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Brain Tissue Oxygenation in Traumatic Brain Injury: Experimental and Clinical Studies
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Traumatic brain injury (TBI) is a major cause of death and disability. TBI is frequently followed by cerebral ischemia which is a great contributor to secondary brain damage. The main causes of cerebral ischemia are pathophysiological changes in cerebral blood flow and metabolism. Treatment of TBI patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted treatment protocols. However, ICP and CPP alone do not provide information of the oxygen availability in the brain. Monitoring of brain tissue oxygenation (BtipO2) may give additional and valuable information about the risk for development of ischemia in TBI patients.

The aims of this thesis were to study BtipO2 monitoring devices in-vitro regarding accuracy and stability, to detect threshold level of cerebral ischemia in-vivo and finally to examine the cerebral oxygen levels and cerebral metabolism in TBI patients.

The BtipO2 probes performed with high accuracy and stability at different clinically relevant oxygen concentrations.

A pig TBI model was developed by step-wise intracranial volume/pressure increase. Volume increase resulted in a gradual increased ICP, decreased CPP, intracranial compliance and BtipO2, respectively. Brain death (BD) was confirmed by negative CPP and negligible amount of previously injected microspheres in the brain tissue. The model simulated the clinical development of BD in humans with a classical pressure-volume response and systemic cardiovascular reactions. The model should be suitable for studies of brain injury mechanisms.

From the same in-vivo model it was also possible to detect the threshold level of cerebral ischemia in the pig, where BtipO2 below 10 mmHg and CPP below 30 mmHg was associated with an impaired cerebral metabolism (microdialysis lactate to pyruvate ratio >30).

BtipO2 together with cerebral microdialysis were studied in 23 severe TBI patients. We observed different patterns of changes in BtipO2 and cerebral microdialysis biomarkers in focal and diffuse TBI.  Increased cerebral microdialysis levels of glutamate, glycerol or the lactate/pyruvate ratio were observed at BtipO2 < 5 mmHg, indicating increased vulnerability of the brain at this critical level of tissue oxygenation in TBI patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. , 74 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 869
Keyword [en]
Brain tissue oxygenation, Cerebral metabolism, Traumatic brain injury, Cerebral ischemia, Threshold levels, Neurovent-PTO, Microdialysis
National Category
Medical and Health Sciences Anesthesiology and Intensive Care Neurosciences
Research subject
Neurosurgery
Identifiers
URN: urn:nbn:se:uu:diva-195867ISBN: 978-91-554-8607-5 (print)OAI: oai:DiVA.org:uu-195867DiVA: diva2:608555
Public defence
2013-04-19, Grönwallsalen, Akademiska sjukhuset, ingång 70, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2013-03-27 Created: 2013-02-28 Last updated: 2013-04-02Bibliographically approved
List of papers
1. Brain tissue oxygen monitoring: a study of in vitro accuracy and stability of Neurovent-PTO and Licox sensors
Open this publication in new window or tab >>Brain tissue oxygen monitoring: a study of in vitro accuracy and stability of Neurovent-PTO and Licox sensors
2010 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 152, no 4, 681-688 p.Article in journal (Refereed) Published
Abstract [en]

OBJECT: Periods of brain tissue ischemia are common after severe head injury, and their occurrence and duration are negatively correlated with outcome. Accurate and reliable measurement of brain tissue oxygenation (B(ti) pO(2)) may be a key to improve patient outcome after severe head injury. Knowledge of stability and accuracy of the B(ti) pO(2) systems is crucial. We have therefore conducted a bench test study of new Neurovent-PTO(R) (NV) and Licox(R) (LX) oxygen tension catheters to evaluate the sensor accuracy, response time to different oxygen tensions, response to temperature changes and long-term stability. METHODS: For all experiments five new fluorescent NV sensors and five new electrochemical LX sensors were used. The catheter probes were placed into a container filled with a buffer solution. The solution was equilibrated with five high precision calibration gases. The accuracy of the probes was recorded after an equilibration period of 20 min in O(2) concentrations of 5, 10, 20, 30 and 40 mmHg at 37.0 +/- 0.2 degrees C. The probe response to an increase in temperature from 37.0 degrees C to 38.5 degrees C to 40.0 degrees C in two different gases with O(2) concentrations of 10 and 20 mmHg were analysed. We also recorded the time for reaching 90% of a new oxygen concentration level when switching from one concentration to another. Finally, to test if there was a time-dependant drift in pO(2) recordings, all sensors were left in 10 mmHg O(2) solution for 10 days, and recordings were taken every 24 h. RESULTS: In all gas concentrations, NV and LX sensors measured pO(2) with high accuracy and stability in vitro (mean differences from calculated values were for NV 0.76-1.6 mmHg and for LX -0.46-0.26 mmHg). Both sensors showed a shorter response time to pO(2) increase (for NV 56 +/- 22 s and for LX 78 +/- 21 s) compared to pO(2) decrease (for NV 131 +/- 42 s and for LX 215 +/- 63 s). NV pO(2) values were more stable for changes in temperature, while LX sensors showed larger standard deviations with increasing temperature (the difference from the calculated values in 19.7 mmHg O(2) at 40 degrees C were for NV probes between 0.5 and 1.7 mmHg and LX between -2.3 and 1.9 mmHg). Both sensors gave stable results with low standard deviations during long-term (10 days) use, but with a slight elevation of measured pO(2) levels by time. CONCLUSIONS: Both NV and LX were accurate in detecting different oxygen tensions, and they did not deviate over longer recording times. However, LX needed a significantly longer time to detect changes in pO(2) levels compared to NV. Furthermore, LX probes showed an increased standard deviation with higher temperatures.

Keyword
Licox, Neurovent-PTO, Brain tissue oxygenation, Accuracy, Neurointensive care, Traumatic brain injury
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-110760 (URN)10.1007/s00701-009-0532-x (DOI)000275945600017 ()19826757 (PubMedID)
Available from: 2009-11-24 Created: 2009-11-24 Last updated: 2017-12-12Bibliographically approved
2. Standardized experimental brain death model for studies of intracranial dynamics, organ preservation, and organ transplantation in the pig
Open this publication in new window or tab >>Standardized experimental brain death model for studies of intracranial dynamics, organ preservation, and organ transplantation in the pig
Show others...
2011 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 39, no 3, 512-517 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES:: Brain death impairs organ function and outcome after transplantation. There is a need for a brain death model to allow studies of organ viability and preservation. For neurointensive care research, it is also of interest to have a relevant brain death model for studies of intracranial dynamics and evaluation of cerebral monitoring devices. Therefore, the objective was to develop a standardized clinically relevant brain death model. METHODS:: Six pigs of both sexes (10-12 wks old; mean weight, 24.5 ± 1.4 kg) were included. Mean arterial blood pressure, heart rate, intracranial pressure, intracranial compliance, cerebral perfusion pressure, and brain tissue oxygenation (BtiPo2) were recorded during stepwise elevation of intracranial pressure by inflation of an epidural balloon catheter with saline (1 mL/20 mins). Brain death criteria were decided to be reached when cerebral perfusion pressure was <0 mm Hg for 60 mins and at least 10 mL saline was inflated epidurally. BtiPo2 and arterial injections of microspheres were used for confirmation of brain death. RESULTS:: A gradual volume-dependent elevation of intracranial pressure was observed. After 10 mL of balloon infusion, mean intracranial pressure was 89.8 ± 9.7 (sd) mm Hg. Intracranial compliance decreased from 0.137 ± 0.069 mL/mm Hg to 0.007 ± 0.001 mL/mm Hg. The mean arterial pressure decreased and the heart rate increased when the intracranial volume was increased to between 5 and 6 mL. All animals showed cerebral perfusion pressure ≤0 after 7 to 10 mL of infusion. In all animals, the criteria for brain death with negative cerebral perfusion pressure and BtiPo2 ∼0 mm Hg were achieved. Only a negligible amount of microspheres were found in the cerebrum, confirming brain death. The kidneys showed small foci of acute tubular necrosis. CONCLUSIONS:: The standardized brain death model designed in pigs simulates the clinical development of brain death in humans with a classic pressure-volume response and systemic cardiovascular reactions. Brain death was convincingly confirmed.

Keyword
brain death, experimental animal model, intracranial pressure, cerebral perfusion pressure, brain tissue oxygenation, organ preservation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-143532 (URN)10.1097/CCM.0b013e318206b824 (DOI)000287480000013 ()21187748 (PubMedID)
Available from: 2011-01-21 Created: 2011-01-21 Last updated: 2017-12-11Bibliographically approved
3. Brain Tissue Oxygenation and Cerebral Perfusion Pressure Thresholds of Ischemia in a Standardized Pig Brain Death Model
Open this publication in new window or tab >>Brain Tissue Oxygenation and Cerebral Perfusion Pressure Thresholds of Ischemia in a Standardized Pig Brain Death Model
2012 (English)In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 16, no 3, 462-469 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. Monitoring brain tissue oxygenation (B(ti)pO(2)) is of considerable clinical interest, but the exact threshold level of ischemia has been difficult to establish due to the complexity of the clinical situation. The objective of this study was to use the Neurovent-PTO (NV) probe, and to define critical cerebral oxygenation- and CPP threshold levels of cerebral ischemia in a standardized brain death model caused by increasing the ICP in pig. Ischemia was defined by a severe increase of cerebral microdialysis (MD) lactate/pyruvate ratio (L/P ratio > 30).

METHODS:

B(ti)pO(2), L/P ratio, Glucose, Glutamate, Glycerol and CPP were recorded using NV and MD probes during gradual increase of ICP by inflation of an epidural balloon catheter with saline until brain death was achieved.

RESULTS:

Baseline level of B(ti)pO(2) was 22.9 ± 6.2 mmHg, the L/P ratio 17.7 ± 6.1 and CPP 73 ± 17 mmHg. B(ti)pO(2) and CPP decreased when intracranial volume was added. The L/P ratio increased above its ischemic levels, (>30) when CPP decreased below 30 mmHg and B(ti)pO(2) to <10 mmHg.

CONCLUSIONS:

A severe increase of ICP leading to CPP below 30 mmHg and B(ti)pO(2) below 10 mmHg is associated with an increase of the L/P ratio, thus seems to be critical thresholds for cerebral ischemia under these conditions.

Keyword
Brain tissue oxygenation, Cerebral perfusion pressure, Microdialysis, Threshold levels, Traumatic brain injury
National Category
Neurosciences
Research subject
Neurosurgery; Neuroscience
Identifiers
urn:nbn:se:uu:diva-170951 (URN)10.1007/s12028-012-9675-3 (DOI)000304619000019 ()
Available from: 2012-03-16 Created: 2012-03-14 Last updated: 2017-12-07Bibliographically approved
4. Brain tissue oxygenation and cerebral metabolic patterns in focal and diffuse traumatic brain injury
Open this publication in new window or tab >>Brain tissue oxygenation and cerebral metabolic patterns in focal and diffuse traumatic brain injury
Show others...
2014 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, 64Article in journal (Refereed) Published
Abstract [en]

Introduction: Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. There are reasons to believe that knowledge of brain tissue oxygenation (BtipO2) would add information with the potential of improving patient outcome. The aim of this study was to examine BtipO2 and cerebral metabolism using the Neurovent-PTO probe and cerebral microdialysis (MD) in TBI patients.

Methods: Twenty-three severe TBI patients with monitoring of physiological parameters, ICP, CPP, BtipO2, and MD for biomarkers of energy metabolism (glucose, lactate, and pyruvate) and cellular distress (glutamate, glycerol) were included. Patients were grouped according to injury type (focal/diffuse) and placement of the Neurovent-PTO probe and MD catheter (injured/non-injured hemisphere).

Results: We observed different patterns in BtipO2 and MD biomarkers in diffuse and focal injury where placement of the probe also influenced the results (ipsilateral/contralateral). In all groups, despite fairly normal levels of ICP and CPP, increased MD levels of glutamate, glycerol, or the L/P ratio were observed at BtipO2 <5 mmHg, indicating increased vulnerability of the brain at this level.

Conclusion: Monitoring of BtipO2 adds important information in addition to traditional ICP and CPP surveillance. Because of the different metabolic responses to very low BtipO2 in the individual patient groups we submit that brain tissue oximetry is a complementary tool rather than an alternative to MD monitoring.

Keyword
brain tissue oxygenation, cerebral metabolism, traumatic brain injury, cerebral ischemia, Neurovent-PTO
National Category
Anesthesiology and Intensive Care
Research subject
Neurosurgery
Identifiers
urn:nbn:se:uu:diva-194684 (URN)10.3389/fneur.2014.00064 (DOI)000209629300064 ()24817863 (PubMedID)
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2013-02-18 Created: 2013-02-18 Last updated: 2017-12-06Bibliographically approved

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