title: The role for osmotic agents in children with acute encephalopathies: a systematic review.
abstract: BACKGROUND
  Raised intracranial pressure (ICP) is known to complicate both traumatic and non-traumatic encephalopathies. It impairs cerebral perfusion and may cause death due to global ischaemia and intracranial herniation. Osmotic agents are widely used to control ICP. In children, guidelines for their use are mainly guided by adult studies. We conducted this review to determine the current evidence of the effectiveness of osmotic agents and their effect on resolution of coma and outcome in children with acute encephalopathy.
  
  
  METHODS
  We searched several databases for published and unpublished studies in English and French languages, between January 1966 and March 2009. We considered studies on the use of osmotic agents in children aged between 0 and 16 years with acute encephalopathies. We examined reduction in intracranial pressure, time to resolution of coma, and occurrence of neurological sequelae and death.
  
  
  RESULTS
  We identified four randomized controlled trials, three prospective studies, two retrospective studies and one case report. Hypertonic saline (HS) achieved greater reduction in intracranial pressure (ICP) compared to mannitol and other fluids; normal saline or ringer's lactate. This effect was sustained for longer when it was given as continuous infusion. Boluses of glycerol and mannitol achieved transient reduction in ICP. Oral glycerol was associated with lower mortality and neurological sequelae when compared to placebo in children with acute bacterial meningitis. HS was associated with lower mortality when compared to mannitol in children with non-traumatic encephalopathies.
  
  
  CONCLUSIONS
  HS appears to achieve a greater reduction in ICP than other osmotic agents. Oral glycerol seems to improve outcome among children with acute bacterial meningitis. A sustained reduction in ICP is desirable and could be achieved by modifying the modes and rates of administration of these osmotic agents, but these factors need further investigation.
authors.affiliation: Centre for Geographic Medicine Research (Coast), KEMRI-Wellcome Trust Collaborative Research Programme, Kilifi, Kenya. sgwer@kilifi.kemri-wellcome.org
authors.forename: Samson
authors.initials: S
authors.lastname: Gwer
authors.forename: Hellen
authors.initials: H
authors.lastname: Gatakaa
authors.forename: Leah
authors.initials: L
authors.lastname: Mwai
authors.forename: Richard
authors.initials: R
authors.lastname: Idro
authors.forename: Charles R
authors.initials: CR
authors.lastname: Newton
mesh_terms: D000208:Acute Disease; D001927:Brain Diseases / Q000188:drug therapy / Q000503:physiopathology*; D002648:Child; D004234:Diuretics, Osmotic / Q000627:therapeutic use*; D005990:Glycerol / Q000627:therapeutic use; D006801:Humans; D019586:Intracranial Hypertension / Q000188:drug therapy*; D007427:Intracranial Pressure / Q000187:drug effects*; D007552:Isotonic Solutions / Q000627:therapeutic use; D008353:Mannitol / Q000627:therapeutic use; D011379:Prognosis; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D004234:Diuretics, Osmotic; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic; D008353:Mannitol; D005990:Glycerol
references.citation: J Pediatr Surg. 2006 Jan;41(1):83-7; discussion 83-7
references.pmid: 16410113
references.citation: Crit Care Med. 2003 Jun;31(6):1683-7
references.pmid: 12794404
references.citation: Acta Neurochir (Wien). 1977;36(3-4):189-200
references.pmid: 848367
references.citation: Acta Neurochir Suppl. 1998;71:22-6
references.pmid: 9779133
references.citation: Clin Infect Dis. 2007 Nov 15;45(10):1277-86
references.pmid: 17968821
references.citation: J Trauma. 2002 Sep;53(3):558-63
references.pmid: 12352497
references.citation: Indian Pediatr. 2006 Sep;43(9):771-9
references.pmid: 17033115
references.citation: Clin Infect Dis. 2004 Feb 1;38(3):384-90
references.pmid: 14727209
references.citation: Acta Neurochir (Wien). 1980;51(3-4):161-72
references.pmid: 6768226
references.citation: Crit Care Med. 2000 Apr;28(4):1136-43
references.pmid: 10809295
references.citation: J Neurosurg. 1992 Jan;76(1):91-8
references.pmid: 1727174
references.citation: Arch Dis Child. 1983 Mar;58(3):184-6
references.pmid: 6838249
references.citation: J Neurosurg. 2004 May;100(5 Suppl Pediatrics):454-9
references.pmid: 15287454
references.citation: Agressologie. 1991;32(8-9 Spec No):381-5
references.pmid: 1844198
references.citation: J Neurosurg. 1982 Mar;56(3):323-31
references.pmid: 7057229
references.citation: Arch Dis Child. 1997 Mar;76(3):219-26
references.pmid: 9135262
references.citation: Brain. 2002 May;125(Pt 5):1084-93
references.pmid: 11960897
references.citation: Neurology. 1982 Apr;32(4):437-40
references.pmid: 6801542
references.citation: Acta Neurochir Suppl. 2006;96:114-8
references.pmid: 16671437
references.citation: Pharmacol Ther. 1998 Jul;79(1):1-53
references.pmid: 9719344
references.citation: J Neurosurg Sci. 1982 Jul-Sep;26(3):193-8
references.pmid: 7182440
references.citation: Pediatrics. 1977 Apr;59(4):606-13
references.pmid: 850600
references.citation: Can J Anaesth. 1996 May;43(5 Pt 1):461-6
references.pmid: 8723852
references.citation: Crit Care Med. 2000 Apr;28(4):1144-51
references.pmid: 10809296
references.citation: J Trop Med Hyg. 1971 Nov;74(11):249-52
references.pmid: 5126296
references.citation: Malar J. 2007 Oct 24;6:138
references.pmid: 17958887
references.citation: J Neurosurg. 2002 Nov;97(5):1045-53
references.pmid: 12450025
references.citation: Acta Neurochir Suppl (Wien). 1990;51:324-5
references.pmid: 2128579
references.citation: J Neurosurg. 1978 Feb;48(2):169-72
references.pmid: 624964
references.citation: J Neurosurg Anesthesiol. 1992 Jan;4(1):4-10
references.pmid: 15815431
references.citation: Intensive Care Med. 2001 Jan;27(1):236-9
references.pmid: 11280641
references.citation: Toxicol Appl Pharmacol. 1999 Apr 15;156(2):96-105
references.pmid: 10198274
references.citation: Neurosurgery. 2002 Apr;50(4):774-9; discussion 779-80
references.pmid: 11904028
references.citation: Neurol Res. 2010 Mar;32(2):139-43
references.pmid: 19309542
references.citation: Crit Care Med. 1998 Jul;26(7):1265-70
references.pmid: 9671379