2. Objectives Describe the basic technology of Bispectral Index (BIS™) monitoring State the key applications for BIS monitoring in the ICU Describe the impact of inappropriate sedation in the critical care setting Identify challenges with sedation assessment 1 2 3 4

3. Sedation: Current Issues Over-sedated increased drug costs delayed weaning increased ICU length of stay increased testing Under-sedated anxiety and agitation awareness and recall post-traumatic stress disorder increased adverse events increased use of paralytics Without a means to objectively titrate the level of sedation, patients may be:

4. Incidence of Inappropriate Sedation Over-sedation On Target Under-sedation 54% 15.4% 30.6% Kaplan L and Bailey H. Critical Care. 2000; 4(1):S110. Olson D et al. NTI Proceedings. 2003; CS82:196. 10% 20% 70% Kaplan L. and Bailey H. 2000 Olson D. et al. 2003

5. Components of Comfort Analgesia Muscle MuscleRelaxation Consciousness/Sedation COMFORT Autonomic & Somatic Response + Pain Scales Movement + Nerve Stimulator Vital Signs + Sedation Scales + BIS Monitoring

6. Bispectral Index (BIS) A practical, processed EEG parameter that measures the direct effects of sedatives on the brain Frontal montage Provides objective information about an individual patient’s response to sedation Optimizes sedation assessment and titration Numerical scale correlates to sedation endpoints

7. GE BIS Display / BIS Sensor GE BIS Display BIS Sensor

8. Philips BIS Display / BIS Sensor BIS Sensor Philips BIS Display

9. BIS Technology BIS Monitor BIS Modules BIS Sensor

10. Sensor Application Apply sensor on forehead at angle Circle #1: Centered, 2 inches above nose Circle #4: Directly above eyebrow Circle #3: On temple, between corner of eye and hairline Press around the edges of each circle to assure adhesion Press each circle for 5 seconds

11. BIS Range Guidelines Titration of sedatives to BIS ranges should be dependent upon the individual goals for sedation that have been established for each patient. These goals and associated BIS ranges may vary over time, in the context of patient status and treatment plan.

12. Objective assessment of sedation during: BIS in the ICU: Key Applications Mechanical Ventilation Neuromuscular Blockade Bedside Procedures Drug Induced Coma

13. Moderate/Deep Sedation During Mechanical Ventilation Challenges/Concerns Over-sedation longer wake-up increased MV time increased drug costs increased length of stay Under-sedation anxiety, agitation failure to effectively ventilate unintended medical device removal NMBA use when adequate sedation cannot be achieved Inadequacy of sedation assessment tools BIS Value Objective measure of level of sedation Improved drug titration May avoid use of NMBA with better controlled sedation Help reduce adverse events associated with over- and under-sedation

14. BIS in Deep Sedation Jaspers et al. Intensive Care Medicine. 1999;25(Suppl 1):S67. Titration to maximal Ramsay Score of 6 (unarousable) Blinded BIS monitoring Results: Ramsay Score remains the same, with significant decrease of BIS values over time. Data suggest possible accumulation of sedatives and inherent risks of over-sedation. BIS Value BIS Ramsay Score* 68 45 31 6 6 6 2 3 4 5 6 * Mondello et al. Minerva Anestesiology. 2002;68(102):37-43. Ramsay

15. BIS in Deep Sedation Riker. AJRCCM 1999 De Deyne. Int Care Med 1998 Unarousable SAS 1 Ramsay 6 Titration to unarousable state by subjective scale Blinded BIS monitoring Results: Patients were unarousable at maximal sedation score. All patients appeared similar clinically, but displayed wide variation in sedation level as measured objectively with BIS monitoring.

16. BIS in the ICU: Reduces Sedative Cost Maintains Adequate Sedation Maintains Adequate Sedation Neurocritical Care Unit at Duke University Hospital Compared cost of propofol pre-BIS monitoring vs. BIS-guided titration Results: Average Cost Savings: $185/patient/day All patients were considered adequately sedated Annual savings (2 patients/day): > $135,000 Olson D et al. Critical Care Nurse. 2003; 23(3):45-52.

17. Neuromuscular Blockade Challenges/Concerns Under-sedation / Awareness Over-sedation / Extended wake-up Inability to use traditional subjective sedation assessment tools BIS Value Provides objective information where sedation scales can not be used More information to assure proper sedation dosage Monitors for the risk of awareness Provides reassurance to staff and family

18. BIS Reduces Sedative Cost & Improves Patient Experience Kaplan L and Bailey H. Critical Care. 2000; 4(1):S110. SICU patients (n=57): Infusions of sedatives & paralytics Control: Sedatives titrated to vital signs and comfort BIS: Sedatives titrated to BIS 70-80 (post-stimulation) BIS-Guided Titration Results: Average sedative savings of $150 per patient Unpleasant recall reduced from 18% to 4% (p<0.05) BIS Titrated Control Sedative Cost / patient ($) 18% Decrease $819 $669 BIS Titrated Control Patient Recall: Frightened / Painful (%) 78% Decrease 18% 4%

19. Drug Induced Coma Challenges/Concerns Traditional EEG monitoring is: complex costly difficult to interpret Ongoing assessment is critical to assure targeted suppression BIS Value Simplified interpretation of patient response to treatment Improve drug titration with continuous, objective information

20. Burst Suppression EEG Pattern Riker RR et al. Pharmacotherapy. 2003; 23(9):1087-1093. Pentobarbital Coma (15 sec) SAS 1 BIS 14 SR 67

21. Bedside Procedures Challenges/Concerns Patients are too sick or unstable to transport to OR Need to assure same standard of care for patients regardless of location Risks associated with over- and under-sedation Over-sedation / Delayed recovery Under-sedation / Awareness BIS Value Improves quality of care by optimizing sedation Allows same standard of care for surgical procedures Monitors for risk of awareness Cost savings potential

22. BIS: Procedural Monitoring Sedation drugs and doses administered at discretion of bronchoscopist Bronchoscopists blinded to BIS values Results: Patients who recalled feeling “too awake” were less sedated as measured by the BIS, despite receiving similar sedative doses. Physicians performing bronchoscopy usually overestimate the adequacy of sedation compared to patients experiencing bronchoscopy. Riker RR, Vijay P, Prato BS. Patient Recall After Bronchoscopy Corresponds to EEG Monitoring (Bispectral Index) But Not Sedative Drug Doses. American Journal Respiratory Critical Care Medicine 1997; 155: A397. * * = p<0.05 * * *

23. Objective sedation assessment Minimize consequences of over- and under-sedation Improve quality of sedation management Value of BIS in the ICU Optimize clinical and economic outcomes

24. For more information about clinical applications for BIS monitoring in critical care, please contact Aspect Medical Systems, Inc. USA: 1 888 247 4633 Outside USA: +31 30 662 9140 www.aspectmedical.com Bispectral Index, the BIS logo and BIS are trademarks of Aspect Medical Systems, Inc. and are registered in the USA, EU and other countries. ©2004, Aspect Medical Systems, Inc. 080-0386 1.00