Optimizing Preeclampsia Postpartum With Point-of-care Ultrasound

Preeclampsia is a condition of the antenatal and postpartum periods, which manifests as new-onset hypertension and proteinuria. Globally, preeclampsia is estimated to affect up to 9% of all pregnancies, though as many as 63% of patients who receive this diagnosis will remain hypertensive beyond the time of postpartum hospital discharge. Because of this, up to 36% of patients with preeclampsia will require antihypertensive therapy at the time of hospital discharge, and between 26 - 74% of patients with preeclampsia will be readmitted during the first six weeks' postpartum. Cumulatively, these preeclampsia-related outcomes result in United States medical expenditures exceeding $36 million annually.

One proposed strategy for improving outcomes among patients with preeclampsia is postpartum administration of diuretics. This treatment is posited to target preeclampsia-related volume overload, which in turn is thought to contribute to continued hypertension in the postpartum period. The earliest trial on the use of diuretics for this purpose was published by Ascarelli et al in 2005 and involved randomization of 264 postpartum patients with preeclampsia to either a 5-day course of oral furosemide 20mg daily or standard preeclampsia management. Outcomes from this study included blood pressure changes over the postpartum hospital stay, need for antihypertensive therapy during hospitalization and at discharge, length of postpartum hospital stay, and other postpartum complications. While this intervention lowered systolic blood pressure by over 10 mm Hg in the first 48 hours postpartum, it did not result in a statistically significant decrease in antihypertensive therapy requirements, postpartum length of stay, or the frequency of other postpartum complications. As recently as 2021, Perdigao and colleagues published the FoR BP trial, which similarly randomized 384 postpartum patients with hypertensive disorders of pregnancy to either a 5-day course of oral furosemide 20mg daily or standard preeclampsia management. Primary outcomes from this study were slightly different from the Ascarelli et al study and included persistent hypertension 7 days postpartum and days to resolution of hypertension. Ultimately, Perdigao et al's results were more promising and demonstrated that a brief course of oral diuretics reduced the incidence of persistent hypertension by nearly 60% in patients with hypertensive disorders of pregnancy.

A potential explanation for this discrepancy in findings from earlier studies is that volume overload affects only a subset of patients with preeclampsia. While preeclamptic patients with volume overload are likely to demonstrate a meaningful response to diuresis, those without significant volume overload are less likely to respond to this treatment. Because the aforementioned studies did not account for patients' volume status at the time of randomization or diuretic administration, it seems possible that they did not sufficiently capture the patient population most likely to respond to the intervention of interest.

With regards to evaluating postpartum volume status and how it might relate to diuretic response, most obstetric practitioners currently rely on findings from physical examination (e.g. jugular venous distension, rales on lung exam, peripheral edema) that are known to have limited sensitivity. However, there is increasing evidence in the obstetric literature that use of POCUS might be a helpful adjunct for determining postpartum volume status. In 2023, Chong et al conducted a prospective cohort study of 31 patients who experienced at least 500mL blood loss during vaginal delivery. These investigators used POCUS to assess the IVC collapsibility index during the first, second, and third stages of labor as well as at the time of bleeding and following rapid resuscitation with 500mL of intravenous fluids. Chong and investigators then compared these indices to heart rate and mean arterial pressure at the same intervals and found that the IVC collapsibility index demonstrated more variation in response to volume status than did either heart rate or mean arterial pressure, both of which instead remained relatively stable over time. Moreover, a review of POCUS' role in monitoring the response to postpartum volume resuscitation was published in the American Journal of Obstetrics & Gynecology in 2024. This review suggested that the presence of three or more B-lines per screen on lung ultrasound is indicative of pulmonary edema during pregnancy and the postpartum period, as B-lines develop when air content in the lungs is replaced by transudate or exudate in the interstitium. It further suggested that an enlarged IVC diameter (> 2.0 cm) or minimal IVC collapsibility index (<15%) identified on POCUS could also be used to determine volume overload antenatally and postnatally.

The purpose of this study is to determine whether point-of-care ultrasound (POCUS) assessment of the lungs and inferior vena cava (IVC), both of which are a proxy for volume status, can be used to guide postpartum diuretic therapy in individuals with preeclampsia, and whether this strategy improves short-term maternal outcomes for this high-risk patient population.

The central study hypothesis is that, when guided by POCUS, use of diuretic therapy will improve postpartum outcomes in patients with preeclampsia relative to standard postpartum management alone. The investigators will test this hypothesis by conducting a pilot prospective cohort study that addresses the following aims:

Specific Aim 1: Assess the feasibility of POCUS assessment of the lungs and IVC in postpartum patients with preeclampsia within 24 hours of delivery.

To date, only a small handful of studies has evaluated the role of POCUS in patients with preeclampsia, the most recent of which was presented at the Society for Maternal-Fetal Medicine's Annual Pregnancy Meeting in February of this year. This pilot study conducted at the University of Tennessee Health Science Center compared the median IVC collapsibility index in 12 participants with preeclampsia with severe features to that in 10 participants without hypertensive disorders of pregnancy. Although the researchers found no significant difference in median IVC collapsibility index between the study groups, the results suggest that POCUS assessment of the IVC is at least feasible in a newly postpartum patient.

Thus, with respect to this specific aim, the investigators hypothesize that POCUS assessment will be able to successfully determine volume status in postpartum patients with preeclampsia. Specifically, the investigators anticipate that POCUS can be reliably used to identify the presence of B-lines in the lungs and to measure the greatest IVC diameter and IVC collapsibility index.

Specific Aim 2: Determine whether use of POCUS assessment to guide diuretic administration improves postpartum outcomes, including persistent hypertension at hospital discharge, time to normotension, antihypertensive use at hospital discharge, and hospital readmission, among patients with preeclampsia.

With respect to this specific aim, the investigators hypothesize that if oral or intravenous furosemide is administered to postpartum patients with preeclampsia following POCUS assessment that identifies 3 or more B-lines, an IVC diameter above 2cm, and/or an IVC collapsibility index less than 15%, there will be a decrease in persistent hypertension at hospital discharge (< 140/90 mm Hg and < 130/80 mm Hg), time to normotension, antihypertensive use at hospital discharge, and hospital readmission.

Inclusion criteria

Historical cohort (group 1):

• Age greater than or equal to 18 years at the time of delivery
• Diagnosis of preeclampsia (without severe features, with severe features, HELLP syndrome, eclampsia) during pregnancy
• Gestational age greater than or equal to 20 weeks' gestation at delivery
• Delivery at the study institution within the 18-month period prior to implementation of the study's POCUS intervention
• Available and complete postpartum clinical data on: Daily blood pressure, diuretic or antihypertensive use, length of postpartum hospital stay, readmission within 30 days of primary hospitalization

Prospective cohorts (groups 2 and 3):

• Age greater than or equal to 18 years at the time of enrollment
• Diagnosis of preeclampsia (without severe features, with severe features, HELLP syndrome, eclampsia) made up until 24 hours postpartum Postpartum and within 24 hours of delivery

Exclusion criteria

Historical cohort (group 1):

• Delivery at an outside facility or incomplete postpartum records available for analysis
• Pre-existing diagnosis of chronic hypertension; selected to mirror prospective cohort exclusion criteria (see below).
• Documentation of chronic kidney disease (CKD stage 3 or higher); selected because diuresis is more likely to be avoided in this patient population even in the presence of physical exam findings suggesting volume overload.
• Documentation of postpartum complications unrelated to preeclampsia that may significantly alter hemodynamics (e.g., sepsis, postpartum hemorrhage); selected because diuresis is more likely to be avoided in this patient population even in the presence of physical exam findings suggesting volume overload.

Prospective cohorts (groups 2 and 3):

• Pre-existing diagnosis of chronic hypertension; selected because previous studies on furosemide use in patients with postpartum preeclampsia have found a significant reduction in hypertension among patients with newly diagnosed hypertensive disorders of pregnancy, but not among those with pre-gestational hypertension, meaning that inclusion of this population might reduce the magnitude of study effects.
• Baseline renal dysfunction with serum creatinine > 1.1 mg/dL; selected as this laboratory finding has been pre-selected as a safety outcome.
• Baseline hypokalemia with serum potassium < 3.5 mEq/L despite previous repletion with intravenous or oral potassium chloride; selected as this laboratory finding has been pre-selected as a safety outcome.
• Known hypersensitivity to furosemide or sulfa drugs; selected because this would preclude exposure to the study medication of interest.
• Current use of diuretics for other indications (e.g. heart failure); selected because this may require a furosemide or other diuretic regimen different from that planned for the study intervention.