Hypertonic saline after traumatic brain injury:why not?

Lt-Colonel H. BORET, Major A. MONTCRIOL, Lt-Colonel P. RAMIARA,Lt-Colonel E. MEAUDREIntensive Care UnitSainte Anne Military Teaching HospitalTOULON - France

boret.henry@neuf.fr

Irak 2008

TBI = 20% of the US troops (concussions+++)

$242 millions for brain injuriesAssociated Press March 2009

What can we do to avoid secondary brain damages?

Battlefield NeurosurgeonBattlefield doctor

MannitolYes…

The most:Classical

Studied (30 years)

Recommended

Mannitol, not HS, was the only osmotherapy  « officially » recommended in 2007

Bratton – J Neurotrauma - 2007

MannitolYes ...

Mannitol 1 g/kg

Mannitol is effective to decrease ICHT

Personnal data Francony – Crit Care Med - 2008

Same osmotic load

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

HS better reduces neuroinflammatory responsenear the contusion in rats than mannitol

Soustiel – Brain Research - 2006

Mannitol

Hypertonic saline

Mannitol… but

« Mannitol (…) may have detrimental effecton mortality when compared to hypertonic saline. »

Wakaï – Cochrane Database - 2007

Effect of HS (control) vs mannitol (treatment) on mortality after TBI

First conclusion

Even if still controversial, there are some research and clinical arguments

to promote hypertonic saline vs mannitol in traumatic brain injury

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

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 comparingstandard of care (Lactate Ringer) vs hypertonic saline6 studies - 223 patients

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

Second conclusion

HS is superior to mannitol for battlefield medicine

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

PtiO2

Cerebral microdialysis

PtiO2 CPP

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

Conclusion

ICP reduction

Improved oxygenation

Effects on neuroinflammatory response

Haemodynamic benefit

Limited volume

Mannitol Yes No Limited No No

HS Yes Yes Yes Yes Yes

So, hypertonic saline after TBI… why not… yet?

Thank you

Questions?