Neutrophil heterogeneity and its role in infectious complications after severe trauma

Hesselink, Lillian; Spijkerman, Roy; Wessem, Karlijn J. P. van; Koenderman, Leo; Leenen, Luke P. H.; Huber‐Lang, Markus; Hietbrink, Falco

doi:10.1186/s13017-019-0244-3

Cited by 50 publications

(68 citation statements)

References 108 publications

(190 reference statements)

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“…Hence, the PICS markers described so far are nonspecific, insensitive and arguable, and there is a need for better biomarkers to identify PICS. Recently, automated flow cytometry became available which enables fast and point-of-care analysis of receptor expression of immune cells [36,37]. Further research should investigate if such analyses can be used to identify patients at risk for PICS in an early stage.…”

Section: Discussionmentioning

confidence: 99%

Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS) after Polytrauma: A Rare Syndrome with Major Consequences

Hesselink

Hoepelman

Spijkerman

et al. 2020

JCM

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Nowadays, more trauma patients develop chronic critical illness (CCI), a state characterized by prolonged intensive care. Some of these CCI patients have disproportional difficulties to recover and suffer from recurrent infections, a syndrome described as the persistent inflammation, immunosuppression and catabolism syndrome (PICS). A total of 78 trauma patients with an ICU stay of ≥14 days (CCI patients) between 2007 and 2017 were retrospectively included. Within this group, PICS patients were identified through two ways: (1) their clinical course (≥3 infectious complications) and (2) by laboratory markers suggested in the literature (C-reactive protein (CRP) and lymphocytes), both in combination with evidence of increased catabolism. The incidence of PICS was 4.7 per 1000 multitrauma patients. The sensitivity and specificity of the laboratory markers was 44% and 73%, respectively. PICS patients had a longer hospital stay (median 83 vs. 40, p < 0.001) and required significantly more surgical interventions (median 13 vs. 3, p = 0.003) than other CCI patients. Thirteen PICS patients developed sepsis (72%) and 12 (67%) were readmitted at least once due to an infection. In conclusion, patients who develop PICS experience recurrent infectious complications that lead to prolonged hospitalization, many surgical procedures and frequent readmissions. Therefore, PICS forms a substantial burden on the patient and the hospital, despite its low incidence.

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Section: Discussionmentioning

confidence: 99%

Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS) after Polytrauma: A Rare Syndrome with Major Consequences

Hesselink

Hoepelman

Spijkerman

et al. 2020

JCM

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“…This is supported by the decrease in phagosomal acidification observed in patients at the time of infection. Moreover, it is possible that the infections caused a migration of well-functioning neutrophils into tissues leading to a further decrease of well-functioning neutrophils in the blood, a phenomenon previously described as a refractory immune state [45].…”

Section: Discussionmentioning

confidence: 99%

New automated analysis to monitor neutrophil function point-of-care in the intensive care unit after trauma

Hesselink

Spijkerman

Fraiture

et al. 2020

ICMx

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Background: Patients 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 pointof-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. Results: Fifteen 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. Conclusion: Neutrophil 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.

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“…Sometimes, however, these processes of inflammatory response become dysregulated, and immune-mediated complications may occur such as multiple organ dysfunction syndrome (MODS) and adult respiratory distress syndrome (ARDS). 4 Several studies including our own have observed that MODS-related and ARDS-related deaths have decreased over the last years resulting in more severely injured patients surviving. 5 6 However, we also observed that many surviving patients developed infectious complications.…”

Section: Introductionmentioning

confidence: 93%

Attenuation of MODS-related and ARDS-related mortality makes infectious complications a remaining challenge in the severely injured

Wessem

Hietbrink

Leenen

2020

Trauma Surg Acute Care Open

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IntroductionThe recent decrease in multiple organ dysfunction syndrome (MODS)-associated and adult respiratory distress syndrome (ARDS)-associated mortality could be considered a success of improvements in trauma care. However, the incidence of infections remains high in patients with polytrauma, with high morbidity and hospital resources usage. Infectious complications might be a residual effect of the decrease in MODS-related/ARDS-related mortality. This study investigated the current incidence of infectious complications in polytrauma.MethodsA 5.5-year prospective population-based cohort study included consecutive severely injured patients (age >15) admitted to a (Level-1) trauma center intensive care unit (ICU) who survived >48 hours. Demographics, physiologic and resuscitation parameters, multiple organ failure and ARDS scores, and infectious complications (pneumonia, fracture-related infection, meningitis, infections related to blood, wound, and urinary tract) were prospectively collected. Data are presented as median (IQR), p<0.05 was considered significant.Results297 patients (216 (73%) men) were included with median age of 46 (27–60) years, median Injury Severity Score was 29 (22–35), 96% sustained blunt injuries. 44 patients (15%) died. One patient (2%) died of MODS and 1 died of ARDS. 134 patients (45%) developed 201 infectious complications. Pneumonia was the most common complication (50%). There was no difference in physiologic parameters on arrival in emergency department and ICU between patients with and without infectious complications. Patients who later developed infections underwent more often a laparotomy (32% vs 18%, p=0.009), had more often pelvic fractures (38% vs 25%,p=0.02), and received more blood products <8 hours. They had more often MODS (25% vs 13%, p=0.005), stayed longer on the ventilator (10 (5–15) vs 5 (2–8) days, p<0.001), longer in ICU (11 (6–17) vs 6 (3–10) days, p<0.001), and in hospital (30 (20–44) vs 16 (10–24) days, p<0.001). There was however no difference in mortality (12% vs 17%, p=0.41) between both groups.Conclusion45% of patients developed infectious complications. These patients had similar mortality rates, but used more hospital resources. With low MODS-related and ARDS-related mortality, infections might be a residual effect, and are one of the remaining challenges in the treatment of patients with polytrauma.Level of evidenceLevel 3.Study typePopulation-based cohort study.

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Neutrophil heterogeneity and its role in infectious complications after severe trauma

Cited by 50 publications

References 108 publications

Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS) after Polytrauma: A Rare Syndrome with Major Consequences

Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS) after Polytrauma: A Rare Syndrome with Major Consequences

New automated analysis to monitor neutrophil function point-of-care in the intensive care unit after trauma

Attenuation of MODS-related and ARDS-related mortality makes infectious complications a remaining challenge in the severely injured

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