Mannitol as adjunct therapy for childhood cerebral malaria in Uganda: A randomized clinical trial

Beatrice Namutangula,Grace Ndeezi,James K Tumwine,Justus S Byarugaba

doi:10.1186/1475-2875-6-138

Abstract

BackgroundSeveral 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.MethodsThis 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.ResultsTime 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.ConclusionMannitol had no significant impact on clinical outcome of cerebral malaria. It is difficult to recommend intravenous mannitol as adjunct therapy for childhood cerebral malaria.Clinical registration numberClinicalTrials.gov ID: NCT00113854

Highlights

Several reports have suggested that raised intracranial pressure (ICP) is a major contributor to death among children with cerebral malaria
Selection criteria Children aged between six months and five years, who fulfilled the WHO case definition of cerebral malaria and those whose caretakers gave informed consent were included
This study was not powered to detect differences in mortality, the fact that fewer children died in the mannitol group compared to the placebo group and that the mortality was within the ranges seen in most African studies, may be an indication that mannitol is not deleterious

Summary

Introduction

Several reports have suggested that raised intracranial pressure (ICP) is a major contributor to death among children with cerebral malaria. 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. Several studies have shown evidence of raised intracranial pressure in children with cerebral malaria and this may be associated with poor outcome[4,5]. An osmotic diuretic lowers intracranial pressure by creating an osmotic gradient that draws water from brain parenchyma into the brain capillaries. A randomized trial was performed to determine the effect of mannitol as adjunct therapy on the clinical outcome of cerebral malaria in children

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