1. An Electroencephalogram Study of Induction and Recovery from Propofol Anesthesia July 7, 2005 PI:Brown CoPI:Walsh, Purdon, Mullaly, Kwo, Harrell, Williams, Dray, Bonmassar, Angelone, Hamalainen, Barlow, Matten An Electroencephalogram Study of Induction and Recovery from Propofol Anesthesia July 7, 2005 PI:Brown CoPI:Walsh, Purdon, Mullaly, Kwo, Harrell, Williams, Dray, Bonmassar, Angelone, Hamalainen, Barlow, Matten MGH DACC Clinical Practices Committee

2. Issues for DACC Permission to conduct EEG/propofol study –Identical to DACC-approved EEG/fMRI/propofol study, but with EEG only, no fMRI Permission to implement protocol at the GCRC Bioimaging Core facility (CNY 149) as an offsite location

3. Overview I.Protocol History II.Research Background III.Walk Through Protocol IV.Human Research Protection/ Safety

4. I.Protocol History Similar to BIS/propofol protocol by Rosow/Kearse (1998) Similar to EEG/fMRI/Anesthesia by Brown –IRB approved (1999-P-010748 MGH) –Reviewed by MGH DACC CPC –MGH Mallinckrodt GCRC (GAC)

5. EEG/propofol vs. EEG/fMRI/propofol EEG only, no fMRI under anesthesia –Study conducted in standard clinical area Airway management with bag-mask ASA I Study Subjects ages 18-36 Conducted in GCRC Bioimaging core –Meets requirements for off-site anesthesia EEG source localization –Requires structural MRI in separate session

6. II.Research Background Site Specific Changes in Neural Activity Induction of Anesthesia  GABA- A,  NMDA (?) Clinical Obs., EEG, BIS EEG Source Localization

7. Combine structural/conductivity information from anatomic MRI to “localize” auditory, somatosensory, and cognitive function Faster time scale than fMRI, but spatial resolution lower w/ limited subcortical visibility Somatosensory- Motor Exp’t: Early somatosensory peak, followed by motor response

8. Our Objective To correlate simultaneous measurements of electroencephalogram (EEG)electroencephalogram (EEG) plasma levels of propofolplasma levels of propofol well-defined behavioral markerswell-defined behavioral markers changes in source localizationchanges in source localization during induction of and recovery from general anesthesia.

9. III.Walk Through Protocol Study subject pre-anesthesia clinical assessmentStudy subject pre-anesthesia clinical assessment –Prior to study –GCRC White 13 Induction and Recovery from PropofolInduction and Recovery from Propofol Study subject follow-upStudy subject follow-up Separate anatomic MRI scan (30 minutes)Separate anatomic MRI scan (30 minutes)

10. Study Protocol: Clinical Assessment Subject RecruitmentSubject Recruitment –Healthy male and female volunteers –Ages 18-36 –Total 44 subjects recruited ASA physical status IASA physical status I Telephone QuestionnaireTelephone Questionnaire Pre-study Assessment (2 hours)Pre-study Assessment (2 hours) History and Physical ExaminationHistory and Physical Examination Toxic Screen and Pregnancy Test (female subjects)Toxic Screen and Pregnancy Test (female subjects)

11. Study Protocol: Clinical Preparation Toxic screen and pregnancy testToxic screen and pregnancy test Standard Anesthesia Monitors:Standard Anesthesia Monitors: – ECG, BP cuff, pulse oximeter, capnogram Additional Monitors:Additional Monitors: –EEG, arterial line Airway Maintenance:Airway Maintenance: – Bag mask Phenylephrine to maintain BPPhenylephrine to maintain BP Additional Drugs:Additional Drugs: –bicitra, ondansetron

12. Study Protocol: Overview DIAGRAM W/ CONCENTRATION PROFILE

13. Equipment/ Supplies at CNY 149 ACLS cartACLS cart DefibrillatorDefibrillator Anesthesia CartAnesthesia Cart Airway equipmentAirway equipment Anesthesia MachineAnesthesia Machine O2 and Air (Wall and E-cylinders)O2 and Air (Wall and E-cylinders) Monitors (FiO2, SaO2, EtCo2, ECG, NIBP, P1)Monitors (FiO2, SaO2, EtCo2, ECG, NIBP, P1) Laboratory Testing (urine pregnancy, tox screen, ABG)Laboratory Testing (urine pregnancy, tox screen, ABG) iSTATiSTAT EEG machine and electrodesEEG machine and electrodes Routinely maintained by Biomedical EngineeringRoutinely maintained by Biomedical Engineering

14. ACLS Cart, Defibrillator PICTUR OF ACLS CART AND DEFIB

15. Anesthesia Cart and Anesthesia Machine PICTURE OF ANESTHESIA CART AND ANESTHESIA MACHINE

16. O2 Supply: Wall + E-cylinders PICTURE OF WALL AIR/02 AND E- CYLINDERS

17. Monitors + iSTAT

18. Nursing Responsibilities Page study PhysicianPage study Physician Urine toxicity screenUrine toxicity screen Urine pregnancy testUrine pregnancy test ART line setup availableART line setup available ABG sampling + analysis w/ iSTATABG sampling + analysis w/ iSTAT Preparation of blood samples for storage (propofol)Preparation of blood samples for storage (propofol)

19. Medical Staff Responsibilities Clinical AnesthesiologistClinical Anesthesiologist –care of study subject –PACU care Study AnesthesiologistStudy Anesthesiologist –organization and execution of study protocol –STANPUMP infusion

20. Preliminary Studies 01234 -40 -20 0 20 40 EEG, 0.0 ug/ml Time (sec) Amplitude (uV) 01234 -40 -20 0 20 40 Time (sec) EEG, 2.0 ug/ml 01234 -40 -20 0 20 40 EEG, 4.0 ug/ml Time (sec) 010203040 0 1000 2000 3000 4000 5000 6000 Power Spectrum, 0.0 ug/ml Frequency (Hz) Power (uV 2 /Hz) 010203040 0 1000 2000 3000 4000 5000 6000 Power Spectrum, 2.0 ug/ml Frequency (Hz) 010203040 0 1000 2000 3000 4000 5000 6000 Power Spectrum, 4.0 ug/ml Frequency (Hz) 020406080100 -1.5 -0.5 0 0.5 1 Post-stimulus latency (msec) Amplitude (uV) MLAEP, 0.0 ug/ml P a N b N a 020406080100 -1.5 -0.5 0 0.5 1 Post-stimulus latency (msec) MLAEP, 2.0 ug/ml N a P a N b 020406080100 -1.5 -0.5 0 0.5 1 Post-stimulus latency (msec) MLAEP, 4.0 ug/ml N a P a N b Propofol:0.0 ug/ml2.0 ug/ml4.0 ug/ml MLAEP EEG Power Spectrum EEG time series