Furosemide to lower antenatal severe hypertension: a randomized placebo-controlled trial

Abstract

Background: Hypertensive disorders of pregnancy are a leading cause of perinatal morbidity, and timely treatment of severely elevated blood pressure is recommended to prevent serious sequelae. In acute hypertension marked by increased blood volume, it is unknown whether diuretics used as an adjunct to antihypertensive medications lead to more effective blood pressure control.

Objective: This study aimed to evaluate whether the addition of intravenous furosemide to first-line antihypertensive agents reduces systolic blood pressure in acute-onset, severe antenatal hypertension with wide (≥60 mm Hg) pulse pressure.

Study design: In this double-blinded randomized trial, participants received 40 mg of intravenous furosemide or placebo in addition to a first-line antihypertensive agent. The primary outcome was mean systolic blood pressure during the first hour after intervention. Secondary outcomes included corresponding diastolic blood pressure; systolic blood pressure, diastolic blood pressure, and pulse pressure at 2 hours after intervention; total reduction from qualifying blood pressure; duration of blood pressure control; need for additional antihypertensive doses within 1 hour; and electrolytes and urine output. A sample size of 35 participants per group was planned to detect a 15-mm Hg difference in blood pressure.

Results: Between January 2021 and March 2022, 65 individuals were randomized: 33 to furosemide and 32 to placebo. Baseline characteristics were similar between the groups. There was no difference in the primary outcome of mean 1-hour systolic blood pressure (147 [14.8] vs 152 [13.8] mm Hg; P=.200). We found a reduction in 2-hour systolic blood pressure (139 [18.5] vs 154 [18.4] mm Hg; P=.007) and a decrease in 2-hour pulse pressure (55 [12.5] vs 67 [15.1]; P=.003) in the furosemide group. Subgroup analysis according to hypertension type showed a significant reduction in 2-hour systolic blood pressure and 2-hour pulse pressure among patients with new-onset hypertension, but not among those with preexisting hypertension. Urine output was greater in the furosemide group, with no difference in electrolytes and creatinine before and after intervention.

Conclusion: Intravenous furosemide in conjunction with a first-line antihypertensive agent did not significantly reduce systolic blood pressure in the first hour after administration. However, both systolic blood pressure and pulse pressure at 2 hours were decreased in the furosemide group. These findings suggest that a 1-time dose of intravenous furosemide is a reasonable adjunct to achieve blood pressure control, particularly in patients in whom increased volume is suspected.

Trial registration: ClinicalTrials.gov NCT04615624.

Keywords: diuretics; furosemide; hyperdynamic; hypertensive disorders of pregnancy; preeclampsia; pulse pressure; severe hypertension; stroke volume.