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

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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00113854.

Figures

Figure 1
Figure 1
Trial profile.
Figure 2
Figure 2
Kaplan Meir survival curve for time to regain consciousness (hours) by treatment group among the children with cerebral malaria.
Figure 3
Figure 3
Kaplan Meier curve for time to begin oral intake (hours) for the children with cerebral malaria in the two treatment arms.
Figure 4
Figure 4
Kaplan Meier curve for time to sit unsupported (in hours) for the children in the two treatment arms.

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