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. 2022 Mar 1;5(3):e220891.
doi: 10.1001/jamanetworkopen.2022.0891.

Comparison of Intracranial Pressure Measurements Before and After Hypertonic Saline or Mannitol Treatment in Children With Severe Traumatic Brain Injury

Patrick M Kochanek  1 , P David Adelson  2 , Bedda L Rosario  3 , James Hutchison  4 , Nikki Miller Ferguson  5 , Peter Ferrazzano  6 , Nicole O'Brien  7 , John Beca  8 , Ajit Sarnaik  9 , Kerri LaRovere  10 , Tellen D Bennett  11 , Akash Deep  12 , Deepak Gupta  13 , F Anthony Willyerd  2 , Shiyao Gao  3 , Stephen R Wisniewski  3 , Michael J Bell  14 ; ADAPT Investigators
Collaborators, Affiliations

Comparison of Intracranial Pressure Measurements Before and After Hypertonic Saline or Mannitol Treatment in Children With Severe Traumatic Brain Injury

Patrick M Kochanek et al. JAMA Netw Open. .

Abstract

Importance: Hyperosmolar agents are cornerstone therapies for pediatric severe traumatic brain injury. Guideline recommendations for 3% hypertonic saline (HTS) are based on limited numbers of patients, and no study to date has supported a recommendation for mannitol.

Objectives: To characterize current use of hyperosmolar agents in pediatric severe traumatic brain injury and assess whether HTS or mannitol is associated with greater decreases in intracranial pressure (ICP) and/or increases in cerebral perfusion pressure (CPP).

Design, setting, and participants: In this comparative effectiveness research study, 1018 children were screened and 18 were excluded; 787 children received some form of hyperosmolar therapy during the ICP-directed phase of care, with 521 receiving a bolus. Three of these children were excluded because they had received only bolus administration of both HTS and mannitol in the same hour, leaving 518 children (at 44 clinical sites in 8 countries) for analysis. The study was conducted from February 1, 2014, to September 31, 2017, with follow-up for 1 week after injury. Final analysis was performed July 20, 2021.

Interventions: Boluses of HTS and mannitol were administered.

Main outcomes and measures: Data on ICP and CPP were collected before and after medication administration. Statistical methods included linear mixed models and corrections for potential confounding variables to compare the 2 treatments.

Results: A total of 518 children (mean [SD] age, 7.6 [5.4] years; 336 [64.9%] male; 274 [52.9%] White) were included. Participants' mean (SD) Glasgow Coma Scale score was 5.2 (1.8). Bolus HTS was observed to decrease ICP and increase CPP (mean [SD] ICP, 1.03 [6.77] mm Hg; P < .001; mean [SD] CPP, 1.25 [12.47] mm Hg; P < .001), whereas mannitol was observed to increase CPP (mean [SD] CPP, 1.20 [11.43] mm Hg; P = .009). In the primary outcome, HTS was associated with a greater reduction in ICP compared with mannitol (unadjusted β, -0.85; 95% CI, -1.53 to -0.19), but no association was seen after adjustments (adjusted β, -0.53; 95% CI, -1.32 to 0.25; P = .18). No differences in CPP were observed. When ICP was greater than 20 mm Hg, greater than 25 mm Hg, or greater than 30 mm Hg, HTS outperformed mannitol for each threshold in observed ICP reduction (>20 mm Hg: unadjusted β, -2.51; 95% CI, -3.86 to -1.15, P < .001; >25 mm Hg: unadjusted β, -3.88; 95% CI, -5.69 to -2.06, P < .001; >30 mm Hg: unadjusted β, -4.07; 95% CI, -6.35 to -1.79, P < .001), with results remaining significant for ICP greater than 25 mm Hg in adjusted analysis.

Conclusions and relevance: In this comparative effectiveness research study, bolus HTS was associated with lower ICP and higher CPP, whereas mannitol was associated only with higher CPP. After adjustment for confounders, both therapies showed no association with ICP and CPP. During ICP crises, HTS was associated with better performance than mannitol.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Adelson reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study and personal fees from Medtronic outside the submitted work. Dr Ferguson reported receiving grants from the NIH during the conduct of the study. Dr Ferrazzano reported receiving grants from the National Institute of Neurological Disorders and Stroke (NINDS) during the conduct of the study. Dr Beca reported receiving grants from the NINDS during the conduct of the study. Dr Sarnaik reported grants receiving from the NINDS during the conduct of the study. Dr LaRovere reported grants from the NINDS during the conduct of the study. Dr Bennett reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the conduct of the study and grants from National Center for Advancing Translational Sciences outside the submitted work. Dr Willyerd reported receiving grants from the NIH during the conduct of the study. Dr Bell reported receiving grants from the NINDS during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. Patient Selection Flowchart
CPP indicates cerebral perfusion pressure; ICP, intracranial pressure.
See this image and copyright information in PMC

Comment in

References

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