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Cerebral Oximetry During Cardiac Surgery: The Association Between Cerebral Oxygen Saturation and Perioperative Patient Variables
Cerebral Oximetry During Cardiac Surgery: The Association Between Cerebral Oxygen Saturation and Perioperative Patient Variables Ioanna Apostolidou, MD,* Greg Morrissette, MD,† Muhammad F. Sarwar, MD,‡ Mojca R. Konia, MD,* Vibhu R. Kshettry, MD, FACS, FRCS,† Joyce A. Wahr, MD,§ Aaron A. Lobbestael, MS,储 and Nancy A. Nussmeier, MD‡ Objective: This “real-world” study was designed to assess the patterns of regional cerebral oxygen saturation (rSO2) change during adult cardiac surgery. A secondary objective was to determine any relation between perioperative rSO2 (baseline and during surgery) and patient characteristics or intraoperative variables. Design: Prospective, observational, multicenter, nonrandomized clinical study. Setting: Cardiac operating rooms at 3 academic medical centers. Participants: Ninety consecutive adult patients presenting for cardiac surgery with or without cardiopulmonary bypass. Interventions: Patients received standard care at each institution plus bilateral forehead recordings of cerebral oxygen saturation with the 7600 Regional Oximeter System (Nonin Medical, Plymouth, MN). Measurements and Main Results: The average baseline (before induction) rSO2 was 63.9 ⴞ 8.8% (range 41%-95%);
preoperative hematocrit correlated with baseline rSO2 (0.48% increase for each 1% increase in hematocrit, p ⴝ 0.008). The average nadir (lowest recorded rSO2 for any given patient) was 54.9 ⴞ 6.6% and was correlated with on-pump surgery, baseline rSO2, and height. Baseline rSO2 was found to be an independent predictor of length of stay (hazard ratio 1.044, confidence interval 1.02-1.07, for each percentage of baseline rSO2). Conclusions: In cardiac surgical patients, lower baseline rSO2 value, on-pump surgery, and height were significant predictors of nadir rSO2, whereas only baseline rSO2 was a predictor of postoperative length of stay. These findings support previous research on the predictive value of baseline rSO2 on length of stay and emphasize the need for further research regarding the clinical relevance of baseline rSO2 and intraoperative changes. © 2012 Elsevier Inc. All rights reserved.
J
Despite the growing volume of literature on the utility of cerebral oximetry, uncertainty exists as to what can be considered the normal range for cerebral saturation at baseline or at critical stages of cardiac surgical procedures or what change from baseline should be tolerated. The authors designed this prospective observational study as a “real-world” study of rSO2 change during cardiac surgery. The cerebral oximetric device used was the EQUANOX Model 7600 Regional Oximeter System with the 8000CA Sensor (Nonin Medical, Inc, Plymouth, MN), which computes cerebral blood oxygen saturation using 2 light-emitting diodes and a dual-detector topology (Fig 1) that uses 3 wavelengths in each emitter (730, 810, and 880 nm). A common oximetric design is a single emitter with 2 detectors: 1 detector is spaced to capture light from the skull and skin only (short path, extracranial saturation) and the other detector is spaced to capture light from the skin, skull, and brain (long path, extra- and intracranial saturations). Subtracting the extracranial saturation from that of the longer path
ÖBSIS INTRODUCED cerebral oximetry in 1970, but its utility and validity were debated for many years.1 Questions raised included the apparent need to account for the length of the path of light in the Beer-Lambert equation, the lack of a gold standard against which to validate cerebral tissue oxygenation values, and a lack of data about the normal versus abnormal parameters of cerebral tissue saturation.2 Advances in the basic science knowledge of near-infrared spectroscopy have allowed the calculation of regional cerebral oxygenation (rSO2) without a precise knowledge of the path length of light.3-5 Likewise, the scientific community has come to accept the calculated arteriovenous saturation (calculated as 70% jugular bulb venous saturation and 30% arterial saturation) as a reasonable gold standard against which to measure the accuracy of cerebral oximeters. The current cerebral oximeters have been validated against this standard.6 Although the correlation between arteriovenous saturation and rSO2 can be affected by bypass parameters (alpha-stat v pH-stat) and by significant changes in the partial pressure of arterial carbon dioxide even during off-pump surgery, steady-state values have been judged to correlate well.7-10 With the resolution of these issues, the use of cerebral oximetry has expanded significantly and is emerging as a useful monitoring device. Numerous case reports and case series have highlighted the ability of cerebral oximetry to alert clinicians to catastrophic events.11-14 Other studies have shown that postoperative outcomes can be predicted by baseline rSO2 or intraoperative changes.15-21 Changes in cerebral oximetry have been shown to occur in the absence of changes in arterial saturation or systemic hemodynamic parameters, evidence that rSO2 provides unique data for clinicians.22-25 Most significantly, in 2 prospective trials, patients randomized to an active display of rSO2 and interventions to correct low rSO2 values during cardiac surgery or abdominal surgery had a lower incidence of postoperative adverse events.22,26
KEY WORDS: cerebral oximetry, cardiac surgery, cerebral oxygen saturation, oximetry, outcomes
From the *Department of Anesthesiology, University of Minnesota, Minneapolis, MN; †Abbott Northwestern Hospital, Minneapolis Heart Institute, Minneapolis, MN; ‡Department of Anesthesiology, SUNY Upstate Medical University, Syracuse, NY; §Department of Anesthesiology, University of Michigan, Ann Arbor, MI; and 储Nonin Medical, Inc, Plymouth, MN. Funding for this study was provided by Nonin Medical, Plymouth, MN. Address reprint requests to Ioanna Apostolidou, MD, Department of Anesthesiology, University of Minnesota, B-515 Mayo Memorial Building, Mayo Mail Code 294, 420 Delaware Street SE, Minneapolis, MN 55455. E-mail: [email protected] © 2012 Elsevier Inc. All rights reserved. 1053-0770/2606-0008$36.00/0 http://dx.doi.org/10.1053/j.jvca.2012.07.011
Journal of Cardiothoracic and Vascular Anesthesia, Vol 26, No 6 (December), 2012: pp 1015-1021
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Fig 1. Schematic of the 8000CA Sensor. (A) The sensor contains 2 light-emitting diodes, each generating 3 near-infrared spectroscopic wavelengths; and 2 detection sensors, each separated from the next optode by a distance of 20 mm. (B) Measurements from the emitters to the closer detector (20 mm) represent shallow (extracranial) tissue saturation; measurements from emitters to farther detectors (40 mm) represent shallow (extracranial) and deep (intracranial) tissue saturations. (Color version of figure is available online.)
(intracranial and extracranial saturations) is assumed to isolate intracranial oxygen saturation.7 With such a design, any difference in the optical properties of the skull and forehead beneath the near versus far detector will influence the calculated intracranial saturation measurement. The 8000CA Sensor has dual emitters and dual detectors, with the long and short paths reversed for each emitter, causing the skull and forehead optical differences associated with each detector to be canceled out. This sensor has been validated in laboratory studies27 and recently has been reported to have less interference from extracranial tissue than the Foresight and the INVOS oximeters.28 This prospective, observational study was designed to collect data about rSO2 changes during cardiac surgery, to examine their temporal distribution, and to determine the percentage of available time data. Also examined were the relations of rSO2 (at baseline and during cardiac surgery) to patient characteristics and intraoperative variables. METHODS This study was a prospective, observational, multicenter, nonrandomized, clinical study of the use of cerebral oximetry in patients undergoing cardiac surgery at 1 of 3 academic medical centers: University of Minnesota, Minneapolis Heart Institute, and SUNY Upstate Medical University. The institutional review board of each participating institution approved the study protocol and all enrolled patients gave written informed consent. Consecutive patients presenting for cardiac surgery with or without cardiopulmonary bypass (CPB) were eligible for enrollment. Inclusion
criteria included patients of either sex who were ⬎18 years of age, who weighed ⱖ40 kg, and who were able to read and communicate in English. Exclusion criteria were an emergency procedure, use of methylene blue or other intravenous dyes ⱕ24 hours of surgery, and a pre-existing skin condition at the site of the anticipated sensor placement. All patients received general endotracheal anesthesia, including a volatile agent, opioids, muscle relaxants, and benzodiazepines, according to standard practice at each institution. Invasive monitoring, including arterial pressure and central venous pressure, was used in all patients. The decision to use a pulmonary artery catheter and transesophageal echocardiography was guided by clinical judgment. Cerebral oximetric sensors were placed on each side of the patient’s forehead before anesthesia induction for continuous, real-time monitoring of rSO2 during surgery (8000CA Sensor, Nonin Medical). No light shields were required or used. The derived rSO2 values were displayed on the monitor and simultaneously recorded in the monitor memory. Use of the cerebral oximetric data for clinical decision-making was at the clinician’s judgment and was not driven by a protocol. Signal losses, interruptions, and dropout rates were recorded, as were possible causes of signal loss and steps taken to restore recordings. Event markers were added to the electronic cerebral oximetric data file and noted on the case-report forms. Predefined noted events included baseline, induction of anesthesia, intubation, skin incision, aortic cannulation, initiation of CPB, initiation of cooling, aortic cross-clamp application and removal, initiation of active rewarming, placement of the side-biter clamp, end of CPB, after protamine, and skin closure. On-pump cases used nonpulsatile moderate hypothermic CPB. Perfusion was maintained at pump flows of 2.2-2.4 L/min/m2 to maintain a mean arterial pressure at 50-80 mmHg. Arterial blood gases were measured at 15-30 minutes on CPB to maintain the partial pressure of arterial carbon dioxide at 35-40 mmHg using alpha-stat correction and partial pressure of arterial oxygen at 150-250 mmHg. Red blood cells were transfused to maintain hematocrit 22%-25% on CPB. Cold cardioplegia was administered for myocardial protection. Off-pump cases were conducted at normothermic temperatures. Systolic blood pressure was maintained at 100-130 mmHg. Arterial blood gases were measured at 30-minute intervals to maintain the partial pressure of arterial carbon dioxide at 35-40 mmHg and the partial pressure of arterial oxygen at ⬎150 mmHg. Red blood cells were transfused to maintain hematocrit at 27%-30% throughout the case. Demographic information, anthropometric data, pertinent cardiac history, and comorbidities were recorded before the surgery. Hospital length of stay was extracted from the patient records. No follow-up visits were performed. The following parameters were computed from cerebral oximetric recordings and were analyzed: ● baseline rSO2 value for each patient, defined as the average of right and left rSO2 readings for ⱖ30 seconds before induction ● nadir rSO2 value for each patient, defined as that patient’s minimum rSO2 value from intubation to skin closure ● changes of rSO2 value at predefined critical stages of the surgical procedure ● incidence and characteristics of patients with any rSO2 value ⬍25% of their baseline value ● incidence and characteristics of patients with any absolute rSO2 value ⬍50% saturation Major study endpoints included device performance and registration rate, rSO2 change from baseline, and nadir rSO2 during the procedure. Registration rate was determined as the percentage of time during surgery that a reading was available. The cerebral oximetric system collected and recorded an rSO2 value every 4 seconds; over the course of 100 seconds, 25 values would be expected. If a single value could not be calculated or recorded, the registration rate would be 96%. A registration rate of ⱖ90% was predefined as acceptable.
CEREBRAL OXIMETRY DURING CARDIAC SURGERY
Secondary objectives were the identification of predictors of baseline rSO2, nadir rSO2, rSO2 values ⬍25% from baseline, and an absolute rSO2 value ⬍50%. Statistical analysis was performed with SAS 9.1 (SAS Inc, Cary, NC). Continuous variables were presented with the mean or median, as appropriate, standard deviation, range, and number of observations. Categoric or discrete variables were presented as fraction and percentage. All data collected were analyzed; imputation methods were not used for missing data. No formal hypothesis testing was planned; summary statistics were generated across the sample. Saturation values for each patient at each event point were averaged across the right and left channels. Differences between rSO2 values across the surgery were analyzed using analysis of variance for normally distributed results or the Kruskal-Wallis test for non-normally distributed results. Normality was tested with the Kolmogorov-Smirnov test. Relations between baseline rSO2 and nadir rSO2 and potential categoric predictors were determined using analysis of variance. Relations among baseline rSO2 and nadir rSO2 and potential continuous predictors were determined using linear regression. Logistic regression was used to determine the relation between categoric endpoints (decrease ⬍25% of baseline rSO2 and decrease below an rSO2 value of 50% saturation) and categoric and continuous predictors. Multivariate models were built by incorporating all variables with a univariate significance of ⬍0.1. Assessment of length of stay was performed using Cox proportional hazards regression. A p value ⬍0.05 was considered to indicate a statistically significant difference. RESULTS
Ninety patients, 30 at each institution, were enrolled from August 2009 through July of 2010 and all patients completed the study. Of the 90 patients enrolled, 4 had corrupted electronic files and in 1 patient the clock times were not synchronized. Eighty-five patients were included in the baseline rSO2 analysis. In addition, end-of-surgery time was not available in 1 patient; 84 patients were included in the nadir rSO2 and rSO2 ⬍50% analyses. Demographic and baseline characteristics are presented in Table 1; surgical details are presented in Table 2. There were differences among sites, in that SUNY performed 52% cases (13/30) off-pump, whereas the Minneapolis Heart
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Table 2. Surgical Details Parameter (Patients With Data)
Surgery performed off-pump Type of surgery (n ⫽ 85) Bypass grafting only Valve only Bypass graft and valve Neither Hematocrit Preoperative (n ⫽ 85) Postoperative (n ⫽ 57)* Serum creatinine Preoperative (n ⫽ 84)* Postoperative (n ⫽ 66)* Duration of surgery (minutes) (n ⫽ 84)† Bypass time (minutes) (n ⫽ 66)‡
Results
16/85 (19%) 40/85 (47%) 33/85 (39%) 6/85 (7%) 6/85 (7%) 39.0 (25.9-49.9) 32.1 (25.1-41.3) 1.0 (0.5-5.6) 1.0 (0.5-4.6) 309 (83-575) 122 (15-345)
NOTE. Data are presented as number/total (percentage) or median (range). *Values not available in all patients. †Duration of surgery unknown in 1 patient because of missing end-of-surgery time. ‡No bypass in off-pump cases (n ⫽ 16; initiation of bypass/end of bypass not indicated in 3 on-pump patients).
Institute and University of Minnesota each performed ⬍10% of their cases off-pump (Fisher exact test, p ⬍ 0.0001). As noted earlier, registration rates could not be calculated in 5 patients. In the remaining 85 patients, 420 hours 34 minutes were recorded during this study, and rSO2 readings were recorded for 96% of this time on ⱖ1 channel and on the 2 channels for 93% of the time. Baseline readings ranged from 41% to 95% and averaged 63.9 ⫾ 8.8% (Fig 2). Five patients had baseline rSO2 readings ⱕ50% and 29 had baseline readings ⬍60%. A univariate relation was observed between baseline rSO2 and body mass
Table 1. Demographic and Baseline Risk Factors of Enrolled Patients Age (y) Male sex Race* African American Hispanic White Other Current smoker† Height (cm) Weight (kg) Body mass index (kg/m2) Prior cardiac surgery Diabetes Cerebrovascular disease Preoperative dialysis
61.5 ⫾ 13.1 56/85 (66%) 6/85 (7%) 2/85 (2%) 77/85 (91%) 2/85 (2%) 13/84 (16%) 172 ⫾ 10.2 90.8 ⫾ 20.6 30.0 ⫾ 7.2 14/85 (16%) 32/85 (38%) 4/85 (5%) 2/85 (2%)
NOTE. Data are presented as mean ⫾ standard deviation or number/total (percentage). *In 2 patients, multiple race categories were noted. †Status not available in 1 patient.
Fig 2. Histogram of baseline regional cerebral oxygen saturation (rSO2) values. Individual patients and their specific baseline regional cerebral oxygen saturation values are noted on the x-axis just below the histogram bars. Seven patients had baseline values <55%.
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Table 3. Multivariate Relation Between Patient Characteristics and Nadir Regional Cerebral Oxygen Saturation Parameter
Relation to Nadir rSO2*
95% CI
p
Age Height Baseline rSO2 On-pump surgery
1-y increase ⫺0.09% 1-cm increase 0.17% 1% increase 0.29% ⫺4.64%
⫺0.18 to ⫺0.006 0.02-0.33 0.13-0.44 7.86-1.43
0.036 0.028 0.0005 0.005
Abbreviations: CI, confidence interval; rSO2, regional cerebral oxygen saturation. *Relations are presented as coefficients (slopes for age, height, and baseline rSO2 and effect for on-pump surgery) from multiple linear regressions and are adjusted for weight, preoperative hematocrit, smoking status, and sex. A negative number indicates a lower nadir value (eg, 1 additional year of age resulted in a 0.09% lower nadir rSO2). Positive estimates indicate a higher nadir value. The minimum rSO2 for a nonsmoking 60-year-old woman, with a body mass index of 31.1 kg/m2, weight of 90 kg, height of 170 cm, preoperative hematocrit of 38, and preoperative creatinine of 1 off-pump, was 40% (eg, model intercept).
index (BMI; p ⫽ 0.05), weight (p ⫽ 0.03), baseline hematocrit (p ⬍ 0.0001), baseline creatinine (p ⫽ 0.002), diabetes (p ⫽ 0.01), and cerebral vascular disease (p ⫽ 0.03). Increases in BMI, baseline hematocrit, and weight were associated with higher baseline rSO2 values, whereas increased creatinine was associated with lower baseline rSO2. Patients with diabetes had significantly lower baseline rSO2 readings than those without (60.8 ⫾ 7.4% v 65.8 ⫾ 9.2%, p ⫽ 0.01) and had lower baseline hematocrit (37.3 ⫾ 5.0% v 40.0 ⫾ 5.5%; analysis of variance, p ⫽ 0.022). A multivariate model was developed that included institution, diabetes, cerebrovascular disease, weight, BMI, baseline creatinine, and baseline hematocrit. In this model, only preoperative hematocrit was an independent predictor of baseline rSO2, where each 1% increase in hematocrit was related to a 0.48% increase in baseline rSO2 (p ⫽ 0.008). The average individual nadir rSO2 was 54.9 ⫾ 6.6 (range 40.0-76.5). Increasing age, lower baseline rSO2, and on-pump surgery were related to lower nadir rSO2 values; increasing weight, height, and hematocrit were related to higher nadir values. As presented in Table 3, age, on-pump surgery, baseline rSO2, and height remained statistically significant predictors of nadir rSO2 in a multivariate analysis. Nine of 84 patients (11%) exhibited a decrease ⬍25% of their baseline value ⱖ1 time during surgery, and 14/84 exhibited an absolute value ⬍50% rSO2. All 9 patients whose rSO2 decreased ⬍25% of baseline were on-pump patients, and all but 1 of the patients whose rSO2 decreased to ⬍50% were on-pump surgical patients. No relations between baseline or surgical characteristics and a decrease ⬍25% of baseline were detected. Height, weight, and preoperative hematocrit were statistically significant independent predictors of an absolute rSO2 value decreasing ⬍50% (Table 4). On-pump versus off-pump surgery was not correlated with an rSO2 ⬍50%.
Figure 3 shows the pattern of rSO2 changes at the critical predefined points during the surgical procedure of on-pump and off-pump patients. In on-pump cases, values below baseline were observed at all CPB points, including placement and removal of aortic clamps (cross-clamp and side-biter). In offpump cases, lower values were observed during side-biter placement and removal. In a multivariate model, only baseline rSO2 was found to be an independent predictor of length of stay (hazard ratio 1.044, confidence interval 1.02-1.07, p ⫽ 0.0017). Each percentage decrease in baseline rSO2 increased the length of stay by a factor of 1.044 (p ⫽ 0.0017). DISCUSSION
These data indicate that the EQUANOX system reliably can provide rSO2 data throughout cardiac surgery, with values provided for ⬎96% of the time. A higher preoperative hematocrit was associated with a higher baseline rSO2 and with a lower risk of a decreasing rSO2 absolute value ⬍50%. Furthermore, younger, taller patients and those with higher baseline rSO2 had higher nadir values. A lower baseline rSO2 was associated with a longer hospital stay. The authors found no published data for registration rates with other cerebral oximetric systems, so they cannot provide a direct comparison. A sophisticated study of pulse oximeters found that the percentage of time the display is blanked out (ie, values calculated, but not displayed) varies among manufacturers, with the Nellcor 3000 at 5.9% of the time, the Agilent CMS A.0 3.6% of the time, and the Masimo 2.3% of the time.29 Dropout times (unable to calculate a value) for pulse oximeters also vary, with the Agilent CMS A.0 at 6.4% of the time and Masimo 3.0% of the time.29 The registration rates for the EQUANOX system appear to be comparable, although caution
Table 4. Multivariate Predictors of an Absolute Regional Cerebral Oxygen Saturation <50% Parameter
Relation to rSO2 ⬍50%*
95% CI
p
Height (cm) Weight (kg) Preoperative hematocrit (%)
OR 0.87 per 1-cm increase OR 0.96 per 1-kg increase OR 0.85 per 1% increase
0.784-0.967 0.928-0.998 0.741-0.981
0.0095 0.038 0.026
Abbreviations: CI, confidence interval; OR, odds ratio; rSO2, regional cerebral oxygen saturation. *Relations are presented as ORs from multivariate logistic regression and estimate the effect on the predicted probability of an rSO2 ⬍50%. The estimates also are adjusted for sex. An OR ⬍1 indicates a lower likelihood of a decrease ⬍50% for each one.
CEREBRAL OXIMETRY DURING CARDIAC SURGERY
Fig 3. Average change from baseline of regional cerebral oxygen saturation (rSO2) values at specific points during the surgical procedure of (A) on-pump and (B) off-pump patients. SD, standard deviation; X-clamp, cross-clamp.
is advised because pulse oximetry and cerebral oximetry are considerably different. This study examined the use of a relatively new cerebral oximeter, the EQUANOX system with the 8000CA Sensor, in the setting of cardiac surgery. The EQUANOX system with this sensor has been validated in a laboratory setting, and has been shown to provide relative accuracy, similar to the INVOS system.6,27 The design of the 8000CA Sensor uses a dualemitter and dual-detector topology, which may decrease contamination by extracranial absorbance.28 A recent evaluation of 3 cerebral oximetric systems showed that the displayed rSO2 value is altered when extracranial blood flow is eliminated using a tourniquet.28 All commercially available oximeters use different sensor designs and algorithms to generate a displayed
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value; such differences may result in different values for brain oxygenation. Further studies will be required to elucidate which sensor is the most accurate in clinical settings, such as the sensor reported here. This study used the 8000CA Sensor, which has been validated as a relative (trend) monitor, but not an absolute monitor. A second-generation Nonin sensor, the 8004CA, has been validated as an absolute monitor27 but was not available at the time of this study. Nearly one third of the present patients had rSO2 values ⬍60% before intubation, with 5% having baseline values ⱕ50%. These data showed a range of baseline values that are in agreement with those reported by Baikoussis et al30 and by Papadopoulos et al31 and somewhat higher than those found by Nauphal et al.10 In the present study population, diabetic patients had a significantly lower baseline rSO2, similar to the relation found by Baikoussis et al in patients scheduled for carotid endarterectomy.30 In a multivariate analysis, however, the authors found that only preoperative hematocrit correlated with baseline rSO2. A higher hematocrit, by maximizing oxygen delivery to the tissues, influences the balance between the brain oxygen supply and demand, resulting in a higher rSO2. The hematocrit is not the sole important variable in the balance equation but consistently has shown a strong association with rSO2 in published studies.17,30 The present data are similar to those of Kishi et al who found patient age and preoperative hematocrit to be correlated significantly with baseline rSO2 values.32 Few studies have examined which preoperative characteristics could predict which patients likely would develop low rSO2 values during surgery. The present results seem intuitive, ie, that older patients would have lower rSO2 values and that higher hemoglobin values would be correlated with higher baseline and higher nadir values. The authors also found that height, but not BMI, was a predictor of nadir values. This finding may be related to the complex relation among height, weight, and hematocrit; taller individuals tend to be men and men tend to have higher hematocrit levels. The calculated BMI can be deceptive because obese individuals of very different height and weight can have the same BMI. A simple weight ratio (milliliters per kilogram) has been found to be the least accurate predictor of plasma or erythrocyte volume; surface area calculations are more accurate.33 Further studies will be needed to understand this relation. The authors also found that on-pump surgery was associated with lower nadir values than off-pump surgery. Prior studies of cerebral oxygenation monitored by a jugular bulb catheter have shown that decreased jugular bulb saturation values tend to occur at rewarming.34 The lower hematocrit associated with CPB also could contribute to lower nadir values in on-pump than in off-pump patients. In a study of acute normovolemic hemodilution, Han et al found that cerebral desaturations were associated with hematocrit levels ⬍30%, a value common in on-pump cardiac patients.35 McCusker et al also found a correlation between on-pump hemodilution and rSO2 values, with a lower hematocrit associated with lower rSO2 values.36 The present finding that off-pump cardiac surgical patients had higher nadir rSO2 values and a lower incidence of decreases ⬍25% of baseline or an absolute rSO2 of ⬍50% seem to differ from those reported by Moritz et al who found that
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positioning of the heart for right coronary grafting in off-pump patients could result in significant decreases in rSO2, presumably owing to the decrease in ventricular filling and cardiac output associated with such positioning.37 The authors did not collect data about positioning of the heart during bypass and, thus, cannot compare these data. The question of what absolute value or relative change in rSO2 constitutes a need for intervention remains unclear, although recent data have provided some insights. De TournayJetté et al found that cardiac surgical patients who had an absolute nadir value of 50% or a relative change of 30% from baseline were at increased risk of postoperative cognitive decline.38 Hong et al did not observe any significant differences in the incidence or duration of decrease in rSO2 values between patients with and those without postoperative cognitive decline but did find that low rSO2 values were correlated with a longer stay.18 Heringlake et al found that an rSO2 of ⱕ50% (absolute) at baseline, despite supplemental oxygen, was an independent risk factor for 30-day survival.17 Fischer et al found that aortic arch surgical patients who spent ⬎30 minutes under an absolute value of 60% had an extended hospital stay of 4 days.15 Very few patients in this study spent any significant amount of time ⬍25% or ⬍50% of baseline, and the calculations for area under the curve did not show any significant relations with any baseline or intraoperative characteristics. However, despite a relatively small sample, the authors, like Heringlake et al17 and Hong et al,18 found a significant correlation between baseline rSO2 and length of stay, with lower baseline values predictive of longer hospitalization. The present study was not designed to identify the underlying pathophysiology that may have been responsible for the low baseline rSO2 values seen in some patients, and the authors do not suggest that a low rSO2 is a causative factor for a longer stay. However, a low baseline rSO2 (⬍50%-60%) may help identify patients who have more significant cardiopulmonary disease and are at risk of a prolonged hospital stay. The present study was not designed to test whether intervening to increase rSO2 would improve outcomes or shorten hospital stay, but other studies have tested those questions. Murkin et al found that patients monitored with cerebral oximetry and who had protocol-defined interventions intended to keep the rSO2 ⬎75% of the baseline value had decreased morbidity and mortality compared with patients whose anesthesiologist was blinded to the rSO2.26 In a similar study in abdominal surgical patients, Casati et al found that patients with active monitoring
and protocol-defined interventions to maintain the rSO2 ⬎75% of baseline had less severe desaturations.24 In patients whose rSO2 values decreased ⬍75% of baseline, postoperative mental status was worse in patients in the blinded group than in the monitored/intervention group, indicating that an intervention to correct rSO2 values ⬍75% of baseline can decrease adverse outcomes.24 Because of the differences in oximetric design, the thresholds identified by Murkin et al26 and Casati et al24 (⬍75% of baseline) may be different in other sensors, including the EQUANOX sensor used in this study. Limitations This study was designed as a “real-world snapshot” to provide insight into how cerebral oximetry performs in the clinical rather than the laboratory realm and to gather data on the range of rSO2 values seen in a cardiac surgical population. Although the authors found correlations between preoperative characteristics and baseline rSO2 values and correlations with the lowest rSO2 and absolute values of rSO2 ⬍50%, the sample was relatively small. In addition, this study was viewed as hypothesis generating, rather than hypothesis testing, so the authors could not ascertain whether the lack of correlation between some characteristics and rSO2 was a true absence of correlation or owing to a lack of statistical power. This study was not designed to test the utility of oximetric monitoring or to compare outcomes between patients managed with and without rSO2 monitoring. The authors did not control tightly the depth of anesthesia or end-tidal CO2, which can influence cerebral blood flow and, presumably, rSO2. The study population included onpump and off-pump surgeries, and this may have obscured some correlations. Furthermore, the operative practices differed among sites; the impact of these differences may have increased the variability further. CONCLUSIONS
These results provide further data on expected rSO2 values at baseline and across time in cardiac surgical patients at different institutions and provide confirmation of prior studies in the correlation between low baseline rSO2 and length of stay. In addition, the authors found that the EQUANOX system provides data ⬎95% of the time. Accumulating data on cerebral oximetry has allowed progress in defining the rSO2 values that represent “normal” or “abnormal” states, but larger population samples and more experience with this new monitoring modality will be required to define those parameters with confidence.
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5. Wyatt JS, Cope M, Delpy DT, et al: Measurement of optical path length for cerebral near-infrared spectroscopy in newborn infants. Dev Neurosci 12:140-144, 1990 6. Pollard V, Prough DS, DeMelo AE, et al: Validation in volunteers of a near-infrared spectroscope for monitoring brain oxygenation in vivo. Anesth Analg 82:269-277, 1996 7. Harilall Y, Adam JK, Biccard BM, et al: Correlation between cerebral tissue and central venous oxygen saturation during off-pump coronary bypass graft surgery. Perfusion 26:83-90, 2011 8. Baraka A, Naufal M, El-Khatib M: Correlation between cerebral and mixed venous oxygen saturation during moderate versus tepid hypothermic hemodiluted cardiopulmonary bypass. J Cardiothorac Vasc Anesth 20:819-825, 2006
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9. Yoshitani K, Kawaguchi M, Iwata M, et al: Comparison of changes in jugular venous bulb oxygen saturation and cerebral oxygen saturation during variations of haemoglobin concentration under propofol and sevoflurane anaesthesia. Br J Anaesth 94:341-346, 2005 10. Nauphal M, El-Khatib M, Taha S, et al: Effect of alpha-stat vs. pH-stat strategies on cerebral oximetry during moderate hypothermic cardiopulmonary bypass. Eur J Anaesthesiol 24:15-19, 2007 11. Cordisco M, Newberger J, Shann KG, et al: Diagnosis of inadvertent cannulation of the azygos vein during cardiopulmonary bypass. J Extra Corpor Technol 42:235-237, 2010 12. Fischer GW, Stone ME: Cerebral air embolism recognized by cerebral oximetry. Semin Cardiothorac Vasc Anesth 13:56-59, 2009 13. Han SH, Kim CS, Lim C, et al: Obstruction of the superior vena cava cannula detected by desaturation of the cerebral oximeter. J Cardiothorac Vasc Anesth 19:420-421, 2005 14. Scholl FG, Webb D, Christian K, et al: Rapid diagnosis of cannula migration by cerebral oximetry in neonatal arch repair. Ann Thorac Surg 82:325-327, 2006 15. Fischer GW, Lin HM, Krol M, et al: Noninvasive cerebral oxygenation may predict outcome in patients undergoing aortic arch surgery. J Thorac Cardiovasc Surg 141:815-821, 2011 16. Goldman S, Sutter F, Ferdinand F, et al: Optimizing intraoperative cerebral oxygen delivery using noninvasive cerebral oximetry decreases the incidence of stroke for cardiac surgical patients. Heart Surg Forum 7:E376-E381, 2004 17. Heringlake M, Garbers C, Käbler JH, et al: Preoperative cerebral oxygen saturation and clinical outcomes in cardiac surgery. Anesthesiology 114:58-69, 2011 18. Hong SW, Shim JK, Choi YS, et al: Prediction of cognitive dysfunction and patients’ outcome following valvular heart surgery and the role of cerebral oximetry. Eur J Cardiothorac Surg 33:560-565, 2008 19. Kazan R, Bracco D, Hemmerling TM: Reduced cerebral oxygen saturation measured by absolute cerebral oximetry during thoracic surgery correlates with postoperative complications. Br J Anaesth 103:811-816, 2009 20. Schoen J, Meyerrose J, Paarmann H, et al: Preoperative regional cerebral oxygen saturation is a predictor of postoperative delirium in on-pump cardiac surgery patients: A prospective observational trial. Crit Care 15:R218, 2011 21. Slater JP, Guarino T, Stack J, et al: Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg 87:36-44, 2009 22. Hemmerling TM, Bluteau MC, Kazan R, et al: Significant decrease of cerebral oxygen saturation during single-lung ventilation measured using absolute oximetry. Br J Anaesth 101:870-875, 2008 23. Murphy GS, Szokol JW, Marymont JH, et al: Cerebral oxygen desaturation events assessed by near-infrared spectroscopy during shoulder arthroscopy in the beach chair and lateral decubitus positions. Anesth Analg 111:496-505, 2010
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24. Casati A, Fanelli G, Pietropaoli P, et al: Continuous monitoring of cerebral oxygen saturation in elderly patients undergoing major abdominal surgery minimizes brain exposure to potential hypoxia. Anesth Analg 101:740-747, 2005 25. Green DW: A retrospective study of changes in cerebral oxygenation using a cerebral oximeter in older patients undergoing prolonged major abdominal surgery. Eur J Anaesthesiol 24:230-234, 2007 26. Murkin JM, Adams SJ, Novick RJ, et al: Monitoring brain oxygen saturation during coronary bypass surgery: A randomized, prospective study. Anesth Analg 104:51-58, 2007 27. Macleod DB, Ikeda K, Vacchiano C, et al: Development and validation of a cerebral oximeter capable of absolute accuracy. J Cardiothorac Vasc Anesth 26:1007-1014, 2012 28. Davie SN, Grocott HP: Impact of extracranial contamination on regional cerebral oxygen saturation: A comparison of three cerebral oximetry technologies. Anesthesiology 116:834-840, 2012 29. Kästle SW, Konecny E: Determining the artifact sensitivity of recent pulse oximeters during laboratory benchmarking. J Clin Monit Comput 16:509-522, 2000 30. Baikoussis NG, Karanikolas M, Siminelakis S, et al: Baseline cerebral oximetry values in cardiac and vascular surgery patients: A prospective observational study. J Cardiothorac Surg 5:41, 2010 31. Papadopoulos G, Karanikolas M, Liarmakopoulou A, et al: Baseline cerebral oximetry values in elderly patients with hip fractures: A prospective observational study. Injury 42:1328-1332, 2011 32. Kishi K, Kawaguchi M, Yoshitani K, et al: Influence of patient variables and sensor location on regional cerebral oxygen saturation measured by INVOS 4100 near-infrared spectrophotometers. J Neurosurg Anesthesiol 15:302-306, 2003 33. Retzlaff JA, Tauxe WN, Kiely JM, et al: Erythrocyte volume, plasma volume, and lean body mass in adult men and women. Blood 33:649-661, 1969 34. Hoover LR, Dinavahi R, Cheng WP, et al: Jugular venous oxygenation during hypothermic cardiopulmonary bypass in patients at risk for abnormal cerebral autoregulation: Influence of alpha-Stat versus pH-stat blood gas management. Anesth Analg 108:1389-1393, 2009 35. Han SH, Ham BM, Oh YS, et al: The effect of acute normovolemic haemodilution on cerebral oxygenation. Int J Clin Pract 58: 903-906, 2004 36. McCusker K, Chalafant A, de Foe G, et al: Influence of hematocrit and pump prime on cerebral oxygen saturation in on-pump coronary revascularization. Perfusion 21:149-155, 2006 37. Moritz S, Rochon J, Völkel S, et al: Determinants of cerebral oximetry in patients undergoing off-pump coronary artery bypass grafting: An observational study. Eur J Anaesthesiol 27:542-549, 2010 38. de Tournay-Jetté E, Dupuis G, Bherer L, et al: The relationship between cerebral oxygen saturation changes and postoperative cognitive dysfunction in elderly patients after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 25:95-104, 2011
preoperative hematocrit correlated with baseline rSO2 (0.48% increase for each 1% increase in hematocrit, p ⴝ 0.008). The average nadir (lowest recorded rSO2 for any given patient) was 54.9 ⴞ 6.6% and was correlated with on-pump surgery, baseline rSO2, and height. Baseline rSO2 was found to be an independent predictor of length of stay (hazard ratio 1.044, confidence interval 1.02-1.07, for each percentage of baseline rSO2). Conclusions: In cardiac surgical patients, lower baseline rSO2 value, on-pump surgery, and height were significant predictors of nadir rSO2, whereas only baseline rSO2 was a predictor of postoperative length of stay. These findings support previous research on the predictive value of baseline rSO2 on length of stay and emphasize the need for further research regarding the clinical relevance of baseline rSO2 and intraoperative changes. © 2012 Elsevier Inc. All rights reserved.
J
Despite the growing volume of literature on the utility of cerebral oximetry, uncertainty exists as to what can be considered the normal range for cerebral saturation at baseline or at critical stages of cardiac surgical procedures or what change from baseline should be tolerated. The authors designed this prospective observational study as a “real-world” study of rSO2 change during cardiac surgery. The cerebral oximetric device used was the EQUANOX Model 7600 Regional Oximeter System with the 8000CA Sensor (Nonin Medical, Inc, Plymouth, MN), which computes cerebral blood oxygen saturation using 2 light-emitting diodes and a dual-detector topology (Fig 1) that uses 3 wavelengths in each emitter (730, 810, and 880 nm). A common oximetric design is a single emitter with 2 detectors: 1 detector is spaced to capture light from the skull and skin only (short path, extracranial saturation) and the other detector is spaced to capture light from the skin, skull, and brain (long path, extra- and intracranial saturations). Subtracting the extracranial saturation from that of the longer path
ÖBSIS INTRODUCED cerebral oximetry in 1970, but its utility and validity were debated for many years.1 Questions raised included the apparent need to account for the length of the path of light in the Beer-Lambert equation, the lack of a gold standard against which to validate cerebral tissue oxygenation values, and a lack of data about the normal versus abnormal parameters of cerebral tissue saturation.2 Advances in the basic science knowledge of near-infrared spectroscopy have allowed the calculation of regional cerebral oxygenation (rSO2) without a precise knowledge of the path length of light.3-5 Likewise, the scientific community has come to accept the calculated arteriovenous saturation (calculated as 70% jugular bulb venous saturation and 30% arterial saturation) as a reasonable gold standard against which to measure the accuracy of cerebral oximeters. The current cerebral oximeters have been validated against this standard.6 Although the correlation between arteriovenous saturation and rSO2 can be affected by bypass parameters (alpha-stat v pH-stat) and by significant changes in the partial pressure of arterial carbon dioxide even during off-pump surgery, steady-state values have been judged to correlate well.7-10 With the resolution of these issues, the use of cerebral oximetry has expanded significantly and is emerging as a useful monitoring device. Numerous case reports and case series have highlighted the ability of cerebral oximetry to alert clinicians to catastrophic events.11-14 Other studies have shown that postoperative outcomes can be predicted by baseline rSO2 or intraoperative changes.15-21 Changes in cerebral oximetry have been shown to occur in the absence of changes in arterial saturation or systemic hemodynamic parameters, evidence that rSO2 provides unique data for clinicians.22-25 Most significantly, in 2 prospective trials, patients randomized to an active display of rSO2 and interventions to correct low rSO2 values during cardiac surgery or abdominal surgery had a lower incidence of postoperative adverse events.22,26
KEY WORDS: cerebral oximetry, cardiac surgery, cerebral oxygen saturation, oximetry, outcomes
From the *Department of Anesthesiology, University of Minnesota, Minneapolis, MN; †Abbott Northwestern Hospital, Minneapolis Heart Institute, Minneapolis, MN; ‡Department of Anesthesiology, SUNY Upstate Medical University, Syracuse, NY; §Department of Anesthesiology, University of Michigan, Ann Arbor, MI; and 储Nonin Medical, Inc, Plymouth, MN. Funding for this study was provided by Nonin Medical, Plymouth, MN. Address reprint requests to Ioanna Apostolidou, MD, Department of Anesthesiology, University of Minnesota, B-515 Mayo Memorial Building, Mayo Mail Code 294, 420 Delaware Street SE, Minneapolis, MN 55455. E-mail: [email protected] © 2012 Elsevier Inc. All rights reserved. 1053-0770/2606-0008$36.00/0 http://dx.doi.org/10.1053/j.jvca.2012.07.011
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Fig 1. Schematic of the 8000CA Sensor. (A) The sensor contains 2 light-emitting diodes, each generating 3 near-infrared spectroscopic wavelengths; and 2 detection sensors, each separated from the next optode by a distance of 20 mm. (B) Measurements from the emitters to the closer detector (20 mm) represent shallow (extracranial) tissue saturation; measurements from emitters to farther detectors (40 mm) represent shallow (extracranial) and deep (intracranial) tissue saturations. (Color version of figure is available online.)
(intracranial and extracranial saturations) is assumed to isolate intracranial oxygen saturation.7 With such a design, any difference in the optical properties of the skull and forehead beneath the near versus far detector will influence the calculated intracranial saturation measurement. The 8000CA Sensor has dual emitters and dual detectors, with the long and short paths reversed for each emitter, causing the skull and forehead optical differences associated with each detector to be canceled out. This sensor has been validated in laboratory studies27 and recently has been reported to have less interference from extracranial tissue than the Foresight and the INVOS oximeters.28 This prospective, observational study was designed to collect data about rSO2 changes during cardiac surgery, to examine their temporal distribution, and to determine the percentage of available time data. Also examined were the relations of rSO2 (at baseline and during cardiac surgery) to patient characteristics and intraoperative variables. METHODS This study was a prospective, observational, multicenter, nonrandomized, clinical study of the use of cerebral oximetry in patients undergoing cardiac surgery at 1 of 3 academic medical centers: University of Minnesota, Minneapolis Heart Institute, and SUNY Upstate Medical University. The institutional review board of each participating institution approved the study protocol and all enrolled patients gave written informed consent. Consecutive patients presenting for cardiac surgery with or without cardiopulmonary bypass (CPB) were eligible for enrollment. Inclusion
criteria included patients of either sex who were ⬎18 years of age, who weighed ⱖ40 kg, and who were able to read and communicate in English. Exclusion criteria were an emergency procedure, use of methylene blue or other intravenous dyes ⱕ24 hours of surgery, and a pre-existing skin condition at the site of the anticipated sensor placement. All patients received general endotracheal anesthesia, including a volatile agent, opioids, muscle relaxants, and benzodiazepines, according to standard practice at each institution. Invasive monitoring, including arterial pressure and central venous pressure, was used in all patients. The decision to use a pulmonary artery catheter and transesophageal echocardiography was guided by clinical judgment. Cerebral oximetric sensors were placed on each side of the patient’s forehead before anesthesia induction for continuous, real-time monitoring of rSO2 during surgery (8000CA Sensor, Nonin Medical). No light shields were required or used. The derived rSO2 values were displayed on the monitor and simultaneously recorded in the monitor memory. Use of the cerebral oximetric data for clinical decision-making was at the clinician’s judgment and was not driven by a protocol. Signal losses, interruptions, and dropout rates were recorded, as were possible causes of signal loss and steps taken to restore recordings. Event markers were added to the electronic cerebral oximetric data file and noted on the case-report forms. Predefined noted events included baseline, induction of anesthesia, intubation, skin incision, aortic cannulation, initiation of CPB, initiation of cooling, aortic cross-clamp application and removal, initiation of active rewarming, placement of the side-biter clamp, end of CPB, after protamine, and skin closure. On-pump cases used nonpulsatile moderate hypothermic CPB. Perfusion was maintained at pump flows of 2.2-2.4 L/min/m2 to maintain a mean arterial pressure at 50-80 mmHg. Arterial blood gases were measured at 15-30 minutes on CPB to maintain the partial pressure of arterial carbon dioxide at 35-40 mmHg using alpha-stat correction and partial pressure of arterial oxygen at 150-250 mmHg. Red blood cells were transfused to maintain hematocrit 22%-25% on CPB. Cold cardioplegia was administered for myocardial protection. Off-pump cases were conducted at normothermic temperatures. Systolic blood pressure was maintained at 100-130 mmHg. Arterial blood gases were measured at 30-minute intervals to maintain the partial pressure of arterial carbon dioxide at 35-40 mmHg and the partial pressure of arterial oxygen at ⬎150 mmHg. Red blood cells were transfused to maintain hematocrit at 27%-30% throughout the case. Demographic information, anthropometric data, pertinent cardiac history, and comorbidities were recorded before the surgery. Hospital length of stay was extracted from the patient records. No follow-up visits were performed. The following parameters were computed from cerebral oximetric recordings and were analyzed: ● baseline rSO2 value for each patient, defined as the average of right and left rSO2 readings for ⱖ30 seconds before induction ● nadir rSO2 value for each patient, defined as that patient’s minimum rSO2 value from intubation to skin closure ● changes of rSO2 value at predefined critical stages of the surgical procedure ● incidence and characteristics of patients with any rSO2 value ⬍25% of their baseline value ● incidence and characteristics of patients with any absolute rSO2 value ⬍50% saturation Major study endpoints included device performance and registration rate, rSO2 change from baseline, and nadir rSO2 during the procedure. Registration rate was determined as the percentage of time during surgery that a reading was available. The cerebral oximetric system collected and recorded an rSO2 value every 4 seconds; over the course of 100 seconds, 25 values would be expected. If a single value could not be calculated or recorded, the registration rate would be 96%. A registration rate of ⱖ90% was predefined as acceptable.
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Secondary objectives were the identification of predictors of baseline rSO2, nadir rSO2, rSO2 values ⬍25% from baseline, and an absolute rSO2 value ⬍50%. Statistical analysis was performed with SAS 9.1 (SAS Inc, Cary, NC). Continuous variables were presented with the mean or median, as appropriate, standard deviation, range, and number of observations. Categoric or discrete variables were presented as fraction and percentage. All data collected were analyzed; imputation methods were not used for missing data. No formal hypothesis testing was planned; summary statistics were generated across the sample. Saturation values for each patient at each event point were averaged across the right and left channels. Differences between rSO2 values across the surgery were analyzed using analysis of variance for normally distributed results or the Kruskal-Wallis test for non-normally distributed results. Normality was tested with the Kolmogorov-Smirnov test. Relations between baseline rSO2 and nadir rSO2 and potential categoric predictors were determined using analysis of variance. Relations among baseline rSO2 and nadir rSO2 and potential continuous predictors were determined using linear regression. Logistic regression was used to determine the relation between categoric endpoints (decrease ⬍25% of baseline rSO2 and decrease below an rSO2 value of 50% saturation) and categoric and continuous predictors. Multivariate models were built by incorporating all variables with a univariate significance of ⬍0.1. Assessment of length of stay was performed using Cox proportional hazards regression. A p value ⬍0.05 was considered to indicate a statistically significant difference. RESULTS
Ninety patients, 30 at each institution, were enrolled from August 2009 through July of 2010 and all patients completed the study. Of the 90 patients enrolled, 4 had corrupted electronic files and in 1 patient the clock times were not synchronized. Eighty-five patients were included in the baseline rSO2 analysis. In addition, end-of-surgery time was not available in 1 patient; 84 patients were included in the nadir rSO2 and rSO2 ⬍50% analyses. Demographic and baseline characteristics are presented in Table 1; surgical details are presented in Table 2. There were differences among sites, in that SUNY performed 52% cases (13/30) off-pump, whereas the Minneapolis Heart
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Table 2. Surgical Details Parameter (Patients With Data)
Surgery performed off-pump Type of surgery (n ⫽ 85) Bypass grafting only Valve only Bypass graft and valve Neither Hematocrit Preoperative (n ⫽ 85) Postoperative (n ⫽ 57)* Serum creatinine Preoperative (n ⫽ 84)* Postoperative (n ⫽ 66)* Duration of surgery (minutes) (n ⫽ 84)† Bypass time (minutes) (n ⫽ 66)‡
Results
16/85 (19%) 40/85 (47%) 33/85 (39%) 6/85 (7%) 6/85 (7%) 39.0 (25.9-49.9) 32.1 (25.1-41.3) 1.0 (0.5-5.6) 1.0 (0.5-4.6) 309 (83-575) 122 (15-345)
NOTE. Data are presented as number/total (percentage) or median (range). *Values not available in all patients. †Duration of surgery unknown in 1 patient because of missing end-of-surgery time. ‡No bypass in off-pump cases (n ⫽ 16; initiation of bypass/end of bypass not indicated in 3 on-pump patients).
Institute and University of Minnesota each performed ⬍10% of their cases off-pump (Fisher exact test, p ⬍ 0.0001). As noted earlier, registration rates could not be calculated in 5 patients. In the remaining 85 patients, 420 hours 34 minutes were recorded during this study, and rSO2 readings were recorded for 96% of this time on ⱖ1 channel and on the 2 channels for 93% of the time. Baseline readings ranged from 41% to 95% and averaged 63.9 ⫾ 8.8% (Fig 2). Five patients had baseline rSO2 readings ⱕ50% and 29 had baseline readings ⬍60%. A univariate relation was observed between baseline rSO2 and body mass
Table 1. Demographic and Baseline Risk Factors of Enrolled Patients Age (y) Male sex Race* African American Hispanic White Other Current smoker† Height (cm) Weight (kg) Body mass index (kg/m2) Prior cardiac surgery Diabetes Cerebrovascular disease Preoperative dialysis
61.5 ⫾ 13.1 56/85 (66%) 6/85 (7%) 2/85 (2%) 77/85 (91%) 2/85 (2%) 13/84 (16%) 172 ⫾ 10.2 90.8 ⫾ 20.6 30.0 ⫾ 7.2 14/85 (16%) 32/85 (38%) 4/85 (5%) 2/85 (2%)
NOTE. Data are presented as mean ⫾ standard deviation or number/total (percentage). *In 2 patients, multiple race categories were noted. †Status not available in 1 patient.
Fig 2. Histogram of baseline regional cerebral oxygen saturation (rSO2) values. Individual patients and their specific baseline regional cerebral oxygen saturation values are noted on the x-axis just below the histogram bars. Seven patients had baseline values <55%.
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Table 3. Multivariate Relation Between Patient Characteristics and Nadir Regional Cerebral Oxygen Saturation Parameter
Relation to Nadir rSO2*
95% CI
p
Age Height Baseline rSO2 On-pump surgery
1-y increase ⫺0.09% 1-cm increase 0.17% 1% increase 0.29% ⫺4.64%
⫺0.18 to ⫺0.006 0.02-0.33 0.13-0.44 7.86-1.43
0.036 0.028 0.0005 0.005
Abbreviations: CI, confidence interval; rSO2, regional cerebral oxygen saturation. *Relations are presented as coefficients (slopes for age, height, and baseline rSO2 and effect for on-pump surgery) from multiple linear regressions and are adjusted for weight, preoperative hematocrit, smoking status, and sex. A negative number indicates a lower nadir value (eg, 1 additional year of age resulted in a 0.09% lower nadir rSO2). Positive estimates indicate a higher nadir value. The minimum rSO2 for a nonsmoking 60-year-old woman, with a body mass index of 31.1 kg/m2, weight of 90 kg, height of 170 cm, preoperative hematocrit of 38, and preoperative creatinine of 1 off-pump, was 40% (eg, model intercept).
index (BMI; p ⫽ 0.05), weight (p ⫽ 0.03), baseline hematocrit (p ⬍ 0.0001), baseline creatinine (p ⫽ 0.002), diabetes (p ⫽ 0.01), and cerebral vascular disease (p ⫽ 0.03). Increases in BMI, baseline hematocrit, and weight were associated with higher baseline rSO2 values, whereas increased creatinine was associated with lower baseline rSO2. Patients with diabetes had significantly lower baseline rSO2 readings than those without (60.8 ⫾ 7.4% v 65.8 ⫾ 9.2%, p ⫽ 0.01) and had lower baseline hematocrit (37.3 ⫾ 5.0% v 40.0 ⫾ 5.5%; analysis of variance, p ⫽ 0.022). A multivariate model was developed that included institution, diabetes, cerebrovascular disease, weight, BMI, baseline creatinine, and baseline hematocrit. In this model, only preoperative hematocrit was an independent predictor of baseline rSO2, where each 1% increase in hematocrit was related to a 0.48% increase in baseline rSO2 (p ⫽ 0.008). The average individual nadir rSO2 was 54.9 ⫾ 6.6 (range 40.0-76.5). Increasing age, lower baseline rSO2, and on-pump surgery were related to lower nadir rSO2 values; increasing weight, height, and hematocrit were related to higher nadir values. As presented in Table 3, age, on-pump surgery, baseline rSO2, and height remained statistically significant predictors of nadir rSO2 in a multivariate analysis. Nine of 84 patients (11%) exhibited a decrease ⬍25% of their baseline value ⱖ1 time during surgery, and 14/84 exhibited an absolute value ⬍50% rSO2. All 9 patients whose rSO2 decreased ⬍25% of baseline were on-pump patients, and all but 1 of the patients whose rSO2 decreased to ⬍50% were on-pump surgical patients. No relations between baseline or surgical characteristics and a decrease ⬍25% of baseline were detected. Height, weight, and preoperative hematocrit were statistically significant independent predictors of an absolute rSO2 value decreasing ⬍50% (Table 4). On-pump versus off-pump surgery was not correlated with an rSO2 ⬍50%.
Figure 3 shows the pattern of rSO2 changes at the critical predefined points during the surgical procedure of on-pump and off-pump patients. In on-pump cases, values below baseline were observed at all CPB points, including placement and removal of aortic clamps (cross-clamp and side-biter). In offpump cases, lower values were observed during side-biter placement and removal. In a multivariate model, only baseline rSO2 was found to be an independent predictor of length of stay (hazard ratio 1.044, confidence interval 1.02-1.07, p ⫽ 0.0017). Each percentage decrease in baseline rSO2 increased the length of stay by a factor of 1.044 (p ⫽ 0.0017). DISCUSSION
These data indicate that the EQUANOX system reliably can provide rSO2 data throughout cardiac surgery, with values provided for ⬎96% of the time. A higher preoperative hematocrit was associated with a higher baseline rSO2 and with a lower risk of a decreasing rSO2 absolute value ⬍50%. Furthermore, younger, taller patients and those with higher baseline rSO2 had higher nadir values. A lower baseline rSO2 was associated with a longer hospital stay. The authors found no published data for registration rates with other cerebral oximetric systems, so they cannot provide a direct comparison. A sophisticated study of pulse oximeters found that the percentage of time the display is blanked out (ie, values calculated, but not displayed) varies among manufacturers, with the Nellcor 3000 at 5.9% of the time, the Agilent CMS A.0 3.6% of the time, and the Masimo 2.3% of the time.29 Dropout times (unable to calculate a value) for pulse oximeters also vary, with the Agilent CMS A.0 at 6.4% of the time and Masimo 3.0% of the time.29 The registration rates for the EQUANOX system appear to be comparable, although caution
Table 4. Multivariate Predictors of an Absolute Regional Cerebral Oxygen Saturation <50% Parameter
Relation to rSO2 ⬍50%*
95% CI
p
Height (cm) Weight (kg) Preoperative hematocrit (%)
OR 0.87 per 1-cm increase OR 0.96 per 1-kg increase OR 0.85 per 1% increase
0.784-0.967 0.928-0.998 0.741-0.981
0.0095 0.038 0.026
Abbreviations: CI, confidence interval; OR, odds ratio; rSO2, regional cerebral oxygen saturation. *Relations are presented as ORs from multivariate logistic regression and estimate the effect on the predicted probability of an rSO2 ⬍50%. The estimates also are adjusted for sex. An OR ⬍1 indicates a lower likelihood of a decrease ⬍50% for each one.
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Fig 3. Average change from baseline of regional cerebral oxygen saturation (rSO2) values at specific points during the surgical procedure of (A) on-pump and (B) off-pump patients. SD, standard deviation; X-clamp, cross-clamp.
is advised because pulse oximetry and cerebral oximetry are considerably different. This study examined the use of a relatively new cerebral oximeter, the EQUANOX system with the 8000CA Sensor, in the setting of cardiac surgery. The EQUANOX system with this sensor has been validated in a laboratory setting, and has been shown to provide relative accuracy, similar to the INVOS system.6,27 The design of the 8000CA Sensor uses a dualemitter and dual-detector topology, which may decrease contamination by extracranial absorbance.28 A recent evaluation of 3 cerebral oximetric systems showed that the displayed rSO2 value is altered when extracranial blood flow is eliminated using a tourniquet.28 All commercially available oximeters use different sensor designs and algorithms to generate a displayed
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value; such differences may result in different values for brain oxygenation. Further studies will be required to elucidate which sensor is the most accurate in clinical settings, such as the sensor reported here. This study used the 8000CA Sensor, which has been validated as a relative (trend) monitor, but not an absolute monitor. A second-generation Nonin sensor, the 8004CA, has been validated as an absolute monitor27 but was not available at the time of this study. Nearly one third of the present patients had rSO2 values ⬍60% before intubation, with 5% having baseline values ⱕ50%. These data showed a range of baseline values that are in agreement with those reported by Baikoussis et al30 and by Papadopoulos et al31 and somewhat higher than those found by Nauphal et al.10 In the present study population, diabetic patients had a significantly lower baseline rSO2, similar to the relation found by Baikoussis et al in patients scheduled for carotid endarterectomy.30 In a multivariate analysis, however, the authors found that only preoperative hematocrit correlated with baseline rSO2. A higher hematocrit, by maximizing oxygen delivery to the tissues, influences the balance between the brain oxygen supply and demand, resulting in a higher rSO2. The hematocrit is not the sole important variable in the balance equation but consistently has shown a strong association with rSO2 in published studies.17,30 The present data are similar to those of Kishi et al who found patient age and preoperative hematocrit to be correlated significantly with baseline rSO2 values.32 Few studies have examined which preoperative characteristics could predict which patients likely would develop low rSO2 values during surgery. The present results seem intuitive, ie, that older patients would have lower rSO2 values and that higher hemoglobin values would be correlated with higher baseline and higher nadir values. The authors also found that height, but not BMI, was a predictor of nadir values. This finding may be related to the complex relation among height, weight, and hematocrit; taller individuals tend to be men and men tend to have higher hematocrit levels. The calculated BMI can be deceptive because obese individuals of very different height and weight can have the same BMI. A simple weight ratio (milliliters per kilogram) has been found to be the least accurate predictor of plasma or erythrocyte volume; surface area calculations are more accurate.33 Further studies will be needed to understand this relation. The authors also found that on-pump surgery was associated with lower nadir values than off-pump surgery. Prior studies of cerebral oxygenation monitored by a jugular bulb catheter have shown that decreased jugular bulb saturation values tend to occur at rewarming.34 The lower hematocrit associated with CPB also could contribute to lower nadir values in on-pump than in off-pump patients. In a study of acute normovolemic hemodilution, Han et al found that cerebral desaturations were associated with hematocrit levels ⬍30%, a value common in on-pump cardiac patients.35 McCusker et al also found a correlation between on-pump hemodilution and rSO2 values, with a lower hematocrit associated with lower rSO2 values.36 The present finding that off-pump cardiac surgical patients had higher nadir rSO2 values and a lower incidence of decreases ⬍25% of baseline or an absolute rSO2 of ⬍50% seem to differ from those reported by Moritz et al who found that
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positioning of the heart for right coronary grafting in off-pump patients could result in significant decreases in rSO2, presumably owing to the decrease in ventricular filling and cardiac output associated with such positioning.37 The authors did not collect data about positioning of the heart during bypass and, thus, cannot compare these data. The question of what absolute value or relative change in rSO2 constitutes a need for intervention remains unclear, although recent data have provided some insights. De TournayJetté et al found that cardiac surgical patients who had an absolute nadir value of 50% or a relative change of 30% from baseline were at increased risk of postoperative cognitive decline.38 Hong et al did not observe any significant differences in the incidence or duration of decrease in rSO2 values between patients with and those without postoperative cognitive decline but did find that low rSO2 values were correlated with a longer stay.18 Heringlake et al found that an rSO2 of ⱕ50% (absolute) at baseline, despite supplemental oxygen, was an independent risk factor for 30-day survival.17 Fischer et al found that aortic arch surgical patients who spent ⬎30 minutes under an absolute value of 60% had an extended hospital stay of 4 days.15 Very few patients in this study spent any significant amount of time ⬍25% or ⬍50% of baseline, and the calculations for area under the curve did not show any significant relations with any baseline or intraoperative characteristics. However, despite a relatively small sample, the authors, like Heringlake et al17 and Hong et al,18 found a significant correlation between baseline rSO2 and length of stay, with lower baseline values predictive of longer hospitalization. The present study was not designed to identify the underlying pathophysiology that may have been responsible for the low baseline rSO2 values seen in some patients, and the authors do not suggest that a low rSO2 is a causative factor for a longer stay. However, a low baseline rSO2 (⬍50%-60%) may help identify patients who have more significant cardiopulmonary disease and are at risk of a prolonged hospital stay. The present study was not designed to test whether intervening to increase rSO2 would improve outcomes or shorten hospital stay, but other studies have tested those questions. Murkin et al found that patients monitored with cerebral oximetry and who had protocol-defined interventions intended to keep the rSO2 ⬎75% of the baseline value had decreased morbidity and mortality compared with patients whose anesthesiologist was blinded to the rSO2.26 In a similar study in abdominal surgical patients, Casati et al found that patients with active monitoring
and protocol-defined interventions to maintain the rSO2 ⬎75% of baseline had less severe desaturations.24 In patients whose rSO2 values decreased ⬍75% of baseline, postoperative mental status was worse in patients in the blinded group than in the monitored/intervention group, indicating that an intervention to correct rSO2 values ⬍75% of baseline can decrease adverse outcomes.24 Because of the differences in oximetric design, the thresholds identified by Murkin et al26 and Casati et al24 (⬍75% of baseline) may be different in other sensors, including the EQUANOX sensor used in this study. Limitations This study was designed as a “real-world snapshot” to provide insight into how cerebral oximetry performs in the clinical rather than the laboratory realm and to gather data on the range of rSO2 values seen in a cardiac surgical population. Although the authors found correlations between preoperative characteristics and baseline rSO2 values and correlations with the lowest rSO2 and absolute values of rSO2 ⬍50%, the sample was relatively small. In addition, this study was viewed as hypothesis generating, rather than hypothesis testing, so the authors could not ascertain whether the lack of correlation between some characteristics and rSO2 was a true absence of correlation or owing to a lack of statistical power. This study was not designed to test the utility of oximetric monitoring or to compare outcomes between patients managed with and without rSO2 monitoring. The authors did not control tightly the depth of anesthesia or end-tidal CO2, which can influence cerebral blood flow and, presumably, rSO2. The study population included onpump and off-pump surgeries, and this may have obscured some correlations. Furthermore, the operative practices differed among sites; the impact of these differences may have increased the variability further. CONCLUSIONS
These results provide further data on expected rSO2 values at baseline and across time in cardiac surgical patients at different institutions and provide confirmation of prior studies in the correlation between low baseline rSO2 and length of stay. In addition, the authors found that the EQUANOX system provides data ⬎95% of the time. Accumulating data on cerebral oximetry has allowed progress in defining the rSO2 values that represent “normal” or “abnormal” states, but larger population samples and more experience with this new monitoring modality will be required to define those parameters with confidence.
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