Clinical Trials For The Treatment Of Sepsis

The incidence of sepsis is increasing as new medical and surgical technologies are applied to an increasingly aging patient population. The treatment of sepsis emphasizes strategies to avoid multiple organ dysfunction, with particular attention to establishing source control, and then modifies the host's response to the excessive inflammatory response which characterizes sepsis. This book is a comprehensive review by internationally recognized experts of the epidemiology, monitoring and treatment of sepsis. Using an "evidence-based" approach, it comprises an extensive review of the literature on sepsis, provides up-to-date recommendations for monitoring and treating sepsis patients, and concludes with explicit recommendations for the design and monitoring of future clinical trials.

This book is open access under a CC BY 4.0 license. It constitutes a unique source of knowledge and guidance for all healthcare workers who care for patients with sepsis and septic shock in resource-limited settings. More than eighty percent of the worldwide deaths related to sepsis occur in resource-limited settings in low and middle-income countries. Current international sepsis guidelines cannot be implemented without adaptations towards these settings, mainly because of the difference in local resources and a different spectrum of infectious diseases causing sepsis. This prompted members of the Global Intensive Care working group of the European Society of Intensive Care Medicine (ESICM) and the Mahidol-Oxford Tropical Medicine Research Unit (MORU, Bangkok, Thailand) - among which the Editors – to develop with an international group of experts a comprehensive set of recommendations for the management of sepsis in resource-limited settings. Recommendations are based on both current scientific evidence and clinical experience of clinicians working in resource-limited settings. The book includes an overview chapter outlining the current challenges and future directions of sepsis management as well as general recommendations on the structure and organization of intensive care services in resource-limited settings. Specific recommendations on the recognition and management of patients with sepsis and septic shock in these settings are grouped into seven chapters. The book provides evidence-based practical guidance for doctors in low and middle income countries treating patients with sepsis, and highlights areas for further research and discussion.

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.

Much research over the past 30 to 40 years has shown that the inflammatory response, while critical for host defense during microbial infection, may itself play a central role in the pathogenesis of sepsis. Although key mediators responsible for this injury have been identified, efforts clinically to augment our conventional antimicrobial and supportive therapies during sepsis with agents modulating the inflammatory response have been unsuccessful. As a result, the mortality associated with this lethal syndrome, especially when complicated by shock, has remained persistently high. Unfortunately, during this same period of time, the incidence of sepsis has accelerated as other fields of medicine have relied increasingly on therapies that predispose to infection. While frustrating, overall this experience in the field of sepsis has not been without value. Most importantly, it has helped define on several different levels the complexity of the septic patient. Recognizing and addressing this complexity as discussed by each of the contributors to Evolving Concepts in Sepsis and Septic Shock may now provide new inroads into the treatment of sepsis.

Randomized clinical trials are the primary tool for evaluating new medical interventions. Randomization provides for a fair comparison between treatment and control groups, balancing out, on average, distributions of known and unknown factors among the participants. Unfortunately, these studies often lack a substantial percentage of data. This missing data reduces the benefit provided by the randomization and introduces potential biases in the comparison of the treatment groups. Missing data can arise for a variety of reasons, including the inability or unwillingness of participants to meet appointments for evaluation. And in some studies, some or all of data collection ceases when participants discontinue study treatment. Existing guidelines for the design and conduct of clinical trials, and the analysis of the resulting data, provide only limited advice on how to handle missing data. Thus, approaches to the analysis of data with an appreciable amount of missing values tend to be ad hoc and variable. The Prevention and Treatment of Missing Data in Clinical Trials concludes that a more principled approach to design and analysis in the presence of missing data is both needed and possible. Such an approach needs to focus on two critical elements: (1) careful design and conduct to limit the amount and impact of missing data and (2) analysis that makes full use of information on all randomized participants and is based on careful attention to the assumptions about the nature of the missing data underlying estimates of treatment effects. In addition to the highest priority recommendations, the book offers more detailed recommendations on the conduct of clinical trials and techniques for analysis of trial data.

Sepsis: New Insights, New Therapies brings together contributions from an international group of experts in diverse fields to consider how the various pathways implicated in early and late sepsis interact, with a particular emphasis on novel concepts and potential new therapeutic approaches. Topics covered include adaptive immunity, inflammation, neuroendocrinology, bioenergetics and metabolism. Several chapters in the latter half of the book are particularly concerned with treatment strategies involving modulation of the neuroendocrine response. Addresses the frequent, but under-recognised condition of sepsis and discusses new ways to prevent and treat it Describes numerous pharmacological approaches to therapy for early and late sepsis Includes detailed discussion of the various physiological systems implicated in sepsis Presents an international perspective, featuring contributions from experts from laboratories worldwide involved in the study of sepsis Sepsis: New Insights, New Therapies is an invaluable resource for all critical care physicians and researchers. It is also informative reading for immunologists, endocrinologists, neuroendocrinologists, physiologists, and pharmacologists.

Sepsis represents a life threatening condition to ICU patients. The evolution of sepsis to severe sepsis or septic shock may occur in an unpredictable way. In the coming millennium the prevention and management of sepsis and organ dysfunction will present a real challenge for researchers and clinicians.