Mannitol in intracerebral hemorrhage: a randomized controlled study. Is there a real treatment for stroke? Clinical and statistical comparison of different treatments in 300 patients. Mannitol as adjunct therapy for childhood cerebral malaria in Uganda: a randomized clinical trial.
To study the usefulness of mannitol in spontaneous intracerebral hemorrhage (ICH) patients.
                128 CT proven supratentorial ICH patients within 6 days of ictus were randomized into study and control groups. The study group received mannitol 20%, 100 ml every 4 h for 5 days, tapered in the next 2 days. The control group received sham infusion. Primary endpoint was 1-month mortality and secondary endpoint functional disability at 3 months assessed by Barthel index score.
                There were 65 patients in study and 63 in control groups. The study and control groups were evenly matched regarding age, Glasgow coma scale (GCS) score, Canadian Neurological Scale (CNS) score, pupillary asymmetry, pyramidal signs on non-hemiplegic side, and location, midline shift and ventricular extension of hematoma. At 1 month, 16 patients died in each group. The primary and secondary endpoints were not significantly different between the two groups.
                Low dose mannitol does not seem to be beneficial in patients with ICH. In the absence of universally accepted criteria for the medical treatment of stroke, we made a rigorously randomized comparative study of different treatments in 300 patients. One group of patients received only a general supportive treatment designed to ensure adequate supplies of water, electrolytes and calories, plus whatever was needed to prevent infection and correct extant associated pathology. Three other groups of patients were treated in the same way but were also given, respectively, one of the following medications: Hydergine (Sandoz) (a mixture of three ergot alkaloids), dexamethasone, and mannitol. No statistically significant difference emerged among any of the treatment groups and the reference group in terms of objective therapeutic results. The authors concluded that, at least with the dosage used in this study, none of the treatments proved more useful than conventional supportive therapy in the first 10 days after a stroke. Several reports have suggested that raised intracranial pressure (ICP) is a major contributor to death among children with cerebral malaria. Mannitol, an osmotic diuretic, effectively lowers ICP and is used to treat post-traumatic raised ICP. It is not clear whether intravenous mannitol given to children with cerebral malaria improves clinical outcome. The objective of this study was to determine the effect of mannitol as adjunct therapy on the clinical outcome of children with cerebral malaria.
                This randomized double-blind placebo controlled clinical trial was carried out at the Emergency Paediatric ward of Mulago Hospital, Uganda's national referral and teaching hospital. One hundred and fifty six children aged 6 to 60 months with cerebral malaria were randomized to either one dose of mannitol 1 g/kg or placebo, in addition to intravenous quinine. Main outcome measures included coma recovery time; time to sit unsupported, begin oral intake; duration of hospitalization; death and adverse effects.
                Time to regain consciousness (p = 0.11), sit unsupported (p = 0.81), time to start oral intake (p = 0.13) and total coma duration (p = 0.07) were similar in both groups. There was no significant difference in the mortality between the placebo (13/80 or 16.3%) and mannitol (10/76 or 13.2%) groups: RR = 1.2 (CI 0.5-2.7). No adverse effects were observed after administration of mannitol.
                Mannitol had no significant impact on clinical outcome of cerebral malaria. It is difficult to recommend intravenous mannitol as adjunct therapy for childhood cerebral malaria.
There is currently not enough evidence to support the routine use of mannitol in acute stroke patients. Further trials are needed to confirm or refute whether mannitol is beneficial in acute stroke.