Critical illness is characterised by a phase of hyperinflammation associated with pro-inflammatory cytokines and subsequent immunosuppression typified by anti-inflammatory response. This phase manifests as immune cell exhaustion, anergy, and deletion of crucial inflammatory cells, rendering patients susceptible to secondary infections, increasing morbidity and mortality rates.
Current management of critically ill patients remains largely supportive; early antimicrobials, organ support in the form of vasopressors, advanced respiratory support (ARS) and dialysis, all improving survival in the early phases of illness. However, many surviving patients go onto endure an extensive immunosuppressive period, with previously immunocompetent patients at risk for secondary bacterial and viral infection. Targeted treatments in sepsis have been trialled including activated protein C, Anakinra and antithrombin III with disappointing results. Application of therapies without considering course of illness may contribute to challenges faced by therapies that showed promise in pre-clinical studies but ultimately failed in clinical trials.
This study aims to elucidate temporal and dynamic changes in immune cell profiles within critically ill patients and discern whether these changes correlate with need for invasive mechanical ventilation (IMV), evolving as patients recover or succumb from cortical illness.
Hypothesis:
Difference in course of immune cell exhaustion will manifest in patients undergoing IMV versus those requiring ARS. This dysfunction will be more profound in IMV patients, predominating in those who do not recover.
Objectives:
Recruit 20 consecutive patients admitted to Intensive Care Unit (ICU) with respiratory sepsis managed with ARS (HFNC, NIV) or IMV (including ARS <72h) with 10 patients in each cohort. Samples will be taken 48 hours after initiation of ARS, at 7 days, and before discharge from ICU.
Determine timescale of impaired immune response in critically ill patients by analysing peripheral blood mononuclear cells (PMBCs) and immune cells from bronchiolar washing samples where bronchoscopy is undertaken for clinical reasons.