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Review Articles: Narrative Review Article

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on the Role of Neuromonitoring in Perioperative Outcomes: Cerebral Near-Infrared Spectroscopy

Thiele, Robert H. MD*; Shaw, Andrew D. MB, FRCA, FFICM, FCCM, MMHC; Bartels, Karsten MD, PhD; Brown, Charles H. IV MD, MHS§; Grocott, Hilary MD, FRCPC, FASE; Heringlake, Matthias MD; Gan, Tong Joo MD#; Miller, Timothy E. MB, ChB, FRCA**; McEvoy, Matthew D. MD††; The Perioperative Quality Initiative (POQI) 6 Workgroup

Author Information
doi: 10.1213/ANE.0000000000005081

Abstract

The brain is the most metabolically active organ in the human body, one of the primary sites of action for anesthetic agents, and at risk for both intra- and postoperative dysfunction following surgical procedures. As the parameters impacting cerebral blood flow (CBF) are complex and normally highly regulated,1,2 there are large interindividual differences in CBF regulation, as well extrinsic determinates of CBF, making estimates of CBF adequacy a challenge.3 Because the boundaries of autoregulation differ among individuals with different diseases and ages, there has been a long-standing interest in measuring the oxygenation of brain tissue to detect (and correct) perturbations in cerebral oxygen supply:demand ratios that can lead to tissue injury or death.2–4 Cerebral oximetry, which uses near-infrared spectroscopy (NIRS) to estimate the oxygen saturation of hemoglobin in brain tissue, was developed in the late 1970s4 and became commercially available in 1989 following the introduction of the NIRO-1000 by Hamamatsu Corporation (Iwata City, Shizuoka Prefecture, Japan).5 Since then, multiple different manufacturers have added to the clinically available devices, 5 of which have obtained clearance by the Food and Drug Administration in the United States.

Reports of using cerebral oximetry to detect adverse perioperative clinical conditions and to guide patient care have been widely published in both cardiac and noncardiac surgical settings.6,7 However, with NIRS devices available from multiple manufacturers, all with differences in wavelengths, number of wavelengths, sensor configuration, and proprietary integrated algorithms used to determine cerebral saturation, important interdevice differences exist. Compounding these challenges is the fact that not all of the algorithms have been published, essentially making these “black box” devices. Accordingly, considerable knowledge gaps exist as to how and when to use the monitoring technology. Here, we attempt to provide clinicians with relevant information on the potential role of cerebral NIRS for improving patient outcomes in perioperative medicine, including both cardiac and noncardiac surgical procedures.

METHODS

Expert Group

An international group of participants with representation from anesthesiology, surgery, and critical care medicine was invited to contribute to the Sixth Perioperative Quality Initiative (POQI-6) consensus conference (see Contributors at the end of the article). These representatives were identified by the POQI-6 leaders (T.J.G., T.E.M., M.D.M.). Content experts were chosen based on a combination of their past clinical trials and publication history relating to neuromonitoring as well as their own personal interest and availability to make substantial contributions to the POQI consensus process. A minority of participants did not have expertise in neuromonitoring but did have expertise in other areas of perioperative medicine, evaluation of scientific literature, and the consensus-generation process. These nonexpert participants are an essential part of the POQI-6 process as they have relatively few preconceived notions about the utility of various forms of neuromonitoring and do not carry the same cognitive biases that might exist in content experts. In total, 21 experts from North America, Europe, and Asia met in Dallas, TX, on November 29 to December 1, 2018 to discuss iteratively the evidence surrounding 2 types of neuromonitoring (cerebral oximetry, electroencephalography [EEG]) and perioperative delirium considerations to develop consensus statements with practical recommendations for clinicians. The results of the EEG and delirium workgroups are reported elsewhere.8,9

Process

We utilized a modified Delphi method to develop and answer important questions related to the use of cerebral oximetry as a neuromonitor.10 A list of relevant questions was developed electronically under the supervision of the conference chairs (M.D.M., T.E.M., T.J.G.) and circulated before the meeting (listed in the Discussion section). Before the meeting, participants in each workgroup were asked to identify relevant peer-reviewed literature for each question. Searches were performed in PubMed following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.11 All search terms were saved (Supplemental Digital Content, Appendix 1, https://links.lww.com/AA/D154) and relevant manuscripts were cataloged for group reference.

In the first plenary session of the meeting, each POQI workgroup presented their set of questions, a draft of proposed consensus statements, and the evidence supporting these statements to the entire POQI conference. Each workgroup then worked independently to formulate more specific consensus statements. This process (receiving feedback from the plenary session, modifying consensus statements in a small group setting) was repeated 3 times. In the final plenary session, GRading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology was utilized to establish the strength of each recommendation (taking into account the opinion of the plenary group) and the level of evidence (LOE) for each consensus statement.12 LOE was graded as follows:

  • A: High quality—further research is very unlikely to change our confidence in the estimate of effect.
  • B: Moderate quality—further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
  • C: Low quality—further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
  • D: Very low quality— any estimate of effect is very uncertain.

According to the GRADE system, recommendations could be given as “strong” or “weak.”

Table 1. - Consensus Statements
No. Consensus Statement Strength of Statement Quality of Evidence Agreement
1 We recommend interpreting perioperative cerebral oximetry measurements in the context of a preinduction baseline value Strong B Unanimous
2 We recommend interpreting perioperative cerebral oximetry measurements in the context of the physiologic variables that affect them Strong B Unanimous
3 We recommend caution in comparing cerebral oximetry values between different manufacturers Strong B Unanimous
4 We recommend the use of preoperative cerebral oximetry to identify patients at increased risk of adverse outcomes after cardiac surgery Weak B Unanimous
5 We recommend intraoperative cerebral oximetry indexed to preinduction baseline to identify patients at increased risk of adverse outcomes after cardiac surgery Weak C Unanimous
6 We recommend using cerebral oximetry to identify and guide management of acute cerebral malperfusion during cardiac surgery Weak D Unanimous
7 We recommend using an intraoperative cerebral oximetry–guided interventional algorithm to reduce ICU length of stay after cardiac surgery Weak C Unanimous
8 There is insufficient evidence to recommend using intraoperative cerebral oximetry to reduce mortality or organ-specific morbidity after cardiac surgery n/a n/a Unanimous
9 There is insufficient evidence to recommend using intraoperative cerebral oximetry to improve outcomes after noncardiac surgery n/a n/a Unanimous
Quality of evidence was graded as follows: A: High quality—further research is very unlikely to change our confidence in the estimate of effect; B: Moderate quality—further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; C: Low quality—further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; D: Very low quality—any estimate of effect is very uncertain.
Abbreviations: ICU, intensive care unit; n/a, not applicable.

In the final session, voting (public) results for each statement concerning the final wording, GRADE, and LOE were recorded from each member of the POQI-6 conference (Table 1).

Technical Considerations

A basic, intuitive understanding of the technical principles of NIRS is essential to interpretation of the published data as well as proper clinical use. These principles are as follows:

  1. Deoxyhemoglobin and oxyhemoglobin are “chromophores” that absorb electromagnetic radiationa (EMR), in particular in the red and near-infrared range.
  2. Deoxyhemoglobin and oxyhemoglobin absorb different amounts of red and infrared EMR (and also other wavelengths). These absorption profiles are unique to each chromophore and referred to as the “absorption spectra.”
  3. NIRS devices emit red and infrared EMR into tissue and measure the amount of red and infrared EMR that is absorbed by the tissue.
  4. By comparing the relative amount of red and infrared EMR absorbed by tissue, an estimate of the ratio of oxyhemoglobin to total hemoglobin in the tissue can be made.

A more detailed description of NIRS technology is provided in the Supplemental Digital Content, Appendix 2, https://links.lww.com/AA/D154.

aThe scientific term EMR has been chosen instead of the more common term “light,” since by definition “light” is something visible, and the NIRS technology is also based on “invisible” radiation in the infrared range.

DISCUSSION

The following questions were considered most relevant to the use of cerebral tissue oxygen saturation (Scto2) as a perioperative neuromonitor:

  1. What physiologic information can Scto2 provide?
  2. How do technical aspects of cerebral oximetry devices influence the Scto2 signal?
  3. What is the utility of Scto2 monitoring in various components of the perioperative period? (preoperative baseline, intraoperative, cardiopulmonary bypass, postoperatively)
  4. Can using a cerebral NIRS-guided interventional algorithm reduce perioperative complications after (cardiac/high-risk noncardiac) surgery?

What Physiologic Information Can Cerebral Oximetry Provide?

The complexity of CBF as well as the devices designed to measure Scto2 require a working knowledge of both brain physiology and the scientific principles of NIRS. Blood flow to the brain is a function of driving pressure and resistance, in accordance with the Hagen-Poiseulle law.13,14 Because of its importance, the human brain has developed the ability to autoregulate blood flow within the “cerebral autoregulatory range”—within this range of perfusion pressures, the brain can adjust regional vascular resistance (RVR) to keep blood flow relatively constant.15 Changes in cerebral RVR are usually induced through changes of cerebral perfusion pressure via autoregulation, cerebral metabolic activity via neurovascular coupling, arterial CO2 partial pressure, or sympathetic nervous activity innervating the cerebral resistance vessels.16

Physiologically, cerebral oximetry may offer information of the balance between cerebral tissue oxygen consumption and supply. This makes cerebral oximetry different from pulse oximetry, the goal of which is to determine the oxygen saturation in arterial blood. Of note, baseline Scto2 values vary between individuals, thus the changes in Scto2 relative to baseline (ie, preinduction of anesthesia) measurements may offer more clinical information than absolute measurements. This concept has been utilized in an observational study of 124 patients undergoing elective shoulder arthroscopy, cerebral desaturation events, defined as at least a 20% decrease from baseline, were more common in patients operated in the beach chair position compared to the lateral decubitus position.17 We recommend interpreting perioperative cerebral oximetry measurements in the context of a preinduction baseline value (strong recommendation, LOE: B) Of note, the purpose of the preinduction baseline should be to measure Scto2 during conditions which mimic the natural state of the patient as much as possible with sufficient time to establish a stable baseline before induction (ie, not placing the sensor and proceeding with induction after the first value is displayed, but giving supplemental oxygen until no further increase in Scto2 is observed, if a patient presents with low systemic oxygen saturation readings; a period of 3–5 minutes should accomplish this goal).

Commercially available cerebral oximeters are only capable of measuring the relative fraction of oxygenated compared to total hemoglobin concentration in an “optical field” interrogated using NIRS.

Clinically utilized NIRS devices analyze all EMR (at specific emitted frequencies) absorbed by the brain and other tissues, as compared to pulse oximeters, which only analyze pulsatile (arterial) absorbance. These devices attempt to remove “extracranial contamination” using “spatially resolved spectroscopy” techniques that have been shown to be imperfect.18

Table 2. - Perioperative Variables That Can Affect Cerebral Blood Flow and Scto2 Measurements
Variablea Impact
Sex Women have higher CBF rates than men
Volatile anesthetic agents Direct cerebrovasodilator
Propofol Reduction in CBF (coupling of metabolism and flow)
Paco 2 Hypercapnea increases cerebral arterial blood volume
Pao 2 Hypoxia leads to an increase in cerebral blood volume
pH Metabolic alkalosis leads to an increase in CBV
Head positioning relative to body Head up position reduces CBV, reduces Scto 2
Neck positioning Flexion, extension, and rotation all impact ICP and likely CBV
Alpha agonist vasoconstriction Phenylephrine decreases Scto 2 despite increasing blood pressure
Abbreviations: CBF, cerebral blood flow; CBV, cerebral blood volume; ICP, intracranial pressure; Paco2, partial pressure arterial carbon dioxide; Pao2, partial pressure arterial oxygen; Scto2, cerebral tissue oxygen saturation.
aSee references 17–28 for more information regarding these variables.

The “tissue saturation” of the blood in the brain (and other tissues) measured by a cerebral oximeter is a combination of arterial, capillary, and venous blood. If one assumes that arterial oxygen saturation is close to 100%, that the volume of capillary blood is relatively small, and that the relative volume (or ratio) of arterial and venous blood is fixed (eg, 30:70, or 25:75, depending on the device manufacturer), the oxygenation of venous blood leaving the cerebral capillary beds can be estimated. However, the true percentage of cerebral venous blood can range from 33% to 84% depending on various factors, such as partial pressure arterial carbon dioxide (Paco2), partial pressure arterial oxygen (Pao2), pH, etc (see Table 2 for a list of variables that affect CBF and Scto2).19–30 Furthermore, animal study suggests that capillary blood volume in the brain is not negligible.21 It is worth pointing out that most of these devices were calibrated in humans using jugular venous bulb measurements (for additional technical details, see Supplemental Digital Content, Appendix 2, https://links.lww.com/AA/D154). Given that the arterial to venous blood ratio in humans is dynamic and is affected by many variables, the workgroup felt it was important to stress that cerebral oximeter values should not be viewed without knowledge of the clinical context: We recommend interpreting perioperative cerebral oximetry measurements in the context of the physiologic variables (Table 2) that affect them (strong recommendation, LOE: B).

How Do Technical Aspects of Cerebral Oximetry Devices Influence the Scto2 Signal?

Cerebral oximeters measure the relative concentration of oxyhemoglobin and deoxyhemoglobin in an optical field that includes the brain. The emitter-detector-brain geometry is a critical parameter of the technology and variations in head sizes according to age need to be considered. The ability of the various commercially available devices to correct for potential extracranial signal contamination has been studied. Using a forehead pressure cuff to decrease perfusion to the scalp, Davie and Grocott18 found that 3 commercially available devices (FORE-SIGHT [CASMED, Branford, CT], INVOS 5100C-PB [Medtronic, Dublin, Ireland], and EQUANOX 7600 [Nonin Medical, Inc, Plymouth, MN]) all responded to cuff inflation (ie, scalp ischemia) with decreasing Scto2. Significant extracranial contamination was also identified by Sørensen et al.31 This suggests that while modern devices attempt to “remove” confounding absorption signals from skin, fat, muscle, and bone, this process is not perfect. The FORE-SIGHT device, for example, appears to be particularly affected by dark skin pigmentation when compared to other devices32 or arterial oxygen saturation (Sao2) changes between 94% and 99%.33

A comparison of 5 commercially available cerebral oximeters during hypoxia in healthy volunteers found the widest limits of agreement (comparing NIRS-derived Scto2 and jugular venous bulb saturation) in the INVOS 5100c 2-wavelength device, and the narrowest limits of agreement in the FORE-SIGHT 4-wavelength device.32 An analysis of preinduction Scto2 in over 3000 patients undergoing cardiac surgery found that African Americans have significantly lower baseline Scto2 than Caucasians, likely due to interference from skin pigmentation (ie, melanin absorption interfering with the measurement of hemoglobin oxygenation; of note, a 2-wavelength device is not capable of resolving 3 chromophores [eg, oxyhemoglobin, deoxyhemoglobin, and melanin]).34

There are also likely differences in the sensitivity of various devices to changes in Paco2 and Pao2. While not studied exhaustively (not all commercially available devices have been analyzed), Scto2 values measured by the FORE-SIGHT device appear to be less sensitive than Scto2 values measured by the INVOS device when Paco2 is decreased from 40 to 30 mm Hg.35

Because each manufacturer uses a unique combination of wavelengths, sensor spacing, and analytic algorithms, all of which impact the sensitivity of Scto2 to extracranial contamination as well as altered cerebral hemodynamics (eg, as occurs in hypocarbia), these devices are noninterchangeable and we recommend caution in comparing cerebral oximetry values between different manufacturers (strong recommendation, LOE: B).

Table 3. - Technical Features of NIRS Devices
Features of NIRS Devices Relevance
Number of wavelengths utilized More wavelengths (eg, 4 vs 3) increases the signal to noise ratio of Sco 2
Wavelength selection Longer wavelengths penetrate deeper into tissue in the red (630–700 nm) and near-infrared range (700–5000 nm). Note that at around 925 nm, water begins to absorb NIR
Source-detector separation The farther apart the source and detector, the deeper the signal penetration, but the lower with signal to noise ratio (assuming other variables are held constant)
Abbreviations: NIR, near-infrared radiation; NIRS, near-infrared spectroscopy; Sco2, cerebral oxygen saturation.

A more complete description of the technical aspects of NIRS can be found in Supplemental Digital Content, Appendix 2, https://links.lww.com/AA/D154. Table 3 lists a number of key technical features for NIRS devices.

What Is the Utility of Scto2 Monitoring in Various Components of the Perioperative Period? (Preoperative Baseline, Intraoperative, Cardiopulmonary Bypass, Postoperatively)?

Once a firm understanding of NIRS has been established, and the technical limitations of cerebral oximetry have been considered, clinicians can use the devices in an effort to optimize patient care. For instance, multiple investigators have sought to determine if Scto2 values at baseline are predictive of complications after surgery (Supplemental Digital Content, Table 1, https://links.lww.com/AA/D154). While any preexisting oxygen therapy should be continued, baseline Scto2 values should be obtained before preoxygenating for induction of general anesthesia, as supplemental oxygen increases Scto2.36 Three studies including 3485 cardiac surgery patients suggest that low preoperative Scto2 is associated with higher probability of mortality (receiver operator curve [ROC] areas of 0.81, 0.84, and 0.79, respectively)37–39 and 2 studies including 480 cardiac surgery patients suggest that preoperative Scto2 is predictive of postoperative delirium.40,41 This suggests that Scto2 may be useful for preoperative risk stratification as a biomarker. One of these studies observed significant associations between preoperative oxygen-supplemented Scto2, left ventricular ejection fraction, and biomarkers reflecting cardiovascular risk (high-sensitive troponin T, N-terminal pro b-type natriuretic peptide [NTproBNP]), all variables related to heart failure.39 Further studies have shown close correlations of the Scto2 signal with the mixed venous oxygen saturation (Svo2),41,42 suggesting that Scto2 may reflect systemic hemodynamics and systemic oxygen balance. Unfortunately, these observations have only been shown for 1 specific cerebral oximeter (INVOS) and it remains to be determined if these associations hold true if using other devices. We recommend intraoperative cerebral oximetry indexed to preinduction baseline to identify patients at increased risk of adverse outcomes after cardiac surgery (weak recommendation; LOE: C). Whether or not this risk stratification can be used to improve outcomes is not known.

Rapid, unilateral changes in Scto2 may indicate a regional cerebral malperfusion event. There are at least 16 published case reports of cerebral oximetry being utilized to detect various pathologies during management of antegrade cerebral perfusion, retrograde cerebral perfusion, and Takayasu arteritis, in addition to those due to failure of the cardiopulmonary bypass oxygenator, aortic dissection during cardiopulmonary bypass, surgical obstruction of the superior vena cava, and cerebral desaturation (compared to baseline) during anaphylaxis (among others, see Supplemental Digital Content, Table 2, https://links.lww.com/AA/D154).43–58 Of note, these case reports are not limited to a single device but are primarily limited to patients undergoing cardiac or major vascular surgery.

Additionally, several observational studies in patients undergoing cardiac as well as noncardiac surgery have shown that decrements in Scto2 from preoperative baseline were associated with adverse outcomes.41,59–67 Study objectives varied substantially, with the overwhelming number of investigations primarily focusing on the association between cerebral desaturation (compared to baseline) and cognitive outcomes (cognitive decline, delirium; Supplemental Digital Content, Table 3, https://links.lww.com/AA/D154). However, despite the association between cerebral desaturation (compared to baseline) and adverse cognitive outcomes in the majority of studies, the lack of clear Scto2 threshold cutoff values that are reproducibly associated with adverse neurological outcomes, the methodology of the tests used, as well as the single-center nature of these studies make it difficult to draw firm conclusions from these observational and cohort studies.

In light of these data, during the final plenary POQI-6 session, the question was raised as to whether cerebral oximetry should be used universally during cardiovascular surgery after considering the capability of this technology to detect potentially catastrophic perioperative events. The plenum felt that the evidence presently available (only based on case reports) does not justify such a general recommendation. However, the group acknowledged that the use of multiple other standard monitoring modalities (ie, pulse oximetry) is similarly not supported by scientific proof of an outcome benefit. Indeed, the most recent Cochrane analysis which analyzed 5 trials including 22,992 patients concluded that there was “no evidence that pulse oximetry affects the outcome of anesthesia for patients.”68 In that context, we recommend using cerebral oximetry to identify and guide management of acute cerebral malperfusion during cardiac surgery (weak recommendation; LOE: D).

Figure.
Figure.:
The utility of cerebral oximetry in the perioperative period: cerebral oximetry may be useful both preoperatively (prediction of adverse outcomes) and intraoperatively (reduction in adverse outcomes). There are insufficient data to recommend the use of cerebral oximetry postoperatively. ICU indicates intensive care unit; Sco 2, cerebral oxygen saturation. Reproduced with permission from Perioperative Quality Initiative (POQI). For permission requests, contact [email protected].

For a visual summary of when and how cerebral NIRS might be used clinically based on available evidence, see the Figure.

Can Using a NIRS-Guided Interventional Algorithm Reduce Perioperative Complications After Surgery?

While individual case reports of cerebral malperfusion detected by cerebral oximetry are compelling, the most important question related to the use of cerebral oximetry is whether or not incorporation of Scto2 into perioperative management strategies can lead to an improvement in clinical outcomes in a broader population of patients. Taking into account the association of the Scto2 signal with systemic oxygen balance and cardiopulmonary function mentioned above, as well as multiple meta-analyses showing that goal-directed measures to improve systemic oxygen balance may improve outcomes from high-risk surgery,69–71 this appears plausible. Two recent meta-analyses were performed to address these questions based on randomized controlled trials (RCTs), including one by the Cochrane Group.72,73 Zorrilla-Vaca et al72 identified 15 studies comprising 2057 patients and Yu et al73 identified 15 RCTs comprising 1822 participants. The average study in these meta-analyses included approximately 130 subjects, which should give the reader caution when interpreting the conclusions. Additionally, the low quality of the available evidence is a particular focus of the Cochrane report.

With those caveats noted, on the question of intensive care unit (ICU) length of stay (LOS), both meta-analyses appear to agree that use of NIRS resulted in a benefit. Zorrilla-Vaca et al72 found a 0.21-day reduction in ICU LOS based on pooled analysis of 8 studies including 1300 patients.70 Yu et al73 analyzed normally and nonnormally distributed LOS data separately (studies with nonnormally distributed data were not pooled for analysis) and reported a 0.29-day reduction in ICU LOS in the normal data (379 subjects).71 We recommend using an intraoperative cerebral oximetry–guided interventional algorithm to reduce ICU LOS after cardiac surgery (weak recommendation; LOE: C).

Regarding mortality and organ-specific morbidity, the rarity of clinically significant events coupled with the small size of published studies severely limits interpretation of the available data. Further, when using a cerebral oximetry–guided interventional algorithm, it remains uncertain, which intervention may ultimately influence outcome (eg, raising blood pressure, altering Paco2, or increasing fraction inspired oxygen [Fio2]). In the studies examined by Yu et al,73 only 3 deaths occurred, and the authors concluded that “We are uncertain whether active cerebral oxygenation monitoring has a crucial effect on intraoperative or postoperative deaths because there was a low number of events and the result was not precise.”71 Similarly, with regards to stroke, the authors determined that “We are uncertain whether active cerebral NIRS monitoring has an important effect on the risk of postoperative stroke because of the low number of events and wide confidence interval.” Based on this analysis and our own interpretation of the data, it is our conclusion that there is insufficient evidence to recommend using intraoperative cerebral oximetry to reduce mortality or organ-specific morbidity after cardiac surgery.

It should be noted that the majority of cerebral oximetry studies have been conducted in patients undergoing cardiac surgery (Supplemental Digital Content, Table 4, https://links.lww.com/AA/D154). While there are some small RCTs using cerebral oximetry74 and muscle oximetry (not the topic of this review)75 in noncardiac surgery,76 as well as studies demonstrating the use of cerebral oximetry during surgical procedures in which the head is elevated (eg, shoulder arthroscopy),17 there is insufficient evidence to recommend using intraoperative cerebral oximetry to improve outcomes after noncardiac surgery.

Future Research Questions

As noted above, the current data concerning the use of NIRS are overwhelmingly in the cardiac surgical population and the overall quality of the data is low. Furthermore, debate remains which Scto2-derived variables are most useful (eg, absolute values, minimum values, area under the preoperative baseline). Accordingly, a number of important questions remain that should guide future research and development.

First, what are the real limits of cerebral autoregulation and can they be known on an individual basis to help guide management? Identifying the limits of cerebral autoregulation (through correlations of changes in CBF with changes in cerebral perfusion pressure) may help target blood pressure goals for individual patients. Cerebral oximetry values are an important and noninvasive component of these methodologies. Over short periods of time, changes in cerebral oximetry values have been used as a surrogate for changes in CBF, with the assumption that several determinants of the cerebral oximetry value (eg, hemoglobin, neuronal metabolic activity, and arterial oxygen saturation) are stable in these short periods. Several observational studies have demonstrated that the time and magnitude of blood pressure below the lower limit of autoregulation (as identified by these NIRS-based methodologies) have been associated with acute kidney injury and other major morbidity and mortality after cardiac surgery.77,78 However, it is unclear if these methodologies can be used to optimize intraoperative blood pressure control to improve postoperative outcomes, and a trial is ongoing to answer this question.79

Second, could Scto2 be used in place of Svo2 (as measured by a Swan-Ganz catheter or from a sample drawn from a central venous catheter)? As described above, NIRS-derived cerebral oxygenation reflects not only cerebral but also systemic oxygen balance, shows moderate to good correlations with Svo2, and has been shown to be significantly associated with biomarkers of cardiopulmonary function. Thus it has been suggested that the brain-derived NIRS signal may be used as an index for systemic perfusion,80 with the caveat that CBF is prioritized and may not exactly mimic blood flow to other major organ systems. Expanding this concept, Scto2 monitoring combined with stroke volume or cardiac output determinations by uncalibrated pulse-contour and/or echocardiography might be used as a non- or less invasive substitute for the Swan-Ganz catheter for perioperative hemodynamic optimization69 in moderate-risk patients in which more sophisticated and invasive monitoring modalities are clinically impractical (ie, for hemodynamic management outside high dependency units).

Third, NIRS technology can also be used to measure somatic tissue oxygen saturation. Although discrepancies between intraoperative Scto2 and somatic tissue oxygen saturation measurements have been described,81 such emerging approaches may prove useful in the future.

Fourth, in addition to autoregulation (described above), there are other emerging enhancements of NIRS technology which, while not yet Food and Drug Administration-approved, deserve further study given their potential to improve outcomes. Diffuse correlation spectroscopy is a related and complimentary optical technique which provides an index of blood flow.82 Combination of indocyanine green injection with NIRS has been shown to accurately measure CBF when compared to perfusion magnetic resonance imaging and blood flow information may complement tissue oxygenation.83 Also promising is the European BabyLux project, which has combined time-resolved NIRS (requiring the use of lasers) and diffuse correlation spectroscopy devices into 1 machine that can measure absolute deoxyhemoglobin and oxyhemoglobin concentrations (and thus true Scto2, as opposed to relative Scto2) as well as information on the cerebral metabolic rate of oxygen consumption (CMRo2).84 Use of “broadband” NIRS, while technically challenging, may provide information on the oxidation state of cytochrome aa3, the terminal component of the electron transport chain (which reflects the balance of oxygen supply and demand at the tissue level).85

Finally, what is the actual value, if any, to the patient and health care system with the use of cerebral oximetry in the perioperative period? Economic and value-based outcome studies are required to address these important issues.

Limitations

Our approach has several limitations. First, our consensus group did not include experts in cerebral diffuse optical spectroscopy and other technical aspects potentially relevant to cerebral oximetry technology. However, experts from anesthesiology, surgery, and critical care medicine commented on the clinical application of this technology. Second, our literature search relied only on PubMed and hence may have missed important literature. However, in addition to making the literature search feasible for every workgroup member, using data sources beyond PubMed has been reported to only confer a modest impact on the results of systematic reviews.86 Finally, available NIRS devices have evolved over the years and some of the studies presented may have used devices no longer being produced. However, this advancement in technology preceding clinical studies is inherent to many aspects of clinical monitoring in perioperative medicine.

SUMMARY

Cerebral oximetry is a promising technology that addresses a relatively common and potentially catastrophic event—neurologic injury after cardiac surgery. In theory, cerebral oximetry can give the clinician insight into the oxygenation of arterial, capillary, and venous blood in a specific brain region, as opposed to pulse oximetry which only monitors arterial blood.

However, cerebral oximetry is a complex technology and its proper use requires knowledge of how Scto2 is calculated as well as which patient-specific and perioperative variables can impact its measurement. Patients with low preoperative Scto2 values tend to have worse clinical outcomes and intraoperative Scto2 desaturations (indexed to baseline) are associated with worse outcomes. Additionally, there are multiple case reports describing the use of Scto2 to identify catastrophic intraoperative malperfusion events. There is no high-quality evidence available to support the widespread use of Scto2-based management algorithms for the reduction of cerebral complications after cardiac surgery. While we recommend the use of intraoperative Scto2 because of its demonstrated ability to detect potentially catastrophic intraoperative malperfusion events, given the lack of higher-quality evidence, as well as the potential for overdiagnosis, the ultimate determination regarding adoption must be based on an institutional-specific cost-benefit analysis.

CONTRIBUTORS

Perioperative Quality Initiative (POQI) 6 Workgroup participants: POQI chairs: Matthew D. McEvoy, MD, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN; Timothy E. Miller, MD, Department of Anesthesiology, Duke University Medical Center, Durham, NC; Tong Joo Gan, MD, MHS, FRCA, MBA, Department of Anesthesiology, Stony Brook University, Stony Brook, NY. Postoperative Delirium Workgroup: Christopher G. Hughes, MD, MS, Department of Anesthesiology, Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center and the Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN; Christina S. Boncyk, MD, Department of Anesthesiology, Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Vanderbilt University Medical Center; Nashville, TN; Deborah J. Culley, MD, Department of Anesthesiology, Perioperative and Pain Medicine; Harvard Medical School, Boston, MA; Lee A. Fleisher, MD, Department of Anesthesiology and Critical Care, Penn Center for Perioperative Outcomes Research and Transformation, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Jacqueline M. Leung, MD, MPH, Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA; David L. McDonagh, MD, Departments of Anesthesiology and Pain Management, Neurological Surgery, and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX. Electroencephalogram Workgroup: Matthew T. V. Chan, MB, BS, PhD, FHKCA, FANZCA, FHKAM, Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China; Traci L. Hedrick, MD, MS, Department of Surgery, University of Virginia Health System, Charlottesville, VA; Talmage D. Egan, MD, Department of Anesthesiology, University of Utah School of Medicine, Salt Lake City, UT; Paul Garcia, MD, PhD, Department of Anesthesiology, Columbia University, New York, NY; Susanne Koch, MD, Department of Anaesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin, Berlin, Germany; Patrick L. Purdon, PhD, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, and Department of Anesthesia, Harvard Medical School, Boston, MA; Michael A. Ramsay, MD, FRCA, Department of Anesthesiology and Pain Management, Baylor University Medical Center, Dallas, TX. Spectroscopy Workgroup: Robert H. Thiele, MD, Divisions of Cardiac, Thoracic, and Critical Care Anesthesiology, Departments of Anesthesiology and Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA; Andrew Shaw, MB, FRCA, FFICM, FCCM, MMHC, Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada; Karsten Bartels, MD, PhD, Departments of Anesthesiology, Medicine, and Surgery, University of Colorado, Aurora, CO; Charles Brown, MD, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD; Hilary Grocott, MD, FRCPC, FASE, Department of Anesthesiology, Perioperative and Pain Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Matthias Heringlake, Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Germany, Lübeck, Germany.

DISCLOSURES

Name: Robert H. Thiele, MD.

Contribution: This author helped served as the chair of NIRS workgroup and helped with conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content.

Conflicts of Interest: R. H. Thiele has received funding from NIH/NIGMS (K08GM115861).

Name: Andrew D. Shaw, MB, FRCA, FFICM, FCCM, MMHC.

Contribution: This author helped served as cochair of NIRS workgroup and helped with conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content.

Conflicts of Interest: A. D. Shaw is a consultant for Edwards Lifesciences, FAST BioMedical, and Astellas.

Name: Karsten Bartels, MD, PhD.

Contribution: This author helped with conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content.

Conflicts of Interest: K. Bartels has received funding from NIH/NIDA (K23DA040923).

Name: Charles H. Brown IV, MD, MHS.

Contribution: This author helped with conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content.

Conflicts of Interest: C. H. Brown IV has received funding from NIH/NIA (K76AG057020) and has consulted for and has a data share agreement with Medtronic.

Name: Hilary Grocott, MD, FRCPC, FASE.

Contribution: This author helped with conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content.

Conflicts of Interest: H. Grocott is editor in chief of the Canadian Journal of Anesthesia and has funding from Canadian Institutes of Health Research (CIHR) investigating transfusion triggers in cardiac surgery (TRICS-III).

Name: Matthias Heringlake, MD.

Contribution: This author helped with conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content.

Conflicts of Interest: M. Heringlake reports honoraria for lectures and scientific advice by Covidien/Medtronic and scientific support by CAS Medical systems.

Name: Tong Joo Gan, MD.

Contribution: This author helped with organization of the conference, conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content.

Conflicts of Interest: T. J. Gan is a consultant for Acacia, Edwards Lifesciences, Mallinckrodt, Medtronic, and Merck.

Name: Timothy E. Miller, MB, ChB, FRCA.

Contribution: This author helped with organization of the conference, conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content.

Conflicts of Interest: T. E. Miller receives research grant and is a consultant for Edwards Lifesciences.

Name: Matthew D. McEvoy, MD.

Contribution: This author helped with organization of the conference, conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content.

Conflicts of Interest: M. D. McEvoy receives research grants from Edwards Lifescience, Cheetah Medical, Tennessee Department of Health, and GE Foundation—all unrelated to this study.

This manuscript was handled by: Gregory J. Crosby, MD.

FOOTNOTE

aThe scientific term EMR has been chosen instead of the more common term “light,” since by definition “light” is something visible, and the NIRS technology is also based on “invisible” radiation in the infrared range.

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