Hypertonic saline reduces cumulative and daily intracranial pressure burdens after severe traumatic brain injury

Halinder S. Mangat Departments of Neurology and
Neurological Surgery, Weill Cornell Brain and Spine Center, and 
NewYork-Presbyterian Hospital; and

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Ya-Lin Chiu Departments of Public Health and

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Linda M. Gerber Departments of Public Health and
Medicine, Weill Cornell Medical College;

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Marjan Alimi Neurological Surgery, Weill Cornell Brain and Spine Center, and 
NewYork-Presbyterian Hospital; and

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Jamshid Ghajar Neurological Surgery, Weill Cornell Brain and Spine Center, and 
The Brain Trauma Foundation, New York, New York

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Roger Härtl Neurological Surgery, Weill Cornell Brain and Spine Center, and 
NewYork-Presbyterian Hospital; and

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OBJECT

Increased intracranial pressure (ICP) in patients with traumatic brain injury (TBI) is associated with a higher mortality rate and poor outcome. Mannitol and hypertonic saline (HTS) have both been used to treat high ICP, but it is unclear which one is more effective. Here, the authors compare the effect of mannitol versus HTS on lowering the cumulative and daily ICP burdens after severe TBI.

METHODS

The Brain Trauma Foundation TBI-trac New York State database was used for this retrospective study. Patients with severe TBI and intracranial hypertension who received only 1 type of hyperosmotic agent, mannitol or HTS, were included. Patients in the 2 groups were individually matched for Glasgow Coma Scale score (GCS), pupillary reactivity, craniotomy, occurrence of hypotension on Day 1, and the day of ICP monitor insertion. Patients with missing or erroneous data were excluded. Cumulative and daily ICP burdens were used as primary outcome measures. The cumulative ICP burden was defined as the total number of days with an ICP of > 25 mm Hg, expressed as a percentage of the total number of days of ICP monitoring. The daily ICP burden was calculated as the mean daily duration of an ICP of > 25 mm Hg, expressed as the number of hours per day. The numbers of intensive care unit (ICU) days, numbers of days with ICP monitoring, and 2-week mortality rates were also compared between the groups. A 2-sample t-test or chi-square test was used to compare independent samples. The Wilcoxon signed-rank or Cochran-Mantel-Haenszel test was used for comparing matched samples.

RESULTS

A total of 35 patients who received only HTS and 477 who received only mannitol after severe TBI were identified. Eight patients in the HTS group were excluded because of erroneous or missing data, and 2 other patients did not have matches in the mannitol group. The remaining 25 patients were matched 1:1. Twenty-four patients received 3% HTS, and 1 received 23.4% HTS as bolus therapy. All 25 patients in the mannitol group received 20% mannitol. The mean cumulative ICP burden (15.52% [HTS] vs 36.5% [mannitol]; p = 0.003) and the mean (± SD) daily ICP burden (0.3 ± 0.6 hours/day [HTS] vs 1.3 ± 1.3 hours/day [mannitol]; p = 0.001) were significantly lower in the HTS group. The mean (± SD) number of ICU days was significantly lower in the HTS group than in the mannitol group (8.5 ± 2.1 vs 9.8 ± 0.6, respectively; p = 0.004), whereas there was no difference in the numbers of days of ICP monitoring (p = 0.09). There were no significant differences between the cumulative median doses of HTS and mannitol (p = 0.19). The 2-week mortality rate was lower in the HTS group, but the difference was not statistically significant (p = 0.56).

CONCLUSIONS

HTS given as bolus therapy was more effective than mannitol in lowering the cumulative and daily ICP burdens after severe TBI. Patients in the HTS group had significantly lower number of ICU days. The 2-week mortality rates were not statistically different between the 2 groups.

ABBREVIATIONS

AUC = area under the curve; CBF = cerebral blood flow; CMH = Cochran-Mantel-Haenszel; CPP = cerebral perfusion pressure; GCS = Glasgow Coma Scale; BTF = Brain Trauma Foundation; HTS = hypertonic saline; ICP = intracranial pressure; ICU = intensive care unit; RCT = randomized controlled trial; TBI = traumatic brain injury.
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  • 1

    Battison C, , Andrews PJ, , Graham C, & Petty T: Randomized, controlled trial on the effect of a 20% mannitol solution and a 7.5% saline/6% dextran solution on increased intracranial pressure after brain injury. Crit Care Med 33:196202, 2005

    • Search Google Scholar
    • Export Citation
  • 2

    Berger S, , Schürer L, , Härtl R, , Messmer K, & Baethmann A: Reduction of post-traumatic intracranial hypertension by hypertonic/hyperoncotic saline/dextran and hypertonic mannitol. Neurosurgery 37:98108, 1995

    • Search Google Scholar
    • Export Citation
  • 3

    Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, AANS/CNS Joint Section on Neurotrauma and Critical Care: Guidelines for the management of severe traumatic brain injury, ed 3. J Neurotrauma 24:Suppl 1 S1S106, 2007. (Erratum in J Neurotrauma 25:276–278, 2008)

    • Search Google Scholar
    • Export Citation
  • 4

    Bratton SL, , Chestnut RM, , Ghajar J, , McConnell Hammond FF, , Harris OA, & Hartl R, et al.: Guidelines for the management of severe traumatic brain injury. II. Hyperosmolar therapy. J Neurotrauma 24:Suppl 1 S14S20, 2007. (Erratum in J Neurotrauma 25:276–278, 2008)

    • Search Google Scholar
    • Export Citation
  • 5

    Burke AM, , Quest DO, , Chien S, & Cerri C: The effects of mannitol on blood viscosity. J Neurosurg 55:550553, 1981

  • 6

    Cohen J: Statistical Power Analysis for the Behavioral Sciences ed 2 Hillsdale, NJ, L Erlbaum Associates, 1988

  • 7

    Cottenceau V, , Masson F, , Mahamid E, , Petit L, , Shik V, & Sztark F, et al.: Comparison of effects of equiosmolar doses of mannitol and hypertonic saline on cerebral blood flow and metabolism in traumatic brain injury. J Neurotrauma 28:20032012, 2011

    • Search Google Scholar
    • Export Citation
  • 8

    Doyle JA, , Davis DP, & Hoyt DB: The use of hypertonic saline in the treatment of traumatic brain injury. J Trauma 50:367383, 2001

  • 9

    Eskandari R, , Filtz MR, , Davis GE, & Hoesch RE: Effective treatment of refractory intracranial hypertension after traumatic brain injury with repeated boluses of 14.6% hypertonic saline. Clinical article. J Neurosurg 119:338346, 2013

    • Search Google Scholar
    • Export Citation
  • 10

    Farahvar A, , Gerber LM, , Chiu YL, , Carney N, , Härtl R, & Ghajar J: Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring. Clinical article. J Neurosurg 117:729734, 2012

    • Search Google Scholar
    • Export Citation
  • 11

    Farahvar A, , Gerber LM, , Chiu YL, , Härtl R, , Froelich M, & Carney N, et al.: Response to intracranial hypertension treatment as a predictor of death in patients with severe traumatic brain injury. Clinical article. J Neurosurg 114:14711478, 2011. (Erratum in J Neurosurg 115: 191, 2011)

    • Search Google Scholar
    • Export Citation
  • 12

    Flury BK, & Riedwyl H: Standard distance in univariate and multivariate analysis. Am Stat 40:249251, 1986

  • 13

    Francony G, , Fauvage B, , Falcon D, , Canet C, , Dilou H, & Lavagne P, et al.: Equimolar doses of mannitol and hypertonic saline in the treatment of increased intracranial pressure. Crit Care Med 36:795800, 2008

    • Search Google Scholar
    • Export Citation
  • 14

    Froelich M, , Ni Q, , Wess C, , Ougorets I, & Härtl R: Continuous hypertonic saline therapy and the occurrence of complications in neurocritically ill patients. Crit Care Med 37:14331441, 2009

    • Search Google Scholar
    • Export Citation
  • 15

    Gerber LM, , Chiu YL, , Carney N, , Härtl R, & Ghajar J: Marked reduction in mortality in patients with severe traumatic brain injury. Clinical article. J Neurosurg 119:15831590, 2013

    • Search Google Scholar
    • Export Citation
  • 16

    Härtl R, , Bardt TF, , Kiening KL, , Sarrafzadeh AS, , Schneider GH, & Unterberg AW: Mannitol decreases ICP but does not improve brain-tissue pO2 in severely head-injured patients with intracranial hypertension. Acta Neurochir Suppl 70:4042, 1997

    • Search Google Scholar
    • Export Citation
  • 17

    Härtl R, , Ghajar J, , Hochleuthner H, & Mauritz W: Hypertonic/hyperoncotic saline reliably reduces ICP in severely head-injured patients with intracranial hypertension. Acta Neurochir Suppl 70:126129, 1997

    • Search Google Scholar
    • Export Citation
  • 18

    Härtl R, , Ghajar J, , Hochleuthner H, & Mauritz W: Treatment of refractory intracranial hypertension in severe traumatic brain injury with repetitive hypertonic/hyperoncotic infusions. Zentralbl Chir 122:181185, 1997

    • Search Google Scholar
    • Export Citation
  • 19

    Härtl R, , Medary MB, , Ruge M, , Arfors KE, , Ghahremani F, & Ghajar J: Hypertonic/hyperoncotic saline attenuates microcirculatory disturbances after traumatic brain injury. J Trauma 42:5 Suppl S41S47, 1997

    • Search Google Scholar
    • Export Citation
  • 20

    Horn P, , Münch E, , Vajkoczy P, , Herrmann P, , Quintel M, & Schilling L, et al.: Hypertonic saline solution for control of elevated intracranial pressure in patients with exhausted response to mannitol and barbiturates. Neurol Res 21:758764, 1999

    • Search Google Scholar
    • Export Citation
  • 21

    Ichai C, , Armando G, , Orban JC, , Berthier F, , Rami L, & Samat-Long C, et al.: Sodium lactate versus mannitol in the treatment of intracranial hypertensive episodes in severe traumatic brain-injured patients. Intensive Care Med 35:471479, 2009

    • Search Google Scholar
    • Export Citation
  • 22

    Jones PA, , Chambers IR, , Lo TY, , Andrews PJ, , Chaudhry W, & Clark A, et al.: Quantification of secondary CPP insult severity in paediatric head injured patients using a pressure-time index. Acta Neurochir Suppl 95:2932, 2005

    • Search Google Scholar
    • Export Citation
  • 23

    Kahraman S, , Dutton RP, , Hu P, , Xiao Y, , Aarabi B, & Stein DM, et al.: Automated measurement of “pressure times time dose” of intracranial hypertension best predicts outcome after severe traumatic brain injury. J Trauma 69:110118, 2010

    • Search Google Scholar
    • Export Citation
  • 24

    Kamel H, , Navi BB, , Nakagawa K, , Hemphill JC III, & Ko NU: Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. Crit Care Med 39:554559, 2011

    • Search Google Scholar
    • Export Citation
  • 25

    Kerwin AJ, , Schinco MA, , Tepas JJ III, , Renfro WH, , Vitarbo EA, & Muehlberger M: The use of 23.4% hypertonic saline for the management of elevated intracranial pressure in patients with severe traumatic brain injury: a pilot study. J Trauma 67:277282, 2009

    • Search Google Scholar
    • Export Citation
  • 26

    Khanna S, , Davis D, , Peterson B, , Fisher B, , Tung H, & O'Quigley J, et al.: Use of hypertonic saline in the treatment of severe refractory posttraumatic intracranial hypertension in pediatric traumatic brain injury. Crit Care Med 28:11441151, 2000

    • Search Google Scholar
    • Export Citation
  • 27

    Koenig MA, , Bryan M, , Lewin JL III, , Mirski MA, , Geocadin RG, & Stevens RD: Reversal of transtentorial herniation with hypertonic saline. Neurology 70:10231029, 2008

    • Search Google Scholar
    • Export Citation
  • 28

    Marks JA, , Li S, , Gong W, , Sanati P, , Eisenstadt R, & Sims C, et al.: Similar effects of hypertonic saline and mannitol on the inflammation of the blood-brain barrier microcirculation after brain injury in a mouse model. J Trauma Acute Care Surg 73:351357, 2012

    • Search Google Scholar
    • Export Citation
  • 29

    Marmarou A, , Anderson RL, , Ward JD, , Choi SC, & Young HF, et al.: Impact of ICP instability and hypotension on outcome in patients with severe head trauma. J Neurosurg 75:Suppl 1s S59S66, 1991

    • Search Google Scholar
    • Export Citation
  • 30

    Marshall LF, , Smith RW, , Rauscher LA, & Shapiro HM: Mannitol dose requirements in brain-injured patients. J Neurosurg 48:169172, 1978

  • 31

    Mendelow AD, , Teasdale GM, , Russell T, , Flood J, , Patterson J, & Murray GD: Effect of mannitol on cerebral blood flow and cerebral perfusion pressure in human head injury. J Neurosurg 63:4348, 1985

    • Search Google Scholar
    • Export Citation
  • 32

    Mortazavi MM, , Romeo AK, , Deep A, , Griessenauer CJ, , Shoja MM, & Tubbs RS, et al.: Hypertonic saline for treating raised intracranial pressure: literature review with meta-analysis. A review. J Neurosurg 116:210221, 2012

    • Search Google Scholar
    • Export Citation
  • 33

    Muizelaar JP, , Lutz HA III, & Becker DP: Effect of mannitol on ICP and CBF and correlation with pressure autoregulation in severely head-injured patients. J Neurosurg 61:700706, 1984

    • Search Google Scholar
    • Export Citation
  • 34

    Muizelaar JP, , Wei EP, , Kontos HA, & Becker DP: Mannitol causes compensatory cerebral vasoconstriction and vasodilation in response to blood viscosity changes. J Neurosurg 59:822828, 1983

    • Search Google Scholar
    • Export Citation
  • 35

    Narayan RK, , Kishore PR, , Becker DP, , Ward JD, , Enas GG, & Greenberg RP, et al.: Intracranial pressure: to monitor or not to monitor? A review of our experience with severe head injury. J Neurosurg 56:650659, 1982

    • Search Google Scholar
    • Export Citation
  • 36

    Nath F, & Galbraith S: The effect of mannitol on cerebral white matter water content. J Neurosurg 65:4143, 1986

  • 37

    Oddo M, , Levine JM, , Frangos S, , Carrera E, , Maloney-Wilensky E, & Pascual JL, et al.: Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension. J Neurol Neurosurg Psychiatry 80:916920, 2009

    • Search Google Scholar
    • Export Citation
  • 38

    Peterson B, , Khanna S, , Fisher B, & Marshall L: Prolonged hypernatremia controls elevated intracranial pressure in head-injured pediatric patients. Crit Care Med 28:11361143, 2000

    • Search Google Scholar
    • Export Citation
  • 39

    Qureshi AI, , Suarez JI, , Castro A, & Bhardwaj A: Use of hypertonic saline/acetate infusion in treatment of cerebral edema in patients with head trauma: experience at a single center. J Trauma 47:659665, 1999

    • Search Google Scholar
    • Export Citation
  • 40

    Rockswold GL, , Solid CA, , Paredes-Andrade E, , Rockswold SB, , Jancik JT, & Quickel RR: Hypertonic saline and its effect on intracranial pressure, cerebral perfusion pressure, and brain tissue oxygen. Neurosurgery 65:10351042, 2009

    • Search Google Scholar
    • Export Citation
  • 41

    Roquilly A, , Mahe PJ, , Latte DD, , Loutrel O, , Champin P, & Di Falco C, et al.: Continuous controlled-infusion of hypertonic saline solution in traumatic brain-injured patients: a 9-year retrospective study. Crit Care 15:R260, 2011

    • Search Google Scholar
    • Export Citation
  • 42

    Rosenbaum PR: Optimal matching for observational studies. J Am Stat Assoc 84:10241032, 1989

  • 43

    Rusnak M, , Janciak I, , Majdan M, , Wilbacher I, & Mauritz W: Severe traumatic brain injury in Austria VI: effects of guideline-based management. Wien Klin Wochenschr 119:6471, 2007

    • Search Google Scholar
    • Export Citation
  • 44

    Schatzmann C, , Heissler HE, , König K, , Klinge-Xhemajli P, , Rickels E, & Mühling M, et al.: Treatment of elevated intracranial pressure by infusions of 10% saline in severely head injured patients. Acta Neurochir Suppl 71:3133, 1998

    • Search Google Scholar
    • Export Citation
  • 45

    Schwartz ML, , Tator CH, , Rowed DW, , Reid SR, , Meguro K, & Andrews DF: The University of Toronto head injury treatment study: a prospective, randomized comparison of pentobarbital and mannitol. Can J Neurol Sci 11:434440, 1984

    • Search Google Scholar
    • Export Citation
  • 46

    Sheth KN, , Stein DM, , Aarabi B, , Hu P, , Kufera JA, & Scalea TM, et al.: Intracranial pressure dose and outcome in traumatic brain injury. Neurocrit Care 18:2632, 2013

    • Search Google Scholar
    • Export Citation
  • 47

    Smith HP, , Kelly DL Jr, , McWhorter JM, , Armstrong D, , Johnson R, & Transou C, et al.: Comparison of mannitol regimens in patients with severe head injury undergoing intracranial monitoring. J Neurosurg 65:820824, 1986

    • Search Google Scholar
    • Export Citation
  • 48

    Vialet R, , Albanèse J, , Thomachot L, , Antonini F, , Bourgouin A, & Alliez B, et al.: Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory post-traumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med 31:16831687, 2003

    • Search Google Scholar
    • Export Citation
  • 49

    Vik A, , Nag T, , Fredriksli OA, , Skandsen T, , Moen KG, & Schirmer-Mikalsen K, et al.: Relationship of “dose” of intracranial hypertension to outcome in severe traumatic brain injury. Clinical article. J Neurosurg 109:678684, 2008

    • Search Google Scholar
    • Export Citation
  • 50

    Wainwright MS, & Lewandowski R: Bioinformatics analysis of mortality associated with elevated intracranial pressure in children. Acta Neurochir Suppl 114:6773, 2012

    • Search Google Scholar
    • Export Citation
  • 51

    Ware ML, , Nemani VM, , Meeker M, , Lee C, , Morabito DJ, & Manley GT: Effects of 23.4% sodium chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a preliminary study. Neurosurgery 57:727736, 2005

    • Search Google Scholar
    • Export Citation
  • 52

    Wells DL, , Swanson JM, , Wood GC, , Magnotti LJ, , Boucher BA, & Croce MA, et al.: The relationship between serum sodium and intracranial pressure when using hypertonic saline to target mild hypernatremia in patients with head trauma. Crit Care 16:R193, 2012

    • Search Google Scholar
    • Export Citation
  • 53

    Willerson JT, , Curry GC, , Atkins JM, , Parkey R, & Horwitz LD: Influence of hypertonic mannitol on ventricular performance and coronary blood flow in patients. Circulation 51:10951100, 1975

    • Search Google Scholar
    • Export Citation
  • 54

    Wisner DH, , Schuster L, & Quinn C: Hypertonic saline resuscitation of head injury: effects on cerebral water content. J Trauma 30:7578, 1990

    • Search Google Scholar
    • Export Citation

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