Abstract
BackgroundPatients often develop infectious complications after severe trauma. No biomarkers exist that enable early identification of patients who are at risk. Neutrophils are important immune cells that combat these infections by phagocytosis and killing of pathogens. Analysis of neutrophil function used to be laborious and was therefore not applicable in routine diagnostics. Hence, we developed a quick and point-of-care method to assess a critical part of neutrophil function, neutrophil phagosomal acidification. The aim of this study was to investigate whether this method was able to analyze neutrophil functionality in severely injured patients and whether a relation with the development of infectious complications was present.ResultsFifteen severely injured patients (median ISS of 33) were included, of whom 6 developed an infection between day 4 and day 9 after trauma. The injury severity score did not significantly differ between patients who developed an infection and patients who did not (p = 0.529). Patients who developed an infection showed increased acidification immediately after trauma (p = 0.006) and after 3 days (p = 0.026) and a decrease in the days thereafter to levels in the lower normal range. In contrast, patients who did not develop infectious complications showed high-normal acidification within the first days and increased tasset to identify patients at risk for infections after trauma and to monitor the inflammatory state of these trauma patients.ConclusionNeutrophil function can be measured in the ICU setting by rapid point-of-care analysis of phagosomal acidification. This analysis differed between trauma patients who developed infectious complications and trauma patients who did not. Therefore, this assay might prove a valuable asset to identify patients at risk for infections after trauma and to monitor the inflammatory state of these trauma patients.Trial registrationCentral Committee on Research Involving Human Subjects, NL43279.041.13. Registered 14 February 2014. https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm.
Highlights
Patients often develop infectious complications after severe trauma
Infection-related mortality rates decreased over the past decades [4], severe infections such as sepsis remain a substantial cause of morbidity and mortality after trauma worldwide [5, 6]
Biomarkers that were suggested after trauma included neutrophil C5aR expression [13, 14], neutrophil extracellular traps (NETs) [17], neutrophil CD64 expression [18, 19], neutrophil cell size [20], and neutrophil formyl-methionyl-leucyl-phenylalanine-induced FcγRII expression, of which only the latter was found to be an early marker in multiple trauma cohorts [21, 22]
Summary
Patients often develop infectious complications after severe trauma. No biomarkers exist that enable early identification of patients who are at risk. It has not been possible to recognize patients who will develop these relatively late complications in an early phase after trauma Used biomarkers such as leukocyte counts and C-reactive protein (CRP) become positive during infections and have limited prognostic value [7]. Neutrophil fMLF-induced FcγRII expression measured immediately after trauma showed high sensitivity (90%) for the prediction of severe sepsis ≥ 5 days post-trauma [21]. This suggests that those patients who are at risk for severe infectious complications can be identified on admission already. There is an unmet need for a biomarker to monitor high-risk trauma patients in the early days after admission
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