Hydralazine and dihydralazine are structurally similar vasodilator drugs that have been used for the treatment of hypertension in pregnancy for over 40 years. Following oral administration, up to 80 percent absorption occurs, and approximately 66 percent of the drug is deactivated in the liver. The half-life is 2-8 hours. Hydralazine and dihydralazine cross the placenta well, and cord-blood drug concentrations may exceed those in the mother (Franke 1986). Although results from animal studies show an increase in uterine blood llow (Lipshitz 1987, Weiner 1986) after hydralazine administration, studies in hypertensive women indicate that changes in intervillous blood llow are, at best, variable or nonexistent (Gudmundsson 1995, Grunewald 1993, Suionio 1986). In the past, hydralazine has been administered by intermittent intramuscular injection or continuous intravenous infusion (Pritchard 1984, Sibai 1984, Garden 1982). Occasionally, continuous intravenous infusion has resulted In a higher incidence of abnormal fetal heart rate tracings (Kirshon 1991, Spinnato 1986), which has led some clinicians to recommend that this route of administration be avoided (Kirshon 1991).
Parenteral hydralazine was the most widely used drug in the acute treatment of hypertensive emergencies during pregnancy in the past. A maternal symptom-complex including headache, flushing, palpitations, nausea, and vomiting may develop, mimicking imminent eclampsia. There is limited experience with prolonged use of hydralazine in pregnancy. Symptomatic neonatal thrombocytopenia, leukopenia, petechial bleeding, and hematomas have been reported after prenatal exposure (Widerlov 1980). Therefore, chronic use should be reserved for refractory patients.
There is little reported experience concerning first-trimester use of hydralazine in the human. The National Collaborative Perinatal Project identified eight infants exposed to hydralazine In the first trimester, none of whom had birth defects (Heinonen 1977). In another study of 40 pregnant women treated in the first trimester, there was only one infant with a birth defect (Rosa, cited in Briggs 2005). To date, there is no conclusive evidence of teratogenic effects in human pregnancy.
Most available information reports on the use of hydralazine in the third trimester to treat PIH. In some cases, liver toxicity was observed in pre-eclamptic patients (Hod 1986).
In patients with severe pre-eclampsia who are hypovolemic, the administration of hydralazine may induce a rapid fall of blood pressure and possibly worsen perinatal outcome if delivery occurs before 32 weeks' gestation. This is probably avoidable if the preexisting hypovolemia is corrected prior to hydralazine administration (Derham 1990).
Concerns have also been expressed that the administration of dihydralazine may decrease myocardial perfusion and increase the risk of maternal arrhythmias in eclampsia (Bhorat 1993). One case report described a temporal association between the maternal administration of hydralazine and fetal premature atrial contractions. The arrhythmia subsided spontaneously once hydralazine administration was discontinued (Lodeiro 1989).
There is also one case report of a woman treated with hydralazine for PI H in which the fetus died 36 hours after delivery from a pericardial effusion and cardiac tamponade (Yemini 1989). A postmortem examination suggested a lupus-like syndrome possibly due to maternal and fetal sensitivity to hydralazine.
Magee (2003) compared the maternal, fetal, and perinatal outcomes of pregnancies with severe hypertension, treated either by hydralazine or by other hypertensive drugs, mostly nifedipine or labetalol, in a meta-analysis. Therapy took place during the second and/or third trimesters. There are conflicting results, but it is clear that hydralazine is not the first-line drug of choice for severe hypertension in pregnancy.
Although there are numerous reports of successful intrapartum control of maternal blood pressure with hydralazine (Rosenfeld 1986, Spinnato 1986), there is a possibility that systemic vasodilatation may be accompanied by decreased placental perfusion resulting in fetal/neonatal bradycardia (Spinnato 1986). Theoretically, this complication is preventable by avoiding maternal hypotension.
Recommendation. (Di)hydralazine may be used for the treatment of hypertension in pregnancy. In acute hypertensive crisis, it is used intravenously.
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