Early mannitol administration improves clinical outcomes of pediatric patients with brain edema

Putu A. Sekarningrum, Dyah K. Wati, IGN Made Suwarba, I Nyoman B. Hartawan, Dewi S. Mahalini, IB Gede Suparyatha

DOI: https://doi.org/10.13181/mji.v27i4.2377


Background: Mannitol 20% is used to treat patients with decreased consciousness and as the first line of treatment to reduce intracranial pressure (ICP). However, its application in pediatric patients is still based on minimal evidence. This study was performed to determine the predictive factors of clinical outcomes in pediatric patients with brain edema in the pediatric intensive care unit (PICU).

Methods: This prospective cohort study was conducted in the PICU, Sanglah Hospital Denpasar, Bali, Indonesia. The subjects were chosen by consecutive sampling from July 2016 to July 2017. The primary outcome variable was the patient’s clinical outcome. A chi-square test was used to evaluate the association between the timing of mannitol administration and the patient’s clinical outcome. Multivariate analysis was performed on all variables with p≤0.25.

Results: Forty-one patients were included in the study, 65% of them were male, 65% had good nutritional status, 90% had non-traumatic brain injury, and 73% had confirmed intracranial infection. The risk of sequelae or death for patients in a coma was 1.8 times greater than that of non-comatose patients (p=0.018; CI 95% 1.119–3.047). Based on the timing of mannitol administration from the onset of decreased consciousness, the risk of sequelae or death in patients who received mannitol after 24 hours was 2.1 times higher than that in patients who received mannitol within 24 hours (p=0.006; CI 95% 1.167–3.779). Based on multivariate analysis, only two variables were associated with the patient’s clinical outcome: pediatric Glasgow coma scale (PGCS) ≤3 (p=0.03) and timing of mannitol administration >24 hours (p=0.01).

Conclusion: Early administration (<24 hours) of mannitol and high PGCS are related to favorable outcomes in patients with brain edema in the PICU.


brain edema, clinical outcome, intracranial pressure, mannitol

Full Text:



  1. Gwer S, Gatakaa H, Mwai L, Idro R, Newton CR. The role of osmotic agents in children with acute encephalopathies: a systematic review. BMC Pediatr. 2010;10:23. https://doi.org/10.1186/1471-2431-10-23
  2. Oertel M, Kelly DF, Lee JH, McArthur DL, Glenn TC, Vespa P, et al. Efficacy of hyperventilation, blood pressure elevation, and metabolic suppression therapy in controlling intracranial pressure after head injury. J Neurosurg. 2002;97(5):1045–53. https://doi.org/10.3171/jns.2002.97.5.1045
  3. Nara I, Shiogai T, Hara M, Saito I. Comparative effects of hypothermia, barbiturate, and osmotherapy for cerebral oxygen metabolism, intracranial pressure, and cerebral perfusion pressure in patients with severe head injury. Acta Neurochir Suppl. 1998;71:22–6. https://doi.org/10.1007/978-3-7091-6475-4_7
  4. Tavakkoli F. Proceedings of the 18th expert committee on the selection and use of essential medicines; 2011 March 21-25; Baltimore, Maryland. USA.
  5. Michinaga S, Koyama Y. Pathogenesis of brain edema and investigation into anti-edema drugs. Int J Mol Sci. 2015;16(5):9949–75. https://doi.org/10.3390/ijms16059949
  6. Shawkat H, Westwood MM, Mortimer A. Mannitol: a review of its clinical uses. Contin Educ Anaesth Crit Care Pain. 2012;12(2):82–5. https://doi.org/10.1093/bjaceaccp/mkr063
  7. Mohanty S, Mishra SK, Patnaik R, Dutt AK, Pradhan S, Das B, et al. Brain swelling and mannitol therapy in adult cerebral malaria: a randomized trial. Clin Infect Dis. 2011;53(4):349–55. https://doi.org/10.1093/cid/cir405
  8. Jha SK. Cerebral edema and its management. Med J Armed Forces India. 2003;59(4):326–31. https://doi.org/10.1016/S0377-1237(03)80147-8
  9. Wani AA, Ramzan AU, Nizami F, Malik NK, Kirmani AR, Bhatt AR, et al. Controversy in use of mannitol in head injury. Indian J Neurotrauma. 2008;5(1):11–3. https://doi.org/10.1016/S0973-0508(08)80022-6
  10. Cruz J, Minoja G, Okuchi K, Facco E. Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial. J Neurosurg. 2004;100(3):376–83. https://doi.org/10.3171/jns.2004.100.3.0376
  11. Li J, Wang B. Hyperosmolar therapy for the intracranial pressure in neurological practice: mannitol versus hypertonic saline. IJAR. 2013;1:56–61. https://doi.org/10.1097/MCC.0b013e32835eba30
  12. Marcin JP, Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, et al. Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema. J Pediatr. 2002;141(6):793–7. https://doi.org/10.1067/mpd.2002.128888

Copyright (c) 2018 Dyah Kanyawati, Anindia Sekarningrum, Made Suwarba, Budi Hartawan, Dewi Sutriani, Ida Bagus Suparyatha

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

All articles and issues in Medical Journal of Indonesia have unique DOI number registered in Crossref.
Unique Visitors