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Hypertonic saline (HS) has been suggested as an osmotic agent to control elevated intracranial pressure (ICP). Mannitol is the most commonly used osmotic agent, and no previous study has compared the effectiveness of HS to mannitol. Using a concurrent cohort design, we propose that HS and mannitol are similarly effective in controlling intracranial hypertension. Twenty-five patients received a total of 82 doses of HS at a dose of 5 ml/kg for the treatment of elevated ICP. Significant reductions in ICP were noted at 30 (p < 0.05), 60, and 120 (p < 0.01) minutes following the administration of HS, and cerebral perfusion pressure (CPP) increased significantly at 60 and 120 minutes (p < 0.05). There was no significant change in heart rate (HR) or mean arterial pressure (MAP). Eighteen patients received a total of 56 doses of mannitol for the treatment of elevated ICP. Significant reductions in ICP were seen at 60 and 120 minutes (p < 0.01) after the administration of mannitol. No significant changes were noted m CPP, HR, or MAP. Both HS and mannitol produced significant and sustained reductions in ICP. HS, however, results in significant and sustained increases in CPP HS reduces elevated ICP in a similar manner to mannitol. The avoidance of hemodynamic instability with the use of HS makes it an attractive alternative to mannitol in the management of increased ICP. These pilot data suggest that a randomized trial to compare the efficacy of HS to mannitol in pediatric patients with increased ICP is necessary.