A Comparative Study of Bolus Dose of Hypertonic Saline, Mannitol, and Mannitol Plus Glycerol Combination in Patients with Severe Traumatic Brain Injury

BACKGROUND: This prospective randomized controlled study compared the efficacy of an equiosmolar and isovolumetric dose of 3% hypertonic saline, 20% mannitol, and 10% mannitol plus 10% glycerol combination in reducing the raised intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI). METHODS: A total of 120 patients of severe TBI with increased ICP were randomized to receive an equiosmolar and isovolumetric dose of 3% hypertonic saline, 20% mannitol, and 10% mannitol plus 10% glycerol combination at a defined infusion rate, which was stopped when ICP was <15 mm Hg. RESULTS: A total of 120 patients with severe TBI (aged >18 years, Glasgow Coma Scale <= 8, and had sustained elevated ICP of >20 mm Hg for more than 5 minutes) were randomized during the study. All data were presented as mean (minimum-maximum). A one-way analysis of variance test was used to analyze the effect across the treatment group, and Tukey's method was used for multiple comparisons. A paired t-test was employed to analyze the effect of the medication within each group. All 3 drugs decreased ICP below 15 mm Hg (P < 0.0001). The maximum change in ICP occurred after a bolus dose of 3% hypertonic saline followed by 10% mannitol plus 10% glycerol combination and then 20% mannitol (60% vs. 57% vs. 55%, respectively). Mean arterial pressure and cerebral perfusion pressure were increased after the bolus dose of study medications. Maximum changes occurred after infusion of 3% hypertonic saline followed by 10% mannitol plus 10% glycerol combination and 20% mannitol (P < 0.0349 and < 0.0013, respectively). There was no statistically significant change in the hematocrit value noted after the bolus dose of any of the study medications. Serum sodium and osmolarity were raised significantly after the bolus dose of study medications. Maximum changes in serum sodium and osmolarity occurred after the bolus dose of 3% hypertonic saline. The mean dose required to reduce ICP below 15 mm Hg for 3% hypertonic saline: 1.4 mL/kg, for 10% mannitol plus 10% glycerine: 1.7 mL/kg, and for 20% mannitol: 2.0 mL/kg. The mean time required to reduce ICP below 15 mm Hg for 3% hypertonic saline: 16 minutes, for 10% mannitol plus 10% glycerine: 19 minutes, and for 20% mannitol: 23 minutes. The maximum change in the Glasgow Coma Scale occurred after the bolus dose of 3% hypertonic saline, followed by 10% mannitol plus 10% glycerol combination and then 20% mannitol. CONCLUSIONS: All 3 osmotic compounds exhibit comparable effectiveness in reducing ICP when a similar osmotic load is administrated, but 3% hypertonic saline appeared to be more effective followed by 10% mannitol plus 10% glycerol combination and 20% mannitol. A dose of 1.4 mL/kg can be recommended as an initial bolus dose for 3% hypertonic saline. Hypertonic saline can be recommended to treat patients with pretreatment hypovolemia, hyponatremia, or renal failure. There is no clear benefit compared with 20% mannitol in regard to neurologic outcome, even though there is a minor positive trend for 3% hypertonic saline and 10% mannitol plus 10% glycerol combination.