Multiple Organ Failure Pathophysiology, Prevention, and Therapy

Inflammation in itself is not to be considered as a disease . . . and in disease, where it can alter the diseased mode of action, it likewise leads to a cure; but where it cannot accomplish that solitary purpose . . . it does mischief - John Hunter, A Treatise on the Blood, ITfIlammation, and Gunshot Woundr (London, 1794)1 As we reached the millennium, we recognized the gap between our scientific knowledge of biologic processes and our more limited clinical capabilities in the care of patients. Our science is strong. Molecular biology is powerful, but our therapy to help patients is weaker and more limited. For this reason, this book focuses on the problems of multiple organ failure (MOF), multiple organ dysfunction syndrome (MODS), and systemic inflammatory response syndrome is, patients who have severe injuries; require major, (SIRS) in high-risk patients, that overwhelming operations; or have serious illnesses requiring intensive care; patients who have diseases elsewhere, in other organs or systems, that limit their capabilities to survive a new insult; and patients who are elderly or at high risk for sepsis or other complications. These are the patients who need our help. They need the advances in science, in molecular biology, immunology, pathophysiology, biochemistry, genetics, high technology, and other areas of maximum support at the bedside. These advances could potentially have the greatest impact on improving patient care.

Multiple-organ failure is one of the most challenging clinical problems in intensive care. This and related conditions, such as the systemic inflammatory response syndrome and the multiple organ dysfunction syndrome, represent the end result of a wide variety of insults, including trauma, sepsis, and poisoning, that lead to extensive tissue injury and, ultimately, organ failure. As the editors point out in their preface, multiple-organ failure is not a disease or even a syndrome but, rather, a concept that attempts to draw together a patchwork of pathologic processes. The goal of this book is to describe the underlying biologic mechanisms that lead to multiple-organ failure and the principles of management that are derived from an understanding of these mechanisms.

The first three sections of the book deal with the epidemiology and mechanisms of injury. Rather than chart a systematic course through the myriad possible mediators, the editors have chosen to focus on particular topics. The result is a series of essays rather than a conventional textbook. Inevitably, however, this approach has resulted in some odd choices. For example, an entire chapter is devoted to mast cells, but there is no chapter on lymphocytes. Remarkably, the section on mediators and effectors does not contain a chapter on cytokines. The chapter on therapeutic complement inhibition seems out of place here. The same idiosyncratic approach is used in the sections on prevention and treatment. There is an erudite chapter on the possible therapeutic role of interleukin-11, but none on strategies aimed at tumor necrosis factor. I was particularly disappointed that, in a book that the editors hope will provide "practical guidance on how to manage patients to prevent organ failure," specific recommendations for choosing antibiotics are few and far between.

Some of the chapters are outstanding. I especially enjoyed the discussion of the approach to maximizing oxygen delivery, which provides a detailed, critical assessment of the experimental and clinical evidence in this controversial area and concludes with specific practical recommendations. Many of the basic-science chapters, as well as the clinical sections, such as those dealing with the circulation, the lungs, and the management of peritonitis, will be of great help both to fellows and to more senior physicians who are looking for clear, didactic accounts of complex topics. Other chapters are less successful, either because they are written more as opinion pieces or because, inevitably, they have been overtaken by events. It is a shame, for instance, that the chapter on endotoxin contains almost no information on the role of toll-like receptors, a family of molecules that has revolutionized our understanding of the ways in which bacteria interact with the host.

It is precisely because multiple-organ failure is in some respects a rather nebulous disorder that it has been so difficult to come to grips with. The basic pathophysiology of multiple-organ failure has been meticulously analyzed, and a huge amount has been learned over the past 15 years. But despite the remarkable advances in our understanding of the mechanisms underlying the disorder, the translation of this knowledge into clinical practice has been slow. Many potential therapeutic approaches have emerged from the basic-science laboratory and have proceeded through early clinical development, only to fail when subjected to rigorous testing in large phase 3 trials. There are doubtless several reasons for these problems, but part of the explanation probably lies in the heterogeneity of affected patients and of the processes that lead to organ failure.

Only very recently has some optimism returned to the field, with the preliminary evidence that such strategies as the administration of low-dose corticosteroids or the manipulation of the coagulation cascade may reduce the substantial mortality rate associated with this condition. But even if this optimism bears fruit, the management of multiple-organ failure in the intensive care unit will continue to require a detailed understanding of its pathophysiologic features and of how it can be manipulated. This book will be a valuable resource for clinicians and scientists seeking that understanding.

J. Cohen, M.D.
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