Debate on Sepsis Biomarkers 'on Blood'
Sepsis represents a major cause of death from infectious diseases. Early identification of patients with a prognosis of sepsis is therefore crucial for their survival and prognosis. In addition to traditional biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT), other markers are being sought that could be used in the differential diagnosis of sepsis. This issue was also addressed at a symposium organized by Beckmann Coulter, which took place on April 28, 2022, as part of the Colours of Sepsis congress in Ostrava.
The debate on sepsis biomarkers included the following participants:
- Prof. MUDr. Martin Matějovič, Ph.D., Head of the First Department of Internal Medicine, Faculty of Medicine, Charles University and Plzeň University Hospital
- Assoc. Prof. MUDr. Helena Lahoda Brodská, Ph.D., Head Physician of the Outpatient Operations of the Central Laboratory, Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague
- MUDr. Václava Adámková, Chief of the Department of Clinical Microbiology and Antibiotic Centre, Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague
The discussion was moderated by MUDr. Roman Kula, CSc., from the Department of Anesthesiology and Resuscitation, Faculty of Medicine, University of Ostrava and Ostrava University Hospital.
Universal sepsis biomarker as the holy grail of intensive care medicine
Of the many dozens of sepsis biomarkers that have appeared in various world publications, only CRP, PCT, and possibly interleukin IL-6 are predominantly used in practice. Their high values represent a warning signal that something serious is happening in the body. On the other hand, even only slightly elevated values of these biomarkers can be found in a patient in septic shock. Finding a universal specific sepsis biomarker is thus one of the research goals that is not easy to achieve, as sepsis represents a heterogeneous interaction between the pathogen, the patient, and therapeutic interventions.
Over the last 2 years, a new hematological biomarker – monocyte distribution width (MDW) – has also been used in early sepsis diagnostics. Its clinical benefit was validated at the Plzeň University Hospital. MDW represents a cheap and easily accessible biomarker for identifying patients at risk of developing severe infections (so-called red flag).
The symposium's title Debate on Sepsis Biomarkers 'on Blood' had a dual symbolism – exploring the possibility of using new hematological biomarkers as well as intense interdisciplinary exchanges of opinions.
Basic questions for discussion and finding answers to them
- Do we need biomarkers? Is it true that the more, the better?
- When does a laboratory parameter become a biomarker?
- The most common biomarker is PCT. Who uses it?
- Isn't the PCT value set too low?
- What can be the causes of non-infectious elevation of PCT?
- Do you still use CRP?
- Can a blood count be used as a biomarker?
1. Do we need sepsis biomarkers? Is it true that the more, the better?
According to Associate Professor Brodská, it is advantageous to have more biomarkers, but it is necessary to think about their interpretation and correlate the values with the clinical picture. Professor Matějovič is primarily interested in whether the patient has an infection, what the origin of this infection is, and how severe the infection is. The sepsis biomarker as such does not exist; sepsis is only an artificial concept capturing the life-threatening nature of the infection. Chief Physician Adámková would recommend a more coordinated use of biomarkers.
2. When does a laboratory parameter become a biomarker?
According to the laconic answer of Professor Matějovič, when it has informational value.
3. The most common biomarker is PCT. Who uses it?
Most symposium participants and discussing experts use PCT as a biomarker. They discussed the significance of the PCT value. According to Professor Matějovič, the greatest benefit is in the negative value of this biomarker, which with a solid degree of probability excludes the bacterial origin of the infection. However, there are exceptions here as well. Generally, for one diagnosis, various PCT values can apply, and similarly, one value can mean several other diagnoses. Associate Professor Brodská pointed out that earlier assessments by semi-quantitative methods were subjectively burdened – dependent even on color vision. She also agreed that the PCT value changes with the development of the infection and that it also depends on when the sampling was performed.
4. Isn't the PCT value set too low?
As the moderator noted, sepsis is a condition typical for older age. Shouldn't the limit value of PCT be higher? Associate Professor Brodská believes it depends on what group and what disease the biomarker is used for. Chief Physician Adámková brought up a controversial point by noting that even with high PCT, she often does not recommend starting antibiotics. According to Professor Matějovič, however, this approach is risky and it is always absolutely necessary to know the clinical context – never decide only based on an isolated biomarker. MUDr. Kula added that a high PCT value can indeed be misleading and can lead to unnecessary antibiotic treatment for non-infectious causes. From the audience, there was also a comment that the interpretation of PCT values in a specific case is important and that guidelines should not be confused with a treatment protocol.
5. What can be the causes of non-infectious elevation of PCT?
Frequent causes of high PCT levels mentioned by Associate Professor Brodská include cardiac arrest or methamphetamine intoxication. Professor Matějovič has experience with PCT elevation in connective tissue diseases, neuroendocrine tumors, or hemodialysis patients. Experts also encounter elevated PCT in pediatrics and some newborns without a known correlation. Stress could also influence PCT.
6. Do you still use CRP?
For Chief Physician Adámková, the CRP value is more beneficial regarding its negative predictive value. Professor Matějovič, on the other hand, uses it as the first marker indicating a possible infection, in case of uncertainty then in combination with PCT.
7. Can a blood count be used as a biomarker?
Evaluation of blood count and differential count ranks among the most commonly performed routine examinations. In addition to traditional use, it can also contain information about the risk of severe infection. According to Professor Matějovič, monocytes react very quickly to infection by changing their volume. A high MDW value should be considered a warning signal, as demonstrated by its evaluation in 1500 patients monitored at the Plzeň University Hospital. This marker is particularly beneficial in combination with other laboratory parameters such as leukocytes or creatinine.
Conclusion
According to experts, a reliable sepsis biomarker is hard to find because there will always be great infectious and non-infectious variability. In practice, CRP and PCT are routinely used, and their values need to be interpreted individually in the context of other laboratory parameters and clinical status. Expanding the use of biomarkers to include MDW, which represents a fast, cheap, and easily accessible option for identifying patients at risk of sepsis, may be beneficial.
MUDr. Andrea Skálová
editorial staff for ProLékaře.cz
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