A randomized, double-blind, placebo-controlled single center investigation of furosemide's effect on postpartum blood pressure control in pregnancies affected by hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy are recognized causes of significant maternal/fetal morbidity and mortality, accounting for approximately 18% of maternal deaths worldwide. While significant research has been done on the evaluation and management of hypertension during pregnancy, studies of postpartum hypertension (PPHTN) are usually limited by their retrospective design and focus on inpatients in the immediate postpartum period (2-6 days), or patients who were readmitted due to complications related to hypertension. Few studies have investigated the incidence and proper management of hypertension in the postpartum period. Furthermore, in the United Kingdom, a review of maternal deaths determined that 10% were related to hypertensive disorders in pregnancy (HDP) in the postpartum period. Postpartum hypertension is also the cause of approximately 27% of readmissions to the hospital. These studies clearly show that PPHTN is associated with significant morbidity and that it is important to develop interventions that can reduce its effects.

In patients with HDP, postpartum blood pressure has been shown to decrease in the first 48 hours postpartum only to then increase in days 3-6 postpartum. This phenomenon is thought to be secondary to large fluid shifts, both secondary from fluid retention during the pregnant state as well as from fluids given intrapartum. Furthermore, large volumes of sodium are also mobilized into the intravascular compartment at this time. Given the latter, furosemide, a loop diuretic that mobilizes sodium and fluid excretion has been posed as a method to prevent severe range blood pressures and their associated maternal morbidity in the postpartum period.

Inclusion Criteria:

• Hypertensive disorder of pregnancy diagnosed antepartum or intrapartum
• Gestational hypertension
• Pre-eclampsia with or without severe features
• Superimposed pre-eclampsia with or without severe features
• New diagnosis of HDP within 24 hours from delivery
• Postpartum, delivery ≥ 20 weeks estimated gestational age
• Age ≥18 years old

Exclusion Criteria:

• History of allergic reaction to furosemide
• High risk comorbidities for which treatment may be indicated or contraindicated: class C or higher diabetes mellitus, chronic kidney disease or baseline creatinine >1.2, cardiac disorders including cardiomyopathy, congenital heart disease, angina or coronary heart disease, rheumatic disease (lupus), sickle cell disease
• Baseline labs with K <3
• Use of furosemide or other diuretics antepartum or intrapartum
• Use of ototoxic agents including aminoglycosides (ie, Gentamicin for >1 dose), cephalosporins (ie Ancef >1 dose),
• Patient unstable for protocol per investigator's judgement

Over 6 weeks postpartum

Study medication (furosemide) and placebo will be stored at room temperature at the University of Pennsylvania research pharmacy. Pharmacy will be responsible for labeling and randomizing the medications.