Abstract
Immunomodulation has long been an adjunct approach in treating critically ill patients with sepsis, acute respiratory distress syndrome (ARDS), and acute pancreatitis (AP). Hyperactive immune response with immunopathogenesis leads to organ dysfunction and alters the clinical outcomes in critically ill. Though the immune response in the critically ill might have been overlooked, it has gathered greater attention during this novel coronavirus disease 2019 (COVID-19) pandemic. Modulating hyperactive immune response, the cytokine storm, especially with steroids, has shown to improve the outcomes in COVID-19 patients. In this review, we find that immune response pathogenesis in critically ill patients with sepsis, ARDS, and AP is nearly similar. The use of immunomodulators such as steroids, broad-spectrum serine protease inhibitors such as ulinastatin, thymosin alpha, intravenous immunoglobulins, and therapies such as CytoSorb and therapeutic plasma exchange may help in improving the clinical outcomes in these conditions. As the experience of the majority of physicians in using such therapeutics may be limited, we provide our expert comments regarding immunomodulation to optimize outcomes in patients with sepsis/septic shock, ARDS, and AP.
Highlights
BackgroundImmune dysfunction is common in critically ill patients who are more vulnerable to infections and the systemic consequences of dysfunctional defense responses
The exaggerated immune response is primarily due to the release of proinflammatory cytokines, often referred to as cytokine storm, which is common in critically ill patients with infections or injuries [5]
Hyperactive immune response with immunopathogenesis is established in the progression of sepsis, acute respiratory distress syndrome (ARDS), and acute pancreatitis (AP)
Summary
Immune dysfunction is common in critically ill patients who are more vulnerable to infections and the systemic consequences of dysfunctional defense responses. A small, single-center study showed mortality benefit with TPE in patients with COVID19 [81] This strategy needs further evaluation in prospective RCTs. Convalescent plasma (CP) use has been suggested in various viral infections, including MERS and H1N1 [82]. In patients with COVID-19associated ARDS, a meta-analysis of 44 studies reported beneficial effects on short-term mortality and reduced need for mechanical ventilation [91]. In patients not receiving mechanical ventilation at baseline, tocilizumab use was associated with a substantially lower rate of a composite outcome of invasive mechanical ventilation or death [103] These results are further supported by observation from a retrospective study that reported a significant reduction in the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia treated with tocilizumab [104]. The utility of various immunomodulators in patients with AP needs to be further explored in prospective studies
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