Point-of-care Ultrasound Abnormalities in Eclampsia

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

Preeclampsia (PE) and eclampsia remain leading causes of maternal morbidity and mortality, in both high-, low-and-middle-income countries. Preeclampsia is a complex, multisystem disease which, in its severe form, affects the cardiovascular, renal, hepatic, neurological and haematological systems. Given the complexity of the disease, anaesthesia management for caesarean section in these patients remains challenging. Preeclampsia may be complicated by the development of eclampsia, which involves one or more seizures, which complicates anaesthesia and obstetrics management, and requires. urgent admission and delivery. 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). 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 research 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.

Study Overview

• Status: Recruiting
• Conditions: Eclampsia
• Intervention / Treatment: Diagnostic test: Point-of-care ultrasound

Detailed Description

Preeclampsia is a life-threatening hypertensive disorder involving the heart and vasculature affecting 5-8% of pregnancies. Untreated, 2-10% of women develop eclampsia, defined as new onset of seizures in the setting of preeclampsia. Eclamptic seizures are estimated to occur in 2-8 per 10.000 deliveries in high-income countries (HIC) and with a higher prevalence of up to 16-69 per 10.000 deliveries in low-income countries (LIC). Eclampsia is associated with significant maternal and neonatal morbidity, with a case fatality rate as high as 25-50 % in LIC, and associated with a 16-26 fold odds of death in HIC. Associated maternal complications include intracranial hemorrhage (ICH), cerebral edema, acute kidney injury, acute respiratory syndrome (ARDS), cardiac failure, coagulopathy and postpartum hemorrhage. Obstetric and medical management include seizure prophylaxis and control, aggressive blood pressure management and the urgent delivery of the baby. Anesthesia management can be challenging and has to be tailored to the clinical condition of the eclamptic woman. Unless the usual contraindications to regional anesthesia (RA) apply, spinal anesthesia (SPA) has been described as the method of choice in parturients in whom the Glasgow Coma Scale (GCS) is ≥ 14, and cardiac failure is absent. For patients with persistent decreased level of consciousness, general anesthesia (GA) is recommended. However, in eclamptic women both anesthesia techniques may be associated with significant complications. Raised intracranial pressure (ICP) present in eclamptic women raises the possibility of cerebellar tonsillar herniation in association with SPA. Cardiac diastolic dysfunction, with or without preserved ejection fraction, has been described in preeclamptic women. With preserved ejection fraction, induction of RA or GA is generally hemodynamically well tolerated. However, in women with decreased systolic function, induction of anesthesia can lead to life-threatening cardiovascular collapse, which may only be prevented by cautious titration of anesthesia agents. This might be in conflict with the need to administer high dosages of induction agents to blunt the hypertensive response to tracheal intubation that, if untreated, may lead to life-threatening ICH and pulmonary edema. Consequently, early detection of increased ICP and knowledge of cardiopulmonary function in the individual case are essential to the obstetric anesthetist to guide appropriate management.

Cardiopulmonary and optic nerve sheath point-of-care ultrasound (POCUS) protocols might be particularly suitable for this purpose. These involve a defined bedside ultrasound examination to identify critical cardiopulmonary pathophysiology, which may remain undetected by clinical examination alone. The identification of increased optic nerve sheath diameter (ONSD) on ultrasound may suggest raised ICP.

It is further well documented that the serum brain natriuretic peptide (BNP) level, a marker of cardiac dysfunction, is increased in preeclampsia. However, no data is available to confirm that elevated BNP levels identify those eclamptic women at risk for cardiopulmonary abnormalities.

Therefore, this study is planned to describe the prevalence and severity of cardiac, lung and ONS US abnormalities in women with eclampsia.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• 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; Email: robert.dyer@uct.ac.za

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: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Diagnosis of preeclampsia following ACOG definition with new onset of tonic-clonic seizures.

Exclusion Criteria:

• Chronic pulmonary disease
• Collagen disorders
• HIV infection if CD4 count <200 cells/ mm3
• Chronic renal or hepatic disease
• Urinary tract infection
• Sepsis
• Body mass index (BMI) > 50 kg/m2
• History of seizure disorder
• Intracranial haemorrhage
• History of benign or malignant intracranial neoplasia

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

Other: Lung- and cardiac ultrasound, as well as optic nerve sheath diameter.; Maternal ultrasound examinations will be performed after normal obstetric treatment protocols have been completed, i.e., the conduction of the study will contribute no delay in routine or emergency patient management. Ultrasound examination will be repeated after 72-96 hours, subject to the same conditions. An ultrasound examination (approximately 35-40 minutes in duration) will be performed. The ultrasound examination will consist of evaluation of lung- and cardiac ultrasound, as well as optic nerve sheath diameter.

Diagnostic test: Point-of-care ultrasound; An ultrasound examination (approximately 35-40 minutes in duration) will be performed. The ultrasound examination will consist of evaluation of lung- and cardiac ultrasound, as well as optic nerve sheath diameter.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The correlation between pulmonary interstitial syndrome (as identified by lung ultrasound), and cardiac dysfunction on echocardiography, in eclamptic women	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 correlation between pulmonary interstitial syndrome and optic nerve sheath diameter, serum brain natriuretic peptide and 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 of cardiac, lung and optic nerve sheath ultrasound	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 21, 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: January 3, 2023
• First Posted (Estimate): January 10, 2023

Study Record Updates

• Last Update Posted (Estimate): January 10, 2023
• Last Update Submitted That Met QC Criteria: January 3, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Cardiac dysfunction; Brain natriuretic peptide; Pulmonary interstitial syndrome
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Eclampsia
• Other Study ID Numbers: POCUS in eclampsia

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The IPD sharing plan is with an Data Transfer Agreement between the two institutions (University of Cape Town and Stanford University), the ultrasound images will be made available to the research team. The results will be shared with fellow clinicians and researchers.
• IPD Sharing Time Frame: 8 months following publication of results.
• IPD Sharing Access Criteria: Participants, clinicians and researchers.
• 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