umin. The patient was pale and was complaining of chest discomfort and a tight feeling in her throat. Her cardiac examination revealed a regular tachycardia and her lungs were clear. Abdominal examination was consistent with a full-term pregnancy. Oxygen and an intravenous line were started, and an electrocardiogram was obtained that showed a narrow complex SVT. Vagal maneuvers and 1-L normal saline bolus did not change the rhythm. The decision was made to give adenosine 12 mg intravenously. Be-
From the Department of Emergency Medicine, University of Mexico School of Medicine, Albuquerque, NM. Manuscript received March 24, 1992; revision accepted May 5, 1992. Address reprint requests to Dr Johnson, Department of Emergency Medicine, University of New Mexico School of Medicine, Ambulatory Care Center, 4-West, Albuquerque, NM 87131-5246. Key Words: Adenosine, pregnancy, supraventricular tachycardia. Copyright 0 1992 by W.B. Saunders Company 0735-6757/92/l 006-0009$5.00/O 548
MD fore giving the adenosine, a fetal doppler with a continuous digital readout was placed on the abdomen to monitor fetal heart tones. The fetal heart rate before giving the adenosine was 161. The fetal heart rate remained between 155 to 165 after the adenosine bolus (Figure 1). The mother had a brief period of asystole and bradycardia before converting to a sinus rhythm at a rate of 118 (Figure 2). After an hour of observation, the mother was sent for obstetrical testing and triage where a normal nonstress test was obtained. A healthy baby was born 36 hours later with Apgar scores of 8 and 9.
DISCUSSION Supraventricular tachycardia during pregnancy is uncommon.’ When vagal maneuvers are unsuccessful, pharmacologic options include digoxin, verapamil, beta blockers, and adenosine. All are classified by the Food and Drug Administration as “category C” in pregnancy. The definition of this category is “studies have shown that the drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in animals or women.‘+ In addition, controlled studies comparing the efficacy of these medications in terminating SVT during pregnancy do not exist. As a result, the clinician must depend on “general pharmacokinetic principles and good clinical judgement” when treating arrhythmias during pregnancy.7 Digoxin, although still classified as a category C drug, has been used for years in pregnancy and is felt by many to be safe.7 Its effectiveness in the treatment of a variety of urgent cardiac disorders has been questioned.’ Verapamil has been used successfully to convert SVT during pregnancy, but there have been isolated reports of sudden intrauterine fetal death following calcium channelblocker administration.6,9 Significant hypotension is also a concern with this agent.7 Disagreement exists as to the fetal hemodynamic effects of beta blockers. While these agents have been used successfully during pregnancy, there is concern that these medications may cause growth retardation and neonatal hypoglycemia.‘,” Animal studies have demonstrated fetal bradycardia and hypoxemia from maternal esmolol.” Adenosine is a naturally occurring antiarrhythmic agent that is rapidly metabolized by adenosine deaminase, giving it a half-life of less than 10 seconds.‘* Theoretically, this should markedly decrease placental exposure to the drug. In studies of an animal model, significant degradation of adenosine took place in the placenta, and only 12% of maternally circulating adenosine was recovered from the fetal circulation.13 The recommended dosage range for adenosine is 6 to 12 mg given by intravenous bolus. Given the significant increase in intravascular volume during pregnancy the larger dose was chosen for this patient. This may not have been
LEFFLER AND JOHNSON n ADENOSINE IN PREGNANCY
pregnancy. Our case demonstrates that this agent may be effective in pregnancy and that fetal heart rate may not be affected.
165
SUMMARY
!
2 c
549
l”lw&A+--155’ 1
9 I
ADENOSINE 12 MG IVP 150 I
While further research is required to delineate the safety of adenosine in early pregnancy, we have reported a case in which adenosine was used successfully in late pregnancy to terminate SVT. Our case further demonstrated that fetal heart rate may not be affected by maternal adenosine. The authors thank Dan Tandberg, MD, for his review of this manuscript and Sandra Mirabal for her assistance in its preparation.
REFERENCES 21
22
FIGURE
23
26 24 25 TIME IN MINUTES
I.
Fetal heart rate.
necessary, however, since the serum concentration of the enzyme responsible for the degradation of this nucleoside declines during pregnancy. I4 Adverse effects from adenosine include dyspnea, chest pain, hypotension, bradyarrhythmias, and transient asystole.2*‘5 Although a recent report of two cases suggests that this drug may have significant, prolonged cardiac effects, in general, side effects resolve rapidly and are well tolerated. 2.123*6Because of its very short half-life, lack of serious side effects, and high rate of conversion of SVT, adenosine appears to be a reasonable drug for the treatment of SVT in
FIGURE 2. Rhythm strip showing SVT and conversion to sinus tachycardia shortly after an intravenous bolus of adenosine 12 mg.
1. DiMarco JP, Sellers TO, Berne RM, et al: Adenosine: Electrophysiologic effects and therapeutic use for terminating paroxysmal supraventricular tachycardia. Circulation 1983;68: 1254-l 263 2. DiMarco JP, Miles W, Akhtar M, et al: Adenosine for paroxysmal supraventricular tachycardia: Dose ranging and comparison with verapamil. Ann Intern Med 1990;113:104-110 3. Overholt ED, Rheuban KS, Gutgesell HP, et al: Usefulness of adenosine for arrhythmias in infants and children. Am J Cardiol 1988;61:336-340 4. Podolski SM, Varon J: Adenosine use during pregnancy. Ann Emerg Med 1991;20:1027-1028 5. Brown CE, Wendel GO: Cardiac arrhythmias during pregnancy. Clin Obstet Gynecol 1989;32:89-102 6. Byerly WG, Hartmann A, Foster DE, et al: Verapamil in the treatment of maternal paroxysmal supraventricular tachycardia. Ann Emerg Med 1991;20:552-554 7. Rotmensch HH, Elkayam U, Frishman W: Antiarrhythmic drug therapy during pregnancy. Ann Intern Med 1983;98:487497 8. Ewy GA: Urgent parenteral digoxin therapy: A requiem. J Am Coll Cardiol 1990;15:1248-1249 9. Gianopoulos JG: Cardiac disease in pregnancy. Med Clin North Am 1989;73:639-651 10. Frishman WH, Chesner M: Beta-adrenergic blockers in pregnancy. Am Heart J 1988;115:147-152 11. Eisenach JC, Castro Ml: Maternally administered esmolol produces fetal adrenergic blockade and hypoxemia in sheep. Anesthesiology 1989;71:718-722 12. Klabunde RE: Dipyridamole inhibition of adenosine metabolism in human blood. Eur J Pharmacol 1983;93:21-26 13. Wheeler C, Yudilevish DL: Transport and metabolism of adenosine in the perfused guinea pig placenta. J Physiol 1988; 405:51 l-525 14. Cairns CB, Niemann JT: intravenous adenosine in the emergency department management of paroxysmal supraventricular tachycardia. Ann Emerg Med 1991;20:717-721 15. Reed R, Falk JL, O’Brien J: Untoward reaction to adenosine therapy for supraventricular tachycardia. Am J Emerg Med 1991;9:566-570 16. Jaqueti J, Martinez-Hernandez 0, Hernandez-Garcia R, et al: Adenosine deaminase in pregnancy serum. Clin Chem 1990; 36:2144
Heart Rate
MD, DAVID R. JOHNSON,
The treatment for supraventricular tachycardia in pregnancy is somewhat controversial. Although a variety of medications have been used to terminate this rhythm during pregnancy, all have actual or theoretical draw backs. Adenosine Is a relatively new medication with an extremely short half-life and is effective in the treatment of supraventricular tachycardia. We report a case in which this medication was used successfully during pregnancy. In addition, we found that adenosine had no effect on fetal heart rate in this case. (Am J Emerg Med 1992;10:548-549. Copyright 0 1992 by W.B. Saunders Company)
Adenosine is a naturally occurring pm-me-based nucleoside with antiarrhythmic properties.’ By transiently depressing sinoatrial node automaticity and slowing atrioventricular conduction time, it is effective in terminating supraventricular tachycardia (SVT).‘.* Adenosine’s effectiveness and safety have been well reported in adults and children.‘” In addition, there has been a recent case report of the successful use of adenosine in pregnancy, although no attempt was made to monitor the fetal response.4 We report a case in which adenosine was successfully used to terminate SVT in a pregnant patient. Fetal heart rate was continuously monitored via Doppler and was unaffected. This case suggests that it may be possible to use adenosine to safely treat SVT in pregnant patients without affecting fetal heart rate. CASE REPORT The 21-year-old patient (gravida 3, para 2) was 41 weeks pregnant by dates. She had a past medical history significant for SVT that had previously been controlled with vagal maneuvers. On the day of presentation the patient was complaining of rapid heart rate. which had been present for more than 1 hour. Vital signs in the emergency department were as follows: pulse rate, 2lO/min; blood pressure, 100/60 mm Hg; respiratory rate, 161 min; and temperature, 36.4”C. Fetal heart tones were measured by Doppler at 16Umin. The patient was pale and was complaining of chest discomfort and a tight feeling in her throat. Her cardiac examination revealed a regular tachycardia and her lungs were clear. Abdominal examination was consistent with a full-term pregnancy. Oxygen and an intravenous line were started, and an electrocardiogram was obtained that showed a narrow complex SVT. Vagal maneuvers and 1-L normal saline bolus did not change the rhythm. The decision was made to give adenosine 12 mg intravenously. Be-
From the Department of Emergency Medicine, University of Mexico School of Medicine, Albuquerque, NM. Manuscript received March 24, 1992; revision accepted May 5, 1992. Address reprint requests to Dr Johnson, Department of Emergency Medicine, University of New Mexico School of Medicine, Ambulatory Care Center, 4-West, Albuquerque, NM 87131-5246. Key Words: Adenosine, pregnancy, supraventricular tachycardia. Copyright 0 1992 by W.B. Saunders Company 0735-6757/92/l 006-0009$5.00/O 548
MD fore giving the adenosine, a fetal doppler with a continuous digital readout was placed on the abdomen to monitor fetal heart tones. The fetal heart rate before giving the adenosine was 161. The fetal heart rate remained between 155 to 165 after the adenosine bolus (Figure 1). The mother had a brief period of asystole and bradycardia before converting to a sinus rhythm at a rate of 118 (Figure 2). After an hour of observation, the mother was sent for obstetrical testing and triage where a normal nonstress test was obtained. A healthy baby was born 36 hours later with Apgar scores of 8 and 9.
DISCUSSION Supraventricular tachycardia during pregnancy is uncommon.’ When vagal maneuvers are unsuccessful, pharmacologic options include digoxin, verapamil, beta blockers, and adenosine. All are classified by the Food and Drug Administration as “category C” in pregnancy. The definition of this category is “studies have shown that the drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in animals or women.‘+ In addition, controlled studies comparing the efficacy of these medications in terminating SVT during pregnancy do not exist. As a result, the clinician must depend on “general pharmacokinetic principles and good clinical judgement” when treating arrhythmias during pregnancy.7 Digoxin, although still classified as a category C drug, has been used for years in pregnancy and is felt by many to be safe.7 Its effectiveness in the treatment of a variety of urgent cardiac disorders has been questioned.’ Verapamil has been used successfully to convert SVT during pregnancy, but there have been isolated reports of sudden intrauterine fetal death following calcium channelblocker administration.6,9 Significant hypotension is also a concern with this agent.7 Disagreement exists as to the fetal hemodynamic effects of beta blockers. While these agents have been used successfully during pregnancy, there is concern that these medications may cause growth retardation and neonatal hypoglycemia.‘,” Animal studies have demonstrated fetal bradycardia and hypoxemia from maternal esmolol.” Adenosine is a naturally occurring antiarrhythmic agent that is rapidly metabolized by adenosine deaminase, giving it a half-life of less than 10 seconds.‘* Theoretically, this should markedly decrease placental exposure to the drug. In studies of an animal model, significant degradation of adenosine took place in the placenta, and only 12% of maternally circulating adenosine was recovered from the fetal circulation.13 The recommended dosage range for adenosine is 6 to 12 mg given by intravenous bolus. Given the significant increase in intravascular volume during pregnancy the larger dose was chosen for this patient. This may not have been
LEFFLER AND JOHNSON n ADENOSINE IN PREGNANCY
pregnancy. Our case demonstrates that this agent may be effective in pregnancy and that fetal heart rate may not be affected.
165
SUMMARY
!
2 c
549
l”lw&A+--155’ 1
9 I
ADENOSINE 12 MG IVP 150 I
While further research is required to delineate the safety of adenosine in early pregnancy, we have reported a case in which adenosine was used successfully in late pregnancy to terminate SVT. Our case further demonstrated that fetal heart rate may not be affected by maternal adenosine. The authors thank Dan Tandberg, MD, for his review of this manuscript and Sandra Mirabal for her assistance in its preparation.
REFERENCES 21
22
FIGURE
23
26 24 25 TIME IN MINUTES
I.
Fetal heart rate.
necessary, however, since the serum concentration of the enzyme responsible for the degradation of this nucleoside declines during pregnancy. I4 Adverse effects from adenosine include dyspnea, chest pain, hypotension, bradyarrhythmias, and transient asystole.2*‘5 Although a recent report of two cases suggests that this drug may have significant, prolonged cardiac effects, in general, side effects resolve rapidly and are well tolerated. 2.123*6Because of its very short half-life, lack of serious side effects, and high rate of conversion of SVT, adenosine appears to be a reasonable drug for the treatment of SVT in
FIGURE 2. Rhythm strip showing SVT and conversion to sinus tachycardia shortly after an intravenous bolus of adenosine 12 mg.
1. DiMarco JP, Sellers TO, Berne RM, et al: Adenosine: Electrophysiologic effects and therapeutic use for terminating paroxysmal supraventricular tachycardia. Circulation 1983;68: 1254-l 263 2. DiMarco JP, Miles W, Akhtar M, et al: Adenosine for paroxysmal supraventricular tachycardia: Dose ranging and comparison with verapamil. Ann Intern Med 1990;113:104-110 3. Overholt ED, Rheuban KS, Gutgesell HP, et al: Usefulness of adenosine for arrhythmias in infants and children. Am J Cardiol 1988;61:336-340 4. Podolski SM, Varon J: Adenosine use during pregnancy. Ann Emerg Med 1991;20:1027-1028 5. Brown CE, Wendel GO: Cardiac arrhythmias during pregnancy. Clin Obstet Gynecol 1989;32:89-102 6. Byerly WG, Hartmann A, Foster DE, et al: Verapamil in the treatment of maternal paroxysmal supraventricular tachycardia. Ann Emerg Med 1991;20:552-554 7. Rotmensch HH, Elkayam U, Frishman W: Antiarrhythmic drug therapy during pregnancy. Ann Intern Med 1983;98:487497 8. Ewy GA: Urgent parenteral digoxin therapy: A requiem. J Am Coll Cardiol 1990;15:1248-1249 9. Gianopoulos JG: Cardiac disease in pregnancy. Med Clin North Am 1989;73:639-651 10. Frishman WH, Chesner M: Beta-adrenergic blockers in pregnancy. Am Heart J 1988;115:147-152 11. Eisenach JC, Castro Ml: Maternally administered esmolol produces fetal adrenergic blockade and hypoxemia in sheep. Anesthesiology 1989;71:718-722 12. Klabunde RE: Dipyridamole inhibition of adenosine metabolism in human blood. Eur J Pharmacol 1983;93:21-26 13. Wheeler C, Yudilevish DL: Transport and metabolism of adenosine in the perfused guinea pig placenta. J Physiol 1988; 405:51 l-525 14. Cairns CB, Niemann JT: intravenous adenosine in the emergency department management of paroxysmal supraventricular tachycardia. Ann Emerg Med 1991;20:717-721 15. Reed R, Falk JL, O’Brien J: Untoward reaction to adenosine therapy for supraventricular tachycardia. Am J Emerg Med 1991;9:566-570 16. Jaqueti J, Martinez-Hernandez 0, Hernandez-Garcia R, et al: Adenosine deaminase in pregnancy serum. Clin Chem 1990; 36:2144