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Anesthesia & Analgesia:
doi: 10.1213/ANE.0b013e318277a255
Neuroscience in Anesthesiology and Perioperative Medicine

Cerebral Near-Infrared Spectroscopy Monitoring and Neurologic Outcomes in Adult Cardiac Surgery Patients: A Systematic Review

Zheng, Fei MPH, MD*; Sheinberg, Rosanne MD*; Yee, May-Sann MD*; Ono, Masa MD, PhD; Zheng, Yueyging MD; Hogue, Charles W. MD*

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Author Information

From the *Department of Anesthesiology & Critical Care Medicine and Division of Cardiac Surgery, The Johns Hopkins University School of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland; and Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Accepted for publication September 6, 2012.

Supported in part by departmental funds and a grant to Dr. Hogue from the National Institutes of Health (R01HL092259-01).

See Disclosures at end of article for Author Conflicts of Interest.

Reprints will not be available from the authors.

Address correspondence to Charles W. Hogue, MD, Department of Anesthesiology & Critical Care Medicine, The Johns Hopkins University School of Medicine, The Johns Hopkins Hospital, 1800 Orleans St., Zayed 6208B, Baltimore, MD 21287. Address e-mail to chogue2@jhmi.edu.

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Abstract

BACKGROUND: Near-infrared spectroscopy is used during cardiac surgery to monitor the adequacy of cerebral perfusion. In this systematic review, we evaluated available data for adult patients to determine (1) whether decrements in cerebral oximetry during cardiac surgery are associated with stroke, postoperative cognitive dysfunction (POCD), or delirium; and (2) whether interventions aimed at correcting cerebral oximetry decrements improve neurologic outcomes.

METHODS: We searched PubMed, Cochrane, and Embase databases from inception until January 31, 2012, without restriction on languages. Each article was examined for additional references. A publication was excluded if it did not include original data (e.g., review, commentary) or if it was not published as a full-length article in a peer-reviewed journal (e.g., abstract only). The identified abstracts were screened first, and full texts of eligible articles were reviewed independently by 2 investigators. For eligible publications, we recorded the number of subjects, type of surgery, and criteria for diagnosis of neurologic end points.

RESULTS: We identified 13 case reports, 27 observational studies, and 2 prospectively randomized intervention trials that met our inclusion criteria. Case reports and 2 observational studies contained anecdotal evidence suggesting that regional cerebral O2 saturation (rScO2) monitoring could be used to identify cardiopulmonary bypass cannula malposition. Six of 9 observational studies reported an association between acute rScO2 desaturation and POCD based on the Mini-Mental State Examination (n = 3 studies) or more detailed cognitive testing (n = 6 studies). Two retrospective studies reported a relationship between rScO2 desaturation and stroke or type I and II neurologic injury after surgery. The observational studies had many limitations, including small sample size, assessments only during the immediate postoperative period, and failure to perform risk adjustments. Two randomized studies evaluated the efficacy of interventions for treating rScO2 desaturation during surgery, but adherence to the protocol was poor in one. In the other study, interventions for rScO2 desaturation were associated with less major organ injury and shorter intensive care unit hospitalization compared with nonintervention.

CONCLUSIONS: Reductions in rScO2 during cardiac surgery may identify cardiopulmonary bypass cannula malposition, particularly during aortic surgery. Only low-level evidence links low rScO2 during cardiac surgery to postoperative neurologic complications, and data are insufficient to conclude that interventions to improve rScO2 desaturation prevent stroke or POCD.

Monitoring of regional cerebral O2 saturation (rScO2) with near-infrared spectroscopy (NIRS) became possible after the pioneering work of Jöbsis,1 who demonstrated that light in the near-infrared spectrum penetrates the skull, allowing measurement of oxyhemoglobin and deoxyhemoglobin concentrations in the brain. The ability to use rScO2 monitoring to determine adequacy of cerebral perfusion during cardiac surgery soon followed.2–4 In the United States (US), clinicians can choose from 5 Food and Drug Administration–approved NIRS devices made by 4 manufacturers (INVOS™, Somanetics/Covidien, Inc., Boulder, CO; FORE-SIGHT™, CAS Medical Systems, Branford, CT; EQUANOX™, Nonin Medical, Inc., Plymouth, MN; and CerOx™, Ornim Medical, Lod, Israel). Other monitors available outside the US include the NIRO (Hamamatsu Photonics, Hamamatsu City, Japan) and TOS-96 (Tostec, Tokyo, Japan) monitors. Although there are many differences in the methods for rScO2 monitoring among manufacturers, NIRS devices all follow several basic principles as previously reviewed.3–6 Noninvasive, self-adhesive optode pads applied to the skin of the forehead emit light in the near-infrared spectrum that is measured by sensors at set distances from the light source. When the intensity of light is constant, the strength of light detected at the sensors is inversely related to the concentration of light-absorbing molecules, or chromophores. Oxyhemoglobin and deoxyhemoglobin have different and characteristic peak absorption in the near-infrared spectrum, but both absorb light at an isobestic wavelength around 800 nm. The absorption of light at the isobestic wavelength allows for the measurement of total hemoglobin concentration. Thus, using a modification of the Beer-Lambert law, NIRS provides a measurement of the concentration of oxygenated hemoglobin in relation to total hemoglobin concentration. The distance of the sensor from the light source determines the spatial resolution of the emitted light.

Many clinical devices use a proprietary algorithm for subtracting O2 saturation from superficial tissue, such as bone and extracerebral tissue, from that obtained from deeper tissue, to yield the rScO2 value of the superficial frontal cortex (Fig. 1). Unlike pulse oximetry, NIRS monitoring does not distinguish between arterial and venous blood. Because approximately 70% to 80% of cerebral blood is venous blood, rScO2 provides an indicator of the balance between regional O2 supply and demand.3,4

Figure 1
Figure 1
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NIRS is increasingly used to monitor patients undergoing cardiac surgery. An objective evaluation of the benefits and costs (>$200 per patient) of NIRS monitoring is needed to assess the potential added value of its use. In 2005, Taillefer and Denault7 reported a systematic review of the clinical efficacy of NIRS monitoring that included many abstracts from scientific meetings that have not since undergone peer review. Since that review was published, a variety of observational studies, case reports, and prospectively randomized studies of NIRS monitoring have been published.8,9 Therefore, we performed a systematic review of the clinical efficacy of NIRS monitoring in adult patients undergoing cardiac surgery to address (1) whether acute decrements in rScO2 during surgery are associated with perioperative stroke or other neurologic dysfunction manifesting as delirium or postoperative cognitive dysfunction (POCD), and (2) whether interventions based on rScO2 monitoring during cardiac surgery lead to improved neurologic or other patient outcomes.

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METHODS

We identified relevant publications by searching PubMed, Embase, and Cochrane databases from inception through January 31, 2012. Our strategy combined 2 broad search terms: “near infrared spectroscopy” and “cardiac surgery.” The search was not limited by languages or date, but it was limited to adult patients. The NIRS category combined the results from MeSH (medical subject headings) terms and the following keywords: “spectroscopy, near-infrared,” “spectroscopy,” “near-infrared,” “near-infrared spectroscopy,” “near infrared spectroscopy,” “NIRS,” and “cerebral oximetry.” The cardiac surgery search category combined the results from MeSH terms and the following keywords: “cardiac surgery,” “heart surgery,” “cardiac surgical procedures,” “cardiac surgery,” “cardiac bypass,” “cardiopulmonary bypass,” “coronary artery bypass,” “CABG,” “coronary bypass graft,” and “CAB”. These 2 broad categories were examined together to ensure that the resulting articles would include only studies that pertain to NIRS use in cardiac surgery patients. We also looked through the secondary references in the retrieved papers to capture articles that might have been missed. Lastly, we visited web sites of manufacturers of approved NIRS monitors to ensure that no relevant articles were overlooked. The review was limited to adult patients because the disease processes that necessitate cardiac surgery differ between pediatric and adult patients (congenital versus acquired heart disease). Furthermore, adult patients often have coexisting diseases, such as diabetes, hypertension, and cerebral vascular disease, that affect cerebral oxygen balance, whereas neonates and children may have right-to-left shunting that reduces rScO2. Finally, the manifestations of neurologic injury may vary between adults and pediatric patients.

We included publications in the review if they addressed either of the following questions: (1) Do decrements in cerebral oximetry lead to stroke or other neurologic dysfunction in adult patients undergoing cardiac surgery? and (2) Do interventions that are based on NIRS results improve neurologic or other patient outcomes? We excluded publications if they did not include original data (e.g., review, commentary) or if they had not been published as a full-length article in a peer-reviewed journal (e.g., abstract only). Each title and/or abstract identified was screened for eligibility, and the full text of eligible papers was then reviewed independently by 2 investigators (FZ, MSY, RS, MO, or YZ). Data regarding the number of subjects, type of surgery, and criteria for diagnosis of neurologic end points were recorded. Other study outcomes were recorded when reported. Only the latest publication was included when duplicate reporting of subjects could not be excluded. The articles were classified as case reports, observational studies, and prospectively randomized studies.

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RESULTS

Figure 2 shows a summary of our search results. The initial strategy identified 913 citations, of which 312 were duplicated studies from the different databases. Review of the abstracts of the remaining citations led to the exclusion of an additional 559 papers for not meeting the inclusion criteria of this review. The latter included 176 papers that involved patients undergoing noncardiac surgery, 298 studies of pediatric patients, 55 animal studies, 16 studies that did not include cerebral NIRS monitoring, and 14 studies that did not assess neurologic outcomes. We reviewed the remaining 43 full-length articles, which included a total of 6399 patients.

Figure 2
Figure 2
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Case Reports

Fourteen case reports were identified that described patients undergoing coronary artery bypass surgery, valve surgery, or aortic arch repair (Table 1).10–23 The authors of these reports suggested that rScO2 monitoring provided warning of cardiopulmonary bypass (CPB) arterial or venous cannula malposition and prompted surgical correction.10,12,14,22 In one report, oxygen delivery failure to the CPB circuit was first detected by an abrupt decrease in rScO2 during surgery.20 Only clinical neurologic assessments were provided in these case reports. In one report, the patient was reported to have severe delirium based on clinical examination.15

Table 1
Table 1
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Observational Studies and Randomized Trials Reporting Secondary NIRS End Points

Our search identified 18 prospective observational and 9 retrospective studies that included a total of 5969 patients (Table 2). We also identified 2 prospectively randomized studies that involved 440 patients and included NIRS end points.

Table 2
Table 2
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Twelve of the observational studies included patients undergoing aortic arch surgery, and 1 study compared femoral and axillary artery cannulation for ascending aorta dissection repair. These studies primarily evaluated the value of rScO2 monitoring for assessment of cerebral perfusion during surgery. Several authors reported that rScO2 monitoring was useful for adjusting or confirming the correct position of selective cerebral perfusion catheters during surgery.24,25 In the report by Orihashi et al.,24 malposition of the selective antegrade cerebral perfusion cannula occurred in 4 (11%) of 35 patients and was manifest as a unilateral or bilateral decrease in rScO2. Others reported that monitoring rScO2 was beneficial for supporting decisions to switch from unilateral to bilateral antegrade cerebral perfusion in patients undergoing aortic arch surgery.26

Fifteen of the studies reported on 4717 patients who underwent coronary artery bypass graft (CABG) and/or cardiac valve surgery. In one of these studies, patients were prospectively randomized to have surgery with or without CPB,27 and in another study, patients were prospectively randomized to receive anesthesia with sevoflurane or propofol.28 One study included only patients who underwent off-pump CABG surgery.29

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Postoperative Stroke

Most of the studies on rScO2 monitoring during aortic arch surgery were small, and the number of strokes was too low to reliably assess any relationship between cerebral O2 desaturation and neurologic outcome. Orihashi et al.30 did report that the duration of rScO2 <55% and <60% during aortic arch surgery with selective antegrade cerebral perfusion was associated with postoperative neurologic events. Neurologic events occurred in 16 (27.1%) of 59 patients and manifested as confusion (n = 5), generalized seizure (n = 5), anisocoria (n = 4), mydriasis (n = 1), and motor deficits (n = 1). Evidence of stroke was found with brain computed tomography or magnetic resonance imaging in 6 of these patients, and the neurologic symptoms were described as transient. In a series of 46 patients, Olsson and Thelin31 reported that patients with postoperative stroke were more likely than those without stroke to have had a reduction in rScO2 during surgery to 65% to 85% of baseline. Schön et al.32 found that stroke after aortic arch surgery with deep hypothermic circulatory arrest was more common in patients with rScO2 <80% of baseline than in those without desaturation. In that study, 11 of 51 patients developed desaturation with rScO2 <80% of baseline. Postoperative stroke occurred in 2 patients (18.1%) in the desaturation group but in none of the patients that did not develop desaturation. Computed tomography brain imaging confirmed that the strokes occurred in the hemisphere with rScO2 desaturation. Fischer et al.33 reported that patients with reduced rScO2 during aortic arch surgery were more likely to have major organ dysfunction than were those without desaturation. In that study, stroke occurred in 3 (10%) of 30 patients. There was a significant relationship between area under the threshold of rScO2 and a composite outcome of severe complications for rScO2 thresholds of 60% (P = 0.038) and 65% (P = 0.025).

Two studies in patients undergoing cardiac surgery reported a link between decreases in rScO2 during surgery and postoperative stroke or combined type I (stroke) and type II (clinical deterioration in intellectual function, memory deficits, delirium, or seizures) neurologic injuries. After introducing a practice of rScO2 monitoring that included a treatment algorithm to maintain a patient’s rScO2 at or near baseline, Goldman et al.34 compared outcomes for 1034 patients who underwent CABG and/or valve surgery over an 18-month period with outcomes of 1245 control patients who had had similar surgery without NIRS monitoring during the previous 18 months. The stroke rate in the patients who had rScO2 monitoring was lower than that of the historical controls (0.97% vs 2.5%, P = 0.044). The authors adjusted the findings for New York Heart Association class and whether surgery was with or without CPB. However, they did not use risk adjustment with multivariate logistic regression analysis to examine whether the use of rScO2 monitoring and an intervention was independently associated with a lower stroke rate. In addition, the authors did not report compliance with the algorithm for treating reduced rScO2.

Edmonds35 reported a retrospective study of 332 patients who had undergone CABG surgery with rScO2 monitoring. In that study, 42% of patients experienced rScO2 desaturation, which was defined as a decrease from baseline of >20%. An algorithm for treating desaturation was in place. They reported that the observed frequency of type I and type II neurologic injuries was less than the expected frequency estimated from the study by Roach et al.36 (3.0% vs expected 6.1%). This observation was attributable mostly to a reduction in type II injury. The nadir rScO2 in patients with neurologic injury (44 ± 10) was lower than that in patients without injury (54 ± 11, P = 0.02). Risk adjustment was not performed to evaluate whether rScO2 values were independently associated with type I or type II neurologic injury, nor was compliance with the treatment algorithm for desaturation reported.

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Postoperative Cognitive Dysfunction

Three studies that encompassed 214 cardiac surgery patients reported cognitive end points as assessed with the Mini-Mental State Examination (MMSE); in one study, the patients were also assessed with the antisaccadic eye movement (ASEM) test. Although Nollert et al.37 and Yao et al.38 found a link between low rScO2 and reduced MMSE, Negargar et al.27 reported that cerebral oximetry did not accurately predict postoperative neurologic complications. These studies defined desaturation at different rScO2 thresholds, and only Yao et al.38 provided a definition of what constituted a change in baseline in the MMSE or ASEM score. The ages of the patients in the studies by Nollert et al.37 (32–76 years) and Negargar et al.27 (mean age, 33.7 ± 13.3 to 54.3 ± 9.6 years) were lower than those in the study by Yao et al.38 (mean age, 66 ± 11 years). Only Yao et al.38 performed multivariate logistic regression analysis, in which they found that having areas of rScO2 <40% was an independent predictor of postoperative ASEM and MMSE impairments. Although it provides a general assessment of memory, orientation, and attention, the MMSE may be insensitive for detecting POCD.39

Investigators in 6 observational studies that encompassed 602 patients undergoing cardiac surgery performed more detailed cognitive assessments with a psychometric battery in accordance with consensus statements,40 although Hong et al.40 used an abridged version of this recommended battery. Four studies did find a relationship between decrements in rScO2 from baseline and POCD,28,41–43 and 2 did not.40,44 The sample sizes of all 6 studies were small (range, 35–128 subjects) and they were all underpowered to exclude type II error. Furthermore, the patients in these studies were relatively young, and the threshold and/or duration of rScO2 decrement used to define significant desaturation varied. Postoperative cognitive assessments were limited to the hospitalization phase in all but 1 study,41 which reported cognitive results 1 month after surgery. In these studies, the definition of cognitive decline was a decrease from baseline of >1 SD on ≥2 psychometric tests. This definition has been questioned because it does not account for correlation between tests that might result in a cognitive deficit in one domain being counted twice.45,46 In subanalysis of a randomized study that compared cognitive outcomes of patients anesthetized with sevoflurane and propofol, Schoen et al.28 used analysis of variance for repeated measures to show that patients with rScO2 desaturation had worse scores than did those without desaturation.

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Delirium

Several observational studies reported on postoperative delirium.26,33,43,47 Only 1 study provided an objective assessment for delirium by using the confusion-assessment-method for the intensive care unit (ICU) inventory.43 The authors reported delirium in 62 (26.8%) of 231 patients. They found that preoperative rScO2 was lower in patients who developed postoperative delirium than in those who did not (mean ± SD, 58.1% ± 7.7% vs 63.1% ± 7.2%, P ≤ 0.001) but that peripheral arterial oxygen saturation did not differ between the 2 groups. Additionally, during surgery, the area under the curve for an rScO2 cutoff of 50% was larger (41.6 ± 114.9 vs 19.5 ± 94.9, P ≤ 0.001) and the minimal rScO2 lower (48.6% ± 9.3% vs 55.1% ± 8.6%, P ≤ 0.001) for patients who developed delirium than for those who did not. The area under the curve for the receiver operating characteristic curve for minimal intraoperative rScO2 for predicting delirium (0.73; confidence interval, 0.66–0.80, P = 0.0001) showed that an rScO2 cutoff of 51% best predicted delirium (sensitivity, 60.0%; specificity, 75.6%). Based on binary logistic regression analysis, older age, lower MMSE score, neurologic or psychiatric disease, and lower baseline rScO2 while breathing O2, but not intraoperative rScO2 desaturation, were independently associated with postoperative delirium.

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Prospectively Randomized Intervention Trials for rScO2 Desaturation

We identified 2 prospectively randomized trials that evaluated interventions for correcting rScO2 desaturation during cardiac surgery (Table 3).8,9 Each trial used a similar threshold for treating decrements in rScO2. Detailed psychometric testing was performed only in the study by Slater et al.9 In a study of 200 patients, Murkin et al.8 reported 1 stroke in the intervention group and 4 in the control group. However, that study was not powered to detect a difference in stroke rate between groups; it was powered to detect a 50% decrease in complications based on a projected complication rate of 40% in controls. The actual rate of complications, however, was only 30%, and the reduction in all complications in the intervention group decreased 23%, a value that was not statistically significant. Furthermore, the major findings were not risk-adjusted to assess whether the interventions for treating a reduction in rScO2 were independently associated with the reduction in patient morbidity or mortality. One or more episodes of desaturation occurred in 56 of 100 patients in the intervention group. Interventions corrected the desaturation with an 80.4% success rate. One intervention was needed in 2 patients, 2 interventions were needed in 10 patients, 3 interventions were needed in 4 patients, and >3 interventions were needed in 40 patients. The interventions included (efficacy in parenthesis) increasing CPB flow (67%), increasing mean arterial blood pressure (62%), normalizing PaCO2 (50%), deepening anesthesia (48%), increasing fraction of inspired oxygen (43%), and instituting pulsatile perfusion (17%).

Table 3
Table 3
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In their study of 240 patients, Slater et al.9 reported poor compliance with the protocol for treating rScO2 decrements during surgery. The result was similar rates of rScO2 desaturation in the intervention (30%) and control (26%) groups. They found that patients with prolonged desaturation (rScO2 >3000%-second below a 50% saturation) had a higher frequency of early postoperative cognitive decline (P = 0.024) and were at higher risk for early POCD compared with those with lower desaturation scores (odds ratio, 2.22; P = 0.024) after adjusting for other demographic and clinical variables. There was no independent relationship between POCD at 3 months after surgery and prolonged rScO2 desaturation or between randomized treatment groups.

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Health Resource Utilization

Two studies have suggested a relationship between low rScO2 and duration of mechanical lung ventilation after surgery,33,34 but a third study failed to confirm these findings.8 Seven studies reported a relationship between low rScO2 during surgery and duration of hospitalization in the ICU or postoperative ward.8,9,28,33,34,40,43 However, 2 studies found no relationship between rScO2 and hospital length of stay.8,34 In the study by Slater et al.,9 patients with rScO2 desaturation >3000%-second had a nearly 3-fold increased risk for prolonged hospitalization (>6 days) compared with those without desaturation (odds ratio, 2.71; 95% confidence interval, 1.31–5.60; P = 0.007).

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DISCUSSION

In this systematic review, we sought to evaluate whether decrements in rScO2 from baseline were associated with stroke, POCD, and/or delirium in adult patients after cardiac or aortic surgery. Although a relationship between rScO2 reductions and these outcomes has been reported, the results were not consistent. In addition, we found no available evidence to support or refute the premise that interventions to correct rScO2 during surgery lead to improved neurologic outcomes.

Monitoring rScO2 with NIRS during cardiac surgery could have many potential benefits for assessing the adequacy of cerebral oxygen balance, particularly for the growing number of elderly patients undergoing surgery and for those with cerebral vascular disease that causes a predisposition to brain injury.48–50 A limitation in interpreting the studies that we reviewed is the variety of devices used by investigators and the varying definitions used to define an abnormality in rScO2. There are key differences among NIRS monitors, including the source of light, the number of wavelengths of light emitted, and the distances between light-emitting optodes and sensors. The most widely used monitors in the US are the INVOS 5100 monitor, the FORE-SIGHT monitor, and the EQUANOX Classic 7600 monitor. For the INVOS monitor, sensors for light detection are placed 30 mm and 40 mm from the light-emitting diode, whereas for the FORE-SIGHT monitor, the sensors are 15 mm and 50 mm from the laser-generated light source. The EQUANOX Classic 7600 monitor system uses 2 separate sets of light-emitting diodes and 2 light sensors that are 20 mm and 40 mm from the light source. The latter device uses a more complex analysis process whereby the 40-mm detector for one light source serves as the proximal sensor for the other device. The CerOx monitor (Ornim Medical) uses a laser light source and has 1 sensor. Unique to this monitor is the use of ultrasound to “tag” the light via the acousto-optic effect. This method allows the light-penetration profile to be assessed, thereby enabling the light to be focused on the desired depth and volume of brain tissue. Monitoring of the reflected ultrasound provides an additional indicator of local tissue cerebral blood flow. The NIRO monitor uses laser light with photodetectors at a distance of 37 mm and 43 mm from the light source. The TOS-96 uses a light-emitting diode with only 1 photodetector placed 40 mm from the light source.

There is no universal definition of what decrement in rScO2 from baseline constitutes an abnormal finding during cardiac surgery. The studies that we reviewed used either a relative decrease in rScO2 from baseline (e.g., 20% decrease) or an absolute threshold rScO2 (e.g., <50%). Thresholds of rScO2 values indicative of cerebral ischemia have been derived mostly from data obtained from patients undergoing carotid endarterectomy. In those studies, a reduction in rScO2 of 5% to 15% from baseline in the hemisphere ipsilateral to the clamped carotid artery was found to be associated with reductions in transcranial Doppler-measured cerebral blood flow velocity, slowing of the electroencephalogram (EEG), or changes in somatosensory evoked potentials (SSEPs) with a sensitivity that ranged from 44% to 100% and specificity between 44% and 82%.51–55 In a study of 323 patients, however, 24 patients (7.4%) had discrepancies between rScO2 changes during carotid artery clamping and EEG or SSEP monitoring results.56 In that study, 7 patients had no change in rScO2 despite marked abnormalities in the EEG or SSEPs, whereas 1 patient had a reduction in rScO2 without EEG or SSEP changes. Other data from patients undergoing carotid endarterectomy under regional anesthesia revealed that a reduction in rScO2 of 20% from baseline identified neurologic symptoms during carotid artery clamping with a sensitivity of 80% and specificity of 82%.57 In that study, rScO2 decreased from a mean of 63.2% ± 8.1% to 51.0% ± 11.6% (P = 0.0002) in patients with neurologic symptoms. In a study of 19 patients undergoing carotid surgery, an rScO2 value between 54% and 56% during carotid clamping predicted EEG slowing.55 It is unclear whether these data can be extrapolated to patients undergoing cardiac surgery, because anesthetic technique and patient body temperature differ from those used for carotid surgery.

In previous studies, rScO2 values may have failed to detect cerebral ischemia during carotid artery clamping because interventions such as shunt placement and increasing the blood pressure may have been instituted based on other monitoring modalities before ischemia reached a critical rScO2 threshold. Another explanation might be contamination of the rScO2 reading by extracranial tissue. Many clinical NIRS monitors use algorithms that subtract light absorption by superficial tissue from light absorption by deeper tissue to yield rScO2. This approach was validated in a study of 14 patients after injection of the near-infrared chromophore indocyanine green into the carotid artery during cerebral angiography.58 Washout curves were measured by sensors with 4 detectors that were 10, 20, 30, and 40 mm from the infrared light source on the right forehead and 15, 25, 35, and 45 mm from the light source on the left forehead. Relative absorption increased with increasing distance of the sensor from the light source when indocyanine green was injected into the internal carotid artery, but attenuation of light absorption was small when dye was injected into the external carotid artery. In a study of 60 patients undergoing carotid endarterectomy, researchers compared the contributions of intracranial and extracranial blood sources for tissue oxygenation measured with the NIRO-300 monitor during selective clamping of the external carotid and internal carotid arteries.59 These investigators found a significant correlation between changes in regional cerebral oxygenation and changes in transcranial Doppler-measured cerebral blood flow velocity (r = 0.56, P < 0.0001) during internal carotid artery clamping. No correlation was observed between skin laser Doppler flow velocity and cerebral tissue oxygenation during external carotid artery clamping. Overall, the sensitivity of NIRS-measured cerebral tissue oxygenation for detecting intracranial and extracranial flow changes was 87.5% and 0%, respectively. The specificity for these measurements was 100% and 0%, respectively. These data support the reliability of NIRS to detect changes in cerebral oxygenation.

The reliability of current light subtraction algorithms has been challenged by a clinical study of patients undergoing spine surgery, in which changes in rScO2 were measured during hypercapnia before and after the inflation of a pneumatic cuff placed circumferentially around the forehead.60 Induction of scalp ischemia by inflation of the scalp tourniquet attenuated hypercapnia-induced changes in rScO2. Scalp ischemia should have caused no change in rScO2 value if subtraction of extracranial light absorption from deep-structure light absorption was reliable. A recent study in volunteers suggested that extracranial contamination of the NIRS signal may be significant but that the magnitude of reduction in the rScO2 reading varies among clinically available devices.61 Whether these findings affect the reliability of rScO2 as a trend monitoring in cardiac surgical patients is not known. More importantly, no one has compared the sensitivity or reliability of the various available NIRS monitors for their ability to identify risk of adverse neurologic outcomes. Thus, whether data obtained with one NIRS device can be extrapolated to another device is not known.

Our review suggests that the most pervasive information supporting the value of rScO2 monitoring is for identifying CPB cannula malposition, particularly malposition of selective antegrade cerebral perfusion catheters used for surgery of the aortic arch. However, these data are mostly anecdotal. Given the relative infrequency of aortic surgery in most centers, obtaining enough patients for a prospective randomized trial to detect differences in rates of stroke between monitored and nonmonitored patients would be difficult. Consequently, clinicians may be satisfied with less-robust evidence when making decisions regarding NIRS monitoring during surgery in which the continuity of cerebral vessels may be compromised. Nonetheless, data on the specificity of rScO2 monitoring for ensuring cerebral perfusion are not currently available. That is, there is little evidence on whether the absence of acute reductions in rScO2 ensures adequate cerebral blood flow.

Several investigations have suggested a link between acute reductions in rScO2 from baseline and POCD and stroke.31,34,41–43,62 Other observational studies have suggested that a reduction in rScO2 is associated with postoperative delirium or longer stays in the ICU or hospital. These reports have many limitations, including the use of insensitive cognitive assessments such as the MMSE, inadequate sample size to allow for risk adjustments with multivariate logistic regression analysis, young patient age, the use of historical controls, failure to report adherence with protocols for treating rScO2 desaturation, failure to report the approach for addressing missing data, testing only in the immediate postoperative period, and using analysis methods that have been suggested to be inappropriate.45,46 Inconsistencies in the definitions of rScO2 desaturation threshold and psychometric test result reporting preclude meta-analysis of these data.

We found only 2 prospectively randomized trials that investigated whether interventions to correct acute reductions in rScO2 improve patient outcomes. In one of those studies, poor adherence with the protocol for treating acute rScO2 reductions precluded interpretation of the results.9 However, Murkin et al.8 reported that interventions for increasing rScO2 were effective in 80% of patients and that such interventions were associated with a lower frequency of the composite end point of death, mechanical ventilation >48 hours, stroke, renal failure requiring dialysis, myocardial infarction, mediastinal reexploration, or deep sternal wound infection compared with nonintervention (P < 0.048). That study was not powered to detect differences in stroke rate between intervention and control patients and did not use risk adjustment to assess independent relationships between the interventions for rScO2 desaturation and complications. In that study, major organ morbidity was a secondary outcome and occurred in 3% of patients in the intervention group and 11% of controls. Furthermore, the direct relationship between interventions aimed at improving rScO2 and some components of the composite outcome, such as myocardial infarction, bleeding, and sternal wound infections, was not clearly elucidated.

The data by Murkin et al.8 support the view that the brain might provide an “index organ” for ensuring organ perfusion during CPB. Major organs such as the brain and kidney are normally protected from hypotension by autoregulatory vascular compensations that maintain a steady flow of oxygenated blood across a range of blood pressures. Thus, maintaining blood pressure in the autoregulatory range for the brain might ensure adequate blood pressure for renal perfusion during CPB. By processing rScO2 signals in relation to blood pressure, we have shown that excursions of blood pressure below the lower limit of cerebral autoregulation are independently associated with risk for acute kidney injury after cardiac surgery.63 Nonetheless, experiments in piglets have shown that neurohumoral compensatory mechanisms that increase systemic vascular resistance during hypotension ensure cerebral blood flow at the expense of splanchnic and renal hypoperfusion.64 In the latter study, renal blood flow was nearly 25% of baseline during hemorrhagic shock before cerebral blood flow was compromised. These and other data support the notion that cerebral blood flow is more dependent on blood pressure during cardiac surgery, whereas renal blood flow may be more dependent on cardiac output or CPB flow rate.65,66

Clinicians often encounter patients with baseline rScO2 <50% that otherwise would be considered below the threshold for cerebral ischemia. Because rScO2 is an indicator of the relationship between cerebral oxygen supply and metabolic oxygen demand, factors such as low cardiac output, pulmonary disease, cerebral vascular disease, and anemia, which can reduce cerebral arterial oxygen supply, cause increases in oxygen extraction by the brain and resultant low rScO2. Thus, whether low rScO2 simply identifies patients with severe cardiopulmonary dysfunction or cerebral vascular disease who are at high risk for neurologic complications, or whether it represents a potentially modifiable risk factor, is not clear. Murkin et al.8 reported that baseline rScO2 was lower in patients at risk for morbidity or mortality after CABG surgery. Additionally, in a study of 1178 patients who underwent cardiac surgery with CPB, patients who had a preoperative rScO2 <50% while breathing oxygen were found to be at increased risk for 30-day and 1-year mortality.67 In that study, rScO2 was correlated with age, gender, body mass index, ASA physical status, EuroSCORE, left ventricular ejection fraction, glomerular filtration rate, and hematocrit. In addition, an rScO2 of 60% in patients who breathed oxygen for 2 minutes identified adjusted risk for morbidity with a sensitivity of 56.1% and specificity of 71.4%. Hence, it is not surprising that low baseline rScO2 identifies patients at high risk for postoperative adverse events, including prolonged mechanical lung ventilation and duration of hospitalization in the ICU or on the postoperative ward.8,9,28,33,34,40,43 Our review extends the findings of Taillefer and Denault,7 who published a systematic review in 2005 of the clinical efficacy of NIRS monitoring during cardiac surgery. Although they identified 48 clinical trials, 28 were published only as abstracts. Most of those abstracts have not been subsequently published as full-length articles. Our review provides an update of the clinical literature related to NIRS monitoring during cardiac surgery. Nonetheless, the conclusions of Tallifer and Denault7 that only low-level clinical evidence supports NIRS use during cardiac surgery remain unchanged. The overall cost-benefit ratio of NIRS monitoring requires more rigorous research.

In conclusion, many reports in the literature (mostly anecdotal) suggest that reductions in rScO2 during cardiac surgery may provide an indication for mechanical mishaps related to CPB cannulas, particularly during aortic surgery. The level of evidence linking decreased rScO2 during cardiac surgery to postoperative neurologic complications is low. Furthermore, current evidence does not definitively show that interventions to improve rScO2 desaturation prevent stroke, delirium, or POCD.

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DISCLOSURES

Name: Fei Zheng, MPH, MD.

Contribution: The author helped design the search strategy, helped perform the search, collected the titles and abstracts of identified papers, read the abstracts to identify papers meeting inclusion criteria, read the identified papers, and helped prepare the manuscript.

Attestation: Fei Zheng has read and approved the manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Rosanne Sheinberg, MD.

Contribution: The author helped read the titles and abstracts of papers identified in the literature search, read the abstracts to identify papers meeting inclusion criteria, read the identified papers, and helped prepare the manuscript.

Attestation: Rosanne Sheinberg has read and approved the manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: May-Sann Yee, MD.

Contribution: The author helped read the titles and abstracts of papers identified in the literature search, read the abstracts to identify papers meeting inclusion criteria, read the identified papers, and helped prepare the manuscript.

Attestation: May-Sann Yee has read and approved the manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Masa Ono, MD, PhD.

Contribution: The author helped read the titles and abstracts of papers identified in the literature search, read the abstracts to identify papers meeting inclusion criteria, read the identified papers, and helped prepare the manuscript.

Attestation: Masa Ono has read and approved the manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Yueyging Zheng, MD.

Contribution: The author helped read the titles and abstracts of papers identified in the literature search, read the abstracts to identify papers meeting inclusion criteria, read the identified papers, and helped prepare the manuscript.

Attestation: Yueyging Zheng has read and approved the manuscript.

Conflicts of Interest: The author has no conflicts of interest to declare.

Name: Charles W. Hogue, MD.

Contribution: The author helped design the search strategy, helped perform the search, collected the titles and abstracts of identified papers, read the abstracts to identify papers meeting inclusion criteria, read the identified papers, and helped prepare the manuscript.

Attestation: Charles W. Hogue has read and approved the manuscript.

Conflict of Interest: The author has received research funding from Covidien, Inc., Boulder, CO, and has served as a consultant to Covidien, Inc. and Ornim Medical, Inc., Tel Aviv, Israel.

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RECUSE NOTE

Dr. Charles W. Hogue is the Associate Editor-in-Chief for Cardiovascular Anesthesiology for the Journal. This manuscript was handled by Dr. Gregory J. Crosby, Section Editor for Neuroscience in Anesthesiology and Perioperative Medicine, and Dr. Hogue was not involved in any way with the editorial process or decision.

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