It's a copycat killer - often mimicking less severe conditions and delaying much-needed, timely treatments. But sepsis - an infection that can lead to multiple organ failure, shock and even death - is a major global health challenge and is associated with one in five deaths worldwide with the burden being carried by low-resource and vulnerable populations.
Now a potential game-changing technology, developed by Rasa Eskandari, an MD-PhD student and professor Mamadou Diop, both in the department of medical biophysics at the Schulich School of Medicine & Dentistry, could turn the tide on this global killer. Their other collaborators included medical biophysics professors Chris Ellis and Dan Goldman and physiology and pharmacology professor Don Welsh.
Using non-invasive optical technologies to detect the early onset of sepsis in rat models, these researchers are coming closer to a frugal device ideal for hospitals and clinics, and with possible applications for wearable technology in remote settings. The device measures how blood is flowing in small blood vessels (microcirculation) in both the brain and the body. It does this continuously, allowing researchers to see changes in microcirculation over time, especially during the early stages of sepsis.
Eskandari explained the benefits of the work, recently published in The FASEB Journal, in a conversation with Schulich Communications.
Why is sepsis such a significant challenge in health care today, and what are the main barriers to detecting it early?
Rasa Eskandari (RE): Sepsis is a major global health challenge due to its high incidence and mortality, as well as the complexities of timely intervention. Its non-specific early symptoms, such as fever and confusion, often mimic less severe conditions, leading to delays in diagnosis and treatment. Sepsis can quickly progress to multiple organ failure and shock; importantly, the risk of dying from sepsis increases by up to eight per cent every hour treatment is delayed. Compounding this issue is the disproportionate impact of sepsis on vulnerable populations and those in low-resource settings with limited access to timely care. Addressing these challenges requires the development of accessible technologies that are sensitive to the early onset of sepsis.
What sparked your interest in sepsis research?
RE: I am particularly drawn to sepsis research due to its devastating global impact. Our group develops bedside optical tools to monitor tissue health and blood flow continuously during critical medical conditions and surgery. These tools work by non-invasively shining light on tissue and monitoring its absorption and scattering to estimate concentrations of proteins involved in oxygen transport (i.e. hemoglobin) and the dynamics of red blood cells.
Interestingly, a potential marker of microvascular dysfunction was recently identified by Paulina Kowalewska, a researcher at Robarts Research Institute and collaborators at Western, using microscopic techniques.
We believed this approach could be replicated using our non-invasive tools. This inspired us to apply our technology to address the global health burden of sepsis through early, rapid diagnosis.
"The potential to transform patient outcomes by enabling timely interventions makes this work incredibly motivating." - Rasa Eskandari, an MD-PhD student in medical biophysics at Schulich Medicine & Dentistry
Your research uses non-invasive imaging methods to monitor skeletal muscle blood flow. What inspired you to explore this approach, and what are the benefits compared to existing detection methods?
RE: The skeletal muscle plays a central role in blood pressure regulation, which is often impaired during sepsis, and serves as an accessible window into the body's peripheral microcirculation. In sepsis, microvascular dysfunction leads to compromised perfusion or passage of fluid through the circulatory system, resulting in tissue damage. Skeletal muscle microcirculation is likely to be sacrificed early in the body's attempt to prioritize vital organs such as the brain. By examining the skeletal muscle microvasculature, we aim to detect early signs of sepsis prior to tissue and organ injury. Unlike traditional methods to assess microvascular function and perfusion, such as capillary refill time and blood lactate, our technology can passively provide continuous assessment of microvascular health. This significant advantage may allow our technology to be applied as a wearable device to continuously monitor for signs of sepsis even outside of a clinical setting.
Can you explain the key findings of your study?
RE: This study demonstrates the feasibility of using non-invasive, point-of-care optical spectroscopy for detecting the onset of sepsis-related microvascular dysfunction before clinical manifestations of the condition. This study further demonstrates that skeletal muscle microvascular dysfunction precedes significant impairment in brain microcirculation, likely reflecting the body's attempt to protect vital organs.
Why are these findings important, particularly for vulnerable populations and low-resource settings, and how could this technology improve sepsis outcomes globally?
RE: These findings are crucial because they offer a novel and accessible approach for detecting sepsis at its earliest stages. Early detection of skeletal muscle microvascular dysfunction, which precedes tissue damage, could allow for timely interventions to prevent progression to organ failure and shock. The non-invasive, continuous and relatively low-cost nature of this optical technology makes it ideal for deployment in both hospitals and clinics. It will also benefit patients in remote settings as wearable devices targeted towards individuals at higher risk of sepsis. By enabling real-time monitoring of microvascular function, this technology has the potential to significantly improve sepsis outcomes globally through earlier diagnosis.
How soon might this technique be available for use in intensive care units or other clinical settings?
RE: There are currently commercial optical spectrometers available in some hospitals, particularly being used for neuromonitoring during surgery. However, sepsis is a highly variable disorder, and while our preclinical findings provide a promising foundation, further clinical studies are necessary to evaluate our technique's efficacy for sepsis detection and monitoring in humans. Over the next three years, we will be conducting clinical studies in pediatric critical care patients in London, Ont. These efforts will be crucial in paving the way for the technology to be adopted in intensive care units and as wearable technology outside of the hospital.
What additional questions about sepsis detection are you hoping to answer in future studies?
RE: In future studies, we hope to explore the potential of our technology to detect early signs of brain injury alongside microvascular dysfunction in sepsis. Since brain injury is a common and devastating complication of sepsis, identifying early markers of cerebral perfusion and oxygen metabolism could provide novel insights that can guide intervention before irreversible damage occurs.
