Point-of-care Ultrasound Abnormalities in Early Onset Preeclampsia

Point-of-care Ultrasound Abnormalities in Early Onset Preeclampsia - Prevalence and Association Between Pulmonary Interstitial Syndrome and Cardiac Dysfunction, Brain Natriuretic Peptide, and Serum Albumin

The study is planned to describe the prevalence and severity of cardiac, lung and optic-nerve sheath diameter (ONSD) ultrasound abnormalities in women with early onset preeclampsia with severe features. These findings will be compared with point-of-care ultrasound (POCUS) abnormalities demonstrated in our recent study on late onset preeclampsia. The primary aim of the current study will be to examine the association between pulmonary interstitial edema (PIS), as identified by lung ultrasound, and cardiac dysfunction on echocardiography, and brain natriuretic peptide (BNP), in early onset preeclampsia, after comprehensive echocardiographic assessment. The secondary aims are to assess ONSD, and to explore the association between PIS or ONSD and serum albumin. A further secondary aim will be to explore the association between POCUS abnormalities and cardiotocography abnormalities and early delivery.

Study Overview

• Status: Recruiting
• Conditions: Preeclampsia; Pulmonary Edema; Cardiac Function
• Intervention / Treatment: Diagnostic test: Lung ultrasound

Detailed Description

Preeclampsia (PE) remains a leading cause of maternal morbidity and mortality, in both high-, low and-middle-income countries. It is a complex, multisystem disease which, in its severe form, affects the cardiovascular, renal, hepatic, neurological and haematological systems. The University of Cape Town-associated medical institutions alone were responsible for the treatment of approximately 800 women in 2019, who were classified as having PE with severe features. Recent studies have demonstrated novel markers of severity of PE, including point-of-care ultrasound (POCUS), acid-base changes secondary to low serum albumin, and brain natriuretic peptide (BNP). A study conducted at Mowbray Maternity Hospital in Cape Town, South Africa, showed that approximately 59% of women had an abnormality shown by POCUS; 24% had elevated lung water (pulmonary interstitial syndrome [PIS]). These findings could serve as non-invasive markers of disease severity, and thus may be used to predict maternal and fetal outcome in preeclamptic women. POCUS is playing an increasing role in perioperative diagnosis, and newer, less expensive devices are continuously being developed. These will in all likelihood play an important role in South Africa in the near future. In a recent trial performed at the University of Cape Town, a comprehensive acid-base analysis in women with PE with severe features demonstrated significant abnormalities in independent acid-base determinants. In addition, strong indications were found that changes in acid-base status following a decrease in serum albumin are more pronounced in early onset PE, and may be associated with urgent delivery. In other clinical arenas in critically ill patients, low serum albumin is associated with increased lung water, increased intracranial pressure, and outcome. The study team hypothesised that similar associations might be found in women with late onset preeclampsia with severe features. Using POCUS, it was found that there was no association between serum albumin level and PIS or optic nerve sheath diameter (ONSD). PIS was however associated with cardiac dysfunction, as was BNP. This study is planned to describe the prevalence of pulmonary (PIS), cardiac and optic nerve sheath abnormalities found on ultrasound in women diagnosed with early onset PE with severe features. In a recent study on POCUS findings in late onset preeclampsia, the absence of PIS may exclude raised LVEDP. As a consequence, the primary aim of the current study is to examine the association between PIS, as identified by lung ultrasound and cardiac dysfunction on echocardiography, and BNP, in early onset PE. For this purpose, a comprehensive echocardiographic assessment will be performed. The secondary aims are to explore the association between PIS or ONSD and serum albumin. These findings will be compared with POCUS abnormalities demonstrated in our recent study on late onset PE. In addition, the association will be explored between POCUS abnormalities and CTG abnormalities and early delivery. Using a prospective observational cohort design, patients diagnosed with early onset PE with severe features will be enrolled. If agreeable to participate in the study, a venous blood sample will be taken for the measurement of serum BNP and serum albumin level, followed by a 25-30 minute non-invasive lung, cardiac and optic nerve ultrasound examination. The risks posed to the patients involved in this study are minimal. Discomfort may be experienced due to the sampling of blood, however these will be performed as part of the routine blood sampling in patients with PE. All ultrasound interventions are non-invasive. Patients not included in the study will not be disadvantaged in any way, as no treatment interventions are being proposed. All study participants will be clinically managed by the attending obstetrics team and collaborative involvement with the team will ensure current management standards at the Maternity Centre at Groote Schuur Hospital in Cape Town are maintained. Thus, the 25-30 minute ultrasound examination will not interfere with or compromise standard healthcare to recruited study participants. This observational study carries minimal risk and has the potential to fill a major knowledge gap in the role of ultrasound in the anaesthesia care of preeclamptic patients. This should be of significant future benefit in the South African context, where PE is a leading cause of maternal mortality and pulmonary oedema is a main contributor.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Margot Flint, PhD; Phone Number: +27214045144; Email: margot.flint@uct.ac.za
• Study Contact Backup: Name: Robert Dyer, MBChB; PhD; Phone Number: +27214045001

Study Locations

• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7599
      • Recruiting
      • Groote Schuur Hospital
      • Contact: Margot Flint, PhD; Phone Number: +2721 4045001; Email: margot.flint@uct.ac.za

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Patients diagnosed and admitted with early onset preeclampsia with severe features

Exclusion Criteria:

1. Body mass index (BMI) > 50 kg/m2
2. Clinical evidence of pulmonary oedema
3. The presence of a non-reassuring fetal heart trace
4. Active labour
5. Chronic pulmonary disease, or acute asthma
6. Collagen disorders
7. Chronic renal or hepatic disease
8. Urinary tract infection
9. Chorioamnionitis
10. Intrauterine fetal death
11. Patients unable to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lung- and cardiac ultrasound, as well as optic nerve sheath diameter.; An ultrasound examination (approximately 25-30 minutes in duration) will be performed at the time of venous blood sampling on admission. The examination will consist of an assessment of systolic and diastolic function, lung ultrasound, and measurement of the optic nerve sheath diameter	Diagnostic test: Lung ultrasound; Lung ultrasound will be performed with the patient in supine position (with or without left uterine displacement, depending on clinical circumstances). A phased-array transducer will be used for lung ultrasound and will be used for the assessment of B-lines, which arise from the pleural line and extend to the bottom of the screen and move with the sliding lung

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between pulmonary interstitial syndrome and cardiac dysfunction on echocardiography	More than 3 B-lines in 2 lung windows bilaterally defines the presence of pulmonary interstitial syndrome. Cardiac dysfunction on echocardiography is defined as raised left ventricular end-diastolic pressure as demonstrated on echocardiography.	35-40 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between pulmonary interstitial syndrome or optic nerve sheath diameter, and serum albumin	Please see description for outcome 1 for pulmonary interstitial syndrome. Abnormal optic nerve sheath diameter is defined as greater than 5.8 mm. Brain natriuretic peptide and serum albumin are continuous variables.	35-40 minutes.
The prevalence and severity of cardiac, lung and optic nerve sheath diameter abnormalities in women with early onset PE	Please see definitions as described under Outcome 1 and Outcome 2.	35-40 minutes

Collaborators and Investigators

• Sponsor: University of Cape Town
• Collaborators: Stanford University
• Investigators: Principal Investigator: Robert Dyer, MBChB, PhD, University of Cape Town

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: November 22, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Actual): December 23, 2022

Study Record Updates

• Last Update Posted (Actual): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pulmonary Edema
• Other Study ID Numbers: POCUS in early preeclampsia

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All collected IPD
• IPD Sharing Time Frame: 6 months following publication.
• IPD Sharing Access Criteria: Any researchers, and clinicians or healthcare workers continuing care of the participants after the study, as well as the participants themselves.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No