Treatment of fetal supraventricular tachycardia by intra-amniotic administration of digoxin.

Abstract

Fetal arrhythmia occurs in as many as 1–3% of pregnancies1. Supraventricular tachycardia (SVT) accounts for about 66–90% of cases of fetal tachyar rhythmia2. First-line therapy has not been determined in randomized trials, but digoxin has been considered the first-choice drug. Flecainide and sotalol have been advocated as second-choice drugs, though flecainide might be more effective as a first-line treatment3. Digoxin has been shown to have incomplete passage across the placenta in cases of fetal hydrops, whereas this is not the case for sotalol and flecainide, which can cross the placenta; combination therapy of digoxin with flecainide or sotalol has therefore been used in hydropic fetuses4. There is a delay between the onset of treatment and the fetal response, the average time being 3 days for digoxin and 4 and 12 days for flecainide and sotalol, respectively5. Perinatal mortality in cases of arrhythmia associated with hydrops has been reported to be 35%4, 5. We present a case of a hydropic fetus with SVT treated by intra-amniotic injection of digoxin. Intermittent SVT (heart rate, 283 bpm) (Figure 1) was detected at 27 weeks' gestation in a fetus with subcutaneous edema in the pelvic and periumbilical areas, free fluid in the abdominal cavity around the liver and estimated fetal weight of 862 ± 126 g (5th percentile). During the 24 h after transplacental treatment with maternal digoxin, we observed worsening of the fetal condition, including disappearance of amniotic fluid, absence of fetal movements and incessant SVT. In pregnant sheep, intra-amniotic digoxin has been found to be taken up rapidly into the fetal circulation from the amniotic cavity and fetal digoxin concentrations were within the therapeutic range for a prolonged period of time6. Furthermore, we observed previously an immediate cardiovascular response in the form of new insufficiency of the mitral valve, within the first minute after intra-amniotic injection of digoxin for feticide, although the digoxin dose for this purpose was much higher (1–1.5 mg). Based on this knowledge, we suggested performing intra-amniotic treatment. The patient received a comprehensive explanation of the risks and benefits of this therapeutic approach. At 27 + 2 weeks, we introduced 50 µg of digoxin into the amniotic cavity (25 µg/kg as a loading dose for a premature neonate of this gestational age plus 25 µg for the volume of distribution in the amniotic cavity (mean amniotic fluid volume between 22 and 39 weeks is 777 mL7)) (Figure 2). Twenty seconds following administration of digoxin, the fetal heart rate was normal with occasional right atrial extrasystoles, fetal movements resumed and amniotic fluid reappeared. Maternal treatment with digoxin was maintained orally, but was then discontinued due to signs of maternal intolerance 24 h after intra-amniotic treatment. After 10 days with no maternal treatment and normal fetal heart rate, intermittent episodes of SVT were detected again, but disappeared within 48 h following maternal flecainide administration (100 mg orally twice a day). The fetal heart rate remained in sinus rhythm until the 35th week of gestation when labor was induced due to a sudden decrease in fetal movements and amniotic fluid volume. At the time of writing, the neonate was in good condition and on antiarrhythmic medication. This case shows for the first time the temporal relationship between fetal SVT and intra-amniotic injection of digoxin. We believe that this represents a new approach to the treatment of SVT when incomplete placental transmission is suspected or when there is a rapid deterioration in fetal condition warranting urgent therapy.