Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial

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Abstract
The authors evaluated long-term clinical outcomes in selected acutely comatose patients with severe diffuse brain swelling and recent clinical signs of impending brain death who received a novel high-dose mannitol treatment compared with those who received conventional-dose mannitol in the emergency room. Forty-four adult patients with traumatic, nonmissile-inflicted, acute, severe diffuse brain swelling were prospectively and randomly evaluated. All patients were selected based on the presence of recent clinical signs of impending brain death on the first emergency room evaluation. These signs included bilateral abnormal pupillary widening and lack of motor responses to painful stimulation (Glasgow Coma Scale score of 3). The study group (23 patients) received ultra-early and fast intravenous high-dose mannitol treatment (approximately 1.4 g/kg), whereas the control group (21 patients) received half that dose (approximately 0.7 g/kg). Ultra-early improvement of bilateral abnormal pupillary widening was significantly more frequent in the high-dose mannitol group than in the conventional-dose group (p < 0.02). High-dose mannitol treatment in the emergency room was also associated with significantly better 6-month clinical outcomes (p < 0.02); the best rate of favorable outcomes was 43.5%, compared with only 9.5% in the conventional-dose mannitol group. The two groups of patients were well matched with respect to all emergency room and head computerized tomography findings, as well as the timing of initial mannitol treatment (approximately 80-90 minutes after the first evaluation at the scene of the injury). Comparative evaluation of bilateral pupillary widening between the scene of the injury and the emergency room showed no significant differences between groups, whereas mannitol dose dependence was statistically significant (p < 0.05), insofar as early pupillary improvement in the emergency room was concerned. Ultra-early high-dose mannitol administration in the emergency room is the first known treatment strategy significantly to reverse recent clinical signs of impending brain death, and also to contribute directly to improved long-term clinical outcomes for these patients who have previously been considered unsalvageable.