PROFESSOR SIR KENNETH L. STUART Pain control has become one ofmedicine's most rapidly growing disciplines, and Iwelcome the opportunity to write this foreword to abook that Iam sure will make its own unique contribution to advancing this discipline. My pleasure in writing it is heightened by my pride in the fact that its editor was at one time an undergraduate student of mine at the University of the West Indies in Jamaica. One of the uncertainties teachers always face is that they can never predict how their charges will turn out. This uncertainty has been happily resolved. Dr. Parris' professional career has been marked by the same dedication and commitment that characterized his undergraduate days and that clearly has been brought to the preparation of this scholarly and practical work. Pain reliefhas been until recently acomparatively neglected field. Its neglect was determined not so much by lack ofprofessional awareness ofits import ance but mainly because so little could be done about it in the past.

Anesthetics produce a reversible state of unconsciousness accompanied by ante- grade amnesia. This remarkable phenomenon brings great relief to surgical patients and wonder to clinicians and scientists. To date, we do not fully understand the mechanisms by which anesthetics ablate conscious sensation and memory. We are, however, making progress. This book presents original results as well as overviews of the current state of knowledge of the problem. It is authored by investigators who know the ?eld well; their research at a number of levels has contributed substantially to our c- rent understanding of anesthetic modulation of memory and consciousness. Most of the contributors were presenters at two workshops organized by Dr. Pearce and Dr. Hudetz at the 40th Annual Winter Conference on Brain Research, held at Snowmass Village, Colorado, from January 27 through February 2, 2007. One workshop focused on anesthetic modulation of consciousness and another on an- thetic modulation of memory. Seven of the chapters are based on material presented at these symposia - appropriately updated with new relevant ?ndings. This infor- tion is supplemented by chapters on anesthesia and sleep, computational analysis of the state of anesthesia, and the clinical phenomenon of "anesthesia awareness," a topic that has recently received much public attention. With these three additional contributions, the book thus includes 10 chapters.

The first international symposium on brain edema was held in Vienna/ Austria in 1965 followed by altogether eight meetings since. The most recent was organized in Y okohama by the Department of Neurosurgery of the Musashino Red Cross Hospital, Tokyo. The continuing interest of both, clinicians and experimental scientists alike may be attributable to the fact that brain edema is a common denominator of many cerebral disorders, which under acute conditions threatens life and weIl-being of afflicted patients. Although progress in understanding as weIl as treatment can be recognized since 1965 many problems remain, particularly concerning the control of brain edema under acute conditions, as in trauma or ischemia. A quantum leap was the distinction of the cytotoxic and vasogenic brain edema prototypes as advanced by Igor Klatzo, providing for transition from a morphological to functional understanding now. The recent brain edema meetings were certainly benefiting from developments of both, molecular neurobiology on the one hand side and functional brain imaging at an ever-increasing resolution on the other, such as magnetic resonance imaging orpositron emission tomography. The international symposium in San Diego 1996 may witness further breakthroughs, hopefully also of effective treatment modalities. The symposium in Y okohama was dedicated to the "Legacy of 28 Years of Brain Edema Research" as a reminder of accomplishments as weIl as remaining challenges.

Until recently, monitoring of cerebral blood flow and metabolism was an unattained goal. Determination of cerebral blood flow was limited to intermittent measurements and particularly difficult to perform in critically ill patients. Meanwhile there are techniques available, however, to monitor cerebral blood flow and cerebral oxygenation, both globally and regionally. Therefore we thought it worthwhile to discuss these new continuous techniques and to compare them with well-known techniques which discontinuously measure CBF. For that purpose, an international workshop with some leading experts in the field was held in October 1992 in Berlin. The workshop consisted of about 20 lectures, either reviews on a special topic, or latest results. These contributions were given by invitation and were extensively discussed. Unfortunately it is impossible to reproduce the discussions. On the other hand, all speakers delivered a manuscript promptly after the meeting so that we were able to edit them within a short time. Since monitoring of cerebral blood flow in intensive care is a rapidly growing and changing topic, the written contributions should be quickly available. Authors, editors and publishers have tried to come close to this ideal. As editors we would like to thank the authors and the publishers who enabled us to come out with this volume of the proceedings as early as possible.

Ischemic brain damage represents a major source of morbidity and mortality in westernized society and poses a significant financial burden on the health care system. To date, few effective therapies have been realized. Recent evidence, however, suggests that channels, pumps, and ionic exchangers are involved in CNS ischemia and ischemic stroke, but the potential contribution of these channels for curing stroke is far less understood than for many other normal and pathological conditions. New Strategies in Stroke Intervention: Ionic Channels, Pumps, and Transporters, analyzes the roles played by targets in stroke development and the potential action of drugs modulating these proteins. This book provides a groundbreaking review of these ionic channels, pumps, and transporters as regulators of neuronal ionic homeostasis, providing a better understanding of ischemic brain disorders and the new pharmacological avenues for a cure.

Opioid treatment for chronic pain has been popularized over the past few decades, and opioid usage has increased several-fold. Opioid treatment of chronic pain increased for several reasons: a sense that chronic pain had previously been undertreated; strong underwriting of medical education by drug companies anxious to sell new "designer" opioids; lifting of the stigma associated opioids, particularly as pain advocacy reestablished opioids as necessary and appropriate treatment for acute and cancer pain. What has emerged is that there are several limitations to chronic opioid treatment. What has become clear in this unfortunate history is that non-specialists were persuaded to prescribe opioids before they could possibly understand the complexity of the treatment. So great were the pressures to prescribe, from drug companies, advocates, and many well-meaning people who saw opioids as the panacea for suffering, opioids were prescribed indiscriminately. It became almost impossible to deny opioids without seeming inhumane. What we learned though, is that while carefully selected and managed opioid therapy can benefit certain patients, casual use fails in several respects. What is needed then is a vast educational effort to help clinicians understand some of the complexities of opioid therapy, and in particular, how to select patients, and subsequently manage and monitor so as to achieve continued efficacy without losing control of pain and drug use. While no one educational effort can solve the whole problem, this book aims to provide clinicians with expert opinion on how to manage certain common scenarios involving opioid management of chronic pain. It will provide the reader not only with an easy reference to the management of common clinical scenarios where opioids are involved, but also with in depth analysis of the difficult issues surrounding a treatment that is both uniquely effective and potentially harmful.

25 years have passed since a small group met for the First International Symposia on Brain Edema in Vienna. Subsequent Symposia were held in Mainz, Montreal, Berlin, Groningen, Tokyo and Baltimore. During this time we have witnessed a virtual explosion of the number of publications in this field and our basic and clinical understanding of this disease process has increased tremendously. Our meetings have always been a landmark to take stock of our experience so far and to provide perspectives toward future developments. In addition, it always was a good opportunity to renew old friendship and to make new friends. This volume is a compilation of papers presented at the Eighth International Symposium on Brain Edema held on June 17-20, 1990 in Bern, Switzerland. During this Symposium 158 papers were presented as oral or poster presentations. This considerable number of papers was chosen from more than 230 abstracts that were received. The organizers wish to thank the Advisory Committee for the work done in paper selection and focus on the Symposium. Appreciation is also given to all persons, who have contributed to the success of this meeting, the Chairmen, the participants and last but not least all the staff who worked behind the scene.

Every so often a gathering of minds and experience occurs that results in an all encompassing overview in depth of such a vast subject as Cerebro-Vascular Malformations, as occurred in Verona in June 1992 and which warrants publication. Professors Da Pian and Pasqualin deserve high compliment and it is a measure of the respect in which they are held that virtually all those most knowledgeable around the world attended, presented their work and thoughts and contributed to intense discussion. Ljunggren's opening historical survey set the stage and must be the most comprehensive yet published. Subarachnoid hemorrhage from aneurysm rupture still constitutes, I dare say, the most difficult problem for neurosurgeons, in relief of the brain injury and arterial reaction and the technical perfection of aneurysm obliteration, even for small, as well as large and giant sacs. Very large high flow A VMs can be as demanding too. The bulk of the conference was devoted to subarachnoid hemorrhage, aneurysms and A VMs which were discussed under about 14 headings each. But vein of Galen malformations, dural A VMs, cavernous angiomas and venous angiomas (renamed developmental venous anomalies) came under scrutiny, not always with consensus. Trends are perceptible such as fibrinolysis of subarachnoid clot, non surgery for Galenic and dural malforma tions, the benignity of venous angioma, but there is still much variation in approach, pharmacologically, technically and with such as the evolving endovascular and radiosurgical stories, used alone or in conjunction."

What is the best way to plan surgical research? What problems are most often encountered in clinical research? How should a research report be presented at a scientific meeting? These questions and more are all answered in Principles and Practice of Research.The second edition has added new sections on animal research models, the molecular and cellular dimension of surgical research, and practical guidelines for obtaining government and third-party funding. Other improvements include a friendlier discussion of statistics and updated material about on-line computer literature searches. This book provides every clinical researcher with a roadmap around the pitfalls of poorly designed studies, through the jungle of incomprehensible statistics, and over the hurdles of research reporting to a successful study from start to finish. From the reviews of the first edition: "For me, it is a bible and a "must" for every Ph.D. or M.D. involved in clinical research, especially in the field of surgery. It should be on the table - not on the book shelf - of both the young as well as the experienced investigator as a readily accessible source of information to avoid the trial-and-error approach to problems in surgical research." #"World Journal of Surgery"#1 ..".a carefully conceived, concise blend of factual theory and principles, practical guidelines, and philosophical perspective... ...I have found it hard to identify any omission (even a selected bibliography on laboratory animals, their care, handling, and anatomy is included) and impossible to single out any individual contribution: each is a treasure - well written, concise, and complete." #"The " "Lancet"#2 "The feature of the book is that, despite attention to detail, it maintains a clear and practical approach to the whole field, beginning with the reasons for carrying out research, the types of research, and above all the reporting of research... ...Almost all aspects of research are covered, from small retrospective studies to departmental, institutional, national and international projects... ...The chapter on writing for publication should be compulsory reading for all budding authors." #"Journal of Bone and Joint" "Surgery"#3

Over the last thirty years, the concern of Pain Medicine practitioners about the potential for their patients to develop a dependence on opioids has left opioid therapy as a largely underutilized treatment. While there is no simple answer to chronic pain, opioids remain the only class of drugs capable of providing relief to patients experiencing serious pain. Opioid Therapy in the 21st Century, Second Edition fills a dearth of clinical knowledge about analgesics to aid practitioners in weighing the risks versus the benefits of opioid therapy for their chronic pain patients. Part of the Oxford American Pain Library, this concise guide serves as a practical, user-friendly reference for physicians across the range of primary care and medical specialties. It includes an overview of appropriate clinical applications of opioids, covering such topics as opioid pharmacology, route selection, and individualization of therapy, as well as strategies for managing and mitigating the risk of abuse, addiction, and diversion. There are also special sections dedicated to the unique needs of pediatric, geriatric, and palliative care patient populations. This second edition discusses opioids approved for use since publication of the first edition, such as Butrans (buprenorphine patch); fentanyl patch and nasal spray; abuse resistant version of Oxycontin; and Embeda (morphine sulfate). Approved indications for older opioids as well as clinical trial information have also been updated.

Great progress has been made in the understanding and prevention of secondary brain damage from acute cerebral disorders, such as trauma and ischemia. Advances may be concerned in particular with better organization and logistics of preclinical emergency care, including rapid arrival of well-trained medical staff on the scene of an accident and of transportation to a competent hospital. Nevertheless, it is a safe assumption that development of secondary brain damage from both intra- and extracranial causes still represents a major factor for the final outcome in severe head injury. Thus, exchanges of experiences and information between various disciplines involved with this important clinical problem - trauma still assumes the number one position as a cause of morbidity and mortality up to an age of 45 years - may provide a basis for in-depth analysis of remaining problems as well as of methods of their solution. This exactly is the purpose of the present publication on concepts and findings pertinent for the general subject of secondary brain damage from various experimental as well as clinical viewpoints. An internationally high-ranking group of experts has been contributing to this collection of reviews on cerebral trauma and ischemia and its adverse sequelae, including cerebral exploration by most modern technologies, such as NMR spectroscopy or PET scanning, among others.

Over the last 10 years the syndrome of severe acute renal failure has progressively changed in its epidemiology. It is now most frequently seen in critically ill patients, typically in the context of sepsis and multiorgan failure. This epidemiologic change has meant that intensive care physicians and nephrologists must now work in close cooperation at all times and must take many com plex issues of prevention, pathogenesis, and management into account that they did not previously have to tackle. Simultaneously, the last 10 years have seen the development of major technical and conceptual changes in the field of renal replacement therapy. There are now previously unavailable therapeutic options that provide physicians with a flexible and rapidly evolving armamentarium. The nutrition of these patients, previously limited by the par tial efficacy of renal replacement therapies, has also become more aggressive and more in tune with the needs of critically ill patients. Increased understanding of the pathogenesis of the multi organ failure syndrome has focused on the role of many soluble "mediators of injury" (cytokines, leukotrienes, prostanoids etc.). These molecules are likely to participate in the pathogenesis of acute renal failure. Their generation and disposal is also affected by different techniques of artificial renal support."

This book reviews the most recent developments in the patho- physiology and therapy of ventilatory failure. It contains contributions by twenty-five internationally recognized aut- horities on respiratory muscle function and investigators actively contributing to our knowledge of the cause, diagno- sis and therapy of ventilatory failure. Of particular inter- estare the descriptions of new modalities of partial and complete ventilatory assistance as well as new knowledge re- garding ventilatory control and fatigue during stressful breathing. The reader will find here a state-of-the-art re- view of the latest research and practical applications in this most critical area of intensive care medicine.

This book has been written for the general health care professional, from every medical and paramedical specialization. Because pain is the most common factor driving patients to seek professional advice, it is likely that every physician, psychologist, and therapist has been clinically exposed to the difficulty and the frequent frustration of dealing with people in pain. All of them may find in this book some explanations for their puzzles and some updated information, which usually are published in specialized journals not ordinarily read by the general practitioner. Actually the book has been addressed to professionals at two different levels of general practice. At one level is the busy practitioner who treats most patients with' 'acute" pain, and who may use this information in daily practice to prevent the onset of chronic pain; a common effort from all professionals currently is needed to curb the "epidemic" of chronic pain in the United States. At another level the book has been addressed to the practitioner who may have a more intense desire to become involved in the actual management of chronic pain patients.

This book deals with the methods and scientific basis of inhalation toxicology. It describes devices and facilities needed to expose animals to inhaled particles and gases as well as approaches to estimating or measuring the fraction of the inhaled material that is retained in the respiratory tract. The book then reviews the evergrowing repertoire of techniques that can be used to measure the responses elicited by the exposure. Quantitative and qualitative anatomical, physiological, and biochemical strategies are discussed in detail. We believe that the toxicology of inhaled materials is an important and timely topic for several'reasons. During the past decade, morbidity and mortality attributable to cardiovascular disease have significantly decreased. Progress in combatting cancer, the second most important cause of death, has been slower, and lung cancer actually became the leading cause of death in men and the second leading cause of cancer death in women. In addition, the incidence of non-neo plastic respiratory diseases such as emphysema, fibrosis, and chronic bronchitis has increased the past decade. In the United States, the National Institutes of Health (NIH) has recently reported that chronic obstructive pulmonary disease affects nearly 10 miliion persons and accounts for 59,000 deaths yearly; indeed, it ranks as the fifth leading cause of death. Because the incidence is increasing, the NIH estimates that it may become the nation's fourth or even third leading cause of death by the year 2000."

The publication of the Vth International Symposium 1995 on "Mechanisms of Secondary Brain Damage" in Mauls/ltaly is a collection of focused reviews reaching from novel molecular- and cell biological findings to aspects of clinical management in head injury and cerebral ischemia. A specific purpose of these series of meetings introduced in 1984 is for an exchange on problems of mutual interest by international high ranking experts from the basic sciences and related clinical disciplines, such as intensive care medicine, neurology, or neurosurgery. The present volume covers three major areas: (a) Molecular and cell biological mechanisms including inflammation (b) Novel findings on mechanisms and treatment in cerebral ischemia (c) Secondary processes in head injury, regeneration and treatment Molecular-and cell biology is currently attracting attention towards activation of genomic processes associated with the demise of cells referred to as "programmed cell death" and "apoptosis" which, actually, might be distinguished from each other. Thus, the phenomenon of delayed neuronal death in selectively vulnerable brain areas following brief interruption of blood flow is scrutinized as to the contribution of the activation of suicide genes. The physiological role of such a response, among others, is removal of surplus neurons during ontogenesis of the brain. Yet, evidence is accumulating that similar mechanisms playa role in cerebral ischemia, probably also trauma, where nerve-and other cells demonstrate features of apoptosis. Observations on protection of neurons by administration of protein synthesis inhibitors in cerebral ischemia provide more direct support.

Sepsis is still the leading cause of death in surgical and general intensive care units. Although our knowledge of this complex syndrome has increased in recent years, it is still far from com- plete. New therapeutic approaches have been developed. Some did not fullfill the high expectations for their use in clinical prac- tice; others are still under clinical evaluation. is the aim of this monograph to offer basic information on the It etiology, definition, pathophysiology, prevention and therapy of sepsis and septic shock to both the clinician and the scientist. We believe that it presents an extensive overview that may help the clinician to better understand and treat sepsis and septic shock. We also hope that this work will give some directions for future research both in the clinical field as well as the laboratory. Jena, Berlin, Jerusalem, K.Reinhart February 1994 K.Eyrich C.Sprung TableofContents I.Definition/Prognosis Sepsis and Septic Shock: Update on Definitions (Jo-L.Vincent) 0 0 0 0 0 0 0 0 0 0 0 0 ******** 3 Clinical Manifestations and Prognostic Indicators in Sepsis (R.C.Bone) ...0 * * * * * * * * * * * * * * * * * * * 16 What Determines Prognosis in Sepsis? Evidence for a Comprehensive Individual Patient Risk Assessment Approach to the Design and Analysis of Clinical Trials (W.A.Knaus, D.P.Wagner, F.E.Harrell, Jr.

Rarely have the many mechanisms that might underlie neural plasticity been examined as explicitly as they are in this broad, lavishly illustrated treatment of plasticity in the somatosensory system. The reader is provided with state-of-the-art knowledge of connections at all levels of the somatosensory system. The authors examine the propensity for changes of connectivity in both the mature and developing mammal and make clear proposals regarding the mechanisms underlying these changes. Their functional significance to relevant psychophysical and neurological observations is also discussed.

Nitric Oxide (NO) is a free radical, a gas, and a pluripotent product of mammalian cells. Only a few years ago, scientific discussions of NO were largely held in the context of the chemistry of air pollution. Now, however, the great significance of NO as a signalling and cytotoxic molecule has captured the attention of the biomedical community. This book provides a very up-to-date review of the role of NO in sepsis and ARDS. Consideration is given to NO both as a pathophysiologic mediator as well as a therapeutic agent. An internationally recognized group of scientists and clinicians have contributed chapters dealing with cutting-edge science and practical clinical strategies. Numerous tables and charts have been included to aid the reader in understanding this fascinating and important subject.

Neuroanesthesia contains the edited presentations of the 42nd Annual Postgraduate Course in Anesthesiology given by the Department of Anesthesiology at the University of Utah School of Medicine, February 1997. The chapters reflect recent advances in neurophysiology, pharmacology and monitoring related to the practice of neuroanesthesiology. The sections on central nervous system trauma, intraoperative management, brain protection and postoperative care provide a conceptual framework for current clinical practices. This textbook is the fifteenth in a continuing series documenting the proceedings of the Postgraduate Course of the Department of Anesthesiology of the University of Utah School of Medicine. It reflects, as well as past and future volumes, the rapid and continuing evolution of anesthesia in the last years of the twentieth century.

Perinatal medicine, which is concerned with the problems of the fetus and newborn, has rapidly developed in the last two decades as an important and challenging specialty. Rapid advances in the field, coupled with tech nological advances, now are making survival of infants with weights as low as 500 grams possible. Ventilator care for severe respiratory problems is on the verge of being replaced by surfactant replacement therapy; on the other hand, development of such technologies as extracorporeal mem brane oxygenation and jet ventilation has revolutionized the care of these sick infants. The advances taking place today in the field of perinatal medicine make periodic updates, like the one provided by this volume, a virtual necessity for clinicians and paramedical personnel alike. A distinguished group of specialists in various aspects of perinatal medicine has contributed to this book. Their wide-ranging experience and points of view should make this book a valuable reference for all physicians and allied health personnel involved in the care of the high-risk fetus and newborn. MANOHAR RATHI, M.D. Acknowledgements. I am grateful to the contributors for their cooperation in preparing the manuscripts, to my associates for their help and support, and to the publishers for their continued interest in this work. Above all, I thank Ms. Rose Aiello-Lech and Ms. MaryAnn Cichowski for their hard work in making this publication possible."

I am very happy and honoured to have so many famous contrib utors from around the world presenting their knowledge and experience in this book, including Dr. Rufer who, as early as 1967, attempted to improve the pressure-volume curve of a child dying from RDS using dried surfactant from dogs; Drs. Enhorn ing and Robertson who were the first to treat rabbit fetuses with surfactant replacement and impressively demonstrated that sur factant improved lung mechanics; and Dr. Fujiwara who at the end of the 1970's had already successfully treated the first babies with surfactant replacement and published this work al ready in 1980. Thus, the idea of surfactant replacement therapy is now more or less 20 years old and almost 10 years have passed since the first publication by Dr. Fujiwara of his impressive clinical results. Up to now (September, 1988) about 2,200 babies have been treated worldwide with tracheal instillation of surfactant, with most promising results. The type of surfactant used varies from pure natural extracts from bovine or pig lungs, to surfactant extracted from human amniotic fluid, to pure phospholipids. To date, however, there is still no surfactant commercially available (except in Japan), in spite of the fact that it is urgently awaited by neonatologists and intensive care doctors throughout the world. This volume is based on the contributions presented at the international congress on Surfactant Replacement Therapy which was held in Rotterdam, The Netherlands, in November 1987."

by E.K. ZSIGMOND, M.D. Department of Anesthesiology University of Illinois Chicago U.S.A. It is, indeed, a distinct honor and privilege to be invited by the authors to write a preface to this monumental monograph, Regional Opioid Analgesia. Regional Opioid Analgesia is a colossal undertaking by Drs. De Castro, Meynadier and Zenz shortly after the introduction of this revolutionary approach to pain relief which opened a new epoch in analgesiology. This is, indeed, the first authentic and comprehensive textbook encompassing the current knowl edge on this novel approach to pain relief. We are indebted to the authors for introducing the new opioids to regional analgesia with the scientists, who de veloped the potent short and ultrashort acting opioids with high therapeutic indices, which many researchers dreamt about but never before materialized. The side effect liabilities of these new opioids are minute as compared to morphine and meperidine. Regional Opioid Analgesia could not have been more authentically written than by Drs. De Castro, Zenz and Meynadier, who have conducted daily clinical investigations on all known opioids for regional analgesia as well as for neurolept analgesia. Therein lies the great value of this monograph: it is the most authentic work on this topic."

This atlas offers a collection of EEG spectral analyses and their corresponding conventional recordings under anes thesio10gical procedures. The EEGs presented here were re corded on general surgical and gynecological patients during the last few years. Premedication, induction and maintenance of anesthesia, recovery the immediate postoperative period, and intensive care are covered. Techniques for operating the necessary equipment and artefacts relevant to the routine clinical use of EEG are briefly outlined. Typical examples of characteristic EEGs are presented at the beginning of each chapter, followed by illustrations of deviations from the norm showing the great variety of anesthesiologically induced changes of cerebral function. The description of each EEG course is assessed in relation to clinical parameters. Sometimes no satisfactory interpreta tion can be made, because many physiological and patho physiological causes of alterations in cerebral function are unknown. Time and again it proves impossible to estimate wether deviations from the norm have their origin in cerebral changes or are secondary to extracerebra1 disturbances. The atlas comprises a complete survey in itself, but it can also be seen as a supplement to the book The Electroenceph alogram in Anesthesia by I. Pich1mayr, U. Lips, and H. Kunkel (Springer, 1983), in which detailed lists of references are quoted that are omitted here."

Assisted Circulation 4 is an authoritative review of the progress which has been achieved in the last 5 years since the publication of "Assisted Circulation 3" in 1989. The present book highlights the work of well-known experts on indications for assisted circulation, cardiac support devices such as bridges, devices for transplantation, devices for chronic mechanical support, biological energy sources, cardiomyoplasty, extracorporeal membraneoxygenation and an overview of cardiac devices support with a specific emphasis on xenotransplantation. Assisted Circulation 4 is the latest product of an ongoing effort by the editors to keep readers regularly informed of recent developments in the field. Assisted Circulation is a standard technology in cardiac surgery and especially in cardiac transplantation.