Hypertonic resuscitation modulates the inflammatory response in patients with traumatic hemorrhagic shock.
OBJECTIVE
To determine the effect of resuscitation with hypertonic saline/dextran (HSD) on the innate immune response after injury.


BACKGROUND
Hypovolemic shock causes a whole body ischemia/reperfusion injury, leading to dysregulation of the inflammatory response and multiple organ dysfunction syndrome. Hypertonicity has been shown to modulate the innate immune response in vitro and in animal models of hemorrhagic shock, but the effect on the inflammatory response in humans is largely unknown.


METHODS
Serial blood samples were drawn (12, 24, 72 hours and 7 days after injury) from patients enrolled in a prospective, randomized, double-blind trial of traumatic hypovolemic shock, HSD (250 mL) versus lactated Ringer's solution (LR) as the initial resuscitation fluid. Neutrophil (PMN) CD11b/CD18 expression was assessed via whole blood FACS analysis with and without stimulation (fMLP 5 micromol/L or PMA 5 micromol/L). PMN respiratory burst was assessed using the nitro-blue tetrazolium assay. Monocytes stimulated with 100 ng LPS for 18 hours were assessed for cytokine production (TNF-alpha, IL-1Beta, IL-6, IL-10, IL-12).


RESULTS
Sixty-two patients (36 HSD, 26 LR) and 20 healthy volunteers were enrolled. CD11b expression, 12 hours after injury, was increased 1.5-fold in patients resuscitated with LR compared with controls. Those resuscitated with HSD had a significant reduction in CD11b expression 12 hours after injury, compared with LR. There was no difference in respiratory burst early after injury. Monocytes from injured patients expressed lower levels of all cytokines in comparison to normal controls. Patients give HSD showed a trend toward higher levels of IL-1beta and IL10 production in response to LPS, 12 hours after injury.


CONCLUSIONS
HSD resuscitation results in transient inhibition of PMN CD11b expression and partial restoration of the normal monocyte phenotype early after injury.
Bulger
Eileen M
EM
Department of Surgery, University of Washington, Harborview Medical Center, Seattle, WA 98104, USA. ebulger@u.washington.edu
Cuschieri
Joseph
J
Warner
Keir
K
Maier
Ronald V
RV
D000328:Adult; D039481:CD11b Antigen / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D018375:Neutrophil Activation / Q000502:physiology; D012151:Resuscitation; D012462:Saline Solution, Hypertonic / Q000494:pharmacology* / Q000627:therapeutic use; D012771:Shock, Hemorrhagic / Q000276:immunology* / Q000628:therapy*
D039481:CD11b Antigen; D012462:Saline Solution, Hypertonic