Despite the progress that has been made in intensive care medicine, sepsis and septic shock are still accompanied by a high mortality rate. In recent years, new therapeutic approaches have been developed on the basis of a better understanding of this complex condition. This monograph contains contributions by well-known scientists and clinicians in the fields of hygienics, microbiology, infectious diseases, physiology, surgery and intensive care medicine. It provides an up-to-date overview of the etiology, pathophysiology, prevention, and therapy of sepsis and its complications.

Concise, recent data are presented on obstetric problems arising in patients with cardiovascular diseases (not only congenital and acquired valvular heart diseases and hypertension, but also uncommon heart lesions) and on cardiological complications encountered in pregnant women. The goal of the book is to provide obstetricians with necessary cardiological information and cardiologists with essential obstetric information to enable both specialists to make optimal decisions regarding the permissibility of pregnancy, management of pregnancy and labour, or termination of pregnancy, and selection of an adequate form of contraception in women with heart and vascular diseases. Along with recent scientific findings, the book contains practical recommendations for examination diagnosis and treatment that is effective for the mother and safe for the fetus.

The past few years have seen the publication of a large number of articles and not a few books on the subject of relief of intractable pain. New ideas have been put forward on pain mechanisms, new methods of treatment have been reported and improved results c1aimed, and a growing catalogue of complications oftreatment has been recorded. The vast and expanding literature on the subject poses for the reader the dual problems of surveil lance and of assessment. The object of the present book is to provide a critical and constructive review of current writings and ideas on a wide range of aspects of the nature of intractable pain, particularly of present day practice and new ideas on treatment. Each chapter is written by an acknowledged authority and the approach throughout is practical rather than academic. In editing the individual chapters an effort was made to achieve a contemporary approach and to eliminate material which was unduly historicalor retrospective in content. At the same time the individ ual style of the authors was retained as far as possible. For decades chronic pain has been a therapeutic 'no man's land'. For the surgeon pain was an unfortunate complication wh ich not infrequently followed surgery; for the physician it was a distressing symptom in a number of disease syndromes; to the psychiatrist it was one of a number of features in many cases of mental illness."

The fifth edition of this popular textbook continues to provide a solid foundation of pharmacological knowledge for all those working in anaesthesia and intensive care. The content has been thoroughly revised to include expanded chapters with clearer figures, ensuring readers are kept abreast of the ever-changing landscape of clinical pharmacology. Conveniently divided into four sections covering the basic principles of pharmacology, core drugs in anaesthetic practice, cardiovascular drugs, and other important drugs and complemented by new diagrams, tables and chemical formulae to facilitate learning. All four chapters on core drugs in anaesthetic practice have been updated along with others exploring applied pharmacokinetic models, antimicrobials, and drugs used in diabetes. An ideal aid to study and practice for junior and trainee anaesthetists and intensive care specialists preparing for exams. Also an invaluable resource for theatre practitioners, ICU nurses and physicians working in areas that demand a solid knowledge of pharmacology.

This book reflects the proceedings of the Boerhaave Course, "Developments in drugs used in Anaesthesia", held on r'lay 7th and 8th 1981 at Leiden University. The goal of the organizers of the course was to obtain a better under standing of the pharmacological and clinical applications of the drugs used in the field of Anaesthesiology. In my opinion, there is a constant need for post-graduate teaching not only on a clinical basis, but also in the so-called "basic sciences". This especially applies to anaesthetists. I would like to express my thanks to the speakers, who were all so kind as to send their manuscripts in time for publishing, and to thank the co-editors of this book, as well as rtr. B.P. Ccmnandeur, from r'lar tinus Nijhoff Publishers for their fruitful co-operation. Last but not least, I would like to thank the secretarial staff of my depar~ent for all the work they did arranging for manuscripts to be in the right places at the right times. Joh. Spierdijk THE USE OF H2 BLOCKERS T.H. STANLEY In the last decade a new important histamine receptor, H2 receptor, has been discovered which has major importance in gastric acid production. In addition, a new drug Cimetidine (Tagamet) which blocks the H2 receptor has been synthesized. The object of this presentation will be to discuss the possible role of this interesting drug (Cimetidine) before and during operation and possible postoperatively as well.

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.

The stories behind drug discovery are fascinating, full of human and scientific interest. This is a book on the history of drug discovery that highlights the intellectual splendor of discoverers as well as the human frailty associated them. History is replete with examples of breakthrough medicines that have saved millions of lives. Ether as an anesthetic by Morton; penicillin as an antibiotic by Fleming; and insulin as an anti-diabetic by Banting are just a few examples. The discoverers of these medicines are doubtlessly benefactors to mankind--for instance, without penicillin, 75% of us probably would not be alive because some of our parents or grandparents would have succumbed to infections.
Dr. Jack Li, a medicinal chemist who is intimately involved with drug discovery, has assembled an astounding amount of facts and information behind important drugs through extensive literature research and interviews with many inventors of the drugs including Viagra and Lipitor. There have been many myths and inaccuracies associated with those legendary drugs. The inventors perspectives afforded this book an invaluable accuracy and insight because history is not history unless it is true.
The text is supplemented by many anecdotes, pictures and postage stamps. Both specialist and layman will find Laughing Gas, Viagra, and Lipitor informative and entertaining. Students in chemistry, pharmacy, and medicine, workers in healthcare and high school science teachers will find this book most useful.

Georg Rodewald University of Hamburg Hamburg, Federal Republic of Germany Allen E. Willner Hillside Hospital Glen Oaks, NY In contrast to the initial years of cardiac surgery (37 years ago), there is now increasing interest in cerebral protection. Rodewald [1] in 1978 was among the first to point out the surgeon's concern with "psychopathological problems" and Taylor [2] in 1989 stressed that" *** the awareness of the cerebral consequences of open heart surgery has risen considerably in recent years * * * " This book reviews the evidence for neurological, psychological, and neuropsycho logical reactions to cardiac surgery. In previous studies one problem is that small samples of patients were studied with different measuring instruments so that it was difficult to ma~e sense of inconsistent findings. Considerable controversy resulted with little ability to sort out discrepant findings. It appeared that a large multi center study using uniform measures might help clarify the picture.

The 1973 Boerhaave Course in Leiden on Measurement in Anaesthesia was composed of the lectures included in this book, supplemented by the series of 'lecture demonstrations' organised by Dr. P. Cliffe and given by the members of the Departments of Clinical Measurement and the Magill Department of Anaesthetics, Westminster Hospital, London. The aim of the 1973 Boerhaave Course on Measurement in Anaesthesia was designed to arouse interest in this subject where it has not already occurred. The subjects discussed in the lectures and presented in this book were those that were considered topical and appropriate. The lectures were meant to give an idea of some basic and advanced possibilities of measurement. It was not intended to be an exhaustive review of all the measurements relevant to anaesthetic practice and research. In this time of monitoring one has to keep in mind that good measurement is the basis of good monitoring. A certain amount of repetition is unavoidable as each lecture was intended to be complete in itsel. However, editing has reduced this to a minimum. Department of Anaesthesiology Johan Spierdijk University Hospital, Leiden Department of Anaesthetics Stanley Feldman Westminster Hospital, London Julian Leigh CONTENTS Preface ... V Contributors VIII PART ONE INTRODUCTION The difference between measurement and monitoring. What is worth measuring? . . . . . . . . . . . . . . . . . . . .. . . . 3 . JOH. SPIERDUK and A. NANDORFF Problems of interference and electrical safety associated with the - cording of biological signals . . . . . . . . . . . . . .. . . . 13 J. P. BLACKBURN 22 The scope of measurements using radioactive isotopes .

The manuscripts in this book were generated from a conference occurring at the University of Heidelberg in September 1996. These manuscripts have been reviewed and updated by the designated authors in late 1997 for publication in early 1998. Conferences occur for a variety of reasons. These include the need to exchange information where complex activities are undergoing reassessment or change. For the emergency and critical care man agement of stroke this is certainly the situation. Today, both the pri mary care and the neurologic physician must provide medical care in an environment where daily change in the knowledge base of: brain function, disease mechanism(s), therapeutic efficacy, and cost control are all occurring. In addition, patient advocacy has become increasingly complex because government, employers, insurers, health care providers as well as families all desire a voice in the phy sician relationship with the patient. Our conference subject was the organization of rapid care delivery and the development of a ration al basis for treatment of a previously untreatable disorder acute stroke. Thus, the obvious need for multiple open and free discus sions about priority setting and modification of current treatment plans. Clearly, the face to face opportunities provided by this first conference on Emergency Management And Critical Care Of Stroke (EMACCOS) are required when patient care issues are as complex as these. Neuroscience is new to the experience of active therapeutic inter vention.

This book is based on the proceedings of a conference held in Tubingen, West Germany, in 1981, at which anesthesiologists, neuro surgeons, pathologists and neurophysiologists met to consider the place of controlled hypotension in neurosurgery. In the first part of the book alternative methods of inducing hypotension are considered, and it is important to emphasize that the techniques which are suitable for neurosurgery may not be so for other types of surgery, and vice versa. In neurosurgery, and par ticularly in aneurysm surgery, the emphasis is on lowering intra luminal pressure and not mainly on reducing blood flow or limiting tissue oozing. Another special consideration in neurosurgery is the influence of drugs used to induce hypotension on intracranial pressure, with nitroprusside (NTP), and especially nitroglycerine, increasing ICP in the closed skull and increasing brain "bulk" when the skull is open. These and other points are extensively covered. The use of a non-essential technique like controlled hypotension demands that the procedure should carry minimal risk to the patient. Contributions in part IV consider the neuropathology associated with too severe a lowering of oxygen supply through hypotension. In the clinical avoidance of such ischemic changes in individual patients, monitoring of the brain electrical function is much the most import ant and practical approach and is discussed in part III. The Editors hope that the publication of these contributions to the Tubingen Symposium will help in the effective and safe appli cation of the technique of controlled hypotension in neurosurgery."

The 14th volume in the series will focus on cutting edge research at the interface of hypoxia and exercise. The work will cover the range from molecular mechanisms of muscle fatigue and muscle wasting to whole body exercise on the world 's highest mountains. State of the art papers on training at high altitude for low altitude athletic performance will also be featured.

Increased intra abdominal pressure as used in laparoscopic surgery produces various changes in the human organism. This book provides surgeons and anesthesiologists with a complete overview on these changes and the consequences for the patient in the perioperative and postoperative period. Special emphasis is laid on the management of pneumoperitoneum related complications.

Monitoring of Cerebral and Spinal Haemodynamics During Neurosurgery is a comprehensive description of subdural monitoring of intracranial pressure (ICP) during neurosurgery. It offers thorough analysis of a comprehensive database consisting of measurements of ICP, cerebral perfusion pressure and other relevant physiological data from more than 1,800 patients subjected to intracranial surgery at Aarhus University Hospital. Features of anaesthesia, both inhalation and total intravenous, are discussed, and measures to reduce ICP are described. A majority of the patients had supratentorial tumours, but the database also includes patients with infratentorial tumours and patients with no intracranial space-occupying lesions. A chapter is reserved for discussion of the special features of children with cerebral tumours.

Advances of cardiovascular engineering prompt one to consider innovative device technology - that is, the development of new replacement heart valves or engineering of a totally implantable energy source for an artificial heart. However, these kinds of advances have often proved unable to achieve a long-lasting benefit as the cardiovascular field has matured so fast. Cardiovascular engineering has matured to the point where a major innovation must not only function, but must continuously function better than existing devices. This is difficult to accomplish in the complex cardiovasculature system, in which energy source, biocompatibility, compliance, and functionality all must be considered. The maturation of the field is evident from the fact that many engineered prosthetic systems perform well - for example, heart valves function for long periods of time, large-vessel vascular grafts are quite adequate, extracorporeal membrane oxygenation has significantly prolonged the feasible length of heart bypass and other surgical operations, and total artificial hearts can be used as a bridge to transplant without serious complications, yet none of these systems is as good as the natural ones it replaces. The reasons for this are many and incompletely understood. The next stage of progress must be better to alterations understandings of the various components of vasculature and their response by our devices, be they at the micro- or macro-circulatory levels, in the blood, or associated with the vascular wall.

This book fills the void to provide a comprehensive review of the theoretical knowledge and scope of opioid pharmacotherapy in pain medicine. While the information provided is obtainable in other major texts already in print, the present format style plus the illustrations will make easy reading and fast accessibility of information on opioids available. Information provided is based on clinical practice rather than pure experimental for use in daily practice.

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.

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.

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.

During the last decade a multitude of studies concerning the dynamic changes in cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and intracranial pressure (ICP) in the acute phase after head injury have been published. These studies have been supplemented with studies of cerebral autoregulation, CO2 reactivity and barbiturate reactivity. Other investigations include studies of cerebrospinal fluid pH, bicarbonate, lactate and pyruvate. In this book experimental and clinical studies of the dynamic changes in CBF, CMRO2, CO2 reactivity and barbiturate reactivity are reviewed. The author's own clinical studies of the dynamic changes in CBF and cerebral metabolism are summarized and discussed, and the therapeutical implication as regards the use of artificial hyperventilation, sedation with barbiturate and mannitol treatment are discussed.

Your awareness of uncommon diseases and possible complications is vital to successful anesthetic patient management. Anesthesia and Uncommon Diseases, 6th Edition, brings you up to date with new information on less commonly seen diseases and conditions, including the latest evidence and management guidelines. This unique medical reference book is essential for a complete understanding of today's best options and potential difficulties in anesthesia. Improve your ability to successfully manage every patient, including those with rare diseases or conditions. Avoid complications with unique coverage of an important aspect of anesthetic management. Access the complete contents and illustrations online at www.expertconsult.com - fully searchable! Stay current with all-new chapters on adult congenital heart disease, rheumatic diseases, and the cancer patient, plus many more revisions throughout. Get outstanding visual guidance with hundreds of illustrations, now in full color. Understand uncommon diseases to avoid anesthetic complications!

Geriatric anesthesia is a rapidly growing and evolving field. The last few years have seen significant advancements in and important new modalities for addressing the needs of an aging population. The editors of Geriatric Anesthesiology's second edition are uniquely situated to put together a text highlighting both essential knowledge and recent breakthroughs of importance to any who work with the elderly. For the second edition, the editors have introduced a streamlined chapter format and have assembled a selection of chapters intended to deepen the understanding of anesthesic management of the geriatric patient.

The decisive factor in trauma is that many processes first occur at the cellular level before they can be determined in laboratory tests, and recognition of them has only recently found its way into intensive care practice. Yet knowledge of the pathophysiology of these processes is essential for an early diagnosis of multiple organ failure and the implementation of adequate therapy, which ultimately make the patient's survival possible. Professor Schlag, an internationally renowned scientist and clinician, has been concerned with the basic pathophysiological principles of shock for many years. In this book he has brought together for the first time an international team of authors primarily from the USA and Europe, who present their collective findings of trauma, shock, development of the organ in shock and early failure and of sepsis-like syndrome, and development of septic multiple organ failure. Patienten mit Multiorganversagen haben immer noch eine schlechte Prognose in der intensivmedizinischen Behandlung, insbesondere wenn sie noch zusatzlich in einen septischen Schock geraten. Hier hilft auch oft eine breite Abdeckung mit modernsten Antibiotika nicht weiter. Neue Ansatze fur eine Therapie dieser problempatienten haben sich in den letzten Jahren durch Erkenntnisse der pathophysiologischeen Vorgange die zum Schock fuhren ergeben. Herr Professor Schlag hat als anerkannte Kapazitat auf dem Gebiet der Traumatologie und Schockforschung fur dieses erste umfassende Werk zu den Grundlagen des Multiorganversagens eine beeindruckende Liste von mehr als 50 international renommierten Autoren zusammenbekommen. Das Buch ist nicht nur eine Aufarbeitung aller Grundlagen des Schocks und Multiorganversagens sondern zudem ein ausgezeichnetes Nachschlagewerk fur jeden intensivmedizinisch tatigen Klinikarzt, egal ob er aus der Anasthesie, der Inneren Medizin oder der Unfallchirurgie kommt."

Dieser Band gibt die Referate des 4. Internationalen An{sthesie-Symposiums, 15.-17. Juni 1989 wieder. Amerikanische und europ{ische Spezialisten der unter- schiedlichsten Fachgebiete diskutieren neueste Entwicklungen der Labor- und klinischen Forschung.

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."