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The Role for Osmotic Agents in Children with Acute Encephalopathies: A Systematic Review

Gwer, Samson MBChB1, 2; Gatakaa, Hellen Msc Biostatistics1, 3; Mwai, Leah B.Pharm1, 2, 4; Idro, Richard MMED (Paediatrics) PhD2, 5; Newton, Charles RJC MD MRCP FRCPCH2, 6, 7

JBI Database of Systematic Reviews and Implementation Reports: Volume 7 - Issue 5 - p 154–174
doi: 10.11124/jbisrir-2009-186

Background Raised intracranial pressure (ICP) is a common complication in children with acute encephalopathies. It compromises cerebral perfusion leading to ischaemia and may cause death when the brainstem is compressed during trans-tentorial herniation. Osmotic agents are widely used to control raised ICP. Their use in children is mainly guided by studies in adults.

Objective We carried out this review to determine the best available evidence of the effectiveness of various osmotic agents and their effect on resolution of coma and outcome (neurological sequelae and mortality) in children with acute encephalopathies.

Selection criteria We searched literature published between January 1966 and January 2008 on the use of osmotic agents in children aged between 0 and 16 years with acute encephalopathies.

Search strategy We searched Medline, Cochrane Library, EMBASE, Cumulative Index to Nursing and Allied Health Literature and other databases for both published and unpublished literature.

Results We identified four randomized controlled trials (RCTs), three prospective observational studies, two retrospective studies and one case report. The use of hypertonic saline appeared to achieve greater reduction in ICP compared to mannitol, normal saline and ringer's lactate. This effect was sustained when it was given as a continuous infusion. Boluses of glycerol and mannitol achieved transient reduction in ICP. Use of repeated doses of oral glycerol was associated with lower mortality and neurological sequelae when compared to placebo in children with acute bacterial meningitis. Hypertonic saline was associated with lower mortality when compared to mannitol in children with non-traumatic encephalopathies.

Discussion All agents resulted in reduction of ICP, albeit transient in a number of occasions. A sustained reduction in ICP is desirable and could be achieved by modifying the modes and rates of administration, factors that need further investigation. Hypertonic saline appears to boost cerebral perfusion pressure, an important determinant of outcome in acute encephalopathies.

Conclusion Hypertonic saline appears to achieve greater reduction in ICP than other osmotic agents. Oral glycerol seems to improve outcome among children with acute bacterial meningitis. However, the evidence is not sufficient to guide change of practice. More studies are needed to examine the safest and most efficacious concentrations of the various agents and the most effective routes and rates of administration of these agents.

1. Joanna Briggs Institute, Evidence Synthesis Group, Kenya Chapter

2. Centre for Geographic Medicine Research (Coast), KEMRI-Wellcome Trust Collaborative Research Programme, Kenya

3. The International Centre of Insect Physiology and Ecology, Kenya

4. University of Oxford, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK

5. Department of Paediatrics and Child Health, Mulago Hospital, Makerere University Medical School, Kampala, Uganda

6. London School of Hygiene and Tropical Medicine, London, UK

7. Department of Neurosciences, Child Health Institute, University of London, UK

Corresponding author: Dr. Samson Gwer, Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute/Wellcome Trust Research Labs, P.O Box 230, Kilifi, Kenya, Email:

Fax: +254-41-522390 Tel: +254-41-522535

© 2009 by Lippincott Williams & Wilkins, Inc.
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