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. Comparison of mannitol regimens in patients with severe head injury undergoing intracranial monitoring. Out-of-hospital administration of mannitol to head-injured patients does not change systolic blood pressure. Effect of mannitol on regional cerebral blood flow in patients with intracerebral hemorrhage. Effects of mannitol in the prevention of lipid peroxidation during liver resection with hepatic vascular exclusion. The University of Toronto head injury treatment study: a prospective, randomized comparison of pentobarbital and mannitol. The effect of mannitol on oxygenation and creatine kinase MB release in patients undergoing multivessel off-pump coronary artery bypass surgery.
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. Eighty patients sustaining head injuries and presenting with Glasgow Coma Scale scores of 8 or less were entered into a prospective randomized study to assess the benefit of intracranial pressure (ICP) monitoring with two regimens of mannitol administration. Group I was treated with mannitol for ICP elevations greater than 25 mm Hg, while Group II received empirical mannitol therapy irrespective of ICP readings. No statistically significant differences in mortality rate or neurological outcome were demonstrated between the two groups. These results are comparable to those of several published series of head-injured patients receiving similar treatment from 1977 to 1982. However, those series must be reassessed in light of recently published studies with treatment initiated at lower levels of ICP. To determine the effect of out-of-hospital mannitol administration on systolic blood pressure (BP) in the head-injured multiple-trauma patient.
                This was a prospective, randomized, double-blind, placebo-controlled clinical trial involving a university-based helicopter air medical service and level-1 trauma center hospital. Endotracheally intubated head-trauma victims with Glasgow Coma Scale (GCS) scores < 12 were enrolled from November 22, 1991, to November 20, 1992, if evaluated by the participating aeromedical transport team within 6 hours of injury. Patients were excluded if they were < 18 years old, had already received mannitol or another diuretic, were potentially pregnant, or were receiving CPR. All patients were intubated prior to study drug (mannitol [1 g/kg] or normal saline) use. Pulse and BP were measured every 15 minutes for 2 hours following study drug administration.
                A total of 44 patients were enrolled. After exclusion of 3 patients who did not meet all inclusion criteria, there were 20 patients in the mannitol group and 21 patients in the placebo group. The groups were similar at baseline in age, pulse, systolic BP (baseline mannitol: 124 +/- 47 mm Hg; placebo: 128 +/- 32 mm Hg), GCS score, and Injury Severity Scale score. Systolic BP did not change significantly throughout the observation period in either group. This study had 83% power to detect a mean systolic BP drop to < 90 mm Hg.
                Out-of-hospital administration of mannitol did not significantly change systolic BP in this group of head-injured multiple-trauma patients. To evaluate the regional cerebral blood flow (rCBF) changes following IV mannitol bolus in patients with intracerebral hemorrhage (ICH).
                In a hospital based randomized placebo controlled study, 21 CT proven ICH patients with Glasgow coma scale (GCS) score of 5 or more were subjected to clinical evaluation including GCS and Canadian Neurological stroke (CNS) scale. Cranial SPECT study was undertaken before and 60 min after 20% mannitol 100 ml IV in 20 min or sham infusion. The SPECT images were semi-quantitatively analyzed and asymmetry index of basal ganglia, frontal, parietal and occipital regions were calculated.
                There were 12 patients in mannitol and nine in control group who were evenly matched for age, mean arterial blood pressure, GCS score and size of hematoma. Only one patient died in mannitol group. Following mannitol, GCS score improved in six, worsened in two and remained unaltered in four patients. In the control group, GCS improved in seven, worsened in none and was unchanged in two patients. SPECT studies revealed reduction in asymmetry index in basal ganglia in four, frontal region in six, parietal in four and occipital region in five patients in mannitol group. In control group, asymmetry index was reduced in basal ganglia in one, frontal and parietal region in three each and occipital region in five patients. These differences between control and study group were not significant.
                Mannitol does not seem to significantly change the regional cerebral blood flow (rCBF) in ICH patients as evaluated by SPECT study. To examine the efficacy of mannitol in the prevention of lipid peroxidation during major liver resections performed during hepatic inflow occlusion.
                Prospective, randomized, open-label study.
                Aretaieion Hospital, a university-affiliated hospital.
                30 ASA physical status II and III patients, less than 75 years of age, scheduled for elective liver resection.
                All patients received combined general and epidural anesthesia. Laparotomy was performed through a bilateral subcostal incision, and hepatectomy was performed by inflow vascular exclusion (Pringle's maneuver). Before this maneuver, and if the patients were hemodynamically stable, they were randomized to receive either mannitol 20% 1.5 mL kg(-1) (group M) or normal saline 1.5 mL kg(-1) (group S) intravenously for 30 minutes.
                Venous blood malondialdehyde (MDA) concentration, as an index of lipid peroxidation, was measured spectrophotometrically at selected time points.
                Patients in both groups presented with raised MDA values (P < 0.05) for the period starting before the release of vascular occlusion until 6 days postoperatively. In patients receiving mannitol, lower MDA values were observed (P < 0.05) compared with group S at the end of operation.
                Mannitol has an antioxidant activity, but we were unable to confirm a positive impact on the postoperative clinical course. Fifty-nine patients were treated in a prospective, randomized comparison of pentobarbital and mannitol for the control of intracranial hypertension resulting from head injury. Patients with elevated intracranial pressure (ICP) after evacuation of intracranial hematomas were randomized to one of two treatment groups; mannitol initially or pentobarbital initially, followed by the second drug as required by further elevation of ICP. Similarly, patients with raised ICP but without hematomas requiring evacuation were randomly assigned to two treatment groups in an identical paradigm. Those with ICP elevation and no hematoma treated with pentobarbital as initial therapy had a 77% mortality compared to a 41% mortality for those with mannitol as initial treatment. Patients with evacuated hematomas had mortalities of 40% and 43% (no significant difference) for pentobarbital and mannitol respectively. In both no-hematoma and hematoma streams pentobarbital was less effective than mannitol for control of raised ICP. Multivariable statistical analysis indicates that pentobarbital coma is not better than mannitol for the treatment of intracranial hypertension and may be harmful in no-hematoma patients with intracranial hypertension after head injury. Despite avoiding cardiopulmonary bypass, off-pump coronary artery bypass surgery is associated with reduction in PaO2 and postoperative respiratory compliance. Also, transient interruption of coronary flow is necessary during distal anastomoses and may impose ischemia-reperfusion myocardial injury. Mannitol is an osmotic diuretic with free radical scavenging properties, and we have evaluated the effects of mannitol on oxygenation and cardiac enzyme release in patients undergoing multivessel off-pump bypass surgery in a prospective, randomized, controlled, double-blind trial.
                Fifty patients were randomly allocated to receive either 20% mannitol 0.5 g/kg (n = 25) or normal saline 2.5 mL/kg (n = 25) during Y-graft construction. Pulmonary variables and serum sodium concentrations were measured 15 minutes after induction of anesthesia and sternum closure. Creatine kinase MB was measured before and after the operation. Intraoperative and postoperative fluid input and output, time to extubation, and intraoperative hemodynamic variables were also recorded.
                PaO2 after sternum closure was significantly higher in the mannitol group, with faster time to extubation and shorter length of stay in the intensive care unit. Intraoperative urine output was significantly greater in the mannitol group, without significant differences in fluid input, serum sodium concentration, and hemodynamic variables. Number of patients with a creatine kinase MB level more than 3 times the upper limit of normal was significantly higher in the control group.
                Mannitol could be safely used without adverse side effects in patients undergoing multivessel off-pump bypass surgery with beneficial effects in terms of preserving oxygenation, earlier extubation, and fewer patients with significant creatine kinase MB elevation.
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.