1. Hypertonic saline after traumatic brain injury: why not? Lt-Colonel H. BORET, Major A. MONTCRIOL, Lt-Colonel P. RAMIARA, Lt-Colonel E. MEAUDRE Intensive Care Unit Sainte Anne Military Teaching Hospital TOULON - France boret.henry@neuf.fr

2. Irak 2008 TBI = 20% of the US troops (concussions+++) $242 millions for brain injuries Associated Press March 2009 What can we do to avoid secondary brain damages? BattlefieldNeurosurgeon Battlefield doctor

3. Mannitol Yes… The most: Classical Studied (30 years) Recommended Mannitol, not HS, was the only osmotherapy « officially » recommended in 2007 Bratton – J Neurotrauma - 2007

4. Mannitol Yes... Mannitol 1 g/kg Mannitol is effective to decrease ICHT Personnal data Francony – Crit Care Med - 2008 Same osmotic load

5. Mannitol … but No oxygenation improvement compared to HS Oddo – JNNP - 2009Sakowitz – J Trauma - 2007 Mannitol PtiO2 PitO2: - normal = 35 mm Hg - Ischemic threshold < 10-15 mm Hg

6. HS better reduces neuroinflammatory response near the contusion in rats than mannitol Soustiel – Brain Research - 2006 Mannitol Hypertonic saline

7. Mannitol … but « Mannitol (…) may have detrimental effect on mortality when compared to hypertonic saline. » Wakaï – Cochrane Database - 2007 Effect of HS (control) vs mannitol (treatment) on mortality after TBI

8. First conclusion Even if still controversial, there are some research and clinical arguments to promote hypertonic saline vs mannitol in traumatic brain injury

9. Other arguments for battlefield medicine Hypertonic saline, not mannitol, is used in case of hemorrhagic shock (small volume ressuscitation) Burgess – Textbook of military medicine Kreimeier – Acta Anaesth Scand - 2002 Velasco – Am J Physiol - 1980

10. Other arguments for battlefield medicine Hypertonic saline is beneficial in case of TBI associated to hypotension Wade – J Trauma - 1997 Discharge survival among brain injured and hypotensive patients comparing standard of care (Lactate Ringer) vs hypertonic saline 6 studies - 223 patients

11. Other arguments for battlefield medicine Mannitol 20% 1 g/kg = 80 g = 400 mL Isotonic saline (compensation of urinary losses) = 800 mL Hypertonic saline 7.5% 2 mL/kg = 160 mL 1,200 mL 160 mL Utilization of HS vs mannitol requires less transported fluids Battlefield, TBI, 80 kg

12. Second conclusion HS is superior to mannitol for battlefield medicine

13. Hypertonic saline: to go further First solution : mortality study Whole mortality (including < 48 h mortality) = 40 +/- 15% Hypothesis : mortality reduction with HS = 5% Sample size = 286 patients Second solution : physiopathological study : what’s going on into the brain parenchyma? Oxygenation = PtiO2 Metabolism = cerebral microdialysis

14. PtiO2 Cerebral microdialysis PtiO2CPP

15. Our study To prove non-inferiority of HS vs mannitol on brain metabolism Sample size : 30 patients 3 patients included 15 mannitol (1 g/kg), 15 HS 7.5% (2 mL/kg) Same osmotic load Main objective : effects on lactate/pyruvate ratio (redox potential) Secondary objectives : effects on ICP, PtiO2, cerebral glucose

16. Conclusion ICP reduction Improved oxygenation Effects on neuroinflammatory response Haemodynamic benefit Limited volume MannitolYesNoLimitedNo HSYes So, hypertonic saline after TBI… why not… yet?

17. Thank you Questions?