title: Hypertonic saline resuscitation: efficacy may require early treatment in severely injured patients.
abstract: BACKGROUND
  Activation of polymorphonuclear neutrophils (PMN) is a critical event leading to host tissue injury and organ damage after trauma. Hypertonic saline (HS) resuscitation prevents PMN activation in vitro and in animal models. Here, we studied how clinical parameters and timing requirements influence the efficacy of HS in suppressing PMN activation.
  
  
  METHODS
  Twenty-six injured patients and 16 healthy volunteers were included as study subjects. To study how clinical parameters affect the efficacy of HS, whole blood samples from patients were collected 24 hours after admission, treated with HS and N-formyl-methionyl-leucyl-phenylalanine (fMLP), and PMN oxidative burst and degranulation were measured using flow cytometry. We studied the effect of timing on the ability of HS to inhibit PMN function by exposing blood of healthy volunteers to plasma samples from trauma patients before or after the addition of fMLP and HS.
  
  
  RESULTS
  Age and gender did not significantly influence the effect of HS on PMN function. The suppressive effect of clinically relevant HS concentrations (20 mmol/L) on PMN oxidative burst correlated weakly with Sepsis Severity Score (SSS) and Acute Physiology and Chronic Health Evaluation II (APACHE II) score but not with the Injury Severity Score (ISS) or Multiple Organ Failure score (MOF). There was no correlation between any of these clinical scores and degranulation. HS was significantly less effective in suppressing oxidative burst of PMN from patients with ISS >10, APACHE II >5, MOF >0, or SSS >1 compared with patients with ISS < or =10, APACHE II < or =5, MOF = 0, or SSS < or =1. HS more effectively suppressed PMN activation when PMN were pretreatment with HS, whereas it was less effective on PMN previously primed in vivo or in vitro by adding trauma plasma. HS was ineffective on PMN previously stimulated in vitro with fMLP.
  
  
  CONCLUSIONS
  Our data suggest that HS resuscitation may prevent PMN activation most effectively when patients are treated with HS early in the field.
authors.affiliation: University of California San Diego School of Medicine, San Diego, California 92103-8236, USA.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hashiguchi
authors.forename: Linda
authors.initials: L
authors.lastname: Lum
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Romeril
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Linda
authors.initials: L
authors.lastname: Yip
authors.forename: David B
authors.initials: DB
authors.lastname: Hoyt
authors.forename: Wolfgang G
authors.initials: WG
authors.lastname: Junger
mesh_terms: D018806:APACHE; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000627:therapeutic use; D018375:Neutrophil Activation / Q000187:drug effects*; D016897:Respiratory Burst / Q000187:drug effects; D012151:Resuscitation / Q000379:methods*; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D012462:Saline Solution, Hypertonic; D009240:N-Formylmethionine Leucyl-Phenylalanine