Using lactate testing to improve maternal sepsis identification: a multi-country test accuracy study and feasibility assessment

"Maternal sepsis" is a medical problem caused by infection during or after pregnancy or childbirth. It occurs when the body's response to infection starts to cause damage to its own organs and tissues. It can be life-threatening if not identified and treated quickly after it has developed. In fact, worldwide it is the 3rd most common cause of death related to pregnancy and childbirth. Internationally, organisations such as the World Health Organisation and United Nations are committed to reducing the numbers of women who die from preventable causes related to their pregnancies. Tackling maternal sepsis is an important part of this effort.

In high income countries research has shown that groups of key treatments given together at the same time can help reduce bad outcomes and deaths from sepsis. These groups of treatments are sometimes called "treatment bundles".

Because of this research, and the importance of tackling maternal sepsis worldwide, a treatment bundle was developed specifically for maternal sepsis. This treatment bundle is called FAST-M and was developed to be used in resource-poor settings and been tested in lots of facilities so we know it can be used to improve care.

The next important research question our team would like to answer is in which women the FAST-M treatment bundle should be started. In high income settings and the general adult population, a blood test is commonly used to help gauge which patients are most unwell from sepsis and at risk of poor outcomes. This blood test measures an acid in the blood called Lactate, which is a helpful test to identify people who need the most urgent treatment. A small hand-held machine can now be used to measure Lactate which means it could be used even in placed that don't have proper laboratory facilities.

However, it is not currently known what happens to lactate when a pregnant or recently pregnant adult has an infection, or if the test works as well if used in low resource setting. Changes in the body around pregnancy and childbirth alter how the body responds to infection which may also alter how the test works. Our team wants to find out if using a rapid lactate test is better than routine observations in identifying women most likely have maternal sepsis and to suffer poor outcomes.

We intend to conduct this research in 3 countries; Malawi, Pakistan and Uganda. We will identify cases of maternal infection within the hospital sites. After gaining the permission of these women we will add taking a blood sample for lactate testing. We will not change the usual treatment but follow what happens to these women till they are discharged from hospital. We will look at the results of the lactate test, compared to usual observations to see how it compares in diagnosing maternal sepsis, and in predicting poor outcomes.

In the second part of the study we want to find out if using this lactate test as part of maternal sepsis care, linked to the FAST-M bundle is possible in low resource settings, and what makes this easier or more difficult. To do this we will use sites in Uganda and Pakistan and see how it Lactate testing works when used. We will look carefully at how staff find using it by measuring what happens to patients and if it has been used correctly and reliably. We will also give questionnaires to staff and talk in detail to healthcare workers and others in the facility to find out their opinions about the test.

This research will help us to know if using the lactate blood test is useful to diagnose cases of maternal sepsis and how the testing can be used in resource limited facilities to improve care. We hope this information will help reduce deaths and poor outcomes from cases of maternal sepsis worldwide.

Maternal sepsis is a major cause of maternal mortality and morbidity requiring increased programmatic focus. Recent estimates suggest that it contributes to half of all maternal deaths world-wide, so without progress in this area the Sustainable Development Goal for maternal mortality will not be achieved.

A "care bundle" approach in the adult population, in high income settings, is effective at reducing sepsis mortality. A care bundle has been optimised and feasibility tested specifically for maternal sepsis in low resource settings. This bundle "FAST-M", developed with broad consensus, includes only elements that are reliably available to healthcare providers in these settings: fluids, antibiotics, source identification and control, transfer (if required) and vital signs monitoring. However triggering the bundle in the correct women remains a major challenge.

We propose to investigate if lactate measurement, available as a point-of-care test, has incremental benefit over conventional maternal vital sign assessment in the diagnosis of sepsis and identification of women at risk of severe morbidity and mortality in low resource settings.

We will determine the diagnostic and prognostic accuracy of venous lactate measurement in the maternity population, in low resource settings, which is unknown.

We will also investigate how to optimally implement this approach in low resource hospital settings, using a mixed methods evaluation. We will determine if the increased complexity of the addition of lactate measurement to the FAST-M approach impacts on compliance. Detailed qualitative and quantitative analysis will be undertaken to provide rich and detailed understanding of the process of implementation.

This study will be multi-country to increase the generalisability of our results under both objectives. The chosen study sites are in Malawi, Pakistan and Uganda.

Mothers with sepsis: This research seeks to improve the care of mothers with sepsis in low income countries, in particular Malawi, Uganda and Pakistan. We will seek to do this by using lactate testing to improving the accuracy of sepsis diagnosis, enabling treatment to be started more quickly and reducing the harm caused to mothers, their babies and families. We will also explore how lactate testing can be incorporated into clinical care as part of a carefully developed approach that will encourage health care providers to use the test correctly and act on the findings.

We will setup support groups for survivors of sepsis in Malawi, Pakistan and Uganda. These forums will provide women with support from a health-care professional and their peers. Members of these groups will also be given the opportunity to work with the study team to highlight this issue in their communities.

The wider public in Malawi, Pakistan and Uganda: The wider public will be actively engaged to participate in the study through patient and public involvement steering groups in each country. These groups will be asked to provide insights into the study processes to ensure that they are optimal for the setting. We will also have lay membership on the key trial oversight group and management group.

The health care providers and health care systems: We hope that the engagement of health care facilities with this study will give providers additional training and understanding of how to better manage maternal sepsis. We anticipate that these benefits will last beyond the life of the trial itself.

Capacity building for researchers: We are working with the WHO HRP Alliance for Capacity Strengthening to provide opportunities for junior researchers from Malawi, Uganda and Pakistan to use this study as a platform to enhance their research skills and knowledge.

Policy change: To maximise the benefit from this research it is important that the findings inform policy, and can therefore impact on practice globally. We are working closely with the WHO who have a vital role in determining health care policy worldwide. We will also ensure that we collaborate with the ministries of health in Malawi, Pakistan and Uganda to inform them of the research findings and implications for care and other key international stakeholders such as the Global Sepsis Alliance, FIGO and national professional organisations.