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Effect of hypertonic saline concentration on cerebral and visceral organ water in an uninjured rodent model

Toung, Thomas J. MD; Nyquist, Paul MD; Mirski, Marek A. MD, PhD

doi: 10.1097/01.CCM.0000295306.52783.1E
Laboratory Investigations
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Objective: Hypertonic saline has been shown to be an effective osmotic agent to reduce brain water and hence brain volume and intracranial pressure. A direct correlation between dose and effect has been demonstrated, but no studies have compared the effects of different concentrations of the same osmotic load of hypertonic saline over time. We compared the effects of different tonicity of infused hypertonic saline on cerebral, lung, and small bowel water extraction over time under controlled conditions.

Design: Laboratory study.

Setting: Medical school.

Subjects: Male Wistar rats (280–450 g).

Interventions: Anesthetized rats were randomized to a 15-min intravenous bolus infusion of 0.9% NaCl or five equisodium but different concentrations of hypertonic saline: 4.2%, 7.5%, 10%, 23.4%, and 30%. Following infusion, animals remained anesthetized for 60, 180, or 300 mins without additional fluids given (n ≥ 6 per group). Blood was sampled, total urine output was measured, and the animal was then killed under deep anesthesia. Cerebral, lung, and small bowel water contents were derived by wet/dry weight measures.

Measurements and Main Results: After 60 mins, hypertonic saline administered at 50 mosm/kg resulted in an increase in serum osmolarity in all hypertonic saline groups (p < .05 vs. normal saline), with a significantly greater increase measured using 23.4% or 30% hypertonic saline (23.4%, 365.0 ± 8.8 mosm/L, p < .05 vs. other lesser hypertonic saline doses). The durable effect was present throughout the 300-min period by all but the lowest hypertonic saline (4.2% NaCl). Lung but not small bowel organ water was diminished by hypertonic saline. Brain water content (79.1 ± 0.2% in normal saline controls) was, however, significantly reduced.

Conclusions: Hypertonic saline is effective in reducing organ water content in a setting of preserved blood-brain barrier but is not as effective in visceral organs. At equiosmotic doses of hypertonic saline, concentration plays no substantial role in altering serum osmolarity but appears to benefit duration of action. At very high concentrations, such as 23.4% NaCl, additional water extraction is also manifested. At such high concentration of NaCl, tonicity, indeed, matters, especially in water shifts across the blood-brain barrier.

From the Departments of Anesthesiology and Critical Care Medicine (TJT, PN, MAM) and Neurology (PN, MAM), Johns Hopkins University School of Medicine, Baltimore, MD.

Supported, in part, by grant NS38684 from the National Institutes of Health Bethesda, MD.

The authors have not disclosed any potential conflicts of interest.

For information regarding this article, E-mail: mmirski@jhmi.edu

© 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins