Three Part Question
In a [child with cerebral malaria] will [intravenous mannitol] [improve mortality or neurological morbidity]?
You are working in an African hospital during the malaria season. A 10 year old boy is admitted in coma with a fever after having had a convulsion at home.
A blood slide shows asexual forms of Plasmodium falciparum, his blood sugar has been checked to be normal, and he has been loaded with Intravenous quinine. Antibiotics have been given until meningitis can be excluded by a normal lumber puncture. Local experience suggests intravenous mannitol is of benefit in unconscious patients with cerebral malaria, its use however, is not recommended by the World Health Organisation (1).
Medline 1966-01/03 using the PubMed interface.
(mannitol AND malaria) no limits applied.
There was a yield of just 15 articles, none being a relevant controlled trial. Further searches of related articles quoted in references found no controlled trial of mannitol use in cerebral malaria.
|Author, date and country
||Study type (level of evidence)
|Newton CR et al,|
|23 Kenyan children with confirmed Plasmodium falciparum cerebral malaria had intracranial pressure monitored. The 14 with severe and intermediate intracranial hypertension received intravenous mannitol||Uncontrolled clinical trial||Intracranial pressure||Mannitol lowered the intracranial pressure in all children||Primary focus of study and outcome measured was measurement of intracranial pressure in cerebral malaria|
|Neurological outcome or mortality||Of the 4 children with severe intracranial hypertension, 2 died and 2 had severe neurological sequelae. Of those with intermediate intracranial hypertension, all survived. 8 had a good outcome, 1 developed hemiparesis and 1 learning difficulty|
Only one article was found which was relevant to the clinical question. Newton et al described the use of mannitol in 14 children with cerebral malaria. Intracranial pressure was lowered in all cases and outcome was good or reasonable in all except the four with severe intracranial hypertension. However, there was no control group with which to compare the benefit of mannitol on case fatality or neurological outcome.
Intracranial hypertension as a feature of cerebral malaria probably contributes to the poor neurological outcome and death of many children with Plasmodium falciparum malaria. A likely cause is an increase in cerebral blood volume due to sequestered parasitised erythrocytes. Mannitol is a relatively cheap osmotic agent which appears to lower intracranial pressure. This may potentially improve the survival and neurological outcome of many children with cerebral malaria. Anecdotal evidence suggests that the conscious level of children with cerebral malaria improves with intravenous mannitol; however, when it should be used is unknown. The benefit may only be temporary; however, in resource limited settings where intensive nursing care may not be optimal, shortening the duration of a coma may have benefits for neurological outcome.
The WHO emphasise that none of the ancillary treatments for cerebral malaria have sufficient supporting evidence to be used. No controlled study for the use of mannitol in paediatric or adult cerebral malaria could be identified and it's use can not be recommended. Further studies are necessary to determine its value and potential side effects.
Clinical Bottom Line
There are no controlled data supporting the use of mannitol for cerebral malaria. Consensus statements should be followed.
- Newton CR, Crawley J, Sowumni A, et al. Intracranial hypertension in Africans with cerebral malaria. Arch Dis Child 1997;76(3):219-26.
- Warrell DA, Molyneux ME, Beales PF. World Health Organisation, Division of Control of Tropical Diseases. Severe and complicated malaria. Trans R Soc Trop Med Hyg 1990;84(suppl 2):1-65.