Resuscitation of Traumatic Hemorrhagic Shock Patients With Hypertonic Saline—Without Dextran—Inhibits Neutrophil and Endothelial Cell Activation

Abstract

Background Post-traumatic inflammation and excessive neutrophil activation cause multiple organ dysfunction syndrome (MODS), a major cause of death among hemorrhagic shock patients. Traditional resuscitation strategies may exacerbate inflammation and thus novel fluid treatments are needed to reduce these post-traumatic complications. Hypertonic resuscitation fluids inhibit inflammation and reduce MODS in animal models. Here we studied the anti-inflammatory efficacy of hypertonic fluids in a controlled clinical trial. Methods Trauma patients in hypovolemic shock were resuscitated in a pre-hospital setting with 250 ml of either 7.5% hypertonic saline (HS; n=9), 7.5% hypertonic saline + 6% dextran-70 (HSD; n=8), or 0.9% normal saline (NS; n=17). Blood samples were collected on hospital admission and 12 and 24 h post-resuscitation. Multi-color flow cytometry was used to quantify neutrophil expression of cell-surface activation/adhesion (CD11b, CD62L, CD64) and degranulation (CD63, CD66b, CD35) markers as well as oxidative burst activity. Circulating concentrations of soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, P-, E-selectins, myeloperoxidase (MPO), and matrix metallopeptidase (MMP)-9 were assessed with immunoassays. Results MODS, leukocytosis, and mortality were lower in the HS and HSD groups than in the NS group. However, these differences were not statistically significant. HS prevented priming and activation and neutrophil oxidative burst and CD11b and CD66b expression. HS also reduced circulating markers of neutrophil degranulation (MPO and MMP-9) and endothelial cell activation (sICAM-1, cVCAM-1, sE-selectin, and sP-selectin). HSD was less capable than HS of suppressing the upregulation of most of these activation markers. Conclusions This study demonstrates that initial resuscitation with HS but neither NS nor HSD can attenuate post-traumatic neutrophil and endothelial cell activation in hemorrhagic shock patients. These data suggest that hypertonic resuscitation without dextran may inhibit post-traumatic inflammation. However, despite this effect, neither HS nor HSD reduced MODS in trauma patients with hemorrhagic shock.

The impact of trauma on neutrophil function

“…Across a range of time-points following traumatic injury, ex vivo studies have reported significant alterations in a multitude of neutrophil functions [5][6][7][8][9][10], which are likely to contribute to the development of secondary complications. For instance, sequestration of hyperactive neutrophils in remote bystander organs is thought to underlie the development of both ARDS and MOF, whilst reduced neutrophil function may be one explanation for the increased susceptibility of hospitalised trauma patients to nosocomial infections [2,11].…”

Influence of different fluid resuscitation techniques on the number of myeloid-derived suppressor cells in rats

“…Animal experiments have shown that hypertonic salt solutions influence the hemodynamics through selective dilation of small arteries that lead to capillaries, supplying oxygen to important organs. Moreover, hypertonic salt solutions are also superior to crystalloid or colloid solutions, in terms of immunomodulatory effect (Chiara et al, 2003;Junger et al, 2012;Kim et al, 2012).…”

Reanimación con fluidos y hemoderivados en trauma

“…El SSH arrastra agua desde el intersticio al intravascular, por lo que su aporte se asocia a un aumento en la volemia de 9 a 10 veces el volumen infundido. Estudios experimentales 28 y estudios fisiológicos 29,30 han reportado resultados positivos, especialmente la disminución de marcadores pro inflamatorios. Sin embargo, 2 estudios clínicos aleatorizados no demostraron mejoría en morbilidad o mortalidad con el uso de SSH 7,5% (250 ml en 15 min) versus cristaloides en el pre hospitalario 31,32 .…”