Setting the Scene

Multiple organ failure (MOF) is a common cause of death in intensive care unit (ICU) patients [1]. But what are the mechanisms underlying the development of MOF? Why, when we can support many of the individual organs, e.g., the kidneys with extracorporeal renal support, the lungs with mechanical ventilation, etc., do we all too often end up withholding/withdrawing these life-supporting therapies whenwe feel that there is no chanceof recovery, ormoreprecisely that the “multiple organ failure” state has become irreversible. Early therapyofpatientswith sepsis is associatedwith improvedoutcomes [2,3] andworseningorgan functionearly in thecourseofdisease is associatedwithworse outcomes. Lopes Ferreira et al. [4] reported that worsening organ dysfunction, as assessed by an increasing sequential organ failure assessment (SOFA) score in the first 48 hours was associated with a mortality rate of at least 50% regardless of the baseline SOFA sore. More recently, we reviewed the time course of organ failure in two placebo-controlled sepsis clinical trials with Eli-Lilly and Co [5]. We found that improved cardiovascular, renal, or respiratory organ function within the first 24 hours following development of sepsis-induced organ dysfunction was associated with increased survival. Improved understanding of the mechanisms underlying the development of organ dysfunction and MOF may enable us to develop therapies targeted at preventing or limiting the early events associated with later development of fatal organ dysfunction, and hence improve outcomes. In this chapter, we will briefly explore some of the possible mechanisms involved in the terminality and irreversibility of organ failure.