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Background
Cerebral blood flow (CBF) is essential for normal metabolism of the brain. Ischemic brain injury occurs when CBF is insufficient to meet metabolic demand, which can occur in acute neurological disorders (e.g. head injury, subarachnoid hemorrhage, or following neurosurgery).
Various imaging techniques have been attempted to identify individuals at risk for secondary ischemic brain injury and manage response to therapies. Some of these techniques are still evolving (e.g., stable-xenon-enhanced computed tomography (XeCT), perfusion computed tomography, perfusion magnetic resonance imaging, single photon emission computed tomography (SPECT) and positron emission tomography (PET)). While these techniques can provide regional information about CBF, the data provided is a single snap shot in time. Methods for the continuous measurement of CBF have been investigated and are now commercially available. One such method is a thermal perfusion probe, which is placed intra-cerebrally via a burr hole in the vascular area of interest in the brain. The probe is connected to a monitor that displays CBF data.
The QFlow 500 probe (Hemedex, Inc, Cambridge, MA) is an example of a commercially available thermal perfusion probe that has received 510(k) marketing clearance from the Food and Drug Administration (FDA). It is used along with the Bowman Perfusion Monitor, Model 500 (Hemedex, Inc, Cambridge, MA). According to the manufactures website, one potential application of the device is for monitoring CBF in patients with traumatic brain injury to help identify secondary ischemic injury to the brain. The manufacturer states that, by measuring continuous, real-time CBF, clinicians may identify cerebral edema and measure tissue blood flow response to therapies. Another potential neurological application is monitoring CBF following neurosurgery (e.g., aneurysm and subarachnoid hemorrhage procedures).
Current literature on thermal perfusion probes has focused on their clinical feasibility and technical capabilities. Jaeger et al (2005) measured regional cerebral blood flow (rCBF) using the QFlow in patients with severe subarachnoid hemorrhage (n = 5) and traumatic brain injury (n = 3) and compared these results to brain tissue oxygen measurements (P(ti)O(2)) using the Licox (GMS, Kiel-Mielkendorf, Germany) for an average of 9.6 days. The data indicated a significantcorrelation between CBF and P(ti)O(2) (r = 0.36). After 400 intervals of 30-min duration, the QFlow and the P(ti)O(2) measurements correlated 72 % of the time when P(ti)O(2) changes were greater than 5 mm Hg (r > 0.6). In 19 % of the intervals a statistically significant correlation was observed (r < 0.6). During the remaining 9 %, no correlation was found (r < 0.3). The authors suggested that the level of P(ti)O(2) is predominately determined by rCBF, since changes in P(ti)O(2) were correlated in 90 % of episodes to simultaneous changes of CBF. Phases of non-monitoring were mostly due to fever of the patient, when the system does not allow monitoring to avoid overheating of the cerebral tissue.
Vajkoczy et al (2003) obtained rCBF using thermal-diffusion (TD) microprobes to prospectively diagnose symptomatic vasospasm in 14 patients with high-grade subarachnoid hemorrhage (SAH) who underwent early clip placement for anterior circulation aneurysms. The TD microprobes were implanted into the white matter of vascular territories that were deemed at risk for developing symptomatic vasospasm. Data on arterial blood pressure, intracranial pressure, cerebral perfusion pressure, rCBF, cerebrovascular resistance (CVR), and blood flow velocities were collected at the patient's bedside. The diagnosis of symptomatic vasospasm was based on the manifestation of a delayed ischemic neurological deficit and/or a reduced territorial level of CBF as assessed using stable XeCT scanning in combination with vasospasm demonstrated by angiography. Bedside monitoring of TD-rCBF and CVR allowed the detection of symptomatic vasospasm. In the 10 patients with vasospasm, the TD-rCBF decreased from 21 +/- 4 to 9 +/- 1 ml/100 g/min), whereas in the 4 other patients the TD-rCBF value remained unchanged (mean TD-rCBF = 25 +/- 4 compared with 21 +/- 4 ml/100 g/min). Based on a comparison of the results of TD-rCBF and Xe-enhanced CT studies, as well as the calculation of sensitivities, specificities, predictive values, and likelihood ratios, the investigators identified a TD-rCBF value of 15 ml/100 g/min as a reliable cutoff for the diagnosis of symptomatic vasospasm. In addition, the investigators found that TD flowmetry was characterized by a more favorable diagnostic reliability than transcranial Doppler ultrasonography. The authors concluded that TD flowmetry represents a promising method for the bedside monitoring of patients with SAH to detect symptomatic vasospasm.
Current literature on thermal perfusion probes has focused on their feasibility and technical capabilities. Prospective clinical outcome studies are needed to determine their clinical value over other standard methods of identifying individuals at risk for secondary ischemic brain injury (e.g., head injury, subarachnoid hemorrhage, or following neurosurgery) and in monitoring response to therapies.
Near infrared spectroscopy (NIRS) is a non-invasive method for the in vivo monitoring of tissue oxygenation. Originally used mainly to evaluate cerebral oxygenation, NIRS has gained widespread popularity in many clinical settings in all age groups. Changes in regional tissue oxygenation as detected by NIRS may reflect the delicate balance between oxygen delivery and consumption in more than one organ system. However, more studies are needed to establish the ability of NIRS monitoring to improve patient outcome (Chakravarti et al, 2008).
Nishikawa (2009) noted that non-invasive monitoring of regional cerebral oxygen saturation has been introduced in clinical settings for estimation of cerebral perfusion and CBF. The author described several issues regarding the usefulness and clinical limitations associated with the use of NIRS or NIRS cerebral oximetry, as well as relevant information on basic principles of monitoring. The author concluded that there is currently insufficient clinical data concerning critical levels of measured variables that are essential for safe peri-operative management of patients susceptible for cerebral ischemia.
Transcranial Doppler for the identification of patients at risk for cerebral hyperperfusion syndrome (CHS) following carotid endarterectomy (CEA) can not be performed in 10 to 15 % of patients because of the absence of a temporal bone window. Pennekamp and colleagues (2009) stated that NIRS may be of additional value in these patients. These researchers compared (i) the value of NIRS related to existing cerebral monitoring techniques in prediction of peri-operative cerebral ischemia, and (ii) the relation between NIRS and the occurrence of CHS. A systematic literature search relating to NIRS and CEA was conducted in PubMed and EMBASE databases. Those included were: (i) prospective studies; (ii) on NIRS for brain monitoring during CEA; (iii) including comparison of NIRS to any other intra-operative cerebral monitoring systems; and (iv) on either symptomatic or asymptomatic patients. These investigators identified a total of 16 studies, of which 14 focused on the prediction of intra-operative cerebral ischemia and shunt indication. Only 2 studies discussed the ability of NIRS in predicting CHS. Values obtained from NIRS correlated well with those from transcranial Doppler and electroencephalography indicating ischemia. However, a threshold for post-operative cerebral ischemia could not be determined. Neither could a threshold for selective shunting be determined since shunting criteria varied considerably across studies. The evidence suggesting that NIRS is useful in predicting CHS is modest. The authors concluded that NIRS seems a promising monitoring technique in patients undergoing CEA. Yet the evidence to define clear cut-off points for the presence of peri-operative cerebral ischemia or identification of patients at high risk of CHS is limited. They stated that a large prospective cohort study addressing these issues is urgently needed.
Mittnacht (2010) summarized recent developments and available data on the use of NIRS in children at risk for low perfusion. During states of low cardiac output, CBF and thus cerebral NIRS may be better preserved than in somatic tissue sites. Consequently, sites other than the frontal cerebral cortex have been investigated for a possible correlation with invasive measures of systemic perfusion and oxygenation (e.g., abdomen, flank, and muscle). The abdominal site seems preferable to the flank site NIRS (kidney region) application. In order to increase the sensitivity, specificity, and positive predictive value of tissue oximetry to detect systemic hypoperfusion, multi-site NIRS such as a combination of cerebral and somatic site NIRS has been suggested. Near-infrared spectroscopy has also been used to evaluate systemic perfusion in patients undergoing first-stage palliation for hypoplastic left heart syndrome. The authors concluded that despite shortcomings in the ability of NIRS technology to accurately reflect validated and directly measured parameters of systemic oxygen delivery and blood flow, NIRS can certainly assist in the detection of low-flow states (low cardiac output). They stated that large, randomized, prospective studies with well defined outcome parameters are still missing and warranted in order to clearly define the role of NIRS in children at risk for low perfusion.
Mittnacht (2010) summarized recent developments and available data on the use of NIRS in children at risk for low perfusion. During states of low cardiac output, CBF and thus cerebral NIRS may be better preserved than in somatic tissue sites. Consequently, sites other than the frontal cerebral cortex have been examined for a possible correlation with invasive measures of systemic perfusion and oxygenation (e.g., abdomen, flank, and muscle). The abdominal site seems preferable to the flank site NIRS (kidney region) application. In order to increase the sensitivity, specificity, and positive predictive value of tissue oximetry to detect systemic hypoperfusion, multi-site NIRS such as a combination of cerebral and somatic site NIRS has been suggested. Near infrared spectroscopy has also been used to evaluate systemic perfusion in patients undergoing first-stage palliation for hypoplastic left heart syndrome. Despite shortcomings in the ability of NIRS technology to accurately reflect validated and directly measured parameters of systemic oxygen delivery and blood flow, NIRS can certainly assist in the detection of low-flow states (low cardiac output). The author concluded that large, randomized, prospective studies with well-defined outcome parameters are still missing and warranted in order to clearly define the role of NIRS in children at risk for low perfusion.
The American College of Cardiology Foundation/American Heart Association clinical practice guideline on coronary artery bypass graft surgery (2011) stated that the effectiveness of routine use of intra-operative or early post-operative monitoring of cerebral oxygen saturation via NIRS to detect cerebral hypo-perfusion in patients undergoing CABG is uncertain.
Aries et al (2012) noted that there is uncertainty whether bilateral NIRS can be used for monitoring of patients with acute stroke. In a pilot study, the NIRS responsiveness to systemic and stroke-related changes was studied over-night by assessing the effects of brief peripheral arterial oxygenation and mean arterial pressure alterations in the affected versus non-affected hemisphere in 9 patients with acute stroke. Significantly more NIRS drops were registered in the affected compared with the non-affected hemisphere (477 drops versus 184, p < 0.001). In the affected hemispheres, nearly all peripheral arterial oxygenation drops (n = 128; 96 %) were detected by NIRS; in the non-affected hemispheres only 23 % (n = 30; p = 0.17). Only a few mean arterial pressure drops were followed by a significant NIRS drop. This was however significantly different between both hemispheres (32 % versus 13 %, p = 0.01). The authors concluded that this pilot study found good responsiveness of NIRS signal to systemic and stroke-related changes at the bedside but requires confirmation in a larger sample.
Lipcsey et al (2012) stated that near infrared spectroscopy of the thenar eminence (NIRSth) is a non-invasive bedside method for assessing tissue oxygenation. The NIRS probe emits light with several wavelengths in the 700- to 850-nm interval and measures the reflected light mainly from a predefined depth. Complex physical models then allow the measurement of the relative concentrations of oxy and deoxyhemoglobin, and thus tissue saturation (StO2), as well as an approximation of the tissue hemoglobin, given as tissue hemoglobin index. These investigators reviewed the current knowledge of the application of NIRSth in anesthesia and intensive care. They performed an analytical and descriptive review of the literature using the terms "near-infrared spectroscopy" combined with "anesthesia," "anesthesiology," "intensive care," "critical care," "sepsis," "bleeding," "hemorrhage," "surgery," and "trauma" with particular focus on all NIRS studies involving measurement at the thenar eminence. They found that NIRSth has been applied as clinical research tool to perform both static and dynamic assessment of StO2. Specifically, a vascular occlusion test (VOT) with a pressure cuff can be used to provide a dynamic assessment of the tissue oxygenation response to ischemia. StO2 changes during such induced ischemia-reperfusion yield information on oxygen consumption and micro-vasculatory reactivity. Some evidence suggested that StO2 during VOT can detect fluid responsiveness during surgery. In hypovolemic shock, StO2 can help to predict outcome, but not in septic shock. In contrast, NIRS parameters during VOT increase the diagnostic and prognostic accuracy in both hypovolemic and septic shock. Minimal data are available on static or dynamic StO2 used to guide therapy. The authors concluded that although the available data are promising, further studies are necessary before NIRSth can become part of routine clinical practice.
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