Hypertonic Saline Resuscitation Restores Inflammatory Cytokine Balance in Post-Traumatic Hemorrhagic Shock Patients

Fluid resuscitation can often exacerbate injury sustained during hemorrhagic shock and is associated with altered immuno-inflammatory events. Early monocyte dysregulation and excessive proinflammatory cytokine production are thought to play a key role in the development of post-traumatic multiorgan dysfunction in resuscitated trauma patients. Compared with standard isotonic crystalloid resuscitation using 0.9% normal saline (NS), 7.5% hypertonic saline with 6% dextran-70 (HSD) has been shown in experimental studies to reduce shock/resuscitation-induced inflammatory reactions and lessen organ dysfunction. However, the immunomodulatory capacity of HSD, has not been evaluated in clinical human trials. In this prospective, randomized controlled trial we show that a single (250 mL) bolus infusion of HSD in hemorrhagic trauma patients restores the balance between pro and antiinflammatory mediators in the early post-resuscitative period. Flow cytometric single-cell analyses revealed that, compared to standard resuscitation with NS, which selectively expands the proinflammatory CD14+CD16+ monocyte phenotype, initial treatment with HSD elicits selective depletion of CD14+CD16+ cells and down-regulates monocytic adhesion molecule expression. Moreover, HSD significantly inhibits intracellular TNFproduction by CD14+CD16+ monocytes, while upregulating both IL-10 and IL-1ra by CD14++CD16– monocytes. This differential profile of monocytic cytokine expression in response to HSD appears to be mediated, at least partly, by attenuation of post-resuscitation noradrenergic-stimulated signaling pathways. These findings demonstrate that HSD promotes a more balanced early inflammatory response in resuscitated hemorrhagic shock patients.