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The black box revelation. What’s new in neuromonitoring?. Giuseppe Citerio. ! Water and the brain ! Monitoring. ! Conclusions. Capillary structure: central nervous system “BBB”. Adrogue HJ, Madias NE. Review article : HYPONATREMIA. N Engl J Med 2000 ; 342 : 1581-9. Distribution in brain - PowerPoint PPT Presentation
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The black box revelationWhat’s new in neuromonitoring?
Giuseppe Citerio
! Water and the brain
! Monitoring
! Conclusions
Capillary structure: central nervoussystem “BBB”
Adrogue HJ, Madias NE. Review article : HYPONATREMIA. N Engl J Med 2000 ; 342 : 1581-9.
Amiry-Moghaddam, M., & Ottersen, O. P. (2003). The molecular basis of water transport in the brain. Nature Reviews Neuroscience, 4(12), 991–1001. doi:10.1038/nrn1252
Distribution in brainof aquaporin-1(AQP1, blue)and AQP4(orange)
Architecture of theaquaporin-1
Amiry-Moghaddam, M., & Ottersen, O. P. (2003). The molecular basis of water transport in the brain. Nature Reviews Neuroscience, 4(12), 991–1001. doi:10.1038/nrn1252
Amiry-Moghaddam, M., Frydenlund, D. S., & Ottersen, O. P. (2004). Anchoringof aquaporin-4 in brain: molecular mechanisms and implications for thephysiology and pathophysiology of water transport. Neuroscience, 129(4),999–1010. doi:10.1016/j.neuroscience.2004.08.049
Postischemic edema (22 h following 90 min ofMCAO)
Amiry-Moghaddam, M., Frydenlund, D. S., & Ottersen, O. P. (2004). Anchoringof aquaporin-4 in brain: molecular mechanisms and implications for thephysiology and pathophysiology of water transport. Neuroscience, 129(4),999–1010. doi:10.1016/j.neuroscience.2004.08.049
Withaquaporins
NOaquaporins
VasogenicBE CytotoxicBE OsmoticBE
Development Increasedpermeabilityofcapillaryendothelialcells(BBBdisruption)
1.IncreasedcellmembraneNa/Kpermeability2.Na/K-ATPasefailure3.Uptakeofosmoticallyactivesolutes
Osmoticgradient(plasma➔tissue)
Permeability Increased Unchanged Unchanged
Edemafluid Richinprotein NoproteinsRichinelectrolytes
Richinelectrolytes(tissuehyper-osmolality)Lowinelectrolytes(serumhyposmolality)
Morphology NocellswellingIncreasedinterstitialspace
CellswellingDecreasedinterstitialspace
Cellswelling
Modified from Unterberg, A (2004). Edema andbrain trauma. NSC, 129(4), 1021–1029.
VasogenicBE CytotoxicBEOsmoticBE
Development Increasedpermeabilityofcapillaryendothelialcells(BBBdisruption)
1.IncreasedcellOsmoticgradientmembrane(plasma➔tissue)Na/Kpermeability2.Na/K-ATPasefailure3.Uptakeofosmoticallyactivesolutes
Permeability Increased UnchangedUnchanged
Edemafluid Richinprotein NoproteinsRichinelectrolytesRichinelectrolytes(tissuehyper-osmolality)
Lowinelectrolytes(serumhyposmolality)
Morphology NocellswellingIncreasedinterstitialspace
CellswellingCellswellingDecreasedinterstitialspace
Modified from Unterberg, A (2004). Edema andbrain trauma. NSC, 129(4), 1021–1029.
How to monitor it ?
The “net” effect: increase in volume
ICP
P
V
Langfitt TW et al, J Neurosurg,1964
Normal
Brain edema
CT scan is suggestive but can’t measure it
Invasive monitoring systems
Odds ratios and 95% confidence intervals [95% CI] of neurological outcomes at 1year, comparing intracranial pressure (ICP) patterns
Glasgow Outcome Score: GR, Good Recovery; MD, Moderate Disability; SD, SevereDisability; V, Vegetative; D, Death
Role of intracranial pressure values and patterns in predicting outcome in traumatic brain injury: a systematic review.Treggiari. Neurocrit Care (2007) 6:104–112
Odds ratios of neurological outcomes at 1 year,comparing intracranial pressure (ICP) patterns
Helbok, R., Ko, S. B., Schmidt, J. M., Kurtz, P., Fernandez, L., Choi, H. A., Connolly, E. S., et al. (2011). Global Cerebral Edema and Brain Metabolism After Subarachnoid Hemorrhage.Stroke. doi:10.1161/STROKEAHA.110.604488
patients with (■) and without (☐) globalcerebral edema (GCE)
Ultrasonography of optic nerve sheath diameter fordetection of raised intracranial pressure
Soldatos, T., Chatzimichail, K., Papathanasiou, M., & Gouliamos, A. (2009). Opticnerve sonography: a new window for the non-invasive evaluation of intracranialpressure in brain injury. Emergency Medicine Journal, 26(9), 630–634. doi:10.1136/emj.2008.058453
Geeraerts, T., Newcombe, V. F. J., Coles, J. P., Abate, M. G., Perkes, I. E., Hutchinson, P. J. A.,Outtrim, J. G., et al. (2008). Use of T2-weighted magnetic resonance imaging of the optic nervesheath to detect raised intracranial pressure. Critical care (London, England), 12(5), R114. doi:10.1186/cc7006
Dubourg J Ultrasonography of optic nerve sheath diameter for detectionof raised intracranial pressure: a systematic review and meta-analysis.Intensive Care Med. 2011;37(7):1059–1068.
A new approach
Goldstein, B., Tasker, R. C., & Wakeland, W. (2012). From Lundberg to SIM-ICP: Computational Physiology and Modeling Intracranial Pressure.Science translational medicine, 4(129), 129fs6. doi:10.1126/scitranslmed.3003925
Kashif, F. M., Verghese, G. C., Novak, V., Czosnyka, M., & Heldt, T. (2012). Model-based noninvasive estimation of intracranial pressure from cerebral bloodflow velocity and arterial pressure. Science translational medicine, 4(129), 129ra44. doi:10.1126/scitranslmed.3003249
Kashif, F. M., Verghese, G. C., Novak, V., Czosnyka, M., & Heldt, T. (2012). Model-based noninvasive estimation of intracranial pressure from cerebral bloodflow velocity and arterial pressure. Science translational medicine, 4(129), 129ra44. doi:10.1126/scitranslmed.3003249
(A) ICP and nICP on 2665 nonoverlappingwindows from 45 patient records.
(B) ICP and nICP on 1673 nonoverlappingwindows from 30 records with bilateralCBFV recordings,
(C) ICP and nICP averaged across allwindows in each of 45 patient records.
Intracranial pressure
When water content increases, volume increases.
Therefore, ICP could rise.
Invasive ICP monitoring
✓ Sensitivity: HIGH
✓ Not specific !!
Brain tissue oxygenation
PbrO2and edema
Moppett, I. K., & Hardman, J. G. (2007). Modeling the causes of variation in brain tissue oxygenation.Anesthesia & Analgesia, 105(4), 1104–12– table of contents. doi:10.1213/01.ane.0000281934.99076.89
Leach RM and Treacher DF BMJ 1998; 317:1370-73
Helbok, R., Ko, S. B., Schmidt, J. M., Kurtz, P., Fernandez, L., Choi, H. A., Connolly, E. S., et al. (2011). Global Cerebral Edema andBrain Metabolism After Subarachnoid Hemorrhage. Stroke. doi:10.1161/STROKEAHA.110.604488
patients with (■) and without (☐) globalcerebral edema (GCE
Fletcher, J. J., Bergman, K., Blostein, P. A., & Kramer, A. H. (2010). Fluid balance, complications, and brain tissue oxygen tensionmonitoring following severe traumatic brain injury. Neurocritical Care, 13(1), 47–56. doi:10.1007/s12028-010-9345-2
PbrO2
When water content increases, diffusivity of O2 is decreased.
Therefore, PbrO2could decrease.
PbrO2
! Sensitivity: MEDIUM
! Not specific !!
Microdyalisis
Helbok, R., Ko, S. B., Schmidt, J. M., Kurtz, P., Fernandez, L., Choi, H. A., Connolly, E. S., et al. (2011). Global Cerebral Edema andBrain Metabolism After Subarachnoid Hemorrhage. Stroke. doi:10.1161/STROKEAHA.110.604488
patients with (■) and without (☐) globalcerebral edema (GCE
Microdyalisis
When water content increases, ischemia could develop.
Therefore, L/Pcould increase.
L/P
! Sensitivity: MEDIUM
! Not specific !!
How to increase specificity?
Lescot, T., Bonnet, M.-P., Zouaoui, A., Muller, J.-C., Fetita, C., Coriat, P., & Puybasset, L. (2005). A quantitative computed tomography assessment of brain weight,volume, and specific gravity in severe head trauma. Intensive Care Medicine, 31(8), 1042–1050. doi:10.1007/s00134-005-2709-y
H2O
Apparent diffusion coefficient - ADC
Vasogenic Cytotoxic
Axial diffusivity
Axial diffusivity
Active thermistor
Thermal Diffusion Flowmetry
Passive Thermistor
Tem
pera
ture
Mea
sure
men
t dia
met
er =
8m
m
conduction = ThermalConductivity [K-value] in braintissue• Extraction of convection= heat transfer within the field• Calculation of perfusion= amount of power to maintaintemperature increment of 2-3°C above baseline
Activethermistor
Passivethermistor
8mm
Thermal Diffusion Flowmetry1mm
• Determination of tissue
Ko, S.-B., Alex Choi, H., Parikh, G., Michael Schmidt, J., Lee, K., Badjatia, N., Claassen, J., et al. (2012). Real time estimation of brainwater content in comatose patients. Annals of Neurology, n/a–n/a. doi:10.1002/ana.23619
Ko, S.-B., Alex Choi, H., Parikh, G., Michael Schmidt, J., Lee, K., Badjatia, N., Claassen, J., et al. (2012). Real time estimation of brainwater content in comatose patients. Annals of Neurology, n/a–n/a. doi:10.1002/ana.23619
Ko, S.-B., Alex Choi, H., Parikh, G., Michael Schmidt, J., Lee, K., Badjatia, N., Claassen, J., et al. (2012). Real time estimation of brainwater content in comatose patients. Annals of Neurology, n/a–n/a. doi:10.1002/ana.23619
! Water in the brain is tightly controlled.
! Brain edema is associated with HICP and worse outcome
! Increase in water content could be evaluated (even if NOTSPECIFIC) with:! ICP! PbrO2
! Microdyalisis
! Imaging could help in defining brain edema
! Water content in the brain could be monitored with ThermalDiffusion Flowmetry
Thank you for the attention