1. Non-Transcranial Electroanesthesia Group 2 Students: Ryan Demeter Matt Jackson Caroline Schulman Caroline Schulman Matthew Whitfield Matthew Whitfield Advisors: Doctor Paul King and Doctor James Berry

2. 2 Project Definition Design, build, and test a system for both administering and recording data related to vagal nerve stimulation. Design, build, and test a system for both administering and recording data related to vagal nerve stimulation. Topics to cover: Project Background, Design Ideas, Stimulation (production and application) Techniques, Testing, Overall Status, Current Status, and Key Issues Topics to cover: Project Background, Design Ideas, Stimulation (production and application) Techniques, Testing, Overall Status, Current Status, and Key Issues

3. 3 Project Background Advisor: Dr. James Berry (Dept. of Anesthesiology Multi-Specialty Division) Advisor: Dr. James Berry (Dept. of Anesthesiology Multi-Specialty Division) Computer Engineering expertise from Dr. Andrew Dozier (Dept. of Electrical/Computer Engineering) Computer Engineering expertise from Dr. Andrew Dozier (Dept. of Electrical/Computer Engineering)

4. 4 Project Background Currently, electroanesthesia devices are in use in Europe. Currently, electroanesthesia devices are in use in Europe. In less developed countries where anesthesia technology is lacking, an electroanesthesia device would reduce both the cost of the procedure and the need for technical personal (anesthesiologist). In less developed countries where anesthesia technology is lacking, an electroanesthesia device would reduce both the cost of the procedure and the need for technical personal (anesthesiologist). S. Leduc --> Europe, Japan, Russia, and Germany S. Leduc --> Europe, Japan, Russia, and Germany Activation of a theoretical pain center Activation of a theoretical pain center 35 V, 4 mA, 100 Hz, rectangular pulsating signal 35 V, 4 mA, 100 Hz, rectangular pulsating signal Alternative method Alternative method Descending mechanism and the interconnections within the brain Descending mechanism and the interconnections within the brain

5. 5Background: Quicker recovery time and less biological effect during and after surgery (Photiades, 218-225) Quicker recovery time and less biological effect during and after surgery (Photiades, 218-225) Heal better (Sances and Larson, 21-27) Heal better (Sances and Larson, 21-27) Less a build up of gases in the body (Sances and Larson, 218-219) Less a build up of gases in the body (Sances and Larson, 218-219) EEG and ECG EEG and ECG Electrolyte levels in extracellular and intracellular fluid of the brain (Sances and Larson, 148-175) Electrolyte levels in extracellular and intracellular fluid of the brain (Sances and Larson, 148-175) Decreased gastric acid secretion (Sances and Larson, 33- 46) Decreased gastric acid secretion (Sances and Larson, 33- 46) FDA FDA Kano et al. (1976) Kano et al. (1976) Vagal Nerve Stimulation (Kirchner et al., Ness et al.) Vagal Nerve Stimulation (Kirchner et al., Ness et al.) Electroanethesia

6. 6 10 th cranial nerve 10 th cranial nerve Location: both sides of the neck Location: both sides of the neck Composition: A, B, and C-fibers Composition: A, B, and C-fibers Function: motor and sensory (visceral afferent) signals Function: motor and sensory (visceral afferent) signals C-fibers and Pain C-fibers and Pain Not fully myelinated until adulthood (Koo et al. 429-433) Not fully myelinated until adulthood (Koo et al. 429-433) Shown to help control seizures and depression Shown to help control seizures and depression Best Route to the Central Nervous System Rutecki (1990) Best Route to the Central Nervous System Rutecki (1990) 7 th cranial nerve Location: both sides of the head by the ear Composition: Branches of fibers Function: motor and sensory signals Facial Expression Myelinated NO research into therapeutic use Does lead into the Central Nervous SystemBackground: Nerve Information Vagal NerveFacial Nerve

7. 7 A-fibers A-fibers Adapt to constant stimulus and exhibit presynaptic inhibition Adapt to constant stimulus and exhibit presynaptic inhibition Respond well to low stimulus (George et al. s56- s61) Respond well to low stimulus (George et al. s56- s61) Conduction Speed: 90 to 30 m/s 1 Conduction Speed: 90 to 30 m/s 1 Selectively activated by low intensity VNS Selectively activated by low intensity VNS No effect on EEG recorded in the rats studied by Hammond et al. (1992) No effect on EEG recorded in the rats studied by Hammond et al. (1992) B-fibers B-fibers Respond well to low stimulus (George et al. s56- s61) Respond well to low stimulus (George et al. s56- s61) Conduction Speed: 20 to 10 m/s 1 Conduction Speed: 20 to 10 m/s 1 No effect on EEG recorded in the rats studied by Hammond et al. (1992) No effect on EEG recorded in the rats studied by Hammond et al. (1992) C-fibers C-fibers Continue to fire with constant stimulus Continue to fire with constant stimulus Conduction Speed: 1.6 to.3 m/s 1 Conduction Speed: 1.6 to.3 m/s 1Background: Vagal Nerve Fiber Information [1] Woodbury, DM and J.W. Woodbury. “Effects of Vagal Stimulation on Experimentally Induced Siezures in Rats.” Epilepsia. 31.Suppl. 2 (1990): s7-s19

8. 8 Methods Computer system Computer system Vital signs monitoring equipment Vital signs monitoring equipment Testing Testing Phase I: Phase I: - Device components connected and tested to assure compatibility -Software integrated and tested to assure compatibility and proper operation -Test inputs and outputs of device Phase II: Applicator testing to assure proper outputs and operation Phase II: Applicator testing to assure proper outputs and operation Phase III: Testing of device operation with a rat Phase III: Testing of device operation with a rat

9. 9 Design 1 Too Complex Un-needed components

10. 10 Design 2 Less Components Needed Laptop keyboard eliminates need for an additional keyboard Internal components dependent on stimulation method

11. 11Cost Gas anesthesia Gas anesthesia In the case of gas anesthesia, more is required for treatment and cost are around twenty to forty dollars a patient (Kurpiers et. al., 69-75). In the case of gas anesthesia, more is required for treatment and cost are around twenty to forty dollars a patient (Kurpiers et. al., 69-75). Liquids Liquids between three and nine times as expensive as gas anesthesia per volume (Kurpiers et. al., 69-75). between three and nine times as expensive as gas anesthesia per volume (Kurpiers et. al., 69-75). Electroanesthesia will reduce the high cost of anesthesia for surgery and other procedures by reducing the need to keep large quantities of liquid and gas anesthesia on hand. Electroanesthesia will reduce the high cost of anesthesia for surgery and other procedures by reducing the need to keep large quantities of liquid and gas anesthesia on hand.

12. 12 Stimulation Parameters Stimulation of both Vagal Nerves Stimulation of both Vagal Nerves 20 Hz Rectangular pulse signal 20 Hz Rectangular pulse signal Pulse length of 250 µs (Liporace et al. 885-886) Pulse length of 250 µs (Liporace et al. 885-886) 50 µA (Kirchner et al. 1167-1171) 50 µA (Kirchner et al. 1167-1171) 25 V 25 V Need to consult more with Dr. Berry to estimate best parameters Need to consult more with Dr. Berry to estimate best parameters

13. 13 Soundcard Virtins Sound Card Signal Generator Virtins Sound Card Signal Generator

14. 14 LabVIEW LabVIEW user interface LabVIEW user interface DAQ controller DAQ controller Expensive to actually buy DAQ controller

15. 15 Block Diagram View

16. 16 Delivering Electroanesthesia Option 1: Cortical Stimulator (Ojemann Cortical Stimulator) Option 1: Cortical Stimulator (Ojemann Cortical Stimulator) - Advantage: Add gain stage - Disadvantage: Knobs not computer not computer compatible, gain stage

17. 17 Delivering Electroanesthesia Option 2: Gain Stage Option 2: Gain Stage - Advantage: Computer compatible - Disadvantage: Noise, unforeseen circuitry problems

18. 18 Recent Contacts Ray Booker - Simulation engineer at Ctr. for Medical Simulation Ray Booker - Simulation engineer at Ctr. for Medical Simulation Discussed head and neck phantoms Discussed head and neck phantoms Cost Cost Availability Availability Function Function

19. 19 Sim-man -Most expensive and limited funds (NEGATIVE) -Not immediately available (NEGATIVE) -Possible damage from device (NEGATIVE)

20. 20 Airway Model -Relatively inexpensive (POSITIVE) -Immediately available (POSITIVE) -Thin, plastic head and neck (NEGATIVE) -No damage from electric shock (POSITIVE)

21. 21 Plaster Cast Inexpensive (POSITIVE) Inexpensive (POSITIVE) Can be made and remade whenever needed (POSITIVE) Can be made and remade whenever needed (POSITIVE) Dimensions somewhat flexible (POSITIVE) Dimensions somewhat flexible (POSITIVE)

22. 22 Current Status Sent out NCIIA report before winter break Sent out NCIIA report before winter break Laptop for project given by Dr. Berry and started programming in LabView Laptop for project given by Dr. Berry and started programming in LabView Applied to BMEidea Applied to BMEidea Divided tasks among group members Divided tasks among group members Consulted Ray Booker for test subjects and materials Consulted Ray Booker for test subjects and materials Assigned weekly meeting times Assigned weekly meeting times

23. 23 Overall Status MonthDescription November 2004 Look into previous research done on VNS and Electroanesthesia. Develop schematics and possible device physical designs. Start design development. December 2004 Proceed with research and finalize our design approach. Assemble basic design components. Develop software and user interface. January 2005Begin designing prototype model and testing. February 2005Proceed with prototype design and testing. Obtain IRB approval to test our device. March 2005 Run experiments if approved and make modifications where necessary. Continue work-up and finalize design. April 2005Continue to finalize Design and prepare paper and presentation poster.

24. 24 Most Important References 10 of 31 Ammons, W. Steve, Robert W. Blair, and Robert D. Foreman. "Vagal Afferent Inhibition of Primate Thoracic Spinothalamic Neurons." Journal if Neurophysiology 50.4 of Primate Thoracic Spinothalamic Neurons." Journal if Neurophysiology 50.4 (October 1983): 926-940. (October 1983): 926-940. Bohning, DE, MP Lomarev, S Denslow, Z Nahas, A Shastri, and MS George. "Feasibility of vagus nerve stimulation-Feasibility of vagus nerve stimulation- "Feasibility of vagus nerve stimulation-Feasibility of vagus nerve stimulation- synchronized blood oxygenation level-dependent functional MRI." Investigative synchronized blood oxygenation level-dependent functional MRI." Investigative Radiology 36.8 (2001): 470-479. Radiology 36.8 (2001): 470-479. Fries, Richard. E-mail interview. 5 2005. “FDA: Significant Risk and Nonsignificant Risk Devices”. Mount Sinai School of Medicine. 1 September 2005. Medicine. 1 September 2005. Hammond, EJ, BM Uthman, SA Reid, and BJ Wilder. "Electrophysiological studies of cervical vagus nerve stimulation in humans: I. EEG effects.." Epilepsia. 33 (1992): cervical vagus nerve stimulation in humans: I. EEG effects.." Epilepsia. 33 (1992): 1013-1020. 1013-1020. Kano, T, GS Cowan, and RH Smith. "Electroanesthesia (EA) studies: EA produced by stimulation of sensory nerves of the scalp in Rhesus produced by stimulation of sensory nerves of the scalp in Rhesus monkeys." Anesthesia and Analgesia (1976): 536-541. monkeys." Anesthesia and Analgesia (1976): 536-541. Kirchner MD, A., F. Birklein MD, H Stefan PhD, and H.O. Handwerker PhD. "Left vagus nerve stimulation suppresses experimentally induced "Left vagus nerve stimulation suppresses experimentally induced pain." Neurology 55.8 (2000): 1167-1171. pain." Neurology 55.8 (2000): 1167-1171. Melzack, Ronald, and Patrick D. Wall. "Pain Mechanisms: A New Theory." Science 150.3699 (1965): 971-979. 150.3699 (1965): 971-979. Sances Jr., Anthony, and Sanford J. Larson. Electroanesthesia Biomedical and Biophysical Studies. New York: Academic Press, Biomedical and Biophysical Studies. New York: Academic Press, Inc., 1975. Inc., 1975. Woodbury, DM and J.W. Woodbury. “Effects of Vagal Stimulation on Experimentally Induced Siezures in Rats.” Epilepsia. 31.Suppl. 2 (1990): s7-s19 31.Suppl. 2 (1990): s7-s19