The immunomodulatory effects of hypertonic saline resuscitation in patients sustaining traumatic hemorrhagic shock: a randomized, controlled, double-blinded trial.
OBJECTIVE
To investigate the potential immunologic and anti-inflammatory effects of hypertonic saline plus dextran (HSD) in hemorrhagic trauma patients.


BACKGROUND
Unbalanced inflammation triggered by shock has been linked to multiorgan dysfunction (MOD) and death. In animal and cellular models, HSD alters the inflammatory response to shock, attenuating MOD and improving outcome. It remains untested whether HSD has similar effects in humans.


METHODS
A single 250-mL dose of either HSD (7.5% NaCl, 6% dextran-70) or placebo (0.9% NaCl) was administered to adult blunt trauma patients in hemorrhagic shock. The primary outcome was to measure changes in immune/inflammatory markers, including neutrophil activation, monocyte subset redistribution, cytokine production, and neuroendocrine changes. Patient demographics, fluid requirements, organ dysfunction, infection, and death were recorded.


RESULTS
A total of 27 patients were enrolled (13 HSD) with no significant differences in clinical measurements. Hyperosmolarity was modest and transient, whereas the immunologic/anti-inflammatory effects persisted for 24 hours. HSD blunted neutrophil activation by abolishing shock-induced CD11b up-regulation and causing CD62L shedding. HSD altered the shock-induced monocyte redistribution pattern by reducing the drop in "classic" CD14 and the expansion of the "pro-inflammatory" CD14CD16 subsets. In parallel, HSD significantly reduced pro-inflammatory tumor necrosis factor (TNF)-alpha production while increasing anti-inflammatory IL-1ra and IL-10. HSD prevented shock-induced norepinephrine surge with no effect on adrenal steroids.


CONCLUSIONS
This first human trial evaluating the immunologic/anti-inflammatory effects of hypertonic resuscitation in trauma patients demonstrates that HSD promotes a more balanced inflammatory response to hemorrhagic shock, raising the possibility that similar to experimental models, HSD might also attenuate post-trauma MOD.
Rizoli
Sandro B
SB
Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. sandro.rizoli@sw.ca
Rhind
Shawn G
SG
Shek
Pang N
PN
Inaba
Kenji
K
Filips
Dennis
D
Tien
Homer
H
Brenneman
Fred
F
Rotstein
Ori
O
D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D003911:Dextrans / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006728:Hormones / Q000096:biosynthesis; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D007962:Leukocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000209:etiology / Q000276:immunology* / Q000628:therapy*; D014949:Wounds, Nonpenetrating / Q000150:complications / Q000276:immunology*
D000954:Antigens, Surface; D016207:Cytokines; D003911:Dextrans; D006728:Hormones; D007155:Immunologic Factors; D012462:Saline Solution, Hypertonic