Organ Failure in the Intensive Care Unit

Organ failure, in which organs are no longer able to perform their required functions without external support, is an important cause of morbidity and mortality in intensive care unit (ICU) patients. Most critically ill patients will experience some degree of organ dysfunction during their illness. Individual organ failures can of course occur as the result of specific disease process, such as respiratory failure in a patient with severe bacterial pneumonia, or hepatic failure in a patient with acetaminophen toxicity. However, many critically ill patients, perhaps particularly those with sepsis, will have dysfunction of several organs simultaneously and risk developing multiple organ failure with its high associated mortality rates.

Although the causes of specific organ dysfunction and failure may be identifiable, the mechanisms underlying many cases of organ failure, perhaps particularly in critically ill patients, are still relatively poorly defined. In this issue of Seminars in Respiratory and Critical Care Medicine, leading intensivists from around the world provide state-of-the-art articles on some of the key aspects of organ dysfunction in the ICU.

In the first article, Drs. Mendonca Pires Ferreira and Sakr put the topic into perspective by discussing the epidemiology of organ failure and the tools used to measure and monitor organ dysfunction and failure in critically ill patients. Modern organ dysfunction scores, such as the sequential organ failure assessment (SOFA), can be used to assess dysfunction of individual organs as well as providing a global picture of the degree and severity of organ dysfunction in individual patients. Higher scores are associated with worse outcomes, and changes in scores over time can be indicative of outcome.

A detailed overview of some of the key mechanisms believed to underlie the development of organ failure, and in particular multiple organ failure, is provided in three of the articles. Dr. Kanoore Edul et al first tackle the microcirculatory alterations that occur in sepsis and other types of critical illness and discuss how these changes in regional flow may influence tissue oxygenation and impair tissue function. New techniques to monitor the microcirculation are helping improve our understanding of these changes, but whether therapies targeted at the microcirculation can have any clinical impact remains uncertain, although this is an exciting area of active research. The next article, by Dr. Opal, moves on to the immunological alterations associated with organ failure. Many conditions seen in critically ill patients, including sepsis, pancreatitis, trauma, and burns, are associated with an inflammatory response, and the cascade of mediators released by this process have direct and indirect effects on multiple aspects of organ and cell function. Drs. Fullerton and Singer continue this theme by concentrating specifically on cellular, notably mitochondrial, alterations and raise the intriguing theory that organ dysfunction and failure result from cellular dysregulation rather than cell death. They suggest that this may be an adaptive state, like hibernation, which could ultimately allow recovery with appropriate therapies or time.

The remaining articles of this issue deal with aspects of individual organ failures, including the cardiac, respiratory, neurological, gut, renal, and hematological systems. These articles cover the causes, epidemiology, pathogenesis, diagnosis, and treatments of these individual organ failures. Detailed analyses of current therapeutic interventions for each organ system are provided, with discussion of relevant recent clinical trials. When available, promising new approaches to treatments are also presented. All the articles emphasize the importance of early diagnosis and appropriate and adequate early therapy on improving outcomes.

Although we still often consider organs as single entities, in terms of diagnostic criteria and, more importantly, for therapeutic purposes, we are increasingly realizing that our organs are in fact intimately related and are continuously “talking” to each other via complex systems of intercellular and interorgan signaling. Nevertheless, until we are better able to understand the clinical implications of organ–organ crosstalk and the underlying mechanisms, it is important to understand the common causes and components of individual organ failures in ICU patients.

I would like to sincerely thank each of the authors who has contributed to this issue of Seminars in Respiratory and Critical Care Medicine dedicated to the important topic of organ failure in the ICU.