Hypertonic saline ameliorates cerebral edema associated with experimental brain tumor

Thomas J K Toung, Betty Tyler, Henry Brem, Richard J Traystman, Patricia D Hurn, Anish Bhardwaj
Journal of Neurosurgical Anesthesiology 2002, 14 (3): 187-93
Cerebral edema commonly accompanies brain tumors and frequently leads to lethal intracranial compartmental shifts and elevated intracranial pressure. Therapeutic modalities for tumor-associated cerebral edema include diuretics, osmotherapy, and corticosteroids. Recently, hypertonic saline (HS) has received attention as an osmotic agent in the treatment of cerebral edema from diverse causes. The effects of continuous HS infusion in brain tumor-associated edema have not been previously reported. Therefore, we tested the hypothesis that HS given as a continuous intravenous infusion ameliorates tumor-associated edema in a rat model of brain tumor. 9L gliosarcoma, propagated as a solid flank tumor, was implanted intracranially over the left hemisphere in adult female Fischer 344 rats (180-220 g). On day 11 after implantation, rats were divided in a blinded, randomized fashion into groups that received no treatment or continuous infusion of 0.9% saline (NS) (0.3 mL/h) and in a subsequent series that included NS + intravenous furosemide 2.5 mg/kg every six hours, NS + intravenous mannitol 2.5 g/kg every six hours, or continuous infusion 7.5% HS (chloride:acetate 50:50) (0.3 mL/h). Hemispheric water content ipsilateral (IH) and contralateral to tumor implantation was determined at day 13 by wet-to-dry weight ratio after 48 hours of therapy. Ipsilateral hemispheric water content (mean +/- SEM) was significantly increased in rats with intracranial tumor on day 11 (80.3 +/- 0.5%) (n = 7) and day 13 (81.4 +/- 0.3%) (n = 10), as compared to naive weight-matched rats without tumor implant (79.3 +/- 0.1%) (n = 13) (P <.05). After 48 hours of treatment, IH water content was attenuated with continuous HS (n = 15) (79.3 +/- 0.2%), mannitol (n = 14) (80.1 +/- 0.2%), and furosemide (n = 15) (79.9 +/- 0.2%) as compared to NS (n = 7) (80.8 +/- 0.5%). Continuous HS infusion attenuated cerebral edema in the affected hemisphere as well as the contralateral noninjured hemisphere to a larger extent than was observed with furosemide or mannitol. These findings suggest a potential new treatment strategy for tumor-associated cerebral edema.

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