The Clinical Utility of Cerebral Oximetry Monitoring

Transcription

1 The Clinical Utility of Cerebral Oximetry Monitoring Edwin G. Avery, IV, M.D., C.P.I. Chief, Division of Cardiac Anesthesia University Hospitals Case Medical Center Associate Professor of Anesthesiology Case Western Reserve University School of Medicine Cleveland, OH Crestock

2 Disclosures Covidien: funded research, consultant, speaker s bureau Alere: funded research Medtronic: funded research

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4 Objectives: To understand the physical principles upon which these monitors function To review laboratory and clinical outcome studies that validate this technology To review the known limitations of this technology in the clinical setting A-Star Research

5 Physical Principles of Operation & General Concepts Somanetics.com

6 General Concepts Measured parameter Near-infrared spectroscopy (NIRS) is used to assess cerebral tissues and involves the use of light (λ = nm) to detect chromophores (specifically, quantities of both total and deoxygenated hemoglobin) Somanetics.com Appl Optics 1989; 28:2245

7 General Concepts rso 2 rso 2 Regional tissue oxygen saturation (15 mm 3 ) Directly measures both deoxy- & total hemoglobin % Back calculates oxyhemoglobin % (i.e. total Hb deoxy-hb) Obtains these continuous, real-time measurements with NIR reflectance spectroscopy Measures only the microcirculation (i.e. < 100 µm) < 100 microns in diameter Somanetics.com 2010 Avery EG, White paper

8 General Concepts rso 2 The rso 2 value is venous weighted parameter Foresight, Cerox, Equanox (70 venous : 30 arterial) INVOS (75 venous : 25 arterial) This ratio is assumed to be static under all monitoring conditions very likely a flawed assumption that will be addressed in future generations of this technology Each device uses different absolute wavelengths, different light sources (LEDs vs Lasers), different numbers of λs &different processing algorithms all with the same goal of most accurately measuring oxy-hb % in the interrogated tissue Additional λs are used to attempt to compensate for other non-hb chromophores J Clin Monit 2000; 16; Avery EG, White paper

9 General Concepts rso 2 Hb is a chromophore (part of molecule responsible for its color in that when it absorbs, transmits or reflects photons of light it changes in color) The human body is full of different chromophores (e.g., H 2 O, bilirubin, Hb, etc.) A derivation of the Beer-Lambert Law allows a calculated estimate of the deoxy- & total Hb % in the interrogated tissue Green Fluorescent Protein (GFP) from the N. American Jellyfish Avery EG, White paper

10 General Concepts - NIRS Emitted light follows a predictable path that resembles a banana like or curvilinear arc. Placing a second, more distal sensor allows for a deeper signal penetration spatial resolution. Modified from Covidien Validation Image Neurol Res 1995;17: 89 Banana arc Arc sensor (distal detector) Arc sensor (proximal detector) Adhesive pad Light emitting diode

11 General Concepts rso 2 Sensor PAD Receptors LED Beer-Lambert Law + scatter correction rso 2

12 General Concepts rso 2 Thus, rso 2 values represent the regional oxygen balance in the frontal lobes, or stated differently rso 2 primarily represents the Cerebral venous reserve capacity following tissue oxygen extraction 70-75% venous blood Courtesy of Covidien 2010 Avery EG, White paper

13 General Concepts rso 2 rso 2 desaturation indicates increased oxygen extraction and/or decreased oxygen delivery to the tissues rso 2 does not reliably reflect tissue ischemia as would be measured by an EEG only decreased venous oxy- Hb saturation (i.e. most commonly O 2 extraction) Avery EG, White paper

14 Cerebral rso 2 The Measured Variable A blurry, not absolute, window allowing insight into tissue O 2 balance rso 2

15 Available devices There are currently five FDA cleared devices that are marketed to assess cerebral oxygenation which include: 2λ Covidien - INVOS CASMED Fore-sight 4λ Laser light (~5 yrs of clinical use) (~20 yrs of clinical use) 4λ Ornim Cerox 3,4λ Ultrasound tagged NIR light Approved 1/2011, not marketed Nonin Equanox (2 models) Devices listed in order of FDA clearance 2010 Avery EG, White paper. Gagnon RE, Macnab AJ, Gagnon FA, et al. Comparison of Two Spatially Resolved NIRS Oxygenation Indices. J Clin Monit 2002;17:385-91

16 General Concepts Clinical Use Bi-frontal adhesive pads applied to hairless skin Room air baseline established (recommended) 2 Strategies: Maintain bilateral rso 2 room air baseline values within 75% of established Maintain bilateral rso2 values above 50% for patients with a baseline value of 50%

17 General Concepts Clinical Use Protocols Index

18 General Concepts Because each device uses a unique processing algorithm and different physical components measuring different λs and number of λs one cannot necessarily assume that the outcomes associated with clinical studies of one device are directly transferrable to the others Avery EG, White paper

19 Validation Courtesy of Covidien

20 Validation Laboratory and clinical validation studies are required to demonstrate the utility of any monitoring modality. Cerebral oximetry is not exempt to this form of validation testing. Despite what may be an obvious advantage to either a non-invasive or invasive monitor previous attempts to validate the utility of monitors in widespread clinical use have not reproducibly produced supportive results. healthsystem.virginia.edu alibaba.com JAMA 1996; 276: 889 Anes 1993; 78: 445

21 Validation No gold standard The validation of rso 2 monitoring is challenged by the fact that there is no gold standard, or index test, invasive or non-invasive of cerebral oxygenation. blogspot.com

22 Validation: Intra-Cranial Sensitivity Balloon test occlusion w/ SPECT + cerebral oximeter + stump pressure (r=0.85; p<0.0001) Desaturation >8% = low flow + ischemic symptoms Kaminogo M, Ochi M, Onizuka M, Takahata H, Shibata S. An Additional Monitoring of Regaionl Cerebral Oxygen Saturation to HMPAO SPECT Study During Balloon Test Occlusion. Stroke. 1999; 30: rso 2 data on file at Covidien, Boulder, CO.

23 Relevant Comparative Variables: SaO 2, SpO 2, TiPO 2, SvO 2, SjvO 2 vs. rso 2 SaO 2 - Systemic arterial oxygen availability SpO 2 - Depends on pulsatile blood flow and measures only the oxy-hb in arterial blood as it leaves the heart T i PO 2 - Partial pressure of O 2 in cerebral tissue SvO 2 - Mixed venous saturation SjvO 2 Jugular venous saturation rso 2 A venous weighted value (75% venous:25% arterial) that measures the regional relative concentrations of oxy-hb and deoxy-hb; it represents the venous reserve capacity following tissue oxygen extraction 2010 Avery EG, White paper; Marin and Moore. Understanding Near-Infrared Spectroscopy. Advances in Neonatal Care. Vol 11, No 6, pp

24 Relevant Comparative Variables: rso 2 vs. SaO 2, TiPO 2, SvO 2, SjvO 2, f SO 2 Reference Title Methods Results Conclusions J Clin Monit 2000;16:191-9 Neurol Res 1997; 19:246-8 Interactive Cardiovasc Thorac Surg 2011; 0 (Dec):1-5 Estimation of Jugular Venous O 2 Saturation from Cerebral Oximetry or Arterial O 2 Saturation During Isocapnic Hypoxia Dynamic Changes of Cerebral Oxygenation Measured by Brain Tissue Oxygen Pressure and Near Infra-red Spectroscopy Non-invasive Cerebral Oxygenation Reflects Mixed Venous Oxygen Saturation During the Varying Haemodynamic Conditions in Patients Undergoing Transapical Transcatheter Aortic Valve Implantation Prospective, observational N=42 healthy adults Varied FiO 2 with isoand hypercapnia INVOS Prospective, observational N=10 Neuro ICU t i PO 2 and rso 2 NIRO 300 Prospective, observational N=20 TA-TAVI SvO 2 and rso 2 at 6 time points FORESIGHT rso 2 & SjvO 2, r=0.9 SaO 2 & SjvO 2, r=0.77 rso 2 & t i PO 2, r=0.73 rso 2 & SvO 2, r=0.76 Compared with SjvO 2, the rso 2 values correlated more closely than SaO 2 ; SjvO 2 changed > rso 2 with hypercapnia Compared with t i PO 2, the rso 2 values correlated well in head injured subjects Compared with SvO 2, the rso 2 values correlated well in TA-TAVI subjects indicating that rso 2 reflects systemic O 2 balance

25 Validation Kim et al, rso 2 & SjvO 2 - Note that SjvO 2 increased slightly more (3-8%) than rso 2 (2-6%) with hypercapnia. Hypercapnia is expected to increase CBF. +2 mmhg above resting ETCO 2 P ET O 2 = 80 mmhg P ET O 2 = 45 mmhg P ET O 2 = 60 mmhg P ET O 2 = 41 mmhg F i O 2 = 50% +7 mmhg above resting ETCO 2 P ET O 2 = 80 mmhg P ET O 2 = 45 mmhg P ET O 2 = 60 mmhg P ET O 2 = 41 mmhg F i O 2 = 50% J Clin Monit 2000; 16; 191

26 Validation Poor man s autoregulation lower limit test Mx = 0.0 Perfect cerebral autoregulation Mx 0.4 Clinically poor autoregulation Mx = 1.0 No cerebral autoregulation Pre-CPB Mx = 0.17 CPB-cooling Mx = 0.28 (34%>0.4) CPB-warming Mx = 0.40 (53%>0.4) Post-CPB Mx = 0.27 Stroke 2010;41: Anes & Analg 2012;116:834-40

27 INVOS Indications for Use The noninvasive INVOS 5100C is intended for use as an adjunct monitor of regional hemoglobin oxygen saturation of blood in the brain or in other tissue beneath the sensor. It is intended for use in individuals greater than 2.5 kg at risk for reduced-flow or non-flow ischemic states. Its FDA clearance was based upon data generated from healthy subjects.

28 Validation Summary Several published laboratory and clinical validation studies of NIRS rso 2 have been conducted and all ultimately conclude that although there is no index test to compare rso 2 values to the data appears to reflect dynamics of regional cerebral oxygen balance. Of note is the fact that the FDA used a synthesized value for an index comparator and all testing data was generated in healthy subjects. rso 2 f SO 2 = (α SaO 2 ) + [(1.0 - α) SjvO 2 ] Courtesy of Covidien Courtesy of Covidien

29 Clinical Studies casmed.com

30 Clinical Studies Cardiac Surgery #1 Cardiac surgical patients provided many of the early clinical outcome data related to the use of rso 2 monitoring. Goldman et al conducted a large retrospective analysis of cardiac surgical patients to determine the impact of rso 2 monitoring coupled with a standardized interventional protocol on stroke incidence for patients demonstrating cerebral desaturation events. A well matched historical control was compared to an active treatment cohort. n = 2,279 = Historical control (1,245) + study group (1,034) 2004 Heart Surg Forum 7(5); E376

31 Clinical Studies Cardiac Surgery #1 The study group had fewer permanent strokes, shorter hospital length of stay and lower incidence of prolonged ventilation Study Group Historical Cohort 10 Strokes (0.97%) 25 Strokes (2.5%) p <.044 Study Group Median Ventilation Time (4 hrs) Historical Cohort Median Ventilation Time (5 hrs) p <.0016 Study Group Prolonged Ventilation (6.8%) Historical Cohort Prolonged Ventilation (10.6%) p <.0014 STS definition >24 hrs Heart Surg Forum 7(5); E376

32 Clinical Studies Cardiac Surgery #1 The study group had a significantly shorter hospital length of stay when assessed by NYHAC, no numerical data was provided Hospital LOS p =? 2004 Heart Surg Forum 7(5); E376

33 Clinical Studies Cardiac Surgery #1 Summary- A large retrospective study with some methodological problems demonstrated that rso 2 monitoring is associated with reduced risk of permanent stroke in cardiac surgical patients that are managed with a standardized interventional protocol for cerebral desaturations. The greatest benefit was noted in the least sick patients studied (NYHAC I). Risk of Stroke 2004 Heart Surg Forum 7(5); E376

34 Clinical Studies Cardiac Surgery # Anesth & Analg 104; 51 Murkin et al prospectively randomized CABG patients to blinded rso 2 monitoring (control) vs open rso 2 monitoring with a standardized interventional protocol for observed desaturation. The authors hypothesized that by using the brain as an index organ, rso 2 interventions would have measurable and systemic benefits in this patient population. Control n = 100 n = 200 Treatment n = 100 Control (electronic blinding) Intervention

35 Efficacy of Desaturation Interventions Murkin J, et al. Overall % Efficacy of Interventions 80.4% 71% (40/56) required > 3 interventions Murkin JM, Adams SJ, Movick RJ, et al. Monitoring Brain Oxygen Saturation During Coronary Bypass Surgery: A Randomized, Prospective Study. Anesth Analg Jan;104(1):51-58.

36 Clinical Studies Cardiac Surgery #2 The percentage of serious desaturations was significantly greater in the control group Control Group rso 2 AUC < 70% Baseline > 150 min % 6 patients Study Group rso 2 AUC < 70% Baseline > 150 min % none p < Avery ASA 2007 Anesth & Analg 104; 51

37 Clinical Studies Cardiac Surgery #2 The ICU length of stay (LOS) was significantly longer in the control group Control Group ICU LOS (days) 1.87 ± 2.67 (mean ± SD) p < Study Group ICU LOS (days) 1.25 ± 0.84 (mean ± SD) rmdhospital.com 2007 Anesth & Analg 104; 51

38 Clinical Studies Cardiac Surgery #2 The 30-day major organ morbidity and mortality (MOMM) was significantly lower in the study group (p < 0.048) *p < p < MOMM as defined by the STS CABG only 2007 Anesth & Analg 104; 51

39 Clinical Studies Cardiac Surgery #2 Summary- The Murkin study employed fairly solid methodological techniques and produced tangible outcome benefits demonstrating the potential clinical and cost benefits of intraoperative rso 2 monitoring in cardiac surgical patients when the brain is used as an index organ edwards.com 2007 Anesth & Analg 104; 51

40 Clinical Studies Abdominal surgery Casati et al prospectively studied elderly abdominal surgery (>2 hrs) patients randomized to either an intervention group (open rso 2 data + standardized intervention protocol) vs. a control group (blinded rso 2 + standard anesthetic manangement). The goal was to determine if rso 2 monitoring and intervention would mitigate cerebral desaturation and/or effect clinical outcomes. n = 122 Control (electronic blinding) Control n = 66 Treatment n = 56 Intervention 2005 Anesth & Analg 101; 740

41 Clinical Studies Abdominal surgery The standardized intervention protocol for rso 2 is presented below Step 1 Check ventilator Check head position Check tubing position FiO 2 ETCO2 if < 35 mmhg BP via IV fluid (250 ml colloid) if SBP 90 mmhg BP via vasoconstrictors (ethylephrine 2-5 mg) if SBP 90 mmhg Step 2 Deepen anesthetic with propofol (0.5 mg/kg) 2005 Anesth & Analg 101; 740

42 Clinical Studies Abdominal surgery For the intervention group the goal was to maintain INVOS rso 2 values above 75% of subject s established room air baseline. The number of subjects experiencing cerebral desaturation was similar between the control and intervention groups. Control Group n = 15 (23%) subjects With rso 2 Desaturation Study Group n = 11 (20%) subjects With rso 2 Desaturation p = Anesth & Analg 101; 740

43 Clinical Studies Abdominal surgery The magnitude of the rso 2 desaturations were significantly smaller in the intervention group suggesting efficacy resulted from their 2 step intervention schema Control Group Mean rso 2 AUC < 75% Baseline 80 min % [2-144 min %] Study Group Mean rso 2 AUC < 75% Baseline 0.4 min % [ min %] p = Avery ASA 2005 Anesth & Analg 101; 740

44 Clinical Studies Abdominal surgery Among the subjects experiencing a rso 2 desaturation the Mini Mental Status Examination (MMSE) score on POD# 7 was lower in the control group (baseline MMSE scores were similar between these groups) Control Group Median MMSE Score 26 Subjects with any rso2 < 75% Baseline Study Group Median MMSE Score 28 Subjects with any rso2 < 75% Baseline p = Anesth & Analg 101; 740

45 Clinical Studies Abdominal surgery Among the subjects experiencing a rso 2 desaturation the PACU discharge time and hospital length of stay (LOS) were both significantly longer in the control group Control Group Median PACU Discharge time 47 min [13-56] Subjects with any rso2 < 75% Baseline p = 0.01 Study Group PACU Discharge time 25 min [15-35] Subjects with any rso2 < 75% Baseline Control Group Median Hospital LOS 24 d [7-53] Subjects with any rso2 < 75% Baseline Study Group Median Hospital LOS 10 d [7-23] Subjects with any rso2 < 75% Baseline p = Anesth & Analg 101; 740

46 Clinical Studies Abdominal surgery Summary- This early study of elderly general surgery patients established that significant cerebral desaturations are common in this patient population ( 20%) Further, it established that the magnitude of the desaturations can be mitigated by a standardized intervention protocol Finally, this analysis demonstrated that among these types of patients who experience a desaturation that they are more likely to have a significantly longer PACU and hospital LOS 2005 Anesth & Analg 101; 740

47 Clinical Studies Carotid endarterectomy surgery The utility of rso 2 monitoring in carotid endarterectomy surgery (CEA) has been investigated in multiple clinical studies by comparison to the indexes of EEG monitoring, stump pressure and awake neuro exam. A review of four studies with this general design demonstrated a similar and somewhat limited utility of rso 2 monitoring for CEA procedures (low sensitivity and specificity for detecting ischemia); however the negative predictive value of rso 2 monitoring was reproducibly excellent.

48 rso 2 and Carotid Surgery Reference Title Methods Results Conclusions J Clin Anes 2005;17:426 A clinical evaluation of near cerebral oximetry in the awake patient to monitor cerebral perfusion during CEA Prospective, observational study. Index EEG, awake exam. N=50 Sensitivity 44% Specificity 82% NPV 94% rso 2 correlates with clinical signs and EEG detected ischemia during CEA S African J Surg 2007; 45:43 Cerebral monitoring during CEA-a comparison between EEG, transcranial cerebral oximetry and carotid stump pressure Prospective, observational study Index-EEG, stump pressure N=100 Sensitivity 100% Specificity 87% NPV 100% PPV 33% rso 2 has a high sensitivity but low specificity for ischemia during CEA when indexed against EEG. rso 2 changed prior to EEG change during ischemia. J Vasc Surg 2008;48:601 Cerebral oximetry does not correlate with EEG and SSEP in determining the need for shunting during CEA Prospective, observational study Index-EEG, SSEP N=323 Sensitivity 68% Specificity 94% NPV 98% PPV 47% rso 2 should not be used as the sole monitor for ischemia during CEA. rso 2 does add information regarding cerebral ischemia when indexed against EEG and SSEP Eur J Vasc Endovasc Surg 2011; 41; 606 The role of cerebral oximetry in combination with awake testing in patients undergoing CEA under local anaesthesia. Prospective, observational study Index-awake exam N=100 Sensitivity 100% Specificity 96% NPV 100% PPV 81% 19% drop in rso 2 has a high sensitivity and specificity for detecting cerebral ischemia compared with awake exam CEA carotid endarterectomy; EEG-electroencephalogram; NPV-negative predictive value; PPV-positive predictive value; SSEPsomatosensory evoke potentials

49 rso2 and Neurocognitive Dysfunction

50 rso 2 and Neurocognitive Dysfunction Previous clinical studies have indicated that cardiac surgery can be associated with an 33-83% incidence of postoperative neurocognitive dysfunction. The association between physiologic variables representative of cerebral oxygenation (e.g., SjvO 2 ) and neurocognitive outcomes was identified almost two decades ago. Recently, studies expanding on this work have demonstrated significant associations between perioperative NIRS rso 2 values and postoperative neurocognitive dysfunction indicating a potential to mitigate these unfavorable outcomes by monitoring and treating observed perioperative cerebral desaturation. Tournay-Jette 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 Cardiothor Vasc Anes 2011;25(1): Croughwell ND, Newmann MF, Blumenthal JA, et al. Jugular bulb saturation and cognitive dysfunction after cardiopulmnary bypass. Ann Thorac Surg 1994; 58:

51 rso 2 and Neurocognitive Dysfunction Reference Title Methods Results Conclusion J Cardio Thorac Vasc Anes 2004; 18: Cerebral oxygen desaturation is associated with early postoperative neuropsychological dysfunction in patients undergoing cardiac surgery Prospective, observational ASEM and MMSE assessed NCD N=101 rso 2 < 40% an independent predictor of incidence of both ASEM & MMSE impairment rso 2 desaturation is associated with early postoperative NCD in studied population J Cardiothor Vasc Anes 2011; 25(1): The relationship between cerebral oxygen saturation changes and postoperative cognitive dysfunction in elderly patients after coronary artery bypass graft surgery Prospective, observational Full neuropsychological testing done Age > 65 years old N=61 rso 2 < 50% during surgery was associated with early NCD. rso 2 < 30% BL associated with late NCD Intraoperative rso 2 desaturation is common (up to 80%) and associated with early & late NCD; Ann Thorac Surg 2009; 87: Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery Prospective, randomized, blinded, controlled standard NCD test battery N=265 AUC rso 2<50% > 3000 sec % had greater risk of postoperative NCD & prolonged hospital stay (>6 d) Intraoperative rso 2 desaturation is significantly associated with NCD and prolonged hospital stay Crit Care 2011; 15: R218 Preoperative regional cerebral oxygen saturation is a predictor of postoperative delirium in on pump cardiac surgery patients: a prospective observational trial Prospective, observational Delirium (CAM-ICU) and MMSE assessed NCD N=230 Lower preoperative rso 2 (< 59.5%) is an independent predictor of postoperative delirium Low preoperative rso 2 is associated with postoperative delirium after on pump cardiac surgery Brit J Anaesth 2012; 108(4): Reduced cerebral oxygen saturation during thoracic surgery predicts early postoperative cognitive dysfunction Prospective, observational in SLV thoracic procedures, MMSE & 24 hrs postop (FORESIGHT); N=76 rso 2 < 65% of BL occurred freq (60%); 29% of pts had MMSE at 3hrs. rso 2 <65% for even just 5 min assoc. w/ OR 2.03 cognitive decline Early cognitive dysfunction after SLV thoracic surgery is positively related to intraop rso 2 ASEM-antisaccadic eye movement test; MMSE-mini-mental state examination; NCD-neurocognitive dysfunction; BL-baseline; CAM-ICUconfusion assessment method for the intensive care unit

52 Baseline rso 2 and Risk Stratification Recently published data suggests that the room air baseline and oxygen supplemented rso 2 values may serve as a simple, noninvasive risk stratification tool for cardiac surgical patients providing useful insight into 30 day and 1 year mortality as well as the propensity for patients to develop postoperative delirium. Heringlake M, Garbers C, Kabler J-H, et al. Preoperative Cerebral Oxygen Saturation and Clinical Outcomes in Cardiac Surgery. Anesthesiology. 2011; 114(1):58-69 Schoen J, Meyerrose J, Paarmann H, et al. Preoperative regional cerebral oxygen saturation is a predictor of postoperative delirium in on-pump cardiac sugery patients: a prospective observational trial. Critical Care 2011;15:R218

53 Preoperative Cerebral Oxygen Saturation and Clinical Outcomes in Cardiac Surgery Heringlake M, Garbers C, Kabler JH, et al. Prospective, observational pilot study n = 1,178 patients undergoing on-pump cardiac surgery in 2008 Preoperative determination of ScO 2 (mostly on the ward) ScO 2 when breathing room air ScO 2 during oxygen supplementation (ScO 2min-ox ) -goal: SaO 2 >98% Concomitant determination of preoperative: NTproBNP - Hematocrit - EuroSCORE hstnt - GFR - LVEF class Follow up including morbidity and mortality Morbidity > 1 major complications (LCOS, stroke, new RRT, reintubation) and/or high dependency unit stay (ICU+ intermediate care) 10 days 30-day and 1-year mortality NTproBNP: N-terminal pro-b-type natriuetic peptide: high sensitivity troponin T; LCOS: low cardiac output syndrome; RRT: renal replacement therapy Heringlake M, Garbers C, Kabler J-H, et al. Preoperative Cerebral Oxygen Saturation and Clinical Outcomes in Cardiac Surgery. Anesthesiology. 2011; 114(1):58-69

54 ScO 2min-ox and 30 Day Mortality Heringlake M, Garbers C, Kabler JH, et al. ScO 2min-ox competes with the EuroSCORE as a predictive index of 30-day mortality. AUC EuroSCORE 0.82 AUC EuroSCORE 0.54 AUC ScO 2min-ox 0.71 (rso 2 51%) AUC ScO 2min-ox 0.77 (rso 2 53%) p=0.015 p= (True+) (False+) Total Cohort EuroSCORE > 10 Cohort Heringlake M, Garbers C, Kabler J-H, et al. Preoperative Cerebral Oxygen Saturation and Clinical Outcomes in Cardiac Surgery. Anesthesiology. 2011; 114(1):58-69

55 ScO 2min-ox 50% and 1 yr Survival Heringlake M, Garbers C, Kabler JH, et al. ScO 2min-ox 50% predicts 1 year mortality compared to ScO 2min-ox > 50% (days) Total Cohort EuroSCORE > 10 Cohort Heringlake M, Garbers C, Kabler J-H, et al. Preoperative Cerebral Oxygen Saturation and Clinical Outcomes in Cardiac Surgery. Anesthesiology. 2011; 114(1):58-69

56 Clinical Studies Baseline rso 2 & Risk Stratification Summary- This study demonstrated remarkably strong correlations between baseline O 2 supplemented rso 2 values and 30-d mortality Further, it established significant relationships between known objective measures of cardiopulmonary function and rso 2 values p=0.015 p= Finally, it established the ScO 2min-ox value as nearly as strong a predictor of 30-d mortality as the EuroSCORE in the studied population and even stronger in a sicker, select sub-group analysis 2011 Anesthesiology 114;58

57 Clinical Studies STS Database First Alert STS Optional Harvest seven rso 2 data fields p= STS Database was queried for the subjective, dichotomous variable (Y/N?) did rso 2 monitoring serve as a first indicator of an intraoperative event (i.e. technical problem or physiologic change) lead that could lead to an adverse outcome. DCRI conducted the query that included rso 2 data from Jan 2008 Dec n = 36, 548 out of which entries indicated that rso 2 monitoring served as a First Alert indicator of a potential adverse outcome Avery NIRS White Paper Review

58 NIRS rso 2 Expanded Use The preponderance of supportive literature related to the clinical use of rso 2 monitoring begs the question of whether it is not appropriate to be using this noninvasive, safe, modestly expensive monitoring modality more broadly? Thoracic surgery (especially single lung ventilation) ECMO patients Vascular surgery procedures Surgical procedures involving controlled hypotension ICU patients with severe pulmonary infections, septic shock or cardiogenic shock Elderly general surgery patients p=0.015 p= Orthopedic surgical patients (beach chair position shoulder surgery) frca.co.uk theuniversityhospital.com ortho.umn.edu 2010 Avery NIRS White Paper Review

59 Technology Limitations No gold standard for comparision Absolutely requires establishment of B/L baseline values to be of the greatest clinical benefit (ideally on room air) Assumes a fixed ratio of venous : arterial blood under all physiologic conditions Vulnerable to rso 2 parameter corruption if significant concentrations of other chromophores are present (e.g., subdural hematoma chromophore sink ) Light piping from hair or ambient light contamination Few prospective RCT data in varied perioperative populations Overwhelming weight of the literature associated with a single manufacturer s device making it unclear if different/additional wavelengths can bring further clinical outcome benefits

60 Technology Summary Appears to be a window into brain oxygen balance that when used clinically can result in diffusely improved organ protection Stand alone baselines can risk stratify perioperative cardiac surgical patients (likely b/c rso 2 represents cardiac/vascular/pulmonary reserve capacity) Full perioperative potential of this monitoring modality has yet to be determined

61 References-1 1. Avery, EG. Cerebral Oximetry is Frequently a First Alert Indicator of Adverse Outcomes. White paper. last accessed Taitelbaum H, Haviin S, Weiss GH. Approximate theory of photon migration in a two-layer medium. Appl Optics 1989; 28 (12): Litscher G, Schwarz G.. Transcranial cerebral oximetry--is it clinically useless at this moment to interpret absolute values obtained by the INVOS 3100 cerebral oximeter? Biomed Tech (Berl). 1997; 42(4): Hongo K, Kobayashi S, Okudera H, et al. Noninvasive cerebral optical spectroscopy: Depth-resolved measurements of cerebral haemodynamics using indocyanine green. Neurol Res. 1995;17(2): Connors AF, Speroff T, Dawson NV, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. JAMA 1996; 276: Moller JT, Johannessen NW, Espersen K, et al. Randomized evaluation of pulse oximetry in 20,802 patients: II Perioperative events and postoperative complications. Anesthesiology 1993; 78:

62 References-2 7. Germon TJ, Young AE, Manara AR, et al. Extracerebral absorption of near infrared light influences the detection of increased cerebral oxygenation monitored by near infrared spectroscopy. J Neurol Neurosurg Psychiatry 1995; 58: Grubhofer G, Lassnigg A, Manlik F, et al. The contribution of extracranial blood oxygenation on near-infrared spectroscopy during carotid thrombendarterectomy. Anaesthesiology 1997; 52: Kaminogo M, MD, Ochi M, Onizuka M, et al. An Additional Monitoring of Regional Cerebral Oxygen Saturation to HMPAO SPECT Study During Balloon Test Occlusion. Stroke1999; 30(2): Kim SB, Ward DS, Cartwright CR, et al. Estimation of jugular venous O2 saturation from cerebral oximetry or arterial O2 saturation during isocapneic hypoxia. J Clin Monitor 2000; 16: Holzschuh M, Woertgen C, Metz C, et al. Dynamic changes of cerebral oxygenation measured by brain tissue oxygen pressure and near infrared spectroscopy. Neurol Res 1997; 19(3): Stroke. 1999;30(2):

63 References Brawanski A, Faltermeier R, Rothoerl RD, at al. Comparison of Near- Infrared Spectroscopy and Tissue PO2 Time Series in Patients after Severe Head Injury and Aneurysmal Subarachnoid Hemorrhage. J Cereb Blood Flow Metab 2002; 22: McLeod AD, Igielman F, Elwell C, et al. Monitoring cerebral oxygenation during normobaric hyperoxia: A comparison of tissue microprobes, nearinfrared spectroscopy Anes & Analg 2003; 97: 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 2004; 7(5): E376-E Murkin JM, Adams SJ, Novick RJ, et al. Monitoring brain oxygen saturation during coronary bypass surgery: A randomized, prospective study. Anesth Analg 2007; 104: Casati A, Fanelli G, Pietropaoli P, et al. Continuous monitorong of cerebral oxygen saturation in elderly patients undergoing major abdominal surgery minimizes brain exposure to potential hypoxia. Anesth Analg 2005; 101:

64 References Rigamonti A, Scandroglio M, Minicucci F, et al. A clinical evaluation of near infrared cerebral oximetry in the awake patient to monitor cerebral perfusion during carotid endarterectomy. J Clin Anes 2005; 17: Botes K, Le Roux DA, Van Marle J. Cerebral monitoring during carotid endarterectomy a comparison between electroencephalography, transcranial cerebral oximetry and carotid stump pressure. South African Journal of Sugery 2007; 45(2); Friedell ML, Clark JM, Graham DA, et al. Cerebral oximetry does not correlate with electroencephalography and somatosensory evoked potentials in determining the need for shunting during carotid endarterectomy. J Vasc Surg 2008; 48: Heringlake M, Garbers C, Käbler J, et al. Preoperative cerebral oxygen saturation and clinical outcomes in cardiac surgery. Anesth 2011; 114(1):

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68 General Concepts - Chromophores Of interest regarding NIRS is the fact that other chromophores are known to reflect near infra-red light, notably the orange chromophore found in Cucurbita styrian, more commonly known as the pumpkin. Somanetics.com Biomed Tech 1997;42(4):74