LMP collaboration yields new POC test for determining ketoacidosis-related deaths

Ketoacidosis is a metabolic condition that occurs when the body produces high levels of ketone bodies, including β-hydroxybutyrate (BHB), acetone, and acetoacetate, leading to a buildup of acids in the blood which can be fatal. Determining cause of death by ketoacidosis can be time-consuming and costly but Forensic Pathologists and Clinical Chemists have collaborated to identify a Point-of-Care (POC) device that may bring faster information for family members and efficiencies to the death investigation system. 

Ketoacidosis can arise from several causes, the most prevalent being Diabetic Ketoacidosis (DKA) which occurs primarily in people with type 1 diabetes. It happens when the body cannot produce enough insulin, leading to high blood sugar levels. The body starts breaking down fat for energy, producing ketones as a byproduct. Alcoholic Ketoacidosis (AKA) occurs in individuals with chronic alcohol use, especially after a period of heavy drinking followed by vomiting and lack of food intake. Other causes can be due to starvation and hypothermia.

Forensic Pathologists usually measure levels of BHB to determine death by ketoacidosis. This is usually done via laboratory analysis, using liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis.

“The current testing methods may take weeks or months to receive a result, which can delay informing death investigation stakeholders and family members. Delayed confirmation of a potential ketoacidotic death may lead to additional testing, further increasing turn-around-time, burden on laboratory resources and public funds”, explains Dr. Jennifer M. Dmetrichuk, Forensic Pathologist, and currently a Regional Supervising Coroner at the Office of the Chief Coroner-Ontario Forensic Pathology Service, and Assistant Professor in the Department of Laboratory Medicine and Pathobiology (LMP) at the University of Toronto. 

She started a collaboration with Dr. Paul Yip, Head of Clinical Biochemistry at Sunnybrook Health Science Centre (SHSC) and Associate Professor in LMP, to find a way to improve testing, the results of which have recently been published in Forensic Science International. He involved two Clinical Chemistry Fellows to assist with the project Dr. Victoria Higgins and Dr. Matthew Nichols.  

“This project was brought to us during our Clinical Chemistry Fellowship rotation at Sunnybrook Health Sciences Centre. It was a very unique opportunity to collaborate with forensic pathology and is a prime example of how interdisciplinary teamwork can address complex challenges. The need for faster, more efficient testing methods in death investigations became increasingly apparent as we learned about the significant delays in current diagnostic processes. By combining our expertise, we developed a solution to streamline the determination of ketoacidosis-related deaths, improving the timeliness of results, optimizing resources, and providing critical information to families faster”, Higgins said of the project. 

The research team tested the POC test for its analytical performance in measuring BHB and glucose in decedent whole blood and vitreous humor from 100 autopsy cases, including both ketoacidosis and non-ketoacidosis deaths. They found that the POC test showed a comparable performance to current standards, making it suitable as a screening tool for ketoacidosis-related death.

“While further validation is necessary, implementing these POC tests in forensic investigations could significantly improve the timeliness in determining ketoacidosis and specifically DKA-related deaths, ultimately benefiting the communication process with loved ones of the deceased, in addition to optimizing laboratory resource utilization,” commented Dmetrichuk.

Yip, who is Chair of a taskforce looking at Clinical Laboratory Quality Indicators and harmonization across GTA hospitals in the LMP Quality Council, noted that the benefits to laboratory utilization were important. “Our work in the LMP Quality Council aims to bring a harmonization across clinical laboratories in terms of testing parameters, quality and efficiency. Validating this test will make a real difference in the workflow of forensic pathology laboratories and bring efficiencies in the use of resources, including time spent on testing, which could be reflected in other areas. It also shows that direct collaboration across institutes and specialisations in laboratory medicine can bring real benefits to many stakeholders.”

"The research was a team effort, including multiple reference laboratories, Clinical Chemistry Fellows, learners, technical and professional staff. The work demonstrates how by bringing our diverse knowledge, skills, training, and expertise together, we can work together to push our fields forward using innovative and creative approaches to solve problems", added Dmetrichuk.

Read the paper

Forensic Science International Point-of-care β-hydroxybutyrate and glucose as candidate screening methods for ketoacidosis-associated death in forensic autopsy investigations - ScienceDirect Victoria Higgins, Matthew Nichols, Helen Jo, Rawan Alsafadi, Amber Manocchio, Paul M. Yip, Jennifer M. Dmetrichuk.

This story showcases the following pillars of the LMP strategic plan: Dynamic Collaboration (pillar 2) and Impactful Research (pillar 3).