Intracranial Pressure is a linking keyword, uniting various aspects of diagnostics and treatment of hydrocephalus, head injury, subarachnoid haemorrhage, and brain ischaemia. This volume contains selected papers presented at the XIth International Symposium on Intracranial Pressure and Brain Biochemical Monitoring, held in Cambridge, UK, in July 2000. Various clinical and experimental methodologies are discussed including multiparameter brain biochemical monitoring (including brain oxygenation, microdialysis and novel imaging techniques), assessment of cerebral autoregulation, measurement of brain compliance, etc. This state-of-the-art volume introduces neuroscientists into a world of new techniques, models, monitoring modalities but also theories and new concepts, which highlight directions for the further research and future clinical practice.

Albumin is the most abundant serum protein produced by the liver. In clinical practice the serum level of albumin continues to be used as an important marker of the presence, progress or ofthe improvement of many diseases, even though it is the complex end result of synthesis, degradation a. nd distribution between intra- and extravascular space. The clinical history of albumin began as early as in 1837, when Ancell first recognized "albumen" and noted that this protein is needed for trans port functions, for maintaining fluidity of the vascular system and for the prevention of edema. However, the important physiological properties of serum proteins and their role in the regulation ofthe oncotic pressure were demonstrated later by the physiologist E. H. Starling in 1895. In 1917 the clinician A. A. Epstein first described the edema in patients with the nephro tic syndrome as being a result of a very low level of serum albumin. Al though the determination of serum albumin concentration became more popular after Howe in 1921 introduced the technique of separation of serum globulins from albumin by sodium sulfate, the first preparations of human serum albumin were made available for clinical use in only 1941 by the development of plasma fractionation by Cohn and his coworkers at Harvard Medical School."

This volume is a compilation of papers presented at the Tenth International Symposium on Brain Edema held on October 20-23, 1996, in San Diego, California. This follows the sequence of meetings that was initiated 31 years ago in the First International Symposium held in Vienna. Subsequent symposiums were held in Mainz, Montreal, Berlin, Groningen, Tokyo, Baltimore, Bern, and Tokyo CY okohama). A considerable number of papers was chosen from over 100 papers that were received. The organizers wish to thank the Advisory Committee for the excellent work done in selection of the papers. We also wish to thank all the persons who contributed to the success of the Tenth International Symposium, especially the staff who worked behind the scenes. These papers were reviewed, edited, approved or disapproved by the Editorial Board. Those manuscripts that were felt not pertinent to this publication were not accepted by the Editorial Board. Therefore, the excellent quality of those that are in the book are a reflection of the authors' dedication and work and that of those of the Editorial Board in their review process. For the reader's convenience, the papers are structured according to the various disease processes which are associated with the primary topic: hypertension, hydrocephalus, infection, ischemia, tumor, etc. We do hope that the reader will enjoy the articles and that they will provide an impetus and insight for future work.

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.

A concise yet complete overview of the treatment of cardiovascular instability in the critically ill patient. The authors consider all aspects, ranging from basic physiology and pathophysiology to diagnostic tools and established and novel forms of therapy. The whole is rounded off with an integration of these principles into a series of clinically relevant scenarios.

A comprehensive text of intensive care would readily fill the equivalent of the Shorter Oxford English Dictionary. This is because the diseases treated are both numerous and varied; thus the patient can be medical, surgical, trauma or obstetric. It follows that the sum total of knowledge which needs to be available is truly encyclopaedic. This compact volume represents only a fragment of such information. The contributors were chosen because of their experience and because their methods were well-tried. The text therefore summarizes the best of current therapy and includes the controversial. The contributors come from four countries, adding an international flavour. One topic - The Recovery Room - outside the confines of intensive care has been included for two reasons. The recovery room is an important but neglected aspect of care, and it also seems important to define its relationships with the intensive care unit. It is hoped that the book will help the nurses and doctors involved in intensive care and, therefore, the patient. ERIC SHERWOOD JONES Vll Contributors P. M. ASHWORTH K. CHATTERJEE Department of N . using * Medicine Cardiology Division University of Manchester University of California San Francisco Stop ford Building Cardiovascular Research Institute Oxford Road Manchester M 13 9PT, UK Moffitt Hospital Rm. 1186 San Francisco California 94143, USA S. T. ATHERTON Intensive Care Unit Whiston Hospital E. M. COOKE Prescot Department of Microbiology Merseyside, UK University of Leeds Leeds LS2 91Z, UK B. J. BAIN W. E.

This volume represents a review of recent work presented by eminent scientists at the Second International Symposium on 'Applied Physiology in Critical Care with Emphasis on Children' at Aruba, Netherlands Antilles, November 28 - 2 December, 1983. We are grateful to the keynote speakers who accepted our invitation and completed their chapters in time for the press. I must thank the Government of Aruba, the Tourist Office of Aruba, Mr Frank Croes and Mr Betico Croes for their support and generosity for organizing this symposium. My sincere thanks go to Mr Rory Arends, Lucy Arends, Simon Meij and Norma van Toornburg for their untiring efforts and cooperation. Omar Prakash, MD IX List of contributors Bryan, A.Ch., MB, BS, PhD, FRCP (C), The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8 Bryan, H., MD, Department of Pediatrics, Room 1241, Mount Sinai Hospital and The Hospital for Sick Children, University of Toronto, Ontario, Canada M5G 1X5 co-authors: A.L. Campbell, Y. Zarfin, M. Groenveld, P. Duffty Enhorning, G., MD, University of Toronto, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8 Gross, I., MD, Perinatal Medicine, Yale University School of Medicine, P.O.

Serious disturbances of fluid and electrolyte balance are frequently encountered in acutely ill patients; somewhat less often in the chronically sick. There seems to be a trend for such cases to increase, due probably to an increase in major surgical procedures on older patients whose renal function is less than adequate. There are already many publications dealing with the physiology of the homeo stasis of fluid and electrolytes, and others dealing with the clinical aspects of the subject. It is often assumed that a knowledge of the basic principles of physiology will enable the doctor to prescribe suitable intravenous therapy. In practice this is often found not to be so and the evidence for this is the frequency of calls for help with electrolyte problems from well-qualified and experienced doctors who are undoubtedly equipped with adequate or even excellent knowledge of the basic It is not an unusual observation that knowledge of theory and principles involved. principles does not necessarily lead to successful practice in this or any other art or craft. Most doctors already possess knowledge of the physiology of the internal envi ronment, but some are aware of being unable to deal effectively with clinical problems related to fluid and electrolyte disturbances and seek guidance to translate theoretical knowledge into practice."

The science of neuroanaesthesia and neurointensive care is fascinating, and the amounts of experimental and clinical studies are overwhelming. Surely, everyone can surf Medline and other database systems in order to get information. If you, however, ask for head injury, cerebral ischaemia or barbiturate, you will get hun dreds, may be thousands of titles and even the same number of abstracts. The aims of this book are to review important experimental and clinical data with emphasis on up-dated references. The text within each issue and sub-issue systematically covers experimental and clinical data separately, and details con cerning cerebral blood flow, cerebral metabolism, intracranial pressure etc. are reviewed accordingly. In our survey of the literature we did not use Medline or other database sys tems systematically. Rather, we used available medical journals which covered the topics of anaesthesia, neuroanaesthesia and neurointensive care. In this way we hope that relevant literature is presented. On the other hand, we cannot exclude that some important issues are omitted. The book covers 12 topics. In three chapters methodology of CBF measure ments, regulation of CBF, and intracranial pressure are described. In the next 6 chapters inhalation anaesthetics, hypnotic agents, analgesics, muscular relaxants, drugs used for control of blood pressure, and the sitting position are reviewed. The last three chapters cover head injury, subarachnoid haemorrhage and cere bral ischaemia."

A cutting-edge review of the fundamental biological principles underlying the more common inflammatory disorders of the nervous system. The authors provide extensive updates on the latest findings concerning the mechanisms of inflammation and introduce such new concepts and methodologies as "endothelial and leukocyte microparticles" and "gene microarray technology" to help explain important links between the central nervous system (CNS) and general inflammatory processes. Among the diseases examined from an inflammatory perspective are multiple sclerosis, acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, CNS vasculitis, neuropsychiatric systemic lupus erythematosis, Alzheimer's disease, and Parkinson's disease. The role of the immune system in neuroinflammation is also explored in such disorders as neurosarcoidois, HIV-Associated dementia, and HTLV-associated neurological disorders.

Information is provided from the basic and clinical sciences on the mechanisms damaging the brain from trauma or ischemia. New aspects involve the endoplasmic reticulum, mitochondrial failure, pathobiology of axonal injury, molecular signals activating glial elements, or the emerging therapeutical role of neurotrophins. Experimental issues involve a better analysis of the ischemic penumbra, the salvagable tissue. Therapeutic contributions reach from the environmental influence to gene expression, including neuroprotection, such as hibernation - mother nature's experiment - or hypothermia which is reported to induce cell swelling. Treatment issues deal also with thrombolysis and combination therapies, or with the clearance of adverse blood components - LDL/fibrinogen - by a novel procedure using heparin. Other highlights are discussing the specificities of pediatric vs. adult brain trauma, or the evolving role of the Apolipoprotein-E e4 gene in severe head injury. An update is also provided on an online assessment of the patient management during the pre- and early hospital phase in Southern Bavaria. The empirical observation of neuroworsening is analyzed in further details, whether this is a specificity autonomously driving the posttraumatic course. Finally, the unsolved question why drug trials in severe head injury have failed so far in view of the promising evidence from the laboratory is subjected to an expert analysis.

In this new, startlingly original book, John D. Lantos weaves a compelling story that captures the dilemmas of modern medical practice. The Lazarus Case: Life-and-Death Issues in Neonatal Intensive Care begins with a fictional malpractice case-an amalgam of typical cases in which Lantos appeared as an expert witness-and uses it as the framework for addressing the ethical issues surrounding neonatal intensive care. Lantos draws on his experience in neonatal medicine, pediatrics, and medical ethics to explore multiple ethical dilemmas through one poignant representative situation. In Lantos's model case, a doctor decides to stop resuscitation of a premature infant, a tiny "preemie" who seems past reasonable care. The baby survives with severe neurological defects and the parents sue the doctor, alleging that stopping treatment was negligent. From this case, Lantos considers our moral obligations to critically ill babies, the meaning of negligence, and the sorts of social structures that shape the moral consciences of doctors. Each chapter begins with Lantos deposing in the conference room of the plaintiffs' lawyers. The questions put to Lantos throughout the deposition spark an engrossing retelling of his personal experiences with premature babies, as well as his thoughtful discussions of ethics, morality, history, and medical statistics. Sprinkled throughout the book are references to fictional works by Camus, Dostoevsky, Shakespeare, Twain, and others. Lantos uses these literary examples to further illustrate the ambiguities, misunderstandings, responsibilities, and evasions that plague our decisions regarding life and death, medical care and medical education, and ultimately the cost and value of preserving the lives of the most vulnerable among us.

"A Quick Reference Text" Easy to read and practical in design, Neurocritical Care is the book specialists will turn to for quick reference. It concentrates on management problems, from diagnostic procedures to therapeutic strategies. Exact descriptions are given for treatment procedures, and it is easy to find the appropriate treatment for a given patient. "International Expertise" More than 100 authors from North America have contributed to the book. The different strategies used on either side of the Atlantic have been described, the sections on neuroimaging have been reviewed by a neuroradiologist. "Comprehensive in Scope" Both frequent and rare neurological diseases that may require critical care treatment and subjects of more general interest such as monitoring strategies, ethical problems, brain death and neurological disorders in internal medicine have been covered. Pathophysiology is also discussed, insomuch as it is important for understanding the treatment strategies.

Nutritional support of critically ill patients is a major treatment modality which will enhance recovery and shorten convalescence. New knowledge has emphasized that much of the organ dysfunction associated with sepsis and altered blood flow is related to oxidative injury. Specific nutrients are highly effective in counteracting these effects and their early administration may attenuate cellular damage and multi-organ failure. Patient outcome may also be enhanced by the route of feeding, administration of newer nutrient combinations, utilization of evolving methods of monitoring and the use of growth factors. This new knowledge has evolved to a new area of metabolic support which is addressed for the first time by a group of international experts. The topics presented and general conclusions are of major importance to the practitioners in this field, for they show, for the first time, a departure from the more traditional approaches of nutritional support in patients with life-threatening diseases.

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.

The simple reason for creating this book was my impression that the law is having an increasing impact on the practice of medicine. There is hardly a physician I know who has not been deeply troubled by legal problems professionally, economically, and most important of all, psychologically. The past decade has seen medical practice premiums steadily rising. Multimillion dollar verdicts have not been unusual. Having disregarded these vital issues for many years, physicians have suddenly become very aware of litigation-related problems. Having been interested for a long time in the logic ofthe law and the romance of legal research, I thought it would be useful to create a book that would result in the blending of great minds in law and medicine. It has been my long standing observation and belief that the approach of professors of medicine, and that of learned members of the bar and bench, when put together, produce unique results. Putting these views together has been the real challenge in editing this book."

Intensive Care Medicine has been continuously growing and expanding, culturally, technically and geographically. Monitoring and instrumentation are continuously improving and more and more hospitals are getting Intensive Care facilities. The costs have proportionally increased over the years, so that ICUs represent today a major cost for health structures. Since the available resources are limited, a real need is emerging to set the limits and indications of Intensive Care. It is understood that the problem not only involves medical considerations, but also ethical and economical aspects of the utmost importance. For the first time in Europe, this book edited by Reis Miranda and his colleagues tackles systematically the many structural aspects of the European Intensive Care. The organisation and financing of health care in the Old Continent is deeply different from the American one, and the results and consequent proposals obtained in the USA cannot simply be transferred to this side of the Atlantic Ocean. Weare extremely pleased to welcome this first European attempt to discuss the Intensive Care problem. It lays no claims to giving definite replies in a continuously developing field, but it will surely become the basis for future discussions and proposals. I am particularly happy that this work has mainly developed within the European Society of Intensive Care, whose final target is to ensure a common standard of therapy in our old Europe, beyond national differences. We warmly congratulate the authors, and I am sure that their work will find wide diffusion and consent.

Therapeutic Hypothermia will provide a review of the subject, in particular, resuscitative hypothermia and include known mechanisms of action and results from both mechanistic and outcome laboratory studies and clinical trials. Cooling methods and potential side effects of hypothermia will be addressed as well as recommendations for future laboratory and clinical research.

This volume will be of interest to both the researcher interested in therapeutic hypothermia as well as the clinician interested in the potential use of therapeutic hypothermia in their patient population.

From the viewpoint of a health economist, the intensive care unit (leU) is a particularly fascinating phenomenon. It is the epitome of "high-tech" medicine and frequently portrayed as the place where life-saving miracles are routinely wrought. But the popular imagina tion is also caught up in the darker side, when agonizing decisions have to be made to avoid futile and inhuman continuation of expen sive treatments. My analytical interests led me to approach these issues by asking what the evidence tells us about which leu activities are very bene ficial in relationship to their costs and which are not. This quickly translates into a slightly different question, namely, which patients are most appropriately treated in an leu and which not. Unfor tunately, it is very hard to answer these questions because it has pro ved very difficult to investigate these issues in the manner which is now regarded as the "gold standard: ' namely by conducting rando mized clinical trials or alternative courses of action. I think this is a pity, and I am not at all convinced that it would be unethical to do so in many cases, because there is wide variation in practice and ge nuine doubt as to which practices are best -the two conditions that need to be fulfilled before such a trial is justifiable."

Until recently, endocrinology and critical care medicine were two specialties in medicine that were rather uncomfortable with each other and hence quite i- lated. Fortunately, these two 'alien' disciplines have joined forces in successful attempts to perform high quality research in order to clarify the unknown. By integrating endocrinology in critical care medicine, or vice-versa depending on the specialty of the observer, new experimental and clinical data on the complex endocrine and metabolic derangements accompanying non-endocrine severe i- nesses came available which generated important novel insights with relevant clinical implications. In addition, the state of the art diagnosis and management of primary endocrine diseases that represent life-threatening situations leading to ICU admission has been updated. This issue of Contemporary Endocrinology aims at compiling the new ?ndings. The book indeed covers both areas of 'Acute Endocrinology' that are often taking care of at very distant sites within hospitals. The ?rst part deals with the classical life-threatening illnesses caused by primary endocrine diseases such as thyrotoxicosis, hypothyroidism, acute adrenal crisis, acute calcium disorders, pheochromocytoma, severe hyper- and hypoglycemia . The second part looks at endocrinology from the ICU side, starting with a g- eral overview of the dynamic neuroendocrine and metabolic stress responses in the condition of intensive care-dependent, non-endocrine critical illness.

Modern critical care is characterized by the collection of large volumes of data and the making of urgent patient care decisions. The two do not necessarily go together easily. For many years the hope has been that ICU data management systems could play a meaningful role in ICU decision support. These hopes now have a basis in fact, and this book details the history, methodology, current status, and future prospects for critical care decision support systems. By focusing on real and operational systems, the book demonstrates the importance of integrating data from diverse clinical data sources; the keys to implementing clinically usable systems; the pitfalls to avoid in implementation; and the development of effective evaluation methods.

Mr. Chairman, ladies and gentlemen, with great pleasure I like to welcome you in the cityofGroningen and hope that you will have an enriching and enlighten ing discussion on the conference theme on risk management in blood trans fusion. The organisation of this symposium aims at scientific networking by discussing in an international forum the most important themes of current interest in relation to the state of the art in transfusion medicine. Dr. Cees Smit Sibinga took the initiative in 1976 to start organising the blood bank symposia as they were named in the beginning. Without doubt these symposia have contributed considerably to the development of transfusion medicine. To illustrate the fact that these symposia came to my attention I recollect that I have attended the symposium in 1978, chaired by Dr. Leo Vroman, in my capacity in those days of alderman deputy mayor of the city. So, it has been a long time since. After having been away from Groningen for 18 years I have been inaugurated last week as a mayor and it is a plcasure to be again in your midst. The scries of annual symposia on blood transfusion have contributed to mark the city of Groningen on the map of the international scientific world. A great number of prestigious institutes all over the world involved in the development of transfusion medicine have linked to Groningen and we are proud of that."

lnflammatory reactions are generated in response to extemal and intemal stimuli, such as infection, trauma, clinical insult or dysregulation of the umnune system. The int1ammatory responses may bc antigen-specific or non-specific, local or systemic, chronic or rapid and severe, characterized by a massive release of mediators, often lethal. The aim of this book is to review selectcd aspects associated with the mechanism of the pathology of int1ammatory processes of ditlerent origin and to evaluate therapeutic strategies aimed at combating various inflamma- tory diseases. The introductory article describcs the inmlllnological status of patients with severe sepsis, with particular attention paid to the roJe of circulating neutrophils. Intcgrin activation and chemokine receptor expression and the roles of IL-15, prostaglandins and leukotriens in inflmmnation and immunity are the subjects of next articles. Subsequent reviews are focused on allergic diseases involving mast cells and Th2 type cytokines, in particular the mech- anisms of atopic dennatitis and signaling hy IL-13. The intlmmnatory responscs elicited by Mycobacterium tuberculosis and Mvcobacferium nviwn are also analyzed with special interest paid to the mechanisms which allow the bacteria to escape the host' s immune reactions. The thcrapeutic potential of IL- I 0 in infection and inflammation and thc possible factors contributing to the devclopment of idiopathic pulmonary fibrosis are rcvicwed in the next articles. The final report demonstrates the advantages of bacteriophage ther- apy in thc context of the aggravating problem of hactcrial resistance to antibi- otics.

86 short papers originating from the 13th International Symposium on Intracranial Pressure and Brain Monitoring held in July 2007 in San Francisco present experimental as well as clinical research data on invasive and non-invasive intracranial pressure and brain biochemistry monitoring. The papers have undergone a peer-reviewing and are organized in eight sections: brain injury: ICP management and cerebral physiology; hydrocephalus and cerebrospinal fluid dynamics; advanced neuromonitoring; biomedical informatics; imaging; ICP: brain compliance, biophysics, and biomechanics; stroke, subarachnoid hemorrhage, and intracerebral hematoma; and experimental studies and models. The papers address the increasing use of decompressive craniectomy for the treatment of brain edema as well after brain injury and the rapidly expanding field of advanced neuromonitoring and neuroimaging.

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.