Mechanisms Of Organ Dysfunction In Critical Illness

The pathophysiology of sepsis can be regarded as a series of steps, beginning with the invasion of normally sterile tissue by microbes and the elaboration of various pro-inflammatory mediators. The final common pathway is often the development of the multiple organ dysfunction syndrome (MODS). Whereas a great deal has been learned during the past quarter century about the inflammatory processes associated with sepsis (and other related conditions, such as ischemia/reperfusion injury), our understanding is far less developed with respect to the pathophysiological events that lead to organ dysfunction under these conditions. Nevertheless, efforts by both clinical and laboratory scientists are leading to new knowledge in this area. The chapters in this volume provide a state-of-the-art overview of many aspects of the pathophysiology of organ dysfunction in critical illness.

There have been tremendous advances in understanding the cellular mechanisms involved in sepsis and contributing to the development of multiple organ dysfunction and mortality in this setting. The chapters in this book provide up-to-date insights into important pathways that are initiated by sepsis.

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.

Severe sepsis is among the most common causes of death in the United States and the most common cause of death in the Intensive Care Units worldwide, and its recognition and treatment remain the most important challenges of critical care medicine. Severe sepsis and septic shock have a profound effect on kidney function and the function of other organs through complex mechanisms, which involve the immune response, multiple pro and anti-inflammatory pathways, intracellular dysfunction and hemodynamic instability. Their optimal management requires complex knowledge of general medicine, immunology, nephrology, extra-corporeal technology, fluid resuscitation and critical care endocrinology. In order to deliver optimal patient care, nephrologists and intensive care medicine specialists need to understand and be highly knowledgeable in the epidemiology of sepsis, the mechanisms of injury which determine outcome and the fundamental aspects of new insights into fluid resuscitation, acid-base physiology and glucose control. They also need to have a clear appreciation of new technical developments in the monitoring of critically ill patients and in the delivery of advanced extra-corporeal blood purification therapies.Experts from the fields of intensive care medicine, nephrology, endocrinology, acid-base physiology, extra-corporeal blood purification technology and immunology have contributed to the present book, providing a cutting edge view of developments in each field which contribute to the care of patients with severe sepsis, acute renal failure and multiple organ failure. The resulting mix of fundamental knowledge and recent developments from clinical trials and laboratory research constitute a valuable tool for all professionals involved in the care of the critically ill patient.

Sepsis is a syndrome or sometimes it is a clinical condition evoked by uncontrolled endotoxin-reactions. These pathophysiological alterations can disturb the organism's homeostasis leading ultimately to a condition of severe organ dysfunction which in itself means a bad prognosis for patient survival. In the last decades researchers and clinicians have been involved in process directed to a better understanding of the basic mechanisms of sepsis and MODS. The best goal will be the achievement of preventive measures and optimization of management in patients suffering severe infections and critical conditions. This objective represents a true challenge at the dawn of the XXI century.

This issue of Critical Care Clinics, edited by Mervyn singer and Manu Shankar-Hari, includes: Sepsis 3.0 Definitions; Epidemiology and Outcomes; Pathophysiology of sepsis; Pathophysiology of Septic shock; Mechanism of organ dysfunction in sepsis; Endocrine and metabolic alterations in sepsis: challenges and treatments; The immune system in sepsis; Nutrition and Sepsis; Common sense approach to managing sepsis; Biomarkers for sepsis and their use; Personalizing sepsis care; Novel interventions - What’s new and the future; and Long term outcomes following Sepsis.

An experienced physician knows how to recognize a patient suffering from sepsis, but cannot accurately determine whether the patient will survive. Cardinal elements of the treatment for sepsis include specific antibiotic and vasoactive drugs, enteral and parenteral nutrition, artificial respiration, and optimization of the oxygen transport to tissues. Nonetheless, with a certain frequency, these techniques are insufficient to ensure the recovery of a critically ill patient, especially when it is necessary to overcome functional alterations subsequent to organ and vital-system overload. The key elements in the progression of the sepsis-MODS syndrome are tied to numerous factors. These include: the severity and location of the lesion; the patient's age; the remaining functional reserve; the presence of mediatory which may be stimulatory, inhibitory or both.

There have been tremendous advances in understanding the cellular mechanisms involved in sepsis and contributing to the development of multiple organ dysfunction and mortality in this setting. The chapters in this book provide up-to-date insights into important pathways that are initiated by sepsis.