Understanding and managing refractory septic shock in the intensive care unit

Refractory septic shock is due to a dysregulated immune response that is caused by a bacterial or a fungal infection in the blood. Endotoxins like lipopolysaccharide (LPS) from bacteria stimulate the release of pro-inflammatory mediators including tumor necrosis factor-alpha (TNF-?) and interleukin-1 (IL-1). These cytokines activate leukocytes resulting in the release of additional inflammatory mediators promoting widespread inflammation. This leads to refractory septic shock, which adversely affects the cardiovascular, respiratory and renal systems. In this review, current therapies to manage septic shock are examined and novel treatments are proposed to make sepsis more manageable in the clinical setting. ICU patients diagnosed at an early stage have the highest rate of survival as they can be effectively treated to prevent the onset of septic shock. However, patients that have progressed into later stages of sepsis have complications due to septic shock. We suggest treating these patients with cytokine inhibitors and anti-LPS molecules (cationic lipids and poly-L-histidines) in addition to therapeutics for organ-localized complications. This two-pronged approach treats the adverse effect due to inflammation that has already occurred and prevents further inflammation, resulting in an improved clinical outcome.