A Systematic Review of the Efficacy of Mannitol Versus Hypertonic Saline in the Treatment of Raised Intracranial Pressure in Adults Suffering from Traumatic Brain Injury
CCCF ePoster library. KUTSOGIANNIS D. 11/07/18; 233346; 1
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Raised intracerebral pressure (ICP) in the setting of traumatic brain injury (TBI) is a common problem and associated with worsening neurological outcomes. Previous systematic reviews have failed to demonstrate a survival advantage of mannitol over hypertonic saline in the management of ICP in TBI patients. However, there are no published systematic reviews comparing the magnitude and temporal durability in the reduction of ICP between the various concentrations of mannitol and hypertonic saline (HTS).



To determine the temporal reduction in ICP using mannitol, HTS and to compare the efficacy of ICP reduction between the two agents and the effects of varying volumes and concentrations.




The review followed the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as the following databases were searched: PubMed (1947 to July 2016), EMBASE (1947 to July 2016), Medline, Cochrane Databases of Systematic Review and Web of Science. The key phrases used in the search were: hypertonic saline, sodium chloride, osmotic diuretic, mannitol, intracranial pressure, traumatic brain injury, head injury. Eligibility criteria for the study included:  use of an osmotic diuretic, raised intracranial pressure, adults older than 16, traumatic brain injury. Few studies had a mixed patient population of TBI and subarachnoid hemorrhage. General estimating equations for correlated longitudinal data were used to model the temporal reduction in study averaged ICP, the effect of mannitol versus HTS, and volume and concentration of therapy. Adjustment was made for study methodology.



1349 records were identified using the search strategy. Eighteen randomized controlled trials and 14 cohort studies were used in the systematic review of which 7 studies (4 randomized trials and 3 cohort studies) compared mannitol with HTS and reported mean ICP values suitable for pooled GEE analysis. Univariable ICP reductions were demonstrated at 60 minutes using HTS (p < 0.0001) and mannitol (p = 0.02) but not at 30 or 120 minutes for either treatment. In the multivariable model, a significant ICP reduction was demonstrated over time (p < 0.0001), however there was no significant difference in ICP reduction between the HTS versus the mannitol group (p = 0.92). Neither treatment volume, concentration nor their interaction were modifiers of the effect of either treatment. However, non-randomized studies did modify the treatment effect [Table 1] When all available data from either single treatment (HTS or mannitol) studies or comparison studies were pooled to model the temporal reduction in ICP by individual treatment type, HTS demonstrated a more significant reduction in ICP at 30 (p=0.002), 60 (p<0.0001) and 120 min (p=0.0004) as compared to mannitol at 30 (p=0.002), 60 (p=0.004) and 120 min (p=0.03). [Figures 1,2] Using individual treatment models, a significant interaction was seen between the volume and concentration of HTS indicating optimal concentrations of ≤ 10% and volumes of ≤ 250 ml.



Both mannitol and HTS are effective at reducing ICP at 30, 60, and 120 minutes after bolus dosing. Although a larger ICP reduction was demonstrated using HTS, this was not statistically significant. A significant interaction was noted between the volume and osmotic concentration using HTS indicating that increasing volumes of low concentration HTS does not result in a greater reduction of ICP.


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