Cerebral monitoring systems such as intracranial pressure (ICP), jugular venous oxygen saturation (SjvO2), transcranial Doppler (TCD), brain tissue oxygen partial pressure (PbtO2) etc., have been used in the neurosurgical intensive care unit (ICU) for detecting ischemic and hypoxic insults and guiding treatment. The value of the ICP monitor for severe traumatic brain injury (TBI) has already been universally recognized. However, the application of PbtO2 monitors in TBI is still controversial.
The term PbtO2 denotes the partial pressure of oxygen in extracellular fluid of the brain. The direct continuous measurement of PbtO2 was firmly established about fifteen years ago. The oxygen sensor placed in the white matter of the brain can detect the regional pbtO2. The normal baseline PbtO2 values range from 25 to 35 mm Hg. The death rate increases with time at or below a PbtO2 of 15 mmHg or with the occurrence of any PbtO2values at or below 6 mmHg. Studies have shown that when CPP is less than 60 mm Hg, PbtO2 decreases. Yet, when CPP is greater than 60 mm Hg, however, the effect on PbtO2 is minimal. Recent studies showed that the mortality rate in severe TBI patients treated with conventional ICP/CPP was significantly higher than that of those treated under the PbtO2-directed protocol. Moreover, the PbtO2-directed protocol produced better 6-month clinical outcomes than standard ICP/CPP-directed therapy.
In the last two decades, no obvious complications of PbtO2 monitoring have been reported. This procedure can provide important data of early warning of ischemic/hypoxic insults, and can serve to predict the outcome. Furthermore, PbtO2 is a safe, effective, and highly sensitive cerebral monitor. The continuous monitoring of PbtO2 may bring about an improved prognosis for patients with brain injury. However, the indication for brain tissue oxygen monitor implantation and the proper way to maintain proper PbtO2 remain a matter of controversy. More clinical trials are needed for a solid conclusion.
The updated treatment principle for traumatic brain injury (TBI) is to prevent secondary brain injury, which will be the major prognostic factor to determine the patient’s outcomes1-4. The main causes of secondary brain injury include the blocking of the delivery of brain oxygen and the blood supply, damaging the cerebral autoregulation, causing increased intracranial pressure (IICP), decreasing in cerebral perfusion pressure(CPP), and hypoxia. Cerebral monitoring systems such as Intracranial Pressure (ICP), Jugular Venous Oxygen Saturation (SjvO2), trancranial Doppler, brain tissue oxygen partial pressure (PbtO2) etc., has been used in neurosurgical intensive care units (ICU) for detecting the ischemic and hypoxic insults and guiding treatments: Use of ICP monitors for severe traumatic brain injury (TBI) have a universal consensus. However, the application of PbtO2 monitors in TBI is still controversial1, 2, 5-8. The continuous monitoring of brain tissue oxygen partial pressure was established in 1993 by Meixensberger et al.9, which can provide information on brain oxygenation and metabolism, prevent secondary brain injury that causes brain tissue ischemia and hypoxia, and facilitate the further assessment of the effects of treatment implementation2, 9-14.
THE SAFETY AND IMPLANTATION OF BRAIN TISSUE OXYGEN MONITORING
The principle of brain tissue oxygen monitoring employs the Clark cell method for measuring tissue oxygenation; a Clark cell polaro-graphic lead is a semi-permeable membrane that embraces a set of bipolar potentials, where one end consists of silver electrodes, and the other of gold ones. The presence of dissolved oxygen penetrates the semi-permeable membrane, resulting in the generation of an electrical current which is delivered to the brain tissue oxygen monitor to display the status of the implanted brain tissue’s oxygenation4,10,14,15. Most articles in the literature suggest that the brain tissue oxygen monitor should be placed around the lesion area, because the measured data from this area will not be affected by the severity of the injury and may decrease further damage to the non-injured area13-15.
Regarding the safety of the implantation of the brain tissue oxygen monitor, there are still some potential risks including cerebral hemorrhage and infection. However, in last decades, there were no major complications reported2.
THE BRAIN TISSUE OXYGEN AND MEASUREMENT PARAMETERS
Several studies have confirmed that there is a correlation between PbtO2 and ICP, CPP, SjvO2, PaO2, PetCO2, and the metabolic rate. These parameters have been recommended to be maintained within a specific optimal range: such as ICP<20mmHg, CPP 60~70mmHg, MAP>90mmHg, PaO2>100mmHg, O2 saturation>98%, PaCO2 30~35mmHg, and PbtO2>20mmHg.
1. Correlation between Brain Tissue Oxygen and CPP
Kiening et al. found that when CPP was lower than 60mmHg, PbtO2 will diminish by 6mmHg, and SjvO2 will also decrease by about 10%; these two changes of oxygenation parameters (PbtO2 and SjvO2) were closely related to each other. When CPP was higher than 60mmHg, its impact of PbtO2 became less significant. In other words, to maintain CPP higher than 60mmHg is very important15,16, Bardt et al. also reported that when PbtO2<10mmHg, 11.5% of patients had ICP>20mmHg and 16.8% had CPP<60mmHg17. However, Stocchetti et al. showed some low PbtO2 conditions were associated with normal CPP, thus indicating that CPP could be an inadequate estimate of rCBF in focal ischemic areas18. Stiefel et al. also revealed brain resuscitation based on current neurocritical care standards (that is, control of ICP and CPP) does not prevent cerebral hypoxia in some patients19.
2. Correlation between Brain Tissue Oxygen and SjvO2
Since the 1980s, SjvO2 has been applied to TBI patients, SjvO2 can reflect the oxygen absorption of blood flow through the brain tissue, and its normal range is 60~70%. If it is lower than 55%, it would reflect a drop in CPP and an increased risk of cerebral ischemia2. Fandino et al reported that in comparison to SjvO2, monitoring of PbtO2 might more accurately detect possible focal ischaemic events21. And most of the studies agreed that monitoring PbtO2 is more reliable than monitoring venous oxygen saturation3, 20-22.
3. Correlation between PbtO2 and metabolic wastes
Brain metabolic wastes have been a subject of recent studies, Baunach et al. found that in glioma patients, the value of PbtO2<10mmHg presented a decrease in glutamate and aspartic acid, which are important neuroendocrine substances or precursors23. Valadka et al. also found that glucose and aspartic acid concentrations are closely related to PbtO2, so when glucose concentration decreases, PbtO2 will also eventually decrease11. Holzschuh et al. suggested that when glucose concentration was decreased, anaerobic respiration will accumulate a large amount of lactic acid, resulting in cell acidification, which also reflects a crucial correlation between “lactic acid-oxygen indicators” and PbtO224.
4. Correlation PbtO2 and Decompression Craniectomy
There is a growing consensus that decompressive craniectomy is effective in reducing the ICP for diffused cerebral edema25. Figaji et al. reported that in selected pediatric patients with TBI, craniectomy for diffuse brain swelling can significantly improve ICP and cerebral oxygenation control. The use of the procedure in appropriate settings does not appear to increase the proportion of disabled survivors26. Studies also showed that ICP and PbtO2 improved significantly in a uniform pattern during bone flap removal and dura opening27, 28.
5. Correlation between PbtO2 and Carbon Dioxide Partial Pressure (PCO2)
Schneider et al. discovered that even though hyperventilation can decrease ICP and increase CPP, however, it will also decrease PbtO2 by 10mmHg29. Several articles confirmed that when hyperventilation is used, it should not be performed for a long period of time and PCO2 level should not be decreased too much; meanwhile, cerebral blood flow and the PbtO2 must be monitored in order to acquire sufficient oxygen to prevent hypoxic conditions30-32.
6. Correlation between PbtO2 and PaO2 and Fraction of Inspired Oxygen (FiO2)
Menzel et al. showed that increased inspired oxygen concentration appears to improve the O2 supply in brain tissue. During the early period after severe head injury, increased lactate levels in brain tissue were reduced by increasing FiO233. Hlatky et al. pointed out that when the cerebral blood flow was <20ml/100g/min, using 100% FiO2 will increase PaO2 and maintain high blood oxygen status, but the PbtO2 increase range will be insignificant; in contrast, when the cerebral blood flow was >20ml/100g/min, increasing FiO2 will increase PaO2 and achieve higher blood oxygen status, and then the PbtO2 will significantly increase; therefore, it is necessary to improve brain perfusion first in order to facilitate oxygen delivery with a high blood oxygen condition34. Rosenthal et al. found that the ratio of PaO2 to FiO2 (PF) had a significant correlation with PaO2. Furthermore, PaO2 fluctuations and PbtO2 were also significantly correlated to each other; it was shown that after oxygen adjustment, the PbtO2 of patients with PF >250 was higher than the PbtO2 of patients with PF ≤250 showing that lung functions are a major factor in maintaining the levels of PbtO235.
7. Correlation between PbtO2 and Positive End-Expiratory Pressure (PEEP)
PEEP can improve oxygenation status, and increase functional residual capacity (FRC) to avoid lung collapse. The major concern of the application of the PEEP for brain injury patients is the compromise of the venous return and MAP, which could influence CPP and increase ICP. Huynh et al. found different PEEP levels (0-5, 6-10, 11-15) could affect ICP, and reported that increased PEEP caused a decrease in ICP and had no influence on oxygen delivery and consumption levels36. Mascia et al. applied higher PEEP to maintain alveolar ventilation, and the results confirmed that this would not affect ICP, but would improve lung compliance, decrease the pulmonary shunt, and increase oxygenation37.
In conclusion, most researchers38-40 believe that higher PEEP would not affect ICP, but would improve lung compliance, decrease the use of FiO2, increase PaO2, sustain proper PbtO2, improve the treatment effect, and reduce the occurrence of complications.
Correlation between PbtO2 and Outcome
Bardt et al. discovered that when PbtO2 was continuously maintained below 10mmHg for more than 30 minutes, 50% of patients would die and 60% of the surviving patients would remain with severe disability or in a vegetative state after discharge. After 6 months of follow-up, if PbtO2 was lower than 10mmHg and the duration was less than 30 minutes, 80% of patients suffered severe disability or vegetative state18. Recent studies showed that the patients who received PbtO2 monitoring had a significantly reduced mortality rate12, 41, more importantly, the improvement of 6-month clinical outcomes was better than that with the standard ICP/CPP-directed therapy41.
Future Directions and Recommendations
Recent developments of multi-modality brain monitoring systems facilitate early interventions, lowering the incidence of secondary brain injuries, reducing IICP, and improving CPP. For the regulation and maintenance of brain tissue oxygen, the literature shows that one must first maintain an adequate cerebral blood flow, Hb >10g/dl, and Hct between 33% and 38%, and a proper CPP1. The PaO2 can be improved by increasing FiO2or PEEP, and these procedures can assure the proper level of PbtO233-40. In addition, if the decrease of PbtO2is caused by IICP, decompressive craniectomy is recommended, and this procedure has been confirmed to be safe and reliable, it can provide a better outcome and reduce the risks of death25-28.
In the future, researchers should focus their efforts on exploring optimal FiO2, the proper ratio between FiO2and PEEP, and the range of PaO2 in order to keep PbtO2 at proper levels. Moreover, clinical trials must also be designed to examine PbtO2 as related to the application of medication (such as sedatives, muscle relaxants, cerebrovascular circulation agents, vasodilators, and vasoconstrictors) and the handling of the brain metabolic wastes.
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Wen-Ta Chiu, MD, PhD, School of Medicine, Taipei Medical University, Taipei, Taiwan;
Ching-Shuan Sun, MSc, Institute of Injury prevention and control, Taipei Medical University, Taipei, Taiwan;
Jia-Wei Lin, MD, PhD, Department of Neurosurgery, Taipei Medical University-Shuang Ho Hospital, Taipei County, Taiwan;
Sheng-Jean Huang, MD, Surgical Department, Medical College and National Taiwan University, Taipei, Taiwan, ROC＊
Address for correspondence
Surgical Department, Medical College and National Taiwan University, Taipei, Taiwan, ROC
Tel.: +886 2 27390217; fax: +886 2 27390387