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View of High Frequency Alternating Currents for Inducing Nerve Block REDUCTION OF THE ONSET RESPONSE IN HIGH FREQUENCY NERVE BLOCK by DOUGLAS MICHAEL ACKERMANN, JR. Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Dissertation Adviser: Niloy Bhadra, M.D., Ph.D. Department of Biomedical Engineering CASE WESTERN RESERVE UNIVERSITY January, 2010 TITLE PAGE CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Douglas Michael Ackermann, Jr. candidate for the Ph.D. degree *. (signed) ______________P. Hunter Peckham______________ (chair of the committee) _______________Kevin L. Kilgore_______________ ______________Cameron McIntyre______________ _________________Niloy Bhadra_________________ ___________________Joe Payer___________________ (date) _____November 23, 2009_____ *We also certify that written approval has been obtained for any proprietary material contained therein. COMMITTEE SIGNATURE PAGE DEDICATION I would like to dedicate this dissertation to my wonderful family, friends and colleagues who make life so much fun. TABLE OF CONTENTS TABLE OF CONTENTS ..................................................................................................... i LIST OF TABLES .............................................................................................................. v LIST OF FIGURES ........................................................................................................... vi ACKNOWLEDGEMENTS ............................................................................................. viii LIST OF ABBREVIATIONS ............................................................................................ xi Abstract ............................................................................................................................... 1 I. CHAPTER I: EXTENDED INTRODUCTION .......................................................... 4 I.A. Clinical Significance of a Local Electrical Nerve Block ..................................... 4 I.B. Review of High Frequency Alternating Currents for Inducing Nerve Block ...... 6 I.C. Mechanisms of Nerve Block Induced By High Frequency Currents ................... 8 I.D. Transient Onset Firing Induced by High Frequency Stimulation ...................... 11 I.E. Clinical Applications of HFAC Nerve Block & Acceptable Onset Response ... 14 I.F. Direct Current Nerve Block ............................................................................... 17 I.G. Primary Dissertation Hypotheses and Corresponding Chapters ........................ 19 II. CHAPTER II: EFFECT OF BIPOLAR CUFF ELECTRODE DESIGN ON BLOCK THRESHOLDS IN HIGH FREQUENCY NEURAL CONDUCTION BLOCK ............ 22 II.A. Abstract ........................................................................................................... 23 II.B. Introduction ........................................................................................................ 24 II.C. Methods .......................................................................................................... 28 i. Double-cable myelinated nerve fiber model (MRG model) .............................. 28 ii. Simulation Protocol for Bipolar Electrode Contact Separation ......................... 28 iii. Animal Experiments and Surgical Procedure ................................................. 32 II.D. Results ............................................................................................................ 36 II.E. Discussion .......................................................................................................... 46 II.F. Conclusions ........................................................................................................ 52 i III. CHAPTER III: RELATIONSHIP BETWEEN MONOPOLAR CONTACT LENGTH AND BLOCK THRESHOLD IN HIGH FREQUENCY NERVE CONDUCTION BLOCK.................................................................................................. 54 III.A. Abstract ........................................................................................................... 55 III.B. Introduction .................................................................................................... 56 III.C. Methods .......................................................................................................... 59 i. Double-cable myelinated nerve fiber model (MRG model) ............................... 59 ii. Computer Simulation Protocol........................................................................... 59 iii. Surgical Preparation & Whole Nerve Experiments ........................................... 63 III.D. Results ............................................................................................................ 67 i. Simulation Results .............................................................................................. 67 ii. Whole Nerve Experiments .................................................................................. 74 III.E. Discussion ....................................................................................................... 78 III.F. Conclusions .................................................................................................... 82 IV. CHAPTER IV: EFFECT OF NERVE CUFF ELECTRODE GEOMETRY ON ONSET FIRING IN CONDUCTION BLOCK OF WHOLE NERVE USING HIGH FREQUENCY CURRENTS ............................................................................................. 84 IV.A. Abstract ........................................................................................................... 85 IV.B. Introduction .................................................................................................... 86 IV.C. Methods .......................................................................................................... 89 i. Surgical Preparation .......................................................................................... 89 ii. Experimental Setup and Design ......................................................................... 89 iii. Data Analysis ..................................................................................................... 93 IV.D. Results ............................................................................................................ 96 i. Conduction Block ............................................................................................... 96 ii. Bipolar Separation Distance Experiments ......................................................... 96 iii. Monopolar Contact Length Experiments ......................................................... 104 IV.E. Discussion ..................................................................................................... 110 IV.F. Conclusions .................................................................................................. 117 V. CHAPTER V: CONDUCTION BLOCK OF PERIPHERAL NERVE USING HIGH FREQUENCY ALTERNATING CURRENTS DELIVERED THROUGH AN INTRAFASCICULAR ELECTRODE ........................................................................... 119 ii V.A. Abstract ............................................................................................................ 120 V.B. Introduction ...................................................................................................... 121 V.C. Methods ............................................................................................................ 123 i. Animal Experiments and Surgical Procedure .................................................. 123 V.D. Results .............................................................................................................. 126 V.E. Discussion ........................................................................................................ 127 VI. CHAPTER VI: CHOOSING AN ELECTRODE FOR BLOCK ............................. 129 VI.A. Cuff vs. Non-Cuff Blocking Electrodes ....................................................... 130 VI.B. Nerve Cuff Electrodes: Choosing a Geometry ............................................. 134 a. The Target Clinical Application Influences the Selection of Electrode Design134 b. Monopolar vs. Multipolar Electrodes .............................................................. 135 c. Minimizing Block Threshold ............................................................................ 136 ii. Minimizing the Onset Response ....................................................................... 147 VI.C. Notes on a Possible Frequency and Electrode Geometry Transition ........... 152 VI.D. Future Work in Blocking Electrode Experimentation and Design ............... 153 VII. CHAPTER VII: CONDUCTION BLOCK OF WHOLE NERVE WITHOUT ONSET FIRING USING COMBINED HIGH FREQUENCY AND DIRECT CURRENTS .................................................................................................................... 155 VII.A. Abstract ......................................................................................................... 156 VII.B. Introduction .................................................................................................. 157 VII.C. Methods ........................................................................................................ 160 i. Surgical Preparation and Experimental Setup ................................................ 160 ii. Measurement of Direct Current Block Thresholds .......................................... 163 iii. Measurement of Nerve Activation
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