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

Lead Research Organisation: University of Liverpool
Department Name: Institute of Translational Medicine

Abstract

"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.

Technical Summary

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.

Planned Impact

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.
 
Title Maternal Sepsis: Working towards an end in Malawi 
Description Short film developed in collaboration with WHO. Filmed, edited and produced. 
Type Of Art Film/Video/Animation 
Year Produced 2023 
Impact Draws attention to maternal sepsis as a leading cause of death during or after pregnancy. 
URL https://www.youtube.com/watch?v=Tgo1XQW9Ye8
 
Title eCRF 
Description eCRF within RedCap 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? No  
Impact TBD 
 
Description Birmingham - Cost-effectiveness & sustainability of programme 
Organisation University of Birmingham
Country United Kingdom 
Sector Academic/University 
PI Contribution we provided data relevant to cost effectivenss and sustainability of the programme's delivery
Collaborator Contribution UoB will analyse the data
Impact None so far, analysis is ongoing but agreement reached
Start Year 2022
 
Description UCL - Analysis of 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Provided data from online surveys for analysis by UCL
Collaborator Contribution UCL doing the analysis and not currently held on LCTC servers. Analysis of data provided from online survey data. Building a model to implement process evaluations for behaviour change during interventions.
Impact Drafted protocol for process evaluation and draft model for how to evaluate it
Start Year 2023
 
Description Videos materials developed to encourage patient and community engagement with healthcare facilities. Video materials developed to encourage staff engagement within facilities. 
Organisation World Health Organization (WHO)
Country Global 
Sector Public 
PI Contribution Provided raw materials for use in developing media. Provided information to identify the need for these resources.
Collaborator Contribution The partners were able to produce media for dissemination to increase staff and public engagement, to improve community engagement with healthcare systems. Targeted for public dissemination.
Impact Videos developed to encourage patient and community engagement with healthcare facilities. Video materials developed to encourage staff engagement within facilities.
Start Year 2021
 
Title APT pocket references 
Description Pocket reference for staff with warning signs and potential treatment options for staff to improve management of sepsis cases. 
Type Preventative Intervention - Behavioural risk modification
Year Development Stage Completed 2024
Development Status Under active development/distribution
Impact Still in distribution 
 
Title Gestational wheels 
Description Gestational wheels for public use, which also contain information on recognising maternal sepsis 
Type Preventative Intervention - Behavioural risk modification
Year Development Stage Completed 2024
Development Status Under active development/distribution
Impact Unaware so far. Recently distributed 
 
Title Maternal sepsis posters 
Description Posters with information on maternal sepsis 
Type Preventative Intervention - Behavioural risk modification
Year Development Stage Completed 2023
Development Status Under active development/distribution
Impact Dissemination of information on recognising signs of maternal sepsis 
 
Title APT Sepsis dashboard 
Description Dashboard displaying maternal sepsis data accessible to staff 
Type Of Technology Webtool/Application 
Year Produced 2023 
Impact N/A 
 
Description Looking for additional cyclone Freddy camps 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A study update meeting that involved finding further cyclone Freddy camps to visit to assist in providing relief items.
Year(s) Of Engagement Activity 2023
 
Description PPI group in response to WHO query 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact WHO raised question via UoL - Should we inform all patients receiving maternity care in a facility randomised to the intervention about the study?
PPI group and MLW staff facilitated discussion.
Year(s) Of Engagement Activity 2023
 
Description PPI group meeting - 17 March 2022 Document review 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact 17 March 2022 Document review: Trained Immunity in BCG Vaccinated African Infants (TIA) study. Advising on the content of father's letter informing them about the study
Year(s) Of Engagement Activity 2022
 
Description PPI group meeting - Inception of the group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Orientation to PPI and to Research and research concepts
Year(s) Of Engagement Activity 2021
 
Description PPI group meeting - O3 December 2021 LACTATE Study document review 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact O3 December 2021 LACTATE Study document review, advising on the content of patient information sheets with the involvement of a local designer
Year(s) Of Engagement Activity 2021,2022
 
Description PPI group meeting - Study progress updates 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Study progress updates: APT, LACTATE and DIPLOMATIC (WKP 1-2-3-4) Studies
Year(s) Of Engagement Activity 2022
 
Description PPI poster presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact PPI Poster presentation
A combined health care provider and
lay patient and public involvement and
engagement in APT Sepsis and LACTATE
Studies. A case for Malawi
Year(s) Of Engagement Activity 2023
 
Description Presentation of LACTATE protocol - Principal Secretary of the of Ministry of Health of Malawi Dr. Charles Mwansambo 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Prof. Lissauer and Dr. Luis Gadama will present the LACTATE protocol to the Principal Secretary of the Ministry of Health of Malawi, to inform potential collaborators of the study aims and methods and build support for its implementation.
Year(s) Of Engagement Activity 2022
 
Description Presentation of LACTATE protocol - Quality Improvement Director of Ministry of Health of Malawi 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Prof Lissauer presented the LACTATE protocol to the Quality Improvement director for the Ministry of Health in Malawi, Dr. Matias Joshua, on 1 December 2021, to create interest in and support for the study aims and objectives in Malawi.
Year(s) Of Engagement Activity 2021
 
Description Public and patient involvement group established 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact We successfully established a public and patient involvement groups for LACTATE in Malawi and in Pakistan, to inform the wider public of the study aims and obtain feedback on the study. Establishment of a group in Uganda is ongoing.
Year(s) Of Engagement Activity 2021
 
Description Training for PPI team members 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact We delivered training for the public and patient involvement groups in Malawi and Pakistan, to educate members about research methods, the LACTATE study, and wider issues impacting maternal health.
Year(s) Of Engagement Activity 2021
 
Description Training for lay members of trial steering committee 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact We provided training for a lay member of the trial steering committee; this member experienced preterm birth in a previous pregnancy and received training in research methods, information about the LACTATE study, and wider issues impacting maternal and newborn health in Malawi.
Year(s) Of Engagement Activity 2021
 
Description Videos created Malawi and Pakistan for public and staff engagement 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Videos created for both Malawi and Pakistan to drive public and staff engagement
Year(s) Of Engagement Activity 2023,2024