Osmotherapy with hypertonic saline attenuates water content in brain and extracerebral organs

Thomas J K Toung, Chih Hung Chen, Christopher Lin, Anish Bhardwaj

Research output: Contribution to journalArticle

24 Citations (Scopus)

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. DESIGN: Prospective laboratory animal study. SETTING: Research laboratory in a teaching hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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.

Original languageEnglish (US)
Pages (from-to)526-531
Number of pages6
JournalCritical Care Medicine
Volume35
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

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Water
Brain
Lung
Osmolar Concentration
Intravenous Infusions
Middle Cerebral Artery Infarction
Stroke
Serum
Brain Injuries
Wistar Rats
Wounds and Injuries
Hypertonic Saline Solutions
Saline Waters
Hemorrhagic Shock
Multiple Trauma
Laboratory Animals
Halothane
Resuscitation
Teaching Hospitals
Chlorides

Keywords

  • Hypertonic saline
  • Osmotherapy
  • Pulmonary edema
  • Stroke

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Osmotherapy with hypertonic saline attenuates water content in brain and extracerebral organs. / Toung, Thomas J K; Chen, Chih Hung; Lin, Christopher; Bhardwaj, Anish.

In: Critical Care Medicine, Vol. 35, No. 2, 02.2007, p. 526-531.

Research output: Contribution to journalArticle

Toung, Thomas J K ; Chen, Chih Hung ; Lin, Christopher ; Bhardwaj, Anish. / Osmotherapy with hypertonic saline attenuates water content in brain and extracerebral organs. In: Critical Care Medicine. 2007 ; Vol. 35, No. 2. pp. 526-531.
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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. DESIGN: Prospective laboratory animal study. SETTING: Research laboratory in a teaching hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: 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. Na{\"i}ve 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. MEASUREMENTS AND MAIN 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.",
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T1 - Osmotherapy with hypertonic saline attenuates water content in brain and extracerebral organs

AU - Toung, Thomas J K

AU - Chen, Chih Hung

AU - Lin, Christopher

AU - Bhardwaj, Anish

PY - 2007/2

Y1 - 2007/2

N2 - 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. DESIGN: Prospective laboratory animal study. SETTING: Research laboratory in a teaching hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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.

AB - 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. DESIGN: Prospective laboratory animal study. SETTING: Research laboratory in a teaching hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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.

KW - Hypertonic saline

KW - Osmotherapy

KW - Pulmonary edema

KW - Stroke

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