Abstract

Background: Critically ill patients, especially following trauma or extensive surgery, experience a systemic immune response, consisting of a pro-inflammatory as well as a counterbalancing anti-inflammatory response. Pro-inflammation is necessary for the initiation of homeostatic control and wound healing of the organism. However, when the counterbalancing mechanisms dominate, a condition of secondary immunodeficiency occurs, which renders the patient susceptible for opportunistic or secondary infections. However, the incidence of this condition is yet illusive.Methods: For a period of 3 months (May to July 2017), 110 consecutive patients admitted to the surgical ICU of the Heidelberg University Hospital, a tertiary university hospital, were enrolled in the study. Monocyte HLA-DR (mHLA-DR), a long-known surrogate of monocyte function, was assessed quantitatively once on admission utilizing a novel point-of-care flow cytometer with single-use cartridges (Accelix system). Patients were followed up for further 28 days and data on ICU stay, antibiotic therapy, microbiological findings, and mechanical ventilation were recorded. Statistical analysis was performed to evaluate the incidence of immunosuppression—defined by different thresholds—as well as its consequence in terms of outcome and clinical course.Results: Depending on the HLA-DR threshold applied for stratification (≤8,000/≤5,000/≤2,000 molecules/cell), a large group of patients (85.5/68.2/40.0%) already presented with a robust decrease of HLA-DR on admission, independent of the cause for critical illness. Analyzed for survival, neither threshold was able to stratify patients with a higher mortality. However, both thresholds of 2,000 and 5,000 were able to discriminate patients with longer ICU stay, ventilation time and duration of antibiotic therapy, as well as higher count of microbiological findings. Moreover, a mHLA-DR value ≤2,000 molecules/cell was associated with higher incidence of overall antibiotic therapy.Conclusion: Single assessment of mHLA-DR using a novel point-of-care flow cytometer is able to stratify patients according to their risk of a complicated course. Therefore, this device overcomes the technical boundaries for measuring cellular biomarkers and paves the way for future studies involving personalized immunotherapy to patients with a high immunological risk profile independent of their background.Trial Registration: German Clinical Trials Register; ID: DRKS00012348.

Highlights

  • Ill patients, especially following trauma or extensive surgery, experience a systemic immune response, consisting of a pro-inflammatory as well as a counterbalancing anti-inflammatory response

  • With nearly two thirds of patients grouped into ASA class III, the cohort exhibited a high burden of co-morbidities, especially of the cardiopulmonary system, and a high degree of illness on admission, as depicted by a median Sequential organ failure assessment score (SOFA) score of 5 and Acute Physiology and Chronic Health Evaluation (APACHE) II score of 19 (Table 2)

  • One patient after esophagectomy was admitted to the Intensive care unit (ICU) in an elective manner, while the large majority of patients presented with either complications in the course of surgical treatment [unclear clinical deterioration: n = 42 (38.2%), surgeryassociated infections: n = 19 (17.3%), bleeding complication: n = 9 (8.2%)], or came as external emergencies [n = 26 (23.6%)]

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Summary

Introduction

Ill patients, especially following trauma or extensive surgery, experience a systemic immune response, consisting of a pro-inflammatory as well as a counterbalancing anti-inflammatory response. When the counterbalancing mechanisms dominate, a condition of secondary immunodeficiency occurs, which renders the patient susceptible for opportunistic or secondary infections. A plethora of counterbalancing mechanism like, e.g., the apoptosis of lymphoid cells or the appearance of antiinflammatory cytokines, occur In their entirety, those are called compensatory anti-inflammatory response syndrome (CARS) [4]. Its assumed evolutionary function is to prevent harm from overshooting inflammation, if this reaction is dominating it implies a higher susceptibility toward secondary and opportunistic infections with poor prognosis. In a nutshell, this acquired condition resembles a secondary immunodeficiency. A vicious cycle between host and pathogens develops, implying tremendous harm to the organism

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