Prehospital Hypertonic Saline Resuscitation Attenuates the Activation and Promotes Apoptosis of Neutrophils in Patients With Severe Traumatic Brain Injury

Abstract

Background Activation of polymorphonuclear neutrophils (PMN) is thought to contribute to traumatic brain injury (TBI). Because hypertonic fluids can inhibit PMN activation, we studied whether hypertonic fluid resuscitation can reduce PMN activation in TBI patients. Methods Trauma patients with severe TBI were resuscitated with 250 ml of either 7.5% hypertonic saline (HS; n=22), HS + 6% dextran-70 (HSD; n=22), or 0.9% normal saline (NS; n=39) and blood samples were collected on hospital admission and 12 and 24 h after resuscitation. PMN activation (CD11b, CD62L, CD64) and degranulation (CD63, CD66b, CD35) markers and oxidative-burst activity as well as spontaneous PMN apoptosis were measured by flow cytometry. Results Relative to healthy controls, TBI patients showed increased PMN activation and decreased apoptosis of PMN. In the HS group, but not in the HSD group, markers of PMN adhesion (CD11b, CD64) and degranulation (CD35, CD66b) were significantly lower than in the NS group. These effects were particularly pronounced 12 h after resuscitation. Treatment with HS and HSD inhibited PMN oxidative burst responses compared to NS-treated patients. HS alone partially restored apoptosis. Despite these differences, the groups did not differ in clinical outcome parameters such as mortality and Extended Glasgow Outcome Scale. Conclusions This study demonstrates that pre-hospital resuscitation with HS can partially restore normal PMN activity and the apoptotic behavior or PMNs, while resuscitation with HSD was largely ineffective. Although the results are intriguing, additional research will be required to translate these effects of HS into treatment strategies that improve clinical outcome in TBI patients.

The impact of trauma on neutrophil function

“…Expression of CD11b, which forms part of the heterodimeric integrin Mac-1 that mediates firm adhesion to the endothelium, has been shown to be significantly increased following both TBI [6] and thermal injury [24]. Combined with the data for L-selectin, this increase in CD11b expression suggests that systemic activation of the circulating neutrophil pool occurs following trauma.…”

“…Compared to values obtained for neutrophils from healthy controls, a significant increase in spontaneous ROS production as well as ROS generation induced by fMLP and Escherichia coli (E. coli) stimulation has been reported for neutrophils isolated from TBI patients [6,10] and individuals that have suffered spinal cord injury (SCI) [7,30]. In the case of spontaneous ROS generation, this increase in oxidative activity was accompanied by a trauma-induced up-regulation of gp91 PHOX , a membrane residing subunit of the ROS generating enzyme nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase [10,30].…”

“…Surface expression of L-selectin, a receptor that facilitates tethering of neutrophils to the endothelium, has been shown to be significantly reduced on circulating neutrophils following blunt chest injury [21], penetrative trauma [22] and traumatic brain injury (TBI) [6]. Recently, Mommsen and co-workers [23] found that stimulating neutrophils in vitro with tumour necrosis factoralpha (TNF-a) resulted in shedding of L-selectin, suggesting that exposure to a pro-inflammatory environment may be one explanation for the reduced expression of L-selectin post trauma.…”

“…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].…”

Choc hémorragique : aspects physiopathologiques et prise en charge hémodynamique

“…Il s'agit soit de soluté salé hypertonique seul (NaCl 7,5 %) ou en association avec un hydroxyléthylamidon (HEA 200/0,5 à 6 % avec NaCl 7,2 % Hyperhes ® ). Ces produits auraient en plus des effets microcirculatoires (en diminuant l'oedème interstitiel) et anti-inflammatoires [31,41,42]. S'il existe un argumentaire théorique pour leur utilisation, leurs effets positifs clinique et en termes de mortalité restent aujourd'hui à démontrer [43].…”