Mannitol and other osmotic diuretics as adjuncts for treating cerebral malaria

Cerebral malaria can lead to coma and death, even when the patient is given anti-malarial drugs. Death is caused by the malaria parasites in the brain that cause brain swelling, leading to pressure in the brain. Mannitol is a drug that sometimes reduces brain swelling in other situations, such as traumatic head injury.

We searched for studies testing mannitol given in addition to anti-malarial drugs in children with cerebral malaria. One study, carried out in Uganda, was found. A total of 156 children were randomly divided to receive either mannitol or placebo (saline solution) in addition to quinine, which is an anti-malarial drug. No difference in either the numbers of deaths, or the time to recover from coma was found in this study. More studies are needed, but from this review mannitol cannot be currently recommended for use in cerebral malaria.

Authors' conclusions: 

There are insufficient data to know what the effects of osmotic diuretics are in children with cerebral malaria. Larger, multicentre trials are needed.

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Background: 

Cerebral oedema occurs with cerebral malaria, and some clinicians think osmotic diuretics, such as mannitol or urea, may improve outcomes.

Objectives: 

To compare mannitol or urea to placebo or no diuretic for treating children or adults with cerebral malaria.

Search strategy: 

We searched the Cochrane Infectious Diseases Group Specialized Register (Issue 4, 2010), CENTRAL (The Cochrane Library Issue 12, 2010), MEDLINE (1966 to November 2010), EMBASE (1974 to November 2010), LILACS (1982 to November 2010), and the reference lists of articles. We contacted relevant organizations and researchers.

Selection criteria: 

Randomized or quasi-randomized controlled trials comparing mannitol or urea to placebo or no treatment in children and adults with cerebral malaria. Primary outcomes were death, life-threatenining sequelae and major neurological sequelae at six months.

Data collection and analysis: 

Two authors applied the inclusion criteria, assessed risk of bias, and extracted data independently.

Main results: 

One trial met the inclusion criteria, comparing mannitol 20% to saline placebo in 156 Ugandan children. Allocation was concealed. No difference in mortality, time to regain consciousness, or neurological sequelae were detected.