preoperative cerebral oxygen_saturation_and.20

Preoperative Cerebral Oxygen Saturation and ClinicalOutcomes in Cardiac Surgery

Matthias Heringlake, M.D.,* Christof Garbers, Cand. Med.,† Jan-Hendrik Kabler, Cand. Med.,†Ingrid Anderson, Cand. Med.,† Hermann Heinze, M.D.,‡ Julika Schon, M.D.,‡Klaus-Ulrich Berger, M.D.,‡ Leif Dibbelt, M.D.,§ Hans-Hinrich Sievers, M.D.,� Thorsten Hanke, M.D.#

ABSTRACT

Background: The current study was designed to determinethe relation between preoperative cerebral oxygen saturation(ScO2), variables of cardiopulmonary function, mortality, andmorbidity in a heterogeneous cohort of cardiac surgery patients.Methods: In this study, 1,178 consecutive patients scheduledfor on-pump surgery were prospectively studied. PreoperativeScO2, demographics, N-terminal pro-B-type natriuretic pep-tide, high-sensitive troponin T, clinical outcomes, and 30-dayand 1-yr mortality were recorded.Results: Median additive EuroSCORE was 5 (range: 0–19).Thirty-day and 1-yr mortality and major morbidity (at leasttwo major complications and/or a high-dependency unit stayof at least 10 days) were 3.5%, 7.7%, and 13.3%, respec-tively. Median minimal preoperative oxygen supplementedScO2 (ScO2min-ox) was 64% (range: 15–92%). ScO2min-ox wascorrelated (all: P value �0.0001) with N-terminal pro-B-type natriuretic peptide (�: �0.35), high-sensitive troponinT (�: �0.28), hematocrit (�: 0.34), glomerular filtration rate

(�: 0.19), EuroSCORE (�: 0.20), and left ventricular ejec-tion fraction class (�: 0.12). Thirty-day nonsurvivors had alower ScO2min-ox than survivors (median 58% [95% CI,50.7–62%] vs. 64% [95% CI, 64–65%]; P � 0.0001).Receiver-operating curve analysis of ScO2min-ox and 30-daymortality revealed an area-under-the-curve of 0.71 (95% CI,0.68–0.73%; P � 0.0001) in the total cohort and an area-under-the-curve of 0.77 (95% CI, 0.69–0.86%; P � 0.0001)in patients with a EuroSCORE more than 10. Logistic regres-sion based on different EuroSCORE categories (0–2; 3–5,6–10, �10), ScO2min-ox, and duration of cardiopulmonary by-pass showed that a ScO2min-ox equal or less than 50% is anindependent risk factor for 30-day and 1-yr mortality.Conclusions: Preoperative ScO2 levels are reflective of theseverity of cardiopulmonary dysfunction, associated with short-and long-term mortality and morbidity, and may add to preop-erative risk stratification in patients undergoing cardiac surgery.

C EREBRAL oxygen saturation (ScO2) monitoring bynear-infrared spectroscopy is increasingly used for as-

sessing the adequacy of cerebral oxygen delivery to demandin patients undergoing cardiac and noncardiac surgery.1–3 Arelative decrease of intraoperative ScO2 to less than 80% ofthe preoperative baseline or to absolute levels lower than50% have been associated with postoperative cognitive dys-

* Professor, Deputy Director, Cardiac Anesthesia Unit, Departmentof Anesthesiology, University of Lubeck, Lubeck, Germany, † MedicalStudent, Department of Anesthesiology, University of Lubeck, ‡ Dep-uty Director, Department of Anesthesiology, University of Lubeck,§ Deputy Director, Department of Clinical Chemistry, University ofLubeck, � Professor, Director, Department of Cardiac and ThoracicVascular Surgery, University of Lubeck, # Deputy Director, Departmentof Cardiac and Thoracic Vascular Surgery, University of Lubeck.

Received from the Department of Anesthesiology, University ofLubeck, Lubeck, Germany. Submitted for publication April 5, 2010.Accepted for publication August 31, 2010. Support was providedsolely from institutional and/or departmental sources. Covidien(Mannheim, Germany) provided technical support through anINVOS4100 monitor to be used outside the operating room. Thehormone analyses were performed by Roche Diagnostics (Gren-zach-Wyhlen, Germany). The author M. Heringlake receives hono-raria for lectures from Covidien (Neustadt, Germany) and scientificsupport from Roche Diagnostics (Mannheim, Germany). The workhas been presented in part at the autumn meeting of the WorkingGroup in Cardiac Anesthesia of the German Association of Anaes-thesiology and Intensive Care, November 12–14, 2009, in Ulm,Germany, and at the 25th Annual Meeting of the European Associ-ation of Cardiothoracic Anesthesiologists, June 9–11, 2010, in Edin-burgh, Scotland.

Address correspondence to Dr. Heringlake: Department of An-esthesiology, University of Lubeck, Lubeck, Ratzeburger Allee 160,D-23538 Lubeck, Germany. [email protected]. This article maybe accessed for personal use at no charge through the Journal Web site,www.anesthesiology.org.

Copyright © 2010, the American Society of Anesthesiologists, Inc. LippincottWilliams & Wilkins. Anesthesiology 2011; 114: 58–69

What We Know about This Topic

• Intraoperative cerebral oxygen saturation (ScO2) monitoringhas been used to assess the adequacy of cerebral oxygendelivery to demand.

What This Article Tells Us That Is New

• Preoperative ScO2 concentrations are reflective of baselineseverity of cardiopulmonary dysfunction, associated withshort- and long-term mortality and morbidity, and may add topreoperative risk stratification in patients undergoing cardiacsurgery.

� This article is featured in “This Month in Anesthesiology.”Please see this issue of ANESTHESIOLOGY, page 9A.

� This article is accompanied by an Editorial View. Please see:Murkin JM: Cerebral oximetry: Monitoring the brain as theindex organ. ANESTHESIOLOGY 2011; 114:12–3.

Anesthesiology, V 114 • No 1 January 201158

function,1,4 a higher rate of stroke or coma,5 increased post-operative morbidity from other nonneurological causes,6 anda prolonged stay in the high-dependency unit or the hospi-tal.7 Sparse data are available about the relation betweenpreoperative ScO2 levels and clinical outcomes in cardiac sur-gery patients. Murkin et al. have shown that patients present-ing with major organ morbiditiy and mortality after coronaryartery bypass grafting (CABG) had lower baseline and nadirScO2 concentrations than those that did not.6 Based on thesefindings and our own clinical observations that cardiac sur-gery patients presenting with decreased preoperative ScO2

(i.e., lower than 50% absolute) often developed complica-tions and needed prolonged therapy in the intensive careunit, we hypothesized that preoperative ScO2 is reflective ofthe global cardiopulmonary function and may be used forrisk stratification. The current study was designed to ex-plore the association of preoperative ScO2 concentrationsand established risk factors in patients scheduled for on-pump cardiac surgery and to determine the relation be-tween these variables and clinical outcomes (i.e., mortalityand morbidity).

Materials and Methods

Study DesignThe study was designed as a prospective cohort study. Pri-mary objectives were to determine anamnestic and cardiovas-cular factors influencing preoperative ScO2 and to explore therelation between preoperative ScO2 and clinical outcome (30-day and 1-yr mortality and morbidity).

PatientsAfter approval by the local ethical committee (Ethikkommis-sion der Universitat zu Lubeck, Lubeck, Germany), all pa-tients scheduled for cardiac surgery with cardiopulmonarybypass (CPB) at the University of Lubeck from January 1,2008, to December 31, 2008, were screened for participationin this prospective, observational trial. Exclusion criteriawere less than 18 yr of age and planned off-pump surgery.Written informed consent was obtained from all elective andurgent patients as well as emergency patients capable of com-munication. In case of sedated or intubated patients sched-uled for emergency surgery, consent was obtained from thenext of kin and reconfirmed after recovery.

Justification of Sample SizeTo our knowledge, the association between preoperativeScO2, cardiovascular and surgical risk factors, and clinicaloutcome has not been formally analyzed previously inlarger studies. The current study may thus be regarded asa pilot trial. The sample size was adjusted to comparablestudies analyzing the association between preoperativevariables and outcome.

RecruitmentDuring the study period, 1,230 patients fulfilled the inclu-sion criteria. Two patients refused to participate in the study,

48 patients’ surgery was cancelled, and no ScO2 measure-ments were performed in 2 patients, leaving 1,178 that couldbe analyzed. As a result of missing either room or oxygen-supplemented ScO2 concentrations or hormone values, 194datasets were partially incomplete. Complete datasets, in-cluding hormones, were obtained from 984 patients.

Determination of ScO2

ScO2 was determined by near-infrared spectroscopy with anINVOS� 4100 or 5100 cerebral oximeter (Somanetics,Troy, MI). With the exception of emergency patients andintubated patients, who were studied upon arrival in theoperating room, all patients were examined preoperativelyon the cardiac surgery ward. In this case, the patients werefully awake and had received neither sedating drugs nor opi-oids. Emergency and intubated patients received sedating oranalgesic drugs, as clinically appropriate.

On the ward, ScO2 was first determined in the resting state inthe semirecumbent position, while the patients breathedroom air, and the lowest value from the left or right hemi-sphere was used for determination of (ScO2min-room). Trans-cutaneous arterial oxygen saturation (SaO2), mean arterialblood pressure, and heart rate were determined concomi-tantly. Thereafter, ScO2 measurements were repeated whenthe patients were breathing oxygen-enriched air until no fur-ther increase in SaO2 was observed. The lowest ScO2 valueduring oxygen supplementation recorded in a patient, eitherfrom the left or the right hemisphere, was determined asScO2min-ox. In 69 patients, no ScO2 measurements with oxy-gen were available; in these patients, ScO2min-room values wereused for further analysis.

Standard Risk Factors and Clinical OutcomesBesides demographic variables serving as potential risk factors,the following specific cardiovascular risk factors were assessed:

● Left ventricular ejection fraction (LVEF)● New York Heart Association grade● Additive EuroSCORE● Estimated glomerular filtration rate

LVEF was derived from the preoperative diagnostics (le-vocardiography or echocardiography) and graded as: se-verely reduced, LVEF less than 30%; moderately reduced,30 – 49%; and normal, �50%. The additive EuroSCOREwas calculated according to Roques et al.8 and analyzed asa continuous variable. Estimated glomerular filtration ratewas calculated from preoperative plasma creatinine by the ab-breviated Modifications of Diet in Renal Disease equation.9

Clinical outcomes (30-day mortality, major complica-tions, and duration of treatment in the high-dependencyunit) were derived from the prospectively sampled cardiacsurgery database. All-cause 1-yr mortality was determinedfrom the hospital database, by contacting the patient’s pri-mary physician, the patient, or the patient’s next of kin. Thefollow-up rate was 98.3%.

PERIOPERATIVE MEDICINE

Anesthesiology 2011; 114:58 – 69 Heringlake et al.59

Determination of High-sensitivity Troponin T andN-terminal Pro-B-type Natriuretic PeptideArterial blood samples for determination of N-terminal pro-B-type natriuretic peptide (NTproBNP) and high-sensitivetroponin T (hsTNT) were obtained immediately before in-duction of anesthesia. EDTA plasma was separated andstored at �80° for further analysis.

hsTNT was determined by the electrochemiluminescencemethod as described recently (ECLIA; Elecsys 2010 analyzer,Roche Diagnostics, Grenzach-Wyhlen, Germany).10 Thelower detection limit of this assay was 3 pg/ml. The interassaycoefficient of variation was 5.4% at 28 pg/ml and 7.1% at2,350 pg/ml.

NTproBNP was determined by an electrochemilumines-cence immunoassay (Elecsys proBNP sandwich immunoas-say; Roche Diagnostics) on Elecsys 2010.11 The interassaycoefficient of variation was 9.3% at 130 pg/ml and 14.4% at3,890 pg/ml. The lower detection limit was 5 pg/ml.

AnesthesiaGeneral anesthesia was induced with etomidate and sufen-tanil and maintained with sevoflurane and remifentanyl,before and after CPB, and with propofol and remifenta-nyl, during CPB. If necessary, midazolam was added toachieve the desired anesthesia depth. Beyond standardanesthesia monitoring, including electrocardiogram, in-vasive arterial blood pressure, and central venous pressuremonitoring, all patients were intraoperatively routinelyequipped bihemispherically with ScO2 sensors (INVOS�Cerebral Oximeter 5100).

CPB ManagementBefore CPB, all patients received 400 IU/kg heparin. Surgerywas performed in moderate hypothermia using antegradeblood cardioplegia. Blood flow during CPB was adjusted toachieve a mean arterial blood pressure between 50–70mmHg, a mixed venous oxygen saturation—measured at theinflow of the CBP circuit—higher than 70%, and relativeScO2 concentrations higher than 80% of the preoperativebaseline determined in the operating room when breathingroom air. To achieve this goal, norepinephrine and nitroglyc-erin were applied as a bolus or a continuous infusion. He-matocrit was adjusted between 26% and 29%. Acid-basebalance was performed after �-stat blood gas principles. Afterweaning from CPB, protamine was applied accordingly.

Surgical ProceduresOf the 1,178 patients, 800 (67.9%) underwent CABG sur-gery (isolated CABG, 571; CABG plus aortic valve surgery,151; CABG plus other valve surgery, 62; CABG plus ascend-ing aortic surgery, 4). Of the total number of patients, 378(32.1%) underwent surgery other than CABG (aortic valvesurgery, 174; mitral valve surgery, 37; tricuspid valve surgery,

7; combined valve surgery, 127; major thoracic vascular sur-gery, 60; other on-pump procedures, 27).

Statistical AnalysesAnalyses were performed in the total cohort and in a group of102 high-risk patients with an additive EuroSCORE morethan 10.12 No adjustments for multiple testing were made.

Data were analyzed by MedCalc 11.3.3 statistical soft-ware package (MedCalc Software bvba, Mariakerke, Bel-gium). Because most of the relevant data were not normallydistributed after Kolmogornov–Smirnov testing, all data, ifnot stated otherwise, are given as median and 25% of 75%quartiles. Statistical significance was assessed at the 5% level(P � 0.05 is statistically significant).

To allow better comparisons with the additive Euro-SCORE, analyses regarding mortality were primarily calcu-lated for 30-day mortality. One-yr mortality was used forconstruction of the Kaplan–Meier survival curves and logis-tic regression analyses.

Postoperative morbidity was defined as a combined end-point of (A) more than 1 point in the major adverse eventsand complications score (MaCS) according to Schon et al.7

(need of renal replacement therapy, reintubation, stroke[Rankin disability score13 �1], and low-cardiac output syn-drome) or (B) need for high-dependence unit (intensive careunit plus intermediate care) treatment of at least 10 days.

Comparisons between groups for univariate predictors ofoutcome were performed by a two-sided chi-square test withYates correction for categorical variables and Mann–Whit-ney test or Kruskal–Wallis test, as appropriate, for continu-ous variables.

Correlation analyses were performed by the Spearmanrank correlation test for continuous variables or Kendall’s� for scaled variables, as appropriate. Cutoff values formortality and morbidity were derived from receiver-oper-ating curve (ROC) analyses. The lowest cutoff values forScO2min-ox derived from the ROC analysis was used forconstruction of a Kaplan–Meier survival curve with log-rank test statistics.

Backward logistic regression analyses were performed byentering additive EuroSCORE, ScO2min-ox, and CPB dura-tion in the model. For the latter variables, the cutoff valuesderived from the ROC analyses were used. EuroSCORE wasadded as a graded variable with the different risk categories(0–2; 3–5, 6–10, and �10) graded as 1–4.

Analyses were performed in the total cohort of patientswith and without entering the cutoff concentrations ofhsTNT and NTproBNP. With respect to the low event ratefor 30-day mortality, additional analyses were performed us-ing 1-yr mortality as the dependent variable.

Results

Demographics and Surgical CourseOf the total number of patients, 70.5% were men. The me-dian age was 68 yr (59–74 yr), weight was 81 kg (72–91 kg),

Preoperative Cerebral Oxygen Saturation and Outcome


height was 172 cm (166–178 cm), and body mass index was27 (24–32). The median American Society of Anesthesiol-ogy classification was 3 (3–3), and median additive Euro-SCORE was 5 (3–8). Of the total number of patients, 484(41%) were graded as New York Heart Association gradeIII/IV, and 694 (59%) were in New York Heart Associationgrade I/II.

Cardiovascular risk factors, preoperative medication,baseline hemodynamics, hematocrit, estimated glomeru-lar filtration rate, hsTNT, and NTproBNP are presentedin table 1.

A recorded 1,058 patients (90%) were in elective surgicalstatus, with 120 (10%) of these cases classified as urgent oremergency surgery. A recorded 635 patients (54%) sufferedfrom angina pectoris, 215 (18%) had a main left stem coronarystenosis, 295 (25%) had a history of myocardial infarction, 108(9%) were scheduled for redo surgery, and 33 patients (2%) hadan active endocarditis. Before surgery, 61 (5%) patients neededcirculatory support (i.e., inotropic and vasopressor support orintraaortic counterpulsation). Main variables of the surgicalcourse and outcomes are presented in table 1. Thirty-day and1-yr mortality and major morbidity (at least two major compli-cations and/or a high-dependency unit stay of at least 10 days)were 3.5%, 7.7%, and 13.3%, respectively.

The subgroup of high-risk patients with a EuroSCOREgreater than 10 consisted of 102 patients with a medianadditive EuroSCORE of 12 (11–14). The patients in thisgroup were older (74 yr [67–78 yr]), weighed less (75 kg[67–97 kg]), and were smaller (170 cm [160–178 cm]; all:P � 0.05) compared with the total cohort.

The surgical mix was comparable with the total group. Inthis group, 60.8% of patients underwent CABG surgery and39.2% were categorized as NO-CABG. Of these high-riskpatients, 57.8% were graded as urgent or emergent. Dura-tion of surgery was 308 min (261–410 min), CPB and aorticcross-clamp time were 150 (116–200 min) and 111 min(78–145 min), respectively. Thirty-day and 1-yr mortalitywere 15.7% and 27.5%. Of these patients, 40.2% fulfilledthe criteria of the combined morbidity endpoint. NT-proBNP concentrations were 2,739 pg/ml (1,074–29,346pg/ml) and hsTNT concentrations were 72.5 ng/ml (17.2–376 ng/ml). With the exception of the surgical mix, all de-picted variables were significantly (P � 0.05) different fromthe total cohort.

Preoperative Cerebral Oxygen and Arterial SaturationScO2 values available with room air were 1,123, and ScO2 valueswhen breathing oxygen-enriched air were 1,109. The ScO2min-

room in the total cohort when patients were breathing room airwith a median SaO2 of 97% (95–98%) was left 62% (57–67%)and right 62% (56–67%). The SaO2 when breathing oxygen-enriched air was 100% (100–100%), and ScO2 with oxygen wasleft 66% (61–71%) and right 66% (61–71%).

ScO2min-ox derived from the measurements during oxygensupplementation in 1,109 patients and from room air mea-surements in 69 patients was 64 (55/69). A histogram ofScO2min-ox values in the total cohort is given in figure 1.

In high-risk patients with an additive EuroSCOREmore than 10, SaO2 with room air was 96% (94 –97%).Mean arterial blood pressure and heart rate were 80mmHg (80 –100 mmHg) and 75 beats/min (66 –91 beats/min), respectively. ScO2min-room was 54% (49 – 60%), andScO2min-ox was 60% (52– 65%). All oximetry results in thehigh-risk group were significantly different from the totalcohort.

Factors Influencing ScO2

Table 2 shows that ScO2min-ox was correlated with variousdemographic and physiologic variables, especially age, gen-der, body mass index, American Society of Anesthesiologygrade, additive EuroSCORE, LVEF, glomerular filtrationrate, and hematocrit.

Analysis of ScO2min-ox in different EuroSCORE groupsshowed significant differences between the groups with higherScO2 concentrations in the decreased additive EuroSCOREgroups (fig. 2). Comparably, patients with a decreased LVEF, ahigher NTproBNP, and a higher hsTNT had lower ScO2min-ox

than the healthier groups of patients (fig. 2).

ScO2 and Clinical OutcomesUnivariate analyses of patients with postoperative mortalityand morbidity revealed that patients with an adverse out-come had decreased preoperative ScO2 levels, a higher addi-tive EuroSCORE, a decreased preoperative hematocrit, anda longer duration of surgery and CPB (table 1).

ROC analysis of ScO2min-ox and 30-day mortality revealedan area under the curve (AUC) of 0.71 (95% CI, 0.68–0.73;P � 0.0001) and a cutoff value of �51% (sensitivity 41.5%,specificity 93.6%) in the total cohort and an AUC of 0.77 (95%CI, 0.69–0.86; P � 0.0001) and a cutoff value of �53% (sen-sitivity 75.0%, specificity 79.1%) in patients with a Euro-SCORE more than 10. The respective results for the combinedmorbidity endpoint (a MaCS of at least two and/or a high-dependency unit time of at least 10 days) revealed an AUC of0.68 (95% CI, 0.65–0.70; P � 0.0001) in the total cohort. Thecutoff value was a ScO2min-ox of �60% with a sensitivity of56.1% and a specificity of 71.4%.

To rule out a possible confounding effect of intubationand controlled ventilation in emergency patients, theROC analyses were also performed in the subgroup ofelective patients. The analysis of ScO2min-ox and 30-daymortality revealed an AUC of 0.66 (95% CI, 0.63– 0.69)with a cutoff value of �53%, a sensitivity of 40.9%, and aspecificity of 90.7% (P � 0.018). The comparable analy-sis in the patients with emergency status revealed an AUCof 0.74 (95% CI, 0.68 – 0.8) with a cutoff ScO2min-ox of�50%, a sensitivity of 47.4%, and a specificity of 91.5%(P � 0.0002).



Table 1. Patient Characteristics, Surgical Course, Mortality, and Morbidity in 1,178 Patients Undergoing On-pumpCardiac Surgery

Patient Characteristics Total Cohort

30-day Mortality Combined Morbidity Endpoint

Alive Deceased Significance Not Fulfilled Fulfilled Significance

Number of cases 1,178 1,137 (96.5%) 41 (3.5%) 1,021 (86.7%) 157 (13.3%)Demographic data

Female 348 (29.5%) 330 (29%) 18 (44%) P � 0.061 290 (28.4%) 58 (36.9%) P � 0.037Male 830 (70.5%) 807 (71%) 23 (56%) 731 (71.6%) 99 (63.1%)Age (yr) 68 (59/74) 68 (59/74) 74 (70/78) P � 0.001 67 (58/74) 72 (67/77) P � 0.001BMI (kg/m2) 27 (24/32) 27 (25/31) 26 (23/29) P � 0.098 27 (25/30) 26 (24/31) P � 0.013

HistoryHyperlipidemia 699 (59.3%) 680 (59.8%) 19 (46.3%) P � 0.163 608 (59.5%) 91 (57.9%) P � 0.764Arterial hypertension 995 (84.5%) 961 (84.5%) 34 (82.9%) P � 0.902 855 (83.7%) 140 (89.2%) P � 0.131Diabetes mellitus 346 (29.4%) 330 (29.0%) 14 (34.1%) P � 0.229 283 (27.7%) 63 (40.1%) P � 0.002Carotid stenosis 20 (1.7%) 18 (1.6%) 2 (4.9%) P � 0.323 17 (1.7%) 3 (1.9%) P � 0.913Peripheral artery

disease80 (6.8%) 76 (6.7%) 4 (9.8%) P � 0.651 61 (6.0%) 19 (12.1%) P � 0.008

Stroke* 41 (3.5%) 38 (3.3%) 3 (7.3%) P � 0.352 35 (3.4%) 6 (3.8%) P � 0.986Preoperative therapy

�-Blockers 685 (58.1%) 662 (58.2%) 23 (56.1%) P � 0.648 596 (58.4%) 89 (56.7%) P � 0.588Amiodarone 22 (1.9%) 21 (1.8%) 1 (2.4%) P � 0.815 20 (1.9%) 1 (0.6%) P � 0.434Antiarrhythmics 18 (1.5%) 17 (1.5%) 1 (2.4%) P � 0.935 18 (1.8%) 0 (0%) P � 0.207Diuretics 542 (46.0%) 521 (45.8%) 21 (51.2%) P � 0.194 459 (44.9%) 83 (52.9%) P � 0.009RAAS antagonists 753 (63.9%) 733 (64.5%) 20 (48.7%) P � 0.259 658 (64.4%) 95 (60.5%) P � 0.968Nitrates po 138 (11.7%) 133 (11.7%) 5 (12.2%) P � 0.915 116 (11.4%) 22 (14.0%) P � 0.249Nitrates iv 67 (5.7%) 64 (5.6%) 3 (7.3%) P � 0.858 50 (4.9%) 17 (10.8%) P � 0.003Digitalis 102 (8.6%) 96 (8.4%) 6 (14.6%) P � 0.163 83 (8.1%) 19 (12.1%) P � 0.072Lipid-lowering drugs 585 (49.7%) 568 (49.9%) 17 (41.4%) P � 0.805 525 (51.4%) 60 (38.2%) P � 0.017Heparin/LMWH 364 (30.9%) 348 (30.6%) 16 (39%) P � 0.116 307 (30.1%) 57 (36.3%) P � 0.027Warfarin 75 (6.4%) 72 (6.3%) 3 (7.3%) P � 0.908 60 (5.9%) 15 (9.6%) P � 0.065Clopidogrel 147 (12.5%) 143 (12.6%) 4 (9.8%) P � 0.972 128 (12.5%) 19 (12.1%) P � 0.981Aspirin 623 (52.9%) 613 (53.9%) 19 (46.3%) P � 0.976 561 (54.9%) 71 (45.2%) P � 0.161Clonidine 12 (1.0%) 12 (1.0%) 0 (0%) P � 0.832 11 (1.1%) 1 (0.6%) P � 0.997Calcium antagonists 223 (18.9%) 219 (19.3%) 4 (9.8%) P � 0.292 198 (19.4%) 25 (15.9%) P � 0.581Direct vasodilatators 40 (3.4%) 39 (3.4%) 1 (2.4%) P � 0.812 38 (3.7%) 2 (1.3%) P � 0.221Risk stratification

NYHA III/IV 484 (41.1%) 461 (40.5%) 23 (56.1%) P � 0.051 398 (39.0%) 86 (54.7%) P � 0.001NYHA I/II 694 (58.9%) 676 (59.5%) 18 (43.9%) 618 (60.5%) 69 (43.9%)LVEF �30% 54 (4.6%) 46 (4.0%) 8 (19.5%) P � 0.001 39 (3.8%) 15 (9.6%) P � 0.003LVEF �50% 277 (23.5%) 261 (22.9%) 16 (39%) P � 0.022 244 (23.9%) 53 (33.7%) P � 0.002

ASA 3 (3/3) 3 (3/3) 3 (3/4) P � 0.001 3 (3/3) 3 (3/4) P � 0.001Additive EuroSCORE 5 (3/8) 5 (3/7) 10 (7/12) P � 0.001 5 (3/7) 8 (6/11) P � 0.001Angina pectoris 635 (53.9%) 617 (54.3%) 18 (43.9%) P � 0.248 92.3 88 (56.0%) P � 0.630Previous MI 295 (25.0%) 280 (24.6%) 15 (36.6%) P � 0.098 243 (23.8%) 52 (33.1%) P � 0.012Previous cardiac

surgery108 (9.2%) 103 (9.0%) 5 (12.2%) P � 0.683 86 (8.4%) 22 (14.0%) P � 0.035

Left main stem stenosis 215 (18.2%) 211 (18.5%) 4 (9.7%) P � 0.219 190 (18.6%) 25 (15.9%) P � 0.505Active endocarditis 33 (2.8%) 31 (2.7%) 2 (4.9%) P � 0.735 21 (2.0%) 12 (7.6%) P � 0.001Circulatory support† 61 (5.2%) 49 (4.3%) 12 (29.3%) P � 0.001 38 (3.7%) 23 (14.6%) P � 0.001

Type of surgeryCABG 800 (67.9%) 772 (67.9%) 28 (68.3%) P � 0.888 692 (67.8%) 110 (70.1%) P � 0.631No CABG 378 (32.1%) 365 (33.0%) 13 (31.7%) 329 (32.2%) 47 (29.9%)

Surgical priorityElective 1,058 (89.8%) 1,032 (90.7%) 26 (63.4%) P � 0.001 943 (92.4%) 115 (73.2%) P � 0.001�12 h and emergency 120 (10.2%) 105 (9.3%) 15 (36.6%) 78 (7.6%) 42 (26.8%)

Physiological statusMAP (mmHg) 95 (87/103) 95 (87/103) 94 (80/100) P � 0.276 95 (87/103) 93 (83/103) P � 0.058Heart rate (/min) 69 (63/81) 69 (62/80) 84 (75/93) P � 0.001 69 (61.5/78) 76 (65/87) P � 0.001SaO2 initial (%) 97 (95/98) 97 (95/98) 96 (95/97) P � 0.058 97 (95/98) 96 (95/97) P � 0.001

ScO2 room air n � 1,123Right (%) 62 (57/67) 62 (57/67) 55 (47/62) P � 0.001 62 (58/67) 57 (52/62) P � 0.001Left (%) 62 (56/67) 62 (57/67) 55 (49/65) P � 0.002 62 (57/67) 57 (51/62) P � 0.001Minimal left or right (%) 60 (55/64) 60 (55/65) 54 (47/61) P � 0.001 61 (56/65) 56 (49/60) P � 0.001

ScO2 with oxygen n � 1,109Right (%) 66 (61/71) 66 (61/71) 60 (50/68) P � 0.001 66 (62/72) 62 (56/67) P � 0.001Left (%) 66 (61/71) 66 (61/71) 61 (51/67) P � 0.001 67 (62/72) 61 (55/67) P � 0.001

Minimal ScO2 with oxygen(ScO2min-ox)‡

n � 1,178

ScO2min-ox (left or right) (%) 65 (59/69) 64 (59/69) 58 (47/64ox) P � 0.001 65 (60/70) 60 (53/65) P � 0.001(continued)



To determine whether the capability of increasing ScO2

concentrations during oxygen supplementation in patientswith a low ScO2min-room had prognostic relevance, patientspresenting with a ScO2min-room of �51% and showing anincrease to ScO2min-ox concentrations higher than 51% dur-ing oxygen application were compared with those patientsthat remained below 51% ScO2min-ox. Of 142 patients, 81with a ScO2min-room of �51% responded to oxygen by in-creasing ScO2min-ox to concentrations higher than 51%; in61 patients, ScO2min-ox remained lower or equal than 51%.Mortality and morbidity were significantly higher in thenonresponders than in the responders (30-day mortality:16.4% vs. 2.5%, P � 0.0081, combined morbidity end-point; a MaCS of at least two and/or a high-dependency unittime of at least 10 days: 37.7% vs. 14.8%, P � 0.0033).

Predictive Accuracy of ScO2 versus Additive EuroSCOREComparative ROC analyses of additive EuroSCORE with re-spect to 30-day mortality and the combined morbidity end-point in the total cohort revealed an AUC of 0.82 (95% CI,0.8–0.84%) for mortality and an AUC of 0.77 (95% CI: 0.74–0.79%) for morbidity. A comparison with ScO2min showed thatthe EuroSCORE had a better accuracy in predicting 30-daymortality (difference between areas, 0.11; P � 0.015; fig. 3) andmorbidity (difference between areas, 0.09; P � 0.001) in thetotal cohort. Comparable results were obtained in patients withan additive EuroSCORE below 10 (data not shown).

In the high-risk group with an additive EuroSCOREmore than 10, ScO2min-ox had a better accuracy for 30-daymortality than the EuroSCORE (EuroSCORE, 0.54 [95%CI, 0.43–0.64%]; ScO2min-ox, 0.79 [CI 95%, 0.7–0.86%]; �AUC 0.25, P � 0.0044) (fig. 3). The predictive capacity formorbidity in the high-risk group was not different betweenthe EuroSCORE and the ScO2min-ox (EuroSCORE, 0.61;[95% CI, 0.51–0.71%]; ScO2min-ox: 0.64 [CI 95%, 0.57–0.76%]; � AUC 0.06, P � n.s.).

Predictive Accuracy of hsTNT and NTproBNPROC analyses of hsTNT and 30-day mortality revealed anAUC of 0.8 (95% CI, 0.77–0.82%; P � 0.001) and an optimalcutoff value of 28 pg/ml with a sensitivity of 81.8% and a spec-ificity of 73.8% in the total cohort. The respective results in thehigh-risk group (EuroSCORE more than 10) were: AUC of0.71 (95% CI: 0.59–0.81%), P � 0.002, a cutoff of 37.1pg/ml, a sensitivity of 100%, and a specificity of 50%.

ROC analysis of the predictive capacity of hsTNT for thecombined morbidity endpoint showed an AUC of 0.72(95% CI, 0.69–0.75%), P � 0.001, and an optimal cutoffof 21.8 pg/ml with a sensitivity of 62.7%, and a specificity of71.5%. The respective analysis in the high-risk group failedto reach statistical significance.

ROC analysis of NTproBNP and 30-day mortalityshowed an AUC of 0.78 (95% CI, 0.76–0.81%), P � 0.001,and a cutoff concentration of 1,743 pg/ml with a sensitivity of75.8% and a specificity of 79.9% in the total cohort. The ROC

Table 1. Continued

Patient Characteristics Total Cohort

30-day Mortality Combined Morbidity Endpoint

Alive Deceased Significance Not Fulfilled Fulfilled Significance

Laboratory analysesNTproBNP (pg/ml)

n � 1,011501 (154/1,471) 463 (151/1,309) 2,330 (1,567/9,474) P � 0.001 427 (137/1,143) 1,459 (419/4,882) P � 0.001

hsTNT (ng/ml) n � 985 14 (7/33) 13 (7/30) 54 (30/582) P � 0.001 12 (7/26) 35 (15/124) P � 0.001Plasma creatinin (mg/dl)

n � 1,1750.93 (0.80/1.13) 0.92 (0.78/1.12) 1.06 (0.83/1.31) P � 0.029 0.92 (0.78/1.01) 1.02 (0.80/1.33) P � 0.001

eGFR§ (ml/min/1.73 m2)n � 1,175

80 (63/99) 81 (64/99) 66 (51/82) P � 0.002 82 (66/100) 67 (50/87) P � 0.001

Hemoglobin (g/l)n � 1,132

135 (124/146) 135 (123/146) 129 (104/146) P � 0.017 136 (125/146) 129 (115/141) P � 0.001

Hematocrit (%)n � 1,132

39 (36/42) 39 (36/42) 37 (31/42) P � 0.033 39 (36/42) 37 (34/42) P � 0.001

Intraoperative courseDuration surgery (min) 249 (209/300) 246 (208/295) 342 (267/426) P � 0.001 243 (207/290) 306 (241/383) P � 0.001Duration CPB (min) 109 (88/141) 108 (88/139) 169 (117/226) P � 0.001 107 (87/136) 138 (105/191) P � 0.001Aortic cross-clamp time

(min)85 (68/110) 85 (67/109) 103 (84/137) P � 0.001 84 (67/107) 102 (78/138) P � 0.001

Data are given as median and (25/75) percentiles for continuous variables and as percentage for categorical variables. The combinedmorbidity endpoint was defined as �2 complications (need of new renal replacement therapy, reintubation, stroke (RANKIN grade �1),and low-cardiac output syndrome) and/or need for a high-dependency unit treatment of �10 days.* History of stroke defined as former ischemic cerebral infarction or hemorrhagic stroke with a Rankin grade �1; † circulatory supportwith intravenous inotropes, vasopressors, or intraaortic counterpulsation; ‡ minimal ScO2 either with or without oxygen; § eGFRcalculated by the Modifications of Diet in Renal Disease equation.ASA � American Society of Anesthesiology grading; BMI � body mass index; CABG � coronary artery bypass grafting; CPB �cardiopulmonary bypass; eGFR � estimated glomerular filtration rate; hsTNT � high-sensitivity troponin T; LMWH � low-molecularweight heparine; LVEF � left ventricular ejection fraction; MAP � mean arterial blood pressure; MI � myocardial infarction; NT-proBNP � N-terminal pro-B-type natriuretic peptide; NYHA � New York Heart Association grading; RAAS antagonists � renin-angiotensin-aldosterone system; SaO2 � arterial oxygen saturation; ScO2 � cerebral oxygen saturation.



analysis of NTproBNP and mortality in the high-risk group wasnot significant. ROC analysis of NTproBNP and morbidityrevealed an AUC of 0.7 (95% CI, 0.67–0.73%), P � 0.001,and a cutoff concentration of 1,061 pg/ml with a sensitivity of61.2% and a specificity of 74.4%.

Comparative analyses on the accuracy of NTproBNP,hsTNT, and ScO2min-ox were performed in the subgroup ofpatients with complete hormone analysis and revealed nosignificant differences in the accuracy for predicting 30-dayand 1-yr mortality in the total cohort (data not shown).

Logistic RegressionBackward logistic regression analyses for 30-day and 1-yr mor-tality was performed using a model with the EuroSCOREgraded in different risk categories (0–2, 3–5, 6–10, �10) andthe lowest cutoff value derived from the different ROC analysesfor ScO2min-ox (�50%). As a marker for the severity of the sur-gical insult, CPB time was added to the model. The cutoff valuefor 30-day mortality derived from ROC analysis for CPB timewas more than 114 min with an AUC of 0.76, a sensitivity of82.9%, and a specificity of 57.2% (P � 0.0001). To allow easiercomparisons in future studies, the CPB time cutoff was set tomore than 120 min. The 30-day mortality rates in the differentEuroSCORE categories were: EuroSCORE 0–2, 0.3%; Euro-SCORE 3–5, 1.3%; EuroSCORE 6–10, 5.2%; EuroSCOREmore than 10, 16.7%.

With respect to the fact that preoperative determinationof NTproBNP and hsTNT cannot be considered routine inmany European heart centers, calculations were either per-formed with or without inclusion of NTproBNP andhsTNT. The results of the logistic regression analyses aregiven in table 3, showing that a ScO2min-ox equal or less than50% is an independent predictor of 30-day mortality, if con-ventional risk factors are used, and of 30-day, as well as 1-yr,mortality, if NTproBNP and hsTNT are entered into themodel. The category EuroSCORE 3–5 was not included inthe regression models because of the low event rate (5 deathsper 401 patients).

Kaplan–Meier Survival AnalysesThe effects of ScO2 on long-term mortality using a ScO2min-ox

�50% as a cutoff value was analyzed by Kaplan–Meier sta-tistics. Log-rank test revealed a significant effect in the totalcohort as well as in the high-risk group with a EuroSCOREmore than 10 (fig. 4).

Discussion

Increasing evidence suggests that decreased ScO2 during sur-gery is associated with unwarranted neurologic effects and acomplicated postoperative course.1,3 Most studies in thisfield have only focused on the relative changes of ScO2 duringcardiac6,14,15 and noncardiac surgery.16,17 To what extentdecreased preoperative ScO2 concentrations are related topostoperative complications and mortality has not been for-mally analyzed in a large cohort of patients.

The findings of the current study, showing that preoperativeScO2 levels are closely related to relevant measures of cardiopul-monary function, postoperative morbidity, and short- and long-term mortality, may help to better understand the role of peri-

Fig. 1. Histogram of the lowest preoperative cerebral oxygensaturation measured during oxygen insufflation (ScO2min-ox) ina cohort of 1,178 cardiac surgery patients.

Table 2. Relationship among Preoperative CerebralOxygen Saturation, Demographics, and VariablesRepresentative of Cardiovascular Status or Risk

Variable

Spearman’s RankTest/Coefficientof Contingence Significance

Age �0.2 P � 0.0001Gender 0.09* P � 0.0026Body mass index 0.19 P � 0.0001Surgical priority

urgent/emergency0.032* P � 0.267

CABG vs. NO-CABG 0.02* P � 0.521Preoperative circulatory

support (IABP,Inotropes, Vasopressors)

0.04* P � 0.225

Heart rate �0.03 P � 0.342LVEF �30% 0.09* P � 0.0016Creatinine (plasma) �0.12 P � 0.0001eGFR 0.19 P � 0.0001NTproBNP �0.35 P � 0.0001hsTNT �0.28 P � 0.0001Hemoglobin 0.37 P � 0.0001Hematocrit 0.34 P � 0.0001Preoperative heparin/

LMWH*0.07* P � 0.022

Kendall’s �ASA �0.10 P � 0.0001Additive EuroSCORE �0.20 P � 0.0001

* Coefficient of contingence: chi-square test.ASA � American Society of Anesthesiology grading; CABG �coronary artery bypass grafting; eGFR � estimated glomerularfiltration rate; hsTNT � high-sensitivity troponin T; IABP � in-traaortic ballon pump; LMWH � lowmolecular weight heparine;LVEF � left ventricular ejection fraction; NTproBNP � N-terminalpro-B-type natriuretic peptide.



operative changes in ScO2 and may have implications forimproving risk stratification in cardiac surgery.

From a technical point of view, ScO2, determined by near-infrared spectroscopy, is reflective of tissue oxygen saturationin a small sample of the frontal cortex, and, with respect tothe distribution of arterial and venous blood, weighted by thevenous compartment.1,18 Various experimental and clinicalstudies have clearly shown that ScO2 determined by near-infrared spectroscopy is directly related to cerebral bloodflow and jugular venous oxygen saturation (SvO2).19,20

Current evidence supports that ScO2 also indirectly re-flects the adequacy of the systemic circulation and cardiopul-monary function. In line with other studies comparing ScO2

and mixed SvO2 in children,21 we were able to show a closecorrelation between ScO2 and SvO2 in extubated patientsafter cardiac surgery.** Comparably, despite the absolute lev-els of ScO2 and SvO2 that were only moderately correlated,Dullenkopf et al. showed that trends in ScO2 reflect changesin ScO2 in intubated patients immediately after cardiac sur-gery.22 Skhirtladze et al. observed that patients with se-verely reduced LVEF being scheduled for implantation ofa defibrillator cardioverter system had lower ScO2 concen-trations than patients with a preserved LVEF.23 Madsen etal. showed that patients presenting with acute heart failure

had lower ScO2 concentrations than healthy control pa-tients and that ScO2 increased during heart failure thera-py.24 Koike et al. showed that the decrease in ScO2 duringexercise in patients with coronary artery disease had prog-nostic effect and was associated with an unfavorableoutcome in these patients.25 Paquet et al. observedthat baseline ScO2 was related to LVEF in patients under-going cardiac surgery and that ScO2 had an acceptableaccuracy to identify left ventricular dysfunction in thesepatients.26

The findings of the current study, showing significantcorrelations between NTproBNP, hsTNT, LVEF, and ScO2

in a large patient sample, support the concept that ScO2 isinfluenced by myocardial function and the performance ofthe cardiopulmonary system.

This may have clinical and scientific implications. First, mostguidelines on ScO2 monitoring for guiding hemodynamics andCPB management during cardiac surgery suggest the adjust-ment of therapy according to relative changes from the preop-erative baseline (i.e., to maintain relative ScO2 concentrationshigher than 80% of baseline).27 Based on our findings, thisconcept may be appropriate for patients starting with a ScO2 ina healthy range but may be inadequate for patients presentingwith decreased preoperative ScO2 as an expression of severe car-diopulmonary dysfunction. Second, these findings offer scien-tific perspectives for using ScO2 as a noninvasive technology forguiding therapy in patients with heart failure as already sug-gested by Madsen et al. more than 10 yr ago.24

The accuracy of ScO2 for predicting 30-day mortality inthe total cohort was lower than the additive EuroSCORE butcomparable with established (NTproBNP)28,29 and emerg-ing (hsTNT)10,30 humoral markers of postoperative risk incardiac surgery. As derived from the ROC and the Kaplan–Meier analyses, the accuracy of ScO2 for predicting short- andlong-term prognosis in high-risk patients is clearly superiorto the EuroSCORE. It is noteworthy that patients with a

** Poster presentation by Julika Schon, M.D., Department ofAnesthesiology, University of Lubeck, Lubeck, Germany at the au-tumn meeting of the Working Group in Cardiac Anesthesia of theGerman Association of Anesthesiology and Intensive Care Medi-cine, November 12–14, 2009, Ulm, Germany.

A

C D

B

Fig. 2. Preoperative oxygen-supplemented cerebral oxygensaturation (ScO2min-ox) in different additive EuroSCORE riskgroups (A), according to preoperative left ventricular ejectionfraction (LVEF) (B), in different quartiles of the plasma con-centration of high-sensitivity troponin T (hsTNT) (C), and N-terminal pro-B-type natriuretic peptide (NTproBNP) (D). * Sig-nificant difference (P � 0.05) compared with the respectivegroups (Kruskal–Wallis test). Data are given as median and95% confidence interval of the median.

Fig. 3. Receiver-operating curve analyses of minimal preop-erative cerebral oxygen saturation during oxygen insufflation(ScO2min-ox, broken line) and additive EuroSCORE (unbrokenline) for 30-day mortality in the total cohort of 1,178 patients(A) and in 102 high-risk patients with a EuroSCORE morethan 10 (B) showing a significantly better predictive accuracyof the EuroSCORE in the total cohort (P � 0.015) and ofScO2min-ox in the high-risk group (P � 0.0044).



EuroSCORE more than 10 and a ScO2min-ox equal or lessthan 50% had a 1-yr mortality that was twice as high as inhigh-risk patients with preserved—more than 50%— ScO2

concentrations. This is a remarkable finding because riskstratification in high-risk cardiac surgery patients by Euro-SCORE, as frequently performed in most European heartcenters, is limited by the fact that the additive and the logisticEuroSCORE overestimate mortality in this group of pa-tients.31,32 Consequently, our findings, if reproduced pro-spectively, may have relevant implications for improving riskstratification in high-risk cardiac surgery patients.

To rule out a possible confounding effect of arterial hyp-oxia on the results of ScO2 monitoring, we measured ScO2

with room air and during oxygen insufflation. The differencebetween the median results with both measures was 4% andcomparable with the 3% difference in transcutaneous oxygensaturation achieved with application. Numerically, the accu-racy for predicting 30-day mortality was not different if the ScO2

values derived with room air or during oxygen supplementationwere used (data not shown). However, an analysis of whetherthe capability to increase ScO2 during oxygen supplementationin patients with a low ScO2 during room air had prognosticrelevance revealed that nonresponders (i.e., patients that failedto increase ScO2 beyond the cutoff value) had a significantlyhigher mortality and morbidity than those showing an in-crease beyond the ScO2 cutoff. This suggests that if ScO2 willbe used for risk stratification, this parameter should ideally bedetermined during oxygen supplementation.

Besides the EuroSCORE, various other risk stratificationmodels are used in cardiac surgery.33 Currently, most of

these models, comparable with the EuroSCORE, have beendeveloped and validated in patients undergoing CABG sur-gery, and the predictive accuracy for patients undergoingother types of surgery is often limited. In contrast, the Societyof Thoracic Surgeons score is available in different versionsfor various kinds of cardiac procedures. This score has anexcellent predictive capacity but needs a large number ofvariables to be entered.34–36 Consequently, at least in Eu-rope, it is less frequently used than the EuroSCORE.

Focusing more on physiologic than historical variables,Ranucci et al. have shown that a simple score consisting of thevariables age, creatinine, and left ventricular ejection fraction hasan accuracy for 30-day mortality that is comparable withthe additive and the logistic EuroSCORE.37 This suggeststhat risk stratification based on age and physiologic vari-ables is feasible and may at least be as predictive as a classicrisk score.

Our findings, regarding the discriminatory capacity of NT-proBNP for predicting 30-day mortality, are in line with previ-ous observations in cardiac28,29 as well as noncardiac patients.29

The accuracy of NTproBNP was comparable with the additiveEuroSCORE and ScO2min. The latter also holds true forhsTNT, an observation that is remarkable in so far as this pre-clinical test has not been used in patients undergoing cardiacsurgery before. It is also of note that the hsTNT cutoff for30-day mortality was highly comparable with the one derivedfrom a large trial in medical patients with heart failure,10 furthersuggesting that hsTNT serves not only as a marker of myocar-dial ischemia but, comparable with NTproBNP, as a measure ofglobal cardiopulmonary dysfunction.

Table 3. Results of Logistic Regression Models for 30-day and 1-year Mortality

Variables30-day Mortality Excluding

NTproBNP and hsTNT30-day Mortality Including

NTproBNP and hsTNT1-yr Mortality IncludingNTproBNP and hsTNT

Number of patients n � 1,178 n � 984 n � 984Number of events n � 41 n � 33 N � 72EuroSCORE 0–2 Reference Reference ReferenceEuroSCORE 3–5 Not included in the model Not included in the model Not included in the modelEuroSCORE 6–10 4.9 (1.7–13.2) P � 0.0015 3.3 (1.1–10.2) P � 0.034 2.1 (1.1–4.2) P � 0.031EuroSCORE �10 12.0 (4.5–31.9) P � 0.0001 6.4 (2.1–19.8) P � 0.006 5.7 (2.7–11.6) P � 0.0001ScO2 min-ox �50% 4.6 (2.2–9.8) P � 0.0001 2.5 (1.0–6.0) P � 0.044 2.6 (1.2–4.2) P � 0.0077Duration of CPB*

�120 min2.0 (0.97–4.4) P � 0.06 Not included in the model 1.7 (0.97–2.9) P � 0.062

hsTNT �28 pg/ml Not applicable 3.6 (1.4–9.2) P � 0.008 1.8 (1.0–3.3) P � 0.042NTproBNP

�1,743 pg/mlNot applicable 3.4 (1.3–8.6) P � 0.01 2.2 (1.2–4.1) P � 0.01

Overall model fit:Chi-squareSignificance

73.5 P � 0.0001 76.8 P � 0.0001 107.4 P � 0.0001

Results of the backward logistic regression are given as odds ratio and 95% confidence interval in parentheses. The models werecalculated using additive EuroSCORE (graded in four categories of different mortality risks: 0–2; 3–5; 6–10; �10) and the cutoff valuesderived from receiver-operating curve analyses of the current study.* The cutoff for 30-day mortality derived from the receiver-operating curve analysis for duration of CPB (114 min) was set to 120 minfor better comparability.CPB � cardiopulmonary bypass; hsTNT � high-sensitivity troponin T; NTproBNP � N-terminal pro-B-type natriureti-peptide; ScO2min-ox �minimal cerebral oxygen saturation derived when breathing oxygen enriched air.



LimitationsThe current study has limitations.

1. The short-time mortality in the study population waslow. Thus, the results presented, despite being statisticallysignificant, are prone to potential error and require pro-spective confirmation. However, our findings are sub-stantiated by the fact that when analyzing 1-yr mortality,the number of patients with an adverse outcome wasmore than twice as high and remained statistically signif-icant not only when focusing on the total cohort but alsoon the subsets of patients with different surgical priority.

2. The ScO2 monitors used in the current study (INVOS�4100 and 5100) only have a Federal Drug Administrationapproval for trend monitoring of ScO2 and not for abso-lute values. Recently, another ScO2 monitoring system(Fore-Sight�; CAS Medical Systems, Branford, CT) hasbeen introduced to the market that, by using four insteadof three wavelengths for determination of oxygenated anddeoxygenated hemoglobin and laser light instead of alight emitting diode, has been suggested to be capable ofmeasuring absolute ScO2 concentrations.3 No compara-tive data of ScO2 concentrations derived by these differentmonitors are available, thus it remains currently specula-tive whether one system is more precise than the other.However, it is likely that any measure improving the re-liability of the near-infrared spectroscopy technology willalso improve the accuracy of ScO2 for risk stratification.

3. Unfortunately, ScO2 concentrations with oxygen were onlyavailable for 1,109 patients and were missing in some pa-tients that have died. However, with respect to the observa-tion that patients with a poor prognosis showed only minorincreases of ScO2 during oxygen supplementation, we have

used the ScO2min-room values from the missing 69 patients forcalculation of ScO2min-ox to allow calculations on the maxi-mal number of patients with adverse events.

4. The modeling strategy of the current study was designedto explore associations, and many of the analyses are basedon post hoc and subgroup analyses of the primary dataset.Consequently, the results of the current study requireprospective replication in an independent sample.

Conclusion

In conclusion, the current study shows that preoperativeScO2 levels determined by near-infrared spectroscopy are re-lated to objective measures of cardiopulmonary function andthat low preoperative ScO2 concentrations are associated withan adverse perioperative course. A ScO2min-ox equal or lessthan 50% is an independent predictor of short- and long-term mortality in patients undergoing on-pump cardiac sur-gery and might serve as a refined marker for preoperative riskstratification in cardiac surgery patients.

The members of the cardiac anesthesia unit and the personnel of theDepartment of Clinical Chemistry (University of Lubeck, Lubeck,Germany) are thanked for their help in data and blood sampleacquisition.

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Fig. 4. One-yr Kaplan–Meier survival curves of patients undergoing on-pump cardiac surgery with (red) or without (blue) apreoperative cerebral oxygen saturation (ScO2min-ox) during oxygen insufflation equal or less than 50% absolute in the totalcohort of 1,178 patients (A) and in a subgroup of 102 patients with an additive EuroSCORE more than 10 (B). Log-rank testindicates that groups differ, both the total cohort and the subgroup with a EuroSCORE more than 10.



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ANESTHESIOLOGY REFLECTIONS

Oehmig’s Monument to Ether, Public Gardens

Unveiled in 1868 on the Boston Public Gardens, the granite “Monument to Ether” avoided taking sides asto which co-patentee, dentist W. T. G. Morton or physician C. T. Jackson, actually deserved credit forbringing ether anesthesia to humankind. As the Ether Controversy raged, Dr. Oliver Wendell Holmes(1805–1894) mused that the granite was a “monument to ether—or either” of the quarreling co-paten-tees. In 1992 Monument to Ether, Public Gardens was painted (left) by Keith S. Oehmig of Brunswick,Maine, and then placed in the American Society of Anesthesiologists’ newly opened WLM Gallery(center). Oehmig captured in oil that the “ordered, defined structure of the monument and footpathscontrast with the soft, amorphous roses and trees of the Garden.” Note that the nebulously painted“Good Samaritan” figure atop the monument (right) was that of a medieval Moorish physician—a figurechosen purposefully to avoid siding with any one person or profession as to “who discovered anesthesia.”(Copyright © the American Society of Anesthesiologists, Inc. This image also appears in the Anesthesi-ology Reflections online collection available at www.anesthesiology.org.)

George S. Bause, M.D., M.P.H., Honorary Curator, ASA’s Wood Library-Museum of Anesthesi-ology, Park Ridge, Illinois, and Clinical Associate Professor, Case Western Reserve University,Cleveland, Ohio. [email protected].



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