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Twenty percent mannitol is widely used to reduce brain bulk and facilitate the surgical approach in intracranial surgery. However, a dose-response relationship has not yet been established. In this study, we compared the effects of 0.7 and 1.4 g·kg−1 mannitol on brain relaxation during elective supratentorial brain tumor surgery.In this prospective, randomized, double-blind study, we enrolled 80 patients undergoing supratentorial craniotomy for tumor resection. Patients were assigned to receive 0.7 g·kg−1 (group L) or 1.4 g·kg−1 (group H) of 20% mannitol at surgical incision. Brain relaxation was assessed immediately after opening of the dura on a scale ranging from 1 to 4 (1 = perfectly relaxed, 2 = satisfactorily relaxed, 3 = firm brain, 4 = bulging brain).There was no significant difference between the 2 groups regarding age, sex, body mass index, and brain tumor localization or size. In group L 52.5% of patients and in group H 77.5% of patients presented a midline shift (P = 0.03). The median scores of brain relaxation (interquantile range) were 2.0 (1.75–3) and 2.0 (1–3) (P = 0.16 for patients in group L and H, respectively). We then used a proportional odds model to adjust for this unbalanced distribution and to assess the group effect (low-dose versus high-dose mannitol) on brain relaxation scores. When adjusted for the presence of midline shift, the use of a higher dose of mannitol resulted in an odds ratio of 2.5 (P = 0.03). This indicates that, considering the effect of a midline shift, the odds of having a 1-level improvement in relaxation score in patients who received a higher dose of mannitol (group H) was 2.5 times as large as the odds for the low-dose group. The odds ratio of 0.29 (P = 0.007) for the midline shift indicates that its occurrence was associated with a higher probability of a lower relaxation score, on average.In this study, we show that 1.4 g·kg−1 of 20% mannitol results in equivalent brain relaxation scores as 0.7 g·kg−1 in patients undergoing craniotomy for supratentorial brain tumor. When corrected for the presence of midline shift, this study reveals that patients in the high-dose group had significantly more chances of obtaining a better relaxation score compared with the lower-dose group.