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Should I Monitor Cerebral Blood Flow After Traumatic Brain Injury?

Paul M. Vespa

BRIEF ANSWER

Background

The treatment of TBI patients centers on preventing secondary cell death in vulnerable brain tissue.¹ This concept is based on several studies that demonstrate that hypotension and hypoxia occur during the early phases of resuscitation and later in the intensive care unit (ICU) (class II data).^2,3 Pathologic postmortem series describe necrotic changes in brain regions remote from the primary insult (class III data).⁴ These pathologic changes are nonspecific, but because many believe that they represent secondary ischemic injury, identification of ongoing ischemia and modification of treatment to avoid brain infarction are important goals. At the same time, treatment of elevated ICP is paramount after TBI. Elevated ICP may result from a variety of factors, including hemorrhagic mass lesions, brain edema, increased blood volume, and impaired cerebrospinal fluid outflow. In the acute postinjury period, treatment of ICP and prevention of brain ischemia are the main goals. It stands to reason that monitoring the effect of treatment would provide guidance and permit success at meeting these treatment goals. Such a model is used in coronary care units, where changes in cardiac performance and electrocardiograms identify ongoing ischemia and provide the basis of guiding treatment. A similar impetus has led to development of several modalities for assessing CBF. This chapter determines the strength of the evidence that assessing CBF makes a difference in patient care by guiding efforts to achieve the main treatment goals of lowering ICP and preventing secondary ischemic deficits.

There is a great deal of difference between believing that prevention of brain ischemia is important to outcome after TBI and demonstrating that monitoring CBF is necessary. To date, no randomized controlled trials demonstrate that monitoring CBF actually reduces the incidence of brain ischemia or improves outcome in TBI patients. A limited number of publications suggest that increasing cerebral perfusion pressure (CPP) >70 mmHg as promoted by Rosner and coworkers⁵ leads to improved outcome (class II data). However, Robertson and coworkers6 found no overall neurologic benefit of using a similar CPP-based therapy (class I data). Neither study actually modified treatment to reach a specific CBF goal, however, thus leaving the door open to the concept that measuring CBF and adjusting therapy to keep CBF in a normal range improves outcome. Thus, the large therapeutic question remains unanswered at present, and several questions remain to be addressed below.

This chapter outlines the evidence that monitoring CBF is useful and may lead to improved outcomes. This approach requires asking several questions about CBF measurements and considering the evidence for each question in turn. The questions are as follows: (1) Are methods of assessing CBF reliable enough to be clinically useful? (2) When should CBF testing be used? (3) Is CBF testing useful in determining prognosis of brain-injured patients? (4) Do the results of CBF testing and monitoring change patient management? Before discussion of these questions, the commonly used methods of measuring CBF in TBI patients are reviewed briefly.

Literature Review

Methods to Determine Cerebral Blood Flow

Several methods may be used to measure CBF: transcranial Doppler ultrasound (TCD), bedside Kety-Schmidt technique using nitrous oxide (N₂O) or radioactive xenon-133, cold xenon computed tomography (XeCT) of the brain, positron emission tomography, and laser Doppler flowmetry. Surrogate markers of CBF that are used to monitor the brain include brain tissue oxygen monitors, jugular venous oximetry, electroencephalography and other brain function monitors, and near-infrared spectroscopy. Although these techniques each have uniquely appealing qualities, some have proven not to be reliable, and others are not available for routine use and will not be outlined here.

The most frequently used modality of monitoring CBF is TCD, a noninvasive means of measuring blood flow velocity in the major extracranial and basal intracranial arteries. TCD is widely used for routine monitoring of patients with subarachnoid hemorrhage, but its use after TBI is less frequent. TCD is completely noninvasive, but it requires a high degree of operator expertise. TCD provides useful measures of changes in CBF, but they are not absolute measures per se. TCD is useful in determining the occurrence of posttraumatic vasospasm (class III and II data),^7,8 increases in ICP as reflected by increased pulsatility indices, and responses of CBF to clinical manipulations such as hyperventilation or to spontaneous changes in CPP (class II data).^9,10 TCD is usually performed as an intermittent diagnostic test rather than continuously. However, continuous monitoring applications have been used to accurately reflect changes in CBF if two conditions are present: (1) preserved angle of insonation, and (2) intact autoregulation.

The most commonly used way to measure CBF today is the XeCT technique involving computed tomography (CT) scanning after a bolus of inactive xenon. This technique has been used in several seminal contributions to the TBI literature.^11,12 It permits creation of a regional map of CBF in absolute units of cc/100 gm/min. In combination with CT scanning, it is useful for determining if mass effect is influencing CBF regionally (e.g., in the region of an intracerebral hematoma), and it can be useful in determining tissue viability (class III data).¹³ However, XeCT cannot be used for continuous monitoring of the brain and entails some risk associated with travel to radiology.

Two bedside methods of measuring CBF may be used in the ICU: radioactive xenon-133 and N₂O techniques. The bedside radioactive xenon-133 technique entails the inhalation or intravenous infusion of a small bolus of the radioactive tracer and detection of the tracer by multiple detectors placed adjacent to the skull in well-defined spaces corresponding to major lobar divisions of the brain.¹⁴ The detection of radioactivity is interpolated over a 15-minute time frame, yielding regional and global measures of CBF. This technique can be repeated in 2 to 4 hours, but the time required for the residual radioactivity to clear limits use of this technique on a continuous basis. This technique has been used in research protocols to evaluate the patterns of CBF early in the course of TBI.^14,15 In contrast, the N₂O technique compares known quantities of administered N₂O to continuously measured amounts of N₂O exiting the brain via the jugular bulb, as outlined by Kety and Schmidt.¹⁶ This method enables serial measurements of CBF in the same patient. It has also been used to test questions of vasoreactivity and responsiveness of CBF to hemodynamic changes. Both the N₂O and xenon-133 techniques are somewhat labor-intensive, requiring quality control of the input and output functions of the test, thus limiting the duration of monitoring of CBF. Thus, like TCD, XeCT, xenon-133, and N₂O provide snapshots of CBF rather than truly continuous monitoring.

The advent of laser Doppler flowmetry (LDF) technology has enabled continuous monitoring of relative changes in CBF. This technique uses a small intraparenchymal probe that obtains a density measurement of moving blood and calibrates it to one of the flow measurement techniques outlined above. In several animal models of brain injury, LDF has had excellent reliability for detecting momentary percentage changes in CBF. Preliminary investigations in human TBI suggest that LDF may be accurately calibrated to XeCT measures of CBF and that clinical monitoring of CBF may be accomplished with this technology.¹⁷

As outlined above, measures of CBF have been tested in controlled settings14 and compared with laboratory autoradiography studies to determine their validity. The XeCT and xenon-133 techniques have very low error rates in their absolute measurements of CBF. However, the heterogeneity of CBF across different brain regions is well documented, and extrapolation of global measures to specific regions of interest may not be valid. Thus, reliability and accuracy should be kept separate in the mind of the user. TCD has been validated as a monitor of relative changes in CBF, but it does not provide an accurate absolute measure of CBF (class II data).¹⁸ Once TCD has been calibrated to a quantitative measure of CBF, it may be used to reliably describe the relationship between percent change in TCD velocities and corresponding changes in CBF.¹⁸ An important question is whether these measures are reliable when used in multiple trauma patients, such as those with adult respiratory distress syndrome. Another issue is whether they are stable enough for continuous measurement or whether such an application will be hampered by potential problems with drift and accuracy that are inherent in clinical measurements. Continuous TCD measurements and automated vasoreactivity studies are labor-intensive and are used mostly as research tools,¹⁰ but vasoreactivity indices may have some prognostic value and may be useful in guiding hemodynamic therapy.