Treatment of Elevated Intracranial Pressure in Experimental Intracerebral Hemorrhage: Comparison between Mannitol and Hypertonic Saline

OBJECTIVE: Elevated intracranial pressure (ICP) is related to mortality after intracerebral hemorrhage (ICH). To develop effective strategies for the medical treatment of ICP in cases of ICH, we evaluated the therapeutic efficacy of mannitol and hypertonic saline in a canine model of ICH. METHODS: We introduced ICH in three groups of anesthetized mongrel dogs, consisting of seven animals each, by autologous blood injection (5.5-7.5 ml) under arterial pressure in the deep white matter adjacent to the left basal ganglia. We evaluated the effect of iso-osmolar doses (5.5 mOsm/kg) of intravenously administered mannitol (1 gm/kg), 3% NaCl (5.3 ml/kg), or 23.4% NaCl (0.7 ml/kg) administered 2 hours after the introduction of hematoma, on the following: ICP, cerebral perfusion pressure, cerebral oxygen extraction and oxygen consumption, and regional cerebral blood flow in regions around and distant to the hematoma. All measurements were recorded at baseline, before treatment, and 15, 30, 60, and 120 minutes after treatment. We also evaluated the water content (wet/dry weight) and blood-brain barrier permeability (Evans blue method) in pathologically demarcated regions of brain. RESULTS: There was an immediate reduction in ICP (mm Hg ± standard error of the mean) in the 23.4% NaCl (27.6 ± 4 to 11.0 ± 2 mm Hg, P = 0.001), 3% NaCl (23.7 ± 3 to 14.7 ± 2 mm Hg, P = 0.009), and mannitol (25.6 ± 3 to 15.9 ± 4 mm Hg, P = 0.02) groups. Compared with pretreatment values, ICP was significantly lower in both the 23.4% NaCl (12.3 ± 2 mm Hg, P = 0.002) and 3% NaCl (17.6 ± 2 mm Hg, P = 0.008) groups but not in the mannitol group (18.7 ± 4 mm Hg, P = 0.08) 15 minutes after the administration of treatment. There was a gradual rise in ICP observed in the 23.4% NaCl and mannitol groups with time. Only in the 3% NaCl group was the ICP significantly lower than the pretreatment value at 120 minutes (18.0 ± 2 mm Hg, P = 0.02). A significantly higher cerebral perfusion pressure (108.4 ± 4 versus 79.6 ± 10 mm Hg, P = 0.048) and lower water content in the lesioned white matter (65.5 ± 1% versus 67.9 ± 1%, P = 0.07) was observed 2 hours after treatment in animals receiving 3% NaCl compared with animals receiving mannitol. There were no significant differences observed in regional cerebral blood flow, oxygen extraction, or oxygen consumption at any time point among the three groups. CONCLUSION: Hypertonic saline, in both 3 and 23.4% concentrations, is as effective as mannitol in the treatment of intracranial hypertension observed in association with ICH. Hypertonic saline may have a longer duration of action, particularly when used in 3% solution. None of three treatment regimens influence regional cerebral blood flow or cerebral metabolism.