Antiarrhythmic
PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Adenosine has been used in all stages of pregnancy for maternal and embryo–fetal indications without harming the embryo or fetus. If indicated, the drug should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Adenosine, an endogenous purine-based nucleoside found in all cells of the body, is used for the treatment of paroxysmal supraventricular tachycardia. Adenosine phosphate and adenosine triphosphate have been used as vasodilators. Ordinarily, adverse fetal effects secondary to adenosine would not be expected because of the widespread, natural distribution of this substance in the body and its very short (<10 seconds) half-life after IV administration. However, the maternal administration of large IV doses of adenosine may potentially produce fetal toxicity, as has been observed with other endogenous agents (e.g., see Epinephrine).
A reproduction study in chick embryos did not observe teratogenicity (1). Injection into the fourth cerebral ventricle of fetal sheep resulted in depressed fetal respiratory drive (2). In pregnant sheep, constant infusions and single injections of adenosine produced alterations in maternal heart rate and a decrease in diastolic pressure, but no changes in maternal systolic pressure or arterial blood gases, and had no effect on fetal heart rate, arterial pressure, or arterial blood gases (3,4). Another experiment using near-term sheep demonstrated that angiotensin II-induced maternal–placental vasoconstriction could not be reversed by a high-dose infusion of adenosine (5).
Endogenous adenosine cord blood levels, measured in 14 fetuses of 19–34 weeks’ gestation, were not related to gestational age, but were significantly increased in anemic fetuses and were positively associated with blood oxygen tension (6). The investigators concluded that the results were compatible with a fetal response to tissue hypoxia.
The first case describing the use of adenosine in human pregnancy appeared in 1991 (7). Recurrent narrow complex tachycardia occurred suddenly in a 40-year-old woman in her 39th week of gestation. She had been hospitalized 6 months before the current episode for a similar condition secondary to mitral valve prolapse and had been taking atenolol for tachyarrhythmia prophylaxis since that occurrence. Maternal blood pressure was 80 mm Hg systolic with a pulse of 240 beats/minute. Fetal heart rate was 140 beats/minute. Two IV bolus doses of adenosine (6 and 12 mg) were administered resulting in conversion to sinus rhythm with a rate of 80 beats/minute. A nonstress test, conducted after stabilization of the mother, was normal. Two weeks later, a healthy 3.6-kg infant was delivered. Both mother and baby were doing well 1 month postpartum.
Since the above case, a number of reports have described the safe use of adenosine to treat maternal or fetal supraventricular tachycardia (8–20) during all phases of gestation, including one woman in active labor (15), eight during the 1st trimester (16), and four cases of direct fetal administration (18–20). The first three of the maternal reports and the first fetal case are described below.
A 19-year-old woman was treated at 38 weeks’ gestation for the arrhythmia during labor (8). Conversion to a normal sinus rhythm required two IV bolus doses (6 and 12 mg). No effect was observed on uterine contractions, fetal heart rate, or variability. A cesarean section was required for failure of the labor to progress. The second case occurred in a 34-year-old woman with onset of supraventricular tachycardia at 30 weeks’ gestation (9). She responded within 30 seconds to a single 6-mg IV adenosine dose with no changes observed in the fetal heart rate tracing. A normal infant was delivered at term. The third woman was a 26-year-old patient with a history of Wolff-Parkinson-White syndrome who was initially treated successfully with 6 mg IV adenosine at 7 months’ gestation (10). She was subsequently treated with atenolol and eventually admitted at term for labor induction. During labor the supraventricular tachycardia recurred and two doses (6 and 12 mg) of adenosine were required to convert to a normal sinus rhythm. During the mother’s arrhythmia, fetal distress demonstrated by recurrent, deep variable decelerations with loss of short-term variability was observed, but fetal bradycardia resolved with a return to a fetal heart rate of 130 beats/minute on conversion of the mother. A third recurrence of the mother’s tachycardia occurred shortly before a cesarean section and this was successfully converted with a 12-mg dose of adenosine. A male infant was delivered with Apgar scores of 1 and 5 at 1 and 5 minutes, respectively. No adverse effects in the fetus or newborn attributable to adenosine were observed in any of the above cases or in the other cited cases.
A 1995 reference described the direct fetal administration of adenosine for the treatment of persistent supraventricular tachycardia with massive hydrops at 28 weeks’ gestation (18). Treatment with digoxin and flecainide for 5 weeks had not been successful in reversing the condition. Based on estimated fetal weight, 0.2 mg/kg of adenosine was given by bolus injection into the umbilical vein and a normal rhythm occurred within seconds. The umbilical serum levels of digoxin and flecainide were determined at the same time and further loading of the fetus with digoxin (0.05 mg/kg) and flecainide (1.0 mg/kg) were administered via the umbilical vein (18). After about 20 minutes of intermittent atrial arrhythmia and tachycardia, the fetal heart converted to a stable, normal rhythm. One week later, the fetus died in utero from what was thought to be a recurrence of the tachycardia or the onset of a drug-induced arrhythmia (18). Massive hydrops fetalis with a structurally normal heart was found at autopsy.
BREASTFEEDING SUMMARY
Because adenosine is used only by IV injection in acute care situations, it is doubtful that any report will be located describing the use of adenosine during human lactation. Moreover, the serum half-life is so short that it is unlikely that any of the drug will pass into milk.
References
1.Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:194.
2.Bissonnette JM, Hohimer AR, Knopp SJ. The effect of centrally administered adenosine on fetal breath movements. Respir Physiol 1991;84:273–85.
3.Mason B, Ogunyemi D, Punla O, Koos B. Maternal and fetal cardiovascular effects of intravenous adenosine (abstract). Am J Obstet Gynecol 1993;168:439.
4.Mason BA, Ogunyemi D, Punla O, Koos BJ. Maternal and fetal cardiorespiratory responses to adenosine in sheep. Am J Obstet Gynecol 1993;168:1558–61.
5.Landauer M, Phernetton TM, Rankin JHG. Maternal ovine placental vascular responses to adenosine. Am J Obstet Gynecol 1986;154:1152–5.
6.Ross Russell RI, Greenough A, Lagercrantz H, Dahlin I, Nicolaides K. Fetal anaemia and its relation with increased concentrations of adenosine. Arch Dis Child Fetal Neonatal 1993;68:35–6.
7.Podolsky SM, Varon J. Adenosine use during pregnancy. Ann Emerg Med 1991;20:1027–8.
8.Harrison JK, Greenfield RA, Wharton JM. Acute termination of supraventricular tachycardia by adenosine during pregnancy. Am Heart J 1992;123:1386–8.
9.Mason BA, Ricci-Goodman J, Koos BJ. Adenosine in the treatment of maternal paroxysmal supraventricular tachycardia. Obstet Gynecol 1992;80:478–80.
10.Afridi I, Moise KJ Jr, Rokey R. Termination of supraventricular tachycardia with intravenous adenosine in a pregnant woman with Wolff-Parkinson-White syndrome. Obstet Gynecol 1992;80:481–3.
11.Leffler S, Johnson DR. Adenosine use in pregnancy. Lack of effect on fetal heart rate. Am J Emerg Med 1992;10:548–9.
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13.Adair RF. Fetal monitoring with adenosine administration. Ann Emerg Med 1993;22:1925.
14.Matfin G, Baylis P, Adams P. Maternal paroxysmal supraventricular tachycardia treated with adenosine. Postgrad Med J 1993;69:661–2.
15.Hagley MT, Cole PL. Adenosine use in pregnant women with supraventricular tachycardia. Ann Pharmacother 1994;28:1241–2.
16.Elkayam U, Goodwin TM Jr. Adenosine therapy for supraventricular tachycardia during pregnancy. Am J Cardiol 1995;75:521–3.
17.Hagley MT, Haraden B, Cole PL. Adenosine use in a pregnant patient with supraventricular tachycardia. Ann Pharmacother 1995;29:938.
18.Kohl T, Tercanli S, Kececioglu D, Holzgreve W. Direct fetal administration of adenosine for the termination of incessant supraventricular tachycardia. Obstet Gynecol 1995;85:873–4.
19.Hubinont C, Debauche C, Bernard P, Sluysmans T. Resolution of fetal tachycardia and hydrops by a single adenosine administration. Obstet Gynecol 1998;92(Part 2):718.
20.Dangel JH, Roszkowski T, Bieganowska K, Kubicka K, Ganowicz J. Adenosine triphosphate for cardioversion of supraventricular tachycardia in two hydropic fetuses. Fetal Diagn Ther 2000;15:326–30.