title: Osmotherapy with hypertonic saline attenuates water content in brain and extracerebral organs.
abstract: OBJECTIVE
  Because of their beneficial effects in patients with hemorrhagic shock and multiple-system trauma, hypertonic saline solutions are increasingly being used perioperatively for volume resuscitation. Although the anti-edema effects of hypertonic saline on brain are well documented in a variety of brain injury paradigms, its effects on the water content on other organs has not been studied rigorously. In this study, we tested the hypothesis that a) hypertonic saline when given as an intravenous bolus and continuous infusion attenuates water content of small bowel, lung, and brain in rats without neuro-injury; and b) attenuation of stroke-associated increases in lung water is dependent on achieving a target serum osmolality.
  
  
  METHODS
  Prospective laboratory animal study.
  
  
  METHODS
  Research laboratory in a teaching hospital.
  
  
  METHODS
  Adult male Wistar rats.
  
  
  METHODS
  In the first series of experiments, under controlled conditions of normoxia, normocarbia, and normothermia, spontaneously breathing, halothane-anesthetized (1.0-1.5%) adult male Wistar rats (280-320 g) were treated in a blinded randomized fashion with 7.5% hypertonic saline or 0.9% normal saline in a 8-mL/kg intravenous infusion for 3 hrs followed by a continuous intravenous infusion (1 mL/kg/hr) of 5% hypertonic saline or normal saline, respectively (n=10 each), for 48 hrs. A second group of rats were treated with continuous infusion only for 48 hrs of either 7.5% hypertonic saline or normal saline (1 mL/kg/hr) (n=10 each) without an intravenous bolus. Naïve rats served as controls (n=10). Tissue water content of small bowel, lung, and brain was determined by comparing the wet-to-dry ratios at the end of the experiment. In a second series of experiments, rats (n=94) were subjected to 2 hrs of transient middle cerebral artery occlusion by the intraluminal occlusion technique. At 6 hrs following middle cerebral artery occlusion, rats were treated in a blinded randomized fashion with a continuous intravenous infusion of normal saline, 3% hypertonic saline, or 7.5% hypertonic saline for 24, 48, 72, and 96 hrs. Surgical shams served as controls (n=7). Hypertonic saline was instituted as chloride/acetate mixture (50:50) in all experiments. Serum osmolality was determined at the end of the experiment in all animals.
  
  
  RESULTS
  In rats without neuro-injury that received intravenous bolus followed by a continuous infusion, lung water content was significantly reduced with hypertonic saline (73.9+/-1.1%; 359+/-10 mOsm/L) (mean+/-sd) compared with normal saline treatment (76.1+/-0.53%; 298+/-4 mOsm/L) as was water content of small bowel (hypertonic saline, 69.1+/-5.8%; normal saline, 74.7+/-0.71%) and brain (hypertonic saline, 78.1+/-0.87%; normal saline, 79.2+/-0.38%) at 48 hrs. Stroke-associated increases in lung water content were attenuated with 7.5% hypertonic saline at all time points. There was a strong correlation between serum osmolality and attenuation of stroke-associated increases in lung water content (r=-.647)
  
  
  CONCLUSIONS
  Bowel, lung, and brain water content is attenuated with hypertonic saline when serum osmolality is >350 mOsm/L without adverse effect on mortality in animals with and without neuro-injury. Attenuation of water content of extracerebral organs with hypertonic saline treatment may have therapeutic implications in perioperative fluid management in patients with and without brain injury.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Thomas J K
authors.initials: TJ
authors.lastname: Toung
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Christopher
authors.initials: C
authors.lastname: Lin
authors.forename: Anish
authors.initials: A
authors.lastname: Bhardwaj
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D011446:Prospective Studies; D051381:Rats; D017208:Rats, Wistar; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D020521:Stroke / Q000628:therapy*; D014867:Water / Q000378:metabolism*
chemical_list: D012462:Saline Solution, Hypertonic; D014867:Water