Furosemide for the Management of Postpartum Hypertension

By Ahizechukwu C. Eke, MD, PhD, MPH

Associate Professor in Maternal Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore

SYNOPSIS: Current evidence does not support the effectiveness of furosemide in reducing the mean arterial pressure within 24 hours before discharge from delivery hospitalization or before starting antihypertensive medications, compared to a placebo.

SOURCE: Emeruwa UN, Azad H, Ona S, et al. Lasix for the prevention of de novo postpartum hypertension: A randomized placebo-controlled trial (LAPP Trial). Am J Obstet Gynecol 2024; Apr 17. doi: 10.1016/j.ajog.2024.04.016. [Online ahead of print].

New onset (de novo) postpartum hypertension affects approximately 10% of pregnancies and is a significant cause of maternal morbidity and mortality in the United States.¹ This condition is characterized by elevated blood pressure that arises after delivery in a previously normotensive woman, and it can lead to serious maternal morbidity if not adequately managed. Although the pathophysiology of postpartum hypertension is unknown, factors such as increased vascular resistance, retained placenta, and the body’s adjustment to the physiologic hemodynamic changes following childbirth have been implicated. Severe postpartum hypertension can lead to life-threatening complications, such as cerebral infarction, seizures, intracerebral hemorrhage, stroke, congestive heart failure, and renal failure.^1,2 Therefore, effective management is crucial to prevent these severe complications.

Furosemide, a loop diuretic, commonly is used in various clinical settings to manage fluid overload and hypertension. It acts on the ascending loop of Henle in the kidneys to inhibit sodium and chloride reabsorption, leading to increased urine output.³ This diuretic effect can reduce intravascular volume, thereby lowering blood pressure. Given its potent diuretic properties, furosemide is considered a medication for use in managing postpartum hypertension, especially in patients who may benefit from rapid fluid excretion, which may be necessary during the postpartum period in patients with fluid overload.

Although previous studies have shown that furosemide can decrease postpartum blood pressure, promote faster normalization of blood pressure, and reduce the need for antihypertensive therapy in patients with antenatal preeclampsia, few have evaluated its use specifically for managing postpartum hypertension.^4,5 To investigate whether administering an oral loop diuretic such as furosemide can prevent de novo postpartum hypertension in high-risk individuals, Emeruwa and colleagues hypothesized that furosemide might reduce hypertensive episodes and the need for antihypertensive therapy in patients at risk for de novo postpartum hypertension.⁶

The Lasix for the Prevention of De Novo Postpartum Hypertension (LAPP) trial is a Phase IV randomized clinical trial conducted at New York Presbyterian/Columbia University Irving Medical Center (CUIMC).⁶ Pregnant women met the inclusion criteria if they had no antenatal diagnosis of hypertension or hypertensive disorders of pregnancy at the time of labor and delivery admission, did not receive magnesium sulfate for seizure prophylaxis by the time of delivery, and were classified as high-risk for the development of de novo postpartum hypertension.⁶ The high-risk classification was based on meeting either one high-risk criterion or two moderate-risk criteria according to a pre-specified, adapted risk factor algorithm. Pregnant women were excluded from the trial if they used diuretics within two weeks before delivery or had a contraindication to diuretic therapy.

Eligible women were randomly assigned in a 1:1 ratio to receive either a five-day course of once-daily oral furosemide 20 mg or an identical-appearing placebo, starting within eight hours after delivery. The primary outcome measure assessed was the mean arterial pressure (MAP) averaged over the 24 hours prior to discharge or before the initiation of antihypertensive therapy, whichever came first. Secondary outcomes, evaluated at discharge, two weeks postpartum, and six weeks postpartum, included the incidence of de novo postpartum hypertension/preeclampsia, the percentage of elevated blood pressure readings, the rate of magnesium sulfate administration, time to discharge, initiation rates of antihypertensive medications, rates of severe maternal morbidity related to hypertension, frequency of triage or emergency department visits and readmissions, breastfeeding continuation rates, and neonatal outcomes such as weight change prior to discharge.

The LAPP trial’s target sample size was determined based on an expected baseline MAP of 83 mmHg from prior studies.⁷ With a two-tailed type-1 error rate of 0.05 and an anticipated loss-to-follow-up rate of 10%, a sample size of 82 women (41 per group) would provide 90% power to detect a clinically significant absolute mean difference of 5 mmHg in the primary outcome. Data were analyzed using the intention-to-treat approach.

Out of 891 women evaluated for eligibility between October 2021 and April 2022, 144 met inclusion criteria. Among them, 82 (57%) consented and were randomized, with 41 assigned to each group. Baseline characteristics were comparable between both groups. For the primary endpoint of MAP averaged over the 24 hours prior to discharge or before the initiation of antihypertensive therapy, there were no statistically significant differences in mean MAP in the 24 hours preceding discharge (or initiation of antihypertensive treatment) between the furosemide group (88.9 ± 7.4 mmHg) and the placebo group (86.8 ± 7.1 mmHg; absolute difference 2.1 mmHg, 95% confidence interval [CI], -1.2 to 5.3, P = 0.21).

Among the 79 participants evaluated for secondary outcomes, 10% (n = 8) developed de novo postpartum hypertension, and 9% (n = 7) commenced antihypertensive therapy. There were no statistically significant differences in the rates of de novo postpartum hypertension, antihypertensive therapy initiation, or severe maternal morbidity between the two groups.

Women in the furosemide group demonstrated a higher median percentage of elevated blood pressures (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg) on discharge (4%; interquartile range [IQR], 0% to 9%), in contrast to those in the placebo group (0%; IQR, 0% to 6%; P = 0.02). There were no statistically significant differences in other secondary outcomes.

COMMENTARY

The results of the LAPP trial demonstrated that prophylactic furosemide administration did not significantly alter MAP 24 hours before discharge or initiation of antihypertensive therapy compared to the placebo group.⁶ Conversely, women in the furosemide group exhibited a higher median percentage of elevated blood pressures at discharge compared to those in the placebo group, but the clinical implication of this finding is unknown and needs further study. There were no notable differences in the rates of other secondary outcome measures between the furosemide and placebo groups.

These findings contribute to the growing body of literature on the use of furosemide in managing postpartum hypertension.^1-5 Several studies have explored the potential benefits of furosemide in this context, with varying results. Some studies have reported favorable outcomes, such as reductions in blood pressure and improved management of postpartum hypertension, while others have found no significant difference between the use of furosemide compared to placebo or alternative interventions.^1-6,8 Discrepancies among these studies may be attributed to differences in study design, patient populations, dosages of furosemide administered, and variations in monitoring protocols.

Given the potential for electrolyte imbalances associated with furosemide use, particularly hypokalemia, careful monitoring and replacement of electrolytes are essential in managing postpartum hypertension in patients receiving furosemide (and other diuretic) therapy. Regular assessment of serum electrolyte levels, particularly potassium, sodium, and magnesium, is crucial to preventing adverse events such as hypokalemia or hypomagnesemia, since imbalances in these electrolytes can exacerbate hypertension, raise the risk for hypokalemia-induced arrhythmias, and increase maternal morbidity and mortality. Close monitoring and appropriate supplementation strategies, such as the use of oral potassium and magnesium supplements in patients on furosemide therapy, should be implemented to maintain electrolyte balance and ensure the safe and effective use of furosemide during the management of postpartum hypertension.

Although the use of furosemide for the treatment of postpartum hypertension is not specifically addressed in the American College of Obstetricians and Gynecologists (ACOG) guidelines, the ACOG recommendations emphasize the importance of individualized treatment plans based on the severity of hypertension, presence of symptoms, and underlying medical conditions.^9,10 Healthcare providers should consider the risks and benefits of furosemide therapy in conjunction with other antihypertensive agents and non-pharmacologic interventions when developing management strategies for postpartum hypertension. Further research is needed to elucidate the role of furosemide in this context and to inform evidence-based recommendations for clinical practice.

REFERENCES

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